COMBICHEM INC, S-1/A, 1997-12-12

COMBICHEM INC
S-1/A, 1997-12-12
COMMERCIAL PHYSICAL & BIOLOGICAL RESEARCH

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AS FILED WITH THE SECURITIES AND EXCHANGE COMMISSION ON DECEMBER 12, 1997

REGISTRATION NO. 333-37981
================================================================================

SECURITIES AND EXCHANGE COMMISSION
WASHINGTON, D.C. 20549
------------------------

AMENDMENT NO. 4

FORM S-1
REGISTRATION STATEMENT
UNDER
THE SECURITIES ACT OF 1933
------------------------

COMBICHEM, INC.
(EXACT NAME OF REGISTRANT AS SPECIFIED IN ITS CHARTER)

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DELAWARE 8731 33-0617379
(STATE OR OTHER JURISDICTION OF (PRIMARY STANDARD INDUSTRIAL (I.R.S. EMPLOYER
INCORPORATION OR ORGANIZATION) CLASSIFICATION CODE NUMBER) IDENTIFICATION NUMBER)
</TABLE>

9050 CAMINO SANTA FE, SAN DIEGO, CALIFORNIA 92121
(619) 530-0484
(ADDRESS, INCLUDING ZIP CODE, AND TELEPHONE NUMBER,
INCLUDING AREA CODE, OF REGISTRANT'S PRINCIPAL EXECUTIVE OFFICES)

DR. VICENTE ANIDO, JR.
PRESIDENT AND CHIEF EXECUTIVE OFFICER
9050 CAMINO SANTA FE
SAN DIEGO, CALIFORNIA 92121
(619) 530-0484
(NAME, ADDRESS, INCLUDING ZIP CODE, AND TELEPHONE NUMBER,
INCLUDING AREA CODE, OF AGENT FOR SERVICE)
------------------------
COPIES TO:

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FAYE H. RUSSELL, ESQ. FREDERICK T. MUTO, ESQ.
THOMAS E. HORNISH, ESQ. ERIC J. LOUMEAU, ESQ.
LANCE S. KURATA, ESQ. CHRISTOPHER W. KRUEGER, ESQ.
BROBECK, PHLEGER & HARRISON LLP COOLEY GODWARD LLP
550 WEST "C" STREET, SUITE 1300 4365 EXECUTIVE DRIVE, SUITE 1100
SAN DIEGO, CALIFORNIA 92101 SAN DIEGO, CA 92121
(619) 234-1966 (619) 550-6000
</TABLE>

APPROXIMATE DATE OF COMMENCEMENT OF PROPOSED SALE TO THE PUBLIC:
As soon as practicable after the effective date of this Registration Statement.

If any of the securities being registered on this Form are to be offered on
a delayed or continuous basis pursuant to Rule 415 under the Securities Act of
1933, check the following box. [ ]

If this Form is filed to register additional securities for an offering
pursuant to Rule 462(b) under the Securities Act, please check the following box
and list the Securities Act registration statement number of the earlier
effective registration statement for the same offering. [ ]
- ------------

If this Form is a post-effective amendment filed pursuant to Rule 462(c)
under the Securities Act, check the following box and list the Securities Act
registration statement number of the earlier effective registration statement
for the same offering. [ ]
- ------------

If delivery of the prospectus is expected to be made pursuant to Rule 434,
please check the following box. [ ]

THE REGISTRANT HEREBY AMENDS THIS REGISTRATION STATEMENT ON SUCH DATE OR
DATES AS MAY BE NECESSARY TO DELAY ITS EFFECTIVE DATE UNTIL THE REGISTRANT SHALL
FILE A FURTHER AMENDMENT WHICH SPECIFICALLY STATES THAT THIS REGISTRATION
STATEMENT SHALL THEREAFTER BECOME EFFECTIVE IN ACCORDANCE WITH SECTION 8(a) OF
THE SECURITIES ACT OF 1933 OR UNTIL THE REGISTRATION STATEMENT SHALL BECOME
EFFECTIVE ON SUCH DATE AS THE COMMISSION, ACTING PURSUANT TO SUCH SECTION 8(a),
MAY DETERMINE.
================================================================================
<PAGE> 2

INFORMATION CONTAINED HEREIN IS SUBJECT TO COMPLETION OR AMENDMENT. A
REGISTRATION STATEMENT RELATING TO THESE SECURITIES HAS BEEN FILED WITH THE
SECURITIES AND EXCHANGE COMMISSION. THESE SECURITIES MAY NOT BE SOLD NOR
MAY OFFERS TO BUY BE ACCEPTED PRIOR TO THE TIME THE REGISTRATION STATEMENT
BECOMES EFFECTIVE. THIS PROSPECTUS SHALL NOT CONSTITUTE AN OFFER TO SELL OR
THE SOLICITATION OF AN OFFER TO BUY NOR SHALL THERE BE ANY SALE OF THESE
SECURITIES IN ANY STATE IN WHICH SUCH OFFER, SOLICITATION OR SALE WOULD BE
UNLAWFUL PRIOR TO REGISTRATION OR QUALIFICATION UNDER THE SECURITIES LAWS
OF ANY SUCH STATE.

SUBJECT TO COMPLETION, DATED DECEMBER 12, 1997

LOGO
2,250,000 SHARES

COMMON STOCK

All of the 2,250,000 shares of Common Stock offered hereby are being sold
by CombiChem, Inc. ("CombiChem" or the "Company"). Prior to this offering, there
has been no public market for the Common Stock of the Company. It is currently
estimated that the initial public offering price will be between $11.00 and
$13.00 per share. See "Underwriting" for information relating to the method of
determining the initial public offering price. The Company has applied for
quotation of the Common Stock on the Nasdaq National Market under the symbol
"CCHM."

--------------------------------------------------------

THE COMMON STOCK OFFERED HEREBY INVOLVES A HIGH DEGREE OF RISK.
SEE "RISK FACTORS" BEGINNING ON PAGE 6.

--------------------------------------------------------

THESE SECURITIES HAVE NOT BEEN APPROVED OR DISAPPROVED BY THE SECURITIES AND
EXCHANGE COMMISSION OR ANY STATE SECURITIES COMMISSION NOR HAS THE COMMISSION OR
ANY STATE SECURITIES COMMISSION PASSED UPON THE ACCURACY OR ADEQUACY OF THIS
PROSPECTUS. ANY REPRESENTATION TO THE CONTRARY IS A CRIMINAL OFFENSE.

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================================================================================================
UNDERWRITING
PRICE TO DISCOUNTS AND PROCEEDS TO
PUBLIC COMMISSIONS(1) COMPANY(2)
- ------------------------------------------------------------------------------------------------
Per Share................................. $ $ $
Total(3).................................. $ $ $
================================================================================================
</TABLE>

(1) The Company has agreed to indemnify the Underwriters against certain
liabilities, including liabilities under the Securities Act of 1933, as
amended. See "Underwriting."

(2) Before deducting expenses payable by the Company estimated at $700,000.

(3) The Company has granted the Underwriters a 30-day option to purchase up to
an additional 337,500 shares of Common Stock, solely to cover
over-allotments if any. See "Underwriting." If such option is exercised in
full, the total Price to Public, Underwriting Discounts and Commissions and
Proceeds to Company will be $ , $ and $ ,
respectively.

--------------------------------------------------------

The Common Stock is offered by the Underwriters as stated herein, subject
to receipt and acceptance by them and subject to their right to reject any order
in whole or in part. It is expected that delivery of such shares will be made
through the offices of BancAmerica Robertson Stephens, San Francisco, California
on or about , 1997.

BANCAMERICA ROBERTSON STEPHENS

DONALDSON, LUFKIN & JENRETTE
SECURITIES CORPORATION

UBS SECURITIES

THE DATE OF THIS PROSPECTUS IS , 1997.
<PAGE> 3

[DEPICTIONS OF COMBICHEM'S DISCOVERY PROCESS]

IN CONNECTION WITH THIS OFFERING, THE UNDERWRITERS MAY OVER-ALLOT OR EFFECT
TRANSACTIONS WHICH STABILIZE OR MAINTAIN THE MARKET PRICE OF THE COMMON STOCK OF
THE COMPANY AT A LEVEL ABOVE THAT WHICH MIGHT OTHERWISE PREVAIL IN THE OPEN
MARKET. SUCH TRANSACTIONS MAY BE EFFECTED ON THE NASDAQ NATIONAL MARKET, OR
OTHERWISE. SUCH STABILIZING, IF COMMENCED, MAY BE DISCONTINUED AT ANY TIME.

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<PAGE> 4

NO DEALER, SALES REPRESENTATIVE OR ANY OTHER PERSON HAS BEEN AUTHORIZED TO
GIVE ANY INFORMATION OR TO MAKE ANY REPRESENTATIONS IN CONNECTION WITH THIS
OFFERING OTHER THAN THOSE CONTAINED IN THIS PROSPECTUS, AND, IF GIVEN OR MADE,
SUCH INFORMATION OR REPRESENTATIONS MUST NOT BE RELIED UPON AS HAVING BEEN
AUTHORIZED BY THE COMPANY OR ANY UNDERWRITER. THIS PROSPECTUS DOES NOT
CONSTITUTE AN OFFER TO SELL, OR A SOLICITATION OF AN OFFER TO BUY, ANY
SECURITIES OTHER THAN THE REGISTERED SECURITIES TO WHICH IT RELATES OR AN OFFER
TO, OR A SOLICITATION OF, ANY PERSON IN ANY JURISDICTION IN WHICH SUCH AN OFFER
OR SOLICITATION WOULD BE UNLAWFUL. NEITHER THE DELIVERY OF THIS PROSPECTUS NOR
ANY SALE MADE HEREUNDER SHALL, UNDER ANY CIRCUMSTANCES, CREATE ANY IMPLICATION
THAT THERE HAS BEEN NO CHANGE IN THE AFFAIRS OF THE COMPANY SINCE THE DATE
HEREOF OR THAT THE INFORMATION CONTAINED HEREIN IS CORRECT AS OF ANY TIME
SUBSEQUENT TO THE DATE HEREOF.

UNTIL , 1997 (25 DAYS AFTER THE DATE OF THIS PROSPECTUS), ALL
DEALERS EFFECTING TRANSACTIONS IN THE REGISTERED SECURITIES, WHETHER OR NOT
PARTICIPATING IN THIS DISTRIBUTION, MAY BE REQUIRED TO DELIVER A PROSPECTUS.
THIS DELIVERY REQUIREMENT IS IN ADDITION TO THE OBLIGATION OF DEALERS TO DELIVER
A PROSPECTUS WHEN ACTING AS UNDERWRITERS AND WITH RESPECT TO THEIR UNSOLD
ALLOTMENTS OR SUBSCRIPTIONS.

------------------------

TABLE OF CONTENTS

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PAGE
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Summary................................................................................ 4
Risk Factors........................................................................... 6
Use of Proceeds........................................................................ 15
Dividend Policy........................................................................ 15
Capitalization......................................................................... 16
Dilution............................................................................... 17
Selected Financial Data................................................................ 18
Management's Discussion and Analysis of Financial Condition and Results of
Operations........................................................................... 19
Business............................................................................... 24
Management............................................................................. 41
Certain Transactions................................................................... 54
Principal Stockholders................................................................. 56
Description of Capital Stock........................................................... 58
Shares Eligible for Future Sale........................................................ 61
Underwriting........................................................................... 63
Legal Matters.......................................................................... 65
Experts................................................................................ 65
Additional Information................................................................. 65
Index to Financial Statements.......................................................... F-1
</TABLE>

------------------------

CombiChem was incorporated in California in May 1994 and subsequently
reincorporated in
Delaware in October 1997. The Company's executive offices are located at 9050
Camino Santa Fe, San Diego, California 92121, and its telephone number is (619)
530-0484.

The Company intends to furnish to its stockholders annual reports
containing audited financial statements certified by an independent public
accounting firm and quarterly reports containing unaudited interim financial
information for each of the first three fiscal quarters of each fiscal year of
the Company.

The Company has filed for trademark protection for the following: Discovery
Engine(TM), Universal Informer Library(TM) and Cascader(TM). All other
trademarks or service marks appearing in this Prospectus are the property of
their respective holders.

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SUMMARY

The following summary is qualified in its entirety by the more detailed
information, including "Risk Factors," and the Financial Statements and Notes
thereto, appearing elsewhere in this Prospectus. This Prospectus may contain
forward-looking statements which involve risks and uncertainties. The Company's
actual results could differ materially from those anticipated in these
forward-looking statements as a result of certain factors, including those set
forth under "Risk Factors" and elsewhere in this Prospectus.

THE COMPANY

CombiChem, Inc. is a computational drug discovery company that is applying
its proprietary design technology and rapid synthesis capabilities to accelerate
the discovery process for new drugs. The Company believes its approach offers
pharmaceutical and biotechnology companies the opportunity to conduct their drug
discovery efforts in a more productive and cost-effective manner. Using its
proprietary Discovery Engine(TM) process, the Company focuses on the generation,
evolution and optimization of potential new lead candidates for its
collaborative partners, who will then develop, manufacture, market and sell any
resulting drugs. CombiChem believes that its process is widely applicable to a
variety of disease targets and therapeutic indications. To date, the Company has
established collaborative agreements with Teijin Limited ("Teijin"), Roche
Bioscience, a division of Syntex (U.S.A.) Inc. ("Roche Bioscience"), Sumitomo
Pharmaceuticals Co., Ltd. ("Sumitomo"), ImClone Systems Incorporated ("ImClone")
and Athena Neurosciences, Inc., a wholly owned subsidiary of Elan Corporation,
plc ("Elan/Athena"). In addition, the Company intends to use its approach on
internal programs to discover new lead candidates and then to outlicense them to
third parties, retaining a larger economic interest.

The Company's proprietary Discovery Engine is a convergent, iterative
process for drug discovery based on libraries (collections of compounds)
designed for information rather than merely diversity. The design of such
libraries requires the use of various computational and combinatorial chemistry
technologies to select molecules that collectively probe the biological target
in a systematic way to determine the chemical characteristics required for
binding to such target. By identifying features that discriminate between active
and inactive compounds, the computer constructs predictive models, called
hypotheses, and then uses those models to select a more focused library of
compounds. The computer selects compounds from the Company's proprietary Virtual
Library, a computational representation of more than 500 billion drug-like
molecules chosen for ease of laboratory synthesis. CombiChem believes that, by
repeating this process of selecting, synthesizing and screening informative
compounds and analyzing the resulting data, the Discovery Engine quickly
converges on the most predictive hypothesis. This hypothesis describes the
characteristics a compound must possess to be active against the target and,
thus, is used to select a variety of potent lead candidates.

CombiChem is applying its drug discovery approach to three important types
of programs: (i) lead generation, where the goal is to find lead candidates
against new biological targets; (ii) lead evolution, where the goal is to
develop alternative structural series with the same biological activity profile;
and (iii) lead optimization, where the goal is to modify a specific drug
template to improve its biological activity. For novel targets where little or
no information is available as well as those targets for which no suitable leads
have been identified, the Company initiates the Discovery Engine process by
making available for screening its Universal Informer Library(TM), which
consists of a computer-designed, proprietary collection of approximately 10,000
physical compounds.

CombiChem believes that its Discovery Engine has the following advantages:
(i) generating lead candidates from multiple structural series that exhibit the
same biological activity; (ii) generating lead structures against a wide range
of targets including those for which little or no information is available;
(iii) achieving rapid generation, evolution and optimization of lead candidates;
and (iv) reducing synthesis and screening costs. The Company's design technology
facilitates the use of small, informative libraries. The efficiency provided by
the use of such informative libraries is expected to shorten the time required
for the identification of lead candidates to less than two years.

The Company's objective is to be the industry leader in the generation,
evolution and optimization of novel lead candidates. The Company intends to
utilize its scientific and technology assets in the discovery process through a
mix of collaborative and internal programs by applying the following business
strategies: (i) to establish multiple collaborations with large pharmaceutical
and biotechnology companies focused on biological targets chosen by the
collaborators; (ii) to partner with companies to apply discovery technologies to
jointly agreed-upon biological targets; (iii) to conduct internal discovery
efforts aimed at selected biological targets, retaining a larger economic
interest in the subsequently outlicensed lead candidates; (iv) to expand
collaborative opportunities in alternative industries such as the agrochemical
field; and (v) to maintain technology leadership in both software development
and rapid synthesis capabilities.

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THE OFFERING

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Common Stock Offered by the Company....... 2,250,000 shares
Common Stock Outstanding after the
Offering................................ 13,168,505 shares(1)
Use of Proceeds........................... To fund research and development, expansion of
laboratory and office facilities, working capital and
general corporate purposes. See "Use of Proceeds."
Proposed Nasdaq National Market symbol.... CCHM
</TABLE>

SUMMARY FINANCIAL DATA
(in thousands, except per share data)

<TABLE>
<CAPTION>
PERIOD FROM
MAY 23, 1994
(INCEPTION) YEAR ENDED NINE MONTHS ENDED
TO DECEMBER 31, SEPTEMBER 30,
DECEMBER 31, ------------------- -----------------------
1994 1995 1996 1996 1997
------------- ------- ------- ----------- -------
<S> <C> <C> <C> <C> <C>
STATEMENT OF OPERATIONS DATA:
Total revenue..................... $ -- $ 50 $ 2,967 $ 1,070 $ 4,599
Total operating expenses.......... (711) (6,763) (8,085) (5,519) (8,341)
----- ------- ------- ------- -------
Loss from operations.............. (711) (6,713) (5,118) (4,449) (3,742)
Net loss.......................... $(706) $(6,675) $(5,118) $(4,461) $(3,669)
===== ======= ======= ======= =======
Pro forma net loss per share(2)... $ (0.66) $ (0.45)
======= =======
Shares used in computing pro forma
net loss per share(2).......... 7,797 8,192
</TABLE>

<TABLE>
<CAPTION>
SEPTEMBER 30, 1997
--------------------------------------------
PRO FORMA AS
ACTUAL PRO FORMA(3) ADJUSTED(3)(4)
-------- ------------ --------------
<S> <C> <C> <C>
BALANCE SHEET DATA:
Cash and cash equivalents.......................... $ 4,287 $ 16,120 $ 40,530
Short-term investments............................. 4,115 4,115 4,115
Working capital.................................... 5,288 16,621 41,031
Total assets....................................... 13,363 25,196 49,606
Long-term obligations, less current portion........ 2,377 2,377 2,377
Redeemable convertible preferred stock............. 23,130 -- --
Accumulated deficit................................ (16,168) (14,835) (14,835)
Total stockholders' equity (deficit)............... (15,852) 18,611 43,021
</TABLE>

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(1) Based on the number of shares outstanding as of September 30, 1997.
Includes: (i) 7,754,933 shares of Common Stock to be issued upon conversion
of redeemable convertible preferred stock, par value $0.001 per share (the
"Preferred Stock"), of the Company; (ii) an aggregate of 1,250,000 shares of
Common Stock issued to ImClone and Elan/Athena in October 1997; and (iii)
901,658 shares of Common Stock which are currently subject to repurchase by
the Company. Excludes: (i) 441,696 shares of Common Stock issuable upon the
exercise of stock options outstanding as of September 30, 1997, with a
weighted average exercise price of $2.81 per share, all of which are
exercisable and 26,177 of which are vested; and (ii) 139,478 shares of
Common Stock issuable upon the exercise of outstanding warrants, with a
weighted average exercise price of $2.27 per share. See "Capitalization."

(2) Computed on the basis described for pro forma net loss per share in Note 1
of Notes to Financial Statements.

(3) Gives effect to (i) the conversion of the Preferred Stock into Common Stock
effective upon the closing of this offering; and (ii) the receipt of $11.833
million for up-front payments and the proceeds from the sale of an aggregate
of 1,250,000 shares of Common Stock to ImClone and Elan/Athena in October
1997.

(4) Adjusted to reflect the sale of 2,250,000 shares of Common Stock offered
hereby, assuming a public offering price of $12.00 per share (the mid-point
of the range set forth on the front cover) less estimated underwriting
discounts and commissions and other expenses of this offering, resulting in
net proceeds to the Company of $24.4 million. See "Use of Proceeds."

Except as otherwise indicated herein, all information contained in this
Prospectus (i) gives effect to a one-for-four reverse split of the Common Stock,
(ii) reflects the conversion of all outstanding shares of Preferred Stock into
an aggregate of 7,754,933 shares of Common Stock, effective upon the closing of
this offering, and (iii) assumes no exercise of the Underwriters' over-allotment
option.

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RISK FACTORS

In addition to the other information in this Prospectus, the following risk
factors should be considered carefully in evaluating the Company and its
business before purchasing shares of the Common Stock offered hereby. The
Prospectus may contain forward-looking statements which involve risks and
uncertainties. The Company's actual results could differ materially from those
anticipated in these forward-looking statements as a result of certain factors,
including those set forth in the following risk factors and elsewhere in this
Prospectus.

NEW AND UNCERTAIN TECHNOLOGY AND BUSINESS

The Company's Discovery Engine process is novel and has not yet been shown
to be successful in the discovery of lead candidates that have been subsequently
developed into commercialized drugs. Furthermore, the Company's drug discovery
efforts are focused on some targets the functions of which are not yet known.
Development of new pharmaceutical products is highly uncertain, and no assurance
can be given that the Company's drug discovery process will result in lead
candidates that will be safe or efficacious or commercially successful as
products. Failure to validate the Company's technology through the successful
discovery of lead candidates would have a material adverse effect on the
Company's business, financial condition and results of operations.

The Company's strategy, which is unproven, is to use its proprietary design
technology for the purpose of rapidly identifying, optimizing and obtaining
proprietary rights to as many lead candidates and development candidates as
possible. The Company's ability to achieve profitability in the near term
depends entirely on its ability to enter into additional collaborative
agreements with third parties and to maintain the agreements it currently has in
place. The pricing and nature of the Company's collaborative relationships is
such that there may only be a limited number of pharmaceutical, biotechnology
and agrochemical companies that will be its potential customers. The Company's
ability to succeed is also dependent upon the acceptance by potential customers
of its Discovery Engine process as an effective tool in new drug discovery.
Historically, pharmaceutical, biotechnology and agrochemical companies have
conducted lead candidate identification and optimization within their own
research departments, due to the highly proprietary nature of the activities
being conducted, the central importance of these activities to their drug
discovery and development efforts and the desire to obtain maximum patent and
other proprietary protection on the results of their internal programs. In order
to achieve its business objectives, the Company must convince these companies
that its technology and capabilities justify the outsourcing of their programs
to the Company. There can be no assurance that the Company will be able to
attract any future customers on acceptable terms for its products and services
or develop a sustainable, profitable business. Failure to do so will have a
material adverse effect on the Company's business, financial condition and
results of operations. See "Business."

LIMITED OPERATING HISTORY; HISTORY OF OPERATING LOSSES; UNCERTAINTY OF FUTURE
PROFITABILITY

The Company has had a limited operating history. For the period from May
23, 1994 (inception) to December 31, 1994, and for the years ended December 31,
1995 and 1996, and the nine months ended September 30, 1997, the Company had net
losses of approximately $0.7 million, $6.7 million, $5.1 million and $3.7
million, respectively. As of September 30, 1997, the Company had an accumulated
deficit of approximately $16.2 million. The Company's expansion of its
operations and enhancements to its Discovery Engine and related drug discovery
technology will result in significant expenses over the next several years that
may not be offset by significant revenue. The Company's ability to achieve
profitability in the near term depends entirely on its ability to enter into
additional collaborative agreements with third parties and to maintain the
agreements it currently has in place. To date, substantially all revenue
received by the Company has been from upfront fees and research and development
funding paid pursuant to existing collaborative agreements with third parties.
The Company has not yet received any revenue from the achievement of milestones
or license fees from the discovery, development or sale of a commercial drug by
a customer, and no such revenue is expected for at least several years, if at
all. An element of the Company's commercialization strategy is

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the potential development and licensing to others of lead compounds or drug
development candidates identified by the Company through its internal programs,
at its own expense, for potential pharmaceutical development. To date, no such
license has been entered into, and there can be no assurance that any such
license will be entered into on acceptable terms in the future, if at all. The
Company is unable to predict when, or if, it will become profitable. See
"Selected Financial Data" and "Management's Discussion and Analysis of Financial
Condition and Results of Operations."

DEPENDENCE OF COMPANY'S STRATEGY ON THIRD PARTIES

The Company's strategy depends upon the formation of multiple collaborative
arrangements with third parties on a regular basis. To date, the Company has
entered into five such arrangements, and substantially all of its revenue has
been from its collaborative arrangements. There can be no assurance that the
Company will be able to continue to establish additional collaborative
arrangements, that any such arrangements will be on terms favorable to the
Company, or that current or any future collaborative arrangements will
ultimately be successful. Failure to enter into additional collaborative
agreements on favorable terms would have a material adverse effect on the
Company's business, financial condition and results of operations. Further,
CombiChem's receipt of revenue from collaborative arrangements is affected by
the timing of efforts expended by the Company and its collaborators and the
timing of lead compound identification by the Company. The Company's products
and services will only result in commercialized pharmaceutical products
generating milestone payments and royalties upon the successful outcome of
significant preclinical and clinical development, the procurement of requisite
regulatory approvals, the establishment of manufacturing, sales and marketing
capabilities and the achievement of successful marketing. The Company does not
currently intend to perform any of these activities. Therefore, the Company will
be dependent upon the expertise and dedication of sufficient resources by third
parties to develop and commercialize products based on library compounds
produced and lead compounds discovered or optimized by the Company. In addition,
there can be no assurance that any such development or commercialization efforts
by third parties would be successful. Should a collaborative partner fail to
develop or commercialize a compound or product to which it has rights from the
Company, the Company may not receive any future milestone payments and will not
receive any royalties associated with such compound or product. In addition, the
Company's collaborative arrangements with its partners do not obligate the
partners to develop or commercialize lead compounds discovered or optimized by
the Company. Each collaborative partner may independently move forward with a
competing lead candidate developed either by such partner internally or by one
of such partners, including the Company's competitors. The potential drugs
developed by a collaborative partner may be derivative of the lead compounds
provided to the customer by the Company. While the Company's existing
collaborative agreements provide that the Company retain milestone and royalty
payment rights with respect to drugs developed from certain derivative
compounds, there can be no assurance that disputes will not arise over the
application of payment provisions to such drugs. There can be no assurance that
current or future collaborative partners, if any, will not pursue alternative
technologies or develop alternative products either on their own or in
collaboration with others, including the Company's competitors, as a means for
developing treatments for the diseases targeted by collaborative arrangements
with the Company. Furthermore, there can be no assurance that conflicts will not
arise between collaborative partners as to proprietary rights to particular
compounds. The amount and timing of resources that current and future
collaborators, if any, devote to collaborations with the Company are not within
the control of the Company. There can be no assurance that such collaborators
will perform their obligations as expected. Further, the Company's
collaborations generally may be terminated by its collaborators upon short
notice and following an uncured material breach, which terminations would result
in a loss of anticipated revenue. Termination of the Company's existing or
future collaborative agreements, if any, could have a material adverse effect on
the Company's business, financial condition and results of operations.

The Company's strategy also involves conducting its own internally funded
discovery programs by choosing biological targets of current scientific interest
and working in collaboration with screening

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<PAGE> 9

companies. There can be no assurance that the Company would continue to have
access to such targets, novel or otherwise, on an ongoing basis. Furthermore,
despite the Company's installation of independent teams to conduct each
collaborative project, there can be no assurance that conflicts will not arise
among collaborators as to the rights to overlapping lead candidate compounds
developed independently as a result of being identified through the use of the
Company's technologies. Failure to manage multiple existing and future
collaborator relationships successfully, maintain confidentiality among such
relationships or prevent the occurrence of such conflicts could lead to disputes
that result in, among other things, a significant strain on management
resources, legal claims involving significant time and expense and loss of
reputation, a loss of capital or a loss of current or future collaborators, any
of which could have a material adverse effect on the Company's business,
financial condition and results of operations. See "Business -- Strategy" and
"Business -- CombiChem's Collaborative Arrangements."

SIGNIFICANT FLUCTUATIONS IN QUARTERLY RESULTS

To date, all revenue received by the Company has been from the payment of
upfront fees and research and development funding paid pursuant to collaborative
agreements. The Company expects that a significant portion of its revenue for
the foreseeable future will be comprised of such payments. The timing of certain
revenue in the future will depend upon the completion of certain milestones as
provided for in the Company's collaborative agreements. In any one fiscal
quarter the Company may receive multiple or no payments from its several
collaborators. Operating results may therefore vary substantially from quarter
to quarter and will not necessarily be indicative of results in subsequent
periods. There can be no assurance that such quarterly fluctuations in revenue
or financial results will not have a material impact on the Company's stock
price.

COMPANY'S SUCCESS DEPENDENT ON INTELLECTUAL PROPERTY RIGHTS

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United States or overseas, or to obtain the appropriate licenses, would have a
material adverse effect on the Company's business, financial condition and
operations. Moreover, there can be no assurance that the Company or its
customers will be able to obtain patent protection for lead compounds or
pharmaceutical products based upon the Company's or such customers'
technologies. There can be no assurance that any patents issued to the Company
or its collaborative partners, or for which the Company has license rights, will
not be challenged, invalidated or circumvented, or that the rights granted
thereunder will provide competitive advantages to the Company. To the extent
that the Company or its consultants or collaborators use intellectual property
owned by others in their work for the Company, disputes may also arise as to the
rights in related or resulting know-how and inventions. Litigation may be
necessary to enforce the Company's patent and license rights or to determine the
scope and validity of others' proprietary rights. Any such litigation whether or
not the outcome thereof is favorable to the Company, could result in substantial
cost to and diversion of effort by the Company. Further, United States patents
do not provide any remedies for infringement that occurred before the patent is
issued. The commercial success of the Company will also depend upon successfully
avoiding the infringement of current and future patents issued to competitors
and upon maintaining the technology licenses upon which certain of the Company's
current products are, or any future products under development might be, based.
If competitors of the Company prepare and file patent applications in the United
States that claim inventions also claimed by the Company or its collaborators,
the Company or its collaborators may have to participate in interference
proceedings declared by the United States Patent and Trademark Office ("PTO") to
determine the priority of invention, which could result in substantial cost to
the Company, even if the outcome is favorable to the Company. An adverse outcome
could subject the Company to significant liabilities to third parties and
require the Company to license disputed rights from third parties or cease using
the technology.

A United States patent application is maintained under conditions of
confidentiality while the application is pending in the PTO, so that the Company
cannot determine the inventions being claimed in pending patent applications
filed by its competitors in the PTO. A number of pharmaceutical and
biotechnology companies and research and academic institutions have developed
technologies, filed patent applications or received patents on various
technologies that may be related to the Company's business. Some of these
technologies, applications or patents may conflict with the Company's
technologies or patent applications. Such conflict could limit the scope of the
patents, if any, that the Company may be able to obtain, or result in the denial
of the Company's patent applications. In addition, there can be no assurance
that the Company would be able to obtain licenses to patents held by third
parties that may cover the Company's activities at a reasonable cost, if at all,
or that the Company would be able to develop or obtain any alternative
technologies. The Company currently has certain licenses from third parties and
in the future may require additional licenses from other parties in order to
refine its Discovery Engine further and to allow its collaborators to develop,
manufacture and market commercially viable products effectively. There can be no
assurance that (i) such licenses will be obtainable on commercially reasonable
terms, if at all; (ii) any patents underlying such licenses will be valid and
enforceable; or (iii) the proprietary nature of any patented technology
underlying such licenses will remain proprietary. The Company relies
substantially on certain technologies that are not patentable or proprietary and
are therefore available to the Company's competitors. The Company also relies on
certain proprietary trade secrets and know-how that are not patentable. Although
the Company has taken steps to protect its unpatented trade secrets and
know-how, in part through the use of confidentiality agreements with its
employees, consultants and certain of its contractors, there can be no assurance
that (i) these agreements will not be breached, (ii) the Company would have
adequate remedies for any breach, or (iii) the Company's trade secrets will not
otherwise become known or be independently developed or discovered by
competitors. Failure by the Company to protect all or part of its patents, trade
secrets and know-how could have a material adverse effect on the Company's
business, financial condition and results of operations. See
"Business -- Patents and Proprietary Information."

9
<PAGE> 11

COMPETITIVE NATURE OF COMPANY'S INDUSTRY AND RISKS OF OBSOLESCENCE OF TECHNOLOGY

Many organizations are actively attempting to identify, optimize and
generate lead compounds for potential pharmaceutical development. The Company
competes with the research departments of pharmaceutical companies,
biotechnology companies, combinatorial chemistry companies and research and
academic institutions as well as other computationally based drug discovery
companies. Many of these competitors have greater financial and human resources
and more experience in research and development than the Company. Historically,
large pharmaceutical companies have maintained close control over their research
activities, including the synthesis, screening and optimization of chemical
compounds. Many of these companies, which represent one of the largest potential
markets for CombiChem's products and services, are internally developing
combinatorial and computational approaches and other methodologies to improve
productivity, including major investments in robotics technology to permit the
automated parallel synthesis of compounds. In addition, these companies may
already have large collections of compounds previously synthesized or ordered
from chemical supply catalogs or other sources against which they may screen new
targets. Other sources of compounds include compounds extracted from natural
products, such as plants and microorganisms, and compounds created using
rational drug design. Academic institutions, governmental agencies and other
research organizations are also conducting research in areas in which the
Company is working, either on their own or through collaborative efforts. The
Company anticipates that it will face increased competition in the future as new
companies enter the market and advanced technologies become available. The
Company's processes may be rendered obsolete or uneconomical by technological
advances or entirely different approaches developed by one or more of the
Company's competitors. The existing approaches of the Company's competitors or
new approaches or technology developed by the Company's competitors may be more
effective than those developed by the Company. See "Business -- Competition."

SUCCESS OF COMPANY DEPENDENT ON SCALE-UP AND MANAGEMENT OF GROWTH

The Company's success will depend on the expansion of its operations to
service additional collaborative arrangements and the management of these
expanded operations. To be cost-effective in its delivery of services and
products, the Company must enhance productivity through further automation of
its processes and improvements to its technology generally. In addition, the
Company must successfully structure and manage multiple additional collaborative
relationships, including maintaining the confidentiality of the research being
provided to multiple customers. There can be no assurance that the Company will
be successful in adding technical personnel as needed to meet the staffing
requirements of any additional collaborative relationship. In addition, there
can be no assurance that the Company will be successful in its engineering
efforts to automate its processes further or in its initiatives to improve its
technology. Failure to achieve any of these goals could have a material adverse
effect on the Company's business, financial condition or results of operations.
See "Business -- CombiChem's Collaborative Arrangements" and
"Business -- Employees."

DEPENDENCE OF COMPANY ON KEY EMPLOYEES

The Company is highly dependent on the principal members of its scientific
and management staff. The loss of one or more key members of the Company's
scientific or management staff could have a material adverse effect on the
Company's business, financial condition and results of operations. The Company's
future success will also depend in part on the continued service of its key
design engineering, scientific, software and management personnel and on its
ability to identify, hire and retain any additional personnel. There is intense
competition for such qualified personnel in the areas of the Company's
activities, and there can be no assurance that the Company will be able to
continue to attract and retain such personnel necessary for the development of
the Company's business. Failure to attract and retain key personnel could have a
material adverse effect on the Company's business, financial condition and
results of operations. See "Business -- Employees" and "Management."

10
<PAGE> 12

GOVERNMENT REGULATION

Regulation by governmental entities in the United States and other
countries will be a significant factor in the production and marketing of any
pharmaceutical products that may be developed by a customer or collaborator of
the Company or, in the event the Company decides to develop a drug beyond the
preclinical phase, by the Company. The nature and the extent to which such
regulation may apply to the Company's customers will vary depending on the
nature of any such pharmaceutical products. Virtually all pharmaceutical
products developed by the Company's customers will require regulatory approval
by governmental agencies prior to commercialization. In particular, human
pharmaceutical therapeutic products are subject to rigorous preclinical and
clinical testing and other approval procedures established by the United States
Food and Drug Administration (the "FDA") and by foreign regulatory authorities.
Various federal and, in some cases, state statutes and regulations also govern
or influence, among other things, the testing, manufacture, safety, efficacy,
labeling, storage, record keeping, approval, advertising and promotion of such
products. Non-compliance with applicable requirements can result in fines,
warning letters, recall or seizure of products, clinical study holds or delays,
total or partial suspension of production, refusal of the government to grant
approvals, and civil and criminal penalties. The process of obtaining these
approvals and the subsequent compliance with appropriate federal and foreign
statutes and regulations are time-consuming and require the expenditure of
substantial resources. Generally, in order to gain FDA approval, a company first
must conduct preclinical studies in the laboratory and in animal models to gain
preliminary information on a compound's efficacy and to identify any safety
problems. Preclinical studies must be conducted by laboratories that comply with
FDA regulations regarding Good Laboratory Practices. The results of these
studies are submitted as a part of an Investigational New Drug application (an
"IND") that the FDA must review before human clinical trials of an
investigational drug can begin. In order to commercialize any products, the
Company or its customer will be required to sponsor and file an IND and will be
responsible for initiating and overseeing the clinical studies to demonstrate
the safety and efficacy that are necessary to obtain FDA and foreign regulatory
authority approval of any such products. Clinical trials are normally done in
three phases and generally take two to five years but may take longer to
complete. After completion of clinical trials of a new product, FDA and foreign
regulatory authority marketing approval must be obtained. If the product is
classified as a new drug, the Company or its customer will be required to file a
New Drug Application (an "NDA") and receive approval before commercial marketing
of the drug. The testing and approval processes require substantial time and
effort, and there can be no assurance that any approval will be granted on a
timely basis, if at all. NDAs submitted to the FDA can take, on average, two to
five years to obtain approval. If questions arise during the FDA review process,
approval can take more than five years. Even if FDA regulatory clearances are
obtained, a marketed product is still subject to continual review, and later
discovery of previously unknown problems or failure to comply with the
applicable regulatory requirements may result in restrictions on the marketing
of a product or withdrawal of the product from the market, as well as possible
civil or criminal sanctions. Domestic manufacturing facilities of the Company or
its customers are subject to biannual inspections by the FDA and must comply
with the FDA's current Good Manufacturing Practices regulations. To comply with
such regulations, a manufacturer must spend funds, time and effort in the areas
of production and quality control to ensure full technical compliance. The FDA
stringently applies regulatory standards for manufacturing. For marketing
outside the United States, the Company or its customer will also be subject to
foreign regulatory requirements governing human clinical trials and marketing
approval for pharmaceutical products. The requirements governing the conduct of
clinical trials, product licensing, pricing and reimbursement vary widely from
country to country.

FUTURE CAPITAL NEEDS; UNCERTAINTY OF ADDITIONAL FUNDING

11
<PAGE> 13

required to raise additional capital over a period of several years in order to
continue to conduct its operations. Such capital may be raised through
additional public or private financings, as well as collaborative arrangements,
borrowings and other available sources. There can be no assurance that the
Company's collaborative arrangements will produce revenue adequate to fund the
Company's operating expenses. The Company's capital requirements depend on
numerous factors, including the ability of the Company to enter into additional
collaborative arrangements, competing technological and market developments,
changes in the Company's existing collaborative relationships, the cost of
filing, prosecuting, defending and enforcing patent claims and other
intellectual property rights, the purchase of additional capital equipment, the
progress of the Company's drug discovery programs and the progress of the
commercialization of milestone- and royalty-bearing compounds by the Company's
customers. The Company does not currently plan independently to develop,
manufacture or market any drugs it discovers. To the extent that additional
capital is needed, it may be raised through the sale of equity or convertible
debt securities, and the issuance of such securities could result in dilution to
the Company's existing stockholders. There can be no assurance that additional
funding, if necessary, will be available on favorable terms, if at all. If
adequate funds are not available, the Company may be required to curtail
operations significantly or to obtain funds through entering into arrangements
with collaborative partners or others that may require the Company to relinquish
rights to certain of its technologies, product candidates, products or potential
markets that the Company would not otherwise relinquish. The failure to receive
additional funding would have a material adverse effect on the Company's
business, financial condition and results of operations. See "Management's
Discussion and Analysis of Financial Condition and Results of Operations."

UNCERTAINTY OF PHARMACEUTICAL PRICING AND HEALTH CARE REFORM

The Company expects that substantially all of its revenue in the
foreseeable future will be derived from products and services provided to the
pharmaceutical and biotechnology industries. Accordingly, the Company's success
in the foreseeable future is directly dependent upon the success of the
companies within those industries and their continued demand for the Company's
products and services. The level of revenue and profitability of pharmaceutical
companies may be affected by the continuing efforts of governmental and
third-party payors to contain or reduce the costs of health care through various
means and the initiatives of third-party payors with respect to the availability
of reimbursement. For example, in certain foreign markets, pricing or
profitability of prescription pharmaceuticals is subject to governmental
control. In the United States, there have been, and the Company expects that
there will continue to be, a number of federal and state proposals to implement
similar governmental control. It is uncertain what legislative proposals may be
adopted or what actions federal, state or private payors for health care goods
and services may take in response to any health care reform proposals or
legislation. To the extent that such proposals or reforms have a material
adverse effect on the business, financial condition and profitability of
pharmaceutical and biotechnology companies that are actual or prospective
collaborators for certain of the Company's products and services, the Company's
business, financial condition and results of operations may be adversely
affected.

COMPANY'S USE OF HAZARDOUS MATERIALS

The research and development processes of the Company involve the
controlled use of hazardous materials. The Company is subject to federal, state
and local laws and regulations governing the use, manufacture, storage, handling
and disposal of such materials and certain waste products. Although the Company
believes that its activities currently comply with the standards prescribed by
such laws and regulations, the risk of accidental contamination or injury from
these materials cannot be completely eliminated. In the event of such an
accident, the Company could be held liable for any damages that result, and any
such liability could exceed the resources of the Company. In addition, there can
be no assurance that the Company will not be required to incur significant costs
to comply with environmental laws and regulations in the future. The occurrence
of any such event could have a material adverse effect on the Company's
business, financial condition and results of operations.

12
<PAGE> 14

SHARES ELIGIBLE FOR FUTURE SALE

Future sales of Common Stock in the public market following this offering
could adversely affect the market price of the Common Stock. Based on the number
of shares outstanding as of September 30, 1997 (after giving effect to the
issuance of an aggregate of 1,250,000 shares to collaborative partners in
October 1997), upon completion of this offering, the Company will have
13,168,505 shares of Common Stock outstanding, assuming no exercise of currently
outstanding options. Of these shares, the 2,250,000 shares sold in this offering
(plus any additional shares sold upon exercise of the Underwriters'
overallotment option) will be freely transferable without restriction under the
Securities Act of 1933, as amended (the "Securities Act"), unless they are held
by "affiliates" of the Company as that term is used under the Securities Act and
the regulations promulgated thereunder. Each holder who signed a lock-up
agreement has agreed, subject to certain limited exceptions, not to sell or
otherwise dispose of any of the shares held by them as of the date of this
Prospectus for a period of 180 days after the date of this Prospectus without
the prior written consent of BancAmerica Robertson Stephens. At the end of such
180-day period, approximately 11,502,437 shares of Common Stock (including
approximately 52,657 shares issuable upon exercise of vested options) will be
eligible for immediate resale, subject to compliance with Rule 144 and Rule 701.
The remainder of the approximately 1,666,068 shares of Common Stock outstanding
or issuable upon exercise of options held by existing stockholders or option
holders will become eligible for sale at various times over a period of less
than two years and could be sold earlier if the holders exercise any available
registration rights or upon vesting pursuant to the Company's standard four year
vesting schedule. The holders of 7,754,933 shares of Common Stock have the right
in certain circumstances to require the Company to register their shares under
the Securities Act for resale to the public. If such holders, by exercising
their demand registration rights, cause a large number of shares to be
registered and sold in the public market, such sales could have an adverse
effect on the market price for the Company's Common Stock. If the Company were
required to include in a Company-initiated registration shares held by such
holders pursuant to the exercise of their piggyback registration rights, such
sales may have an adverse effect on the Company's ability to raise needed
capital. In addition, the Company expects to file immediately upon the effective
date of this registration statement, a registration statement on Form S-8
registering a total of approximately 1,925,606 shares of Common Stock including
those outstanding shares which may be repurchased by the Company and shares
issuable upon exercise of outstanding stock options or reserved for issuance
under the Company's stock incentive plan and employee stock purchase plan. See
"Management -- Benefit Plans," "Description of Capital Stock -- Registration
Rights," "Shares Eligible for Future Sale" and "Underwriting."

CONTROL BY MANAGEMENT AND EXISTING STOCKHOLDERS

Upon completion of this offering, the Company's executive officers,
directors and affiliated entities together will beneficially own approximately
30.1% of the outstanding shares of Common Stock (29.4% if the Underwriters'
overallotment option is exercised in full). As a result, these stockholders will
be able to exercise control over matters requiring stockholder approval,
including the election of directors and mergers, consolidations and sales of all
or substantially all of the assets of the Company. This may prevent or
discourage tender offers for Common Stock unless the terms are approved by such
stockholders. See "Principal Stockholders."

NO PRIOR PUBLIC MARKET FOR COMMON STOCK; POSSIBLE VOLATILITY OF STOCK PRICE

Prior to this offering, there has been no public market for the Common
Stock, and there can be no assurance that an active public market for the Common
Stock will develop or be sustained after the offering. The initial offering
price will be determined by negotiations between the Company and the
Underwriters and is not necessarily indicative of the market price at which the
Common Stock of the Company will trade after this offering. The market prices
for securities of life sciences companies have been highly volatile, and the
market has experienced significant price and volume fluctuations that are
unrelated to the operating performance of particular companies. Announcements of
technological

13
<PAGE> 15

innovations or new commercial products by the Company or its competitors,
developments concerning proprietary rights, including patents and litigation
matters, publicity regarding actual or potential results with respect to
products or compounds under development by the Company or its strategic
partners, regulatory developments in both the United States and foreign
countries, public concern as to the efficacy of new technologies, general market
conditions, as well as quarterly fluctuations in the Company's revenue and
financial results among other factors, may have a significant impact on the
market price of the Common Stock. In particular, the realization of any of the
risks described in these "Risk Factors" could have a dramatic and adverse impact
on such market price. See "Underwriting."

ANTI-TAKEOVER EFFECT OF CERTAIN CHARTER AND BY-LAW PROVISIONS AND DELAWARE LAW

The Company's Amended and Restated Certificate of Incorporation (the
"Certificate of Incorporation") authorizes the Board of Directors to issue,
without stockholder approval, 5,000,000 shares of Preferred Stock with voting,
conversion and other rights and preferences that could adversely affect the
voting power or other rights of the holders of Common Stock. Although the
Company has no current plans to issue any shares of Preferred Stock, the
issuance of Preferred Stock or of rights to purchase Preferred Stock could be
used to discourage an unsolicited acquisition proposal. In addition, the
possible issuance of Preferred Stock could discourage a proxy contest, make more
difficult the acquisition of a substantial block of the Company's Common Stock
or limit the price that investors might be willing to pay in the future for
shares of the Company's Common Stock. The Company's Certificate of Incorporation
provides for staggered terms for the members of the Board of Directors. A
staggered Board of Directors and certain provisions of the Company's by-laws and
of Delaware law applicable to the Company could delay or make more difficult a
merger, tender offer or proxy contest involving the Company. Further, the
Company's stock option plans generally provide for the acceleration of vesting
of options granted under such plans in the event of certain transactions which
result in a change of control of the Company. In addition, the Company is
subject to Section 203 of the General Corporate Law of Delaware which, subject
to certain exceptions, restricts certain transactions and business combinations
between a corporation and a stockholder owning 15% or more of the corporation's
outstanding voting stock (an "interested stockholder") for a period of three
years from the date the stockholder becomes an interested stockholder. These
provisions may have the effect of delaying or preventing a change of control of
the Company without action by the stockholders and, therefore, could adversely
affect the price of the Company's Common Stock. See "Management," "Description
of Capital Stock -- Preferred Stock" and "Description of Capital
Stock -- Possible Anti-Takeover Effect of Certain Charter Provisions -- Delaware
Anti-Takeover Statute."

BROAD MANAGEMENT DISCRETION IN USE OF PROCEEDS

The Company's management will have broad discretion to allocate proceeds of
this offering to uses that it believes are appropriate. There can be no
assurance that the proceeds of this offering can or will be invested to yield a
positive return. See "Use of Proceeds."

RISK OF IMMEDIATE AND SUBSTANTIAL DILUTION

Purchasers of the shares of Common Stock offered hereby will experience
immediate and substantial dilution estimated at $8.73 per share in the net
tangible book value of their investment from the initial offering price.
Additional dilution will occur upon exercise of outstanding options. See
"Dilution" and "Shares Eligible for Future Sale."

14
<PAGE> 16

USE OF PROCEEDS

The net proceeds to the Company from the sale of the 2,250,000 shares of
Common Stock offered hereby are estimated to be approximately $24.4 million
($28.2 million if the Underwriters' over-allotment option is exercised in full),
assuming a public offering price of $12.00 per share (the mid-point of the range
set forth on the front cover) and after deducting the estimated underwriting
discounts and commissions and other estimated offering expenses.

The principal purposes of this offering are to increase the Company's
equity capital and to create a public market for the Company's Common Stock in
order to facilitate future access by the Company to public equity markets as
well as to create liquidity for its existing stockholders. The Company intends
to use the net proceeds of this offering, together with its existing cash and
cash equivalents and short-term investments, to fund research and development
(approximately $10.0 million), expansion of laboratory and office facilities
(approximately $5.0 million), working capital (approximately $2.0 million) and
the remainder for general corporate purposes. The Company may also use a portion
of the net proceeds for the acquisition of businesses, technologies or products
complementary to those of the Company. There are no present arrangements or
agreements for any such acquisitions.

The amounts actually expended for each purpose may vary significantly
depending upon numerous factors, including the amount and timing of additional
collaborative agreements, the progress of the Company's development,
technological advances, the commercial potential of the Company's services and
the status of the Company's competitors. The Company believes that its existing
cash, cash equivalents and short-term investments, combined with the net
proceeds of this offering, projected funding from equipment leases and interest
income will be adequate to satisfy its capital requirements and fund operations
at least through 1998. Pending application of the net proceeds as described
above, the Company intends to invest the net proceeds of this offering in
short-term investment-grade securities.

DIVIDEND POLICY

The Company has never declared or paid dividends on its capital stock. The
Company does not anticipate paying any cash dividends in the foreseeable future.
Payments of future dividends, if any, will be at the discretion of the Company's
Board of Directors after taking into account various factors, including the
Company's financial condition, operating results, current and anticipated cash
needs and plans for expansion. See "Management's Discussion and Analysis of
Financial Condition and Results of Operations -- Liquidity and Capital
Resources."

15
<PAGE> 17

CAPITALIZATION

The following table sets forth as of September 30, 1997 (i) the actual
capitalization of the Company, (ii) the pro forma capitalization of the Company,
after giving effect to the receipt of up-front payments and the sale of Common
Stock to ImClone and Elan/Athena in October 1997 and the conversion of all
outstanding shares of Preferred Stock into Common Stock effective upon the
closing of this offering, and (iii) pro forma as adjusted to give effect to the
sale by the Company of 2,250,000 shares of Common Stock offered hereby, assuming
a public offering price of $12.00 per share (the mid-point of the range set
forth on the front cover) less estimated underwriting discounts and commissions
and other expenses of this offering.

<TABLE>
<CAPTION>
SEPTEMBER 30, 1997
--------------------------------------------
PRO FORMA
AS
ACTUAL PRO FORMA(2) ADJUSTED(2)(3)
-------- ------------ --------------
(in thousands)
<S> <C> <C> <C>
Cash and cash equivalents............................ $ 4,287 $ 16,120 $ 40,530
Short-term investments............................... 4,115 4,115 4,115
======== ======== ========
Long-term obligations, less current portion.......... $ 2,377 $ 2,377 $ 2,377
Redeemable convertible preferred stock:
Preferred Stock, $0.001 par value; 63,196,296
shares authorized and 7,754,933 shares issued
and outstanding actual; 5,000,000 shares
authorized and no shares issued and outstanding
pro forma and pro forma as adjusted............. 23,130 -- --
Stockholders' equity (deficit):......................
Common Stock, $0.001 par value; 80,000,000 shares
authorized actual; 1,913,572 shares issued and
outstanding actual; 40,000,000 shares authorized
pro forma and pro forma as adjusted; 10,918,505
shares issued and outstanding pro forma; and
13,168,505 shares issued and outstanding pro
forma as adjusted(1)............................ 2 11 13
Additional paid-in capital......................... 2,349 35,470 59,878
Notes receivable from stockholders................. (336) (336) (336)
Deferred compensation.............................. (1,699) (1,699) (1,699)
Accumulated deficit................................ (16,168) (14,835) (14,835)
-------- -------- --------
Total stockholders' equity (deficit)............ (15,852) 18,611 43,021
-------- -------- --------
Total capitalization....................... $ 9,655 $ 20,988 $ 45,398
======== ======== ========
</TABLE>

- ---------------

(1) Includes 901,658 shares of Common Stock which are currently subject to
repurchase by the Company. Excludes: (i) 441,696 shares of Common Stock
issuable upon the exercise of stock options outstanding as of September 30,
1997, with a weighted average exercise price of $2.81 per share, all of
which are exercisable and 26,177 of which are vested; and (ii) 139,478
shares of Common Stock issuable upon the exercise of outstanding warrants,
with a weighted average exercise price of $2.27 per share.

(2) Gives effect to (i) the conversion of the Preferred Stock into Common Stock
effective upon the closing of this offering; and (ii) the receipt of $11.833
million for up-front payments and the proceeds from the sale of an aggregate
of 1,250,000 shares of Common Stock to ImClone and Elan/Athena in October
1997.

(3) Adjusted to reflect the sale of 2,250,000 shares of Common Stock offered
hereby, assuming a public offering price of $12.00 per share (the mid-point
of the range set forth on the front cover) less estimated underwriting
discounts and commissions and other expenses of this offering, resulting in
net proceeds to the Company of $24.4 million. See "Use of Proceeds."

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<PAGE> 18

DILUTION

The pro forma net tangible book value of the Company at September 30, 1997
was $18,611,000 or $1.71 per share of Common Stock. Pro forma net tangible book
value per share of Common Stock represents the amount of total tangible assets
of the Company less total liabilities divided by the number of shares of the
Common Stock outstanding after giving effect to the conversion of all
outstanding shares of Preferred Stock into 7,754,933 shares of Common Stock upon
the completion of this offering and the sale of an aggregate of 1,250,000 shares
of Common Stock to ImClone and Elan/Athena in October 1997. After giving effect
to the sale of the 2,250,000 shares of Common Stock offered hereby assuming a
public offering price of $12.00 per share, the mid-point of the range set forth
on the front cover, less estimated underwriting discounts and commissions and
other expenses of this offering, the Company's net tangible book value as of
September 30, 1997 would have been $43,021,000 or $3.27 per share of Common
Stock. This represents an immediate increase in pro forma net tangible book
value per share of Common Stock of $1.56 to existing stockholders and immediate
dilution in pro forma net tangible book value of $8.73 per share to new
investors purchasing Common Stock in this offering. The following table
illustrates the per share dilution:

<TABLE>
<S> <C> <C>
Assumed initial public offering price............................... $12.00
Pro forma net tangible book value of Common Stock as of
September 30, 1997........................................... $1.71
Increase attributable to new investors......................... 1.56
Pro forma net tangible book value of Common Stock after this
offering.......................................................... 3.27
------
Dilution to new investors(1)........................................ $ 8.73
======
</TABLE>

- ---------------

(1) If the Underwriters' over-allotment option is exercised in full, dilution
per share to new investors would be $8.54.

The following table summarizes, on a pro forma basis as of September 30,
1997 (after giving effect to the sale of 1,250,000 shares of Common Stock to
collaborative partners in October 1997), the number of shares of Common Stock
purchased from the Company, the total consideration paid (based on value
received by the Company at the time of issuance) and the average price per share
paid by the existing stockholders and by new investors purchasing shares in this
offering (before deduction of estimated underwriting discounts and commissions
and other expenses of this offering):

<TABLE>
<CAPTION>
SHARES PURCHASED TOTAL CONSIDERATION AVERAGE
---------------------- ----------------------- PRICE PER
NUMBER PERCENT AMOUNT PERCENT SHARE
----------- ------- ----------- ------- ---------
<S> <C> <C> <C> <C> <C>
Existing stockholders....... 10,918,505 82.9% $33,833,859 55.6% $ 3.10
New investors............... 2,250,000 17.1 27,000,000 44.4 12.00
------------ ---- ---------- ----
Total..................... 13,168,505 100.0% $60,833,859 100.0%
============ ==== ========== ====
</TABLE>

All of the above computations assume no exercise of outstanding options or
warrants to purchase Common Stock. The shares purchased and total consideration
paid by existing shareholders reflects the proceeds from the sale of 1,250,000
shares of Common Stock to ImClone and Elan/Athena, and does not include costs
incurred by the Company to issue Common and Preferred Stock. As of September 30,
1997, options to purchase 441,696 shares of Common Stock were outstanding at a
weighted average exercise price of approximately $2.81 per share under the
Company's stock option plan and warrants to purchase 139,478 shares of Common
Stock were outstanding at a weighted average exercise price of approximately
$2.27 per share. To the extent these options become vested and are exercised, or
the warrants are exercised, there will be further dilution to new investors.

17
<PAGE> 19

SELECTED FINANCIAL DATA

The selected financial data set forth below with respect to the Company's
statements of operations for the period from May 23, 1994 (inception) to
December 31, 1994, the years ended December 31, 1995 and 1996 and the nine
months ended September 30, 1997, and with respect to the Company's balance
sheets at December 31, 1995 and 1996 and September 30, 1997, are derived from
the financial statements of the Company that have been audited by Ernst & Young
LLP, which are included elsewhere herein and are qualified by reference to such
financial statements. The balance sheet data at December 31, 1994 has been
derived from the financial statements audited by Ernst & Young LLP, which are
not included herein. The unaudited statement of operations data for the nine
months ended September 30, 1996 have been derived from unaudited financial
statements also appearing herein which in the opinion of management include all
adjustments, consisting only of normal recurring adjustments, necessary for a
fair statement of the financial position and results of operations for the
unaudited interim periods. The selected financial data set forth below should be
read in conjunction with "Management's Discussion and Analysis of Financial
Condition and Results of Operations" and the Company's financial statements and
notes thereto appearing elsewhere in this Prospectus.

<TABLE>
<CAPTION>
PERIOD FROM
MAY 23, 1994 YEAR ENDED NINE MONTHS ENDED
(INCEPTION) TO DECEMBER 31, SEPTEMBER 30,
DECEMBER 31, ------------------- -------------------
1994 1995 1996 1996 1997
-------------- ------- ------- ------- -------
(in thousands, except per share data)
<S> <C> <C> <C> <C> <C>
STATEMENT OF OPERATIONS DATA:
Total Revenue...................... $ -- $ 50 $ 2,967 $ 1,070 $ 4,599
Expenses:
Research and development:
Collaborative................. -- -- 420 263 2,631
Proprietary................... 413 4,763 4,820 3,547 3,354
------ -------- -------- -------- --------
413 4,763 5,240 3,810 5,985
General and administrative...... 298 2,000 2,845 1,709 2,356
------ -------- -------- -------- --------
Total operating expenses........... 711 6,763 8,085 5,519 8,341
Loss from operations............... (711) (6,713) (5,118) (4,449) (3,742)
Interest income, net............... 5 38 -- (12) 273
Foreign tax expense................ -- -- -- -- (200)
------ -------- -------- -------- --------
Net loss........................... $ (706) $(6,675) $(5,118) $(4,461) $(3,669)
====== ======== ======== ======== ========
Pro forma net loss per share(1).... $ (0.66) $ (0.45)
======== ========
Shares used in computing pro forma
net loss per share(1)........... 7,797 8,192
-------- --------
</TABLE>

<TABLE>
<CAPTION>
DECEMBER 31,
---------------------------------- SEPTEMBER 30,
1994 1995 1996 1997
-------- -------- -------- -------------
(in thousands)
<S> <C> <C> <C> <C>
BALANCE SHEET DATA:
Cash and cash equivalents.................... $ 1,622 $ 3,136 $ 367 $ 4,287
Short-term investments....................... -- -- 12,166 4,115
Working capital.............................. 1,420 1,990 9,271 5,288
Total assets................................. 1,796 4,150 16,658 13,363
Long-term obligations, less current
portion.................................... -- 424 1,753 2,377
Redeemable convertible preferred stock....... 2,250 9,650 23,107 23,130
Accumulated deficit.......................... (706) (7,381) (12,499) (16,168)
Total stockholders' equity (deficit)......... (682) (7,261) (12,363) (15,852)
</TABLE>

- ---------------

(1) See Note 1 of Notes to Financial Statements for information concerning the
computation of pro forma net loss per share and shares used in computing pro
forma net loss per share.

18
<PAGE> 20

MANAGEMENT'S DISCUSSION AND ANALYSIS OF
FINANCIAL CONDITION AND RESULTS OF OPERATIONS

The following Management's Discussion and Analysis of Financial Condition
and Results of Operations may contain forward-looking statements which involve
risks and uncertainties. The Company's actual results could differ materially
from those anticipated in these forward-looking statements as a result of
certain factors, including those set forth under "Risk Factors" and elsewhere in
this Prospectus.

OVERVIEW

CombiChem is a computational drug discovery company that is applying its
proprietary design technology and rapid synthesis capabilities to accelerate the
discovery process for new drugs. The Company believes its approach offers
pharmaceutical and biotechnology companies the opportunity to conduct their drug
discovery efforts in a more productive and cost-effective manner. Using its
proprietary Discovery Engine process, the Company focuses on the generation,
evolution and optimization of potential new lead candidates for its
collaborative partners, who will then develop, manufacture, market and sell any
resulting drugs. CombiChem believes that its process is widely applicable to a
variety of disease targets and therapeutic indications. Through September 30,
1997, the Company has established collaborative agreements with Teijin, Roche
Bioscience and Sumitomo, and in October 1997 the Company established
collaborative agreements with ImClone and Elan/Athena. In addition, the Company
intends to use its approach on internal programs to discover new lead candidates
and then to outlicense them to third parties, while retaining a larger economic
interest. Since inception in May 1994, and including the October 1997
collaborative agreements, the Company has raised $33.8 million through private
sales of equity securities.

The Company's revenue to date is primarily attributable to three major
corporate collaborations: Teijin, entered into in March 1996, Roche Bioscience,
entered into in October 1996, and Sumitomo, entered into in August 1997. Under
these collaborations, the Company has received aggregate payments of $8.7
million through September 30, 1997 and has recognized an aggregate of $7.5
million as revenue, including $4.5 million of project initiation fees and $3.0
million of contract research revenue, of which $1.5 million was recognized in
connection with the Teijin collaboration, $3.7 million was recognized in
connection with the Roche Bioscience collaboration and $2.3 million was
recognized in connection with the Sumitomo collaboration. Substantially all of
the $2.9 million revenue recognized under collaborative agreements in 1996 was
due to project initiation fees, and a significant portion of the $4.6 million
revenue recognized in the nine months ended September 30, 1997 is due to project
initiation fees. Revenue from milestone payments will be recognized when the
results or events stipulated in the agreement have been achieved. To date, the
Company has not achieved any milestones under any of its collaboration
agreements. Cost of services under the Company's collaborative agreements
generally approximate the research revenue received under the agreement. Project
initiation fees and milestone payments have no associated cost of services. The
Company is also entitled to receive royalty payments if any product is
commercialized under the collaborations. To date, the Company has not earned any
revenue related to product sales, and such revenue is not expected for the next
few years, if at all.

The Company has not been profitable since inception and has incurred a
cumulative net loss of $16.2 million through September 30, 1997. Losses have
resulted principally from costs incurred in research and development activities
related to the Company's efforts to develop its technologies and from the
associated administrative costs required to support these efforts. The Company's
ability to achieve profitability is dependent on its ability to market its
technology to pharmaceutical, biotechnology or agrochemical companies.

In connection with the collaborative agreements entered into in October
1997, the Company received aggregate proceeds of $10.0 million from the sale of
Common Stock and a cash payment of $1.3 million for a project initiation fee to
be recognized as revenue in the fourth quarter of 1997.

19
<PAGE> 21

RESULTS OF OPERATIONS

Nine Months Ended September 30, 1997 and 1996

Revenue

The Company's revenue for the nine-month period ended September 30, 1997
increased $3.5 million to $4.6 million from $1.1 million for the same period in
1996. The revenue for the nine-month period ended September 30, 1997 included
$2.3 million from Sumitomo, $1.8 million from Roche Bioscience and $0.5 million
from Teijin. The revenue from the nine-month period ended September 30, 1996
included $0.8 from Teijin. This was attributable to revenue related to the
Company's increased number of collaborative agreements and the project
initiation fee received from Sumitomo. The Company began recognizing revenue
from the Teijin and Roche Bioscience collaborations in March and October 1996,
respectively. The Company began recognizing contract research revenue from the
Sumitomo collaboration in August 1997. In October 1997, the Company entered into
collaborations with ImClone and Elan/Athena. To date, all revenue received by
the Company has been from the payment of upfront fees and research and
development funding paid pursuant to its collaborative agreements. Upfront fees
are received from the Company's collaborators upon, or shortly following,
execution of the collaborative agreement. Research and development funding is
received by the Company in connection with the performance of research and
development services under the collaborative agreement. Such funding typically
will be received only during the life of the research program under the
particular collaboration. The collaborative activities under these agreements
for which the Company receives revenue typically occur over a one to three-year
period, although the agreements provide for earlier termination in certain
circumstances. See "Business -- CombiChem's Collaborative Arrangements." The
Company expects that a significant portion of its revenue for the foreseeable
future will be comprised of such payments, although the receipt of upfront fees
will be dependent on the Company's ability to enter into additional
collaborative agreements for which upfront fees are due. In addition, the timing
of certain revenue in the future will depend upon the completion of certain
milestones as provided for in the Company's collaborative agreements, which are
contingent and uncertain. In any one fiscal quarter the Company may receive
multiple or no payments from its several collaborators. Operating results may
therefore vary substantially from period to period and will not necessarily be
indicative of results in subsequent periods. While the termination or conclusion
of any individual collaboration, including, without limitation, the agreement
with Teijin which it anticipated to conclude in March 1998 would not have a
material adverse effect on the Company's financial condition and results of
operations, the failure of the Company to enter into additional collaborative
agreements on favorable terms would have a material adverse effect on the
Company's financial condition and results of operations.

Operating Expenses

The Company's research and development expenses for the nine-month period
ended September 30, 1997 increased $2.2 million to $6.0 million from $3.8
million for the same period in 1996. This increase reflects increased research
and development expenses incurred both on behalf of collaborators through the
addition of chemists and software application staff for each project team and in
support of the development of the Company's technology including the addition of
software development and analytical staff, the depreciation of laboratory
equipment and the establishment of an advanced technology group. The Company has
the ability to direct its scientific personnel to work either on its
collaborative agreements or on its internal research projects as needs arise.
The Company expects research and development spending to increase over the next
several years due to increased activities related to collaborations, internal
programs and technology development.

The Company's general and administrative expenses for the nine-month period
ended September 30, 1997 increased $0.7 million to $2.4 million from $1.7
million for the same period in 1996. This increase reflects increased business
development activities, including outside consulting fees and increased travel
costs, and administrative support for the Company's expansion in 1997. These
expenses will likely continue to increase in future periods to support the
projected growth of the Company.

20
<PAGE> 22

Net Loss

The Company's net loss for the nine-month period ended September 30, 1997
decreased $0.8 million to $3.7 million from $4.5 million for the same period in
1996. The decrease is primarily attributable to additional revenue generated
from corporate collaborations during 1997.

Years Ended December 31, 1996 and 1995

Revenue

The Company's revenue for the year ended December 31, 1996 increased to
$3.0 million from $50,000 for the same period in 1995. The revenue for the year
ended December 31, 1996 included $2.0 million from Roche Bioscience and $1.0
million from Teijin. No revenue was received from the Company's collaborators in
the year ended December 31, 1995. This increase was attributable to revenue
related to the Company's collaborative agreements with Teijin and Roche
Bioscience which were entered into during 1996.

Operating Expenses

The Company's research and development expenses for the year ended December
31, 1996 increased $0.4 million to $5.2 million from $4.8 million for the same
period in 1995. This increase reflects increased research and development
expenses on behalf of collaborators and for the development of the Company's
technology, including investment in the Company's discontinued automated
synthesis instruments. The Company discontinued development of its automated
synthesis instruments in the second quarter of 1996, after incurring expenses of
approximately $4.0 million from inception of the Company through discontinuance.

The Company's general and administrative expenses for the year ended
December 31, 1996 increased $0.8 million to $2.8 million from $2.0 million for
the same period in 1995. This increase was primarily due to costs associated
with increased business development activities and administrative support, which
accompanied the Company's expansion during 1996.

Net Loss

The Company's net loss for the year ended December 31, 1996 decreased $1.6
million to $5.1 million from $6.7 million for the same period in 1995. The
decrease was primarily attributable to the increase in revenue generated from
the Teijin and Roche Bioscience collaborations.

Year Ended December 31, 1995 and Eight-Month Period Ended December 31, 1994

Revenue

The Company's revenue for the year ended December 31, 1995 consisted of
$50,000 of grant revenue. No revenue was earned by the Company in 1994.

Operating Expenses

The Company's research and development expenses for the year ended December
31, 1995 increased $4.4 million to $4.8 million from $0.4 million for the
eight-month period ended December 31, 1994. This increase primarily reflects the
expansion and development of the Company's technologies and a full year of
operations in 1995.

The Company's general and administrative expenses for the year ended
December 31, 1995 increased $1.7 million to $2.0 million from $0.3 million for
the eight-month period ended December 31, 1994, reflecting increased business
development activities and administrative support as well as a full year of
operations in 1995.

Net Loss

The Company's net loss for the year ended December 31, 1995 increased $6.0
million to $6.7 million from $0.7 million for the eight-month period ended
December 31, 1994. This increase was primarily attributable to the Company's
scale-up of research and development activities and a full year of operations.

21
<PAGE> 23

LIQUIDITY AND CAPITAL RESOURCES

At September 30, 1997, the Company held cash and cash equivalents and
marketable securities with a value of $8.4 million. The Company's working
capital at September 30, 1997 was $5.3 million. After giving effect to the
execution of the two additional collaborative agreements in October 1997 cash
and cash equivalents and marketable securities would have been $20.2 million and
working capital would have been $16.6 million. The Company has funded operations
to date with sales of preferred stock and common stock totaling $33.8 million,
payments from corporate collaborators totaling $10.5 million, and the
utilization of capital equipment lease financing totaling $4.6 million. The
Company has maintained capital lease arrangements since 1994. Under these
arrangements, the Company has funded certain capital expenditures with lease
terms ranging from 36 to 48 months in duration. As of September 30, 1997, the
Company had utilized $4.6 million of the available $7.9 million financing
facility.

Net cash used in financing activities for the nine-month period ended
September 30, 1997 was $164,000, primarily reflecting payments on capital
equipment financing. Net cash provided by financing activities for the year
ended December 31, 1996 was $12.2 million, largely due to a $13.0 million equity
investment. Net cash provided by financing activities for the year ended
December 31, 1995 was $7.3 million, resulting mainly from capital contributions
and proceeds from bridge financing.

Net cash used in operating activities for the nine-month period ended
September 30, 1997 and for the year ended December 31, 1996 was $3.7 million and
$2.4 million, respectively, primarily due to the Company's scale-up of research
and development activities.

Net cash provided by investing activities during the nine-month period
ended September 30, 1997 was $7.8 million, resulting primarily from maturities
of short-term investments. Net cash used in investing activities for the year
ended December 31, 1996 was $12.6 million as compared to $0.2 million for the
year ended December 31, 1995. This increase primarily reflects purchases of
short-term investments.

Although the Company anticipates that its existing capital resources,
including the proceeds from the October 1997 collaborations and the net proceeds
from this offering, will be adequate to fund the Company's operations at least
through 1998, there can be no assurance that changes will not occur that would
consume available capital resources before such time. The Company anticipates
that it will be required to raise additional capital over a period of several
years in order to continue to conduct its operations. Such capital may be raised
through additional public or private financings, as well as collaborative
arrangements, borrowings and other available sources. The Company expects that a
significant portion of its revenue for the foreseeable future will be comprised
of upfront fees and research and development funding paid pursuant to its
collaborative agreements, although the receipt of upfront fees will be dependent
on the Company's ability to enter into additional collaborative agreements for
which upfront fees are due. There can be no assurance that the Company's
collaborative arrangements will produce revenue adequate to fund the Company's
operating expenses. The Company's capital requirements depend on numerous
factors, including the ability of the Company to enter into additional
collaborative arrangements, competing technological and market developments,
changes in the Company's existing collaborative relationships, the cost of
filing, prosecuting, defending and enforcing patent claims and other
intellectual property rights, the purchase of additional capital equipment, the
progress of the Company's drug discovery programs and the progress of the
commercialization of milestone- and royalty-bearing compounds by the Company's
customers. The Company does not currently plan independently to develop,
manufacture or market any drugs it discovers. To the extent that additional
capital is needed, it may be raised through the sale of equity or convertible
debt securities, and the issuance of such securities could result in dilution to
the Company's existing stockholders. There can be no assurance that additional
funding, if necessary, will be available on favorable terms, if at all. If
adequate funds are not available, the Company may be required to curtail
operations significantly or to obtain funds through entering into arrangements
with collaborative partners or others that may require the Company to relinquish
rights to certain of its technologies, product candidates, products or potential
markets that the Company would not otherwise relinquish. The failure to receive
additional funding would have a material adverse effect on the Company's
business, financial condition and results of operations.

22
<PAGE> 24

NET OPERATING LOSSES

At December 31, 1996, the Company had available net operating loss ("NOL")
carryforwards of approximately $11.7 million for federal and California income
tax purposes, which will begin to expire in 2009 and 2002, respectively. In
addition, the Company had federal and California research and development credit
carryforwards of approximately $104,000 and $144,000, respectively, which will
begin to expire in 2010. The Company's ability to utilize such NOL carryforwards
may be limited under Section 382 of the Internal Revenue Code in the event of
certain cumulative changes of ownership of the Company. However, the Company
does not believe such limitation will have a material effect upon the
utilization of these carryforwards.

NEW ACCOUNTING PRONOUNCEMENTS

In February 1997, the Financial Accounting Standards Board issued Statement
of Financial Accounting Standards No. 128, Earnings Per Share (SFAS No. 128),
which supersedes APB Opinion No. 15. SFAS No. 128 replaces the presentation of
primary earnings per share (EPS) with "Basic EPS" which reflects only the
weighted-average common shares outstanding for the period. Companies with
complex capital structures, including the Company, will also be required to
present "Diluted EPS" that reflect the potential dilution, if any, of common
stock equivalents such as employee stock options and warrants to purchase common
stock. SFAS No. 128 is effective for financial statements issued for periods
ending after December 15, 1997.

23
<PAGE> 25

BUSINESS

OVERVIEW

CombiChem is a computational drug discovery company that is applying its
proprietary design technology and rapid synthesis capabilities to accelerate the
discovery process for new drugs. The Company believes its approach offers
pharmaceutical and biotechnology companies the opportunity to conduct their drug
discovery efforts in a more productive and cost-effective manner. Using its
proprietary Discovery Engine process, the Company focuses on the generation,
evolution and optimization of potential new lead candidates for its
collaborative partners who will then develop, manufacture, market and sell any
resulting drugs. CombiChem believes that its process is widely applicable to a
variety of disease targets and therapeutic indications. To date, the Company has
established collaborative agreements with Teijin, Roche Bioscience, Sumitomo,
ImClone and Elan/Athena. In addition, the Company intends to use its approach on
internal programs to discover new lead candidates and then to outlicense them to
third parties, retaining a larger economic interest in such candidates.

INDUSTRY BACKGROUND

During the past decade, significant advances in life sciences research and
the increasing appreciation of the complexity of biological processes have
highlighted the productivity limitations of traditional approaches to drug
discovery. These limitations, together with increased competition in the
pharmaceutical and biotechnology industries, have created intense pressure on
companies involved with drug development to reconsider the allocation of their
research budgets and to improve the cost-effectiveness of their drug discovery
process.

Between 1976 and 1996, the number of new chemical entities approved by the
FDA remained relatively constant, ranging between 12 to 30 per year, despite a
more than 10-fold increase in research and development spending by
pharmaceutical and biotechnology companies. Furthermore, it typically takes 12
to 15 years from the original concept of modulating the activity of a particular
biological target to the market introduction of a drug that performs such a
function. The average cost of bringing a new drug to market has been estimated
to be in excess of $300 million.

Frustrated with the inefficiencies of traditional drug discovery
approaches, pharmaceutical and biotechnology companies are beginning to embrace
new enabling technologies, such as combinatorial chemistry, genomics,
structure-based drug design, high-throughput screening and information
technologies, in order to gain a competitive advantage by accelerating the time
to develop and commercialize new compounds. These technologies also have the
potential to reduce significantly the cost associated with drug discovery.

The Traditional Drug Discovery Process and its Limitations

The traditional path to discovering a therapeutic drug compound typically
begins with the identification of one or more biological targets that are
believed to mediate a disease state. A biological test or assay based on a
target is then developed, predicated on the scientific belief that a compound
binding with this target may have a therapeutic benefit with respect to the
disease under study. Such an assay facilitates the screening (testing to
determine which of the compounds have the desired activity against the target)
of a collection of hundreds to thousands of candidate compounds (a library) that
have been synthesized in the laboratory. Compounds that bind to the target
protein and modulate its activity are referred to as hits. Medicinal chemists
optimize these hits until they have sufficient potency to become lead candidates
and then improve their preclinical characteristics (such as potency, specificity
and in vivo profile) further with the goal of producing drug development
candidates.

24
<PAGE> 26

In summary, the traditional drug discovery process consists of the
following steps:

LOGO

The traditional drug discovery process shown above is extremely expensive,
inefficient and unreliable. Failure at any point during this discovery process
would typically force the scientist either to abandon the project or to return
to the initial starting point and repeat the process. As a result, the discovery
of a novel therapeutic agent for a specified target can take years or can fail
entirely.

In recent years, the advent of robotic high-throughput screening and
automated synthesis technologies, such as combinatorial chemistry and parallel
synthesis, has begun to relieve one apparent bottleneck involving screening,
synthesis and purification of compounds in the library. While these technologies
facilitate the mechanics of drug discovery, they address neither the
unreliability of the process nor its principal inefficiency: the number of
iterations required to find a lead candidate. To address these problems, a novel
approach is needed that can provide information to improve the selection of each
subsequent library of compounds to synthesize, potentially reducing the number
of iterations. Only by improving the processes of data analysis and compound
selection can a laborious, iterative procedure be forced to converge on the lead
candidates with the most desirable pharmacological profiles.

Current Combinatorial Chemistry and Computational Approaches and Their
Limitations

Combinatorial chemistry involves the rapid creation of large collections of
chemical compounds for the purpose of identifying hits through random screening.
Combinatorial chemistry has made possible the synthesis of thousands or even
millions of molecules in a short period of time instead of the traditional
approach of synthesizing only one molecule at a time. Over the last decade, the
field of combinatorial chemistry has evolved from only companies that design and
synthesize molecules to include those that develop software and automation to
facilitate design and synthesis. These companies tend to use highly varied
approaches, including: focusing on single, pure compounds versus making
mixtures; building large versus small, focused libraries; automating part versus
all of the process; and using or not using medicinal chemistry as a principal
guiding force.

Computational methods are also employed in drug discovery. These methods
involve the use of computer-based and information technologies to manage large
chemical databases, to examine X-ray crystal structures of the target when
available (structure-based drug design), to operate the assorted automated
devices available for the synthesis of libraries, to determine how changes in
the structure affect the activity of a molecule (SAR activity) and to generate
"virtual libraries" using chemical building blocks from readily available
sources.

Currently, the dominant method of pursuing drug discovery focuses on
screening large libraries to search for a lead candidate directly in the
library, or at least a hit, which can then be optimized by the more traditional
techniques of medicinal chemistry to generate a development candidate. The
Company believes this brute-force, trial-and-error approach is flawed because
limited or no information has been factored into the library design to force the
iterative drug discovery process to converge. This limitation in current
combinatorial chemistry approaches is underscored by the fact that most compound
libraries used for screening have been constructed with the sole objective of
isolating a development candidate with the highest binding affinity to a target.
In order to achieve this objective against all possible targets, it is believed
such libraries would have to contain in excess of 100 million

25
<PAGE> 27

compounds, which size is well beyond current synthesis capabilities. In
addition, the challenge of drug discovery is not only to find a lead candidate
that exhibits activity against a biological target. It is also important to
ensure that the lead candidate will have characteristics that will enable it to
overcome the more difficult in vivo hurdles of toxicity, metabolism or problems
with oral administration, none of which will become evident until early
preclinical testing. Unless information can be extracted about which
characteristics are most necessary for binding, it is difficult to know how to
modify a compound to maintain tight binding affinity while overcoming in vivo
hurdles. Furthermore, if no hits are found after the screening of a traditional
combinatorial library, a scientist has no starting point for the drug discovery
process.

While both combinatorial chemistry and computational approaches are useful
in drug discovery to some degree, they are severely taxed by the complexity of
properly using the information available for library design, as evidenced by the
following drawbacks: (i) the inability to derive and integrate information both
from compounds that are active and those that are inactive against the target;
(ii) the inability to probe the target in order to compute ways of improving the
predictive models or hypotheses; and (iii) the inability to handle the dual
requirements of speed and quality when large data sets must be analyzed. The
Company believes that these inabilities to use information efficiently
constitute fundamental reasons that current discovery approaches have been only
moderately successful in generating lead candidates and development candidates,
despite the large number of initial hits.

COMBICHEM'S SOLUTION AND ADVANTAGES

The Company believes that it offers a solution to drug discovery by
combining its proprietary design technology and rapid synthesis capabilities in
a unique way. The Company's convergent, iterative process for drug
discovery -- its Discovery Engine (see the following diagram) -- is based on
libraries designed for information.

The design of libraries for information involves the selection of compounds
that collectively probe the biological target in a systematic way to determine
the chemical characteristics required for binding to such target. By identifying
features that discriminate between active and inactive compounds, the computer
constructs predictive models, called hypotheses, and then uses those models to
select a more focused library of compounds. The computer selects compounds from
the Company's proprietary Virtual Library, a computational representation of
more than 500 billion drug-like molecules chosen for the ease of laboratory
synthesis. CombiChem believes that by repeating this process of selecting,
synthesizing and screening informative compounds and analyzing the resulting
data, the Discovery Engine quickly converges on the most predictive hypothesis.
This hypothesis describes the characteristics a compound must possess to be
active against the target and, thus, is used to select a variety of potent lead
candidates.

Each cycle of the Discovery Engine refines the computer's definition of the
best hypothesis for the target in question. After several cycles, the resulting
hypothesis can be used to design highly potent compounds from a broad range of
chemical classes including those not readily amenable to combinatorial synthesis
techniques. By facilitating the design of a variety of potent compounds for
preclinical testing, the Discovery Engine has the potential to increase greatly
the likelihood that at least one of these compounds passes the in vivo and other
downstream hurdles and eventually becomes a commercial drug.

26
<PAGE> 28

LOGO

CombiChem believes that the advantages of its Discovery Engine include the
following:

Generating lead candidates from multiple structural series that exhibit the
same biological activity. By using predictive hypotheses to search the more than
500 billion-molecule Virtual Library, multiple structural series of compounds
that have the same effect on the target can be identified. The availability of
multiple structural series increases the likelihood that at least one of these
molecules will overcome the in vivo hurdles in preclinical development. In
addition, this provides an opportunity for the Company and its collaborators to
enhance the intellectual property position that potentially can be developed
around these compounds by having more than one patentable structural series.

Generating lead structures against a wide range of targets including those
for which little or no information is available. The Universal Informer Library
consists of a computer-designed, proprietary collection of approximately 10,000
physical compounds that can be screened against targets where little or no
information is available about the molecular structures that may be active
against those targets. Once the Universal Informer Library has been screened,
the information obtained can be used to start the Discovery Engine process. In
addition, because the technology is not dependent on having prior knowledge
about the target (e.g., an X-ray crystal structure representative of the
target), it can potentially be used to discover drugs against any target the
activity of which could be modified through binding a small molecule.

Achieving rapid generation, evolution and optimization of lead
candidates. By combining flexible design technology and rapid synthesis, the
Company's Discovery Engine can produce lead candidates for any of the three
types of drug discovery programs -- lead generation, lead evolution or lead
optimization -- with less than two years of effort. See "CombiChem's Discovery
Programs."

Reducing synthesis and screening costs. The Company's design technology
facilitates the use of small, informative libraries. Use of these small
libraries decreases the costs associated with synthesis

27
<PAGE> 29

and screening. In addition, the Virtual Library of drug-like molecules has been
explicitly constructed for the ease of laboratory synthesis.

STRATEGY

To establish multiple collaborations with large pharmaceutical and
biotechnology companies focused on biological targets chosen by the
collaborators. The Company intends to collaborate with large pharmaceutical and
biotechnology companies on fully funded programs aimed at biological targets
chosen by these collaborators. The Company's collaborative efforts are
exclusively focused on the discovery process, with a particular emphasis on the
discovery of novel compounds against biological targets. The Company believes
its technology platform provides it with opportunities to establish multiple
collaborations, which may be for the same disease state, thereby building a
portfolio of opportunities that may include upfront fees, research support,
milestone payments and royalties.

To partner with companies to apply discovery technologies to jointly
agreed-upon biological targets. In addition to collaborations on designated
biological targets, the Company intends to establish arrangements for jointly
funded discovery programs aimed at jointly agreed-upon biological targets,
typically with biotechnology companies. In these arrangements, the Company and
its partner will choose an appropriate biological target, the Company will apply
its discovery technologies to develop novel compounds against the specific
target, and the partner will fully fund and complete the drug development
process. The Company and its partner will share in the economic interest
resulting from their efforts.

To conduct internal discovery efforts aimed at selected biological targets,
retaining a larger economic interest in the subsequently outlicensed lead
candidates. The Company also intends to conduct its own internally funded
discovery programs by choosing biological targets of current scientific interest
and working in collaboration with screening companies. After identifying lead
candidates that are ready for development, the Company intends to outlicense
them, retaining a larger economic interest in such candidates as they are
developed and commercialized by a third party.

To expand collaborative opportunities in alternative industries such as the
agrochemical field. The Company has initially targeted large pharmaceutical and
biotechnology companies in its marketing efforts. The Company is considering
additional opportunities in alternative industries, including the agrochemical
field.

To maintain technology leadership in both software development and rapid
synthesis capabilities. The Company intends to continue to extend its technology
leadership through enhancements of existing software, design of future
generations of software and continued advancements of its synthesis
capabilities. The Company believes that these developments will allow it to
decrease the time required to discover lead candidates and to maintain its
technology leadership and competitive advantage.

COMBICHEM'S PROCESS: THE DISCOVERY ENGINE

The successful implementation of the Company's Discovery Engine process
requires the direct involvement of and interaction between its chemists and its
software applications team. This process consists of the following steps:

Data analysis -- the compilation and analysis of screening data, literature
information and available data about the target. The starting point for a drug
discovery program varies depending on the amount of prior information that is
available. The collaborator may have tested its corporate collection of
compounds or some other chemical library and have information regarding
structures of compounds that are initial hits (moderately active compounds),
information regarding structures that are inactive

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against the particular target or prior information about the target structure
itself. On the other hand, if little or no prior information or screening data
is available on the initial hits or target, the Company will make available for
screening its proprietary Universal Informer Library as a way of generating a
relevant set of information with which to initiate the Discovery Engine. See
"CombiChem's Proprietary Technologies -- Universal Informer Library."

The analysis of the available information is a critical step in the process
because it will determine what type of program will be undertaken -- lead
generation, lead evolution or lead optimization -- and the resources that will
be required. See "CombiChem's Discovery Programs."

Hypothesis generation -- the software-based generation of models that
predict the biological activity of molecular structures. Once the analysis of
the available data is completed by the Company's chemists and software
applications team, the information is used as input for hypothesis generation,
the first step of which involves conformational analysis.

- Conformational analysis. Conformational analysis is performed on each
active and inactive molecule to determine which shapes or conformations
such molecules can take. Because it is typically unknown which of these
shapes a particular molecule will assume when it shows its greatest
activity against a biological target, all reasonable conformations are
computationally described and analyzed. The Company's proprietary
technology allows for the analysis of large data sets and complex
molecular structures to be completed with both quality and speed.

- Hypothesis generator. Using the screening data and the results of
conformational analysis, the hypothesis generation software produces
computational models (called hypotheses) that attempt to explain the
observed differences in biological activity between active and inactive
molecules. In the early phases of a discovery program, the hypothesis
generator will often generate many hypotheses that are consistent with
the data, but the repeated application of the Discovery Engine
systematically tests the hypotheses, eliminating some while strengthening
others by providing supporting data. Repeating this procedure quickly
results in predictive hypotheses. The Company believes that its
proprietary design technology differs from others currently in use in
that it (i) includes all of the screening data (including inactives) in
generating hypotheses, (ii) takes into account a much broader
characterization of molecule-target interaction and (iii) forces
convergence to a predictive model of the important binding features by
probing the target systematically using rapid synthesis and screening.

Virtual Library search -- the computational search of the Virtual Library
to find molecular structures that fit the hypotheses. Once the hypotheses have
been generated, they are used to search the Company's proprietary Virtual
Library to identify molecular structures that have the features represented in
the hypotheses. The Virtual Library is a computational representation of more
than 500 billion drug-like molecules chosen for the ease of laboratory
synthesis. For each hypothesis that is generated, a more focused library of tens
to hundreds of molecules from the Virtual Library will be chosen by the computer
for synthesis in the laboratory. The Virtual Library is generated and searched
by proprietary design technology, which can exploit much larger libraries than
is possible with commercially available tools. See "CombiChem's Proprietary
Technologies -- Virtual Library."

Library synthesis -- the laboratory synthesis of molecular structures that
are selected from the Virtual Library using a wide range of chemistries. Once
the more focused library of compounds is designed, using molecules chosen from
the Virtual Library, the Company's chemists are responsible for synthesizing the
compounds in the laboratory. Unlike many combinatorial chemistry groups, the
chemists are not restricted to particular chemical reactions or a limited list
of structural templates, thus providing maximum flexibility to synthesize the
libraries quickly. See "CombiChem's Proprietary Technologies -- Synthesis and
Analytical Chemistry Technology."

The above four steps in the Discovery Engine process are completed by
project teams within the Company. Once the molecules are synthesized, those
libraries are then sent to the partner (or a contract group) for screening. Data
from these assays will be available to the Company for the next

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iteration of the cycle. With each such iteration, the Discovery Engine provides
more information, improving the hypotheses and increasing the likelihood of
discovering active molecules with desirable pharmacological characteristics.
Eventually, the hypotheses will converge to provide lead compounds that warrant
further testing as development candidates. It currently takes the Company's
scientists approximately three months to advance through the steps in one
Discovery Engine cycle. Depending upon the information available to start a
project, it may take two to four iterations of the cycle to generate strongly
predictive hypotheses that may eventually yield novel and highly active lead
candidates.

The Company's Discovery Engine process is being validated by both its
active collaborative programs and retrospective analysis of drug discovery
examples taken from the recent scientific literature. In one such example, the
Company applied its design technology to a project where the data provided was a
compilation of third-party research into the design of HIV protease inhibitors.
The objective was to determine whether CombiChem's process could be used to
discover novel inhibitors for the enzyme given a collection of only weakly
active hits from screening. The Company generated hypotheses with distinct
features by collecting information on eight weakly active HIV protease
inhibitors and 500 randomly selected inactive molecules with the same drug-like
characteristics as the weakly active compounds. Each of these weakly active
compounds was found by either an academic or commercial team in the early phases
of trying to discover an HIV protease drug. To assess whether the generated
hypotheses are, in fact, able to predict the activities of new molecules,
several highly potent HIV protease inhibitors, including currently marketed
drugs, were added to a virtual library of several hundred inactive compounds.
Using the hypotheses, the computer searched the Virtual Library, and the search
produced a list of highly ranked protease inhibitors with a variety of chemical
structures, including some of the highly potent HIV protease inhibitors
currently under development or marketed by major pharmaceutical companies. The
structures selected from the Virtual Library differ significantly from those
used to develop the hypotheses, validating the Company's capabilities in lead
evolution. The Company has similarly validated its technology on over a dozen
other literature data sets and on several programs with collaborators. In one
lead evolution program with a collaborator, for example, the Company has already
been successful in evolving from one structural series to multiple, novel
structural series while improving the biological activity. These results and a
variety of equally successful applications of the Discovery Engine demonstrate
the viability of the Company's computational drug discovery methods and the
strength of its proprietary technology.

COMBICHEM'S PROPRIETARY TECHNOLOGIES

To implement its Discovery Engine process, CombiChem has developed and
assembled an integrated set of proprietary technologies. These include the
following:

Universal Informer Library

The use of many traditional drug discovery approaches presupposes the
existence of prior information to start the process. However, recent efforts
such as the Human Genome Project and others are producing a number of novel
targets about which there is limited prior information. In addition, there are
many known targets for which no suitable leads have been identified. To address
these situations, CombiChem completed development of a Universal Informer
Library ("UIL") in mid-1997. The UIL consists of a computer-designed,
proprietary collection of approximately 10,000 physical compounds. Unlike other
libraries that are used to identify lead structures directly after screening,
the UIL is used to gather information concerning the relevant binding features
that are important to the target. The compounds in the UIL are highly
promiscuous molecules, which are molecules with the potential to bind to many
different targets. Screening against the UIL is therefore intended to provide a
few, weakly active compounds against the background of many, varied inactive
compounds. Using this data, hypotheses may be extracted, which allow the
Discovery Engine to be initiated.

The UIL was designed to provide hits for virtually all possible targets,
but if there is some reason to expect certain structural features to be relevant
to a particular target, the UIL can be augmented

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with compounds that contain those features. In this way, information gained from
prior experience can be incorporated into the UIL; this may improve the
hypotheses and therefore reduce the number of cycles required to converge.

The Company completed validation of its UIL approach by screening a subset
of the UIL against a wide range of targets and achieving an outcome comparable
to that typically seen in the pharmaceutical industry with libraries containing
hundreds of thousands of compounds.

Virtual Library

CombiChem's Virtual Library is a computational representation of more than
500 billion drug-like molecules chosen for the ease with which they can be
synthesized in the laboratory. To maximize the likelihood that the Virtual
Library will contain potent, patentable compounds active against most targets,
the Company has populated it with hundreds of novel structural templates, each
of which has two to four sites at which a wide variety of structural changes can
be made synthetically using available chemicals. This chemistry can also be
scaled up to give ready access to quantities of each lead candidate sufficient
to perform early preclinical testing. The Virtual Library is generated and
searched by two components of the Company's proprietary software: Virtual
Library Cascader(TM) software and Virtual Library Search software. See
"-- Design Technology."

Synthesis and Analytical Chemistry Technology

Once the Virtual Library is searched for collections of molecules that
match the hypotheses, the Company's chemists initiate synthesis of these
molecules in the laboratory. The challenge for CombiChem's chemists is to select
the technique that will most quickly achieve the synthesis of the library. While
there is considerable debate throughout the industry about the relative merits
of various methods of chemical synthesis (solid versus solution phase, for
example), CombiChem's chemists have the flexibility to use the appropriate
approach for each specific synthesis task. The Company believes it has expertise
in most or all of the readily used techniques and, in addition, has access to a
number of new proprietary methods.

As long as relatively straightforward chemistry is applied to library
production, synthesis is generally not the rate-limiting step. The challenge
lies in the isolation and purification of the library compounds. The Company
applies several approaches, including a number of proprietary semi-automated
techniques, to facilitate these procedures in order to achieve its purity
standards of greater than 85%.

Design Technology

The Company relies on its proprietary design technology in order to
complete several of the key steps in its Discovery Engine. The proprietary
design technology includes:

Conformational analysis software -- a computer program for identifying the
distinct three-dimensional shapes of a molecule. Conformational analysis is
performed on each active and inactive molecule to determine which shapes or
conformations such molecules can take. Because it is typically unknown which of
these shapes a particular molecule will assume when it shows its greatest
activity against a biological target, all reasonable conformations are
computationally described and analyzed. The Company has developed proprietary
conformational analysis software, which rapidly determines all the distinct,
reasonable shapes each molecule can assume. Both the speed and the thoroughness
of the conformational analysis software distinguish it from commercial chemistry
software and permit the Discovery Engine to handle large data sets.

Hypothesis generation software -- a computer program for analyzing
screening data to identify the requirements a potential drug must satisfy to
bind to this target. Once conformational analysis has been applied to each of
the screened molecules, the Company's proprietary hypothesis generation software
produces computational models that can estimate the biological activity of
chemical structures. These

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models, called hypotheses, are generated by applying methods from statistics,
information theory, physical chemistry and computer science to the screening
data in order to identify the differences between active compounds and inactive
compounds. The predictive capabilities of the computational models and the novel
algorithms used to produce them distinguish the Company's hypothesis generator
from commercial chemistry software.

Virtual Library Cascader software -- a computer program for conveniently
describing virtual libraries. The Cascader software facilitates the rapid
specification of virtual libraries to the computer. By providing databases of
reagents and descriptions of reactions to the Cascader, a chemist can quickly
describe large libraries of compounds to the computer. The Cascader can use the
resulting description to construct explicit subsets of the large virtual library
and to present the structures to the chemist and to the Virtual Library Search
software.

Virtual Library Search software -- a computer program for selecting
molecules from the Virtual Library that, when synthesized and screened, will
provide the most information about additional binding requirements. The Virtual
Library search software uses hypotheses to estimate computationally the potency
of prospective compounds in order to increase the likelihood that the chemists
devote their synthesis efforts to compounds that fit the hypotheses and are thus
most likely to bind to the target. By using the computer to test the compounds
in the Virtual Library against the hypotheses, the Discovery Engine can rapidly
identify both putatively active compounds (which satisfy several different
hypotheses) and informative ones (which discriminate among hypotheses).
Searching virtual libraries with billions of compounds has generally not been
possible with commercial chemistry software.

Each cycle of the Discovery Engine refines the computer's assessment of the
best hypothesis for the target in question. After several cycles, the resulting
hypothesis can be used to design highly potent compounds from a broad range of
chemical classes including those not readily amenable to combinatorial synthesis
techniques. By facilitating the design of a variety of potent compounds for
preclinical testing, the Discovery Engine has the potential to increase greatly
the likelihood that at least one of these compounds passes the in vivo and other
downstream hurdles and eventually becomes a commercial drug.

COMBICHEM'S DISCOVERY PROGRAMS

The Company has applied, and intends to continue to apply, its technology
to discover lead compounds for biological targets chosen by its collaborators.
In addition, the Company will select, either jointly with a partner (most likely
a biotechnology company) or on its own, a biological target of interest.

In the first instance, where the Company is working on a target chosen by a
collaborator, the commercial terms are negotiated based on a number of factors,
including the number of targets to be included in the collaboration and the type
of program -- lead generation, lead evolution or lead optimization. Depending
upon the type of program, CombiChem will work on the program for a period of one
to two years. A dedicated project team, funded by the collaborator, consisting
of applications scientists and synthetic, medicinal and analytical chemists will
be assigned. The team composition and size is dependent upon the type of program
and its objectives. To ensure confidentiality, the Company provides target
exclusivity to each of its collaborators, and each team works in a dedicated
laboratory. At the conclusion of the program, assuming its objectives have been
met, the program team will transfer the lead structure(s) to the collaborator.
At this point, the work at CombiChem will be completed, but the partner will
continue to develop the lead candidate. As the collaborator develops the lead
candidate and reaches certain agreed-to objectives, the Company will receive
milestone payments. Eventually, when the lead candidate becomes a marketed drug,
the Company will receive royalties on the sales of the drug.

In the jointly funded programs or the internal programs, the Company will
pay for all or part of the work to be completed and, either jointly or on its
own, will outlicense the lead structures to a partner for the development and
commercialization phases.

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Depending upon the data available, the Discovery Engine can be applied to
three types of discovery programs undertaken by the Company: lead generation,
lead evolution and lead optimization. Lead generation uses the UIL to generate
information for the Discovery Engine in situations where little or no prior
information is known about the target. Lead evolution begins with existing
information (either from the collaborator or from the scientific literature)
regarding a lead candidate with the objective of identifying different
structural series that can provide either other development options or an
enhanced patent position. The evolution path may be chosen either as an
outgrowth of a lead optimization program or directly from a collaborator's
established lead candidate series. Lead optimization involves a lead candidate
provided by a collaborator that requires improvement prior to being identified
as a drug development candidate. Using CombiChem's computational drug discovery
approach, initial libraries are constructed around a given template. Using a
convergent, iterative process, subsequent libraries are increasingly focused as
increased activity (e.g., affinity, selectivity) is achieved.

Current Collaborative Discovery Programs

The Company's current collaborative discovery programs are as follows:

<TABLE>
<CAPTION>
- ---------------------------------------------------------------------------------------------------
COMPANY NAME TARGET OR THERAPEUTIC AREA OF FOCUS TYPE OF PROGRAM
- ---------------------------------------------------------------------------------------------------
<S> <C> <C>
Teijin G-protein coupled receptor Lead evolution(1)

Roche Bioscience Protein-Protein interaction Lead optimization
Enzyme Lead evolution
Receptor Lead optimization

Sumitomo Target implicated in osteoarthritis Lead evolution
and rheumatoid arthritis

ImClone Multiple targets in oncology Lead generation, lead evolution

Elan/Athena Multiple targets in central nervous Lead generation, lead evolution,
system conditions lead optimization
- ---------------------------------------------------------------------------------------------------
</TABLE>

(1) Started as a lead optimization program.

Internal Discovery Programs

The Company intends to pursue a number of internal programs as a means of
enhancing its ability to generate revenue and profits. The Company has selected
dopamine D-4, a target believed to have a role in schizophrenia, as its first
internally funded program. The Company believes the schizophrenia market has
significant potential, as currently marketed drugs have a number of unwanted
side effects. The Company intends to identify lead candidates for the D-4
receptor (with partial D-2 activity) as well as other future internal targets
and thereafter to outlicense such lead candidates to third parties, retaining a
larger economic interest in these programs. Additional internal programs will be
identified and funded as the Company's resources allow.

COMBICHEM'S COLLABORATIVE ARRANGEMENTS

The Company's business model is to enter into collaborative arrangements
focused on drug discovery efforts to improve the Company's chances of achieving
profitability and to minimize its financing requirements. Commercial terms of a
collaborative arrangement are driven by the number and nature of the targets.
The key components of the commercial terms typically contained in the Company's
collaborations include upfront fees, research support, milestone payments and
royalties.

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The Company has the following collaborative arrangements:

Teijin Limited

In March 1996, the Company entered into a collaborative agreement with
Teijin providing for a one-year program on a G-protein coupled receptor target.
In March 1997, the Company and Teijin amended their agreement to extend the
collaboration for an additional year. While the initial focus of the
collaboration was lead optimization, the effort was redirected to lead evolution
during the course of the research. Under the agreement, Teijin made an upfront
payment to CombiChem and agreed to provide research funding and milestone
payments upon the achievement of certain preclinical and clinical milestones.
Teijin also committed internal resources to the discovery effort. Teijin will
make royalty payments on products resulting from the collaboration. CombiChem
retains the rights to the compounds arising under this collaboration in North
and South America; Teijin has rights to these compounds in Asia and Europe with
a right of first negotiation to acquire CombiChem's rights. Under the original
agreement, Teijin has rights to expand or extend the program for up to two
successive one-year terms. Either party may terminate the agreement in the event
of a material breach remaining uncured for 60 days. As of September 30, 1997,
Teijin had paid the Company an aggregate of $1.5 million.

Roche Bioscience, a division of Syntex (U.S.A.) Inc.

In October 1996, the Company entered into a collaborative agreement with
Roche Bioscience providing for a broad two-year program to perform research
against three initial targets, including a protein-protein interaction, an
enzyme and a receptor, with an option to add additional targets. Roche
Bioscience can elect one of the approaches -- lead generation, lead evolution or
lead optimization -- for each research program against each collaboration
target. A program may be initiated at any time during the term of the
collaboration, thereby extending the term to allow for completion of each
program. Under the agreement, Roche Bioscience made an upfront payment to
CombiChem and agreed to provide research funding and to make milestone payments
upon the achievement of certain preclinical and clinical milestones. Roche
Bioscience will make royalty payments on worldwide sales of products resulting
from the collaboration. Upon completion of the first year of the agreement,
Roche Bioscience may terminate the collaboration at any time upon six months'
prior written notice. Certain special conditions could also allow Roche
Bioscience to terminate with 45 days' prior written notice. As of September 30,
1997, Roche Bioscience had paid the Company an aggregate of $4.0 million.

Sumitomo Pharmaceuticals Co., Ltd.

In August 1997, the Company entered into a collaborative agreement with
Sumitomo providing for a two-year lead evolution program on a target that is
believed to play a fundamental role in osteoarthritis and rheumatoid arthritis.
Under the agreement, Sumitomo made an upfront payment and agreed to provide
research funding and milestone payments upon the achievement of certain
preclinical and clinical milestones. Sumitomo will make royalty payments on
worldwide sales of products resulting from the collaboration. Sumitomo may
extend the research period for up to four successive six-month periods upon
mutual agreement. The agreement may be terminated by either party 90 days
following an uncured material breach. As of September 30, 1997, Sumitomo had
paid the Company an aggregate of $3.3 million.

ImClone Systems Incorporated

In October 1997, the Company entered into a collaborative agreement with
ImClone providing for a two-year program to identify and characterize novel
small molecule inhibitors to multiple targets for development in oncology. The
agreement provides for ImClone's access to the Company's Universal Informer
Library and Virtual Library under the supervision of the research management
committee composed of representatives of the Company and ImClone. Under the
terms of the agreement, ImClone will provide the Company with research support
payments, milestone payments upon the

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achievement of certain program objectives and royalties on worldwide product
sales of therapeutic products that may arise out of the collaboration. The
agreement may be terminated by either party 90 days following an uncured
material breach or by ImClone within 30 days prior to the one-year anniversary
by providing 90 days' prior written notice. In connection with the collaborative
agreement, ImClone purchased 250,000 shares of Common Stock for $2.0 million,
and made an advance payment for contract research of $500,000.

Athena Neurosciences, Inc., a wholly owned subsidiary of Elan Corporation, plc

In October 1997, the Company entered into a collaborative agreement with
Athena Neurosciences, Inc., a wholly owned subsidiary of Elan Corporation, plc.
providing for a three-year program to discover novel therapeutic compounds for
treatment of central nervous system conditions. The agreement provides for
Elan/Athena's access to the Universal Informer Library as deemed necessary by
the research management committee composed of Elan/Athena and CombiChem
representatives. Under the agreement, Elan/Athena will provide the Company with
upfront and research support payments, as well as milestone payments upon the
achievement of pre-determined objectives. Elan/Athena will also make royalty
payments on worldwide sales of products resulting from the collaboration. The
agreement may be terminated by either party 90 days following an uncured
material breach or by Elan/Athena after the one-year anniversary upon 90 days
prior written notice. In connection with the collaborative agreement, Elan
International Services Ltd., an affiliate of Elan/Athena, purchased 1,000,000
shares of Common Stock for $8.0 million and made a cash payment of $1.333
million for an up-front technology license and access fee.

RESEARCH AND DEVELOPMENT

The Company's expenses for Company-sponsored research and development
activities for the years ended December 31, 1994, 1995 and 1996 were $0.4
million, $4.8 million and $4.8 respectively. The Company's expenses for
collaborator-sponsored research and development activities for the years ended
December 31, 1994, 1995 and 1996 were $0, $0 and $0.4 million respectively.

COMPETITION

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PATENTS AND PROPRIETARY INFORMATION

The Company's success will depend in large part on its own, its licensees'
and its licensors' ability to obtain and defend patents for each party's
respective technologies and the compounds and other products, if any, resulting
from the application of such technologies, maintain trade secrets and operate
without infringing upon the proprietary rights of others, both in the United
States and in foreign countries. The patent positions of pharmaceutical and
biotechnology companies, including the Company, are uncertain and involve
complex legal and factual questions for which important legal principles are
largely unresolved. The Company has pending United States and foreign patent
applications relating to various aspects of its technology, certain systems,
materials and methods used in screening compounds and the libraries or compounds
contained therein. These patent applications are either owned by the Company or
rights under them are licensed to the Company. To date, none of the patent
applications owned by the Company have been issued. To the extent that any
foreign patent application filed in the European Patent Office or the Japanese
Patent Office issues as a patent, a challenge to the validity of such patent may
be presented in an opposition proceeding. There can be no assurance that patents
will issue as a result of any such pending applications or that, if issued, such
patents will be sufficiently broad to afford protection against competitors with
similar technologies. The Company is aware of three United States patents issued
to a third party that claim proprietary rights; two of the three patents are
entitled "System and method for automatically generating chemical compounds with
desired properties" and the third is entitled "System, method, and computer
program for at least partially automatically generating chemical compounds
having desired properties." Although the Company believes that its current
activities do not infringe these patents, there can be no assurance that the
Company's belief would be affirmed in any litigation over the patents or that
the Company's future technological developments would be outside the scope of
these patents. Further, there can be no assurance that the third party will not
seek to assert such patent rights against the Company, which would result in
significant legal costs and require substantial management resources, and there
can be no assurance that the Company would be able to obtain a license from the
third party, if required, on commercially reasonable terms, if at all. The
inability of the Company either to demonstrate non-infringement of these and
other current and future patents, whether issued in the United States or
overseas, or to obtain the appropriate licenses, would have a material adverse
effect on the Company's business, financial condition and operations. Moreover,
there can be no assurance that the Company or its customers will be able to
obtain patent protection for lead compounds or pharmaceutical products based
upon the Company's or such customers' technologies. There can be no assurance
that any patents issued to the Company or its collaborative partners, or for
which the Company has license rights, will not be challenged, invalidated or
circumvented, or that the rights granted thereunder will provide competitive
advantages to the Company. To the extent that the Company or its consultants or
collaborators use intellectual property owned by others in their work for the
Company, disputes may also arise as to the rights in related or resulting
know-how and inventions. Litigation may be necessary to enforce the Company's
patent and license rights or to determine the scope and validity of others'
proprietary rights. Any such litigation, whether or not the outcome thereof is
favorable to the Company, could result in substantial cost to and diversion of
effort by the Company. Further, United States patents do not provide any
remedies for infringement that occurred before the patent is issued. The
commercial success of the Company will also depend upon successfully avoiding
the infringement of current and future patents issued to competitors and upon
maintaining the technology licenses upon which certain of the Company's current
products are, or any future products under development might be, based. If
competitors of the Company prepare and file patent applications in the United
States that claim inventions also claimed by the Company or its collaborators,
the Company or its collaborators may have to participate in interference
proceedings declared by the PTO to determine the priority of invention, which
could result in substantial cost to the Company, even if the outcome is
favorable to the Company. An adverse outcome could subject the Company to
significant liabilities to third parties and require the Company to license
disputed rights from third parties or cease using the technology.

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GOVERNMENT REGULATION

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demonstrate the safety and efficacy that are necessary to obtain FDA and foreign
regulatory authority approval of any such products. Clinical trials are normally
done in three phases and generally take two to five years but may take longer to
complete. After completion of clinical trials of a new product, FDA and foreign
regulatory authority marketing approval must be obtained. If the product is
classified as a new drug, the Company or its customer will be required to file
an NDA and receive approval before commercial marketing of the drug. The testing
and approval processes require substantial time and effort, and there can be no
assurance that any approval will be granted on a timely basis, if at all. NDAs
submitted to the FDA can take, on average, two to five years to obtain approval.
If questions arise during the FDA review process, approval can take more than
five years. Even if FDA regulatory clearances are obtained, a marketed product
is still subject to continual review, and later discovery of previously unknown
problems or failure to comply with the applicable regulatory requirements may
result in restrictions on the marketing of a product or withdrawal of the
product from the market, as well as possible civil or criminal sanctions.
Domestic manufacturing facilities of the Company or its customers are subject to
bannial inspections by the FDA and must comply with the FDA's current Good
Manufacturing Practices regulations. To comply with such regulations, a
manufacturer must spend funds, time and effort in the areas of production and
quality control to ensure full technical compliance. The FDA stringently applies
regulatory standards for manufacturing. For marketing outside the United States,
the Company or its customer will also be subject to foreign regulatory
requirements governing human clinical trials and marketing approval for
pharmaceutical products. The requirements governing the conduct of clinical
trials, product licensing, pricing and reimbursement vary widely from country to
country.

MARKETING

The Company markets its products directly to customers through
participation in trade conferences and seminars and publications in scientific
and trade journals.

To date, the Company has sold its product offering to its collaborative
partners primarily through the efforts of its senior management and dedicated
business development professionals. In addition, the Company utilizes outside
consultants to supplement its business development activities in targeted
geographies or industries.

FACILITIES

The Company currently leases and occupies approximately 34,000 square feet
of laboratory and office space in San Diego, California. The Company also leases
office space in Palo Alto, California at two separate locations and under two
separate leases; one lease is for approximately 4,500 square feet and the other
is for approximately 6,000 square feet. The Company is currently planning to
move its Palo Alto operations from the smaller location to the larger location
and to sublet the smaller space. The San Diego lease expires in May 2006; the
Palo Alto lease for 4,500 square feet expires in October 1998; and the Palo Alto
lease for 6,000 square feet expires in October 2002.

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<PAGE> 40

EMPLOYEES

As of September 30, 1997, the Company had 56 full-time employees, 31 of
whom have Ph.D. degrees. Of these employees, 42 were engaged in research and
development and 14 were engaged in marketing and general administration. None of
the Company's employees is covered by collective bargaining agreements.
Management considers its relations with its employees to be good.

LEGAL PROCEEDINGS

The Company is not a party to any legal proceedings.

SCIENTIFIC ADVISORY BOARD

The Company has formed a Scientific Advisory Board ("SAB"), which consists
of eight individuals with demonstrated expertise in the fields of molecular
biology, medicinal and synthetic chemistry, computer science and biochemistry.

Members of the SAB review the Company's research, development and
operations activities and are available for consultation with the Company's
management and staff relating to their respective areas of expertise. The SAB
holds regular meetings. The Scientific Advisors are reimbursed for their
expenses in connection with their service and are paid for attending meetings.
In addition, the Scientific Advisors either hold options to purchase Common
Stock or own varying amounts of Common Stock of the Company that were purchased
pursuant to their individual consulting agreements with the Company. The
Scientific Advisors are expected to devote only a small portion of their time to
the business of the Company.

The Scientific Advisors are all employed by or have consulting agreements
with entities other than the Company. Each Scientific Advisor has entered into a
consulting agreement with the Company that contains confidentiality and
nondisclosure provisions that prohibit the disclosure of confidential
information to anyone outside the Company. Also, the consulting agreements
contain exclusivity provisions restricting the Scientific Advisors from
providing service to or investing in any competitor of the Company without the
Company's consent. All inventions, discoveries or other intellectual property
that comes to the attention of each Scientific Advisor while performing services
under a consulting agreement with the Company will be assigned to the Company.
The current members of the SAB are as follows:

Sydney Brenner, Ph.D. Dr. Brenner is the President and Director of Science
at The Molecular Sciences Institute, Inc. This follows an academic career at the
University of Cambridge, UK, where he pioneered many of the developments in
modern biology and molecular biology.

Dennis Curran, Ph.D. Dr. Curran is the Distinguished Service Professor of
Chemistry and the Bayer Professor of Chemistry at The University of Pittsburgh.
His research focus is fluorous chemistry.

Samuel J. Danishefsky, Ph.D. Dr. Danishefsky holds a Chair in Chemistry at
Columbia University and the Kettering Chair at The Sloan-Kettering Institute for
Cancer Research. Following the award of his Ph.D. by Harvard University in 1962,
he has had a distinguished career in synthetic and medicinal chemistry.

Kim Janda, Ph.D. Dr. Janda is the Ely R. Callaway, Jr., Professor of
Chemistry at The Scripps Research Institute ("TSRI"), Department of Chemistry
and holds a joint appointment with The Skaggs Institute for Chemical Biology at
TSRI. Dr. Janda is widely recognized for his work in combinatorial chemistry and
biochemistry. Dr. Janda received a B.S. in Clinical Chemistry from the
University of South Florida, a M.S. in Organic Chemistry from the University of
Arizona and a Ph.D. in Organic Chemistry with a minor in Medicinal Chemistry
from the University of Arizona.

William Jorgensen, Ph.D. Dr. Jorgensen is the Whitehead Professor of
Chemistry at Yale University, where he has been since 1990. Dr. Jorgensen is
widely known for his work in organic and

39
<PAGE> 41

computational chemistry. He received a B.A. in Chemistry from Princeton and a
Ph.D. in Chemical Physics from Harvard University.

Richard Lathrop, Ph.D. Dr. Lathrop is an Assistant Professor at the
University of California, Irvine in the Department of Information and Computer
Science, where he has been since July 1995. Dr. Lathrop is widely recognized for
his work in the area of advanced computational techniques with applications in
the domain of molecular biology. Dr. Lathrop received a B.A. in Mathematics from
Reed College in Portland, and an M.S. in Computer Science and a Ph.D. in
Artificial Intelligence from the Massachusetts Institute of Technology. His
research interests are focused on artificial intelligence and advanced
computational techniques.

William Scott, Ph.D. Dr. Scott received a Ph.D. in Biochemistry in 1967
from the California Institute of Technology. His subsequent career has spanned
both academia at Rockefeller University, and industry with Bristol-Myers Squibb.
Dr. Scott is also a Director of the Company. See "Management -- Executive
Officers, Key Employees and Directors."

Chi-Huey Wong, Ph.D. Dr. Wong is a Professor and Ernest W. Hahn Chair in
Chemistry at TSRI, where he has been since 1989, and holds a joint appointment
with The Skaggs Institute for Chemical Biology at TSRI. Dr. Wong has published
numerous papers in the area of Bioorganic and Synthetic Chemistry. Dr. Wong
received a B.S. in Chemistry and Biochemistry and an M.S. in Biochemistry from
National Taiwan University, received a Ph.D. in Organic Chemistry from the
Massachusetts Institute of Technology and was a Postdoctoral Fellow in Chemistry
at Harvard University.

40
<PAGE> 42

MANAGEMENT

EXECUTIVE OFFICERS, KEY EMPLOYEES AND DIRECTORS

The executive officers, key employees and directors of the Company as of
October 15, 1997, are as follows:

<TABLE>
<CAPTION>
NAME AGE POSITION
- ------------------------------------------ --- ------------------------------------------
<S> <C> <C>
Pierre R. Lamond(1)(3).................... 67 Chairman of the Board and Director
Vicente Anido, Jr., Ph.D.(1).............. 44 President, Chief Executive Officer and
Director
Peter L. Myers, Ph.D...................... 53 Vice President, Chief Scientific Officer,
Chief Operating Officer and Director
Karin Eastham............................. 47 Vice President, Finance and Administration
and Chief Financial Officer
Klaus Gubernator, Ph.D. .................. 44 Vice President, Special Projects
Lee R. McCracken.......................... 39 Vice President, Business Development
John Saunders, Ph.D....................... 49 Vice President, Medicinal Chemistry
Steven L. Teig............................ 36 Vice President, Advanced Technology
Philippe O. Chambon, M.D., Ph.D.(1)(2).... 39 Director
Arthur Reidel(3).......................... 46 Director
William Scott, Ph.D.(2)................... 57 Director
</TABLE>

- ---------------

(1) Member of Executive Committee.

(2) Member of Compensation Committee.

(3) Member of Audit Committee.

Pierre R. Lamond. Mr. Lamond has served as Chairman of the Board and a
Director of the Company since May 1995. Mr. Lamond is a General Partner of
Sequoia Capital, a venture capital limited partnership with over $500 million
under management. Prior to joining Sequoia Capital in 1981, Mr. Lamond was a
Vice President and Technical Director of National Semiconductor Corporation
("National Semiconductor") from 1976 to 1981. He began his career in 1957 at
Transitron Corporation and joined Fairchild Semiconductor Company in 1961. In
1967, he was one of the co-founders of National Semiconductor where he managed
the semiconductor division until 1974. From 1974 through 1975, he was President
of Coherent, Inc., a laser company. He served as President of Advent, an early
pioneer of projection television from 1975 through 1976. Mr. Lamond is Chairman
of Cypress Semiconductor Corporation and Vitesse Semiconductor Corporation,
Director of CKS Group, and a director of a number of private companies.

Vicente Anido, Jr., Ph.D. Dr. Anido has served as President and Chief
Executive Officer and as a Director of the Company since joining the Company in
March 1996. Prior to that, Dr. Anido served as President of the Americas Region
at Allergan, Inc. from June 1993, where he was responsible for that company's
commercial operations for North and South America with approximately $500
million in revenue. Prior to that, Dr. Anido spent almost 18 years at Marion
Laboratories and Marion Merrell Dow, Inc. and served as Vice President, Business
Management of its U.S. Prescription Products Division from 1991 until June 1993.
Dr. Anido holds a B.S. in Pharmacy from West Virginia University, an M.S. in
Pharmaceutical Sciences from West Virginia University and a Ph.D. in Pharmacy
Administration from the University of Missouri, Kansas City.

Peter L. Myers, Ph.D. Dr. Myers has served as a Director, Vice President
and Chief Scientific Officer of the Company since joining the Company in March
1995. Dr. Myers has also served as Chief Operating Officer of the Company since
September 1995 and served as the acting Chief Executive Officer from September
1995 to March 1996. Prior to joining the Company, Dr. Myers served as Vice
President, Drug Discovery and Development at Onyx Pharmaceuticals Inc. from
November 1993

41
<PAGE> 43

through March 1995, where he was responsible for all aspects of drug discovery
and development leading to potential novel classes of anti-cancer drugs. Prior
to that, Dr. Myers served as Vice President, Chemistry Research of Glaxo Inc.
Research Institute from January 1991 through December 1993. Dr. Myers holds a
B.S. in Chemistry and a Ph.D. in Organic Chemistry from Leeds University.

Karin Eastham. Ms. Eastham joined the Company as Vice President, Finance
and Administration and Chief Financial Officer in April 1997. Prior to joining
the Company, Ms. Eastham served as Vice President, Finance and Administration
and Chief Financial Officer of Cytel Corporation, a drug research and
development company, from October 1992 through April 1997. Prior to that, Ms.
Eastham was Vice President, Finance and Administration of Pritsker Corporation,
a simulation-based computer software company, from May 1990 through October
1992. Ms. Eastham received a B.S. in Accounting and an M.B.A. from Indiana
University. She is a Certified Public Accountant.

Klaus Gubernator, Ph.D. Dr. Gubernator joined the Company in August 1997 as
Vice President, Special Projects. Prior to joining the Company, he served as
Research Section Head in Pharmaceutical Research at F. Hoffmann-La Roche Ltd. in
Basel, Switzerland from 1987 to 1997, contributing to cardiovascular and
antibacterial projects as well as developing structure-based design and
bioinformatics technologies. Dr. Gubernator received his Ph.D. degree in
Chemistry from the University of Heidelberg.

Lee R. McCracken. Mr. McCracken has served as Vice President, Business
Development since joining the Company in May 1996. Prior to joining the Company,
Mr. McCracken served as Vice President, Business Development at Watson
Laboratories, the operating subsidiary of Watson Pharmaceuticals, from January
1996 through May 1996. Prior to that, Mr. McCracken served as Managing Director
of Pacific Pharma and as Director, Business Development, for the Americas Region
at Allergan, Inc. from May 1992 through December 1995. Prior to entering the
pharmaceutical industry, Mr. McCracken was a venture capitalist with 3i Capital
and Union Venture Corporation. Mr. McCracken received a B.S. in Marketing from
Santa Clara University, an M.S. in Computer Science from the University of
Dayton and an M.B.A. from The Anderson School at UCLA.

John Saunders, Ph.D. Dr. Saunders joined the Company in October 1995 as
Vice President, Medicinal Chemistry. Prior to joining the Company, Dr. Saunders
served as Head of Medicinal Chemistry II from August 1989 through September 1995
and also as Head of the Antiviral Research Management Committee from July 1995
through September 1995 at Glaxo-Wellcome, plc. Dr. Saunders received a first
class honors degree in Chemistry from Newcastle University in England and a
Ph.D. from Cambridge University.

Steven L. Teig. Mr. Teig has served as Vice President, Advanced Technology
since February 1997 and previously served as Vice President, Design Technology
from July 1995. Prior to joining the Company, Mr. Teig co-founded BioCAD Corp.,
a commercial developer of drug discovery software for medicinal chemists, in
June 1989 and served as its Chief Technical Officer until its merger with
Molecular Simulations, Inc. ("MSI"). Thereafter, Mr. Teig served as President
and Chief Technical Officer of Entropix Corporation, a subsidiary of MSI, from
August 1994 through July 1995. Prior to pursuing drug discovery technology, Mr.
Teig co-founded Tangent Systems Corporation, a developer of integrated circuit
design software, which was subsequently acquired by Cadence Design Systems, Inc.
Mr. Teig holds a B.S.E. in Electrical Engineering and Computer Science from
Princeton University.

Philippe O. Chambon, M.D., Ph.D. Dr. Chambon is a General Partner of the
Sprout Group. He joined Sprout in May 1995. From May 1993 to April 1995, Dr.
Chambon served as Manager in the Healthcare Practice of The Boston Consulting
Group, a leading management consulting firm. Previously, Dr. Chambon was an
executive with Sandoz Pharmaceuticals Corporation, a leading pharmaceutical
company, from September 1987 to April 1993. In his last capacity there, he was
the Executive Director of New Product Management. He is currently a director of
Transcend Therapeutics and of several private companies. Dr. Chambon received an
M.D. (with honors) and Ph.D. from the University of Paris and an M.B.A. from
Columbia University.

42
<PAGE> 44

Arthur Reidel. Mr. Reidel has served as a director of the Company since
September 1997. He currently serves as President, Chief Executive Officer and
Chairman of the Board of Pharsight Corporation, a privately held software
corporation, a position he has held since April 1996, and as a director from
April 1995. Prior to that, he was a private investor/consultant from April 1995
to March 1996. From October 1994 to March 1995, he served as Vice President,
Business Development of Viewlogic Systems, Inc., a publicly held software firm.
Mr. Reidel has served as a director of MacNeil Schwendler from December 1993 and
as a director of Formation Systems, Inc. from 1996 to the present. Mr. Reidel
has also served as President and Chief Executive Officer, Sunrise Test Systems,
Inc., a privately held software firm, from December 1992 to March 1994
(Viewlogic Systems, Inc. acquired Sunrise Test Systems, Inc. in September 1994),
and Vice President of Weitek Corporation from July 1991 to December 1992. Mr.
Reidel received an B.S. in mathematics from Massachusetts Institute of
Technology.

William Scott, Ph.D. Dr. Scott has served as a director of the Company
since January 1997. Since March 1997, Dr. Scott has served as the Chief
Executive Officer of Physiome Sciences, Inc. From 1983 until December 1996, Dr.
Scott served in various executive positions with Bristol-Myers Squibb
Pharmaceutical Research Institute and as its Senior Vice President, Drug
Discovery Research since 1991. Dr. Scott received a B.S. in Chemistry from the
University of Illinois and a Ph.D. in Biochemistry from the California Institute
of Technology and was an NIH Postdoctoral Fellow at The Rockefeller University.
Dr. Scott serves on the Board of Directors of a private company.

Members of the Board currently hold office and serve until the next annual
meeting of the stockholders of the Company or until their respective successors
have been elected. The Board is currently comprised of six directors. Under the
Company's Bylaws, as amended, beginning with the next annual meeting of
stockholders the Company's Board will be classified into three classes of
directors serving staggered three-year terms, with one class of directors to be
elected at each annual meeting of stockholders. The classification of directors
has the effect of making it more difficult to change the composition of the
Board. See "Description of Capital Stock -- Possible Anti-Takeover Effect of
Certain Charter Provisions."

All executive officers are appointed annually by and serve at the
discretion of the Board. All of the Company's executive officers are employed by
the Company at will.

Pursuant to the Company's 1997 Stock Incentive Plan, which was adopted by
the Board and approved by the Company's stockholders in October, 1997, directors
who are not officers or employees of the Company will receive periodic option
grants beginning with the next annual meeting of stockholders. See "-- Benefit
Plans."

COMMITTEES OF THE BOARD OF DIRECTORS

The Company has a standing Compensation Committee currently composed of Dr.
Chambon and Dr. Scott. The Compensation Committee reviews and acts on matters
relating to compensation levels and benefit plans for executive officers and key
employees of the Company, including salary and stock options. The Compensation
Committee is also responsible for granting stock awards, stock options and stock
appreciation rights and other awards to be made under the Company's existing
incentive compensation plans. The Company also has a standing Audit Committee
composed of Mr. Lamond and Mr. Reidel. The Audit Committee assists in selecting
the Company's independent auditors and in designating services to be performed
by, and maintaining effective communication with, those auditors. The Company
also has a standing Executive Committee currently composed of Mr. Lamond, Dr.
Anido and Dr. Chambon. The Executive Committee has the authority to exercise all
powers of the Board of Directors not designated to another committee when the
Board of Directors is not in session.

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<PAGE> 45

EXECUTIVE COMPENSATION

Summary of Cash and Certain Other Compensation

The following table sets forth the aggregate compensation earned by the
Company's President and Chief Executive Officer (both current and former) and
each of the other four most highly compensated executive officers whose salary
and bonus for 1996 exceeded $100,000 (the "Named Executive Officers") for
services rendered in all capacities to the Company for the year ended December
31, 1996:

SUMMARY COMPENSATION TABLE(1)

<TABLE>
<CAPTION>
LONG-TERM
COMPENSATION
AWARDS
ANNUAL COMPENSATION ---------------
------------------------------------ SECURITIES
OTHER ANNUAL UNDERLYING ALL OTHER
NAME AND PRINCIPAL POSITION SALARY(2) BONUS(3) COMPENSATION OPTIONS/SARS(#) COMPENSATION
- -------------------------------- --------- -------- ------------- --------------- ------------
<S> <C> <C> <C> <C> <C>
Vicente Anido, Jr., Ph.D.(4)
President, Chief Executive
Officer and Director.......... $ 200,417 $55,226 $ -- 422,417 $ --
Peter L. Myers, Ph.D.(5)
Chief Scientific Officer
and Chief Operating Officer,
Acting Chief Executive
Officer and Director.......... 225,233 43,050 -- -- --
John Saunders, Ph.D.
Vice President,
Medical Chemistry............. 145,000 23,200 27,125(6) -- --
Lee R. McCracken(7)
Vice President,
Business Development.......... 101,740 16,917 -- 72,500 --
Steven L. Teig
Vice President,
Advanced Technology........... 137,025 21,924 -- -- --
Lynn Caporale, Ph.D.(8)
Vice President, Strategic
Development................... 144,834 22,000 -- -- 130,572(9)
</TABLE>

- ---------------

(1) Pursuant to Instruction to Item 402(b) of Regulation S-K promulgated by the
Securities and Exchange Commission (the "Commission"), information with
respect to fiscal years prior to 1996 has not been included as the Company
was not a reporting company pursuant to Section 13(a) or 15(d) of the
Securities Exchange Act of 1934, as amended (the "Exchange Act"), and the
information has not been previously reported to the Commission in response
to a filing requirement.

(2) Includes amounts deferred pursuant to the Company's 401(k) Plan.

(3) Includes cash payments for bonuses earned by the Named Executive Officers
during 1996.

(4) Dr. Anido was hired in March 1996.

(5) Dr. Myers served as the Company's Chief Executive Officer from August 1995
until March 1996.

(6) Payments to cover relocation expenses.

(7) Mr. McCracken was hired in May 1996.

(8) Dr. Caporale resigned from the Company in November 1996.

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<PAGE> 46

(9) Represents payments of $27,572 made in 1996 for accrued vacation and
severance benefits, and payments of $103,000 made in 1997 for severance
payments accrued in 1996. See "-- Employment Arrangements and Change of
Control Arrangements."

Stock Options

The following table sets forth information concerning stock option grants
made to each of the Named Executive Officers for the year ended December 31,
1996. The Company granted no stock appreciation rights ("SARs") to Named
Executive Officers during 1996.

OPTION GRANTS IN LAST FISCAL YEAR

<TABLE>
<CAPTION>
POTENTIAL
REALIZABLE
INDIVIDUAL GRANTS VALUE AT ASSUMED
------------------------------------------------------- ANNUAL RATES OF
NUMBER OF % OF TOTAL STOCK PRICE
SECURITIES OPTIONS APPRECIATION FOR
UNDERLYING GRANTED TO EXERCISE OPTION TERMS(3)
OPTIONS/SARS EMPLOYEES IN PRICE EXPIRATION -------------------
NAME GRANTED(1) FISCAL YEAR PER SHARE(2) DATE 5% 10%
- --------------------------- ------------ ------------ ------------ ---------- -------- --------
<S> <C> <C> <C> <C> <C> <C>
Vicente Anido, Jr.,
Ph.D..................... 422,417 79.5% $ 0.30 03/13/06 $208,717 $343,050
Peter L. Myers, Ph.D....... -- -- -- -- -- --
John Saunders, Ph.D........ -- -- -- -- -- --
Lee R. McCracken........... 72,500 13.6 0.30 05/08/06 35,822 58,878
Steven L. Teig............. -- -- -- -- -- --
Lynn Caporale, Ph.D........ -- -- -- -- -- --
</TABLE>

- ---------------

(1) The grant dates for these options are as follows: March 14, 1996 for Dr.
Anido's option and May 9, 1996 for Mr. McCracken's option. Each option has a
maximum term of 10 years measured from the grant date, subject to earlier
termination upon the optionee's cessation of service with the Company. Each
option is immediately exercisable for all the option shares; however, any
shares purchased under the option will be subject to repurchase by the
Company, at the option exercise price paid per share, should the optionee
leave the Company prior to vesting in the shares. Dr. Anido's option was
fully vested with respect to 10% of the option shares on the grant date,
another 15% of the option shares vested upon his completion of one year of
service measured from the grant date, and the balance of the option shares
vest in a series of equal monthly installments over Dr. Anido's 36-month
period of service measured from the first anniversary of the grant date. The
shares subject to Mr. McCracken's option vest as follows: 25% upon his
completion of one year of service measured from the grant date and the
balance in a series of 36 successive equal monthly installments over his
continued period of service thereafter. The options were granted under the
1995 Stock Option/Stock Issuance Plan and will be incorporated into the new
1997 Stock Option Plan on the effective date of the Offering, but will
continue to be governed by their existing terms. See "Benefit Plans -- 1997
Stock Incentive Plan."

(2) The exercise price per share of options granted represented the fair market
value of the underlying shares of Common Stock on the dates the respective
options were granted as determined by the Board, considering all relevant
factors. The exercise price may be paid in cash or in shares of Common Stock
valued at fair market value on the exercise date or a combination of cash
and shares or any other form of consideration approved by the Board. After
the effective date of the Registration Statement of which this Prospectus is
a part, the fair market value of shares of Common Stock will be determined
in accordance with certain provisions of the Company's 1995 Stock
Option/Stock Issuance Plan based on the closing selling price per share of
Common Stock on the date in question on the primary exchange or national
market system on which the Company's common stock is listed or reported. If
shares of the Common Stock are not listed or admitted to trading on any
stock exchange nor traded on the Nasdaq National Market, then the fair
market value shall be determined by the Plan Administrator after taking into
account such factors as the Plan Administrator shall deem appropriate.

45
<PAGE> 47

(3) The 5% and 10% assumed annual rates of compounded stock price appreciation
are mandated by rules of the Commission. The price used for computing this
appreciation is the exercise price of the options, not the price of Common
Stock in this offering. There is no assurance provided to any executive
officer or any other holder of the Company's securities that the actual
stock price appreciation over the 10-year option term will be at the assumed
5% or 10% levels or at any other defined level.

Option Exercises and Holdings

The following table provides information concerning option exercises during
1996 by the Named Executive Officers and the value of unexercised options held
by each of the Named Executive Officers as of December 31, 1996. No SARs were
exercised during 1996 or outstanding as of December 31, 1996.

AGGREGATE OPTION EXERCISES IN LAST FISCAL YEAR AND FISCAL YEAR-END OPTION VALUES

<TABLE>
<CAPTION>
NUMBER OF SECURITIES
UNDERLYING VALUE OF UNEXERCISED
UNEXERCISED OPTIONS AT IN-THE-MONEY OPTIONS
SHARES DECEMBER 31, 1996(#) AT DECEMBER 31, 1996(3)
ACQUIRED ON VALUE ------------------------------ ------------------------------
NAME EXERCISE(#) REALIZED(1) EXERCISABLE(2) UNEXERCISABLE EXERCISABLE(2) UNEXERCISABLE
- --------------------- ----------- ----------- -------------- ------------- -------------- -------------
<S> <C> <C> <C> <C> <C> <C>
Vicente Anido, Jr.,
Ph.D............... -- $-- 422,417 -- $ 42,242 $--
Peter L. Myers,
Ph.D............... -- -- -- -- -- --
John Saunders,
Ph.D............... -- -- -- -- -- --
Lee R. McCracken..... 72,500 -- -- -- -- --
Steven L. Teig....... -- -- -- -- -- --
Lynn Caporale,
Ph.D............... -- -- -- -- -- --
</TABLE>

- ---------------

(1) "Value realized" is calculated on the basis of the fair market value of the
Common Stock on the date of exercise minus the exercise price and does not
necessarily indicate that the optionee sold such stock.

(2) The options are immediately exercisable, but any shares purchased thereunder
will be subject to repurchase by the Company, at the original option
exercise price paid per share, should Dr. Anido leave the Company prior to
vesting in the shares. As of October 15, 1997, Dr. Anido had vested in
167,204 of those shares.

(3) "Value" is defined as fair market price of the Common Stock at fiscal
year-end ($0.40) less exercise price.

COMPENSATION COMMITTEE INTERLOCKS AND INSIDER PARTICIPATION

During the year ended December 31, 1996, the Compensation Committee of the
Company's Board established the levels of compensation for the Company's
executive officers. The current members of the Company's Compensation Committee
are Dr. Chambon and Dr. Scott. See "Certain Transactions."

EMPLOYMENT ARRANGEMENTS AND CHANGE OF CONTROL ARRANGEMENTS

In March 1996, the Company and Dr. Anido entered into an agreement whereby
Dr. Anido is employed as President and Chief Executive Officer of the Company.
Pursuant to his agreement, Dr. Anido receives an annual base salary of $260,000,
which is reviewed annually by the Board of Directors, and is eligible for a
bonus of up to 25% of his annual base salary to be awarded at the discretion of
the Board of Directors. In the event the Company terminates Dr. Anido's
employment without "cause," Dr. Anido will be entitled to receive an aggregate
severance benefit of 12 months of his base salary and benefits less amounts
received by Dr. Anido from other full-time employment during that period. In
addition, pursuant to his employment agreement Dr. Anido received options to

46
<PAGE> 48

purchase 420,000 shares of Common Stock with an exercise price of $0.30 per
share. The shares subject to the option vest over Dr. Anido's four-year period
of service with the Company measured from the option grant date. Dr. Anido's
employment agreement also provides Dr. Anido with a right to maintain his pro
rata interest in the Company by purchasing new securities issued in a financing
other than a public offering, subject to certain exceptions.

In March 1995, the Company and Dr. Myers entered into an agreement whereby
Dr. Myers is employed as Chief Scientific Officer and Chief Operating Officer of
the Company. Pursuant to his agreement, Dr. Myers (i) received a signing bonus
of $26,250 towards the purchase of Company stock, (ii) receives an annual base
salary of $210,000, which is reviewed annually by the President and Chief
Executive Officer, and (iii) is eligible for a bonus of up to 25% of his annual
base salary to be awarded at the discretion of the Board of Directors. In
connection with the employment agreement, Dr. Myers was provided a home loan. In
the event the Company terminates Dr. Myers' employment without "cause," Dr.
Myers will be entitled to receive an aggregate severance benefit of nine months
of his base salary and benefits, unless he obtains full-time employment prior to
the end of that period, and nine months accelerated vesting to be applied to any
vesting requirements under any stock option or stock purchase agreements
outstanding between Dr. Myers and the Company at the time of his termination
without cause. Simultaneous with the execution of Dr. Myers' employment
agreement, the Company and Dr. Myers entered into a Stock Purchase Agreement
whereby Dr. Myers purchased 87,500 shares of Common Stock at $0.30 per share.
Those shares vest over Dr. Myers' four-year period of service with the Company
measured from the option grant date.

In March 1997, the Company and Ms. Eastham entered into an agreement
whereby she is employed as Vice President, Finance and Administration and Chief
Financial Officer. Pursuant to her agreement, Ms. Eastham (i) receives an annual
base salary of $186,000, which is reviewed annually by the Chief Executive
Officer and Board of Directors, and (ii) is eligible for a bonus of up to 20% of
her annual base salary to be awarded at the discretion of the Board of
Directors. In the event the Company terminates Ms. Eastham's employment without
"cause" within two years after her date of hire, Ms. Eastham will be entitled to
receive an aggregate severance benefit of her base salary and benefits for six
months, unless she obtains full-time employment prior to the end of that
six-month period. Simultaneous with the execution of Ms. Eastham's employment
agreement, the Company and Ms. Eastham entered into a Stock Option Agreement
granting her an option to purchase 87,500 shares of Common Stock with an
exercise price of $0.40 per share. The shares subject to the option vest over
her four-year period of service with the Company measured from the grant date.

In January 1996, the Company and Dr. Saunders entered into an agreement
whereby Dr. Saunders is employed as Vice President, Medicinal Chemistry of the
Company. Pursuant to his agreement, Dr. Saunders receives an annual base salary
of $145,000, which is reviewed annually by the President and Chief Executive
Officer, and is eligible for a bonus of up to 20% of his annual base salary to
be awarded at the discretion of the Board of Directors. Simultaneous with the
execution of the employment agreement, the Company and Dr. Saunders entered into
a stock option agreement granting him an option to purchase 83,825 shares of the
Company's common stock with an exercise price of $0.248 per share. The shares
subject to that option vest over Dr. Saunders' four-year period of service with
the Company measured from the option grant date.

In May 1996, the Company and Mr. McCracken entered into an agreement
whereby he is employed as Vice President, Business Development of the Company.
Pursuant to his agreement, Mr. McCracken received a signing bonus of $10,000 and
receives an annual base salary of $145,000, which is reviewed annually by the
President and Chief Executive Officer. In addition, Mr. McCracken is eligible
for a bonus of up to 20% of his annual base salary. In the event the Company
terminates Mr. McCracken's employment without "cause," Mr. McCracken will be
entitled to receive an aggregate severance benefit of nine months of his base
salary and benefits. Simultaneous with the execution of Mr. McCracken's
employment agreement, the Company and Mr. McCracken entered into a stock option
agreement granting Mr. McCracken an option to purchase 72,500 shares of Common

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<PAGE> 49

Stock with an exercise price of $0.30 per share. The shares subject to the
option vest over Mr. McCracken's four-year period of service measured from the
option grant date.

In July 1995, the Company and Mr. Teig entered into an agreement whereby he
is employed as Vice President of the Company. Pursuant to his agreement, Mr.
Teig receives an annual base salary of $135,000, which is reviewed annually by
the Board of Directors. In addition, Mr. Teig is eligible for a bonus of up to
20% of his annual base salary to be awarded at the discretion of the Board of
Directors. Simultaneous with the execution of the employment agreement, the
Company and Mr. Teig entered into a stock purchase agreement whereby Mr. Teig
purchased 50,000 shares of Common Stock at $0.30 per share. Under such stock
purchase agreement, the shares will vest, and the Company's repurchase rights
will accordingly lapse over Mr. Teig's four-year period of employment measured
from the date of issuance. Pursuant to his employment agreement, Mr. Teig was
granted, and subsequently exercised, an option to purchase 61,250 shares of
Company's Common Stock with an exercise price of $0.40 per share. Those shares
vest over Mr. Teig's four-year period of service measured from option grant
date.

In November 1994, the Company and Dr. Caporale entered into an agreement
whereby she was employed as Vice President, Strategic Development. Pursuant to
the agreement, Dr. Caporale received an annual base salary of $160,000 subject
to review and adjustments by the Board of Directors, and a bonus of up to 20% of
her annual base salary. In November 1996, Dr. Caporale resigned from the Company
and the employment agreement terminated. As a result of her termination, Dr.
Caporale received an aggregate severance benefit of nine months of her base
salary and benefits. Simultaneous with the execution of the employment
agreement, the Company and Dr. Caporale entered into a stock purchase agreement,
whereby Dr. Caporale purchased 43,750 shares of Common Stock at $0.20 per share,
and 29,785 were vested at the termination of Dr. Caporale's employment with the
Company.

In connection with an acquisition of the Company by merger or asset sale,
each outstanding option held by the Chief Executive Officer and the other Named
Executive Officers under the Predecessor Plan will terminate, unless those
options are assumed by the successor corporation. However, any options granted
to such individuals in the future under the 1997 Stock Incentive Plan will
automatically accelerate in full, except to the extent such options are to be
assumed by the successor corporation. See "Benefit Plans -- 1997 Stock Incentive
Plan." In addition, the Compensation Committee as Plan Administrator of the 1997
Stock Incentive Plan will have the authority to provide for the accelerated
vesting of the shares of Common Stock subject to outstanding options held by the
Chief Executive Officer and the Named Executive Officers, or any unvested shares
of Common Stock subject to direct issuances held by such individuals, in
connection with the termination of the officer's employment following: (i) a
merger or asset sale in which these options are assumed or the repurchase rights
applicable to those shares are assigned or (ii) certain changes in control of
the Company.

DIRECTOR COMPENSATION

The Company reimburses its directors for all reasonable and necessary
travel and other incidental expenses incurred in connection with their
attendance at meetings of the Board. Directors are not currently compensated for
serving on the Board. The Company has previously granted to certain non-employee
Board members an option to purchase 20,000 shares of Common Stock. Each
non-employee Board member who is serving as such on the effective date of the
1997 Stock Incentive Plan will receive a similar 20,000-share option, provided
he or she has not received a prior option grant from the Company. Each
individual who first becomes a non-employee Board member at any time after this
offering will receive a 20,000-share option grant on the date such individual
joins the Board. In addition, beginning with the first annual meeting of
stockholders following this offering, each such non-employee Board member who is
to continue to serve as a non-employee Board member will automatically be
granted an option to purchase 5,000 shares of Common Stock, provided such
individual has served on the Board for at least six months. These options will
have an exercise price equal to 100% of the fair market value of the Common
Stock on the grant date. The shares subject to each 20,000-share automatic
option grant will vest over a four-year period, with 25% of the option

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<PAGE> 50

shares vesting upon completion of one year of Board service from the grant date
and the balance of the option shares vesting in equal monthly installments over
the optionee's continued period of Board service over the next three years. The
shares subject to each 5,000-share annual automatic option will vest upon the
optionee's completion of one year of Board service measured from the grant date.
See "-- Benefit Plans -- 1997 Stock Incentive Plan."

BENEFIT PLANS

1997 Stock Incentive Plan

The Company's 1997 Stock Incentive Plan (the "1997 Plan") is intended to
serve as the successor equity incentive program to the Company's 1995 Stock
Option/Stock Issuance Plan, as amended (the "Predecessor Plan"). The 1997 Plan
was adopted by the Board and the stockholders on October 7, 1997. The 1997 Plan
is to become effective on the date the Underwriting Agreement for this offering
is executed (the "Plan Effective Date").

A total of 1,080,603 shares of Common Stock have been authorized for
issuance under the 1997 Plan. Such share reserve consists of (i) the number of
shares available for issuance under the Predecessor Plan on the Plan Effective
Date, including the shares subject to outstanding options, and (ii) an
additional increase of approximately 800,000 shares. To the extent any unvested
shares of Common Stock issued under the Predecessor Plan are repurchased by the
Company after the Plan Effective Date, at the exercise price paid per share, in
connection with the holder's termination of service, those repurchased shares
will be added to the reserve of Common Stock available for issuance under the
1997 Plan. In no event may any one participant in the 1997 Plan receive option
grants, separately exercisable stock appreciation rights or direct stock
issuances for more than 500,000 shares of Common Stock in the aggregate per
calendar year.

On the Plan Effective Date, outstanding options and unvested shares issued
under the Predecessor Plan will be incorporated into the 1997 Plan, and no
further option grants will be made under the Predecessor Plan. The incorporated
options will continue to be governed by their existing terms, unless the Plan
Administrator elects to extend one or more features of the 1997 Plan to those
options. Except as otherwise noted below, the incorporated options have
substantially the same terms as will be in effect for grants made under the
Discretionary Option Grant Program of the 1997 Plan.

The 1997 Plan is divided into five separate components: (i) the
Discretionary Option Grant Program under which eligible individuals in the
Company's employ or service (including officers, non-employee Board members and
consultants) may, at the discretion of the Plan Administrator, be granted
options to purchase shares of Common Stock at an exercise price not less than
100% of their fair market value on the grant date, (ii) the Stock Issuance
Program under which such individuals may, in the Plan Administrator's
discretion, be issued shares of Common Stock directly, through the purchase of
such shares at a price not less than 100% of their fair market value at the time
of issuance or as a bonus tied to the performance of services, (iii) the Salary
Investment Option Grant Program which may, in the Plan Administrator's sole
discretion, be activated for one or more calendar years and, if so activated,
will allow executive officers and other highly compensated employees the
opportunity to apply a portion of their base salary to the acquisition of
special below-market stock option grants, (iv) the Automatic Option Grant
Program under which option grants will automatically be made at periodic
intervals to eligible non-employee Board members to purchase shares of Common
Stock at an exercise price equal to 100% of their fair market value on the grant
date and (v) the Director Fee Option Grant Program which may, in the Plan
Administrator's sole discretion, be activated for one or more calendar years
and, if so activated, will allow non-employee Board members the opportunity to
apply a portion of the annual retainer fee, if any, otherwise payable to them in
cash each year to the acquisition of special below-market option grants.

The Discretionary Option Grant Program and the Stock Issuance Program will
be administered by the Compensation Committee. The Compensation Committee as
Plan Administrator will have complete discretion to determine which eligible
individuals are to receive option grants or stock issuances

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<PAGE> 51

under those programs, the time or times when such option grants or stock
issuances are to be made, the number of shares subject to each such grant or
issuance, the status of any granted option as either an incentive stock option
or a non-statutory stock option under the Federal tax laws, the vesting schedule
to be in effect for the option grant or stock issuance and the maximum term for
which any granted option is to remain outstanding. The Compensation Committee
will also have the exclusive authority to select the executive officers and
other highly compensated employees who may participate in the Salary Investment
Option Grant Program in the event that program is activated for one or more
calendar years, but neither the Compensation Committee nor the Board will
exercise any administrative discretion with respect to option grants under the
Salary Investment Option Grant Program or under the Automatic Option Grant or
Director Fee Option Grant Program for the non-employee Board members. All grants
under those three latter programs will be made in strict compliance with the
express provisions of each such program.

The exercise price for the shares of Common Stock subject to option grants
made under the 1997 Plan may be paid in cash or in shares of Common Stock valued
at fair market value on the exercise date. The option may also be exercised
through a same-day sale program without any cash outlay by the optionee. In
addition, the Plan Administrator may provide financial assistance to one or more
optionees in the exercise of their outstanding options or the purchase of their
unvested shares by allowing such individuals to deliver a full-recourse,
interest-bearing promissory note in payment of the exercise price and any
associated withholding taxes incurred in connection with such exercise or
purchase.

The Plan Administrator will have the authority, with the consent of the
affected option holders, to effect the cancellation of outstanding options under
the Discretionary Option Grant Program (including options incorporated from the
Predecessor Plan) in return for the grant of new options for the same or
different number of option shares with an exercise price per share based upon
the fair market value of the Common Stock on the new grant date.

Stock appreciation rights are authorized for issuance under the
Discretionary Option Grant Program which provide the holders with the election
to surrender their outstanding options for an appreciation distribution from the
Company equal to the excess of (i) the fair market value of the vested shares of
Common Stock subject to the surrendered option over (ii) the aggregate exercise
price payable for such shares. Such appreciation distribution may be made in
cash or in shares of Common Stock. None of the incorporated options from the
Predecessor Plan contain any stock appreciation rights.

In the event that the Company is acquired by merger or asset sale, each
outstanding option under the Discretionary Option Grant Program which is not to
be assumed by the successor corporation will automatically accelerate in full,
and all unvested shares under the Discretionary Option Grant and Stock Issuance
Programs will immediately vest, except to the extent the Company's repurchase
rights with respect to those shares are to be assigned to the successor
corporation. The Plan Administrator will have complete discretion to grant one
or more options under the Discretionary Option Grant Program which will become
fully exercisable for all the option shares in the event those options are
assumed in the acquisition and the optionee's service with the Company or the
acquiring entity terminates within a designated period following such
acquisition. The vesting of outstanding shares under the Stock Issuance Program
may be accelerated upon similar terms and conditions. The Plan Administrator
will also have the authority to grant options which will immediately vest upon
an acquisition of the Company, whether or not those options are assumed by the
successor corporation. The Plan Administrator is also authorized under the
Discretionary Option Grant and Stock Issuance Programs to grant options and to
structure repurchase rights so that the shares subject to those options or
repurchase rights will immediately vest in connection with a change in control
of the Company (whether by successful tender offer for more than 50% of the
outstanding voting stock or a change in the majority of the Board by reason of
one or more contested elections for Board membership), with such vesting to
occur either at the time of such change in control or upon the subsequent
termination of the individual's service within a designated period following
such change in control. The options

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<PAGE> 52

incorporated from the Predecessor Plan will terminate upon an acquisition of the
Company by merger or asset sale, unless those options are assumed by the
successor entity. However, the Plan Administrator will have the discretion to
extend the acceleration provisions of the 1997 to those options.

In the event the Plan Administrator elects to activate the Salary
Investment Option Grant Program for one or more calendar years, each executive
officer and other highly compensated employee of the Company selected for
participation may elect, prior to the start of the calendar year, to reduce his
or her base salary for that calendar year by a specified dollar amount not less
than $10,000 nor more than $50,000. If such election is approved by the Plan
Administrator, the individual will automatically be granted, on the first
trading day in January of the calendar year for which that salary reduction is
to be in effect, a non-statutory option to purchase that number of shares of
Common Stock determined by dividing the salary reduction amount by two-thirds of
the fair market value per share of Common Stock on the grant date. The option
will be exercisable at a price per share equal to one-third of the fair market
value of the option shares on the grant date. As a result, the total spread on
the option shares at the time of grant (the fair market value of the option
shares on the grant date less the aggregate exercise price payable for those
shares) will be equal to the amount of salary invested in that option. The
option will vest in a series of 12 equal monthly installments over the calendar
year for which the salary reduction is to be in effect and will be subject to
full and immediate vesting upon certain changes in the ownership or control of
the Company.

The Company has previously granted to certain non-employee Board members an
option to purchase 20,000 shares of Common Stock, and each non-employee Board
member who is serving as such on the Plan Effective Date and who has not
received such a grant will automatically receive an option at that time to
purchase 20,000 shares of Common Stock. Each individual who first becomes a
non-employee Board member at any time after the Plan Effective Date will also
receive a 20,000-share option grant on the date such individual joins the Board.
In addition and on the date of each Annual Stockholders Meeting held after the
Plan Effective Date, each such non-employee Board member who is to continue to
serve as a non-employee Board member will automatically be granted an option to
purchase 5,000 shares of Common Stock, provided such individual has served on
the Board for at least six months.

Each automatic grant for the non-employee Board members will have a term of
10 years, subject to earlier termination following the optionee's cessation of
Board service. Each automatic option will be immediately exercisable for all of
the option shares; however, any unvested shares purchased under the option will
be subject to repurchase by the Company, at the exercise price paid per share,
should the optionee cease Board service prior to vesting in those shares. The
shares subject to each initial 20,000-share automatic option grant will vest
over a four-year period, as follows: (i) 25% of the option shares upon the
optionee's completion of one year of Board service measured from the grant date
and (ii) the balance of the option shares in a series of 36 successive equal
monthly installments upon the optionee's completion of each additional month of
service measured from the first anniversary of the grant date. The shares
subject to each annual 5,000-share grant will vest upon the optionee's
completion of one year of Board service measured from the grant date. However,
the shares subject to each automatic option grant will immediately vest in full
upon certain changes in control or ownership of the Company or upon the
optionee's death or disability while a Board member.

Should the Director Fee Option Grant Program be activated in the future,
each non-employee Board member will have the opportunity to apply all or a
portion of any annual retainer fee otherwise payable in cash to the acquisition
of a below-market option grant. The option grant will automatically be made on
the first trading day in January in the year for which the retainer fee would
otherwise be payable in cash. The option will have an exercise price per share
equal to one-third of the fair market value of the option shares on the grant
date, and the number of shares subject to the option will be determined by
dividing the amount of the retainer fee applied to the program by two-thirds of
the fair market value per share of Common Stock on the grant date. As a result,
the total spread on the option (the fair market value of the option shares on
the grant date less the aggregate exercise price payable for those shares) will
be equal to the portion of the retainer fee invested in that option. The option
will

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<PAGE> 53

become exercisable for the option shares in a series of 12 equal monthly
installments over the calendar year for which the election is to be in effect.
However, the option will become immediately exercisable for all the option
shares upon (i) certain changes in the ownership or control of the Company or
(ii) the death or disability of the optionee while serving as a Board member.

The shares subject to each option under the Salary Investment Option Grant,
Automatic Option Grant and Director Fee Option Grant Programs will immediately
vest upon (i) an acquisition of the Company by merger or asset sale or (ii) the
successful completion of a tender offer for more than 50% of the Company's
outstanding voting stock or a change in the majority of the Board effected
through one or more contested elections for Board membership.

Limited stock appreciation rights will automatically be included as part of
each grant made under the Automatic Option Grant, Salary Investment Option Grant
and Director Fee Option Grant Programs and may be granted to one or more
officers of the Company as part of their option grants under the Discretionary
Option Grant Program. Options with such a limited stock appreciation right may
be surrendered to the Company upon the successful completion of a hostile tender
offer for more than 50% of the Company's outstanding voting stock. In return for
the surrendered option, the optionee will be entitled to a cash distribution
from the Company in an amount per surrendered option share equal to the excess
of (i) the highest price per share of Common Stock paid in connection with the
tender offer over (ii) the exercise price payable for such share.

The Board may amend or modify the 1997 Plan at any time, subject to any
required stockholder approval. The 1997 Plan will terminate on the earliest of
(i) October 31, 2007, (ii) the date on which all shares available for issuance
under the 1997 Plan have been issued as fully vested shares or (iii) the
termination of all outstanding options in connection with certain changes in
control or ownership of the Company.

1997 Employee Stock Purchase Plan

The Company's 1997 Employee Stock Purchase Plan (the "Purchase Plan") was
adopted by the Board and approved by the stockholders in October 1997 and will
become effective immediately upon the execution of the Underwriting Agreement
for this offering. The Purchase Plan is designed to allow eligible employees of
the Company and participating subsidiaries to purchase shares of Common Stock,
at semi-annual intervals, through their periodic payroll deductions under the
Purchase Plan, and a reserve of 150,000 shares of Common Stock has been
established for this purpose.

The Purchase Plan will be implemented in a series of successive offering
periods, each with a maximum duration for 12 months. However, the initial
offering period will begin on the execution date of the Underwriting Agreement
and will end on the last business day in January 1999. The next offering period
will commence on the first business day in February 1999, and subsequent
offering periods will commence as designated by the Plan Administrator.

Individuals who are eligible employees (scheduled to work more than 20
hours per week for more than 5 calendar months per year) on the start date of
any offering period may enter the Purchase Plan on that start date or on any
subsequent semi-annual entry date (the first business day of February or August
each year). Individuals who become eligible employees after the start date of
the offering period may join the Purchase Plan on any subsequent semi-annual
entry date within that offering period.

Payroll deductions may not exceed 10% of the employee's base salary, and
the accumulated payroll deductions of each participant will be applied to the
purchase of shares on his or her behalf on each semi-annual purchase date (the
last business day in January and July each year) at a purchase price per share
equal to 85% of the lower of (i) the fair market value of the Common Stock on
the participant's entry date into the offering period or (ii) the fair market
value on the semi-annual purchase date. In no event, however, may any
participant purchase more than 1,250 shares on any one semi-annual purchase
date.

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<PAGE> 54

Should the fair market value per share of Common Stock on any purchase date
be less than the fair market value per share on the start date of the two-year
offering period, then that offering period will automatically terminate, and a
new two-year offering period will begin on the next business day, with all
participants in the terminated offering to be automatically transferred to the
new offering period.

In the event the Company is acquired by merger or asset sale, all
outstanding purchase rights will automatically be exercised immediately prior to
the effective date of such acquisition. The purchase price will be equal to 85%
of the lower of (i) the fair market value per share of Common Stock on the
participant's entry date into the offering period in which such acquisition
occurs or (ii) the fair market value per share of Common Stock immediately prior
to such acquisition.

The Purchase Plan will terminate on the earlier of (i) the last business
day in July 2007, (ii) the date on which all shares available for issuance under
the Purchase Plan shall have been sold pursuant to purchase rights exercised
thereunder or (iii) the date on which all purchase rights are exercised in
connection with an acquisition of the Company by merger or asset sale.

The Board may at any time alter, suspend or discontinue the Purchase Plan.
However, certain amendments to the Purchase Plan may require stockholder
approval.

LIMITATIONS ON LIABILITY AND INDEMNIFICATION MATTERS

The Company's Certificate of Incorporation eliminates, subject to certain
exceptions, directors' personal liability to the Company or its stockholders for
monetary damages for breaches of fiduciary duties. The Certificate of
Incorporation does not, however, eliminate or limit the personal liability of a
director for (i) any breach of the director's duty of loyalty to the Company or
its stockholders, (ii) acts or omissions not in good faith or which involve
intentional misconduct or a knowing violation of law, (iii) unlawful payments of
dividends or unlawful stock repurchases or redemptions as provided in Section
174 of the Delaware General Corporation Law or (iv) any transaction from which
the director derived an improper personal benefit.

The Company's Bylaws provide that the Company shall indemnify its directors
and executive officers to the fullest extent permitted under the Delaware
General Corporation Law and may indemnify its other officers, employees and
other agents as set forth in the Delaware General Corporation Law. In addition,
the Company has entered into indemnification agreements with its directors and
officers. The indemnification agreements contain provisions that require the
Company, among other things, to indemnify its directors and executive officers
against certain liabilities (other than liabilities arising from intentional or
knowing and culpable violations of law) that may arise by reason of their status
or service as directors or executive officers of the Company or other entities
to which they provide service at the request of the Company and to advance
expenses they may incur as a result of any proceeding against them as to which
they could be indemnified. The Company believes that these provisions and
agreements are necessary to attract and retain qualified directors and officers.
The Company has obtained an insurance policy covering directors and officers for
claims that such directors and officers may otherwise be required to pay or for
which the Company is required to indemnify them, subject to certain exclusions.

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CERTAIN TRANSACTIONS

Since its formation in May 1994, the Company has issued, in private
placement transactions, shares of its Preferred Stock as follows (not adjusted
for the one-for-four reverse stock split): 1,000,000 shares of Series A
Preferred Stock at a price of $0.50 per share in August and November 1994;
2,226,667 shares of Series B Preferred Stock at a price of $0.75 per share in
November 1994; 17,158,486 shares of Series C Preferred Stock at a price of $0.62
per share in August 1995, September 1995 and April 1996; 9,869,205 shares of
Series D Preferred Stock at a price of $1.00 per share in November 1996; 232,500
shares of Series J Preferred Stock at a price of $0.10 per share in June 1997;
200,000 shares of Series Z Preferred Stock at a price of $0.50 in October 1994;
and 337,777 shares of Series Z as consideration pursuant to an asset purchase
agreement. The purchasers of Preferred Stock include, among others, the
following directors, executive officers and holders of more than 5% of the
Company's outstanding stock and their respective affiliates (all shares of
Preferred Stock are convertible into Common Stock on a four-for-one basis):

<TABLE>
<CAPTION>
PREFERRED STOCK
EXECUTIVE OFFICERS, DIRECTORS -------------------------------------------------------- TOTAL
AND 5% STOCKHOLDERS SERIES A SERIES B SERIES C SERIES D SERIES J CONSIDERATION
- ---------------------------------------- -------- --------- --------- --------- --------- -------------
<S> <C> <C> <C> <C> <C> <C>
Pierre R. Lamond(1)..................... 400,000 1,333,334 2,169,801 948,837 -- $ 3,494,114
Philippe O. Chambon, M.D., Ph.D.(2)..... -- -- 4,838,710 1,168,198 -- 4,168,198
Vicente Anido, Jr., Ph.D................ -- -- -- 240,000 -- 240,000
Lee R. McCracken(3)..................... -- -- -- 35,000 -- 35,000
Steven L. Teig.......................... -- -- -- 20,000 122,500 32,250
Entities affiliated with Sequoia
Capital(1)............................ 400,000 1,333,334 2,169,801 948,837 -- 3,494,114
Entities affiliated with Sprout
Capital(2)............................ -- -- 4,838,710 1,168,198 -- 4,168,198
Entities affiliated with Sorrento Growth
Partners(4)........................... -- -- 2,419,357 584,099 -- 2,084,100
Entities affiliated with Brinson Venture
Capital Fund(5)....................... -- -- 3,225,807 600,000 -- 2,600,000
</TABLE>

- ---------------

(1) Includes 4,348,842 shares purchased by Sequoia Capital VI, 238,949 shares
purchased by Sequoia Technology Partners VI, 128,043 shares purchased by
Sequoia XXIV and 63,115 shares purchased by Sequoia 1995, each of which is
affiliated with Sequoia Partners. Sequoia Partners is the general partner of
Sequoia Capital VI. Sequoia Partners has eight general partners, who are
also the general partners of Sequoia Technology Partners VI. Also includes
73,023 shares issuable to the entities affiliated with Sequoia Partners upon
exercise of warrants at an exercise price of $0.62 per share. In addition,
the entities affiliated with Sequoia Partners purchased 100,000 shares of
Common Stock of the Company in November 1994 (see below). Mr. Lamond is a
Director of the Company and a general partner of Sequoia Partners. Mr.
Lamond disclaims beneficial ownership of such shares except to the extent of
his pecuniary interest therein.

(2) Includes 5,545,317 shares purchased by Sprout Capital VII, L.P. and 461,591
shares purchased by DLJ Capital Corporation. Dr. Chambon is a Director of
the Company and a general partner of Sprout Capital VII, L.P., and DLJ
Capital Corporation is the general partner of Sprout Capital VII, L.P. Dr.
Chambon is a Divisional Vice President of DLJ Capital Corporation. Dr.
Chambon disclaims beneficial ownership of such shares except to the extent
of his pecuniary interest therein.

(3) Held by The Rufus L. McCracken Trust, dated 6/21/91, of which Mr. McCracken
is the sole trustee.

(4) Includes 999,206 shares purchased by Sorrento Ventures II, L.P. and
2,004,250 shares purchased by Sorrento Growth Partners I, L.P.

(5) Includes 536,452 shares purchased by the First National Bank of Chicago as
Custodian to the Brinson Trust Company as Trustee of the Brinson MAP Venture
Capital Fund III and 3,289,355

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<PAGE> 56

shares purchased by the First National Bank of Chicago as Custodian to the
Brinson Venture Capital Fund III, L.P.

Holders of Preferred Stock are entitled to certain registration rights with
respect to the Common Stock issued or issuable upon conversion thereof. See
"Description of Capital Stock -- Registration Rights."

In November 1994, the Company sold the following number of shares of Common
Stock to the respective entities at a price of $0.20 per share: 22,750 shares to
Sequoia Capital VI; 1,250 shares to Sequoia Technology Partners VI; and 1,000
shares to Sequoia XXIV.

In October 1997, the Company sold 1,000,000 shares of its Common Stock to
Elan International Services Ltd. in conjunction with entering into a
collaborative agreement.

In February 1997, the Company made a loan in the amount of $96,000 to Dr.
Anido, the President, Chief Executive Officer and a Director of the Company,
which loan is secured by shares of Common Stock issuable to Dr. Anido upon the
exercise of options. The loan is represented by a promissory note which is due
and payable on the earlier of February 23, 2002 or the occurrence of certain
events, such as the expiration of the 190-day period following completion of an
initial public offering. The loan bears no interest. The entire amount of the
loan is currently outstanding.

In June 1997, the Company made a loan in the amount of $23,044 to Dr. Anido
which is secured by shares of Common Stock issuable to Dr. Anido upon the
exercise of options. The loan is represented by a promissory note which is due
and payable in three annual installments and is due in full upon the third
anniversary of the loan. The loan bears an interest rate of 6.14%. The entire
amount of the loan is currently outstanding.

In September 1995, the Company made a loan in the amount of $150,000 to Dr.
Myers, the Vice President, Chief Scientific Officer, Chief Operating Officer and
a Director of the Company, which loan is secured by shares of Common Stock. The
loan is represented by a promissory note which is due and payable on the earlier
of September 5, 2000 or the occurrence of certain events, such as the expiration
of the 180-day period following completion of a public offering. The loan bears
an interest equal to the applicable minimum Federal rate on the date of the
loan. The entire amount of the loan is currently outstanding.

In August 1996, the Company made a loan in the amount of $66,125 to Dr.
Saunders for relocation in connection with employment, which is secured by a
deed of trust. The loan is represented by a promissory note which is due and
payable on the earlier of August 28, 1999 or the occurrence of certain events,
such as the expiration of the 30-day period following the date Dr. Saunders
ceases to be a full-time employee of the Company. The loan bears no interest.
Dr. Saunders has made a principal payment of $22,000.

For information regarding employment agreements with Named Executive
Officers, see "Management -- Employment Agreements and Change of Control
Arrangements."

All of the Company's officers are employed by the Company at will. The
Company has entered into indemnification agreements with each of its directors
and executive officers. See "Management -- Limitations on Liability and
Indemnification Matters."

The Company expects that all future transactions between the Company and
its officers, directors and principal stockholders and their affiliates will be
approved in accordance with the Delaware General Corporation Law by a majority
of the Board, as well as by a majority of the independent and disinterested
directors of the Board, and will be on terms no less favorable to the Company
than could be obtained from unaffiliated third parties.

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<PAGE> 57

PRINCIPAL STOCKHOLDERS

The following table sets forth certain information regarding the beneficial
ownership of the Common Stock as of October 15, 1997, and as adjusted to reflect
the sale of the shares of the Common Stock offered hereby by the Company, by (i)
all those known by the Company to be beneficial owners of more than 5% of its
outstanding Common Stock, (ii) each director of the Company, (iii) each of the
Named Executive Officers of the Company and (iv) all directors and executive
officers of the Company as a group.

<TABLE>
<CAPTION>
PERCENTAGE OF SHARES
SHARES BENEFICIALLY OWNED(2)
BENEFICIALLY ----------------------------------
NAME AND ADDRESS OF BENEFICIAL OWNER OWNED(1) PRIOR TO OFFERING AFTER OFFERING
- -------------------------------------------------------- ------------ ----------------- --------------
<S> <C> <C> <C>
Sprout Capital VII, L.P. and affiliated entities(3)..... 1,501,729 13.7% 11.4%
3000 Sand Hill Road
Building 3, Suite 170
Menlo Park, CA 94025
Sequoia Capital VI and affiliated entities(4)........... 1,237,999 11.3% 9.4%
3000 Sand Hill Road
Building 4, Suite 280
Menlo Park, CA 94025
Elan International Services Ltd......................... 1,000,000 9.1% 7.6%
102 St. James Court
Flatts
Smiths, FL04
Bermuda
Brinson MAP Venture Capital Fund III and affiliated
entities(5)........................................... 956,453 8.7% 7.2%
209 S. LaSalle Street
Chicago, IL 60604-1295
Sorrento Growth Partners I, L.P. and affiliated
entities(6)........................................... 750,867 6.8% 5.7%
4370 La Jolla Village Dr., Suite 1040
San Diego, CA 92122
Pierre R. Lamond(4)..................................... 1,237,999 11.3% 9.4%
Vicente Anido, Jr., Ph.D.(7)............................ 582,417 5.3% 4.4%
Peter L. Myers, Ph.D.(8)................................ 272,500 2.5% 2.0%
Philippe O. Chambon, MD., Ph.D.(3)...................... 1,501,729 13.7% 11.4%
Arthur Reidel(9)........................................ 20,000 * *
William Scott, Ph.D.(10)................................ 20,000 * *
Lee R. McCracken(11).................................... 93,750 * *
John Saunders, Ph.D..................................... 83,825 * *
Steven L. Teig(12)...................................... 246,875 2.2% 1.9%
Lynn Caporale, Ph.D..................................... 38,062 * *
One Sherman Square
New York, NY 10023
All directors and executive officers
as a group (9 persons)(13)............................ 4,067,145 36.2% 30.1%
</TABLE>

- ---------------

* Represents beneficial ownership of less than one percent of the outstanding
shares of the Company's Common Stock.

(1) Except as indicated in the footnotes to this table, the persons named in
the table have sole voting and investment power with respect to all shares
of Common Stock shown as beneficially owned by them. Share ownership in
each case includes shares issuable upon exercise of certain

56
<PAGE> 58

outstanding options as described in the footnotes below. The address for
those individuals for which an address is not otherwise indicated is: 9050
Camino Santa Fe, San Diego, CA 92121.

(2) Percentage of ownership is calculated pursuant to Commission Rule
13d-3(d)(1).

(3) Includes 1,386,331 shares purchased by Sprout Capital VII, L.P. and 115,398
shares purchased by DLJ Capital Corporation. DLJ Capital Corporation is the
managing general partner of Sprout Capital VII, L.P. Dr. Chambon is a
Director of the Company, a general partner of Sprout Capital VII, L.P. and
Divisional Vice President of DLJ Capital Corporation. Dr. Chambon disclaims
beneficial ownership of such shares except to the extent of his pecuniary
interest therein.

(4) Includes 1,109,962 shares held by Sequoia Capital VI, 60,988 shares held by
Sequoia Technology Partners VI, 33,012 shares held by Sequoia XXIV and
15,780 shares held by Sequoia 1995, each of which is affiliated with
Sequoia Partners. Sequoia Partners is the general partner of Sequoia
Capital VI. Sequoia Partners has eight general partners, who are also the
general partners of Sequoia Technology Partners VI. Also includes 16,613,
913 and 731 shares held by Sequoia Capital VI, Sequoia Technology Partners
VI and Sequoia XXIV, respectively, issuable upon exercise of warrants
exercisable within 60 days of October 15, 1997. Mr. Lamond is a Director of
the Company and a general partner of Sequoia Partners. Mr. Lamond disclaims
beneficial ownership of such shares except to the extent of his pecuniary
interest therein.

(5) Includes 134,113 shares purchased by the First National Bank of Chicago as
Custodian to the Brinson Trust Company as Trustee of the Brinson MAP
Venture Capital Fund III and 822,340 shares purchased by The First National
Bank of Chicago as Custodian to the Brinson Venture Capital Fund III, L.P.

(6) Includes 249,803 shares held by Sorrento Ventures II, L.P. and 501,064
shares held by Sorrento Growth Partners I, L.P.

(7) Includes 100,000 shares issuable upon exercise of options exercisable
within 60 days of October 15, 1997.

(8) Includes 50,000 shares issuable upon exercise of options exercisable within
60 days of October 15, 1997.

(9) Includes 20,000 shares issuable upon exercise of options exercisable within
60 days of October 15, 1997.

(10) Includes 20,000 shares issuable upon exercise of options exercisable within
60 days of October 15, 1997.

(11) Includes 8,750 shares held by the Rufus L. McCracken Trust, dated 6/21/91,
of which Mr. McCracken is the sole Trustee.

(12) Includes 50,000 shares issuable upon exercise of options exercisable within
60 days of October 15, 1997.

(13) Includes 270,757 shares issuable upon the exercise of options or warrants
exercisable within 60 days of October 15, 1997.

57
<PAGE> 59

DESCRIPTION OF CAPITAL STOCK

Upon completion of this offering, the Company will be authorized to issue
40,000,000 shares of Common Stock, $0.001 par value per share, and 5,000,000
shares of undesignated Preferred Stock, $0.001 par value per share.

COMMON STOCK

As of September 30, 1997, there were 9,668,505 shares of Common Stock
outstanding and held of record by approximately 125 stockholders. The holders of
Common Stock are entitled to one vote for each share held of record on all
matters submitted to a vote of the stockholders. Subject to preferences that may
be applicable to any outstanding shares of Preferred Stock, holders of Common
Stock are entitled to receive ratably such dividends as may be declared by the
Board out of funds legally available. See "Dividend Policy." All outstanding
shares of Common Stock are fully paid and nonassessable.

PREFERRED STOCK

After completion of this offering, the Board will have the authority,
without further action by the stockholders, to issue up to 5,000,000 shares of
Preferred Stock in one or more series and to fix the rights, priorities,
preferences, qualifications, limitations and restrictions, including dividend
rights, conversion rights, voting rights, terms of redemption, terms of sinking
funds, liquidation preferences and the number of shares constituting any series
or the designation of such series, which could decrease the amount of earnings
and assets available for distribution to holders of Common Stock or adversely
affect the rights and powers, including voting rights, of the holders of the
Common Stock. The issuance of Preferred Stock could have the effect of delaying
or preventing a change in control of the Company or make removal of management
more difficult. Additionally, the issuance of Preferred Stock may have the
effect of decreasing the market price of the Common Stock and may adversely
affect the voting and other rights of the holders of Common Stock. There are
currently no shares of Preferred Stock outstanding and the Company has no
current plans to issue any of the Preferred Stock.

WARRANTS

In December 1994, in conjunction with an equipment lease financing, the
Company issued a warrant to Comdisco, Inc. to purchase up to 20,914 shares of
Common Stock at $2.00 per share, exercisable at any time and prior to the
earlier of December 20, 2004 or five years following the Company's initial
public offering. The warrant contains provisions for the adjustment of the
exercise price and the aggregate number of shares issuable upon exercise of the
warrant under certain circumstances, including stock dividends, stock splits,
reorganizations, reclassifications or consolidations. The warrant provides that
the warrant holder may exercise the warrant without payment of cash by
surrendering the warrant and receiving shares of Common Stock equal to the value
of the warrant surrendered.

In June 1995, in connection with a product development collaboration, the
Company issued a warrant to LJL BioSystems, Inc. to purchase 8,750 shares of
Common Stock, exercisable at any time and prior to June 15, 2000, at $0.30 per
share. The warrant contains provisions for the adjustment of the exercise price
and the aggregate number of shares issuable upon exercise of the warrant under
certain circumstances, including stock dividends, stock splits, reorganizations,
reclassifications or consolidations.

In August 1995, in connection with the Series C Preferred Stock private
placement, the Company issued warrants to five investors to purchase an
aggregate of 30,242 shares of Common Stock, exercisable at any time and prior to
August 2000 at $2.48 per share. Each warrant contains provisions for the
adjustment of the exercise price and the aggregate number of shares issuable
upon exercise of the warrant under certain circumstances, including stock
dividends, stock splits, reorganizations, reclassifications or consolidations.
Each warrant provides that the warrant holder may exercise the

58
<PAGE> 60

warrant without payment of cash by surrendering the warrant and receiving shares
of Common Stock equal to the value of the warrant surrendered.

In April 1996, in conjunction with equipment lease financings, the Company
issued warrants to Comdisco, Inc. to purchase up to an aggregate of 35,383
shares of Common Stock at $2.48 per share, exercisable at any time and prior to
the earlier of April 2003 or three years after the Company's initial public
offering. The number of shares issuable pursuant to these warrants was dependent
on the aggregate amount financed with Comdisco, and pursuant to these warrants,
Comdisco has the right to purchase an aggregate of 26,647 shares of the Company.
Each warrant contains provisions for the adjustment of the exercise price and
the aggregate number of shares issuable upon exercise of each warrant under
certain circumstances, including stock dividends, stock splits, reorganizations,
reclassifications or consolidations. Each warrant provides that the warrant
holder may exercise the warrant without payment of cash by surrendering the
warrant and receiving shares of Common Stock equal to the value of the warrant
surrendered.

In May 1996, in conjunction with an equipment lease financing, the Company
issued warrants to Silicon Valley Bank and MMC/GATX Partnership No. 1 to
purchase up to 6,896 and 21,331 shares of Common Stock, respectively, at $2.48
per share, respectively, exercisable at any time and prior to the earlier of May
2006 or five years following the Company's initial public offering. Each warrant
contains provisions for the adjustment of the exercise price and the aggregate
number of shares issuable upon exercise of each warrant under certain
circumstances, including stock dividends, stock splits, reorganizations,
reclassifications or consolidations. Each warrant provides that the warrant
holder may exercise the warrant without payment of cash by surrendering the
warrant and receiving shares of Common Stock equal to the value of the warrant
surrendered.

In June 1996, in conjunction with equipment lease financings, the Company
issued warrants to Comdisco, Inc. to purchase up to an aggregate of 24,698
shares of Common Stock at $2.48 per share, exercisable at any time and prior to
the earlier of June 2003 or three years after the Company's initial public
offering. Each warrant contains provisions for the adjustment of the exercise
price and the aggregate number of shares issuable upon exercise of each warrant
under certain circumstances, including stock dividends, stock splits,
reorganizations, reclassifications or consolidations. Each warrant provides that
the warrant holder may exercise the warrant without payment of cash by
surrendering the warrant and receiving shares of Common Stock equal to the value
of the warrant surrendered.

REGISTRATION RIGHTS

The holders of approximately 7,754,933 shares of Common Stock or their
permitted transferees (the "Holders") are entitled to certain rights with
respect to the registration of such shares under the Securities Act. Under the
terms of agreements between the Company and such Holders, if the Company
proposes to register any of its securities under the Securities Act for its own
account, such Holders are entitled to notice of such registration and are
entitled to include shares of such Common Stock therein, provided, among other
conditions, that the underwriters of any such offering have the right to limit
the number of shares included in such registration. In addition, Holders of at
least 50% of approximately 7,754,933 shares of Common Stock with demand
registration rights may require the Company to prepare and file a registration
statement under the Securities Act with respect to the shares entitled to demand
registration rights, and the Company is required to use its diligent best
efforts to effect such registration, subject to certain conditions and
limitations. The Company is not obligated to effect more than two of these
stockholder-initiated registrations nor to effect such a registration within 180
days following an offering of the Company's securities, including the Offering
made hereby. The Holders may also request the Company to register such shares on
Form S-3 provided the shares registered have an aggregate market value of at
least $500,000. The Company is not obligated to effect more than one of these
registrations pursuant to Form S-3 in any 12-month period. Generally, the
Company is required to bear the expense of all such registrations. The
registration rights of each Holder expires at such time after the Offering as
all shares held by such Holder can be

59
<PAGE> 61

sold within any three-month period pursuant to Rule 144. All rights of the
Holders to require registration of the resale of their shares in connection with
this Offering have been waived.

POSSIBLE ANTI-TAKEOVER EFFECT OF CERTAIN CHARTER PROVISIONS

Restated Certificate of Incorporation and Restated Bylaws

The Company's Restated Certificate of Incorporation authorizes the Board to
establish one or more series of undesignated Preferred Stock, the terms of which
can be determined by the Board at the time of issuance. See "-- Preferred
Stock." The Restated Certificate of Incorporation also provides that all
stockholder action must be effected at a duly called meeting of stockholders and
not by a consent in writing. The Company's Restated Bylaws provide that the
Company's Board will be classified into three classes of directors beginning at
the next annual meeting of stockholders. See "Management -- Executive Officers,
Key Employees and Directors." In addition, the Restated Bylaws do not permit
stockholders of the Company to call a special meeting of stockholders; only the
Company's Chief Executive Officer, President, Chairman of the Board or a
majority of the Board are permitted to call a special meeting of stockholders.
The Restated Bylaws also require that stockholders give advance notice to the
Company's secretary of any nominations for director or other business to be
brought by stockholders at any stockholders' meeting and require a supermajority
vote of members of the Board and/or stockholders to amend certain Restated Bylaw
provisions. These provisions of the Restated Certificate of Incorporation and
the Restated Bylaws could discourage potential acquisition proposals and could
delay or prevent a change in control of the Company. Such provisions may also
have the effect of preventing changes in the management of the Company.

Delaware Anti-Takeover Statute

The Company is subject to Section 203 of the Delaware General Corporation
Law ("Section 203") which, subject to certain exceptions, prohibits a Delaware
corporation from engaging in any business combination with any interested
stockholder (defined as any person or entity that is the beneficial owner of at
least 15% of a corporation's voting stock) for a period of three years following
the time that such stockholder became an interested stockholder, unless: (i)
prior to such time, the board of directors of the corporation approved either
the business combination or the transaction that resulted in the stockholder's
becoming an interested stockholder; (ii) upon consummation of the transaction
that resulted in the stockholder's becoming an interested stockholder, the
interested stockholder owned at least 85% of the voting stock of the corporation
outstanding at the time the transaction commenced, excluding, for purposes of
determining the number of shares outstanding, those shares owned (x) by persons
who are directors and also officers and (y) by employee stock plans in which
employee participants do not have the right to determine confidentially whether
shares held subject to the plan will be tendered in a tender or exchange offer;
or (iii) at or subsequent to such time, the business combination is approved by
the Board and authorized at an annual or special meeting of stockholders, and
not by written consent, by the affirmative vote of at least two-thirds of the
outstanding voting stock that is not owned by the interested stockholder.

Section 203 defines business combination to include:. (i) any merger or
consolidation involving the corporation and the interested stockholder; (ii) any
sale, lease, exchange, mortgage, transfer, pledge or other disposition involving
the interested stockholder and 10% or more of the assets of the corporation;
(iii) subject to certain exceptions, any transaction which results in the
issuance or transfer by the corporation of any stock of the corporation to the
interested stockholder; (iv) any transaction involving the corporation that has
the effect of increasing the proportionate share of the stock of any class or
series of the corporation beneficially owned by the interested stockholder; or
(v) the receipt by the interested stockholder of the benefit of any loans,
advances, guarantees, pledges or other financial benefits provided by or through
the corporation.

TRANSFER AGENT AND REGISTRAR

The transfer agent and registrar for the Common Stock is American Stock
Transfer and Trust Company.

60
<PAGE> 62

SHARES ELIGIBLE FOR FUTURE SALE

Based upon the number of shares outstanding as of September 30, 1997 (after
giving effect to the issuance of an aggregate of 1,250,000 shares to
collaborative partners in October 1997), upon completion of this offering, there
will be 13,168,505 shares of Common Stock of the Company outstanding. There were
also approximately 26,177 shares covered by vested options outstanding, which
are not considered to be outstanding shares. Of the outstanding shares,
3,183,575 shares, including the 2,250,000 shares of Common Stock sold in this
offering, will be immediately eligible for resale in the public market without
restriction under the Securities Act, except that any shares purchased in this
offering by affiliates of the Company ("Affiliates"), as that term is defined in
Rule 144 under the Securities Act ("Rule 144"), may generally only be resold in
compliance with applicable provisions of Rule 144. Beginning approximately 90
days after the date of this Prospectus, approximately 867,573 additional shares
of Common Stock (including approximately 42,727 shares covered by options
exercisable within the 90-day period following the date of this Prospectus) will
become eligible for immediate resale in the public market, subject to compliance
as to certain of such shares with applicable provisions of Rules 144 and 701.

The Company, the executive officers and directors of the Company and
certain security holders have agreed pursuant to lock-up agreements that they
will not, without the prior written consent of BancAmerica Robertson Stephens,
offer, sell or otherwise dispose of the shares of Common Stock beneficially
owned by them for a period of 180 days from the date of this Prospectus. Each
holder who signed a lock-up agreement has agreed, subject to certain limited
exceptions, not to sell or otherwise dispose of any of the shares held by them
as of the date of this Prospectus for a period of 180 days after the date of
this Prospectus without the prior written consent of BancAmerica Robertson
Stephens. At the end of such 180-day period, approximately 11,502,437 shares of
Common Stock (including approximately 52,657 shares issuable upon exercise of
vested options) will be eligible for immediate resale, subject to compliance
with Rule 144 and Rule 701. The remainder of the approximately 1,666,068 shares
of Common Stock outstanding or issuable upon exercise of options held by
existing stockholders or option holders will become eligible for sale at various
times over a period of less than two years and could be sold earlier if the
holders exercise any available registration rights or upon vesting pursuant to
the Company's standard four year vesting schedule.

In general, under Rule 144 as recently amended, beginning approximately 90
days after the effective date of the Registration Statement of which this
Prospectus is a part, a stockholder, including an Affiliate, who has
beneficially owned his or her restricted securities (as that term is defined in
Rule 144) for at least one year from the later of the date such securities were
acquired from the Company or (if applicable) the date they were acquired from an
Affiliate is entitled to sell, within any three-month period, a number of such
shares that does not exceed the greater of 1% of the then outstanding shares of
Common Stock (approximately 132,000 shares immediately after the offering) or
the average weekly trading volume in the Common Stock during the four calendar
weeks preceding the date on which notice of such sale was filed under Rule 144,
provided certain requirements concerning availability of public information,
manner of sale and notice of sale are satisfied. In addition, under Rule 144(k),
if a period of at least two years has elapsed between the later of the date
restricted securities were acquired from the Company or (if applicable) the date
they were acquired from an Affiliate of the Company, a stockholder who is not an
Affiliate of the Company at the time of sale and has not been an Affiliate of
the Company for at least three months prior to the sale is entitled to sell the
shares immediately without compliance with the foregoing requirements under Rule
144.

Securities issued in reliance on Rule 701 (such as shares of Common Stock
that may be acquired pursuant to the exercise of certain options granted prior
to this offering) are also restricted securities and, beginning 90 days after
the date of this Prospectus, may be sold by stockholders other than an Affiliate
of the Company subject only to the manner of sale provisions of Rule 144 and by
an Affiliate under Rule 144 without compliance with its one-year holding period
requirement.

61
<PAGE> 63

Prior to this offering, there has been no public market for the Common
Stock. No prediction can be made as to the effect, if any, that market sales of
shares or the availability of shares for sale will have on the market price of
the Common Stock prevailing from time to time. The Company is unable to estimate
the number of shares that may be sold in the public market pursuant to Rule 144,
since this will depend on the market price of the Common Stock, the personal
circumstances of the sellers and other factors. Nevertheless, sales of
significant amounts of the Common Stock of the Company in the public market
could adversely affect the market price of the Common Stock and could impair the
Company's ability to raise capital through an offering of its equity securities.

In addition, the Company intends to register on the effective date of this
offering a total of 1,925,606 shares of Common Stock subject to outstanding
options or reserved for issuance under the Company's 1997 Stock Incentive Plan
or outstanding shares which are subject to repurchase by the Company plus
150,000 shares of Common Stock reserved for issuance under its 1997 Employee
Stock Purchase Plan. Further, upon expiration of such lock-up agreements,
holders of approximately 7,754,933 shares of Common Stock will be entitled to
certain registration rights with respect to such shares. If such holders, by
exercising their registration rights, cause a large number of shares to be
registered and sold in the public market, such sales could have a material
adverse effect on the market price of the Common Stock.

62
<PAGE> 64

UNDERWRITING

The Underwriters named below, acting through their representatives,
BancAmerica Robertson Stephens, Donaldson, Lufkin & Jenrette Securities
Corporation and UBS Securities LLC (the "Representatives"), have severally
agreed with the Company, subject to the terms and conditions of the Underwriting
Agreement, to purchase the numbers of shares of Common Stock set forth opposite
their respective names below. The Underwriters are committed to purchase and pay
for all such shares if any are purchased.

<TABLE>
<CAPTION>
NUMBER
OF
UNDERWRITER SHARES
------------------------------------------------------------------ ----------
<S> <C>
BancAmerica Robertson Stephens....................................
Donaldson, Lufkin & Jenrette Securities Corporation...............
UBS Securities LLC................................................
---------
Total................................................... 2,250,000
=========
</TABLE>

The Representatives have advised the Company that the Underwriters propose
to offer shares of the Common Stock to the public at the initial public offering
price set forth on the cover page of this Prospectus and to certain dealers at
such price less a concession of not in excess of $ per share, of which
$ may be reallowed to other dealers. After the initial public offering,
the public offering price, concession and reallowance to dealers may be reduced
by the Representatives. No such reduction shall change the amount of proceeds to
be received by the Company as set forth on the cover page of this Prospectus.

The Company has granted to the Underwriters an option, exercisable during
the 30-day period after the date of this Prospectus, to purchase up to 337,500
additional shares of Common Stock, at the same price per share as will be paid
for the 2,250,000 shares that the Underwriters have agreed to purchase. To the
extent that the Underwriters exercise such option, each of the Underwriters will
have a firm commitment to purchase approximately the same percentage of such
additional shares that the number of shares of Common Stock to be purchased by
it shown in the above table represents as a percentage of the 2,250,000 shares
offered hereby. If purchased, such additional shares will be sold by the
Underwriters on the same terms as those on which the 2,250,000 shares are being
sold.

The Underwriting Agreement contains covenants of indemnity among the
Underwriters and the Company against certain civil liabilities, including
liabilities under the Securities Act and liabilities arising from breaches of
representations and warranties contained in the Underwriting Agreement.

Each officer and director and certain holders of shares of the Company's
Common Stock have agreed with the Representatives, for a period of 180 days
after the date of this Prospectus (the "Lock-Up Period"), subject to certain
exceptions, not to offer to sell, contract to sell, or otherwise sell, dispose
of, loan, pledge or grant any rights with respect to any shares of Common Stock,
any options or warrants to purchase any shares of Common Stock, or any
securities convertible into or exchangeable for shares of Common Stock owned as
of the date of this Prospectus or thereafter acquired directly by such holders
or with respect to which they have or hereafter acquire the power of
disposition, without the prior written consent of BancAmerica Robertson
Stephens. However, BancAmerica Robertson Stephens may, in its sole discretion
and at any time without notice, release all or any portion of the securities
subject to lock-up agreements. There are no agreements between the
Representatives and any of the Company's stockholders providing consent by the
Representatives to the sale of shares prior to the expiration of the Lock-Up
Period. The Company has agreed that during the Lock-Up Period, the Company will
not, subject to certain exceptions, without the prior written consent of
BancAmerica Robertson Stephens, (i) consent to the disposition of any shares
held by stockholders prior to the expiration of the Lock-Up Period or (ii)
issue, sell, contract to sell or otherwise dispose of, any shares of Common
Stock, any options or warrants to purchase any shares of Common Stock or any
securities convertible into, exercisable for or exchangeable for shares of
Common Stock, other than the Company's sale of shares in this offering, the
issuance of Common Stock upon the exercise of

63
<PAGE> 65

outstanding options and warrants and the Company's issuance of options and stock
under the existing stock option and stock purchase plans. See "Shares Eligible
for Future Sale."

The Underwriters do not intend to confirm sales to any accounts over which
they exercise discretionary authority in excess of 5% of the number of shares of
Common Stock offered hereby.

Prior to this offering, there has been no public market for the Common
Stock of the Company. Consequently, the initial public offering price for the
Common Stock offered hereby will be determined through negotiations between the
Company and the Representatives. Among the factors to be considered in such
negotiations are prevailing market conditions, certain financial information of
the Company, market valuations of other companies that the Company and the
Representatives believe to be comparable to the Company, estimates of the
business potential of the Company, the present state of the Company's
development and other factors deemed relevant.

Certain persons participating in this offering may engage in transactions,
including syndicate covering transactions or the imposition of penalty bids,
which may involve the purchase of Common Stock on the Nasdaq National Market or
otherwise. Such transactions may stabilize or maintain the market price of the
Common Stock at a level above that which might otherwise prevail in the open
market and, if commenced, may be discontinued at any time.

The Representatives have advised the Company that, pursuant to Regulation M
under the Securities Act, certain persons participating in the offering may
engage in transactions, including stabilizing bids, syndicate covering
transactions or the imposition of penalty bids, which may have the effect of
stabilizing or maintaining the market price of the Common Stock at a level above
that which might otherwise prevail in the open market. A "stabilizing bid" is a
bid for or the purchase of the Common Stock on behalf of the Underwriters for
the purpose of fixing or maintaining the price of the Common Stock. A "syndicate
covering transaction" is the bid for or the purchase of the Common Stock on
behalf of the Underwriters to reduce a short position incurred by the
Underwriters in connection with the offering. A "penalty bid" is an arrangement
permitting the Representatives to reclaim the selling concession otherwise
accruing to an Underwriter or syndicate member in connection with the offering
if the Common Stock originally sold by such Underwriter or syndicate member is
purchased by the Representatives in a syndicate covering transaction and has
therefore not been effectively placed by such Underwriter or syndicate member.
The Representatives have advised the Company that such transactions may be
effected on the Nasdaq National Market or otherwise and, if commenced, may be
discontinued at any time.

The offering is being conducted in accordance with Rule 2720 ("Rule 2720")
of the National Association of Securities Dealers, Inc. (the "NASD") which
provides that, among other things, when an NASD member firm participates in the
offering of equity securities of a company with whom such member has a "conflict
of interest" (as defined in Rule 2720), the initial public offering price can be
no higher than that recommended by a "qualified independent underwriter" (as
defined in Rule 2720) (a "QIU"). BancAmerica Robertson Stephens is serving as
the QIU in the offering and will recommend a price in compliance with the
requirements of Rule 2720. BancAmerica Robertson Stephens has performed due
diligence investigations and reviewed and participated in the preparation of
this Prospectus and the Registration Statement of which this Prospectus forms a
part. BancAmerica Robertson Stephens, in its capacity as QIU, will receive no
additional compensation as such in connection with the offering.

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<PAGE> 66

LEGAL MATTERS

The validity of the Common Stock offered hereby will be passed upon for the
Company by Brobeck, Phleger & Harrison LLP, San Diego, California. Partners of
such firm own 2,500 shares of the Company's Common Stock. Certain legal matters
will be passed upon for the Underwriters by Cooley Godward LLP, San Diego,
California.

EXPERTS

The financial statements of CombiChem for the period from May 23, 1994
(inception) to December 31, 1994, the years ended December 31, 1995 and 1996 and
the nine months ended September 30, 1997 appearing in this Prospectus and the
Registration Statement have been audited by Ernst & Young LLP, independent
auditors, as set forth in their report thereon appearing elsewhere herein and
are included in reliance upon such report given upon the authority of such firm
as experts in accounting and auditing.

ADDITIONAL INFORMATION

The Company has filed with the Commission the Registration Statement under
the Securities Act with respect to the Common Stock offered hereby. This
Prospectus, which is part of the Registration Statement, does not contain all of
the information set forth in the Registration Statement and the exhibits and
schedules filed therewith. For further information with respect to the Company
and the Common Stock offered hereby, reference is hereby made to such
Registration Statement and to the exhibits and schedules filed therewith.
Statements contained in this Prospectus regarding the contents of any contract
or other document are not necessarily complete, and in each instance reference
is made to the copy of such contract or document filed as an exhibit to the
Registration Statement, each such statement being qualified in all respect by
such reference. The Registration Statement, including the exhibits and schedules
thereto, may be inspected without charge at the principal office of the
Commission, 450 Fifth Street, N.W., Washington, D.C. 20549, and at the regional
offices of the Commission located at Seven World Trade Center, Suite 1300, New
York, New York 10048 and Citicorp Center, 500 West Madison Street, Suite 1400,
Chicago, Illinois 60661, and copies of all of any part thereof may be obtained
at prescribed rates from the Commission's Public Reference Section at such
addresses. Also, the Commission maintains a World Wide Web site on the Internet
at http://www.sec.gov that contains reports, proxy and information statements
and other information regarding registrants that file electronically with the
Commission. Upon approval of the Common Stock for quotation on the Nasdaq
National Market, such reports, proxy and information statements and other
information also can be inspected at the office of Nasdaq Operations, 1735 K
Street, N.W., Washington, D.C. 20006.

65
<PAGE> 67

COMBICHEM, INC.

INDEX TO FINANCIAL STATEMENTS

<TABLE>
<S> <C>
Report of Ernst & Young LLP, Independent Auditors..................................... F-2
Balance Sheets at December 31, 1995 and 1996 and September 30, 1997................... F-3
Statements of Operations for the period from May 23, 1994 (inception) to December 31,
1994, the years ended December 31, 1995 and 1996 and the nine months ended September
30, 1996 (unaudited) and 1997....................................................... F-4
Statements of Redeemable Preferred Stock and Stockholders' Equity (Deficit) for the
period from May 23, 1994 (inception) through September 30, 1997..................... F-5
Statements of Cash Flows for the period from May 23, 1994 (inception) to December 31,
1994, the years ended December 31, 1995 and 1996 and the nine months ended September
30, 1996 (unaudited) and 1997....................................................... F-6
Notes to Financial Statements......................................................... F-7
</TABLE>

F-1
<PAGE> 68

REPORT OF ERNST & YOUNG LLP, INDEPENDENT AUDITORS

The Board of Directors and Stockholders
CombiChem, Inc.

We have audited the accompanying balance sheets of CombiChem, Inc. as of
December 31, 1995 and 1996 and September 30, 1997, and the related statements of
operations, redeemable preferred stock and stockholders' equity (deficit), and
cash flows for the period from May 23, 1994 (inception) to December 31, 1994,
the years ended December 31, 1995 and 1996 and the nine months ended September
30, 1997. These financial statements are the responsibility of the Company's
management. Our responsibility is to express an opinion on these financial
statements based on our audits.

We conducted our audits in accordance with generally accepted auditing
standards. Those standards require that we plan and perform the audit to obtain
reasonable assurance about whether the financial statements are free of material
misstatement. An audit includes examining, on a test basis, evidence supporting
the amounts and disclosures in the financial statements. An audit also includes
assessing the accounting principles used and significant estimates made by
management, as well as evaluating the overall financial statement presentation.
We believe that our audits provide a reasonable basis for our opinion.

In our opinion, the financial statements referred to above present fairly,
in all material respects, the financial position of CombiChem, Inc. at December
31, 1995 and 1996 and September 30, 1997, and the results of its operations and
its cash flows for the period from May 23, 1994 (inception) to December 31,
1994, the years ended December 31, 1995 and 1996 and the nine months ended
September 30, 1997, in conformity with generally accepted accounting principles.

ERNST & YOUNG LLP
San Diego, California

December 9, 1997

F-2
<PAGE> 69

COMBICHEM, INC.

BALANCE SHEETS

ASSETS

<TABLE>
<CAPTION>
PRO FORMA
STOCKHOLDERS'
EQUITY AT
DECEMBER 31, SEPTEMBER 30, SEPTEMBER 30,
--------------------------- ------------- -------------
1995 1996 1997 1997
----------- ------------ ------------- -------------
(unaudited)
<S> <C> <C> <C> <C>
Current assets:
Cash and cash equivalents.................... $ 3,135,588 $ 366,983 $ 4,286,957
Short-term investments....................... -- 12,166,132 4,114,700
Restricted cash.............................. -- 325,000 --
Prepaid expenses and other current assets.... 191,076 543,647 518,568
----------- ------------ ------------
Total current assets................. 3,326,664 13,401,762 8,920,225
Property and equipment, net.................... 634,230 2,899,155 4,080,130
Deposits and other assets...................... 36,018 138,095 156,481
Notes receivable from employee/stockholders.... 152,866 218,991 206,301
----------- ------------ ------------
Total assets......................... $ 4,149,778 $ 16,658,003 $ 13,363,137
=========== ============ ============
LIABILITIES AND STOCKHOLDERS' EQUITY (DEFICIT)
Current liabilities:
Accounts payable and accrued expenses........ $ 636,033 $ 1,243,139 $ 1,422,516
Deferred revenue............................. -- 2,130,000 1,187,501
Notes payable................................ 540,000 -- --
Current portion of obligations under capital
leases.................................... 160,521 758,085 1,021,946
----------- ------------ ------------
Total current liabilities............ 1,336,554 4,131,224 3,631,963
Deferred rent.................................. -- 30,409 76,023
Obligations under capital leases, less current
portion...................................... 423,711 1,752,646 2,377,410
Commitments
Redeemable convertible preferred stock, $.001
par value, 63,196,296 shares authorized;
3,868,063, 7,696,808 and 7,754,933 shares
issued and outstanding at December 31, 1995
and 1996 and September 30, 1997, respectively
(5,000,000 shares authorized, no shares
issued and outstanding pro forma)............ 9,650,425 23,106,728 23,129,968 $ --
Stockholders' equity (deficit):
Common stock, $.001 par value, 80,000,000
shares authorized; 660,165, 711,605, and
1,913,572 shares issued and outstanding at
December 31, 1995 and 1996 and September
30, 1997, respectively, (40,000,000 shares
authorized, 9,668,505 shares issued and
outstanding pro forma).................... 660 712 1,913 9,668
Additional paid-in capital................... 119,057 135,340 2,349,325 25,471,538
Deferred compensation........................ -- -- (1,698,494) (1,698,494)
Notes receivable from stockholders........... -- -- (336,562) (336,562)
Accumulated deficit.......................... (7,380,629) (12,499,056) (16,168,409) (16,168,409)
----------- ------------ ------------ ------------
Total stockholders' equity
(deficit).......................... (7,260,912) (12,363,004) (15,852,227) 7,277,741
----------- ------------ ------------ ------------
Total liabilities and stockholders'
equity (deficit)................... $ 4,149,778 $ 16,658,003 $ 13,363,137 $ 13,363,137
=========== ============ ============ ============
</TABLE>

See accompanying notes.

F-3
<PAGE> 70

COMBICHEM, INC.

STATEMENTS OF OPERATIONS

<TABLE>
<CAPTION>
PERIOD FROM
MAY 23, 1994 NINE MONTHS ENDED
(INCEPTION) TO YEAR ENDED DECEMBER 31, SEPTEMBER 30,
DECEMBER 31 ------------------------- -------------------------
1994 1995 1996 1996 1997
-------------- ----------- ----------- ----------- -----------
(unaudited)
<S> <C> <C> <C> <C> <C>
Revenue:
Revenue under collaborative
agreements................ $ -- $ -- $ 2,920,000 $ 1,022,500 $ 4,598,999
Grant revenue................ -- 50,440 47,400 47,400 --
--------- ----------- ----------- ----------- -----------
Total revenue........ -- 50,440 2,967,400 1,069,900 4,598,999
Operating expenses:
Research and development:
Collaborative............. -- -- 420,000 262,500 2,630,775
Proprietary............... 413,305 4,763,043 4,820,253 3,547,828 3,354,590
--------- ----------- ----------- ----------- -----------
413,305 4,763,043 5,240,253 3,810,328 5,985,365
General and administrative... 297,313 2,000,652 2,845,074 1,708,842 2,355,942
--------- ----------- ----------- ----------- -----------
Total operating
expenses........... 710,618 6,763,695 8,085,327 5,519,170 8,341,307
Loss from operations........... (710,618) (6,713,255) (5,117,927) (4,449,270) (3,742,308)
Interest income................ 4,547 94,737 144,639 86,153 437,594
Interest expense............... -- (56,040) (145,139) (97,570) (164,639)
Foreign tax expense............ -- -- -- -- (200,000)
--------- ----------- ----------- ----------- -----------
Net loss....................... $ (706,071) $(6,674,558) $(5,118,427) $(4,460,687) $(3,669,353)
========= =========== =========== =========== ===========
Pro forma net loss per share... $ (0.66) $ (0.45)
=========== ===========
Shares used in calculating pro
forma net loss per share..... 7,797,050 8,191,596
=========== ===========
</TABLE>

See accompanying notes.

F-4
<PAGE> 71

COMBICHEM, INC.

STATEMENTS OF REDEEMABLE PREFERRED STOCK AND STOCKHOLDERS' EQUITY (DEFICIT)
<TABLE>
<CAPTION>
STOCKHOLDERS' EQUITY (DEFICIT)
REDEEMABLE CONVERTIBLE ----------------------------------------------
PREFERRED STOCK COMMON STOCK ADDITIONAL
----------------------- ------------------ PAID-IN DEFERRED
SHARES AMOUNT SHARES AMOUNT CAPITAL COMPENSATION
--------- ----------- --------- ------ ---------- ------------
<S> <C> <C> <C> <C> <C> <C>
Issuance of common stock........................ -- $ -- 433,125 $ 433 $ 23,567 $ --
Sale of Series A preferred stock................ 250,000 500,000 -- -- -- --
Issuance of Series Z preferred stock for
technology.................................... 50,000 100,000 -- -- -- --
Sale of Series B preferred stock................ 550,000 1,650,000 -- -- -- --
Net loss........................................ -- -- -- -- -- --
--------- ----------- --------- ------ ---------- -----------
Balance at December 31, 1994...................... 850,000 2,250,000 433,125 433 23,567 --
Sale of common stock............................ -- -- 194,750 195 58,230 --
Issuance of common stock for technology......... -- -- 100,000 100 39,900 --
Sale of Series B preferred stock................ 6,669 20,000 -- -- -- --
Sale of Series C preferred stock................ 2,808,702 6,877,749 -- -- -- --
Conversion of notes payable and interest into
Series C preferred stock...................... 202,692 502,676 -- -- -- --
Repurchase and cancellation of common stock..... -- -- (67,710) (68) (2,640) --
Net loss........................................ -- -- -- -- -- --
--------- ----------- --------- ------ ---------- -----------
Balance at December 31, 1995...................... 3,868,063 9,650,425 660,165 660 119,057 --
Sale of common stock............................ -- -- 74,000 74 22,126 --
Sale of Series C preferred stock................ 1,278,240 3,142,045 -- -- -- --
Sale of Series D preferred stock................ 2,467,310 9,853,345 -- -- -- --
Conversion of notes payable and interest into
Series Z preferred stock...................... 83,195 460,913 -- -- -- --
Repurchase and cancellation of common stock..... -- -- (22,560) (22) (5,843) --
Net loss........................................ -- -- -- -- -- --
--------- ----------- --------- ------ ---------- -----------
Balance at December 31, 1996...................... 7,696,808 23,106,728 711,605 712 135,340 --
Sale of common stock............................ -- -- 32,500 32 19,718 --
Sale of Series J preferred stock................ 58,125 23,240
Deferred compensation related to stock
options....................................... -- -- -- -- 1,773,972 (1,773,972)
Amortization of deferred compensation........... -- -- -- -- -- 75,478
Sale of common stock for notes receivable....... -- -- 1,169,467 1,169 420,295 --
Repayment of notes receivable................... -- -- -- -- -- --
Net loss........................................ -- -- -- -- -- --
--------- ----------- --------- ------ ---------- -----------
Balance at September 30, 1997..................... 7,754,933 $23,129,968 1,913,572 $1,913 $2,349,325 $(1,698,494)
========= =========== ========= ====== ========== ===========

NOTES
RECEIVABLE TOTAL
FROM ACCUMULATED STOCKHOLDERS'
STOCKHOLDERS DEFICIT EQUITY (DEFICIT)
------------ ------------ ----------------
<S> <C> <C> <C>
Issuance of common stock........................ $ -- $ -- $ 24,000
Sale of Series A preferred stock................ -- -- --
Issuance of Series Z preferred stock for
technology.................................... -- -- --
Sale of Series B preferred stock................ -- -- --
Net loss........................................ -- (706,071) (706,071)
--------- ------------ ------------
Balance at December 31, 1994...................... -- (706,071) (682,071)
Sale of common stock............................ -- -- 58,425
Issuance of common stock for technology......... -- -- 40,000
Sale of Series B preferred stock................ -- -- --
Sale of Series C preferred stock................ -- -- --
Conversion of notes payable and interest into
Series C preferred stock...................... -- -- --
Repurchase and cancellation of common stock..... -- -- (2,708)
Net loss........................................ -- (6,674,558) (6,674,558)
--------- ------------ ------------
Balance at December 31, 1995...................... -- (7,380,629) (7,260,912)
Sale of common stock............................ -- -- 22,200
Sale of Series C preferred stock................ -- -- --
Sale of Series D preferred stock................ -- -- --
Conversion of notes payable and interest into
Series Z preferred stock...................... -- -- --
Repurchase and cancellation of common stock..... -- -- (5,865)
Net loss........................................ -- (5,118,427) (5,118,427)
--------- ------------ ------------
Balance at December 31, 1996...................... -- (12,499,056) (12,363,004)
Sale of common stock............................ -- -- 19,750
Sale of Series J preferred stock................
Deferred compensation related to stock
options....................................... -- -- --
Amortization of deferred compensation........... -- -- 75,478
Sale of common stock for notes receivable....... (421,464) -- --
Repayment of notes receivable................... 84,902 -- 84,902
Net loss........................................ -- (3,669,353) (3,669,353)
--------- ------------ ------------
Balance at September 30, 1997..................... $ (336,562) $(16,168,409) $(15,852,227)
========= ============ ============
</TABLE>

See accompanying notes.

F-5
<PAGE> 72

COMBICHEM, INC.

STATEMENTS OF CASH FLOWS

<TABLE>
<CAPTION>
PERIOD FROM
MAY 23, 1994 NINE MONTHS ENDED
(INCEPTION) TO YEAR ENDED DECEMBER 31, SEPTEMBER 30,
DECEMBER 31, ------------------------- -------------------------
1994 1995 1996 1996 1997
-------------- ----------- ----------- ----------- -----------
(unaudited)
<S> <C> <C> <C> <C> <C>
Cash flows from operating activities:
Net loss......................................... $ (706,071) $(6,674,558) $(5,118,427) $(4,460,687) $(3,669,353)
Adjustments to reconcile net loss to net cash used
in operating activities:
Depreciation and amortization.................... 4,946 106,763 310,765 211,094 559,823
Deferred rent.................................... -- -- 30,409 -- 45,614
Deferred revenue................................. -- -- 2,130,000 212,500 (942,499)
In-process research and development acquired for
convertible notes payable and accrued
interest....................................... -- 591,358 -- -- --
In-process research and development acquired for
note payable................................... 35,000 -- -- -- --
Amortization of deferred compensation............ -- -- -- -- 75,478
Stock issued for technology...................... 100,000 40,000 -- -- --
Interest payable converted to preferred stock.... -- 2,676 20,913 20,913 --
Change in operating assets and liabilities:
Prepaid expenses and other current assets...... (26,081) (135,440) (352,571) (333,809) 25,079
Accounts payable and accrued expenses.......... 192,938 443,095 607,106 (50,909) 179,377
---------- ----------- ----------- ----------- -----------
Net cash used in operating activities..... (399,268) (5,626,106) (2,371,805) (4,400,898) (3,726,481)
Cash flows from investing activities:
Purchases of short-term investments.............. -- -- (12,166,132) -- (3,601,045)
Maturities of short-term investments............. -- -- -- -- 11,652,477
Purchases of property and equipment.............. (107,061) -- (238,315) (237,590) (235,203)
Deposits and other assets........................ (45,941) 9,923 (102,077) 7,444 (18,386)
Notes receivable from employees.................. -- (179,555) (66,125) (79,165) 12,690
---------- ----------- ----------- ----------- -----------
Net cash provided by (used in) investing
activities.............................. (153,002) (169,632) (12,572,649) (309,311) 7,810,533
Cash flows from financing activities:
Principal payments under capital lease
obligations.................................... -- (108,870) (410,876) (176,528) (616,970)
Issuance of redeemable convertible preferred
stock, net of issuance costs................... 2,150,000 6,897,749 12,995,390 3,151,156 11,063
Issuance of common stock, net of repurchased
shares......................................... 24,000 55,717 16,335 (2,195) 116,829
Payments on note payable......................... -- (35,000) (100,000) (100,000) --
Restricted cash given as collateral for letter of
credit......................................... -- -- (325,000) (325,000) 325,000
Proceeds from convertible notes payable.......... -- 750,000 -- -- --
Repayments of convertible notes payable.......... -- (250,000) -- -- --
---------- ----------- ----------- ----------- -----------
Net cash provided by (used in) financing
activities.............................. 2,174,000 7,309,596 12,175,849 2,547,433 (164,078)
---------- ----------- ----------- ----------- -----------
Net increase (decrease) in cash and cash
equivalents...................................... 1,621,730 1,513,858 (2,768,605) (2,162,776) 3,919,974
Cash and cash equivalents at beginning of period... -- 1,621,730 3,135,588 3,135,588 366,983
---------- ----------- ----------- ----------- -----------
Cash and cash equivalents at end of period......... $1,621,730 $ 3,135,588 $ 366,983 $ 972,812 $ 4,286,957
========== =========== =========== =========== ===========
Supplemental disclosures of cash flow information
Interest paid...................................... $ -- $ 56,040 $ 124,226 $ 64,636 $ 169,329
========== =========== =========== =========== ===========
Supplemental schedule of noncash investing and
financing activities
Capital lease obligations entered into for
equipment........................................ $ -- $ 693,102 $ 2,337,375 $ 1,168,828 $ 1,523,627
========== =========== =========== =========== ===========
Conversion of convertible notes payable and
interest payable to redeemable convertible
preferred stock.................................. $ -- $ 502,676 $ 440,000 $ 440,000 $ --
========== =========== =========== =========== ===========
</TABLE>

See accompanying notes.

F-6
<PAGE> 73

COMBICHEM, INC.

NOTES TO FINANCIAL STATEMENTS
(INFORMATION FOR THE NINE MONTHS ENDED SEPTEMBER 30, 1996 IS UNAUDITED)

1. ORGANIZATION AND SUMMARY OF SIGNIFICANT ACCOUNTING POLICIES

Organization and Business

CombiChem, Inc. is a computational drug discovery company that is applying
its proprietary design technology and rapid synthesis capabilities to accelerate
the discovery process for new drugs. The Company believes its approach offers
pharmaceutical and biotechnology companies the opportunity to conduct their drug
discovery efforts in a more productive and cost-effective manner. Using its
Discovery Engine(TM) process, the Company focuses on the generation, evolution
and optimization of potential new lead candidates for its collaborative
partners, who will then develop, manufacture, market and sell any resulting
drugs. CombiChem believes that its process is widely applicable to a variety of
disease targets and therapeutic indications. In addition, the Company intends to
use its approach on internal programs to discover new lead candidates and then
to outlicense them to third parties, retaining a larger economic interest in
such candidates.

Cash, Cash Equivalents and Short-term Investments

Cash and cash equivalents consist of cash and highly liquid investments
with maturities of three months or less when purchased. The Company generally
invests its excess cash in U.S. government securities. Short-term investments
are recorded at amortized cost plus accrued interest which approximates market
value.

The Company applies Statement of Financial Accounting Standards No. 115,
Accounting for Certain Investments in Debt and Equity Securities (SFAS No. 115)
to its investments. Under SFAS No. 115, the Company classifies its short-term
investments as "Available-for-Sale" and records such assets at estimated fair
value in the balance sheet, with unrealized gains and losses, if any, reported
in stockholders' equity. As of December 31, 1996 and September 30, 1997, the
cost of cash equivalents and short-term investments approximated estimated fair
value.

Concentration of Credit Risk

The Company invests its excess cash in debt instruments of financial
institutions and corporations with strong credit ratings. The Company has
established guidelines relative to diversification and maturities that maintain
safety and liquidity. The Company historically has not experienced any material
losses on its cash equivalents or short-term investments.

Property and Equipment

Property and equipment are carried at cost. Depreciation of equipment is
computed using the straight-line method over the estimated useful lives of the
assets, generally three to seven years. Leasehold improvements are amortized
over the shorter of the estimated useful lives of the assets or the remaining
term of the lease. Amortization of equipment under capital leases is reported
with depreciation of property and equipment.

Impairment of Long-Lived Assets

In 1996, the Company adopted Statement of Financial Accounting Standards
No. 121, Accounting for the Impairment of Long-Lived Assets and for Long-Lived
Assets to Be Disposed Of (SFAS No. 121), which requires impairment losses to be
recorded on long-lived assets used in operations when indicators of impairment
are present and the undiscounted cash flows estimated to be generated by those
assets are less than the assets' carrying amount. SFAS No. 121 also addresses
the accounting for

F-7
<PAGE> 74

COMBICHEM, INC.

NOTES TO FINANCIAL STATEMENTS (CONTINUED)
(INFORMATION FOR THE NINE MONTHS ENDED SEPTEMBER 30, 1996 IS UNAUDITED)

1. ORGANIZATION AND SUMMARY OF SIGNIFICANT ACCOUNTING POLICIES (CONTINUED)
long-lived assets that are expected to be disposed of. The adoption had no
impact on the Company's financial statements.

New Accounting Standards

Revenues under Collaborative Agreements and Research and Development Costs

The Company currently generates revenue primarily through its collaborative
agreements, which provide for the analysis of data, design of informative
compound libraries and synthesis of compounds utilizing the Company's
proprietary technology. Contract research revenue is recognized at the time that
research activities are performed under the terms of the research contracts.
Contract payments are generally received in advance of the performance of the
related research activities. Such payments received in excess of amounts earned
are recorded as deferred contract research revenue.

Project initiation fees are recognized as revenue upon contract execution.
These fees are nonrefundable, and the Company has no future performance
obligations related to such fees.

Research and development costs are expensed as incurred. Costs of services
under the Company's collaborative agreements generally approximate the research
revenue received under such agreements. Project initiation fees and milestone
payments do not have associated cost of services.

Net Loss Per Share

Historical net loss per share is computed using the weighted average number
of common shares outstanding during the periods presented. Common equivalent
shares resulting from stock options, warrants to purchase redeemable convertible
preferred stock and redeemable convertible preferred stock are excluded from the
computation as their effect would be antidilutive, except that the Securities
and Exchange Commission requires common and common share equivalents issued
during the twelve-month period prior to the initial filing of a proposed public
offering to be included in the calculation as if they were outstanding for all
periods presented (using the treasury stock method and the assumed initial
public offering price).

Historical net loss per share information is as follows:

<TABLE>
<CAPTION>
PERIOD FROM
MAY 23, 1994
(INCEPTION) TO NINE MONTHS ENDED
DECEMBER 31, YEAR ENDED DECEMBER 31, SEPTEMBER 30,
-------------- ------------------------ -----------------------
1994 1995 1996 1996 1997
-------------- ---------- ---------- ---------- ----------
<S> <C> <C> <C> <C> <C>
Net loss per share......................... $ (0.29) $ (2.33) $ (1.73) $ (1.51) $ (1.24)
========= ========= ========= ========= =========
Shares used in computing net loss per
share.................................... 2,406,794 2,869,475 2,962,113 2,962,113 2,962,113
========= ========= ========= ========= =========
</TABLE>

F-8
<PAGE> 75

COMBICHEM, INC.

NOTES TO FINANCIAL STATEMENTS (CONTINUED)
(INFORMATION FOR THE NINE MONTHS ENDED SEPTEMBER 30, 1996 IS UNAUDITED)

1. ORGANIZATION AND SUMMARY OF SIGNIFICANT ACCOUNTING POLICIES (CONTINUED)

Pro Forma Net Loss Per Share

Pro forma net loss per share has been computed as described above and also
gives effect to the conversion of the redeemable convertible preferred stock,
which will convert to common stock upon completion of the Company's initial
public offering, using the as if-converted method from the original date of
issuance.

Stock-Based Compensation

As permitted by Statement of Financial Accounting Standards No. 123, the
Company has elected to follow Accounting Principles Board Opinion No. 25,
Accounting for Stock Issued to Employees (APB 25), and related Interpretations
in accounting for its employee stock options. Under APB 25, when the exercise
price of the Company's employee stock options is not less than the market price
of the underlying stock on the date of grant, no compensation expense is
recognized.

Use of Estimates

The preparation of financial statements in conformity with generally
accepted accounting principles requires management to make estimates and
assumptions that affect the reported amounts of assets and liabilities and
disclosure of contingent assets and liabilities at the date of the financial
statements and the reported amounts of revenues and expenses during the
reporting period. Actual results could differ from those estimates.

Interim Financial Information

The accompanying financial statements for the nine months ended September
30, 1996 are unaudited but include all adjustments (consisting only of normal
recurring adjustments) which the Company considers necessary for a fair
statement of the operating results and cash flows for such period.

Pro Forma Stockholders' Equity

In September 1997, the Board of Directors authorized management of the
Company to file a Registration Statement with the Securities and Exchange
Commission for the Company to sell shares of its common stock in an initial
public offering. If the initial public offering contemplated by this Prospectus
is consummated under the terms presently anticipated, all outstanding shares of
redeemable convertible preferred stock at September 30, 1997 will automatically
convert into 7,754,933 common shares. The pro forma stockholders' equity does
not reflect the equity investments made in conjunction with the collaboration
agreements described in Note 10.

2. BALANCE SHEET INFORMATION

Investments

There were no realized gains or losses on the sale of securities for either
the period ended September 30, 1997 or the year ended December 31, 1996.

F-9
<PAGE> 76

COMBICHEM, INC.

NOTES TO FINANCIAL STATEMENTS (CONTINUED)
(INFORMATION FOR THE NINE MONTHS ENDED SEPTEMBER 30, 1996 IS UNAUDITED)

2. BALANCE SHEET INFORMATION (CONTINUED)

The amortized cost of debt securities at September 30, 1997, by contractual
maturity, are shown below. The amortized costs approximates fair value. Actual
maturities may differ from contractual maturities because the issuers of the
securities may have the right to prepay obligations with out prepayment
penalties.

<TABLE>
<CAPTION>
COST
----------
<S> <C>
Available for sale:
Due in one year or less........................................ $3,610,293
Due in one to five years....................................... 504,407
----------
$4,114,700
==========
</TABLE>

Property and Equipment

Property and equipment consist of the following:

<TABLE>
<CAPTION>
DECEMBER 31, SEPTEMBER 30,
---------------------- -------------
1995 1996 1997
--------- ---------- -------------
<S> <C> <C> <C>
Laboratory and computer equipment......... $ 670,948 $1,759,990 $ 3,055,611
Leasehold improvements.................... -- 1,373,465 1,689,685
Office furniture, fixtures and
equipment............................... 74,991 188,174 317,131
--------- ----------- -----------
745,939 3,321,629 5,062,427
Less accumulated depreciation and
amortization............................ (111,709) (422,474) (982,297)
--------- ----------- -----------
$ 634,230 $2,899,155 $ 4,080,130
========= =========== ===========
</TABLE>

3. NOTES PAYABLE

During 1996, the Company repaid a $100,000 non-interest bearing note with
cash and converted two notes payable totaling $440,000 and the related accrued
interest into 83,195 shares of Series Z convertible preferred stock.

4. COMMITMENTS

Leases

The Company leases its facilities under an operating lease agreement that
expires in May 2006. Rent expense was approximately $86,000, $383,000, $232,000
and $395,000 for the years ended December 31, 1995 and 1996, and the nine months
ended September 30, 1996 and 1997, respectively. Lease payments are subject to
future increases based upon the Consumer Price Index.

The Company leases certain equipment under capital lease obligations. Cost
and accumulated amortization of equipment under capital leases were $349,000 and
$104,000 at December 31, 1995, $3,054,000 and $349,000 at December 31, 1996 and
$4,578,000 and $845,000 at September 30, 1997, respectively.

F-10
<PAGE> 77

COMBICHEM, INC.

NOTES TO FINANCIAL STATEMENTS (CONTINUED)
(INFORMATION FOR THE NINE MONTHS ENDED SEPTEMBER 30, 1996 IS UNAUDITED)

4. COMMITMENTS

Annual future minimum obligations for operating and capital leases as of
September 30, 1997 are as follows:

<TABLE>
<CAPTION>
OPERATING CAPITAL
LEASES LEASES
---------- -----------
<S> <C> <C>
Three months ending December 31:
1997.................................. $ 113,524 $ 358,431
Year ending December 31:
1998.................................. 458,365 1,433,722
1999.................................. 421,201 1,194,044
2000.................................. 437,638 641,923
2001.................................. 449,966 296,634
2002.................................. 346,207 --
Thereafter....................................... 1,862,189 --
---------- -----------
Total minimum lease payments....................... $4,089,090 3,924,754
==========
Less amount representing interest.................. (525,398)
-----------
Present value of obligations under capital
leases........................................... 3,399,356
Less current portion............................... (1,021,946)
-----------
Long-term obligations under capital leases......... $ 2,377,410
===========
</TABLE>

Consulting Agreements

The Company has entered into various consulting agreements with members of
its Scientific Advisory Board and others for aggregate minimum annual fees of
approximately $118,000. The agreements are cancelable by either party with
limited notice. During the years ended December 31, 1995 and 1996 and the nine
months ended September 30, 1996 and 1997, the Company expensed approximately
$27,000, $43,000, $35,000 and $42,000, respectively, for fees and expense
reimbursements paid to these consultants.

5. REDEEMABLE CONVERTIBLE PREFERRED STOCK AND STOCKHOLDERS' EQUITY (DEFICIT)

Changes in Capitalization

In September 1997, the Company's Board of Directors approved the
reincorporation of the Company in Delaware which was accomplished through a
merger of the existing California corporation into a new Delaware corporation.
The ratio of exchange was one share of the California corporation to one share
of the Delaware corporation. Subsequent to the reincorporation, the Company
effected a one-for-four reverse stock split of the Common Stock. The number of
authorized shares of the new Delaware corporation are 40,000,000 shares of
Common Stock and 5,000,000 shares of Preferred Stock. All share and per share
amounts and stock option data have been restated to retroactively give effect to
the reincorporation, the reverse stock split and the related change in shares
outstanding.

F-11
<PAGE> 78

COMBICHEM, INC.

NOTES TO FINANCIAL STATEMENTS (CONTINUED)
(INFORMATION FOR THE NINE MONTHS ENDED SEPTEMBER 30, 1996 IS UNAUDITED)

5. REDEEMABLE CONVERTIBLE PREFERRED STOCK AND STOCKHOLDERS' EQUITY (DEFICIT)
(CONTINUED)

Redeemable Convertible Preferred Stock

A summary of redeemable convertible preferred stock issued and outstanding
is as follows:

<TABLE>
<CAPTION>
LIQUIDATION
SHARES PREFERENCE
---------- -----------
<S> <C> <C>
Series A.............................................. 250,000 $ 500,000
Series B.............................................. 556,669 1,670,000
Series C.............................................. 4,289,634 10,638,261
Series D.............................................. 2,467,310 9,869,205
--------- -----------
7,563,613 $22,677,466
========= ===========
</TABLE>

In 1994, the Company issued Series A and B redeemable convertible preferred
stock for cash at $2.00 and $3.00 per share, respectively. In October 1994, the
Company acquired certain intellectual property rights in exchange for 50,000
shares of the Company's Series Z convertible preferred stock valued at $2.00 per
share. During 1996, the Company converted two outstanding notes and related
accrued interest totalling $460,913 into 83,195 shares of Series Z convertible
preferred stock.

In August 1995, the Company received approximately $6.9 million in net
proceeds from the issuance of 2,808,702 shares of Series C redeemable
convertible preferred stock at $2.48 per share. Pursuant to the terms of certain
promissory notes, the Company converted $502,676 of principal and accrued
interest into 202,692 shares of Series C redeemable convertible preferred stock
at $2.48 per share. In April 1996, upon the achievement of certain milestones,
the Company received an additional $3.1 million in net proceeds from the
issuance of an additional 1,278,240 shares of Series C redeemable convertible
preferred stock at $2.48 per share.

In November 1996, the Company received approximately $9.9 million in net
proceeds from the issuance of 2,467,310 shares of Series D redeemable
convertible preferred stock at $4.00 per share.

At the option of the holder, the shares of Series A, B, C and D redeemable
convertible preferred stock and Series Z convertible preferred stock are
convertible at any time into common stock on a one-for-four basis, subject to
certain anti-dilution adjustments. The preferred shares automatically convert
into common stock upon the earlier of: 1) the closing of an underwritten public
offering of common stock at not less than $16.00 per common share and an
aggregate offering price of not less than $12 million or 2) the written election
of at least 70% of the preferred stockholders. The preferred stockholders have
voting rights equal to the common shares they would own upon conversion. The
Company has reserved 7,563,613 shares of common stock for issuance upon
conversion of the Series A, B, C and D redeemable convertible preferred stock.

The Company's Amended and Restated Articles of Incorporation provide for
redemption of Series A, B, C and D redeemable convertible preferred stock at any
time after December 31, 1998, at the request of at least 70% of the holders of
such series. The redemption price is equal to the original issue price plus any
declared but unpaid dividends.

The preferred shareholders are entitled to noncumulative annual dividends
of $0.16, $0.24, $0.20, $0.32 and $0.16 per share of Series A, B, C and D
redeemable convertible preferred stock and Series Z convertible preferred stock,
respectively, if and when such dividends are declared by the Board of Directors.
No dividends have been declared to date.

In connection with employment agreements, certain employees received
options to purchase the Company's Series J convertible preferred stock
exercisable upon the achievement of certain mile-

F-12
<PAGE> 79

COMBICHEM, INC.

NOTES TO FINANCIAL STATEMENTS (CONTINUED)
(INFORMATION FOR THE NINE MONTHS ENDED SEPTEMBER 30, 1996 IS UNAUDITED)

5. REDEEMABLE CONVERTIBLE PREFERRED STOCK AND STOCKHOLDERS' EQUITY (DEFICIT)
(CONTINUED)
stones. Some of the milestones were met during 1997, and in connection
therewith, the Company issued 58,125 shares of Series J convertible preferred
stock to the employees.

1995 Stock Option/Stock Issuance Plan

In 1995, the Board of Directors adopted the 1995 Stock Option/Stock
Issuance Plan (the Plan), under which 2,355,069 shares of common stock are
reserved for issuance upon exercise of options or stock issuances by the Company
to certain employees of and consultants to the Company. Under the stock option
program, options may be designated as incentive stock options or nonstatutory
stock options. Options under the Plan have a term of up to ten years from the
date of grant. The exercise price of incentive stock options must equal at least
the fair market value on the date of grant, and the exercise price of
nonstatutory stock options may be no less than 85% of the fair market value on
the date of grant. Options generally vest over four to five years.

The Company recorded $1,613,550 of deferred compensation for options
granted during the nine months ended September 30, 1997, representing the
difference between the option exercise price and management's estimate of the
fair value for financial statement presentation purposes. Management's estimate
of fair value of the common stock was based upon the sale of Series D Preferred
Stock completed in November 1996 and the sale of common stock to Elan/Athena and
ImClone in October 1997. Between the dates of these equity sales, management's
estimate of the fair value of common stock was periodically increased as the
Company signed collaborative agreements, hired key personnel, and achieved
scientific progress on its research programs, including the completion of the
Universal Informer Library. The Company is amortizing the deferred compensation
over the vesting period of the options. The Company recorded $75,476 of
compensation expense during the nine months ended September 30, 1997.

The Company recorded $160,422 of additional deferred compensation
representing the difference between the option exercise price and management's
estimate of the fair value for financial statement presentation purposes for
stock options granted in October 1997.

Under the stock issuance program, selected employees and consultants may be
issued shares of common stock at no less than 85% of the fair market value on
the date of grant. The vesting schedule for each share issuance is determined by
the Board of Directors as Plan Administrator. The Company has the option to
repurchase, at the original issue price, the unvested shares in the event of
termination of service. At September 30, 1997, 901,658 shares were subject to
repurchase by the Company.

F-13
<PAGE> 80

COMBICHEM, INC.

NOTES TO FINANCIAL STATEMENTS (CONTINUED)
(INFORMATION FOR THE NINE MONTHS ENDED SEPTEMBER 30, 1996 IS UNAUDITED)

5. REDEEMABLE CONVERTIBLE PREFERRED STOCK AND STOCKHOLDERS' EQUITY (DEFICIT)
(CONTINUED)
Information with respect to the Plan is as follows:

<TABLE>
<CAPTION>
WEIGHTED
AVERAGE
SHARES EXERCISE PRICE
---------- --------------
<S> <C> <C>
Granted........................................... 562,980 $ 0.30
Exercised......................................... -- --
Cancelled......................................... -- --
----------
Balance at December 31, 1995........................ 562,980 0.30
Granted........................................... 531,479 0.30
Exercised......................................... (72,589) 0.30
Cancelled......................................... (12,536) 0.30
----------
Balance at December 31, 1996........................ 1,009,334 0.30
Granted........................................... 621,813 2.15
Exercised......................................... (1,159,377) 0.36
Cancelled......................................... (30,074) 0.33
---------- -----
Balance at September 30, 1997....................... 441,696 $ 2.81
========== =====
</TABLE>

At September 30, 1997, options to purchase 441,696 shares were exercisable
and 681,407 shares remain available for grant.

Following is a further breakdown of the options outstanding as of September
30, 1997:

<TABLE>
<CAPTION>
WEIGHTED
AVERAGE
WEIGHTED WEIGHTED EXERCISE
RANGE OF AVERAGE AVERAGE PRICE OF
EXERCISE OPTIONS REMAINING EXERCISE OPTIONS OPTIONS
PRICES OUTSTANDING LIFE IN YEARS PRICE EXERCISABLE EXERCISABLE
- ------------- ----------- ------------- -------- ----------- -----------
<S> <C> <C> <C> <C> <C>
$0.30 - $0.40 107,195 8.54 $ 0.33 107,195 $0.33
$1.00 29,375 9.81 1.00 29,375 1.00
$2.00 - $3.00 28,879 8.45 2.43 28,879 2.43
$4.00 276,247 4.90 4.00 276,247 4.00
------- ---- ----- ------- -----
441,696 6.37 $ 2.81 441,696 $2.81
======= ==== ===== ======= =====
</TABLE>

Adjusted pro forma information regarding net loss and net loss per share is
required by SFAS 123, and has been determined as if the Company had accounted
for its employee stock options and stock purchase plan under the fair value
method of SFAS 123. The fair value for these options was estimated at the date
of grant using the "Minimum Value" method for option pricing with the following
assumptions for 1995, 1996 and 1997: risk-free interest rates of 6.50%; dividend
yield of 0%; and a weighted-average expected life of the options of five years.

F-14
<PAGE> 81

COMBICHEM, INC.

NOTES TO FINANCIAL STATEMENTS (CONTINUED)
(INFORMATION FOR THE NINE MONTHS ENDED SEPTEMBER 30, 1996 IS UNAUDITED)

5. REDEEMABLE CONVERTIBLE PREFERRED STOCK AND STOCKHOLDERS' EQUITY (DEFICIT)
(CONTINUED)
For purposes of adjusted pro forma disclosures, the estimated fair value of
the options are amortized to expense over the vesting period. The Company's
adjusted pro forma information is as follows:

<TABLE>
<CAPTION>
NINE MONTHS
YEAR ENDED DECEMBER 31, ENDED
--------------------------- SEPTEMBER 30,
1995 1996 1997
----------- ----------- -------------
<S> <C> <C> <C>
Adjusted pro forma net loss............ $(6,678,067) $(5,137,253) $(3,692,783)
Adjusted pro forma net loss per
share................................ $ (2.33) $ (0.66) $ (0.45)
</TABLE>

The weighted-average fair value of options granted during 1995 and 1996 was
$.08 and during 1997 was $0.56.

The pro forma effect on net loss for 1995, 1996 and 1997 is not likely to
be representative of the pro forma effects on reported net income or loss in
future years because these amounts reflect less than four year of vesting.

Warrants

At September 30, 1997, the Company has issued warrants to purchase an
aggregate of 130,728 shares of redeemable convertible preferred stock at prices
ranging from $2.00 to $2.48 per share. The warrants are exercisable in whole or
in part through various dates.

The Company also has issued warrants to purchase 8,750 shares of common
stock at $0.30 per share. The warrants are exercisable in whole or in part at
any time at or prior to June 2000.

6. NOTES RECEIVABLE FROM EMPLOYEE/STOCKHOLDERS

During 1995, the Company lent $150,000 to an employee and stockholder for
the purchase of a residence in connection with the individual's employment
agreement. The note bears interest at approximately 5.8% and matures on the
earlier of (i) September 5, 2000, (ii) 30 days following cessation of
employment, (iii) 180 days following the date at which the Company completes a
successful initial public offering of shares of its common stock, or (iv) the
date on which more than 50% of the Company's outstanding shares of common stock
are acquired by a single purchaser or a group of purchasers. The note is secured
by 87,500 shares of the Company's common stock owned by the employee at the date
of the note, plus any capital stock thereafter acquired.

In August 1996, the Company lent $66,125 to an employee for relocation in
connection with employment, which is secured by a deed of trust. The loan is
represented by a promissory note which is due and payable on the earlier of
August 28, 1999 or the occurrence of certain events, such as expiration of the
30-day period following the date the individual ceases to be a full time
employee of the Company. The loan bears no interest, and principal payments of
$22,000 have been made to date.

During 1997, the Company instituted an employee loan program whereby the
proceeds of the loan are used to purchase common stock from the exercise of the
employee's stock options. Under the program, the employee pays 25% of the total
exercise price, and the Company loans the employee the remaining 75% of the
purchase price. The loans bear interest at an adjustable rate that is the
minimum rate allowable by the Internal Revenue Service, subject to quarterly
adjustments by the Company. The loans will be repaid through 3 equal payments on
the first three anniversary dates of the loan. The Company has $337,000 in loans
outstanding at September 30, 1997.

F-15
<PAGE> 82

COMBICHEM, INC.

NOTES TO FINANCIAL STATEMENTS (CONTINUED)
(INFORMATION FOR THE NINE MONTHS ENDED SEPTEMBER 30, 1996 IS UNAUDITED)

7. COLLABORATIVE RESEARCH AND DEVELOPMENT AGREEMENTS

Teijin Limited

In March 1996, the Company entered into a collaborative agreement with
Teijin Limited ("Teijin") providing for a one-year program on a G-protein
coupled receptor target. In March 1997, the Company and Teijin amended their
agreement to extend the collaboration for an additional year. While the initial
focus of the collaboration was lead optimization, the effort was redirected to
lead evolution during the course of the research. Under the agreement, Teijin
made an upfront payment to CombiChem and agreed to provide research funding and
milestone payments upon the achievement of certain preclinical and clinical
milestones. Teijin also committed internal resources to the discovery effort.
Teijin will make royalty payments on products resulting from the collaboration.
CombiChem retains the rights to the compounds arising under this collaboration
in North and South America; Teijin has rights to these compounds in Asia and
Europe with a right of first negotiation to acquire CombiChem's rights. Under
the original agreement, Teijin has rights to expand or extend the program for up
to two successive one-year terms. Either party may terminate the agreement in
the event of a material breach remaining uncured for 60 days. As of September
30, 1997, Teijin had paid the Company an aggregate of $1.46 million, of which
$0.9 million was recognized as revenue in 1996, and $0.5 million has been
recognized as revenue in 1997.

Roche Bioscience, a division of Syntex (U.S.A.) Inc.

Sumitomo Pharmaceuticals Co., Ltd.

In August 1997, the Company entered into a collaborative agreement with
Sumitomo Pharmaceuticals, Co., Ltd. (Sumitomo) providing for a two-year lead
evolution program on a target that is believed to play a fundamental role in
osteoarthritis and rheumatoid arthritis. Under the agreement, Sumitomo made an
upfront payment and agreed to provide research funding and milestone payments
upon the achievement of certain preclinical and clinical milestones. Sumitomo
will make royalty payments on worldwide sales of products resulting from the
collaboration. Sumitomo may extend the research period for up to four successive
six-month periods upon mutual agreement. The agreement may be terminated by
either party 90 days following an uncured material breach. As of September 30,
1997, Sumitomo had paid the Company an aggregate of $3.3 million, of which

F-16
<PAGE> 83

COMBICHEM, INC.

NOTES TO FINANCIAL STATEMENTS (CONTINUED)
(INFORMATION FOR THE NINE MONTHS ENDED SEPTEMBER 30, 1996 IS UNAUDITED)

7. COLLABORATIVE RESEARCH AND DEVELOPMENT AGREEMENTS (CONTINUED)

$2.3 million was recognized as revenue in 1997. Certain amounts remain as
deferred revenue at September 30, 1997.

8. BENEFIT PLAN

Company sponsors a benefit plan which covers employees who meet certain age
and service requirements. Employees may contribute a portion of their earnings
each plan year subject to certain Internal Revenue Service limitations. The
Company made no contributions to the Plan for the years ended December 31, 1994,
1995 and 1996, and the nine months ended September 30, 1996 and 1997,
respectively.

9. INCOME TAXES

At December 31, 1996, the Company had federal and California income tax net
operating loss carryforwards of approximately $11,694,000 and $11,652,000,
respectively.

The federal and California tax loss carryforwards will begin to expire in
2009 and 2002, respectively, unless previously utilized. The Company also has
federal and California research tax credit carryforwards of approximately
$104,000 and $144,000, respectively, which will begin to expire in 2010 unless
previously utilized.

Pursuant to Sections 382 and 383 of the Internal Revenue Code, annual use
of the Company's net operating loss and credit carryforwards may be limited
because of cumulative changes in ownership of more than 50% which occurred
during 1995. However, the Company does not believe such limitation will have a
material effect upon the utilization of these carryforwards.

Significant components of the Company's deferred tax assets are shown
below. A valuation allowance, which was increased by $2,253,000 in 1996, has
been recognized to offset the deferred tax assets as of December 31, 1995 and
1996 as realization of such assets is uncertain.

<TABLE>
<CAPTION>
DECEMBER 31,
---------------------------
1995 1996
----------- -----------
<S> <C> <C>
Deferred tax assets:
Net operating loss carryforwards................ $ 2,651,000 $ 4,792,000
Research and development credits................ 179,000 198,000
Other........................................... 29,000 122,000
----------- -----------
Total deferred tax assets......................... 2,859,000 5,112,000
Valuation allowance for deferred tax assets....... (2,859,000) (5,112,000)
----------- -----------
Net deferred tax assets........................... $ -- $ --
=========== ===========
</TABLE>

The Company recorded foreign tax expense of $200,000 in the nine months
ended September 30, 1997 for taxes payable to a Japanese tax authority resulting
from the revenue recognized on the Sumitomo collaboration.

10. SUBSEQUENT EVENTS

Collaborative Agreements

ImClone Systems Incorporated

In October 1997, the Company entered into a collaborative agreement with
ImClone Systems Incorporated (ImClone) providing for a two-year program to
identify and characterize novel small molecule inhibitors to multiple targets
for development in oncology. The agreement provides for

F-17
<PAGE> 84

COMBICHEM, INC.

NOTES TO FINANCIAL STATEMENTS (CONTINUED)
(INFORMATION FOR THE NINE MONTHS ENDED SEPTEMBER 30, 1996 IS UNAUDITED)

10. SUBSEQUENT EVENTS (CONTINUED)
ImClone's access to the Company's Universal Informer Library and Virtual Library
under the supervision of the research management committee composed of
representatives of the Company and ImClone. Under the terms of the agreement,
ImClone will provide the Company with research support payments, milestone
payments upon the achievement of certain program objectives and royalties on
worldwide product sales of therapeutic products that may arise out of the
collaboration. The agreement may be terminated by either party 90 days following
an uncured material breach or by ImClone within 30 days prior to the one-year
anniversary by providing 90 days' prior written notice. In connection with the
collaborative agreement, ImClone purchased 250,000 shares of Common Stock for
$2.0 million, and made an advance payment for contract research of $500,000.

Athena Neurosciences, Inc., a wholly owned subsidiary of Elan Corporation, plc

In October 1997, the Company entered into a collaborative agreement with
Athena Neurosciences, Inc., a wholly owned subsidiary of Elan Corporation, plc.
(Elan/Athena) providing for a three-year program to discover novel therapeutic
compounds for treatment of central nervous system conditions. The agreement
provides for Elan/Athena's access to the Universal Informer Library as deemed
necessary by the research management committee composed of Elan/Athena and
CombiChem representatives. Under the agreement, Elan/Athena will provide the
Company with upfront and research support payments, as well as milestone
payments upon the achievement of pre-determined objectives. Elan/Athena will
also make royalty payments on worldwide sales of products resulting from the
collaboration. The agreement may be terminated by either party 90 days following
an uncured material breach or by Elan/Athena after the one-year anniversary upon
90 days prior written notice. In connection with the collaborative agreement,
Elan International Services Ltd., an affiliate of Elan/Athena, purchased
1,000,000 shares of Common Stock for $8.0 million and made a cash payment of
$1.333 million for project initiation fee.

1997 Stock Incentive Plan

The Company's 1997 Stock Incentive Plan (the 1997 Plan) is intended to
serve as the successor equity incentive program to the Company's 1995 Stock
Option/Stock Issuance Plan, as amended (the "Predecessor Plan"). The 1997 Plan
was adopted by the Board and the stockholders on October 7, 1997, and a total of
1,080,603 shares of Common Stock have been authorized for issuance under the
1997 Plan. Under the stock option program, options may be designated as
incentive stock options or nonstatutory stock options. Options under the plan
have a term of up to ten years from the date of grant. The exercise price of
options shall be fixed by the plan administrator, but shall not be less than
100% of the fair market value per share of common stock on the option grant
dates.

1997 Employee Stock Purchase Plan

In October 1997, the Company adopted the 1997 Employee Stock Purchase Plan
(the "Purchase Plan") and reserved 150,000 shares for issuance, thereunder. The
Purchase Plan permits eligible employees of the Company to purchase shares of
Common Stock, at semi-annual intervals, through periodic payroll deductions.
Payroll deductions may not exceed 10% of the participant's base salary, and the
purchase price will not be less than 85% of the lower of the fair market value
of the stock at either the beginning or the end of the semi-annual intervals.

F-18
<PAGE> 85

[DEPICTIONS OF ACTIVE SITES AND COMPOUNDS]

Using only the structures of compounds screened against a known HIV
protease target, CombiChem's Discovery Engine(TM) has generated a hypothesis (a
computational model), as depicted here, which illustrates potentially important
characteristics of the HIV protease active site.

X-ray crystallography has determined the actual three-dimensional structure
of the active site of the HIV protease target, as shown here.

CombiChem's computer-generated hypothesis has accurately identified the
important characteristics of the HIV protease active site in detail as
demonstrated by the lock-and-key structural fit depicted in this overlay.
<PAGE> 86

[LOGO]
<PAGE> 87

PART II

INFORMATION NOT REQUIRED IN PROSPECTUS

ITEM 13. OTHER EXPENSES OF ISSUANCE AND DISTRIBUTION.

The following table sets forth all expenses, other than underwriting
discounts and commissions, payable by the Registrant in connection with the sale
of the Common Stock being registered. All the amounts shown are estimates,
except for the registration fee, the Nasdaq National Market filing fee and the
NASD fee.

<TABLE>
<S> <C>
Registration fee.................................................. $ 10,194
Nasdaq National Market fee........................................ 50,000
NASD fee.......................................................... 3,864
Blue Sky fees and expenses........................................ 10,000
Printing and engraving expenses................................... 180,000
Legal fees and expenses........................................... 250,000
Accounting fees and expenses...................................... 125,000
Transfer Agent and Registrar fees................................. 5,000
Miscellaneous expenses............................................ 65,942
--------
TOTAL................................................... $700,000
========
</TABLE>

ITEM 14. INDEMNIFICATION OF OFFICERS AND DIRECTORS.

Section 145 of the Delaware General Corporation Law permits indemnification
of officers and directors of the Company under certain conditions and subject to
certain limitations. Section 145 of the Delaware General Corporation Law also
provides that a corporation has the power to purchase and maintain insurance on
behalf of its officers and directors against any liability asserted against such
person and incurred by him or her in such capacity, or arising out of his or her
status as such, whether or not the corporation would have the power to indemnify
him or her against such liability under the provisions of Section 145 of the
Delaware General Corporation Law.

Article VII, Section 1 of the Restated Bylaws of the Company provides that
the Company shall indemnify its directors and executive officers to the fullest
extent not prohibited by the Delaware General Corporation Law. The rights to
indemnity thereunder continue as to a person who has ceased to be a director,
officer, employee or agent and inure to the benefit of the heirs, executors and
administrators of the person. In addition, expenses incurred by a director or
executive officer in defending any civil, criminal, administrative or
investigative action, suit or proceeding by reason of the fact that he or she is
or was a director or officer of the Company (or was serving at the Company's
request as a director or officer of another corporation) shall be paid by the
Company in advance of the final disposition of such action, suit or proceeding
upon receipt of an undertaking by or on behalf of such director or officer to
repay such amount if it shall ultimately be determined that he or she is not
entitled to be indemnified by the Company as authorized by the relevant section
of the Delaware General Corporation Law.

As permitted by Section 102(b)(7) of the Delaware General Corporation Law,
Article V, Section (A) of the Company's Restated Certificate of Incorporation
provides that a director of the Company shall not be personally liable for
monetary damages for breach of fiduciary duty as a director, except for
liability (i) for any breach of the director's duty of loyalty to the Company or
its stockholders, (ii) for acts or omissions not in good faith or acts or
omissions that involve intentional misconduct or a knowing violation of law,
(iii) under Section 174 of the Delaware General Corporation Law or (iv) for any
transaction from which the director derived any improper personal benefit.

The Company has entered into indemnification agreements with each of its
directors and executive officers. Generally, the indemnification agreements
attempt to provide the maximum

II-1
<PAGE> 88

protection permitted by Delaware law as it may be amended from time to time.
Moreover, the indemnification agreements provide for certain additional
indemnification. Under such additional indemnification provisions, however, an
individual will not receive indemnification for judgments, settlements or
expenses if he or she is found liable to the Company (except to the extent the
court determines he or she is fairly and reasonably entitled to indemnity for
expenses), for settlements not approved by the Company or for settlements and
expenses if the settlement is not approved by the court. The indemnification
agreements provide for the Company to advance to the individual any and all
reasonable expenses (including legal fees and expenses) incurred in
investigating or defending any such action, suit or proceeding. In order to
receive an advance of expenses, the individual must submit to the Company copies
of invoices presented to him or her for such expenses. Also, the individual must
repay such advances upon a final judicial decision that he or she is not
entitled to indemnification.

The Company has purchased directors' and officers' liability insurance. The
Company intends to enter into additional indemnification agreements with each of
its directors and executive officers to effectuate these indemnity provisions.

The Underwriting Agreement (Exhibit 1.1 hereto) contains provisions by
which the Underwriters have agreed to indemnify the Company, each person, if
any, who controls the Company within the meaning of Section 15 of the Securities
Act, each director of the Company, and each officer of the Company who signs
this Registration Statement, with respect to information furnished in writing by
or on behalf of the Underwriters for use in the Registration Statement.

ITEM 15. RECENT SALES OF UNREGISTERED SECURITIES.

Since September 30, 1994, the Company has sold and issued the following
unregistered securities (which numbers have not been adjusted for the
one-for-four reverse stock split effected in October 1997).

(1) From September 30, 1994 to September 30, 1997, the Company issued an
aggregate of 6,694,638 options to purchase Common Stock with exercise
prices ranging from $0.062 to $0.25 per share under the Predecessor Plan
and an aggregate of 4,927,858 shares of Common Stock were issued through
the exercise of options granted under the Predecessor Plan for an aggregate
exercise price of $405,241. For additional information concerning these
transactions, reference is made to the information contained under the
caption "Management -- Benefit Plans" in the form of the Prospectus
included herein.

(2) On October 12, 1995, the Company issued 200,000 shares of Series Z
Preferred Stock to Sydney Brenner for an aggregate consideration of
$100,000.

(3) On October 18, 1994, the Company issued 500,000 shares of Common Stock to
Robert A. Curtis, former Chief Executive Officer of the Company, at $.01
per share, of which 229,160 were vested as of the date of the termination
of his employment in October 1995.

(4) On October 18, 1994, the Company issued an aggregate of 2,500 shares of
Common Stock to one investor for an aggregate consideration of $25.

(5) On November 1, 1994, the Company issued an aggregate of 400,000 shares of
Series A Preferred Stock to certain funds advised by Sequoia Capital for an
aggregate consideration of $200,000.

(6) From November 23, 1994 through January 15, 1995, the Company issued an
aggregate of 2,226,667 shares of Series B Preferred Stock to certain funds
advised by Sequoia Capital, Forward Ventures II, L.P. and an individual
investor for an aggregate consideration of $1,670,000.

(7) On November 1, 1994, the Company issued an aggregate of 100,000 shares of
Common Stock to certain venture funds advised by Sequoia Capital for an
aggregate consideration of $5,000.

(8) On November 8, 1994, the Company issued an aggregate of 175,000 shares of
Common Stock to one investor for an aggregate consideration of $8,750.

II-2
<PAGE> 89

(9) On November 18, 1994, the Company issued an aggregate of 10,000 shares of
Common Stock to one investor for an aggregate consideration of $500.

(10) In December 1994, the Company issued a warrant to purchase 83,655 shares of
Series Z Preferred Stock to Comdisco, Inc. at an exercise price of $0.50
per share in connection with an equipment lease financing.

(11) From January 1, 1995 through April 24, 1995, the Company issued an
aggregate of 130,000 shares of Common Stock to eight investors for an
aggregate consideration of $9,750.

(12) On March 20, 1995, the Company issued an aggregate of 400,000 shares of
Common Stock to The Scripps Research Institute for an aggregate
consideration of $40,000.

(13) From April 25, 1995 through July 30, 1995, the Company issued an aggregate
of 650,000 shares of Common Stock to three investors for an aggregate
consideration of $48,750.

(14) On June 15, 1995, the Company issued a warrant to purchase 35,000 shares of
Common Stock to LJL BioSystems, Inc. at an exercise price of $0.075.

(15) In connection with an asset purchase agreement dated August 4, 1995, the
Company issued an aggregate of 332,777 shares of Series Z Preferred Stock
to Molecular Simulations, Inc. from June 1996 through July 1996 in
consideration for certain technology rights.

(16) On August 5, 1995, the Company issued 6,000 shares of Common Stock to Ken
Rubenstein at $.075 per share in connection with a consulting agreement.

(17) On August 17, 1995, August 25, 1995 and September 11, 1995, the Company
issued an aggregate of 12,045,576 shares of Series C Preferred Stock to
various venture capital funds and certain other investors for an aggregate
consideration of $7,468,257.

(18) On August 17, 1995, the Company issued warrants to purchase 120,968 shares
of Series C Preferred Stock at an exercise price of $0.62 per share.

(19) On September 7, 1995, the Company issued 8,065 shares of Series C Preferred
Stock to one investor for an aggregate consideration of $5,000.

(20) In December 1995, the Company issued an aggregate of 232,500 shares of
Series J Preferred Stock to three employees upon the exercise of options to
purchase Series J Preferred Stock at an exercise price of $0.10.

(21) On April 9, 1996, the Company issued an aggregate of 5,104,845 shares of
Series C Preferred Stock to various venture capital funds and certain other
investors for an aggregate consideration of $3,165,003.

(22) In April 1996 and June 1996, the Company issued warrants to purchase an
aggregate of 240,321 shares of Series C Preferred Stock to Comdisco, Inc.
at an exercise price of $0.62 per share in connection with an equipment
lease financing.

(23) In May 1996, the Company issued warrants to purchase an aggregate of
112,903 shares of Series Z Preferred Stock to Silicon Valley Bank and
MMC/GATX Partnership No. 1 at an exercise price of $0.62 per share in
connection with an equipment lease financing.

(24) On November 15, 1996, the Company issued an aggregate of 9,869,205 shares
of Series D Preferred Stock to various venture capital funds and certain
other investors for an aggregate consideration of $9,869,205.

(25) On January 23, 1997, the Company issued an aggregate of 5,000 shares of
Common Stock to one investor at $0.10 per share pursuant to a Restricted
Stock Issuance Agreement for an aggregate consideration of $500.

II-3
<PAGE> 90

(26) On June 11, 1997, the Company issued an aggregate of 40,000 shares of
Common Stock to one investor at $0.075 per share for an aggregate
consideration of $4,000.

(27) On July 1, 1997, the Company issued an aggregate of 45,000 shares of Common
Stock to the University of Pittsburgh for technology rights valued at
$11,250.

(28) On October 7, 1997, the Company issued an aggregate of 50,000 shares of
Common Stock to two investors for past services rendered to the Company.

(29) On October 10, 1997, the Company issued an aggregate of 1,000,000 shares of
Common Stock to ImClone Systems Incorporated in conjunction with a
collaboration agreement.

(30) On October 15, 1997, the Company issued an aggregate of 4,000,000 shares of
Common Stock to Elan International Services Ltd., in conjunction with a
collaboration agreement.

The sales and issuances of securities in the above transactions were deemed
to be exempt under the Act by virtue of Section 4(2) thereof and/or Regulation D
and Rule 701 promulgated thereunder as transactions not involving any public
offering. The purchasers in each case represented their intention to acquire the
securities for investment only and not with a view to the distribution thereof.
Appropriate legends were affixed to the stock certificates issued in such
transactions. Similar representations of investment intent were obtained and
similar legends imposed in connection with any subsequent transfers of any such
securities. The Company believes that all recipients had adequate access,
through employment or other relationships, to information about the Company to
make an informed investment decision.

ITEM 16. EXHIBITS AND FINANCIAL STATEMENT SCHEDULES.

(a) Exhibits.

<TABLE>
<CAPTION>
EXHIBIT
NUMBER DESCRIPTION
- -------- --------------------------------------------------------------------------------
<C> <S>
1.1++ Form of Underwriting Agreement.
3.1++ Certificate of Incorporation of the Company, as amended.
3.2++ Form of Amended and Restated Certificate of Incorporation of the Company to
become effective immediately prior to the Offering.
3.3++ Bylaws of the Company, as amended.
3.4++ Form of Restated Bylaws of the Company to be effective upon completion of the
Offering.
4.1++ Form of Certificate for Common Stock.
5.1++ Opinion of Brobeck, Phleger & Harrison LLP with respect to the Common Stock
being registered.
10.1++ Preferred Stock Purchase Agreement for Series A Preferred Stock between the
Company and Forward Ventures II, L.P., dated August 26, 1994.
10.2++ Preferred Stock Purchase Agreement for Shares of Series Z Preferred Stock
between the Company and Sydney Brenner, dated October 14, 1994.
10.3++ Stock Purchase Agreement for Shares of Series A Preferred Stock and Common Stock
between the Company and the investors listed on Exhibit A thereto, dated
November 1, 1994.
10.4++ Stock Purchase Agreement Series B Preferred Stock between the Company and the
purchasers listed on Exhibit A thereto, dated November 29, 1994.
10.5++ Series C Preferred Stock Purchase Agreement between the Company and the
purchasers listed on Schedule A thereto, dated August 17, 1995.
10.6++ Stock Purchase Agreement for Series C Preferred Stock between the Company and
Todd Schmidt dated September 7, 1995.
</TABLE>

II-4
<PAGE> 91

<TABLE>
<CAPTION>
EXHIBIT
NUMBER DESCRIPTION
- -------- --------------------------------------------------------------------------------
<C> <S>
10.7*++ Supplemental Purchase Agreement between the Company and the purchasers on
Schedule A thereto, dated April 8, 1996.
10.8*++ Series D Preferred Stock Purchase Agreement between the Company and the
purchasers listed on Schedule A thereto, dated November 15, 1996.
10.9++ Amended and Restated Investors' Rights Agreement between the Company and the
stockholders listed on Schedule A thereto, dated November 15, 1996.
10.10++ Series J Preferred Stock Purchase Agreement between the Company and Steve Teig,
dated June 10, 1997.
10.11++ Series J Preferred Stock Purchase Agreement between the Company and Jonathan
Greene, dated June 11, 1997.
10.12++ Series J Preferred Stock Purchase Agreement between the Company and Andrew
Smellie, dated June 11, 1997.
10.13++ Warrant Agreement to Purchase Shares of the Series Z Preferred Stock, as amended
between the Company and Comdisco, Inc., dated December 20, 1994.
10.14++ Common Stock Purchase Warrant between the Company and LJL BioSystems, Inc.,
dated June 15, 1995.
10.15++ Form of Warrant to Purchase Shares of Series C Preferred Stock between the
Company and the purchasers listed on Schedule A thereto, dated August 17, 1995.
10.16++ Form of Warrant Agreement to Purchase Shares of Series C Preferred Stock of the
Company, between the Company and Comdisco, Inc. in the amounts listed on
Schedule A thereto.
10.17++ Form of Warrant to Purchase Shares of Series Z Preferred Stock between the
Company and the purchasers listed on Schedule A thereto, dated May 20, 1996.
10.18++ Master Lease Agreement with the Company and Comdisco Inc., dated November 6,
1994, Schedule VL-1, dated November 11, 1994, Schedule VL-2 dated April 15, 1996
and Schedule VL-3 dated April 15, 1996.
10.19*++ Collaboration Agreement between the Company and Teijin Limited, dated March 29,
1996, as amended.
10.20*++ Collaborative Research and License Agreement between the Company and Roche
Bioscience, dated October 25, 1996.
10.21*++ Research and Technology Development Agreement between the Company and Sumitomo
Pharmaceuticals Co., Ltd., dated August 18, 1997.
10.22* Collaborative Research and License Agreement between the Company and ImClone
Systems Incorporated, dated October 10, 1997.
10.23* Collaborative Research and License Agreement between the Company and Athena
Neurosciences, Inc., dated October 15, 1997.
10.24++ Full Recourse Secured Promissory Note and Stock Pledge Agreement between the
Company and Peter Myers, dated September 5, 1995.
10.25++ Promissory Note Secured by Deed of Trust between the Company and John Saunders,
dated August 30, 1996.
10.26++ Promissory Note between the Company and Vicente Anido, Jr., dated February 24,
1997.
10.27++ Pledge Agreement between the Company and Vicente Anido, Jr., dated February 24,
1997.
10.28++ Promissory Note Secured by Stock Pledge Agreement between the Company and
Vicente Anido, Jr., dated June 6, 1997
10.29++ Stock Pledge Agreement between the Company and Vicente Anido, Jr., dated June 6,
1997.
10.30++ Employment Agreement with Peter Myers, dated March 1, 1995.
</TABLE>

II-5
<PAGE> 92

<TABLE>
<CAPTION>
EXHIBIT
NUMBER DESCRIPTION
- -------- --------------------------------------------------------------------------------
<C> <S>
10.31++ Employment Agreement with John Saunders, dated January 1, 1996.
10.32++ Employment Agreement with Steven Teig, dated July 1, 1995.
10.33++ Employment Agreement with Vicente Anido, Jr., dated March 14, 1996.
10.34++ Employment Agreement with Lee R. McCracken, dated May 13, 1996.
10.35++ Employment Letter with Karin Eastham, dated March 14, 1997.
10.36++ Standard Industrial/Commercial Single-Tenant Lease between the Company and
Campson corporation, dated December 22, 1995.
10.37++ Standard Office Lease-Full Service between the Company and Nearon Enterprises,
LLC, dated October 24, 1996.
10.38++ Lease Agreement between Harbor Investment Partners and the Company, dated
October 6, 1997.
10.39++ 1995 Stock Option/Stock Issuance Plan.
10.40++ 1995 Stock Option/Stock Issuance Plan Form of Notice of Grant.
10.41++ 1995 Stock Option/Stock Issuance Plan Form of Stock Option Agreement.
10.42++ 1995 Stock Option/Stock Issuance Plan Form of Stock Purchase Agreement.
10.43++ 1995 Stock Option/Stock Issuance Plan Form of Restricted Stock Issuance
Agreement.
10.44++ 1997 Stock Incentive Plan.
10.45++ 1997 Employee Stock Purchase Plan.
10.46++ Form of Indemnification Agreement between the Company and each of its directors.
10.47++ Form of Indemnification Agreement between the Company and each of its officers.
10.48++ 1997 Stock Incentive Plan Form of Notice of Grant of Stock Option
10.49++ 1997 Stock Incentive Plan Form of Stock Option Agreement
10.50++ 1997 Stock Incentive Plan Form of Addendum to Stock Option Agreement
(Involuntary Termination Following Corporate Transaction/Change in Control)
10.51++ 1997 Stock Incentive Plan Form of Addendum to Stock Option Agreement (Limited
Stock Appreciation Right)
10.52++ 1997 Stock Incentive Plan Form of Stock Issuance Agreement
10.53++ 1997 Stock Incentive Plan Form of Addendum to Stock Issuance Agreement
(Involuntary Termination Following Corporate Transaction/Change in Control)
10.54++ 1997 Stock Incentive Plan Form of Notice of Grant of Automatic Stock Option
(Initial Grant)
10.55++ 1997 Stock Incentive Plan Form of Notice of Grant of Automatic Stock Option
(Annual Grant)
10.56++ 1997 Stock Incentive Plan Form of Automatic Stock Option Agreement
10.57++ 1997 Employee Stock Purchase Plan Form of Stock Purchase Agreement
11.1++ Statement of Computation of pro forma net loss per share.
23.1++ Consent of Brobeck, Phleger & Harrison LLP (contained in their opinion filed as
Exhibit 5.1).
23.2 Consent of Ernst & Young LLP, Independent Auditors.
24.1++ Power of Attorney (see page II-8).
27.1++ Financial Data Schedule.
</TABLE>

- ---------------

++ Previously filed with the Commission.

II-6
<PAGE> 93

* Certain confidential portions of this Exhibit were omitted by means of
redacting a portion of the text (the "Mark"). This Exhibit has been filed
separately with the Secretary of the Commission without the Mark pursuant to
the Company's Application Requesting Confidential Treatment under Rule 406
under the Securities Act.

(b) Financial Statement Schedules included separately in the Registration
Statement.

All other schedules are omitted because they are not required, are not
applicable or the information is included in the Financial Statements or Notes
thereto.

ITEM 17. UNDERTAKINGS.

The undersigned hereby undertakes to provide to the Underwriters at the
closing specified in the Underwriting Agreement certificates in such
denominations and registered in such names as required by the Underwriters to
permit prompt delivery to each purchaser.

Insofar as indemnification for liabilities arising under the Securities Act
may be permitted to directors, officers and controlling persons of the Company
pursuant to the provisions described in Item 14, or otherwise, the Company has
been advised that in the opinion of the Securities and Exchange Commission such
indemnification is against public policy as expressed in the Securities Act and
is, therefore, unenforceable. In the event that a claim for indemnification
against such liabilities (other than the payment by the Company of expenses
incurred or paid by a director, officer or controlling person of the Company in
the successful defense of any action, suit or proceeding) is asserted by such
director, officer or controlling person in connection with the securities being
registered, the Company will, unless in the opinion of its counsel the matter
has been settled by controlling precedent, submit to a court of appropriate
jurisdiction the question whether such indemnification by it is against public
policy as expressed in the Securities Act and will be governed by the final
adjudication of such issue.

The undersigned registrant hereby undertakes that:

(1) For purposes of determining any liability under the Securities
Act, the information omitted from the form of prospectus filed as part of
this registration statement in reliance upon Rule 430A and contained in a
form of prospectus filed by the registrant pursuant to Rule 424(b)(1) or
(4) or 497(h) under the Securities Act shall be deemed to be part of this
registration statement as of the time it was declared effective.

(2) For the purpose of determining any liability under the Securities
Act, each post-effective amendment that contains a form of prospectus shall
be deemed to be a new registration statement relating to the securities
offered therein, and the offering of such securities at that time shall be
deemed to be the initial bona fide offering thereof.

II-7
<PAGE> 94

SIGNATURES

Pursuant to the requirements of the Securities Act of 1933, the Company has
duly caused this Amendment No. 4 to this Registration Statement to be signed on
its behalf by the undersigned, thereunto duly authorized, in the City of San
Diego, County of San Diego, State of California, on the 11th day of December,
1997.

COMBICHEM, INC.

By: /s/ VICENTE ANIDO, JR.
------------------------------------
Vicente Anido, Jr.
President and Chief Executive
Officer

Pursuant to the requirements of the Securities Act of 1933, this
Registration Statement has been signed below by the following persons in the
capacities and on the dates indicated.

<TABLE>
<CAPTION>
SIGNATURE TITLE DATE
- ----------------------------------- ----------------------------------- ------------------
<S> <C> <C>

/s/ VICENTE ANIDO, JR. President, Chief Executive Officer December 11, 1997
- ----------------------------------- and Director (Principal Executive
(Vicente Anido, Jr.) Officer)

Vice President of December 11, 1997
Finance and Administration and
Chief
/s/ KARIN EASTHAM Financial Officer (Principal
- ----------------------------------- Financial
(Karin Eastham) and Accounting Officer)

* Chairman of the Board and Director December 11, 1997
- -----------------------------------
(Pierre Lamond)

/s/ PETER L. MYERS Director December 11, 1997
- -----------------------------------
(Peter L. Myers)

* Director December 11, 1997
- -----------------------------------
(Philippe O. Chambon)

* Director December 11, 1997
- -----------------------------------
(Arthur Reidel)

* Director December 11, 1997
- -----------------------------------
(William Scott)
</TABLE>

By: /s/ VICENTE ANIDO, JR.
----------------------------------
Vicente Anido, Jr.,
Attorney-in-fact

II-8
<PAGE> 95

EXHIBIT INDEX

<TABLE>
<CAPTION>
SEQUENTIALLY
EXHIBIT NUMBERED
NUMBER DESCRIPTION PAGE
- -------- ------------------------------------------------------------------- ------------
<C> <S> <C>
1.1++ Form of Underwriting Agreement.
3.1++ Certificate of Incorporation of the Company, as amended.
3.2++ Form of Amended and Restated Certificate of Incorporation of the
Company to become effective immediately prior to the Offering.
3.3++ Bylaws of the Company, as amended.
3.4++ Form of Restated Bylaws of the Company to be effective upon
completion of the Offering.
4.1++ Form of Certificate for Common Stock.
5.1++ Opinion of Brobeck, Phleger & Harrison LLP with respect to the
Common Stock being registered.
10.1++ Preferred Stock Purchase Agreement for Series A Preferred Stock
between the Company and Forward Ventures II, L.P., dated August 26,
1994.
10.2++ Preferred Stock Purchase Agreement for Shares of Series Z Preferred
Stock between the Company and Sydney Brenner, dated October 14,
1994.
10.3++ Stock Purchase Agreement for Shares of Series A Preferred Stock and
Common Stock between the Company and the investors listed on
Exhibit A thereto, dated November 1, 1994.
10.4++ Stock Purchase Agreement Series B Preferred Stock between the
Company and the purchasers listed on Exhibit A thereto, dated
November 29, 1994.
10.5++ Series C Preferred Stock Purchase Agreement between the Company and
the purchasers listed on Schedule A thereto, dated August 17, 1995.
10.6++ Stock Purchase Agreement for Series C Preferred Stock between the
Company and Todd Schmidt dated September 7, 1995.
10.7*++ Supplemental Purchase Agreement between the Company and the
purchasers on Schedule A thereto, dated April 8, 1996.
10.8*++ Series D Preferred Stock Purchase Agreement between the Company and
the purchasers listed on Schedule A thereto, dated November 15,
1996.
10.9++ Amended and Restated Investors' Rights Agreement between the
Company and the stockholders listed on Schedule A thereto, dated
November 15, 1996.
10.10++ Series J Preferred Stock Purchase Agreement between the Company and
Steve Teig, dated June 10, 1997.
10.11++ Series J Preferred Stock Purchase Agreement between the Company and
Jonathan Greene, dated June 11, 1997.
10.12++ Series J Preferred Stock Purchase Agreement between the Company and
Andrew Smellie, dated June 11, 1997.
10.13++ Warrant Agreement to Purchase Shares of the Series Z Preferred
Stock, as amended between the Company and Comdisco, Inc., dated
December 20, 1994.
10.14++ Common Stock Purchase Warrant between the Company and LJL
BioSystems, Inc., dated June 15, 1995.
10.15++ Form of Warrant to Purchase Shares of Series C Preferred Stock
between the Company and the purchasers listed on Schedule A
thereto, dated August 17, 1995.
</TABLE>
<PAGE> 96

<TABLE>
<CAPTION>
SEQUENTIALLY
EXHIBIT NUMBERED
NUMBER DESCRIPTION PAGE
- -------- ------------------------------------------------------------------- ------------
<C> <S> <C>
10.16++ Form of Warrant Agreement to Purchase Shares of Series C Preferred
Stock of the Company, between the Company and Comdisco, Inc. in the
amounts listed on Schedule A thereto.
10.17++ Form of Warrant to Purchase Shares of Series Z Preferred Stock
between the Company and the purchasers listed on Schedule A
thereto, dated May 20, 1996.
10.18++ Master Lease Agreement with the Company and Comdisco Inc., dated
November 6, 1994, Schedule VL-1, dated November 11, 1994, Schedule
VL-2 dated April 15, 1996 and Schedule VL-3 dated April 15, 1996.
10.19*++ Collaboration Agreement between the Company and Teijin Limited,
dated March 29, 1996, as amended.
10.20*++ Collaborative Research and License Agreement between the Company
and Roche Bioscience, dated October 25, 1996.
10.21*++ Research and Technology Development Agreement between the Company
and Sumitomo Pharmaceuticals Co., Ltd., dated August 18, 1997.
10.22* Collaborative Research and License Agreement between the Company
and ImClone Systems Incorporated, dated October 10, 1997.
10.23* Collaborative Research and License Agreement between the Company
and Athena Neurosciences, Inc., dated October 15, 1997.
10.24++ Full Recourse Secured Promissory Note and Stock Pledge Agreement
between the Company and Peter Myers, dated September 5, 1995.
10.25++ Promissory Note Secured by Deed of Trust between the Company and
John Saunders, dated August 30, 1996.
10.26++ Promissory Note between the Company and Vicente Anido, Jr., dated
February 24, 1997.
10.27++ Pledge Agreement between the Company and Vicente Anido, Jr., dated
February 24, 1997.
10.28++ Promissory Note Secured by Stock Pledge Agreement between the
Company and Vicente Anido, Jr., dated June 6, 1997
10.29++ Stock Pledge Agreement between the Company and Vicente Anido, Jr.,
dated June 6, 1997.
10.30++ Employment Agreement with Peter Myers, dated March 1, 1995.
10.31++ Employment Agreement with John Saunders, dated January 1, 1996.
10.32++ Employment Agreement with Steven Teig, dated July 1, 1995.
10.33++ Employment Agreement with Vicente Anido, Jr., dated March 14, 1996.
10.34++ Employment Agreement with Lee R. McCracken, dated May 13, 1996.
10.35++ Employment Letter with Karin Eastham, dated March 14, 1997.
10.36++ Standard Industrial/Commercial Single-Tenant Lease between the
Company and Campson corporation, dated December 22, 1995.
10.37++ Standard Office Lease-Full Service between the Company and Nearon
Enterprises, LLC, dated October 24, 1996.
10.38++ Lease Agreement between Harbor Investment Partners and the Company,
dated October 6, 1997.
10.39++ 1995 Stock Option/Stock Issuance Plan.
10.40++ 1995 Stock Option/Stock Issuance Plan Form of Notice of Grant.
</TABLE>

<PAGE> 97

<TABLE>
<CAPTION>
SEQUENTIALLY
EXHIBIT NUMBERED
NUMBER DESCRIPTION PAGE
- -------- ------------------------------------------------------------------- ------------
<C> <S> <C>
10.41++ 1995 Stock Option/Stock Issuance Plan Form of Stock Option
Agreement.
10.42++ 1995 Stock Option/Stock Issuance Plan Form of Stock Purchase
Agreement.
10.43++ 1995 Stock Option/Stock Issuance Plan Form of Restricted Stock
Issuance Agreement.
10.44++ 1997 Stock Incentive Plan.
10.45++ 1997 Employee Stock Purchase Plan.
10.46++ Form of Indemnification Agreement between the Company and each of
its directors.
10.47++ Form of Indemnification Agreement between the Company and each of
its officers.
10.48++ 1997 Stock Incentive Plan Form of Notice of Grant of Stock Option
10.49++ 1997 Stock Incentive Plan Form of Stock Option Agreement
10.50++ 1997 Stock Incentive Plan Form of Addendum to Stock Option
Agreement (Involuntary Termination Following Corporate
Transaction/Change in Control)
10.51++ 1997 Stock Incentive Plan Form of Addendum to Stock Option
Agreement (Limited Stock Appreciation Right)
10.52++ 1997 Stock Incentive Plan Form of Stock Issuance Agreement
10.53++ 1997 Stock Incentive Plan Form of Addendum to Stock Issuance
Agreement (Involuntary Termination Following Corporate
Transaction/Change in Control)
10.54++ 1997 Stock Incentive Plan Form of Notice of Grant of Automatic
Stock Option (Initial Grant)
10.55++ 1997 Stock Incentive Plan Form of Notice of Grant of Automatic
Stock Option (Annual Grant)
10.56++ 1997 Stock Incentive Plan Form of Automatic Stock Option Agreement
10.57++ 1997 Employee Stock Purchase Plan Form of Stock Purchase Agreement
11.1++ Statement of Computation of pro forma net loss per share.
23.1++ Consent of Brobeck, Phleger & Harrison LLP (contained in their
opinion filed as Exhibit 5.1).
23.2 Consent of Ernst & Young LLP, Independent Auditors.
24.1++ Power of Attorney (see page II-8).
27.1++ Financial Data Schedule.
</TABLE>

- ---------------

++ Previously filed with the Commission.

<PAGE> 1
EXHIBIT 10.22

COLLABORATIVE RESEARCH AND LICENSE AGREEMENT

BETWEEN

COMBICHEM, INC.

AND

IMCLONE SYSTEMS INCORPORATED

OCTOBER 10, 1997

<PAGE> 2

COLLABORATIVE RESEARCH AND LICENSE AGREEMENT

THIS COLLABORATIVE RESEARCH AND LICENSE AGREEMENT (the "Agreement")
is entered into and made effective as of October 10, 1997 (the "Effective
Date"), by and between COMBICHEM, INC., a Delaware corporation having its
principal offices at 9050 Camino Santa Fe, San Diego, California ("CombiChem"),
and IMCLONE SYSTEMS INCORPORATED, a Delaware corporation having its principal
offices located at 180 Varick Street, 7th Floor, New York, New York ("ImClone").

WHEREAS, CombiChem has developed and owns certain drug discovery
technology and intellectual property rights, including but not necessarily
limited to chemical library design software, multi-parallel synthesis and
purification methods, chemical libraries suitable for biological screening
assays and medicinal chemistry (collectively, "CombiChem Technology");

WHEREAS, ImClone desires to utilize CombiChem Technology for its drug
discovery activities under ImClone know-how concerning the identification and
characterization of novel small molecule inhibitors for development as
therapeutics for treatment of human disease in the area of oncology;

WHEREAS, the parties wish to collaborate in a Research Program
against Collaboration Target(s) ("Collaboration");

WHEREAS, for purposes of the Collaboration, the Parties intend to
focus on up to *** Collaboration Targets per *** related to ImClone's Areas of
Interest;

NOW, THEREFORE, the Parties agree as follows:

1. DEFINITIONS

1.1 "Abandoned Compound" shall have the meaning set forth in Section
3.1.

1.2 "Abandoned Target" shall have the meaning set forth in Section
3.1.

1.3 "Active Compound(s)" means a compound (or compounds) which

(a) (i) is selected by either Party under the Research Program
from Collaboration Compounds, or

(ii) is derived from a Collaboration Compound; and

(b) shows In Vitro Activity.

1.4 "Additional Target(s)" means a Target that is added to the
Collaboration in accordance with Section 4.2.

*** Portions of this page have been omitted pursuant to a request for
Confidential Treatment and filed separately with the Commission.

<PAGE> 3

1.5 "Affiliate" of a Party means any corporation or other business
entity controlled by, controlling or under common control with, such Party. For
this purpose "control" shall mean direct or indirect beneficial ownership of
more than fifty percent (50%) of the voting securities or income interest in
such corporation or other business, or if not meeting the preceding
requirements, any company owned or controlled by or owning or controlling such
Party at the maximum control or ownership right permitted in the country where
such company exists.

1.6 "Areas of Interest" shall include *** ***.

1.7 "Collaboration" has the meaning set forth in the preamble.

1.8 "Collaboration Compound(s)" means a compound (or compounds) which
(a) is synthesized following the Effective Date for screening against a
Collaboration Target under the Research Program, (b) is a pre-existing CombiChem
Compound which CombiChem desires to designate as a Collaboration Compound, or
(iii) is a pre-existing ImClone Compound which ImClone desires to designate as a
Collaboration Compound.

1.9 "Collaboration Target(s)" means either an Initial Target or an
Additional Target.

1.10 "CombiChem Compound" means a chemical compound that is
proprietary to CombiChem, or whose use or manufacture is proprietary to
CombiChem.

1.11 "CombiChem Technology" has the meaning set forth in the
preamble.

1.12 "Confidential Information" includes, but is not limited to,

(a) all information and materials received by either Party from
the other Party pursuant to this Agreement;

(b) all information and materials developed in the course of
the Collaboration; and

1.13 "Development Compound(s)" means a compound (or compounds) which

(a) (i) is a Lead Compound or (ii) is derived from a Lead
Compound; and

(b) are determined by ImClone to be appropriate for preclinical
studies for the purpose of IND filing by ImClone.

1.14 "Due Diligence" means the use of the resources of ImClone or its
licensees or CombiChem in a manner which is consistent with the exercise of
prudent scientific and

*** Portions of this page have been omitted pursuant to a request for
Confidential Treatment and filed separately with the Commission.

<PAGE> 4

business judgment as applied to other programs of ImClone or CombiChem, as the
case may be, targeting products aimed at markets or patient groups of similar
sizes and of similar scientific and commercial potential. With respect to any
Development Compound, "Due Diligence" shall also require ImClone or its
licensees to conduct all necessary preclinical studies and to file an IND for
such Development Compound within *** from the date upon which ImClone has
designated such Development Compound from any Lead Compound or its derivatives.

1.15 "Exclusivity Period" means the Research Period plus twelve (12)
months.

1.16 "Field" means all therapeutic indications of human disease for
the Collaboration Target.

1.17 "First Commercial Sale" of a Product shall mean the first sale
for use or consumption of such Product in a country after required marketing and
pricing approval has been granted by the governing health regulatory authority
of such country. Sale to an Affiliate or licensee shall not constitute a First
Commercial Sale unless the Affiliate or licensee is the end user of the Product.

1.18 "FTE" means full time equivalent with respect to employees of
CombiChem.

1.19 "ImClone Compound" means a chemical compound that is proprietary
to ImClone, or whose use or manufacture is proprietary to ImClone.

1.20 "Inactive Compound(s)" means a Collaboration Compound(s) which
does not have the In Vitro Activity required for an Active Compound.

1.21 "In Vitro Activity" shall mean the observation of *** *** .

1.22 "Initial Target" shall have the meaning set forth in Section 4.1
hereof.

1.23 "Lead Compound(s)" means a compound (or compounds) which

(a) is selected from an Active Compound(s) by the RMC under the
Research Program, or

(b) is derived from Active Compound(s) and is selected by the
RMC.

1.24 "Net Sales" means the gross sales invoiced by ImClone or its
Affiliates or licensees for Products to non-Affiliated Third Parties less actual
deductions of returns (including withdrawals and recalls), rebates (price
reductions, including Medicaid and similar types of rebates e.g. chargebacks),
volume (quantity) discounts, discounts granted at the time of invoicing, the
cost of transport, insurance, delivery, sales taxes and other taxes (other than
income taxes) directly linked to and included in the gross sales amount, as
computed on a product-by-product basis for the countries concerned, whereby the
amount of such sales in foreign currencies is

*** Portions of this page have been omitted pursuant to a request for
Confidential Treatment and filed separately with the Commission.

<PAGE> 5

converted into United States dollars at the exchange rate of the last business
day for each calendar month as reported by Citibank, N.A. (New York).

1.25 "Patent" means, (a) valid and enforceable Letters Patent,
including any extension (including Supplemental Protection Certificate),
registration, confirmation, reissue, continuation, divisionals,
continuation-in-part, reexamination or renewal thereof, or (b) pending
applications for any of the foregoing.

1.26 "Payments" shall have the meaning set forth in Section 9.3

1.27 "Party" means CombiChem or ImClone, as the case may be,
including their respective Affiliates, permitted successors and assigns.

1.28 "Product(s)" means any product containing a Development Compound
with such compound as the active ingredient and which is granted regulatory
approval by the governing health regulatory authority of the applicable country
for marketing in the Field.

1.29 "Project Team" shall have the meaning set forth in Section
2.1(c).

1.30 "Research Management Committee" or" RMC" has the meaning set
forth in Article 6 below.

1.31 "Research Period" means the initial twenty-four (24) month term
of the Collaboration, which can be extended in accordance with Section 7.1
below.

1.32 "Research Plan" means the mutually-agreed research plan for the
Collaboration attached hereto as Appendix A.

1.33 "Research Program" means the research to be conducted as part of
the Collaboration under the Research Plan, and shall include, without
limitation, the activities and items set forth in Sections 2.1 and 2.2 of this
Agreement.

1.34 "Returned Compound" shall have the meaning set forth in Section
9.2.

1.35 "Royalty Term" means, in the case of any Product, in any
country, the period of time commencing on the First Commercial Sale and ending
upon the later of (a) fifteen (15) years from the date of First Commercial Sale
in such country; or (b) the expiration of the last-to-expire Patent resulting
from the Research Program filed in the Field with claims covering that Product
in the relevant country.

1.36 "Target" means a biomolecular entity that a small molecule is
screened against in order to determine whether the small molecule demonstrates
relevant activity.

1.37 "Territory" means the entire world.

1.38 "Third Party" means an entity other than CombiChem or ImClone or
their respective Affiliates.

<PAGE> 6

1.39 "Universal Informer Library" shall mean CombiChem's proprietary
Universal Informer Library of compounds.

2. RESEARCH COLLABORATION

2.1 CombiChem Responsibilities. CombiChem shall with Due Diligence
conduct the following activities under the Research Program in accordance with
the terms of this Agreement and as more fully described in the Research Plan:

(a) During the Research Period, CombiChem shall (i) review data
and information regarding the Collaboration Targets
provided by ImClone; (ii) based on such data and
information and using the CombiChem Technology, design
informative compound libraries; and (iii) supply all lead
chemistries and synthesize compounds as provided in Section
5.3 below.

(b) During the Research Period, CombiChem shall keep ImClone
informed of its activities performed in connection with the
Collaboration, including, without limitation, providing
ImClone with data and information regarding Collaboration
Compounds prior to the meetings of the Research Management
Committee.

(c) Subject to Article 4 and at all times during the Research
Period, CombiChem shall dedicate a project team of five (5)
FTEs comprised of synthetic and analytical chemists,
compound control scientists, and a computational scientist
(the "Project Team") to conduct all of its activities in
connection with the Collaboration; provided, however, that
the RMC may at any time during the Research Period
substitute employees for the FTEs described above;
provided, further, that ImClone may request that CombiChem
expand its Project Team by adding additional FTEs to work
on the Collaboration at the rate and in the manner
specified in Section 8.2(b).

2.2 ImClone Responsibilities. ImClone shall with Due Diligence
provide CombiChem with the following resources under the Research Program as
more fully described in the Research Plan:

(a) ImClone shall provide CombiChem with support and assistance
useful or necessary for the conduct of the Research
Program, including providing data and information
(including leads and/or screening hits to the extent
available) relating to Collaboration Targets, certain
chemistries useful in compound synthesis, information
concerning assay methods and screening data.

(b) During the Research Period, ImClone shall provide CombiChem
with data and information regarding Collaboration Compounds
and

<PAGE> 7

the Collaboration Target assays developed by ImClone under
the Research Program prior to the meetings of the Research
Management Committee.

(c) During the Exclusivity Period and with Due Diligence,
ImClone shall screen Collaboration Compounds for In Vitro
and, where appropriate, in vivo activity against the
Collaboration Target.

(d) During the Exclusivity Period and with Due Diligence,
ImClone shall (i) screen Lead Compounds, (ii) endeavor to
determine Development Compounds, and (iii) develop
Products.

2.3 Research Plan. The Parties hereby agree that the Research Program
shall be carried out in accordance with the Research Plan which is attached
hereto as Appendix A. At the direction of the RMC, the Research Program shall
involve the use of CombiChem's Universal Informer Library in order to initiate
CombiChem's discovery process with the objective of identifying Lead Compounds
with respect to a specific Collaboration Target. The Research Management
Committee shall review the Research Plan on an ongoing basis and may make
changes to the Research Plan so long as such changes are mutually agreed to by
CombiChem and ImClone.

2.4 Annual Reports. Following the first IND filing through First
Commercial Sale, ImClone shall provide CombiChem with an annual report
summarizing ImClone's activities in developing Development Compounds.

2.5 Third Party Licenses. Each Party shall be solely responsible for
any Third Party license fees required to perform its obligations under this
Agreement subject to Section 8.4. Any agreements between a Party and a Third
Party shall in all material respects permit performance under this Agreement.

3. EXCLUSIVITY

3.1 Collaboration Target Exclusivity. So long as ImClone or its
licensee is proceeding with Due Diligence, CombiChem shall not work on a
Collaboration Target with any Third Parties. In the event that ImClone or its
licensee fails to exercise Due Diligence with respect to, or notifies CombiChem
that it has abandoned work on, any Collaboration Target (an "Abandoned Target")
and any Collaboration Compound, other than an ImClone Compound which is subject
to the rights of a Third Party licesor, associated with such Collaboration
Target (together with all derivatives of such Collaboration Compound, an
"Abandoned Compound"), then, (a) such Abandoned Target shall not be subject to
any provision hereunder, and (b) such Abandoned Compound shall be available to
CombiChem for any purpose thereafter.

3.2 Active Compounds.

(a) Following the designation of any Collaboration Compound as
an Active Compound, such Active Compound shall be exclusively available to
ImClone during the

<PAGE> 8

Research Period. Following the expiration of the Research Period, Active
Compounds with respect to which ImClone fails to proceed with Due Diligence
shall be deemed to be Inactive Compounds for all purposes hereunder; provided,
that any Active Compound which is the subject of claim(s) under a pending Patent
shall continue to be treated as an Active Compound during the Exclusivity Period
so long as ImClone exercises Due Diligence with respect to any Collaboration
Compound.

(b) Prior to the existence of Patent(s) in accordance with
Section 5.2, ImClone shall have exclusive rights in all intellectual property
relating to Active Compounds, their use, and method of manufacture so long as
ImClone continues to show Due Diligence under this Agreement; provided, however,
that ImClone acknowledges and agrees that CombiChem reserves the right to assign
or grant exclusive rights, including rights to Active Compounds, to a third
party collaborator who first identifies a novel compound, a novel use of a
compound, or a novel method of manufacturing a compound, to the extent CombiChem
is obligated to do so under its existing contractual obligations. Upon notice by
ImClone that it intends to file a Patent application with respect to any Active
Compound, Lead Compound, Development Compound or Product, CombiChem shall
promptly inform ImClone whether CombiChem has the power to grant the exclusive
rights in accordance with this Section 3.2 and the assignments in accordance
with Section 5.2; provided, however, that under no circumstances CombiChem will
grant assurances to ImClone to the effect that any Active Compound, Lead
Compound, Development Compound or Product is not covered under the patent claims
of Third Parties wherein such claims are not the direct result of a
collaboration between the Third Party and CombiChem.

3.3 Inactive Compounds/Returned Compounds. Subject to Section 9.4,
Inactive Compounds and Returned Compounds shall be available to both Parties for
any purpose.

4. TARGETS

4.1 Initial Targets. During the Research Period, ImClone may
designate up to *** Collaboration Targets per *** under the Research Program.
During the initial *** *** of the Research Program, subject to the Research Plan
it is anticipated that the Collaboration shall initially focus on up to ***
Targets as follows: **** *** (collectively, the "Initial Targets"). With respect
to Colloboration Targets, the RMC will determine whether to continue to pursue
work against designated Collaboration Targets and will prioritize the activities
of teh Project Team against such Collaboration Targets. In the event that the
results of the initial screeening activities of ImClone with respect to the
Initial Targets specified in Section 4.1 *** *** which shall determine whether
such Targets are suitable for designation as Additional Targets. Subject to the
dispute resolution mechanism provided for in Article 6, ImClone shall have the
right to make a final determination as to whether to continue or pursue work
against any Collaboration Target if the respective Chief Executive Officers of
CombiChem and ImClone are unable to resolve any dispute concerning the same. In
addition, ImClone's right to designate or substitute a Target (including those
Additional Targets set forth in Section 4.2) relating to ImClone's Areas of
Interest shall be subject to the written notice and approval requirements
specified in Section 4.2(b).

*** Portions of this page have been omitted pursuant to a request for
Confidential Treatment and filed separately with the Commission.

<PAGE> 9

4.2 Additional Targets.

(a) Within ninety (90) days prior to the commencement of the
second 12-month period of the Research Program, ImClone may add up to ***
relating to ImClone's Areas of Interest to the Collaboration by notifying
CombiChem in writing that it wishes to designate such Target(s) as Additional
Target(s); it being understood that the Project Team shall be obligated to
simultaneously work on no more than *** Collaboration Targets as directed by the
RMC.

(b) If CombiChem has already committed to wkring on a proposed
Additional Target or has delivered a term sheet to any Third Party and remains
in discussions to enter into a binding agreement with such Third Party with
respect to the proposed Target at the time of notification, CombiChem shall
inform ImClone that such proposed Additional Target is not available. Otherwise,
the RMC shall establish the specific scientific achievements (to be mutually
agreed between CombiChem and ImClone) for such Target and the same shall be
designated as an Additional Target for the Collaboration and subject to the
terms (including the commercial terms) of this Agreement.

4.3 Expansion of Project Team. Notwithstanding the provisions of
Sections 4.1 and 4.2, ImClone may request that CombiChem expand its Project Team
during the Research Period in order to accelerate work on Collaboration Targets
and/or to add additional Target(s). In such event, the RMC shall promptly confer
as to the appropriate number of FTEs to be added to Project Team to work on the
Collaboration at a cost to ImClone as specified in Section 2.1(c).

5. COLLABORATION COMPOUNDS

5.1 Pre-Existing Compounds. ImClone shall have no rights to any
pre-existing CombiChem Compound unless and until such compound is designated as
a Collaboration Compound by CombiChem. Additionally, CombiChem may decline to
synthesize a particular compound or library of compounds by reason of existing
Patents or contractual obligations. CombiChem shall have no rights to any
pre-existing ImClone Compound which is not utilized in the Research Program.

5.2 Intellectual Property Rights; Assignment to ImClone. Subject to
Section 3.2(b) above, ImClone shall have the right and responsibility at
ImClone's expense to file, maintain and prosecute Patents relating to Active
Compounds, Lead Compounds, Development Compounds and Products, their use, and
their methods of manufacture. At ImClone's request, CombiChem shall assign all
its right, title and interest in such Patents to ImClone. If ImClone fails to so
file, maintain or prosecute such Patent, CombiChem shall have the right to
request ImClone to do so. If ImClone elects not to file, maintain or prosecute
such Patent, CombiChem shall have the right to take over such filing,
maintenance or prosecution of such Patent, at its sole expense, and ImClone
shall assign all intellectual property rights it may have in the Active
Compound, Lead Compound, Development Compound or Product to CombiChem.

5.3 Supply of Collaboration Compounds. Aliquots of *** of any
Collaboration Compound that has been synthesized will be prepared and given to
ImClone.

*** Portions of this page have been omitted pursuant to a request for
Confidential Treatment and filed separately with the Commission.

<PAGE> 10

CombiChem shall replenish that amount upon ImClone's reasonable request.
CombiChem shall maintain aliquots of any Collaboration Compound that has been
synthesized by CombiChem. CombiChem shall also provide ImClone with additional
requirements of samples at CombiChem's cost.

6. RESEARCH MANAGEMENT COMMITTEE

The design, review and conduct of the Research Program will be
coordinated by the Research Management Committee, which will meet regularly on a
mutually-agreeable schedule. The Research Management Committee may establish and
amend or revise the Research Plan as necessary to reflect the scientific
progress and work performed under the Research Program, such amendments to be
mutually agreed to by ImClone and CombiChem. The Research Management Committee
will consist of an equal number of members from ImClone and CombiChem and will
include appropriate representatives from ImClone and CombiChem as mutually
agreed. The co-chairs of the Research Management Committee will initially be the
Vice President, Chemistry of CombiChem and the Vice President for Research of
ImClone and subsequently may change as mutually-agreed upon by the Parties.
Decisions of the Research Management Committee shall be by consensus. If a
decision is not reached by the RMC with respect to management of the Research
Program, the dispute will be referred to the co-chairs of the RMC. If the
co-chairs of the RMC are unable to resolve the dispute, the dispute will be
referred to the respective Chief Executive Officers of CombiChem and ImClone.

7. RESEARCH PERIOD; TERMINATION OF RESEARCH PROGRAM

7.1 Research Period: Option to Extend the Research Period. The
initial term of the Collaboration shall be the Research Period, subject to
extension upon mutual agreement. To extend the Research Period, ImClone must
notify CombiChem no later than ninety (90) days prior to the then-current
expiration date and the Parties shall negotiate in good faith the terms and
conditions of any such extension.

7.2 Termination of Research Program.

(a) The Research Program may be terminated by a Party for the
material breach by the other Party of obligations under the Research Program by
giving the breaching party notice of the breach and of the intent of the
non-breaching Party to terminate the Research Program unless the breach is cured
within ninety (90) days of notification. The non-breaching Party may terminate
the Research Program following such ninety (90) day period by providing the
breaching party with ninety (90) days' prior written notice that the Research
Program is terminated, and the Research Program shall be terminated on the 90th
day following such date.

(b) Within thirty (30) days prior to the one (1) year
anniversary of this Agreement, ImClone and CombiChem senior and scientific
management personnel shall meet to review the status of the Collaboration. If,
based upon such review, the status of the Collaboration is satisfactory to
ImClone, ImClone shall make the Second Research Payment described in Section 8.2
to CombiChem on or before the one (1) year anniversary of this Agreement;
provided, however, that ImClone may, in its discretion, make such Second
Research Payment at any time

<PAGE> 11

prior to the date which is the one (1) year anniversary of this Agreement.
If however, based upon such review, the status of the Collaboration is
unsatisfactory to ImClone, ImClone may terminate the Research Program by
providing 90-days' prior written notice to CombiChem that the Research Program
shall be terminated. Upon receipt of such notice by CombiChem, ImClone shall
have no further obligation to make the Second Research Payment to CombiChem (if
such payment has not already been made to CombiChem), and the Research Program
shall be terminated on the 90th day following such date.

(c) CombiChem shall, within thirty (30) days following the
effective date of termination under Section 7.2(a) or 7.2(b), pay to ImClone
such amount as is calculated by taking *** *** *** shall be based upon ***. Any
amount due by CombiChem under this Section 7.2(c) may be in the form, at
CombiChem's discretion, of *** *** ***.

8. CONSIDERATION

8.1 Equity Purchase. Upon execution of this Agreement, ImClone shall
purchase 1,000,000 shares (on a pre-split basis and subject to adjustment) of
Common Stock of CombiChem at a per share purchase price equal to $2.00 per share
for an aggregate purchase price of U.S. $2 million, pursuant to the terms of
that certain Common Stock Purchase Agreement, dated as of the Effective Date, by
and between CombiChem and ImClone (together with all ancillary agreements
thereto, the "Stock Purchase Agreement"). In the event that CombiChem closes an
initial public offering of its common stock at a sales price per share to the
public (the "IPO Price") which is less than $2.50 per share (on a pre-split
basis), then, upon the closing of such initial public offering, CombiChem shall
issue to ImClone, without further consideration other than the purchase price
paid by ImClone pursuant to the Stock Purchase Agreement, such additional
number of shares of CombiChem common stock equal to:

2,000,000
-------------- = 1,000,000
Adjusted Price

wherein the "Adjusted Price" = the IPO Price X .80 if the IPO Price is less than
$2.50 per share. All shares of CombiChem common stock issued pursuant to this
Section 8.1 shall be deemed to be "Shares" within the meaning of the Stock
Purchase Agreement.

8.2 Program Funding.

(a) ImClone shall support CombiChem's efforts in conducting the
Research Program by making a payment upon the execution of this Agreement in the
sum of U.S. $0.5 million as direct research support. In addition, subject to
Section 7.2(b), ImClone shall make a payment (the "Second Research Payment") to
CombiChem prior to October 10, 1998 in the amount of ***

*** Portions of this page have been omitted pursuant to a request for
Confidential Treatment and filed separately with the Commission.

<PAGE> 12

in the form either, at ImClone's discretion, of (i) cash, or (ii) ImClone common
stock by delivering to CombiChem that number of shares of ImClone common stock
equal to the quotient obtained by dividing (i) *** by (ii) the average of the
last reported sales price of the ImClone common stock as quoted on the National
Market System of the National Association of Securities Dealer's Automated
Quotation System during the thirty (30) consecutive trading days ending on the
day prior to delivery of such shares (the "ImClone Price Per Share").

(b) In the event that the Project Team is expanded in accordance
with Section 4.3, ImClone shall make payments, in cash, to CombiChem, at a per
annum rate of U.S. *** payable quarterly in advance of the work to be performed
by such additional FTE(s).

(c) Any shares of the ImClone common stock issued to CombiChem
under this Section 8.2 shall be restricted securities under the Securities Act
of 1933, as amended and shall be issued pursuant to a stock issuance agreement
between ImClone and CombiChem which shall contain provisions for representations
and warranties equivalent to, and registration rights and indemnification (and
such other relevant provisions) with respect to the shares of ImClone common
stock issued thereunder no less favorable than, those contained in the Stock
Purchase Agreement.

8.3 Milestone Payments. Within thirty (30) days of the occurrence of
a development milestone triggered by the activities of ImClone as shown on
Appendix B, ImClone shall pay CombiChem the related milestone payment in U.S.
dollars as set forth on Appendix B. Alternatively, in the event that ImClone
shall outlicense the Patents covering any Product, CombiChem shall be entitled
to the payments set forth in Section 9.3 in lieu of any payments pursuant to
this Section 8.3.

8.4 Royalties.

(a) Direct Sales by ImClone

(i) Subject to Section 8.4(c), during the Royalty Term,
ImClone will pay CombiChem a running royalty of *** of Net Sales of Products
sold by ImClone or its Affiliates in all countries in the Territory. Each
payment of royalties shall be accompanied by a report of Net Sales of Products
in sufficient detail to permit confirmation of the accuracy of the royalty
payment made.

(ii) The royalties owed under Section 8.4(a)(i) shall not
be reduced in accordance with Sections 8.4(c)(i) through 8.4(c)(iii) in an
amount which results in a royalty payable to CombiChem of less than *** of Net
Sales for Products sold directly by ImClone or its Affiliate.

(b) Sales by ImClone's Licensees

In the event that ImClone outlicenses Active Compounds,
Lead Compounds, Development Compounds and resulting Products are sold by
ImClone's licensees

*** Portions of this page have been omitted pursuant to a request for
Confidential Treatment and filed separately with the Commission.

<PAGE> 13

in any country in the Territory, ImClone's royalty payable to CombiChem shall be
as follows:

<TABLE>
<CAPTION>
ImClone Royalty
from Outlicensing CombiChem Royalty due to Outlicensing
- ----------------- -------------------------------------
<S> <C>
Greater than *** (1) *** of ImClone royalty, but no greater
than ***

(2) Subject to reduction as outlined in
Sections 8(c)(i) through 8(c)(iii), but
such reductions shall not reduce CombiChems
royalty below *** except as otherwise
provided in Section 8.4(c)(iii).

Less than or equal to *** (1) *** of ImClone royalty and not subject to
reduction as outlined in Sections 8(c)(i)
and and 8(c)(ii).
</TABLE>

(i) In any country in which Patents do not include a valid
issued patent covering a Product sold by ImClone or its licensee, and/or where a
generic equivalent has been approved for sale and is being sold in such country,
the royalty provided for in Section 8.4(a)(i) and in Section 8.4(b), as
indicated therein, shall be reduced by *** .

(ii) In any country in which ImClone pays a Third Party
royalty for patents and related technology in order to sell a Product, *** of
such Third Party royalty shall be *** the royalty payment owed by ImClone to
CombiChem in accordance with Section 8.4(a)(i) and Section 8.4(b), as indicated
therein. During the Research Period, the RMC will make the determination whether
to include any Third Party royalty-bearing patents and related technology in the
Collaboration. After the Research Period, ImClone shall, in its discretion, make
the determination whether to enter into any agreements with respect to Third
Party royalty-bearing patents and related technology for purposes of this
Agreement.

(iii) In any country in which CombiChem receives any
Additional Payments in respect of payments received by ImClone which are treated
as an advance against royalties due ImClone from its licensee, such Additional
Payments shall be *** the royalties provided for in Section 8.4(b) that are
derived from such licensee.

8.5 Manner and Place of Payment. Royalty payments and reports for Net
Sales of Products shall be calculated in local currencies and reported for each
calendar quarter. All royalty payments owed under this Agreement shall be made
by wire transfer to the bank account to be designated by CombiChem within thirty
(30) days following the end of each such calendar quarter.

8.6 Records and Audit. During the term of this Agreement and for a
period of five (5) years thereafter, ImClone shall keep complete and accurate
records pertaining to the sale or other disposition of Products in sufficient
detail to permit CombiChem to confirm the accuracy of all payments due
hereunder. CombiChem shall have the right to cause an independent certified
public accounting firm reasonably acceptable to ImClone to audit such

*** Portions of this page have been omitted pursuant to a request for
Confidential Treatment and filed separately with the Commission.

<PAGE> 14

records to confirm ImClone's Net Sales for the preceding year. Any information
obtained during such audit shall be treated as Confidential Information. Such
audits may be exercised during normal business hours of ImClone no more than
once each year. CombiChem shall bear the full cost of such audit unless such
audit discloses a variance of more than five percent (5%) in ImClone's favor
from the amount of the Net Sales reported by ImClone for such audited period. In
such case, ImClone shall bear the fill cost of such audit.

8.7 Taxes. All income and other taxes levied on account of the
royalties and other payments accruing to CombiChem under this Agreement shall be
paid by CombiChem, including taxes levied thereon as income to CombiChem. If
provision is made in law or regulation for withholding, such tax shall be
deducted from the royalty or other payment made by ImClone to the proper taxing
authority and a receipt of payment of the tax secured and promptly delivered to
CombiChem. Each Party agrees to assist the other Party in claiming exemption
from such deductions or withholdings under any double taxation or similar
agreement or treaty from time to tune in force.

9. LICENSE GRANTS; OUTLICENSE

9.1 CombiChem License Grant to ImClone. Subject to the terms and
conditions of this Agreement, CombiChem hereby grants to ImClone an exclusive
worldwide license, with the right to sublicense, to use such CombiChem
Technology as is necessary to make, have made, use, have used, sell, have sold
and import Collaboration Compounds or Products in the Territory. Such license
shall remain exclusive in relation to each Collaboration Compound and/or Product
so long as ImClone or its licensee continues to develop and commercialize such
Collaboration Compound and/or Product containing such Collaboration Compound
against a Collaboration Target with Due Diligence.

9.2 ImClone License Grant to CombiChem. Subject to the terms and
conditions of this Agreement and following the failure of ImClone or its
licensee to develop and commercialize with Due Diligence a Lead Compound, a
Development Compound or Product, as the case may be, (collectively, and together
with all Abandoned Compounds, "Returned Compound"), ImClone shall grant to
CombiChem an exclusive license (exclusive even as to ImClone and its
Affiliates), with the right to sublicense, under those ImClone Patents and
know-how which are resulting from the Research Program and related exclusively
to the Returned Compound to make, have made, use, have used, sell, have sold and
import such Returned Compound in the Territory.

9.3 ImClone Outlicense. ImClone shall have a right to outlicense the
Patents covering the Product to a Third Party subject to CombiChem's right to
receive (a) royalties as provided in Section 8.4(b), and (b) additional payments
("Additional Payments") such that CombiChem has received, as of each Payment
Date, the greater of (i) the cumulative amount due CombiChem by ImClone upon the
attainment of the milestones set forth in Appendix B by ImClone' s licensee, or
(ii) the cumulative amount equal to *** of the *** *** ***

*** Portions of this page have been omitted pursuant to a request for
Confidential Treatment and filed separately with the Commission.

<PAGE> 15

*** *** but excluding, to the extent reasonable and customary, all *** ***
(collectively, the royalties described in clause (a) and the payments described
in clause (b) of this sentence, the "Payments") received by ImClone from such
Third Party in connection with such license. The royalty Payments described in
clause (a) of the preceding sentence shall be remitted to CombiChem within
thirty (30) days after receipt by ImClone of such Payments from its licensee.
The Additional Payments described in clause (b) of the preceding sentence shall
be paid to CombiChem within thirty (30) days following each date (a "Payment
Date") upon which any milestone designated in Appendix B is achieved and/or
ImClone receives a payment (as described above) from its licensee. As an express
condition of any such outlicense, any such licensee shall be required to agree
in writing to be bound by royalty reporting and recordkeeping and inspection
provisions consistent with those contained in this Agreement. In addition,
CombiChem shall have the right to receive all audit reports relating to sales of
Products of ImClone's licensees, and to cause ImClone or its successor to have
an independent certified public accounting firm audit such licensees records on
the same terms as those specified in Section 8.6. All payments shall be made by
wire transfer to such bank account designated by CombiChem. Failure of such
licensee to make any milestone or royalty payment in respect of such Product
shall not relieve ImClone of its obligations to make royalty and milestone
payments to CombiChem hereunder.

9.4 Rights to Inactive Compounds/Returned Compounds. No provision of
this Agreement shall prevent either Party from making, having made, using,
having used, selling, having sold, or importing Inactive Compounds, products
containing Inactive Compounds, Returned Compounds or products containing
Returned Compounds or screening Inactive Compounds and Returned Compounds
against any target other than the Collaboration Targets. In the event that
either ImClone or CombiChem (the "Contracting Party") shall enter into a binding
agreement with a Third Party to develop, market and/or sell any product
containing any Inactive Compound or Returned Compound as an active ingredient (a
"Third Party Transaction"), then the other Party hereto (the "Other Party")
shall be entitled to *** of *** by the Contracting Party from such Third Party
in respect of such Third Party Transactions. All such payments shall be sent by
wire transfer to such bank account designated by the Other Party within thirty
(30) days after the Contracting Party's receipt of such payments and shall be
subject to the recording and auditing provisions of Section 8.6.

9.5 Miscellaneous License. In addition to any other rights granted by
either Party in accordance with this Article 9, each Party grants to the other
party a non-exclusive license without the right to grant sublicenses, under any
intellectual property rights the granting Party has the power to grant in order
for the other Party to carry out its rights and obligations under this Agreement
including, but not necessarily limited to, conducting the Research Program and
manufacturing, developing, selling and importing Products.

10. TERM AND TERMINATION

10.1 Term. The term of this Agreement shall commence upon the
Effective Date of this Agreement, and shall expire on the expiration of the last
royalty obligation under this

*** Portions of this page have been omitted pursuant to a request for
Confidential Treatment and filed separately with the Commission.

<PAGE> 16

Agreement, except as provided hereunder.

10.2 Termination by ImClone or CombiChem. Subject to Section 7.2, if
either Party materially breaches this Agreement and fails to remedy that breach
within ninety (90) days of receiving written notice thereof from the other
Party, or enters into any arrangement of composition with its creditors or goes
into liquidation, insolvency, bankruptcy, receivership or reorganization
proceedings, whether voluntarily or compulsorily which is not dismissed within
ninety (90) days, then the other Party may at any time, by notice in writing or
by telefax, terminate this Agreement.

10.3 After Termination.

(a) Upon any termination of the Research Program under Section
7.2(a) due to a material breach of this Agreement by ImClone, ImClone's rights
pursuant to Sections 3.1, 3.2, 5.3, 9.1, 9.3 and 9.5 shall immediately cease,
and all rights granted hereunder with respect to Targets and Collaboration
Compounds, Active Compounds, Lead Compounds, Development Compounds, or Products
shall immediately revert to CombiChem without further obligation to ImClone.
ImClone's rights pursuant to Section 5.2 and 9.3 above that accrue prior to such
termination shall be retained by ImClone. ImClone may make, use, sell and import
Active Compounds, Lead Compounds, Development Compounds or Products under rights
retained by ImClone pursuant to this Section 10.3(a) so long as ImClone
continues to satisfy all of its royalty, milestone, and Payment obligations in
accordance with Sections 8.3, 8.4, 9.3 and 9.4.

(b) Upon any termination of the Research Program under Section
7.2(a) due to a material breach of this Agreement by CombiChem with respect to a
Collaboration Compound, Active Compound, Lead Compound, Development Compound or
Product, all of ImClone's rights pursuant to Sections 3.1, 3.2, 5.2, 5.3, 9.1,
9.3 and 9.5 shall be retained by ImClone. ImClone may make, use, sell or import
Active Compounds, Lead Compounds, Development Compounds and Products with
respect to which ImClone is not in material breach under rights retained by
ImClone pursuant to this Section 10.3(b) so long as ImClone continues to satisfy
all of its royalty, milestone, and Payment obligations in accordance with
Sections 8.3, 8.4, 9.3 and 9.4, except that ImClone shall not be required to
satisfy such obligations with respect to any Collaboration Compound, Active
Compound, Lead Compound, Development Compound or Product with respect to which
CombiChem is in material breach.

(c) If ImClone materially breaches this Agreement following the
Research Period with respect to an Active Compound, Lead Compound, Development
Compound or Product for any reason including, but not limited to, failing to
satisfy its royalty, milestone and Payment obligations pursuant to Sections 8.3,
8.4, 9.3 and 9.4, ImClone shall not make, use, sell or import Active Compounds,
Lead Compounds, Development Compounds or Products with respect to which ImClone
is in material breach. ImClone shall retain the right to make, use, sell and
import Active Compounds, Lead Compounds, Development Compounds or Products with
respect to which ImClone is not in material breach so long as ImClone continues
to satisfy all of its royalty, milestone, and Payment obligations in accordance
with Sections 8.3, 8.4, 9.3 and 9.4.

<PAGE> 17

(d) If CombiChem materially breaches this Agreement following
the Research Period for any reason including, but not limited to, failing to
satisfy its confidentiality and warranty obligations under Articles 11 and 19,
ImClone shall have the right to make, use, sell or import Active Compounds, Lead
Compounds, Development Compounds and Products with respect to which ImClone is
not in material breach so long as ImClone continues to satisfy all of its
royalty, milestone, and Payment obligations in accordance with Sections 8.3,
8.4, 9.3 and 9.4.

(e) Upon any expiration or earlier termination of this Agreement
for any reason, ImClone shall not be entitled to any refund of any payments made
to CombiChem hereunder except as provided in Section 7.2(c).

10.4 Effect of Termination on Licensees. In the event of any
termination of this Agreement pursuant to this Article 10 where such termination
shall not have been caused by the action or inaction on the part of any
respective licensee of ImClone or CombiChem, or by any breach by such licensee
of its obligations under its licensee from ImClone or CombiChem, as appropriate,
such termination of this Agreement shall be without prejudice to the rights of
each non-breaching licensee and such licensee shall be deemed to be a direct
licensee hereunder.

11. CONFIDENTIAL INFORMATION

11.1 Nondisclosure. During the term of the Collaboration and for a
period of five (5) years after termination thereof, each Party will maintain all
Confidential Information in trust and confidence and will not disclose any
Confidential Information to any third party for any purpose except (i) as
expressly authorized by this Agreement, or (ii) as required by law or court
order, or (iii) to its consultants, subcontractors or agents who need to know to
accomplish the purposes of this Agreement. Each Party may use such Confidential
Information only to the extent required to accomplish the purposes of this
Agreement. Each Party will use at least the same standard of care as it uses to
protect proprietary or confidential information of its own to ensure that its
Affiliates, employees, agents, consultants and other representatives do not
disclose or make any unauthorized use of the Confidential Information. Each
Party will promptly notify the other upon discovery of any unauthorized use or
disclosure of the Confidential Information. Confidential Information is
understood to include, but not necessarily to be limited to, the structures of
chemical compounds and the identification of chemical compounds as Collaboration
Compounds, Active Compounds, Inactive Compounds, Lead Compounds, Development
Compounds, or Products.

11.2 Exceptions. Confidential Information shall not include any
information which the receiving Party can prove by competent evidence: (a) is
now, or hereafter becomes, through no act or failure to act on the part of the
receiving Party, generally known or available; (b) is known by the receiving
Party at the time of receiving such information, as evidenced by its records;
(c) is hereafter disclosed to the receiving Party by a Third Party, as a matter
of right and without restriction on disclosure; (d) is independently developed
by the receiving Party without the aid, application or use of Confidential
Information; (e) is the subject of a written permission to disclose provided by
the disclosing Party; or (f) is necessary to obtain regulatory approval for a
Product, or patent protection with respect to Active Compounds, Lead Compounds,
Development Compounds, or Products, and the uses and methods of manufacturing
thereof.

<PAGE> 18

12. PUBLICATIONS AND PUBLIC STATEMENTS

12.1 Publications. Each Party shall be permitted to publish any
information, except Confidential Information, relating to the Research Program
as long as the Party has the prior written permission of the other Party. Such
permission shall be approved or disapproved within twenty-one (21) days of
written request for permission. Such permission shall not be unreasonably
withheld.

12.2 Public Statements. Neither Party shall use the name of the other
Party in any public statement, prospectus, annual report or press release or
other public communication (collectively "Public Statements") without the prior
written approval of the other Party, which may not be unreasonably withheld or
delayed; provided, however, that both Parties shall endeavor in good faith to
give the other Party a minimum of two (2) business days to review such Public
Statements; provided, further, that, upon approval of any such Public Statement,
both Parties may disclose to third parties the information contained in such
Public Statement without the further approval of the other; and provided,
further, that if a Party does not approve such Public Statement, either Party
may still use the name of the other Party in any Public Statement without the
prior written approval of the other Party, if such Party is advised by counsel
that such disclosure is required to comply with applicable law.

13. INDEMNIFICATION

13.1 EACH PARTY HEREBY AGREES TO SAVE, DEFEND AND HOLD THE OTHER
PARTY AND ITS OFFICERS, DIRECTORS, EMPLOYEES, CONSULTANTS AND AGENTS HARMLESS
FROM AND AGAINST ANY AND ALL SUITS, CLAIMS, ACTIONS, DEMANDS, LIABILITIES,
EXPENSES AND LOSSES, INCLUDING REASONABLE LEGAL EXPENSES AND ATTORNEYS' FEES
("LOSSES") RESULTING DIRECTLY OR INDIRECTLY FROM ANY ACTIVITY PERFORMED BY THE
INDEMNIFYING PARTY PURSUANT TO THIS AGREEMENT, INCLUDING BUT NOT NECESSARILY
LIMITED TO THE MANUFACTURE, DEVELOPMENT, USE, HANDLING, STORAGE, SALE OR OTHER
DISPOSITION OF CHEMICAL AGENTS, COLLABORATION COMPOUNDS, ACTIVE COMPOUNDS, LEAD
COMPOUNDS, DEVELOPMENT COMPOUNDS OR PRODUCTS BY SUCH PARTY, ITS AFFILIATES OR
LICENSEES except to the extent such Losses result from the gross negligence or
willful misconduct of the Party claiming a right of indemnification under this
Article 13.

13.2 Indemnification.

(a) Subject to Section 13.2(c) below, ImClone shall hold
CombiChem and its officers, directors, employees, consultants, and agents
harmless from and against any and all losses resulting from the infringement of
any Patent of a Third Party due to the performance by ImClone of any activity
contemplated hereunder, including, but not necessarily limited to, ImClone's
responsibilities under Section 2.2 above, developing Products, and selling
Products.

(b) Subject to Section 13.2(c) below, CombiChem shall hold
ImClone and its officers, directors, employees, consultants, and agents harmless
from and against any and all losses resulting from the infringement of any
Patent of a Third Party due to the performance

<PAGE> 19

by CombiChem of any activity contemplated hereunder, including, but not
necessarily limited to, CombiChem's responsibilities under Section 2.1 above.

(c) The indemnity provided in Sections 13.2(a) and 13.2(b) above
shall not apply where the loss is due to the breach by the indemnified Party of
a warranty made in Article 19.

13.3 Procedures. If either Party seeks indemnification under this
Article 13, it shall inform the other Party of a claim as soon as reasonable
practicable after it receives notice of the claim, shall permit the other Party
to assume direction and control of the defense of the claim (including the right
to settle me claim solely of the other Party), and shall give reasonable
cooperation (at the expense of the other Party) in the defense of the claim.

14. ASSIGNABILITY

This Agreement may not be assigned by either Party without the prior
written consent of the other Party; provided, however, that either Party may
assign this Agreement, in whole or in part, to an Affiliate or to a successor of
a Party in connection with the merger, consolidation or sale of all or
substantially all of such Party's assets or that portion of its business
pertaining to the subject matter of this Agreement.

15. DISPUTE RESOLUTION PROCEDURES

15.1 Senior Executives Discussions. If a decision is not reached by
the RMC, the dispute will be resolved as set forth in Article 6 above. If a
dispute arises between CombiChem and ImClone with respect to matters other than
the management of the Research Program, either during or after the Research
Period, such dispute will be referred to the appropriate senior management in
the area of the dispute. If such senior management are unable to resolve such
dispute, such dispute will be referred to the Chief Executive Officers of
CombiChem and ImClone. If such officers are unable to reach an agreement within
thirty (30) days following the initiation of discussions between them, such
dispute shall be settled by arbitration as described in Section 15.2 below.

15.2 Binding Arbitration. If the parties have not been able to
resolve the dispute as provided in Section 15.1 above, the dispute shall be
finally settled by binding arbitration. Any arbitration hereunder shall be
conducted under rules of the American Arbitration Association. The arbitration
shall be conducted before one (1) arbitrator chosen by mutual agreement of the
Parties. If the Parties cannot agree on the choice of the arbitrator within a
period of thirty (30) days after submission, then the arbitrator shall be
appointed by the Court of Arbitration of the American Arbitration Association.
Any such arbitration shall be held in a mutually agreeable location; provided,
however that if the parties cannot so agree, the location(s) for such
arbitration(s) shall alternate between San Diego, California and New York, New
York, with the first such arbitration to be located in San Diego, California.
The arbitrators shall have the authority to grant specific performance, and to
allocate between the parties the costs of arbitration in such equitable manner
as he or she may determine. The arbitral award (i) shall be final and binding
upon the parties; and (ii) may be entered in any court of competent
jurisdiction.

<PAGE> 20

15.3 Injunctive Relief. Nothing contained in this Article 15 or any
other provisions of this Agreement shall be construed to limit or preclude a
Party from bringing any action in any court of competent jurisdiction for
injunctive or other provisional relief to compel the other Party to comply with
its obligations hereunder before or during the pendency of arbitration
proceedings.

16. NOTICES

Any notice required or permitted to be given hereunder shall be
deemed sufficient if sent by facsimile letter or overnight courier, or delivered
by hand to ImClone or CombiChem at the respective addresses and facsimile
numbers as set forth below or at such other address and facsimile number as
either Party hereto may designate. If sent by facsimile letter, notice shall be
deemed given when the transmission is completed if the sender has a confirmed
transmission report. If a confirmed transmission report does not exist, then the
notice will be deemed given when the notice is actually received by the person
to whom it is sent. If delivered by overnight courier, notice shall be deemed
given when it has been signed for. If delivered by hand, notice shall be deemed
given when received.

if to CombiChem, to: CombiChem, Inc.
9050 Camino Santa Fe San Diego, California 92121
Attention: President
Fax number: (619) 530-9998

with a copy to: Brobeck, Phleger & Harrison LLP
550 South Hope Street, 21st Floor
Los Angeles, California 90071
Attention: Laurie A. Allen, Esq.
Fax number: (213) 239-1324

if to ImClone, to: ImClone Systems Incorporated
180 Varick Street
New York, New York 10014
Attn: Vice President, Business Development
Fax number: (212) 645-2054

with a copy to: Hoffmann and Baron
350 Jericho Turnpike
Jericho, New York 11753
Attn: Irving N. Feit, Esq.
Fax number: (516) 822-3582

17. SURVIVAL

The provisions of Sections 2.5, 5.1, 5.2, 7.2(c),10.3, 10.4, and
Articles 1, 3, 8, 9, 11, 12, 13, 14, 15, 16, 18 and this Article 17 shall
survive termination of this Agreement in addition to those provisions which by
their terms survive.

<PAGE> 21

18. ADDITIONAL TERMS

18.1 Entire Agreement. This Agreement and the Common Stock Purchase
Agreement constitute the entire understanding between the Parties with respect
to the subject matter hereto and supersedes and replaces all previous
negotiations, understandings, representations, writings and contract provisions
and rights relating hereof. The Parties agree that all services provided
hereunder shall be subject to and governed by the terms and provisions set forth
herein, and none of the terms and conditions contained on any proposal, purchase
order, invoice or other writing shall have any effect or change the provisions
of this Agreement.

18.2 Amendment; No Waiver. No provision of this Agreement may be
amended, revoked or waived except by a writing signed and delivered by an
authorized officer of each Party. Any waiver on the part of either Party of any
breach or any fight or interest hereunder shall not imply the waiver of any
subsequent breach or waiver of any other right or interest.

18.3 Validity. The invalidity or unenforceability of any provision of
this Agreement shall not affect the validity or enforceability of any other
provision of this Agreement, each of which shall remain in full force and
effect. In addition, should the invalidity or unenforceability of any provision
of this Agreement cause an unintended result or result in any unfairness to
either Party, then ImClone and CombiChem shall promptly meet and negotiate in
good faith to modify or amend this Agreement to change such result or to
eliminate such unfairness.

18.4 Headings. The descriptive headings are inserted for convenience
of reference only and are not intended to be part of or to affect the meaning of
or interpretation of this Agreement.

18.5 Counterparts. This Agreement may be executed in one or more
counterparts, each of which shall be deemed an original, and all of which
together shall be deemed to be one and the same instrument.

18.6 Governing Law. This Agreement shall be governed by and construed
and enforced in accordance with the laws of the State of California, without
regard to conflicts of laws principles.

19. WARRANTY

Each Party warrants that it has the power to grant all of the rights
granted and make such required assignments, and to assume all of the obligations
required, under this Agreement. If, at the time a Patent application is to be
filed by ImClone with respect to any Active Compound, Lead Compound, Development
Compound or Products, CombiChem informs ImClone that CombiChem has the power to
grant the exclusive rights to such Active Compound, Lead Compound, Development
Compound or Products, and to assign such Patents related thereto, to ImClone in
accordance with Sections 3.2 and 5.2 above, CombiChem further warrants that, in
fact, as of such date, it has such power subject to the proviso that under no
circumstances does CombiChem warrant to ImClone that its rights in any Active
Compound, Lead Compound, Development Compound or Products are exclusive to the
extent such Active Compound, Lead

<PAGE> 22

Compound, Development Compound or Products may be covered under the patent
claims of Third Parties wherein such claims are not the direct result of a
collaboration between the Third Party and CombiChem.

IN WITNESS WHEREOF, the parties have executed this Agreement to be
effective as of the Effective Date.

COMBICHEM, INC. IMCLONE SYSTEMS INCORPORATED

By: /s/ Vicente Anido By: /s/ illegible
-------------------- --------------------------------------------
Its: President and CEO Its: CFO

<PAGE> 23

Appendix A

***

*** Portions of this page have been omitted pursuant to a request for
Confidential Treatment and filed separately with the Commission.

<PAGE> 24

Appendix B

Milestone Payments
(Triggered by Activities of ImClone or Its Licensees)

<TABLE>
<CAPTION>
Development Milestone Milestone Payment
- --------------------- -----------------
<S> <C>
***
*** U.S. ***

*** U.S. ***
***

*** U.S. ***
***
***
------------
Total U.S. ***
</TABLE>

*** Portions of this page have been omitted pursuant to a request for
Confidential Treatment and filed separately with the Commission.

<PAGE> 1
EXHIBIT 10.23

COLLABORATIVE RESEARCH AND LICENSE AGREEMENT

BETWEEN

COMBICHEM, INC.

AND

ATHENA NEUROSCIENCES, INC.

OCTOBER 15, 1997

<PAGE> 2

COLLABORATIVE RESEARCH AND LICENSE AGREEMENT

THIS COLLABORATIVE RESEARCH AND LICENSE AGREEMENT (the
"Agreement") is entered into and made effective as of October 15, 1997 (the
"Effective Date"), by and between COMBICHEM, INC., a Delaware corporation having
its principal offices at 9050 Camino Santa Fe, San Diego, California 92121
("CombiChem") and ATHENA NEUROSCIENCES, INC., a Delaware corporation and a
wholly-owned subsidiary of Elan Corporation, plc ("Elan"), having its principal
offices located at 800 Gateway Boulevard, South San Francisco, California 94080
("Athena").

WHEREAS, CombiChem has developed and owns certain drug discovery
technology and intellectual property rights, including chemical library design
software, multi-parallel synthesis and purification methods, chemical libraries
suitable for high throughput biological screening assays and medicinal chemistry
(collectively, "CombiChem Technology");

WHEREAS, as of the Effective Date, Elan, Athena and their
Affiliates have developed and own certain drug discovery and intellectual
property rights, including certain assays, methods and know how regarding the
Initial Targets and the Optional Targets, among other things (collectively
"Athena Technology");

WHEREAS, Athena desires to utilize CombiChem Technology for its
drug discovery activities under Athena know-how concerning the identification
and characterization of novel small molecule inhibitors for development as
therapeutics for treatment of central nervous system conditions in humans;

WHEREAS, the parties wish to collaborate in a Research Program
against Collaboration Target(s) ("Collaboration");

WHEREAS, during the Research Period and for purposes of the
Collaboration, the Parties intend to focus on up to six (6) Collaboration
Targets;

NOW, THEREFORE, the Parties agree as follows:

1. DEFINITIONS

1.1 "Abandoned Target" shall have the meaning given in Section
4.1.

1.2 "Abandoned Compound" shall have the meaning given in Section
4.1.

1.3 "Active Compound(s)" means a compound (or compounds) which

(a) (i) is selected by the RMC under the Research
Program from Collaboration Compounds under
Section 4.2, or

<PAGE> 3

(ii) is a Derivative of a Collaboration Compound
which is so selected by the RMC; and

(b) shows In Vitro Activity.

1.4 "Affiliate" of a Party means any corporation or other
business entity controlled by, controlling or under common control with, such
Party. For this purpose "control" shall mean direct or indirect beneficial
ownership of more than fifty percent (50%) of the voting securities or income
interest in such corporation or other business, or if not meeting the preceding
requirements, any company owned or controlled by or owning or controlling such
Party at the maximum control or ownership right permitted in the country where
such company exists.

1.5 "Athena Compound" means a chemical compound that is
proprietary to Athena or whose use or manufacture is proprietary to Athena or
its Affiliates.

1.6 "Athena Technology" shall have the meaning set forth in the
preamble of this Agreement.

1.7 "Collaboration" has the meaning set forth in the preamble.

1.8 "Collaboration Compound(s)" means a compound (or compounds)
which (a) is synthesized following the Effective Date for screening against a
Collaboration Target under the Research Program, (b) is a pre-existing or
hereafter acquired CombiChem compound which CombiChem desires to designate as a
Collaboration Compound, or (iii) is a pre-existing or hereafter acquired Athena
compound which Athena desires to designate as a Collaboration Compound.

1.9 "Collaboration Library" means a library synthesized under the
direction of the RMC, containing compounds designed to provide information
regarding activity against a specific Collaboration Target.

1.10 "Collaboration Target(s)" means either an Initial Target or
an Optional Target.

1.11 "CombiChem Compound" means a chemical compound that is
proprietary to CombiChem, or whose use or manufacture is proprietary to
CombiChem.

1.12 "CombiChem Technology" has the meaning set forth in the
preamble.

1.13 "Confidential Information" includes, but is not limited
to,

(a) all information and materials received by either
Party from the other Party pursuant to this
Agreement which is confidential under Article 11;

2
<PAGE> 4

(b) all information and materials by either Party
arising out of the Collaboration during the
Research Period;

(d) the financial terms of this Agreement.

1.14 "Daughter Libraries" shall mean the compound libraries which
are designed and synthesized as a part of the Collaboration.

1.15 "Derivative" shall mean a compound (or compounds) which has
resulted from subsequent chemical synthesis to generate an Active Compound or
Development Compound in support of the Research Program.

1.16 "Development Compound(s)" means a compound (or
compounds) which

(a) (i) is an Active Compound or (ii) is a
Derivative of an Active Compound; and

(b) is determined by Athena to be appropriate for
preclinical studies for the purpose of IND filing
by Athena.

1.17 "Due Diligence" means the use of by a Party of its or its
Affiliates' resources in a manner which is consistent with the exercise of
reasonable and prudent scientific and business judgment as applied to other
programs of Athena or CombiChem, as the case may be, targeting products aimed at
markets or patient groups of similar sizes and of similar scientific and
commercial potential. With respect to any Development Compound, "Due Diligence"
shall also require Athena or its Affiliates to use commercially reasonable
efforts to conduct all necessary preclinical studies and to file an IND for such
Development Compound within two (2) years from the date upon which Athena has
designated such Development Compound from any Active Compound or its
Derivatives. For purposes of this Agreement, failure to exercise Due Diligence
by any Party shall be established if such Party receives written notice
describing such failure and does not cure such failure within ninety (90) days
of the receipt of such notice.

1.18 "Exclusivity Period" means the Research Period plus
twelve (12) months.

1.19 "Field" means all therapeutic and diagnostic indications in
humans for any target against which an Active Compound, Development Compound or
Products may be directed.

1.20 "First Commercial Sale" of a Product shall mean the first
sale for use or consumption of such Product in a country after required
marketing and pricing approval has been granted by the governing health
regulatory authority of such country. Sale to an Affiliate shall not constitute
a First Commercial Sale unless the Affiliate is the end user of the Product.

3
<PAGE> 5

1.21 "FTE" shall mean a full-time equivalent employee of
CombiChem. For purposes of this Agreement, the FTEs shall include synthetic and
analytical chemists, compound control scientists and computational scientists.

1.22 "Inactive Compound(s)" means a Collaboration Compound(s)
which does not have the In Vitro Activity required for an Active Compound.

1.23 "In Vitro Activity" shall mean the observation of *** in
assays as described by Athena in the Research Plan for each Collaboration
Target.

1.24 "Initial Target" shall have the meaning set forth in
Section 3.1 hereof.

1.25 "Net Sales" means the gross sales invoiced by Athena or its
Affiliates for Products to non-Affiliated Third Parties (and to Affiliates who
are the end users of such Products) less actual deductions or returns (including
withdrawals and recalls), rebates (price reductions, including formulary or
Medicaid and similar types of rebates, e.g. chargebacks), cash, trade or volume
(quantity) discounts, discounts granted at the time of invoicing, the cost of
transport, insurance, delivery, sales taxes and use, tariff, excise or other
taxes (other than income taxes) directly linked to and included in the gross
sales amount as computed on a product-by-product basis for the countries
concerned, whereby the amount of such sales in foreign currencies is converted
into United States dollars at the exchange rate of the last business day for
each calendar month as reported in The Wall Street Journal.

1.26 "Optional Target(s)" means a Target that is added to the
Collaboration in accordance with Section 3.2.

1.27 "Patent" means (a) valid and enforceable Letters Patent, and
any non-U.S. equivalent, including any extension (including Supplemental
Protection Certificates), registration, confirmation, reissue, continuation,
divisionals, continuation-in-part, reexamination or renewal thereof, or (b)
pending applications for any of the foregoing, whether filed or issued before or
after the Effective Date of this Agreement.

1.28 "Party" means CombiChem or Athena, as the case may be,
including their respective Affiliates, permitted successors and assigns.

1.29 "Product(s)" means any product containing an Active Compound
or Development Compound with such compound as the active ingredient and which is
granted regulatory approval by the governing health regulatory authority of the
applicable country for marketing in the Field.

1.30 "Project Team" shall have the meaning set forth in Section
2.1(c).

1.31 "Proposed Targets" shall have the meaning given in Section
3.1.

*** Portions of this page have been omitted pursuant to a request for
Confidential Treatment and filed separately with the Commission.

<PAGE> 6

1.32 "Related Target(s)" shall mean those targets identified by
Athena in writing to CombiChem as having a direct relationship to Collaboration
Targets or Proposed Targets, which will provide Athena exclusivity as outlined
in Section 4.5.

1.33 "Research Management Committee" or "RMC" has the meaning set
forth in Article 6 below.

1.34 "Research Period" means the initial term of the
Collaboration commencing on the Effective Date and ending on December 31, 2000,
unless earlier terminated, which can be extended in accordance with Section 7.1
below.

1.35 "Research Plan" means the research plan to be agreed in
writing between the Parties, which describes the research activities to be
performed for each Collaboration Target.

1.36 "Research Program" means the research to be conducted for
the Collaboration including, without limitation, the activities described in the
Research Plan and set forth in Sections 2.1 and 2.2 of this Agreement.

1.37 "Returned Compound" shall have the meaning set forth in
Section 9.2.

1.38 "Royalty Term" means, in the case of any Product, in any
country, the period of time commencing on the First Commercial Sale and ending
upon the later of (a) ten (10) years from the date of First Commercial Sale in
such country; or (b) the expiration of the last-to-expire Patent resulting from
the Research Program filed in the Field during the Exclusivity Period with
claims covering that Product in the relevant country.

1.39 "Target" means a biomolecular entity that a small molecule
is synthesized against wherein the small molecule demonstrates relevant
activity.

1.40 "Territory" means the entire world.

1.41 "Third Party" means an entity other than CombiChem or Athena
or their respective Affiliates.

1.42 "UIL" means CombiChem's proprietary Universal Informer
Library(TM).

2. RESEARCH COLLABORATION

2.1 CombiChem Responsibilities. CombiChem shall with Due
Diligence provide the following resources to Athena and conduct the following
activities under the Research Program and as more fully described in the
Research Plan:

(a) During the Research Period, CombiChem shall (i)
review data and information regarding the
Collaboration Targets provided by Athena; (ii)
based on such data and information and using the

<PAGE> 7

CombiChem Technology, design Daughter Libraries;
and (iii) supply all lead chemistries and
synthesize compounds as provided in Section 5.4
below.

(b) During the Research Period, CombiChem shall keep
Athena informed of its activities performed in
connection with the Collaboration, including,
without limitation, providing Athena with data and
information (and, upon Athena's request, reasonable
quantities of samples pursuant to Section 5.4)
regarding the status of all Collaboration Compounds
prior to the meetings of the Research Management
Committee.

(c) Subject to Section 2.3, Article 3 and Section 8.3,
and at all times during the Research Period,
Combichem shall dedicate, in separate laboratory
facilities as to its chemistry efforts, one or more
project team(s) ("Project Team"), each consisting
of such number of FTEs as determined by the RMC to
conduct all of CombiChem's activities in connection
with the collaboration at a per annum rate of U.S.
*** to be paid by Athena. The initial Project Team
shall consist of a minimum of five (5) CombiChem
FTEs, unless the RMC determines other use.

2.2 Athena Responsibilities. Athena shall with Due Diligence
provide the following resources to CombiChem and conduct the following
activities under the Research Program as more fully described in the Research
Plan:

(a) Athena shall provide CombiChem with funding for the
Collaboration as set forth in Article 8, provide
screening, biological and structural data and
information (including leads and/or screening hits
and assay methods relating to Collaboration
Compounds) to CombiChem with respect to the
Collaboration necessary for CombiChem to perform
its duties under this Agreement, and will assume
scientific, financial and administrative
responsibility for screening and biological support
activities, drug development and regulatory filings
during and after the term of the Collaboration on
the terms set forth below. At its option, Athena
may also provide pre-existing screening data and
related information for the Collaboration.

(b) During the Research Period, Athena shall provide
CombiChem with data and information regarding
Collaboration Compounds and the Collaboration
Target assays developed by Athena under the
Research Program prior to the meetings of the
Research Management Committee.

*** Portions of this page have been omitted pursuant to a request for
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<PAGE> 8

(c) During the Exclusivity Period, Athena shall screen
Collaboration Compounds for In Vitro Activity and,
where appropriate, in vivo activity against the
Collaboration Target.

(d) During the Exclusivity Period, with respect to any
Collaboration Target against which an Active
Compound has designated by the RMC, Athena shall
(i) screen Active Compound, (ii) endeavor to
determine Development Compounds, and (iii) endeavor
to develop Products. At any time during the
Collaboration, Athena may apply chemistry effort to
any Collaboration Compound, including synthesis, as
coordinated by the RMC.

(e) Following the first IND filing through First
Commercial Sale, Athena shall provide CombiChem
with an annual report summarizing Athena's
activities in developing Development Compounds.

2.3 Conduct of Research Program. The Parties hereby agree that
the Research Programs shall be carried out in accordance with the Research Plan,
as amended from time to time. The Research Management Committee shall review the
Research Plan on an ongoing basis and may make changes to the Research Plan so
long as such changes are mutually agreed to by CombiChem and Athena. For each
Research Program, the RMC will determine the appropriate size and composition of
the Project Team (i.e., the identity and number of CombiChem FTEs in each
relevant scientific discipline), and shall prioritize the activities of the
Project Team against such Collaboration Target(s) within the scope of that
Research Program.

Athena shall designate the first Collaboration Target from
the Proposed Targets by notice in writing to CombiChem. The Research Program
against that Target shall commence *** against the *** Collaboration Target. The
commencement date of the Research Program(s) for the subsequent Initial Targets
(other than the first Collaboration Target) and any Optional Targets shall be as
set forth in Section 3.1.

2.4 Third Party Licenses. Each Party shall be solely responsible
for any Third Party license fees required to perform its obligations under this
Agreement.

3. TARGETS

3.1 Initial Targets. During the Research Period, Athena may
designate *** "Proposed Targets" (with the right of substitution) as "Initial
Targets" to be worked on by Project Teams for purposes of the Collaboration. The
Proposed Targets and the Initial Targets shall be those designated in writing by
the Chief Operating Officer of Elan within *** of the Effective Date. No
activity with respect to any Initial Targets shall be conducted by the Project
Teams until a date to be mutually agreed upon by the Parties. The Project Teams

*** Portions of this page have been omitted pursuant to a request for
Confidential Treatment and filed separately with the Commission.

<PAGE> 9

shall work on Initial Targets as directed by the RMC. The project fee set forth
in Section 8.1(a) shall include all *** Initial Targets.

3.2 Optional Targets. Subject to timely payment of its
obligations set forth in Article 8 (including the project initiation fee set
forth in Section 8.1(b) and the payments required in Sections 8.3, 8.4, 8.5 and
9.3) and provided that all *** Initial Targets have been designated by Athena
and the Research Programs covering such Initial Targets are or have been active,
during the Research Period, Athena may designate (by providing written notice in
the manner described in Section 3.1) *** additional Proposed Targets (or other
Targets as may be mutually agreed) as Optional Targets, with the Research
Program for each such Optional Target to begin within ninety (90) days of such
written notification or as mutually agreed by the parties; it being understood
that the Project Teams shall work on Optional Targets as directed by the RMC.
The project initiation fee set forth in Section 8.1(b) shall include ***
Optional Targets. Upon such designation, the RMC shall establish the specific
scientific achievements (to be mutually agreed between CombiChem and Athena) for
such Optional Target and the same shall be designated as an Optional Target for
the Collaboration and subject to the terms (including the commercial terms) of
this Agreement.

4. EXCLUSIVITY

4.1 Collaboration Target Exclusivity. Prior to designating a
Collaboration Target for an active Research Program under Article 3, and
thereafter so long as Athena or its Affiliates are proceeding with Due Diligence
for that Target, CombiChem shall not knowingly work on or knowingly provide
information regarding a Collaboration Target with or to any Third Parties,
except (a) as provided for in Section 12.2 with regard to any Public Statements,
and (b) with respect to any Third Parties who are collaborators or proposed
collaborators of CombiChem, CombiChem shall have the right, consistent with its
corporate policy (but without identifying any Collaboration Target), to notify
any such Third Party of its decision and/or inability to work on such Target
with that Third Party. In the event that Athena or its Affiliates have not
transferred or assigned control of its program for that Target to a Third Party
under due diligence obligations no less stringent than those set forth herein
and have failed to exercise Due Diligence with respect to, or notifies CombiChem
in writing that it has abandoned work on, any Collaboration Target (an
"Abandoned Target") and any Collaboration Compound associated with such
Abandoned Target (together with all Derivatives of such Collaboration Compound,
an "Abandoned Compound"), then such Abandoned Target and/or Abandoned Compound
shall be available to CombiChem (excluding any Athena Compounds and Athena
Technology) and to Athena for any purpose thereafter.

4.2 Active Compounds. Following the designation of any
Collaboration Compound as an Active Compound, such Active Compound shall be
exclusively available to Athena for research or application to any Target,
within or outside the Collaboration, during the Exclusivity Period and CombiChem
shall not knowingly work on or knowingly provide information regarding such
Active Compound to any Third Party, except to reject and take any steps
necessary to protect Athena's exclusivity hereunder. Following the expiration of
the Exclusivity Period Active Compounds for that Target upon which a Patent has
not been filed

*** Portions of this page have been omitted pursuant to a request for
Confidential Treatment and filed separately with the Commission.

<PAGE> 10

within ninety (90) days following the Research Period shall be deemed to be
Inactive Compounds for all purposes hereunder; provided, that any Active
Compound which is the subject of claim(s) under a pending Patent shall continue
to be treated as Active Compounds until a Patent is issued with respect to one
or more of such claims; or until all of such Patent claims have been denied, at
which time the compounds which are the subject to those claims shall be Inactive
Compounds hereunder.

4.3 Inactive and Returned Compounds. Any Inactive Compounds and
Returned Compounds shall be available to CombiChem (except for any pre-existing
Athena Compound) and Athena for any purpose following the designation of a
Collaboration Compound as an Inactive Compound or Returned Compound.

4.4 Duration of Exclusivity for Collaboration Targets.
Notwithstanding any other provision of this Agreement, it is understood and
agreed that once a research Program has been initiated by the RMC for a
Collaboration Target, CombiChem's obligations under Section 4.1 shall continue
until Athena has (a) released CombiChem from the effect of this Section 4.4 by
written notice from the Chief Operating Officer of Elan, or (b)(i) failed to
exercise Due Diligence with respect to that Target, and (ii) has not transferred
or assigned its control of the development of its program for that Target to a
Third Party with due diligence requirements no less stringent than those set
forth in this Agreement. In the event of such transfer or assignment to a Third
Party, the Exclusivity Period provided in this Section 4.4 with respect to such
Target shall continue until the earlier of (a) receipt by CombiChem of a written
release from such Third Party or (b) the failure of such Third Party to exercise
Due Diligence with respect to that Target.

4.5 Exclusivity of Related Targets. (a) During the Research
Period (and thereafter, as provided in Section 4.5(c) below), CombiChem shall
not knowingly work on or knowingly provide information regarding a Related
Target with or to any Third Party, except (i) as provided for in Section 12.2
with regard to any Public Statements, and (ii) with respect to any Third Parties
who are collaborators or proposed collaborators of CombiChem, CombiChem shall
have the right, consistent with its corporate policy (but without identifying
any Collaboration Target or Related Target) to notify any such Third Party of
its decision and/or inability to work on such Target with that Third Party.

(b) *** *** has conducted scientific inquiry or research
regarding that Target. The RMC may from time to time discuss the status
of Athena's inquiry or research into any such additional Related
Targets. Athena shall notify CombiChem in writing if it abandons its
inquiry or research regarding any additional Related Targets, at which
point it shall no longer be a Related Target.

(c) The exclusivity provided in Section 4.5(a) shall be
extended for an additional year following the Research Period upon the
initiation of a Research Program for each of the *** Collaboration
Targets, for a maximum extension of three years following the Research
Period.

*** Portions of this page have been omitted pursuant to a request for
Confidential Treatment and filed separately with the Commission.

<PAGE> 11

(d) If a Related Target or additional Related Target
becomes a Collaboration Target, then all of the other provisions of
this Agreement (including without limitation the exclusivity provisions
of this Article 4) shall apply to such Collaboration Target.

4.6 Survival. This Article 4 shall survive termination or
expiration of this Agreement.

5. COLLABORATION COMPOUNDS

5.1 Pre-Existing Compounds. Neither Party shall have any rights
to any pre-existing compound of the other Party unless and until such compound
is designated as a Collaboration Compound by such Party. Additionally, CombiChem
may decline (after informing Athena) to synthesize a particular compound or
library of compounds by reason of existing Patents or contractual obligations.

5.2 Intellectual Property Rights; License to Athena. Subject to
Section 9.2, and except as set forth in this Section 5.2, Athena shall own and
have exclusive rights in all Patents and intellectual property (whether or not
patentable) relating to Active Compounds and the subject matter contained
therein and resulting from the Research Program during the Exclusivity Period
and thereafter so long as Athena continues to show Due Diligence for that
Target. Notwithstanding the foregoing, Athena acknowledges and agrees that
CombiChem reserves the right to assign or grant exclusive rights to any compound
to a third party collaborator who completes an act of invention with regard to
such compound to the extent CombiChem is obligated to do so under CombiChem's
existing contractual obligations and further provided that CombiChem has timely
(but in any event within *** after notification from Athena that such compound
shows In Vitro Activity) notified Athena in writing of such assignment or grant
and its designation as an unavailable compound. Athena shall be responsible for
filing, maintaining and prosecuting all Patents relating to Active Compounds at
its sole expense. Prior to the filing of any such Patent applications, CombiChem
shall assign to Athena or its designee all intellectual property rights it may
have in the Active Compounds and the subject matter claimed therein which are
necessary for the development and commercialization by Athena or its designee.
If Athena fails to so file, maintain or prosecute such Patent, CombiChem shall
have the right to request Athena to do so. If Athena elects not to file,
maintain or prosecute such Patent, on a country-by-country basis, CombiChem
shall have the right to take over such filing, maintenance or prosecution of
such Patent, at its sole expense, and, as a result, *** shall be entitled to
recover from the proceeds of any infringement action brought by CombiChem in any
such country (i) *** , and (ii) *** , with the remainder to be paid *** .

5.3 Structural Information. Neither Party shall disclose the
structure of any Active Compound to any Third Party without the other Party's
written permission, unless required to do so by law, in which case such Party
shall promptly notify the other Party of such required disclosure. If a subpoena
or other legal process concerning the same is served upon either Party, the
other Party shall cooperate with the Party served in any effort to contest the
validity of such subpoena or other legal process.

*** Portions of this page have been omitted pursuant to a request for
Confidential Treatment and filed separately with the Commission.

<PAGE> 12

5.4 Supply of Collaboration Compounds. Aliquots of at least ***
milligrams of any Collaboration Compound that has been synthesized will be
prepared and given to Athena. CombiChem shall replenish that amount upon
Athena's reasonable request. CombiChem shall maintain aliquots of any
Collaboration Compound that has been synthesized by CombiChem. CombiChem shall
also provide Athena with additional requirements of samples at CombiChem's cost.

6. RESEARCH MANAGEMENT COMMITTEE

The design, review and conduct of the Research Program will be
coordinated by the Research Management Committee, which will meet regularly on a
mutually-agreeable schedule. Each Party shall bear its own expenses related to
such meetings. The Research Management Committee may establish and amend or
revise the Research Plan as reasonable and necessary to reflect the scientific
progress and work performed under the Research Program, such amendments to be
mutually agreed to in writing by Athena and CombiChem. The Research Management
Committee will consist of an equal number of members from Athena and CombiChem
and will include appropriate representatives from Athena and CombiChem as
mutually agreed. The co-chairs of the Research Management Committee will
initially be the Vice President, Chemistry of CombiChem and the Vice President,
Research of Athena and subsequently may change as each Party determines for its
co-chair. Decisions of the Research Management Committee shall be by consensus.
If Athena elects not to file, maintain or prosecute such Patent, on a
country-by-country basis, CombiChem shall have the right to take over such
filing, maintenance or prosecution of such Patent, at its sole expense, and, as
a result, CombiChem shall be entitled to recover from the proceeds of any
infringement action brought by CombiChem in any such country (i) 200% of its
out-of-pocket costs, and (ii) 50% of the balance of the proceeds of such action,
with the remainder to be paid to Athena.

7. RESEARCH PERIOD; TERMINATION OF RESEARCH PROGRAM

7.1 Research Period: Option to Extend the Research Period. The
initial term of the Collaboration shall be the Research Period subject to
extension upon mutual agreement. To extend the Research Period, Athena must
notify CombiChem no later than ninety (90) days prior to the then-current
expiration date and the Parties shall negotiate in good faith the terms and
conditions of any such extension.

7.2 Termination of Research Program Upon Breach. The Research
Program and/or this Agreement may be terminated by a Party for the material
breach by the other Party as provided by Section 10.2.

7.3 Termination by Athena. Athena may terminate this Agreement
effective at any time after one (1) year from the Effective Date, in its sole
discretion, upon ninety (90) days' prior written notice. Athena may also
terminate any part of the Research Program directed at one or more of the
Collaboration Targets, also upon ninety (90) days' prior written notice, at any
time during the Collaboration, in which case the RMC shall reallocate the FTEs
affected to any of the other Collaboration Targets.

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<PAGE> 13

8. CONSIDERATION

8.1 Project Initiation Fee. Athena shall pay CombiChem (a) within
ten (10) days following the Effective Date a non-refundable, noncontingent
project initiation fee of U.S. $1,333,333 in cash to initiate the Research
Program for the Initial Targets (Collaboration Targets *** ) and (b) upon the
designation of any Optional Target (Collaboration Targets *** ), a
non-refundable project initiation fee of U.S. *** per Optional Target (for a
total of *** ), payable upon the later of (i) the date of commencement of a
Research Program with respect to such Optional Target, or (ii) *** .

8.2 Equity Purchase. Elan International Services, Ltd. ("EIS"),
an Affiliate of Athena, shall purchase shares of Common Stock of CombiChem
pursuant to the terms of that certain Common Stock Purchase Agreement, dated as
of the Effective Date, by and between CombiChem and EIS (the "Stock Purchase
Agreement"). In the event that CombiChem closes an initial public offering of
its common stock at a sales price per share to the public (the "IPO Price")
which is less than $2.50 per share (on a pre-split basis), then, upon the
closing of such initial public offering, CombiChem shall issue to ImClone,
without further consideration other than the purchase price paid by ImClone
pursuant to the Stock Purchase Agreement, such additional number of shares of
CombiChem common stock equal to:

2,000,000
--------- = 1,000,000
Adjusted Price

wherein the "Adjusted Price" = the IPO Price X .80 if the IPO Price is less
than $2.50 per share. All shares of CombiChem common stock issued pursuant to
this Section 8.1 shall be deemed to be "Shares" within the meaning of the Stock
Purchase Agreement.

8.3 Program Funding.

(a) Research Support for Project Team. At all times
during the Research Period, Athena shall make payments to CombiChem for direct
research support for its Project Team, which shall consist of a minimum of five
(5) full time employees ("FTEs") of CombiChem, unless the RMC determines
otherwise. The total amount payable per FTE shall be U.S. *** . All payments for
direct research support shall be paid by Athena to CombiChem, quarterly in
advance, and adjusted as necessary in subsequent quarters, of such amounts as
are equal to the product of (i) the number of CombiChem FTEs (a minimum of five
(5) FTEs at all times unless the RMC determines otherwise) allocated to the
Research Program by the RMC for the calendar quarter to which each such payment
applies, multiplied by (ii) U.S. *** (i.e., the quarterly amount per Combichem
FTE on the basis of U.S. *** ). All such FTEs shall be CombiChem's employees.
Athena shall not be responsible for, and CombiChem shall indemnify and hold
Athena harmless from, any salary, benefits, or employment-related claims of any
kind asserted by CombiChem's employees.

(b) Expansion of Project Team. Athena may request that
CombiChem expand its Project Team during the Research Period in order to
accelerate work on Collaboration Targets and/or to add Optional Targets. In such
event, the RMC shall promptly confer as to the appropriate number of FTEs to be
added to the Project Team, at a cost to Athena of U.S. *** per FTE to be paid as
specified in Section 8.3(a).

8.4 Milestone Payments. Within thirty (30) days of the occurrence
of a development milestone triggered by the activities of Athena or its
Affiliates as shown on Appendix A, Athena shall pay CombiChem the related
milestone payment in U.S. dollars as set forth on Appendix A. Such payments
shall apply to any milestone reached by an Active Compound, Development Compound
or Product, whether the Target is within or outside the Collaboration.

*** Portions of this page have been omitted pursuant to a request for
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<PAGE> 14

8.5 Royalties. During the Royalty Term, Athena will pay CombiChem
a *** of Net Sales of Products sold by Athena or its Affiliates in all countries
in the Territory. Each payment of royalties shall be accompanied by a report of
Net Sales of Products in sufficient detail to permit confirmation of the
accuracy of the royalty payment made.

8.6 Manner and Place of Payment. Royalty payments and reports for
Net Sales of Products shall be calculated in local currencies and reported for
each calendar quarter. All royalty payments owed under this Agreement shall be
made by wire transfer to the bank account to be designated by CombiChem within
sixty (60) days following the end of each such calendar quarter.

8.7 Records and Audit. During the term of this Agreement and for
a period of three (3) years thereafter, Athena shall keep complete and accurate
records pertaining to the sale or other disposition of Products in sufficient
detail to permit CombiChem to confirm the accuracy of all payments due
hereunder. CombiChem shall have the right to cause an independent certified
public accounting firm reasonably acceptable to Athena to audit such records to
confirm Athena's Net Sales for the preceding year. Any information obtained
during such audit shall be treated as Confidential Information. Such audits may
be exercised after reasonable notice during normal business hours of Athena no
more than once each year. CombiChem shall bear the full cost of such audit
unless such audit discloses a deficiency of the greater of *** or more than ***
from the amount of the Net Sales reported by Athena for such audited period. In
such case, Athena shall bear the reasonable cost of such audit.

8.8 Taxes. All income and other taxes levied on account of the
royalties and other payments accruing to CombiChem under this Agreement shall be
paid by CombiChem, including taxes levied thereon as income to CombiChem. If
provision is made in law or regulation for withholding, such tax shall be
deducted from the royalty or other payment made by Athena to the proper taxing
authority and a receipt of payment of the tax secured and promptly delivered to
CombiChem. Each Party agrees to assist the other Party reasonably in claiming
exemption from such deductions or withholdings under any double taxation or
similar agreement or treaty from time to time in force.

9. LICENSE GRANTS; OUTLICENSE

9.1 CombiChem License Grant to Athena. Subject to the terms and
conditions of this Agreement, CombiChem hereby grants to Athena an exclusive,
royalty-free, worldwide license, with the right to sublicense to use such
CombiChem Technology as is necessary to make, have made, use, have used, sell,
have sold, import and export Collaboration Compounds or Products in the
Territory. Such license shall remain exclusive (including as to CombiChem) in
relation to each Active Compound, Development Compound and/or Product so long as
Athena or its licensee continues to develop and commercialize such Active
Compound, Development Compound and/or Product against a Collaboration Target
with Due Diligence.

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<PAGE> 15

9.2 Athena License Grant to CombiChem. Subject to Article 4 and
following the failure of Athena or its licensee to develop and commercialize
with Due Diligence an Active Compound, a Development Compound or Product, as the
case may be (collectively, and together with all Abandoned Compounds, "Returned
Compounds"), Athena shall grant to CombiChem a non-exclusive, royalty-free
license, with the right to sublicense, under those Athena Patents and know-how
which are resulting from the Research Program and related exclusively to the
Returned Compound, to make, have made, use, have used, sell, have sold, import
and export such Returned Compound in the Territory.

9.3 Athena Outlicense. Athena shall have the right to transfer,
assign or outlicense to a Third Party the Products or Patents covering the
Products, subject to CombiChem's right to receive (a) royalties as provided in
Appendix A, and (b) the percentage of the Third Party Payments set forth in
Appendix A. For purpose of this Section 9.3, "Third party Payments" shall mean
all payments **** *** , which shall include, but not be limited to, *** *** ***
. All Payments shall be made to CombiChem by wire transfer to such bank account
designated by CombiChem within five (5) business days after receipt by Athena or
its Affiliates of such Payments from the Third Party. As an express condition of
any such outlicense, any such licensee shall be required to agree in writing to
be bound by due diligence, royalty reporting and recordkeeping and inspection
provisions no less stringent than those contained in this Agreement. In
addition, CombiChem shall have the right to receive all audit reports relating
to sales of Products of Athena's licensees, and to cause Athena or its
Affiliates or successors to have an independent certified public accounting firm
(reasonably acceptable to Athena) audit such licensee's records on the same
terms as those specified in Section 8.6. Failure of such licensee to make any
milestone or royalty payment in respect of such Product shall not relieve Athena
of its obligations to make royalty and milestone payments to CombiChem
hereunder.

9.4 Rights to Inactive Compounds. Except for any Athena Compounds
(which remain proprietary to Athena), each of Athena and, subject to Athena's
Patent rights, CombiChem shall have rights to make, have made, use, have used,
sell, have sold, import and export Inactive Compounds or products containing
Inactive Compounds. Specifically, each party shall be free to screen Inactive
Compounds against any target other than the Collaboration Targets. In the event
that either Athena or CombiChem shall develop, market and/or sell, or enter into
a binding agreement with a Third Party to develop, market and/or sell, any
product containing the Inactive Compound as an active ingredient, then the other
Party hereto shall not be entitled to any payments, milestones, royalties, fees
or compensation of any kind.

10. TERM AND TERMINATION OF THE AGREEMENT

10.1 Term. The term of this Agreement shall commence upon the
Effective Date of this Agreement, and unless earlier terminated as provided in
this Agreement, shall expire on December 31, 2000.

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<PAGE> 16

10.2 Termination by Athena or CombiChem. If either Party
materially breaches this Agreement and fails to remedy that breach within ninety
(90) days of receiving written notice thereof from the other Party, or enters
into any arrangement of composition with its creditors or goes into liquidation,
insolvency, bankruptcy, receivership or reorganization proceedings, whether
voluntarily or compulsorily which is not dismissed within ninety (90) days, then
the other Party may at any time, by notice in writing or by telefax, terminate
this Agreement. Within sixty (60) days following termination for any Research
Program and/or research related to any Target under this Agreement, the RMC
shall prepare a detailed, final written report to each Party, and provide any
remaining supply of compounds in synthesis to date, for each Target or Research
Program being terminated.

10.3 After Termination. Any termination of this Agreement or the
Research Program shall be without prejudice to the accrued rights of either
Party prior to the termination. In case of termination of this Agreement or the
Research Program pursuant to Section 10.2 above, all royalty, milestone, Payment
and confidentiality obligations set forth in Sections 8.1, 8.4, 8.5, 9.3, 9.4
and Articles 11 and 12 shall survive any such termination. Moreover, Athena
shall not be entitled to any refund of any payments made to CombiChem hereunder
upon the expiration of the term of this Agreement or earlier termination
pursuant to this Article 10.

10.4 Effect of Termination on Licensees. In the event or any
termination of this Agreement pursuant to this Article 10 where such termination
shall not have been caused by the action of inaction on the part of any
respective licensee of Athena or CombiChem, or by any breach by such licensee of
its obligations under its licensee from Athena or CombiChem, as appropriate,
such termination of this Agreement shall be without prejudice to the rights of
each non-breaching licensee and such licensee shall be deemed to be a direct
licensee hereunder.

11. CONFIDENTIAL INFORMATION

11.1 Nondisclosure. During the term of this Agreement and for a
period of *** *** after termination thereof, each Party will maintain all
Confidential Information in trust and confidence and will not disclose any
Confidential Information to any third party or use any Confidential Information
for any purpose except (i) as expressly authorized by this Agreement, (ii) as
required by law or court order, after as much advance notice as is practical to
the other Party, (iii) to its consultants, subcontractors or agents who need to
know to accomplish the purposes of this Agreement and who are bound by
equivalent written confidentiality obligations. Each Party may use the other
Party's Confidential Information only to the extent required to accomplish the
purposes of this Agreement. Each Party will use at least the same standard of
care as it uses to protect proprietary or confidential information of its own to
ensure that its Affiliates, employees, agents, consultants and other
representatives do not disclose or make any unauthorized use of the Confidential
Information. Each Party will promptly notify the other upon discovery of any
unauthorized use or disclosure of the Confidential Information.

*** Portions of this page have been omitted pursuant to a request for
Confidential Treatment and filed separately with the Commission.

<PAGE> 17

(b) is known by the receiving Party at the time of receiving such information,
as evidenced by its records; (c) is hereafter disclosed to the receiving Party
by a Third Party, as a matter of right and without restriction on disclosure;
(d) is independently developed by the receiving Party without the aid,
application or use of Confidential Information; or (e) is the subject of a
written permission to disclose provided by the disclosing Party.

12. PUBLICATIONS AND PUBLIC STATEMENTS

12.1 Publications. Without affecting obligations under Article 11
above, neither Party shall publish any information with respect to Collaboration
Compounds or Development Compound during the Exclusivity Period without the
prior written permission of the other Party. Such permission shall be approved
or disapproved within thirty (30) days of written request for permission unless
the other Party requests additional time (not to exceed ninety (90) days) for
the purpose of protecting its intellectual property position. Such permission
shall not be unreasonably withheld. The Party proposing to publish such
information shall give the other Party ninety (90) days prior written notice and
an opportunity to review such manuscript in order to determine the patentability
of the information contained therein.

12.2 Public Statements. Neither Party shall use the name of the
other Party in any public statement, prospectus, annual report or press release
or other public communication (collectively "Public Statements") without the
prior written approval of the other Party, which may not be unreasonably
withheld or delayed; provided, however, that both Parties shall endeavor in good
faith to give the other Party a minimum of two (2) business days to review such
Public Statements; provided, further, that, upon approval of any such Public
Statement, both Parties may disclose to Third Parties the information contained
in such Public Statement without the further approval of the other; and
provided, further, that if a Party does not approve such Public Statement,
either Party may still use the name of the other Party in any Public Statement
without the prior written approval of the other Party, if such Party is advised
by counsel that such disclosure is required to comply with applicable law.

13. INDEMNIFICATION

13.1 EACH PARTY HEREBY AGREES TO SAVE, DEFEND AND HOLD THE OTHER
PARTY AND ITS OFFICERS, DIRECTORS, EMPLOYEES, CONSULTANTS AND AGENTS HARMLESS
FROM AND AGAINST ANY AND ALL SUITS, CLAIMS, ACTIONS, DEMANDS, LIABILITIES,
EXPENSES AND LOSSES, INCLUDING REASONABLE LEGAL EXPENSES AND ATTORNEYS' FEES
("LOSSES") RESULTING DIRECTLY OR INDIRECTLY FROM THE INDEMNIFYING PARTY'S ACTS
OR OMISSIONS IN CONNECTION WITH THE MANUFACTURE, DEVELOPMENT, USE, HANDLING,
STORAGE, SALE OR OTHER DISPOSITION OF CHEMICAL AGENTS, COLLABORATION COMPOUNDS,
ACTIVE COMPOUNDS, DEVELOPMENT COMPOUNDS OR PRODUCTS BY SUCH PARTY, ITS
AFFILIATES OR LICENSEES except to the extent such Losses result from the
negligence, breach of this Agreement or willful misconduct of the Party claiming
a right of indemnification under this Article 13.

<PAGE> 18

13.2 Infringement

(a) Subject to Section 13.2(c) below, Athena shall hold
CombiChem and its officers, directors, employees, consultants, and agents
harmless from and against any and all losses resulting from the infringement of
any Third Party's Patent issued as of the Effective Date due to the performance
by Athena or its Affiliates of any activity contemplated hereunder, including,
but not necessarily limited to, Athena's responsibilities under Section 2.2
above, developing Products, and selling Products.

(b) Subject to Section 13.2(c) below, CombiChem shall hold
Athena and its officers, directors, employees, consultants, and agents harmless
from and against any and all losses resulting from the infringement of any Third
Party's Patent issued as of the Effective Date due to the performance by
CombiChem of any activity contemplated hereunder, including, but not necessarily
limited to, CombiChem's responsibilities under Section 2.1 above.

(c) The indemnity provided in Sections 13.2(a) and 13.2(b)
above shall not apply where the loss is due to the breach by the indemnified
Party of a warranty made in Article 19.

13.3 Procedures. If either Party (the "Indemnified Party") seeks
indemnification under this Article 13, it shall inform the other Party (the
"Indemnifying Party") of a claim as soon as reasonably practicable after it
receives notice of the claim, shall permit the Indemnifying Party to assume
direction and control of the defense of the claim (including the right to settle
any claim brought against the Indemnified Party upon prior written consent,
which shall not be unreasonably withheld), and shall give reasonable cooperation
(at the expense of the Indemnifying Party) in the defense of such claim.

14. ASSIGNABILITY

This Agreement may not be assigned by either Party without the
prior written consent of the other Party, not to be unreasonably withheld;
provided, however, that either Party may assign this Agreement, in whole or in
part, to an Affiliate (which may, in Athena's case, include an *** or to a
successor of a Party in connection with the merger, consolidation or sale of all
or substantially all of such Party's assets or that portion of its business
pertaining to the subject matter of this Agreement (and upon doing so will
promptly notify the other Party in writing); provided that the assigning Party
remains fully liable as obligated hereunder.

15. DISPUTE RESOLUTION PROCEDURES

15.1 Senior Executives Discussions. If a decision on a matter
regarding the management of the Research Program as provided herein is not
reached by the RMC, the dispute will be resolved as set forth in Article 6
above. If a dispute arises between CombiChem and Athena with respect to matters
other than the management of the Research Program, either during or after the
Research Period, such dispute will be referred to the appropriate senior
management in the area of the dispute. If such senior management are unable to
resolve such dispute, such

*** Portions of this page have been omitted pursuant to a request for
Confidential Treatment and filed separately with the Commission.

<PAGE> 19

dispute will be referred to the Chief Operating Officer of Elan and the Chief
Executive Officer of CombiChem. If such officers are unable to reach an
agreement within thirty (30) days following the initiation of discussions
between them, such dispute shall be settled by arbitration as described in
Section 15.2 below.

15.2 Binding Arbitration. If the parties have not been able to
resolve the dispute as provided in Section 15.1 above, the dispute shall be
finally settled by binding arbitration. Any arbitration hereunder shall be
conducted under rules of the American Arbitration Association. The arbitration
shall be conducted before three arbitrators chosen according to the following
procedure: each of the parties shall appoint one arbitrator and the two so
nominated shall choose the third. If the arbitrators chosen by the parties
cannot agree on the choice of the third arbitrator within a period of thirty
(30) days after their appointment, then the third arbitrator shall be appointed
by the Court of Arbitration of the American Arbitration Association. If
CombiChem brings an arbitration action, such arbitration shall occur in San
Francisco, California. If Athena brings an arbitration action, such arbitration
shall occur in San Diego, California. The arbitrators shall have the authority
to grant specific performance, and to allocate between the parties the costs of
arbitration in such equitable manner as they determine. The arbitral award (i)
shall be final and binding upon the parties; and (ii) may be entered in any
court of competent jurisdiction.

15.3 Injunctive Relief. Nothing contained in this Article 15 or
any other provisions of this Agreement shall be construed to limit or preclude a
Party from bringing any action in any court of competent jurisdiction for
injunctive or other provisional relief to compel the other Party to comply with
its obligations hereunder before or during the pendency of arbitration
proceedings.

16. NOTICES

Any notice required or permitted to be given hereunder shall be
deemed sufficient if sent by facsimile letter or overnight courier, or delivered
by hand to Athena or CombiChem at the respective addresses and facsimile numbers
as set forth below or at such other address and facsimile number as either Party
hereto may designate. If sent by facsimile letter, notice shall be deemed given
when the transmission is completed if the sender has a confirmed transmission
report. If a confirmed transmission report does not exist, then the notice will
be deemed given when the notice is actually received by the person to whom it is
sent. If delivered by overnight courier, notice shall be deemed given when it
has been signed for. If delivered by hand, notice shall be deemed given when
received.

if to CombiChem, to:

CombiChem, Inc.
9050 Camino Santa Fe
San Diego, California 92121
Attention: President
Fax number: (619) 530-9998

<PAGE> 20

with a copy to:

Brobeck, Phleger & Harrison LLP
550 South Hope Street, 21st Floor
Los Angeles, California 90071
Attention: Laurie A. Allen, Esq.
Fax number: (213) 239-1324

if to Athena, to:

Athena Neurosciences, Inc.
800 Gateway Boulevard
South San Francisco, California 94080
Attn: General Counsel
Fax number: (415) 875-3620

17. SURVIVAL

The provisions of Sections 2.4, 5.1, 5.2, 5.3, 10.3, 10.4 and Articles
4, 8, 9, 11, 12, 13, 15, and this Article 17 shall survive termination of this
Agreement in addition to those provisions which by their terms survive.

18. ADDITIONAL TERMS

18.4 Headings. The descriptive headings are inserted for convenience of
reference only and are not intended to be part of or to affect the meaning of or
interpretation of this Agreement.

18.5 Counterparts. This Agreement may be executed in one or more
counterparts, each of which shall be deemed an original, and all of which
together shall be deemed to be one and the same instrument.

<PAGE> 21

18.6 Governing Law. This Agreement shall be governed by and construed
and enforced in accordance with the laws of the State of California, without
regard to conflicts of laws principles.

18.7 Further Assurances. At any time and from time to time after the
Effective Date, the Parties shall each do, execute, acknowledge and deliver, and
cause to be done, executed, acknowledged or delivered, all such further acts,
transfers, conveyances, or assignments as may be reasonably required to carry
out the transactions contemplated by this Agreement

19. REPRESENTATIONS AND WARRANTIES

19.1 Authorization. All action on the part of each of CombiChem, Athena
and their respective officers, directors and stockholders necessary for the
authorization, execution and delivery of this Agreement and the performance of
all obligations of CombiChem, Athena and Athena, respectively, hereunder has
been taken. CombiChem represents that it has no present intention of materially
changing the manner in which it generally conducts its activities which are the
subject of the Collaboration.

19.2 Compliance with Other Instruments. The execution, delivery and
performance by CombiChem of this Agreement and the consummation of the Research
Program hereunder will not result in a violation of, or be in material conflict
with, or constitute a material default, under any agreement in existence as of
the Effective Date between CombiChem and its Third Party Collaborators. Subject
to Section 5.2 and except for the rights expressly reserved by CombiChem
therein, from the Effective Date until the expiration or termination of this
Agreement, CombiChem agrees that it shall not enter into any agreement with any
Third Party collaborator which would be in material conflict with, or cause a
default under, this Agreement.

19.3 Rights to Intellectual Property. Each Party warrants that it has
the power to grant all of the rights granted and make such required assignments,
and to assume all of the obligations required, under this Agreement. Under no
circumstances does CombiChem warrant to Athena that its rights in any Active
Compound, Development Compound or Products are exclusive to the extent such
Active Compound, Development Compound or Products may be covered under the
patent claims of Third Parties wherein such claims are not the direct result of
a collaboration between the Third Party and CombiChem.

<PAGE> 22

IN WITNESS WHEREOF, the parties have executed this Agreement to be
effective as of the Effective Date.

COMBICHEM, INC. ATHENA NEUROSCIENCES, INC.

By: /s/ Vicente Anido By: /s/ Illegible
---------------------- ---------------------

Its: President & CEO Its: Vice President & General Counsel

[SIGNATURE PAGE TO THE COLLABORATIVE
RESEARCH AND LICENSE AGREEMENT]

<PAGE> 23

Appendix A

A. Milestones - Direct Marketing By Athena/Affiliates

Milestone Payments (in U.S. Dollars)

<TABLE>
<CAPTION>
Milestone(1) Milestone Payment(2)
<S> <C>

***
*** in:

*** ***
*** ***
*** ***

***
***

*** ***
*** ***
*** ***

***
***

*** ***
*** ***
*** ***

Total ***
</TABLE>

(1) Based on Athena or its Affiliates having marketing responsibility for
Products

(2) Paid for each Compound which achieves the stated milestone

B. Outlicense By Athena/Affiliates

Royalty: *** of royalties received by Athena or its Affiliates, up to a
maximum of *** of all licensee net sales

Third Party Payments: *** of Third Party Payments received by Athena or
its Affiliates. In the case of outlicensing in *** a maximum of ***
(each), inclusive of any *** .

*** Portions of this page have been omitted pursuant to a request for
Confidential Treatment and filed separately with the Commission.

<PAGE> 1
EXHIBIT 23.2

CONSENT OF ERNST & YOUNG LLP, INDEPENDENT AUDITORS

We consent to the reference to our firm under the captions "Selected Financial
Data" and "Experts" and to the use of our report dated December 9, 1997, in
Amendment No. 4 to the Registration Statement (Form S-1) and related Prospectus
of CombiChem, Inc. for the registration of 2,587,500 shares of its common stock.

San Diego, California /s/ Ernst & Young LLP
December 10, 1997