<PAGE>
As filed with the Securities and Exchange Commission on March 10, 2000.
Registration No. 333-31456
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SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
--------------
AMENDMENT NO. 1 TO
FORM S-3
REGISTRATION STATEMENT
UNDER
THE SECURITIES ACT OF 1933
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RIBOZYME PHARMACEUTICALS, INC.
(Exact name of Registrant as specified in its charter)
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Delaware 2834 34-1697351
(State or other (Primary standard (I.R.S. Employer
jurisdiction of industrial identification number)
incorporation or classification code
organization) number)
2950 Wilderness Place
Boulder, Colorado 80301
(303) 449-6500
(Address, including zip code, and telephone number,
including area code, of registrant's principal executive offices)
--------------
RALPH E. CHRISTOFFERSEN
Chief Executive Officer and President
2950 Wilderness Place
Boulder, Colorado 80301
(303) 449-6500
(Name, address, including zip code, and telephone number, including area code,
of agent for service)
COPIES:
HERBERT H. DAVIS III JAMES R. TANENBAUM
ROTHGERBER JOHNSON & LYONS LLP STROOCK & STROOCK & LAVAN LLP
1200 17th Street, Suite 3000 180 Maiden Lane
Denver, Colorado 80202 New York, New York 10038
(303) 623-9000 (212) 806-5400
--------------
Approximate date of commencement of proposed sale to the public: As soon as
practicable after the Registration Statement becomes effective.
If the only securities being registered on this Form are being offered
pursuant to dividend or interest reinvestment plans, please check the
following box: [_]
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, other than securities offered only in connection with dividend or
interest reinvestment plans, 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,
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 SEC, acting pursuant to said
section 8(a), may determine.
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<PAGE>
++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++
+The information in this prospectus is not complete and may be changed. We may +
+not sell these securities until the registration statement filed with the +
+Securities and Exchange Commission is effective. This prospectus is not an +
+offer to sell securities, and we are not soliciting offers to buy these +
+securities, in any state where the offer or sale is not permitted. +
++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++
SUBJECT TO COMPLETION, DATED MARCH 10, 2000
3,150,000 Shares
Ribozyme Pharmaceuticals, Inc.
[LOGO][LOGO]
Common Stock
------------
Ribozyme Pharmaceuticals, Inc. is offering 3,150,000 shares of its common
stock. Our common stock is quoted on the Nasdaq National Market under the
symbol "RZYM." On March 9, 2000 the last reported sale price of the common
stock on the Nasdaq National Market was $55.88 per share.
Investing in our common stock involves a high degree of risk.
See "Risk Factors" beginning on page 7.
------------
Neither the Securities and Exchange Commission nor any state securities
commission has approved or disapproved these securities, or passed upon the
adequacy or accuracy of this prospectus. Any representation to the contrary is
a criminal offense.
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<TABLE>
<CAPTION>
Per Share Total
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<S> <C> <C>
Public Offering Price........................................ $ $
Underwriting Discounts and Commissions....................... $ $
Ribozyme's proceeds.......................................... $ $
</TABLE>
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The underwriters have an option to purchase up to an additional 472,500
shares of common stock from certain selling stockholders to cover over-
allotments. If the underwriters exercise their option, we will not receive any
proceeds from the sale of those shares by the selling stockholders. The
underwriters expect to deliver the shares to purchasers on or about ,
2000.
ING Barings Chase H&Q
, 2000
<PAGE>
INSIDE FRONT COVER
[ILLUSTRATION: three figures of ANGIOZYME, an anti-angiogenic cancer compound;
Figure 1: Shows blood vessels, endothelial cells, a tumor and VEGF-1 receptor
with the text "Inception: Tumor sends chemical "signal" to VEGF-1 receptor on
nearby blood vessel (endothelial cell), stimulating blood vessel growth."
Figure 2: Shows cancer spreading via new blood vessel with the text "Growth:
Blood vessel supplies needed nutrients, tumor grows and begins to spread to
other body parts via the new blood supply."
Figure 3: Shows ANGIOZYME destroying the VEGF-1 receptor with the text
"ANGIOZYME intervenes at inception: ANGIOZYME prevents reception of the tumor's
chemical signal by "destroying" the VEGF-1 receptor in each endothelial cell,
stopping growth of new blood vessels to the tumor, thus retarding tumor growth
and metastases."]
ANGIOZYME(TM) and HERZYME(TM) are trademarks of Ribozyme Pharmaceuticals.
<PAGE>
PROSPECTUS SUMMARY
This summary highlights selected information contained elsewhere in this
prospectus. This summary does not contain all of the information that you
should consider before investing in our common stock. You should read the
entire prospectus carefully, including "Risk Factors" and the financial
statements and related notes, before making an investment decision. Except as
otherwise noted, we have assumed that the offering price will be $55.88 per
share. Unless otherwise noted, references in this prospectus to "Ribozyme
Pharmaceuticals,""we," "our" and "us" refer to Ribozyme Pharmaceuticals, Inc.,
a Delaware corporation, and its subsidiaries.
Ribozyme Pharmaceuticals, Inc.
Business overview
We are developing a new class of drugs based on engineered molecules called
"ribozymes." Ribozymes are a form of ribonucleic acid that have the ability to
cleave RNA, including messenger RNA, and thereby selectively inhibit protein
production or viral replication. Because many human diseases result from
abnormal protein production or viral replication, we believe that ribozymes
may prevent, treat or cure a broad range of human diseases.
We are currently in clinical development and preclinical testing for the
following three product candidates:
. ANGIOZYME, for which we are conducting a Phase I/II clinical trial for
the treatment of solid tumor cancers in collaboration with Chiron
Corporation;
. an anti-HCV ribozyme which is being developed for the treatment of
Hepatitis C in collaboration with Eli Lilly and Company; and
. HERZYME, which we are developing for the treatment of breast and other
cancers in collaboration with Elan Corporation plc and its affiliates.
We expect to identify and begin preclinical testing on an additional product
candidate by the end of 2000 and develop new ribozyme product candidates in
the future.
The ribozyme advantage
We believe that ribozymes offer significant advantages over other
approaches to treating human diseases. Human diseases are often the direct
result of the abnormal production of proteins. Protein production is the
result of the "expression" of genes through an intermediary process using
messenger RNA, or mRNA. Ribozymes have the ability to act as "molecular
scissors" by cutting mRNA molecules into two ineffective strands, thereby
preventing gene function and protein production. Ribozymes can also be used to
cut viral RNA, thus preventing viral replication.
Since ribozymes can be applied (in principle) to any RNA sequence, they
have the potential to have broad applicability as an entirely new class of
therapeutic agents. Because ribozymes attach to and cut only a specific
targeted RNA, their use minimizes the risk of unwanted side effects caused by
other cellular reactions to a given therapeutic agent. Unlike traditional
therapeutic products which temporarily prevent gene function, ribozymes
permanently destroy the target RNA and stop the associated protein production
or viral replication.
Our technology, which is based on the Nobel prize-winning discoveries of
Dr. Thomas R. Cech, is supported by more than 110 issued or allowed patents
and over 100 patent applications. We believe that this patent portfolio gives
us rights to control the manufacture, use and sale of ribozymes.
3
<PAGE>
Our product programs
ANGIOZYME
We are developing ANGIOZYME in collaboration with Chiron primarily as a
treatment for solid tumors and associated metastases in cancers such as lung,
breast, prostate, colon and rectum. These cancers account for over 650,000 new
cancer cases and nearly 300,000 deaths per year in the United States alone.
Animal studies using ANGIOZYME alone and in conjunction with existing
cytotoxic cancer therapies for treatment of solid tumors have shown dramatic
reduction in tumor growth and metastases. We have completed Phase Ia and Ib
clinical trials to demonstrate safety and tolerability of single doses of
ANGIOZYME. We initiated a Phase I/II multi-dose clinical trial in cancer
patients in November 1999 to evaluate the overall safety, tolerability and
other effects and to make observations regarding disease progression. We expect
to complete the Phase I/II trial by the end of 2000. Subject to FDA approval,
we would expect to initiate a pivotal efficacy trial in 2001 which is intended
to be the basis for a New Drug Application, or NDA.
ANTI-HCV RIBOZYME
Our anti-HCV ribozyme is being developed in collaboration with Eli Lilly to
treat Hepatitis C, a viral disease of the liver. There are over four million
people in the United States chronically infected with Hepatitis C and over 170
million people worldwide. The disease infects approximately 50,000 people and
results in over 10,000 deaths per year in the United States alone. Current
treatments for Hepatitis C are effective in less than 50% of existing patients
and have serious side effects. Our research and preclinical testing have
indicated that our anti-HCV ribozyme, formerly known as HEPTAZYME(TM),
selectively cuts Hepatitis C RNA in a manner that significantly inhibits viral
replication in cell culture. In February 2000, clinical trials were initiated
for the anti-HCV ribozyme.
HERZYME
We have recently formed a joint venture with Elan to develop HERZYME, a
treatment for breast and other cancers. More than 170,000 new breast cancer
patients are diagnosed each year in the United States. Approximately 30% of
these patients overexpress the Her-2 gene, indicating that regulation of the
Her-2 gene could have a beneficial impact on the disease. HERZYME specifically
targets and downregulates Her-2 and is expected to have a more benign side
effect profile than other therapeutic drugs targeting the Her-2 gene. HERZYME
is currently in preclinical testing.
Atugen
We have also used ribozymes for target discovery and validation, the process
by which the life science industry identifies genes that cause or contribute to
human diseases. In 1998, we decided to focus on the therapeutic potential of
ribozymes and transferred our target discovery and validation technology to a
newly formed company, Atugen AG, for a significant equity stake. Currently we
own a 48.4% interest in Atugen.
Strategy
Our strategy is to use our unique and patented ribozyme technology to
identify and develop a new class of drugs to treat human diseases for which
there are large numbers of patients and insufficient treatments. The principal
elements of our strategy are to:
. develop ribozyme drugs by pursuing multiple product candidates across a
number of diseases;
. maximize value of new product candidates through expanded internal
development;
. focus on human therapeutics and license other applications of our
technology; and
. maintain and expand our patent portfolio and proprietary technology.
Our corporate headquarters are located at 2950 Wilderness Place, Boulder,
Colorado 80301, and our telephone number is (303) 449-6500. Our web site
address is www.rpi.com. Information contained on our web site does not
constitute part of this prospectus.
4
<PAGE>
The Offering
Common stock offered by us.... 3,150,000 shares
Common stock to be
outstanding after the
offering..................... 15,144,279 shares
Use of proceeds............... To fund preclinical studies and clinical trials
of our product candidates, research and
development, repayment of $6.9 million of our
outstanding borrowings from Schering AG and for
working capital and other general corporate
purposes.
Nasdaq National Market
symbol....................... RZYM
- --------
This information is based on the number of shares outstanding at March 9, 2000.
It excludes:
. 1,698,902 shares reserved for issuance under our stock option plan, of which
1,640,965 shares are outstanding at a weighted average exercise price of
$4.97 per share;
. 1,337,458 shares issuable upon the exercise of outstanding warrants at a
weighted average exercise price of $18.00 per share;
. 142,105 shares issuable to Schering AG upon conversion of outstanding debt,
based upon the closing price of $55.88 of our common stock on March 9, 2000;
. 134,216 shares issuable to Eli Lilly upon conversion of five shares of our
Series L convertible preferred stock, based upon the closing price of $55.88
of our common stock on March 9, 2000;
. an undeterminable number of shares issuable to Elan in May 2001 for a total
purchase price of $5.0 million;
. up to 1,200,000 shares issuable to Elan upon conversion of 12,015 shares of
our Series A convertible exchangeable preferred stock;
. an undeterminable number of shares issuable to Elan upon conversion of shares
of our Series B convertible preferred stock that Elan may receive in the
future upon conversion of our convertible promissory note to Elan;
. 29,959 shares available for issuance under our 401(k) salary reduction plan
and trust; and
. 85,761 shares available for issuance under our employee stock purchase plan.
5
<PAGE>
SUMMARY FINANCIAL DATA
(in thousands except per share amounts)
The selected historical financial data presented below is derived from the
financial statements of Ribozyme Pharmaceuticals. The financial statements for
each of the five years ended December 31, 1995, 1996, 1997, 1998 and 1999 have
been audited by Ernst & Young LLP, independent auditors. The pro forma balance
sheet data summarized below reflects the following transactions with Elan in
January 2000: the sale of 641,026 shares of our common stock to Elan for $5.0
million and the sale of 12,015 shares of our Series A convertible exchangeable
preferred stock to Elan for $12.0 million. The pro forma as adjusted balance
sheet data reflects the Elan transactions; the application of the net proceeds
from the sale of the 3,150,000 shares of common stock offered by Ribozyme
Pharmaceuticals after deducting the underwriting discounts and estimated
offering expenses; and the repayment of $6.9 million of our outstanding
borrowings from Schering AG.
<TABLE>
<CAPTION>
Year Ended December 31,
------------------------------------------------
1995 1996 1997 1998 1999
-------- -------- -------- -------- --------
<S> <C> <C> <C> <C> <C>
Statement of Operations
Data:
Total revenues.............. $ 1,280 $ 773 $ 1,983 $ 8,988 $ 7,664
Expenses:
Research and development.. 12,204 14,189 15,170 16,941 15,395
General and
administrative........... 1,397 1,943 1,886 1,813 2,132
-------- -------- -------- -------- --------
Total operating expenses.. 13,601 16,132 17,056 18,754 17,527
-------- -------- -------- -------- --------
Operating loss.............. (12,321) (15,359) (15,073) (9,766) (9,863)
Total other income
(expense).................. (159) 91 (49) (1,152) (798)
-------- -------- -------- -------- --------
Net loss.................... $(12,480) $(15,268) $(15,122) $(10,918) $(10,661)
======== ======== ======== ======== ========
Net loss per share (basic
and diluted)............... $ (3.86) $ (2.61) $ (2.04) $ (1.22) $ (1.05)
Shares used in computing net
loss per share (basic and
diluted) .................. 3,230 5,845 7,420 8,978 10,158
</TABLE>
<TABLE>
<CAPTION>
December 31, 1999
-------------------------------
Pro Pro Forma
Actual Forma As Adjusted
-------- -------- -----------
<S> <C> <C> <C>
Balance Sheet Data:
Cash, cash equivalents and securities
available-for-sale........................... $ 14,000 $ 19,000 $177,359
Working capital............................... 14,086 19,086 177,445
Total assets.................................. 25,092 42,107 200,466
Capital lease obligations and long-term debt,
net of current portion....................... 6,811 6,811 --
Accumulated deficit........................... (84,083) (84,083) (84,083)
Total stockholders' equity.................... 14,881 31,896 197,197
</TABLE>
6
<PAGE>
FORWARD-LOOKING STATEMENTS
Certain statements under the captions "Prospectus Summary," "Risk Factors,"
"Use of Proceeds," "Management's Discussion and Analysis of Financial Condition
and Results of Operations," "Business," and elsewhere in this prospectus are
"forward-looking statements." These forward-looking statements include, but are
not limited to, statements about our plans, objectives, expectations and
intentions and other statements contained in this prospectus that are not
historical facts. When used in this prospectus, the words "expect,"
"anticipate," "intend," "plan," "believe," "seek," "estimate" and similar
expressions are generally intended to identify forward-looking statements.
Because these forward-looking statements involve risks and uncertainties, there
are important factors that could cause actual results to differ materially from
those expressed or implied by these forward-looking statements, including our
plans, objectives, expectations and intentions and other factors discussed
under "Risk Factors."
RISK FACTORS
You should carefully consider the following risk factors and all other
information contained in this prospectus before purchasing our common stock.
Investing in our common stock involves a high degree of risk. Any of the
following risks could materially adversely affect our business, operating
results and financial condition and could result in a complete loss of your
investment.
We are a biotechnology company in the early stage of development and have only
a limited operating history for you to review in evaluating our business and
prospects.
Our ribozyme technology is in an early stage of development and represents a
new and unproven approach to therapeutic products. There can be no assurance
that our technologies will enable us or any of our collaborators to discover
and develop therapeutic products.
All of our products are in early stages of development, have never generated
any sales and require extensive testing before commercialization. We do not
expect any of our product candidates to be commercially available for at least
four years. You must consider, based on our limited history, our ability to:
. obtain the financial resources necessary to develop, test, manufacture
and market products;
. engage corporate partners to assist in developing, testing,
manufacturing and marketing our products;
. satisfy the requirements of clinical trial protocols, including patient
enrollment;
. establish and demonstrate the clinical efficacy of our products;
. obtain necessary regulatory approvals; and
. market our products to achieve acceptance and use by the medical
community in general.
We have a history of losses, expect future losses and cannot assure you that we
will ever become or remain profitable.
We have incurred significant losses and have had negative cash flows from
operations since inception. To date, we have dedicated most of our financial
resources to research and development and general and administrative expenses.
We have funded our activities primarily from sales of stock, revenues under
research and development agreements and lines of credit. As of December 31,
1999, our accumulated deficit was $84.1 million.
We expect to incur losses for at least the next several years because we
plan to spend substantial amounts on research and development of our products,
including preclinical studies and clinical trials, and, if we obtain necessary
regulatory approvals, on sales and marketing efforts.
7
<PAGE>
We depend upon our collaborative relationships and our collaborators have
rights under these agreements which if exercised could adversely affect our
ability to develop our products and our operating results.
Engaging corporate partners and other third parties to develop, test and
manufacture our initial products has been, and is expected to continue to be, a
key element of our strategy. Our current partners, Chiron, Eli Lilly and Elan,
have the right to unilaterally terminate our existing agreements or discontinue
funding their share of product development expenses. If any of them were to
terminate its funding of the development of a particular product, we may not
have the right to continue development of that product on our own.
In addition, there are many aspects of our collaborations that have been and
will continue to be outside of our control including:
. decisions by our collaborators to extend or renew our agreements and
relationships;
. the pace of development of our products including the achievement of
performance milestones;
. development by our collaborators of competing technologies or products;
. exercise by our collaborators of marketing or manufacturing rights; and
. the loss of our rights to products or the profits from our products if
we are unable to fund our share of development costs.
We have granted exclusive rights to certain of our collaborators to products
targeting specific gene sequences which could delay development of those
products and prevent us from entering into other collaborative agreements.
Under our current collaborations, up to an aggregate of 50 targets may be
reserved at any time. Development of the products subject to these exclusivity
provisions is out of our control. These products will not be available to us
during the exclusivity term either to develop internally or in collaboration
with third parties.
Some of our collaborators have the right to reserve exclusive rights to
specified products for a period of time, even if they are not developing that
product. Also, many of our collaboration agreements require us to offer our
collaborators a right of first offer for certain targets and products.
Because we must obtain regulatory approval to market our products in the United
States and foreign jurisdictions, we cannot predict whether or when we will be
permitted to commercialize our products.
The pharmaceutical industry is subject to stringent regulation by a wide
range of authorities. We cannot predict whether regulatory clearance will be
obtained for any product we develop. A pharmaceutical product cannot be
marketed in the United States until it has completed rigorous preclinical
testing and clinical trials and an extensive regulatory clearance process
implemented by the FDA. Satisfaction of regulatory requirements typically takes
many years, is dependent upon the type, complexity and novelty of the product
and requires the expenditure of substantial resources. Of particular
significance are the requirements covering research and development, testing,
manufacturing, quality control, labeling and promotion of drugs for human use.
Before commencing clinical trials in humans, we must submit and receive
approval from the FDA of an Investigational New Drug application, or IND.
Clinical trials are subject to oversight by institutional review board and the
FDA and:
. must be conducted in conformance with the FDA's good laboratory practice
regulations;
. must meet requirements for institutional review board oversight;
. must meet requirements for informed consent;
. must meet requirements for good clinical practices;
8
<PAGE>
. are subject to continuing FDA oversight;
. may require large numbers of test subjects; and
. may be suspended by us or the FDA at any time if it is believed that the
subjects participating in these trials are being exposed to unacceptable
health risks or if the FDA finds deficiencies in the IND or the conduct
of these trials.
Before receiving FDA clearance to market a product, we must demonstrate that
the product is safe and effective on the patient population that will be
treated. Data obtained from preclinical and clinical activities are susceptible
to varying interpretations that could delay, limit or prevent regulatory
clearances. In addition, delays or rejections may be encountered based upon
additional government regulation from future legislation or administrative
action or changes in FDA policy during the period of product development,
clinical trials and FDA regulatory review. Failure to comply with applicable
FDA or other applicable regulatory requirements may result in criminal
prosecution, civil penalties, recall or seizure of products, total or partial
suspension of production or injunction, as well as other regulatory action
against our potential products or us. Additionally, we have limited experience
in conducting and managing the clinical trials necessary to obtain regulatory
approval.
If regulatory clearance of a product is granted, this clearance will be
limited to those disease states and conditions for which the product is
demonstrated through clinical trials to be safe and efficacious. We cannot
ensure that any compound developed by us, alone or with others, will prove to
be safe and efficacious in clinical trials and will meet all the applicable
regulatory requirements needed to receive marketing clearance.
Outside the United States, our ability to market a product is contingent
upon receiving a marketing authorization from the appropriate regulatory
authorities. This foreign regulatory approval process includes all of the risks
associated with FDA clearance described above.
For additional information concerning regulatory approval of our prospective
products, see "Business--Government regulation of our drug development
activities."
We are involved in pending litigation and cannot at this time predict the
ultimate outcome or possible loss that could result from that litigation.
We, along with our chief executive officer, are defendants in several
related lawsuits which purport to be class actions on behalf of purchasers of
our common stock on November 16 and 17, 1999. The lawsuits, which are
substantially identical, allege the defendants violated certain federal
securities laws based upon an allegedly misleading announcement made on
November 15, 1999. Although we believe none of these legal proceedings have any
merit, we are unable to predict the ultimate outcome of these proceedings or
determine the total expense or possible loss, if any, that may ultimately be
incurred in the resolution of these proceedings.
If we cannot obtain additional financing, we may have to dilute your interest,
curtail our research and development, relinquish our rights to some or all of
our products or declare bankruptcy.
The net proceeds of this offering, together with our existing financial
resources and expected revenues from our collaborations, should be sufficient
to meet our operating and capital requirements through 2002; however, we may
have to raise substantial additional capital thereafter if:
. changes in our research and development plans cause unexpected large
future expenditures; or
. changes in our collaborative relationships cause a significant reduction
in our expected revenues from our collaborations.
If we raise funds by selling more stock, your ownership share in us will be
diluted. We may grant future investors rights superior to those of the common
stock that you are purchasing. In addition, we do not know if additional
funding will be available or on acceptable terms when needed.
9
<PAGE>
Our products require materials that may not be readily available or cost
effective, which may adversely affect our competitive position or
profitability.
The products we are developing are new chemical entities which are not yet
available in commercial quantities. Raw materials necessary for the manufacture
of our products may not be available in sufficient quantities or at a
reasonable cost in the future. Therefore, our products may not be available at
a reasonable cost in the future. We recently entered into an agreement with
Avecia Limited to manufacture ribozyme products for us based on technology we
licensed to them. Delays or failures in obtaining raw materials or in product
manufacturing, including deliveries from Avecia, could delay our product
submission for regulatory approval and our initiation of new development
programs which could, in turn, materially impair our competitive position and
potential profitability.
There is a significant degree of uncertainty relating to our patents that could
cause us to incur substantial costs and delays as a result of proceedings and
litigation regarding patents and other proprietary rights, possibly resulting
in additional expenses and the loss of some patent protection.
Our basic patents, the Cech patents, expire in 2008 in the United States and
in 2007 in Europe and Japan. Although our license to these patents extends
through the expiration of the Cech patents or any extensions thereof, our
licensor preserves the right to terminate our license before such time under
certain circumstances. We have received approval of some additional patent
applications covering various aspects of the ribozyme technology, and we have
filed patent applications for other improvements and modifications which have
not yet been approved.
We cannot be certain that the named inventors of subject matter claimed by
our patents and patent applications were the first to invent or the first to
file patent applications for these inventions. Furthermore, we cannot guarantee
that any patents will issue from any pending or future patent applications
owned by or licensed to us. Existing or future patents may be successfully
challenged, invalidated, found to be unenforceable, infringed upon, or
circumvented by others so that our patent rights would not create an effective
competitive barrier. We also cannot assure you that the scope of our issued
patents will be sufficiently broad to offer meaningful protection against
competitive products. We have filed documents in opposition of two patents
granted to a competitor in Europe. Competitors have filed documents in
opposition of our Cech patents in Europe and Japan. The patent opposition in
Japan has been resolved in our favor. The European opposition proceeding is in
progress. We may not have identified all United States and foreign patents that
pose a risk of infringement.
We may be forced to litigate if an intellectual property dispute arises.
This litigation could be extremely expensive. Proceedings and litigation
involving our patents or patent applications also could result in adverse
findings about:
. the patentability of our inventions and product candidates; or
. the enforceability, validity or scope of protection provided by our
patents.
As discussed above, our competitors have taken the position in patent
oppositions and elsewhere that our patents are invalid or that our activities
infringe on their patent rights. While we do not believe we are infringing on
the patent rights of our known competitors, we may have to incur substantial
costs if litigation is brought against us by these competitors.
The manufacture, use or sale of our products may infringe on the patent
rights of others. If we are unable to avoid infringing another party's patent
rights, we may be required to seek a license, defend an infringement action or
challenge the validity of the patents in court. Patent litigation is costly and
time consuming. We may
10
<PAGE>
not have sufficient resources to bring these actions to a successful
conclusion. In addition, if we do not obtain a license, do not successfully
defend an infringement action or are unable to have infringed patents declared
invalid, we may:
. incur substantial monetary damages;
. encounter significant delays in marketing our products; and
. be unable to participate in the manufacture, use or sale of products or
methods of treatment requiring licenses.
In addition, we regularly enter into agreements to in-license technologies
and patent rights. Should we fail to comply with the terms of those agreements,
including payment of any required maintenance fees or royalties, we would lose
the rights to those technologies and patents.
Disclosure of our trade secrets could hurt our competitive position.
Because trade secrets and other unpatented proprietary information are
critical to our business, we attempt to protect our trade secrets by entering
into confidentiality agreements with third parties, employees and consultants.
However, these agreements can be breached and, if they are, there may not be an
adequate remedy available to us. In addition, third parties may independently
discover trade secrets and proprietary information. Costly and time-consuming
litigation could be necessary to enforce and determine the scope of our
proprietary rights.
We lack sales and marketing experience and will rely upon third parties to
market our products which will result in a loss of control over the marketing
process.
We intend to rely on third parties with established direct sales forces to
market, distribute and sell many of our products. These third parties may have
significant control over important aspects of the commercialization of our
products, including market identification, marketing methods, pricing, sales
force recruitment and management and promotional activities. We may be unable
to control the actions of these third parties. We may be unable to make or
maintain arrangements with third parties to perform these activities on
favorable terms.
Our success may depend on third-party reimbursement of patients' costs for our
products which could result in price pressure or reduced demand for our
products.
Our ability to market products successfully will depend in part on the
extent to which various third parties are willing to reimburse patients for the
costs of our products and related treatments. These third parties include
government authorities, private health insurers and other organizations, such
as health maintenance organizations. Third-party payors are increasingly
challenging the prices charged for medical products and services. Accordingly,
if less costly drugs are available, third-party payors may not authorize or may
limit reimbursement for our products, even if our products are safer or more
effective than the alternatives. In addition, the trend toward managed
healthcare and government insurance programs could result in lower prices and
reduced demand for our products. Cost containment measures instituted by
healthcare providers and any general healthcare reform could affect our ability
to sell our products and may have a material adverse effect on us. We cannot
predict the effect of future legislation or regulation concerning the
healthcare industry and third-party coverage and reimbursement on our business.
You will experience immediate and substantial dilution.
Purchasers in this offering will pay more for their shares than existing
stockholders or individuals who acquire shares by exercising options granted
before this offering. You will experience immediate dilution of $43.06 per
share in pro forma net tangible book value. You will also experience additional
dilution upon:
. the exercise by holders of outstanding options and warrants;
. the conversion by Schering AG of outstanding debt into shares of our
common stock;
. the conversion by Eli Lilly of our Series L convertible preferred stock
into shares of our common stock; or
. the conversion by Elan of shares of our Series A convertible
exchangeable preferred stock into a maximum of 1,200,000 shares of our
common stock.
11
<PAGE>
Our common stock has limited trading volume and a history of volatility which
could impair your investment.
You may be unable to sell shares purchased in this offering at the time or
price desired. The market price of our common stock has fluctuated dramatically
in recent years. The trading price of our common stock may continue to
fluctuate substantially due to:
. quarterly variations in our operating results;
. our ability to raise additional funds;
. changes in the status of our corporate collaborative agreements;
. changes in earnings estimates by market research analysts;
. clinical trials of products;
. research activities, technological innovations or new products by us or
our competitors;
. developments or disputes concerning patents or proprietary rights;
. purchases or sales of our stock by our executive officers, directors or
substantial holders of our common stock;
. timing or denial by the FDA of clinical trial protocols or marketing
applications;
. securities class actions or other litigation; and
. changes in government regulations.
These fluctuations have sometimes been unrelated to our operating
performance. As a result, the value of your shares could vary significantly
from time to time. The historical trading volume of our common stock has been
limited. After this offering, an active public market for the common stock may
not develop or be sustained.
Both our corporate documents and Delaware law have anti-takeover provisions
that may discourage transactions involving actual or potential changes of
control at premium prices.
Our corporate documents:
. require procedures to be followed and time periods to be met for any
stockholder to propose matters to be considered at annual meetings of
stockholders, including nominating directors for election at those
meetings; and
. authorize our Board of Directors to issue up to 5,000,000 shares of
preferred stock without stockholder approval and to set the rights,
preferences and other designations, including voting rights, of those
shares as the Board of Directors may determine.
In addition, we are subject to provisions of the Delaware General
Corporation Law that may make some business combinations more difficult.
Accordingly, transactions that otherwise could involve payment of a premium
over prevailing market prices to holders of common stock may be discouraged or
more difficult for our company than for other companies organized in other
jurisdictions.
12
<PAGE>
USE OF PROCEEDS
We are offering 3,150,000 shares of our common stock. We will receive an
estimated $165,300,000 in net proceeds from the sale of these shares of common
stock after deducting the underwriting discounts and estimated offering
expenses.
We intend to use proceeds from this offering to fund preclinical studies and
clinical trials of our product candidates, research and development, repayment
of approximately $6.9 million of our outstanding borrowings from Schering AG
and for working capital and other general corporate purposes. We expect to use
a significant portion of the proceeds from the offering to fund the ANGIOZYME
clinical program and other product development activities.
The amounts we actually expend will vary significantly depending on a number
of factors, including:
. results of preclinical studies and clinical trials of products;
. progress of our research and development programs;
. cost and timing of regulatory approvals;
. terms of any collaborative arrangements into which we enter;
. commercial potential of our products;
. status of competitive products;
. technological advances; and
. hiring of additional personnel.
As a result, we will retain significant discretion in the application of
these funds.
We anticipate that the net proceeds of this offering, together with our
existing financial resources and expected revenues from our collaborations,
should be sufficient to meet our anticipated operating and capital requirements
through 2002. This estimate is based on assumptions that could be negatively
impacted by the matters discussed in "Risk Factors" and "Management's
Discussion and Analysis of Financial Condition and Results of Operations--
Liquidity and Capital Resources."
Until we use the net proceeds as described above, we will invest them in
short-term, interest-bearing, investment-grade securities.
13
<PAGE>
PRICE RANGE OF COMMON STOCK AND DIVIDENDS
Our common stock is traded on the Nasdaq National Market under the symbol
"RZYM." The following table sets forth, for the periods indicated, the high and
low sales prices of our common stock as reported on the Nasdaq National Market.
<TABLE>
<CAPTION>
High Low
------ -----
<S> <C> <C>
Year Ended December 31, 1997
First Quarter............................................. $16.50 $9.88
Second Quarter............................................ 12.38 8.63
Third Quarter............................................. 12.00 7.38
Fourth Quarter............................................ 11.38 7.00
Year Ended December 31, 1998
First Quarter............................................. 9.34 5.13
Second Quarter............................................ 10.50 4.88
Third Quarter............................................. 6.25 2.00
Fourth Quarter............................................ 7.63 3.31
Year Ended December 31, 1999
First Quarter............................................. 5.75 4.06
Second Quarter............................................ 6.88 3.88
Third Quarter............................................. 7.00 4.25
Fourth Quarter............................................ 22.00 4.81
Year Ended December 31, 2000
First Quarter (through March 9, 2000)..................... 71.88 9.50
</TABLE>
The last reported sale price of our common stock as reported on the Nasdaq
National Market on March 9, 2000, was $55.88. At March 9, 2000, there were
11,994,279 shares of our common stock outstanding held by approximately 159
holders of record of our common stock.
We have never declared or paid cash dividends on our common stock and do not
anticipate paying any cash dividends in the foreseeable future. We are also
party to agreements restricting our ability to pay dividends.
14
<PAGE>
CAPITALIZATION
The following table sets forth our capitalization as of December 31, 1999:
. on an actual basis;
. on a pro forma basis, giving effect to the Elan transactions as if they
had occurred on December 31, 1999; and,
. on a pro forma as adjusted basis giving effect to the sale of common
stock offered by us and the estimated net proceeds from the offering of
$165,300,000 and giving effect to the repayment of $6.9 million of our
outstanding borrowings from Schering AG.
<TABLE>
<CAPTION>
December 31, 1999
-------------------------------
Pro Pro Forma
Actual forma As Adjusted
-------- -------- -----------
(in thousands)
<S> <C> <C> <C>
Capital lease obligations and long-term debt,
net of current portion........................ $ 6,811 $ 6,811 $ --
Stockholders' equity:
Preferred stock, $.01 par value per share,
5,000,000 shares authorized:
Series A convertible exchangeable preferred
stock, no shares outstanding actual, 12,015
shares outstanding pro forma and pro forma
as adjusted (preference in liquidation of
$12,015,000)............................... -- -- --
Series B convertible preferred stock, no
shares outstanding actual, pro forma and
pro forma as adjusted...................... -- -- --
Series L convertible preferred stock, 5
shares outstanding actual, pro forma and
pro forma as adjusted (preference in
liquidation of $7,500,000)................. -- -- --
Common stock, $0.01 par value per share;
20,000,000 shares authorized;
11,263,252 shares outstanding actual,
11,904,278 shares outstanding pro forma and
15,054,278 shares outstanding pro forma as
adjusted*................................... 113 119 151
Additional paid-in capital................... 98,894 115,903 281,172
Deferred compensation and other.............. (43) (43) (43)
Accumulated deficit.......................... (84,083) (84,083) (84,083)
-------- -------- --------
Total stockholders' equity................. 14,881 31,896 197,197
-------- -------- --------
Total capitalization....................... $ 21,692 $ 38,707 $197,197
======== ======== ========
</TABLE>
- -------
* This information is based on the number of shares outstanding at March 9,
2000. It excludes:
. 90,001 shares issued upon the exercise of stock options subsequent to
December 31, 1999;
. 1,698,902 shares reserved for issuance under our stock option plan, of
which 1,640,965 shares were outstanding at a weighted average exercise
price of $4.97 per share;
. 1,337,458 shares issuable upon the exercise of outstanding warrants at a
weighted average exercise price of $18.00 per share;
. 142,105 shares issuable to Schering AG upon conversion of outstanding
debt, based upon the closing price of $55.88 of our common stock on March
9, 2000;
. 134,216 shares issuable to Eli Lilly upon conversion of five shares of
our Series L convertible preferred stock, based upon the closing price of
$55.88 of our common stock on March 9, 2000;
. an undeterminable numbers of shares issuable to Elan in May 2001 for a
total purchase price of $5.0 million;
. up to 1,200,000 shares issuable to Elan upon conversion of 12,015 shares
of our Series A convertible exchangeable preferred stock;
. an undeterminable number of shares issuable to Elan upon conversion of
shares of our Series B convertible preferred stock that Elan may receive
in the future upon conversion of our convertible promissory note to Elan;
. 29,959 shares available for issuable under our 401(k) salary reduction
plan and trust; and
. 85,761 shares available for issuance under our employee stock purchase
plan.
15
<PAGE>
DILUTION
Our net tangible book value as of December 31, 1999 was approximately $10.6
million, or $0.95 per share. Giving effect to the Elan transactions in January
2000, our pro forma net tangible book value as of December 31, 1999 would have
been approximately $27.7 million, or $2.32 per share.
Giving effect to the sale of 3,150,000 shares of our common stock, after
deducting the underwriting discounts and estimated offering expenses, our pro
forma as adjusted net tangible book value per share would have been $193.0
million, or $12.82 per share. This represents an immediate increase in pro
forma net tangible book value of $10.50 per share to existing stockholders and
an immediate dilution in net tangible book value of $43.06 per share to
purchasers in this offering. Pro forma net tangible book value represents our
pro forma total tangible assets less pro forma total liabilities. Dilution
represents the difference between the amount per share paid by the purchasers
in this offering and the pro forma as adjusted net tangible book value per
share upon completion of this offering. The following table illustrates this
per share dilution:
<TABLE>
<S> <C> <C>
Public offering price per share.................................. $55.88
Pro forma net tangible book value per share as of December 31,
1999.......................................................... $2.32
Increase per share attributable to new investors............... 10.50
-----
Pro forma as adjusted net tangible book value per share after
this offering................................................... 12.82
------
Dilution per share to new investors.............................. $43.06
======
</TABLE>
To the extent outstanding options and warrants are exercised, convertible
preferred stock or convertible debt is converted, or additional shares are
issued, there will be further dilution to new investors.
16
<PAGE>
SELECTED FINANCIAL DATA
(in thousands except per share amounts)
The following yearly selected financial data are derived from our audited
financial statements. Our financial statements for 1995, 1996, 1997, 1998 and
1999 have been audited by Ernst & Young LLP, independent auditors. These
historical results do not necessarily indicate future results. When you read
this data, it is important that you also read our financial statements and
related notes, as well as the section "Management's Discussion and Analysis of
Financial Condition and Results of Operations."
<TABLE>
<CAPTION>
Years Ended December 31,
------------------------------------------------
1995 1996 1997 1998 1999
-------- -------- -------- -------- --------
<S> <C> <C> <C> <C> <C>
Statement of Operations
Data:
Revenues:
Collaborative agreements.. $ 1,178 $ 759 $ 1,976 $ 8,963 $ 5,797
Collaborative agreements--
related parties.......... -- -- -- -- 1,867
Grant and other income.... 102 14 7 25 --
-------- -------- -------- -------- --------
Total revenues.......... 1,280 773 1,983 8,988 7,664
Expenses:
Research and development.. 12,204 14,189 15,170 16,941 15,395
General and
administrative........... 1,397 1,943 1,886 1,813 2,132
-------- -------- -------- -------- --------
Total operating
expenses............... 13,601 16,132 17,056 18,754 17,527
-------- -------- -------- -------- --------
Operating loss.............. (12,321) (15,359) (15,073) (9,766) (9,863)
Other income (expense):
Interest income........... 395 936 795 634 614
Interest expense.......... (554) (845) (844) (704) (552)
Equity in loss of
unconsolidated
affiliate................ -- -- -- (1,082) (860)
-------- -------- -------- -------- --------
Total other income
(expense).............. (159) 91 (49) (1,152) (798)
-------- -------- -------- -------- --------
Net loss.................... $(12,480) $(15,268) $(15,122) $(10,918) $(10,661)
======== ======== ======== ======== ========
Net loss per share (basic
and diluted)............... $ (3.86) $ (2.61) $ (2.04) $ (1.22) $ (1.05)
Shares used in computing net
loss per share
(basic and diluted)........ 3,230 5,845 7,420 8,978 10,158
<CAPTION>
December 31,
------------------------------------------------
1995 1996 1997 1998 1999
-------- -------- -------- -------- --------
<S> <C> <C> <C> <C> <C>
Balance Sheet Data:
Cash, cash equivalents and
securities
available-for-sale......... $ 6,420 $ 17,594 $ 16,102 $ 6,512 $ 14,000
Working capital............. 4,648 15,788 13,238 4,467 14,086
Total assets................ 14,223 25,292 24,850 19,224 25,092
Capital lease obligations
and long-term
debt, current portion...... 1,898 1,724 2,078 498 200
Capital lease obligations
and long-term debt, net of
current portion............ 3,179 2,430 2,752 4,545 6,811
Accumulated deficit......... (32,115) (47,383) (62,505) (73,422) (84,083)
Total stockholders' equity.. 8,478 20,362 18,870 11,034 14,881
</TABLE>
17
<PAGE>
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 should be read in conjunction with the financial
statements of Ribozyme Pharmaceuticals and related notes included elsewhere in
this prospectus. Our discussion contains forward-looking statements based upon
current expectations that involve risks and uncertainties, such as our plans,
objectives, expectations and intentions. Our actual results and the timing of
certain events could differ materially from those anticipated in these forward-
looking statements as a result of certain factors, including those set forth
under "Risk Factors," "Business" and elsewhere in this prospectus.
Overview of our Business
We are developing a new class of drugs based on engineered molecules called
"ribozymes." Ribozymes are a form of ribonucleic acid which have the ability to
cleave RNA, including mRNA, and thereby selectively inhibit protein production.
Because many human diseases result from abnormal protein production, we believe
that ribozymes are applicable to a broad range of human diseases. We are
currently in clinical development and preclinical testing for three product
candidates and expect to begin preclinical testing on one additional product
candidate by the end of 2000.
We are conducting a Phase I/II clincal trial for our lead product candidate,
ANGIOZYME, for the treatment of solid tumor cancers in collaboration with
Chiron and expect to complete this trial before the end of 2000. Also, clinical
trials for our anti-HCV ribozyme for the treatment of Hepatitis C have been
initiated with Eli Lilly. We have recently formed a joint venture with Elan to
develop HERZYME, a treatment for breast and other cancers.
To date, we have committed substantially all our resources to our research
and product development programs. We have not generated any revenues from
product sales, nor do we anticipate generating any revenues in the foreseeable
future. Revenue recorded from our collaborative agreements consists of:
. Up-front revenue. Up-front revenue is fully recognized upon signing an
agreement and is related to the value of the research at that point in
time. Up-front revenue may also include a reimbursement to us of recent
expenses related to product development which we incurred.
. Research revenue. Typically research revenue is based on the fully
burdened cost of a researcher working on a collaboration. Rates are
billed per employee, per year, pro-rated for time worked on a project.
This revenue is typically invoiced on a quarterly basis, either up front
or in arrears. Revenue is recognized ratably over the period, with the
balance reflected as deferred revenue until earned. The revenue is
typically recurring over the term of a collaboration.
. License revenue. License revenue is recognized ratably over the term of
the license. Payments received in advance are recorded as deferred
revenue until earned.
. Milestone revenue. Milestone revenue is recognized in full when the
related milestone performance goal is achieved. Milestone revenue is
typically not consistent or recurring in nature.
Our revenue has consisted primarily of research revenue payments from our
collaborators. All revenues are either deferred as a liability or recognized
upon satisfying revenue criteria. As of December 31, 1999, all revenues that
have been recognized are earned, and no further obligation exists for
recognized revenue. We depend upon funding from external financing and
corporate collaborations for our research and product development programs and
expect to do so for the foreseeable future.
We have not been profitable since inception and have an accumulated deficit
of $84.1 million as of December 31, 1999. Losses have resulted primarily from
our research and development programs. We expect to
18
<PAGE>
incur additional losses as ANGIOZYME, the anti-HCV ribozyme, HERZYME and other
potential product candidates advance through development and commercialization.
In addition, future milestone payments under some of our collaborations are
contingent upon our meeting particular research or development goals. The
amount and timing of future milestone payments are contingent upon the terms of
each collaboration agreement. Milestone performance criteria are specific to
each agreement and based upon future performance. In some instances, we may
forfeit milestone payments if we fail to accomplish a predetermined goal within
a certain time frame. Therefore, we are subject to significant variation in the
timing and amount of our revenues and results of operations from period to
period.
In 1998, we transferred our target discovery and validation technology to
Atugen in exchange for a substantial equity interest. We will continue our
existing target discovery and validation agreements with our collaborators by
subcontracting to Atugen the services to be performed. We currently own 48.4%
of Atugen and will record our share of future profits. In 1999, we completely
expensed our remaining investment in Atugen.
Our revenues are denominated in U.S. dollars, therefore, we have not been
exposed to foreign currency translation risks and have not engaged in any
hedging instruments.
Results of Operations for Twelve Months Ended December 31, 1999 and 1998
Revenues from collaborative agreements decreased $1.3 million to $7.7
million for the year ended December 31, 1999 from $9.0 million for the
corresponding period in 1998. The decrease is primarily due to approximately
$6.2 million of revenue recognized from the Chiron collaboration related to the
development of ANGIOZYME in 1998, compared to $4.0 million recognized from the
Chiron collaboration in 1999. Of the $6.2 million recognized from the Chiron
collaboration in 1998, $5.0 million was a nonrecurring up-front payment for
50.0% of past expenses we incurred for the preclinical development of
ANGIOZYME. There are no future obligations between us and Chiron for these
recognized revenues. The nonrefundable payment became due when Chiron agreed to
resume our collaboration in the development of ANGIOZYME. In addition, 1998
revenues include approximately $2.6 million related to our target discovery and
validation collaborations with Glaxo Wellcome, Parke-Davis, Roche Bioscience
and Schering AG. In 1999, we subcontracted all existing target discovery and
validation work to Atugen and therefore did not record any revenues related to
those agreements. However, in 1999, we recorded $1.9 million in revenues from
Atugen related to a service agreement in which we received payments for:
. management and administrative services we provided;
. oligonucleotides and other chemicals; and
. prosecution of relevant patents.
In addition, in 1999, we recorded approximately $1.7 million in research
revenues related to our collaboration with Eli Lilly for the development of the
anti-HCV ribozyme.
Research and development expenses decreased to $15.4 million in 1999 from
$16.9 million in 1998. Approximately $1.2 million of the decrease was primarily
attributable to the transfer of approximately 15 employees and their related
expenses to Atugen. In addition, we had decreases of approximately $750,000 in
outside services, consultants and professional fees. However, during 1999, we
had an approximately $450,000 increase in personnel expenses. The increase was
primarily due to hiring additional personnel related to the overall scale-up of
research and product development. Research and development expenses consist
primarily of:
. clinical and preclinical supplies and related costs;
. salaries and benefits for scientific, regulatory, quality control and
pilot manufacturing personnel;
. consultants;
. supplies;
19
<PAGE>
. occupancy costs; and
. depreciation for laboratory equipment and facilities.
We expect future research and development expenses to increase from current
levels as ANGIOZYME, the anti-HCV drug and HERZYME proceed through clinical and
preclinical trials. The effect of increased expenses related to HERZYME will be
absorbed by us indirectly through our equity investment in Medizyme, our
unconsolidated affiliate.
General and administrative expenses increased to $2.1 million in 1999 from
$1.8 million in 1998. The increase was primarily attributable to lower expenses
incurred in 1998 because of $480,000 of reimbursements we received from Atugen
related to the time our management devoted to Atugen operations. In 1999,
Atugen hired most of its own management; our management currently devotes
limited time to Atugen. Increases of approximately $180,000 during 1999 are
primarily attributable to increased staffing and associated expenses necessary
to manage and support our expanding product and business development efforts.
We expect general and administrative expenses to continue to increase as a
result of increasing legal and other professional fees in connection with the
overall scale-up of our operations, our business development, our patent
protection efforts and anticipated legal fees due to current litigation.
Interest income decreased slightly to $614,000 in 1999 from $635,000 in
1998. The decrease is due to lower average balances in our cash, cash
equivalents and securities available-for-sale during 1999 compared to 1998.
Interest income generally fluctuates as a result of cash available for
investment and prevailing interest rates.
Interest expense decreased to $552,000 in 1999 from $704,000 in 1998. The
decrease is due to the repayment of a loan for tenant improvements and
equipment in December 1998.
Equity in loss of unconsolidated affiliate was $860,000 for 1999 compared to
$1.1 million for 1998. This expense is a result of our equity investment in
Atugen.
Results of Operations for Twelve Months Ended December 31, 1998 and 1997
Revenues from collaborative agreements increased from $2.0 million for the
year ended December 31, 1997, to $9.0 million in 1998. The increase was
primarily due to $6.2 million of revenue recognized in 1998 from the Chiron
collaboration related to the development of ANGIOZYME. Of the $6.2 million
recognized from the Chiron collaboration in 1998, $5.0 million was a
nonrecurring payment for 50.0% of past expenses incurred by us for the
preclinical development of ANGIOZYME. In addition, we received approximately
$2.6 million in collaborative revenue in 1998 due to target discovery and
validation agreements with Glaxo Wellcome, Parke-Davis, Roche Bioscience and
Schering AG. Revenues of $2.0 million in 1997 consisted primarily of $1.5
million from Schering AG for our target validation and discovery agreement.
Research and development expenses increased from $15.2 million in 1997 to
$16.9 million in 1998. The increase was a result of the initiation of the
development of ANGIOZYME and increased target discovery and validation
activities.
General and administrative expenses decreased slightly to $1.8 million in
1998 compared to $1.9 million for in 1997. The decrease in 1998 was primarily
due to reimbursements related to the time our management devoted to Atugen
operations.
Interest income was $635,000 in 1998 compared to $795,000 in 1997. Interest
income decreased due to declining cash balances. Interest income generally
fluctuates as a result of cash available for investment and prevailing interest
rates.
Interest expense was $704,000 in 1998 compared to $844,000 in 1997. Interest
expense declined in 1998 due to lower average balances of outstanding debt.
20
<PAGE>
In 1998, we recorded our share of Atugen's 1998 net loss of $1.1 million as
equity in loss of unconsolidated affiliate. Atugen did not exist prior to 1998,
and therefore there was no recorded loss in the prior year.
Liquidity and Capital Resources
We have financed our operations since inception through sales of equity
securities in public offerings, private placements of preferred and common
stock, funds received under our collaborative agreements and financing under
equipment and tenant improvement loans. From inception through December 31,
1999, we have received approximately:
. $29.0 million in net proceeds from private placements;
. $36.4 million in net proceeds from public offerings;
. $56.4 million from our collaborations; and
. $9.8 million from equipment financing.
We had cash, cash equivalents and securities available-for-sale of $14.0
million at December 31, 1999 compared with $6.5 million at December 31, 1998.
The $7.5 million increase in cash, cash equivalents and securities available-
for-sale is primarily the result of $5.4 million used for operations, net of
revenues of $7.7 million, and $1.8 million used for investments in equipment,
patents and loans to officers, offset by:
. $1.5 million in net borrowings;
. $7.5 million received in the sale of preferred stock to a corporate
collaborator; and
. $5.3 million received, net of expenses, in a public offering of our
common stock.
We invest our cash, cash equivalents and securities available-for-sale in
interest-bearing, investment-grade securities.
Accounts receivable at December 31, 1999 were $2.0 million compared to $3.9
million at December 31, 1998. Accounts receivable at December 31, 1999 included
$485,000 due from Atugen for administrative services and patent expenses,
$525,000 due from Eli Lilly for research support for our anti-HCV ribozyme
program and $1.0 million due from Chiron for reimbursement of ANGIOZYME fourth
quarter expenses. Accounts receivable at December 31, 1998 primarily consisted
of a $2.0 million license fee from Atugen, $730,000 for start-up and operating
expenses due from Atugen and $1.1 million due from Chiron for 1998 fourth
quarter research revenue related to ANGIOZYME clinical development. All
outstanding receivables due from 1998 were received in 1999.
Total additions for property, plant and equipment for the twelve months
ending December 31, 1999 were $1.1 million, most of which were financed through
our existing equipment loan facility with Schering AG. We anticipate future
equipment needs to be financed by the Schering AG loan facility for the next
two years.
As part of our target discovery and validation program, Schering AG made a
$2.5 million equity investment in us in May 1997 in exchange for 212,766 shares
of common stock and made an additional equity investment of $2.5 million for
465,117 shares in April 1998. Separately, Schering AG provided loans of
$2.0 million in each of 1997, 1998 and 1999 and has agreed to provide loans of
up to $2.0 million annually through 2001, provided that the collaboration is
continued. If Schering AG does not continue the collaboration, we may need to
seek alternative sources of financing. Amounts not used in any calendar year
may be carried forward to future years. According to the terms of our agreement
with Schering AG, 50.0% of any borrowings on the line of credit must be
collateralized by equipment purchases. The loans, which carry an interest rate
of 8.0% per annum, are immediately convertible into equity at the option of
Schering AG. At December 31, 1999, the outstanding borrowings of $6.8 million
were convertible into approximately 649,000 shares of our common
21
<PAGE>
stock. Subject to the conversion rights referred to above, principal and
interest payments are deferred until maturity of the loans which is in April
2004. As a result of the Atugen formation in 1998, we now subcontract all of
our existing target discovery and identification programs to Atugen. We intend
to use proceeds of approximately $6.9 million from this offering to repay our
outstanding borrowings from Schering AG. However, as long as our collaboration
continues with Schering AG, we anticipate continuing to borrow funds from
Schering AG.
In July 1994, we entered into an agreement with Chiron to collaborate
exclusively on up to five specific targets selected by Chiron. Four targets are
currently subject to the exclusivity provision, including ANGIOZYME. Currently,
ANGIOZYME is being developed in collaboration with Chiron and in accordance
with the terms of agreement, we share equally all development costs and profits
with Chiron. In 1998, this agreement resulted in revenues recognized by us of
$6.2 million, which included a non-recurring payment of $5.0 million for
reimbursement for 50.0% of past expenses we incurred for the preclinical
development of ANGIOZYME. In 1999, we recorded $4.0 million in revenues due
from Chiron for reimbursement of expenses incurred for the clinical development
of ANGIOZYME. We expect 2000 expenses related to ANGIOZYME to be approximately
$11.0 million, of which Chiron is expected to reimburse us approximately $5.5
million.
In March 1999, we entered into a collaboration with Eli Lilly to conduct
research, development and commercialization of our anti-HCV ribozyme for the
treatment of Hepatitis C virus infection. We granted Eli Lilly the exclusive
worldwide right to develop and commercialize the anti-HCV ribozyme in return
for funding all research, development and commercialization costs for the drug.
Under the terms of the agreement, we received approximately $9.2 million during
1999, which included $1.7 million of funding for research and clinical trial
expenses and a $7.5 million equity investment through the purchase of five
shares of our Series L convertible preferred stock. Each share of Series L
convertible preferred stock is convertible into shares of our common stock
based upon milestones related to the development and commercialization of the
anti-HCV ribozyme. Depending on the achievement of certain milestones, each
share of convertible preferred stock will convert into either $500,000 or $1.5
million of our common stock valued at the average closing price over the 30
days prior to conversion. Including development milestones, which we will be
entitled to receive if a commercial product is developed for sale in the United
States, Europe and Japan, we could receive additional funding of up to $29
million. This includes approximately $2.9 million in 2000 for research in
addition to a $500,000 milestone payment for having filed the IND.
In January 2000, we entered into a joint venture with Elan for the
development and commercialization of HERZYME, our potential product to treat
breast and other cancers. As part of the joint venture, Medizyme
Pharmaceuticals Ltd., we contributed $12.0 million in initial funding to
Medizyme in exchange for 80.1% of Medizyme's capital stock. Our capital
contribution was funded by our sale to Elan of our Series A convertible
exchangeable preferred stock for $12.0 million. The Series A preferred stock
has a dividend rate of 6.0%. At the end of the development period, expected to
be mid-2002, Elan has the right to exchange our Series A preferred stock for
30.1% of the capital stock of Medizyme owned by us or convert it prior to
January 2006 into up to approximately 1.2 million shares of our common stock.
Elan purchased 641,026 shares of our common stock for $5.0 million and
committed to purchase an additional $5.0 million of common stock in May 2001 at
a per share price representing a premium of up to 30% of the price based on the
average closing price for the 45 trading days preceding the purchase, but not
less than such 45 trading-day average. In addition, Elan received warrants to
purchase 500,000 shares of our common stock at an average exercise price of
$18.00.
Medizyme paid a license fee of $15.0 million to Elan for the use of its
MEDIPAD(R) drug delivery technology. As a result of this licensing transaction,
it is likely that Medizyme will capitalize the entire license fee and amortize
the balance over the three-year term of the agreement. We will account for our
investment in Medizyme under the equity method. We have estimated that Medizyme
will require $15.0 million in funding through the development period to cover
future operating and development costs. Elan has provided us with a $12.0
million credit facility on a draw-down basis to fund our portion of Medizyme's
operating costs over a 30-month period. Elan may convert this debt into shares
of our Series B convertible preferred stock. The Series B
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preferred stock has a dividend rate of 12.0% and may be converted at any time
into our common stock at a 50% premium to the average price of our common stock
for the 60 trading days prior to the time of the applicable draw down on the
credit facility.
We anticipate that net proceeds of this offering, together with our existing
financial resources and expected revenues from our collaborations, should be
sufficient to meet our anticipated operating and capital requirements through
2002. We expect to incur substantial additional costs, including:
. costs related to our research, drug discovery and development programs;
. preclinical studies and clinical trials of our products, if developed;
. prosecuting and enforcing patent claims;
. general administrative and legal items; and
. manufacturing and marketing of our products, if any.
At December 31, 1999, we had available net operating loss carryforwards,
research and development credit carryforwards and state investment credit
carryforwards of $83.3 million, $2.1 million and $17,000, respectively, for
income tax purposes. Our ability to utilize our net operating loss
carryforwards is subject to an annual limitation in future periods pursuant to
the "change in ownership" rules under Section 382 of the Internal Revenue Code.
Impact of Year 2000
In the prior year, we discussed the nature and progress of our plans to
become Year 2000 ready. In late 1999, we completed our remediation and testing
of systems. As a result of those planning and implementation efforts, we
experienced no significant disruptions in mission critical information
technology and non-information technology systems, and we believe those systems
successfully responded to the Year 2000 date change. We expensed approximately
$60,000 during 1999 in connection with remediating our systems. We are not
aware of any material problems resulting from Year 2000 issues, either with our
research, internal systems or the products and services of third parties. We
will continue to monitor our mission critical computer applications and those
of our suppliers and vendors throughout the year 2000 to ensure that any latent
Year 2000 matters that may arise are addressed promptly.
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BUSINESS
An overview of our company
We are developing a new class of drugs based on "ribozymes." Ribozymes are
engineered molecules that have the ability to cleave RNA, including mRNA, and
thereby selectively inhibit protein production. Because many human diseases
result from abnormal protein production or viral replication, ribozymes are
expected to be useful in developing pharmaceutical candidates for a broad range
of human diseases.
We are conducting a Phase I/II (safety and dosage) clinical trial for our
lead product candidate, ANGIOZYME, for the treatment of solid tumor cancers in
collaboration with Chiron. We expect to complete this trial before the end of
2000. Subject to FDA approval, we would expect to initiate a pivotal efficacy
trial in 2001, which is intended to be the basis for a NDA.
We have two other ribozymes in development with collaborators, an anti-HCV
ribozyme and HERZYME. We are collaborating with Eli Lilly for the development
and commercialization of an anti-HCV ribozyme, as a treatment of Hepatitis C, a
viral liver disease. Clinical trials for our anti-HCV ribozyme were initiated
in February 2000. In January 2000, we entered into a joint venture with Elan to
develop HERZYME for the treatment of breast and other cancers. We expect to
identify and begin preclinical testing on an additional product candidate by
the end of 2000 and will continue to develop new ribozyme product candidates in
the future.
We have also used ribozymes for target discovery and validation, the process
by which the life science industry identifies genes that cause or contribute to
human diseases. In 1998, we decided to focus on the therapeutic potential of
ribozymes and transferred our target discovery and validation technology to a
newly-formed German company, Atugen AG, for a significant equity position in
Atugen. Currently, we own a 48.4% interest in Atugen. Atugen is performing
target discovery and validation for AstraZeneca, Axys, Glaxo Wellcome, Roche
Bioscience and Schering AG. We have retained rights to develop ribozymes or
other oligonucleotides against any targets validated by Atugen on its own or
for its partners.
Genetic function and human disease
The abnormal production of proteins directly causes many human diseases. The
abnormality may be due to a defective gene or to the over- or under-production
of a protein by a "normal" gene. The abnormal production of proteins may have
direct effects on cells within the body or may initiate a series of events
involving other proteins within the body, thereby producing disease. The gene
functions of infectious agents, such as viruses, allow replication and growth
of infectious agents in the human body.
Production of proteins from genes, called "protein expression," generally
involves two steps. First, the information from the DNA sequence of the gene is
"transcribed" to mRNA. The second step involves "translation" of the mRNA and
its information into a protein. The process by which genetic information is
"expressed" in the form of a protein is highly selective; production of a
particular protein generally requires its own specific DNA sequence which leads
to a corresponding specific mRNA sequence. Blocking a gene's function, and
hence the production of its associated proteins, is an increasingly vital tool
in diagnosing and treating human diseases. The process of protein expression is
depicted below.
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[Figure depicting the process of protein expression appears here.]
Our ribozyme technology
Our approach to drug discovery and development begins by either identifying
a gene in humans causing or contributing to disease or identifying an essential
gene in a disease-causing infectious agent. We analyze the nucleotide sequence
of the target gene and create a complementary ribozyme nucleotide sequence.
A ribozyme is a sequence of nucleotides that has binding sequences along
with a catalytic core capable of cleaving a specific RNA molecule, including
mRNA. Ribozymes act as "molecular scissors" by cutting RNA molecules into two
ineffective strands, thereby preventing protein production. Each ribozyme
destroys only a specifically targeted RNA sequence, thereby minimizing the risk
of unwanted side effects. Since ribozymes can be applied to any RNA in
principle, we have the potential to develop ribozymes as an entirely new class
of therapeutic agents having broad applicability. The process by which
ribozymes cut mRNA and other RNA molecules is depicted below.
[Figure depicting the process by which ribozymes
cut mRNA and other RNA molecules appears here.]
In addition, ribozymes can be used to identify gene function and to validate
the disease contributing function of a specific gene. In this way, ribozymes
assist in the identification of new drug candidates. Our ribozyme technology is
an important bridge between the growing knowledge regarding gene sequences,
gene function and their contribution to the treatment or prevention of human
diseases.
We initially test the effectiveness of the ribozyme in cell culture or in
animal models. If the ribozyme reduces or stops production of the protein
associated with the disease, or slows the associated growth or spread of the
disease, not only has the disease contributing function of the gene been
validated, but also a drug candidate has been identified.
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Once we identify a target gene and related ribozyme, we optimize the
ribozyme's effectiveness by varying the length of the portion of the ribozyme
which binds to the RNA to maximize the ribozyme's selectivity and by modifying
the chemical structure to increase the ribozyme's stability in the human body.
To date, we have achieved a number of significant milestones important to the
development of ribozymes and related technical issues, including the following:
Design. We have developed a proprietary computer program to design ribozymes
against sites in a target RNA sequence. This program allows us to accelerate
the identification of potential ribozyme product candidates and to design
multiple back-up candidates.
Stability. To be useful as a treatment, a ribozyme must remain stable in
human serum and cells long enough to destroy the targeted RNA and ideally long
enough for each ribozyme molecule to destroy several RNA molecules. Unmodified
ribozymes are stable and fully active in human serum for only a few seconds. We
have successfully produced chemically-modified ribozymes that are stable and
fully active in human serum for more than 10 days. We believe this level of
stability will be sufficient for ribozymes to be effective drugs.
Selectivity. Based on third-party studies and our internal work, we believe
that a ribozyme with a binding region of approximately 15 nucleotides is
optimal. A binding region of this length is expected to match, on a statistical
basis, only one specific RNA sequence in the coding region of the entire human
genome. Since the ribozyme should interact only with the target RNA, it should
not affect other genes' functions and, therefore, should not have side effects
when used as a drug. The high degree of selectivity of ribozymes has been
demonstrated both by us and by third parties, including our collaborators.
Delivery. Successful development of any drug requires that the drug be
delivered to the desired site in the body. We are exploring a number of
delivery possibilities, including local and systemic delivery of chemically
synthesized ribozymes. For example, we have demonstrated systemic delivery of
chemically synthesized ribozymes without any delivery vehicle using either
intravenous or subcutaneous delivery in several animal models and in humans. We
have also shown that ribozymes can be delivered via a single subcutaneous
injection by patients at home with extended presence of the ribozymes in the
patient's blood. This method provides increased convenience to patients and
facilitates compliance with prescribed protocols.
Safety. We have completed single and multiple dose animal safety studies
with several ribozymes that have confirmed the ribozymes' lack of toxicity. For
example, ANGIOZYME has shown a lack of toxicity in rodents and monkeys. As a
result, the FDA allowed initial human clinical trials to be carried out in
healthy volunteers. A Phase Ia trial in healthy volunteers and a Phase Ib trial
in cancer patients have now been completed and ANGIOZYME has shown an excellent
safety and tolerability profile.
Effectiveness. We have demonstrated through internal research and in
conjunction with our collaborators that our ribozymes reduce the amount of
target RNA and the level of corresponding protein produced as well as inhibit
the spread of disease. Studies showing the effectiveness of ribozymes have been
conducted in multiple animal models for cancer in both models of solid tumor
growth and metastases, and in cell cultures for viral replication.
Manufacturing. To meet our needs for preclinical studies, clinical trials
and the eventual commercialization of ribozymes, we must have the ability to
manufacture a sufficient amount of ribozymes. We and our collaborators have
developed proprietary technology allowing us to synthesize up to 2000
stabilized ribozymes in hundreds of microgram quantities per month. These
quantities are sufficient to permit us to perform direct cell-based screening
of multiple potential target sites in short periods of time. We have also
developed the capability to manufacture kilogram quantities under the FDA's
current good manufacturing practices. In addition, in January 2000, we signed
an agreement with Avecia Limited providing for the transfer of our proprietary
manufacturing processes and intellectual property to enable Avecia to
manufacture ribozyme products for us. We expect to be able to produce those
drugs currently under development in sufficient quantities at commercially
feasible cost, and of the quality required by the FDA, for anticipated clinical
trials of our current product candidates.
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The potential advantages of ribozymes in treating a disease
We believe that ribozymes offer the following significant advantages over
traditional approaches to treating diseases:
Broad Applicability. Once a gene has been identified, a ribozyme can be
designed to target and destroy the associated mRNA to inhibit the related gene
function. Therefore, all diseases for which a gene can be identified as a cause
or an essential contributing factor of diseases are potentially treatable with
a ribozyme drug. In addition, identifying the essential genes of viruses and
other infectious agents that cause human disease creates the potential to
develop ribozyme products to inhibit these genes from functioning and,
consequently, prevent the targeted infectious agent from reproducing.
High Selectivity. The mechanism by which traditional drugs act on a target
gene or protein often is not well understood. Consequently, the side effects of
such drugs are difficult to predict and characterize. Side effects may be
reduced or avoided by using ribozymes designed to attach to and cut only a
specific targeted RNA, a significant advantage over traditional drug therapies.
We have observed the selectivity of ribozymes in both animal studies and human
clinical trials. Because of this selectivity, only the function of the targeted
genetic sequence is affected; other molecules and gene functions are not
altered.
Destruction of Target. Instead of temporarily preventing gene function like
traditional drugs, ribozymes destroy the target RNA and stop the associated
protein production. By contrast, most drugs do not destroy their target. This
inherent feature of ribozymes may offer a significant advantage in the
treatment of diseases caused by infectious agents such as viruses. For example,
cleavage of target viral RNA by ribozymes will inhibit the virus's ability to
propagate, which may result in significant reduction in viral load in the
patient.
Our business strategy
Our strategy is to use our unique and patented ribozyme technology to
identify and develop a new class of drugs to treat human diseases for which
there are large numbers of patients and insufficient treatments. The primary
elements of our strategy are to:
Develop Ribozyme Drugs by Pursuing Multiple Product Candidates Across a
Number of Diseases. Our strategy is to take advantage of the broad
applicability of ribozymes by expanding the number of diseases upon which we
are focused. Our first three product candidates target large and diverse
markets including solid tumor cancers, metastatic cancers and viral diseases.
We have research underway on ribozymes which address multiple other diseases
with large and unmet markets. Additionally, we expect that our relationship
with Atugen will prove an important source of new therapeutic product
candidates. Our near-term goal is to augment our existing pipeline by
introducing one new product candidate into preclinical development before the
end of 2000.
Maximize Value of New Product Candidates through Expanded Internal
Development. We have entered into and intend to continue to collaborate with
major pharmaceutical companies to develop and commercialize many of our leading
product candidates. Prior to entering into future collaboration agreements, we
intend to demonstrate our new product candidate's commercial potential through
preclinical testing or clinical trials. We believe that by extending the period
during which we maintain complete control over new product candidates, we will
be able to negotiate more favorable terms in future collaboration agreements.
We may also pursue commercialization of certain new product candidates
independently.
Focus on Human Therapeutics and License Other Applications of Our
Technology. In 1998, we decided to concentrate our research and development
efforts on the therapeutic potential of ribozymes and transferred our target
discovery and validation technology to Atugen. We expect Atugen to continue to
build the target discovery and validation business by actively pursuing new
collaborations with major pharmaceutical and biotechnology companies. We will
look for further opportunities to license our technology for certain non-
therapeutic applications, including agricultural applications, to third
parties.
Maintain and Expand Our Patent Portfolio and Proprietary Technology. We
currently own, or have exclusive licenses to over 110 issued or allowed patents
worldwide and have more than 100 patent applications pending worldwide. In
1999, we acquired certain ribozyme intellectual property from Innovir
Laboratories, Inc.
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to further strengthen our intellectual property portfolio. We dedicate
substantial resources to the discovery of new inventions to maximize the value
of our proprietary technology. We aggressively pursue patent protection to
maintain worldwide rights to control the development and sale of ribozymes.
Our product programs
The development process for our products starts with research and
preclinical development. Research includes identification of a target protein,
synthesis of an appropriate ribozyme to block expression of the target protein,
and testing the activity of the ribozyme in a specific cell population.
Preclinical testing includes pharmacology and toxicology testing in cell
cultures and animal models, product formulation, dosage studies and
manufacturing scale-up for submission of the necessary data to comply with
regulatory requirements of the FDA and similar agencies in other countries
prior to commencement of human trials.
ANGIOZYME
We are developing ANGIOZYME primarily as a treatment for solid tumor and
associated metastases in cancers such as lung, breast, prostate, colon and
rectal. These cancers account for over 650,000 new cancer cases and nearly
300,000 deaths per year in the United States alone. In addition, ANGIOZYME
could be used in products for the treatment of other diseases in which
angiogenesis is a contributor such as macular degeneration and diabetic
retinopathy.
For a cancerous tumor to grow, the body must generate new blood vessels in
the tumor to supply the blood necessary for tumor growth, a process known as
angiogenesis. In many cases, the Vascular Endothelial Growth Factor, known as
VEGF, molecule and its receptor are essential to angiogenesis. ANGIOZYME was
developed to inhibit the production of the high affinity VEGF receptor, thereby
slowing or stopping angiogenesis and related tumor growth and metastases. We
and independent third parties have conducted animal studies which have shown
dramatic reduction in tumor growth and metastases using ribozymes alone and in
conjunction with existing cytotoxic cancer therapies.
In January 1999, we completed a Phase Ia clinical trial in healthy
volunteers. This trial, conducted on 14 healthy volunteers, demonstrated safety
and tolerability and showed no drug related side effects. In 1999, we also
completed a Phase Ib clinical trial to test for safety and tolerability in 16
cancer patients with a history of solid tumors and metastases. No clinically
significant drug related side effects were seen, and the presence of ANGIOZYME
in the blood of patients in excess of amounts needed to show efficacy in
animals was observed up to 24 hours when ANGIOZYME was administered
subcutaneously.
We initiated a Phase I/II multi-dose clinical trial in cancer patients in
November 1999. This trial is examining the effects of ANGIOZYME when given
daily to cancer patients for 28 continuous days. ANGIOZYME is given via a
subcutaneous injection once a day, at home, by the patients themselves. We
expect to complete the Phase I/II trial by the end of 2000 and evaluate overall
safety, tolerability and other effects and make observations regarding disease
progression. Subject to FDA approval, we expect to initiate a pivotal efficacy
trial in 2001 which is intended to be the basis for a NDA.
We are developing ANGIOZYME in collaboration with Chiron. While we share all
development costs and profits equally with Chiron, we have the final decision-
making authority on all development decisions and activities and we have
retained the right to manufacture ANGIOZYME. If one party discontinues funding
its share of the costs of clinical development, that party would not share
equally in the profits from product sales but would receive a royalty based on
net sales of that product. However, the non-participating party may regain its
interest in the profits of ANGIOZYME by repaying the other party one-half of
the development costs incurred solely by the other party, plus a predetermined
risk premium, at either the commencement of Phase III testing or the filing of
a NDA or Product License Application.
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ANTI-HCV RIBOZYME
Our anti-HCV ribozyme is being developed in collaboration with Eli Lilly to
treat Hepatitis C, a viral disease of the liver. There are over four million
chronically infected persons in the United States and over 170 million
worldwide. Hepatitis C infects approximately 50,000 people and has over 10,000
deaths associated with it each year in the United States. It is the most common
blood borne infection in the United States and has been identified as a "silent
epidemic" and "a daunting challenge to public health" by the United States
Congress.
Current therapies for Hepatitis C are effective in less than 50% of existing
patients and have serious side effects. Our research and preclinical testing
have indicated that the anti-HCV ribozyme selectively cuts Hepatitis C RNA in a
manner that significantly inhibits viral replication in cell culture. It is
also expected to be effective against all known Hepatitis C sub-types, which
now number over 90. Preclinical data for our anti-HCV ribozyme was published in
the February 2000 issue of Hepatology. In February 2000, clinical trials were
initiated for our anti-HCV ribozyme.
In March 1999, we entered into a collaboration with Eli Lilly pursuant to
which they were granted the exclusive worldwide right to develop and
commercialize the anti-HCV ribozyme and any other ribozyme drug for the
treatment of Hepatitis C in return for payment of all research, development and
commercialization costs of the anti-HCV ribozyme. In addition, we will be
entitled to royalties on the sale of the anti-HCV product. In 1999, Eli Lilly
paid us $9.2 million pursuant to this agreement which included a $7.5 million
equity investment and $1.7 million of research funding. Including development
milestones, which we will be entitled to receive if our product is
commercialized in the United States, Europe and Japan, we could receive
additional funding of up to $29 million. This includes approximately $2.9
million in 2000 for research in addition to a $500,000 milestone payment for
having filed the IND.
If Eli Lilly abandons or does not diligently pursue the development of the
anti-HCV ribozyme or another ribozyme drug for the treatment of Hepatitis C,
all rights to the anti-HCV ribozyme and such other ribozymes revert to us,
subject to the right of Eli Lilly to receive royalty payments, if applicable,
on the sale of products developed by us or our third-party collaborators. Eli
Lilly may terminate the collaboration at any time by giving us 90 days' notice.
HERZYME
We are developing HERZYME, a potential product to treat breast and other
cancers. More than 170,000 new breast cancer patients are diagnosed each year
in the United States. Approximately 30% of these patients overexpress the Her-2
gene indicating that regulation of the Her-2 gene could have a beneficial
impact on the disease. HERZYME specifically targets and downregulates Her-2,
and is expected to have a benign side effect profile similar to other ribozymes
in clinical development. HERZYME is currently in preclinical development.
In January 2000, we completed formation of a joint venture with Elan whereby
we have licensed HERZYME and Elan licensed its MEDIPAD(R) drug delivery
technology to the joint venture, Medizyme. The MEDIPAD(R) system is a
disposable continuous subcutaneous drug delivery system that allows a patient
to administer the drug at home over two to three days with a single MEDIPAD(R)
device, thus avoiding hospitalization, intravenous delivery and doctor visits.
Medizyme paid a license fee of $15.0 million to Elan for the use of its
MEDIPAD(R) drug delivery technology.
We contributed $12.0 million in initial funding to Medizyme in exchange for
80.1% of Medizyme's capital stock. Our capital contribution was funded by our
sale to Elan of 12,015 shares of our Series A preferred stock for
$12.0 million. The Series A preferred stock has a dividend rate of 6.0%. At the
end of the development period, expected to be mid-2002, Elan has the right to
exchange our Series A preferred stock for 30.1% of the capital stock of
Medizyme owned by us or convert it prior to January 2006 into up to
approximately 1.2 million shares of our common stock.
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Elan purchased 641,026 shares of our common stock for $5.0 million and
committed to purchase an additional $5.0 million of common stock in May 2001 at
a per share price representing a premium of up to 30% of the price based on the
average closing price for the 45 trading days preceding the purchase, but not
less than such 45 trading day average. In addition, Elan received warrants to
purchase 500,000 shares of our common stock at an average exercise price of
$18.00.
We have estimated that Medizyme will require $15.0 million in funding
through the development period to cover future operating and development costs.
Elan has provided us with a $12.0 million credit facility on a draw-down basis
for us to use, if desired, to fund our portion of Medizyme's operating costs
over a 30 month period. Elan may convert this debt into shares of our Series B
convertible preferred stock. The Series B preferred stock has a dividend rate
of 12.0% and may be converted at any time into our common stock at a 50%
premium to the average price of our common stock for the 60 trading days prior
to the time of the applicable draw down on the credit facility.
Atugen
We have also used ribozymes and other oligonucleotides for target discovery
and validation, the process by which genes that cause or contribute to human
diseases are identified. These technologies use ribozymes and other
oligonucleotides to block the function of genetic sequences. The effect of the
ribozyme or other oligonucleotides in cell cultures or animal models is then
analyzed to determine whether the protein associated with the disease or the
disease itself is reduced or eliminated. Alternatively, a genetic sequence, the
function of which is unknown, can be analyzed using ribozyme or other
oligonucleotide inhibition in a collection of cell culture assays or animal
models that represent a broad range of biological functions.
In 1998, we decided to focus on the therapeutic potential of ribozymes and
transferred our target discovery and validation technologies to Atugen in
exchange for a significant equity interest in Atugen. Financing for Atugen
consisted of a $2.0 million cash contribution by us and a venture capital
investment of $7.0 million. In addition, Atugen received commitments from the
German government for grants and loans for up to $10.0 million.
We will benefit from Atugen's activities in the future in several ways:
. we currently own 48.4% of Atugen's outstanding voting stock;
. we have the right to develop ribozymes or other oligonucleotides against
targets validated by Atugen;
. we will be paid by Atugen for ribozymes and other material manufactured
by us pursuant to our exclusive manufacturing rights;
. we will be paid by Atugen for a portion of our costs of prosecuting
patents applicable to Atugen's business;
. we will be paid by Atugen for certain administrative and other services
rendered by us to Atugen; and
. we retain the right to use the target discovery and validation technology
in non-high throughput applications for our own use and in connection
with limited research and development collaborations with third parties.
Atugen's primary goal is to accelerate discovery and validation of human
health therapeutic targets. It will provide a variety of technologies and
services to utilize information emerging from human genome sequencing efforts
to determine which genes are key factors causing human disease. The significant
technology base transferred by us to Atugen combined with the substantial
initial capitalization should allow Atugen to improve the speed and certainty
of discovering and validating new therapeutic targets both for corporate
partners and for internal use. Atugen is performing target discovery and
validation for AstraZeneca, Axys Pharmaceuticals, Glaxo Wellcome, Millennium
Pharmaceuticals, Roche Bioscience and Schering AG.
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We have the right to name two designees to Atugen's Board of Directors,
including the Chairman of the Board, as long as we own 30% of Atugen's
outstanding stock. Nonetheless, most corporate actions taken by Atugen require
a 75% vote or consent of the holders of Atugen's outstanding stock. Atugen
currently has approximately 40 employees.
As part of the formation, Atugen received exclusive royalty-free licenses to
our extensive patents and technologies for target discovery and validation. We
received a one-time $2.0 million license payment in 1999 for a portion of the
licensed technology. The initial technology base includes our entire gene
function identification and target validation technologies for both chemically
synthesized and expressed nucleic acids, including target site selection, cell
culture assays, RNA and other assays, optimized delivery vehicles and animal
pharmacology.
Our competition
We are engaged in the rapidly changing business of developing treatments for
human disease through gene modulation. Competition among entities attempting to
develop gene modulation products for disease treatment is intense and is
expected to increase. We face direct competition from other companies engaged
in the research, development and commercialization of ribozyme-based technology
as well as competition from companies attempting other methods of gene
expression control. In addition, we compete with large pharmaceutical companies
and established biotechnology firms, many of whom are developing new products
for the treatment of the same diseases targeted by us. In some cases, those
companies have already commenced clinical trials for their products. Many of
these companies have significantly greater financial resources and expertise in
research and development, manufacturing, preclinical studies and clinical
trials, obtaining regulatory approvals and marketing than we do. Our
collaborators and licensees may be conducting research and development programs
using non-ribozyme technologies directed at the same diseases that we are
targeting. Smaller companies may also prove to be significant competitors,
particularly through collaborative arrangements with large pharmaceutical and
biotechnology companies. In addition, our competitors may complete clinical
trials, obtain required regulatory approvals and commence commercial sales of
their products before us, thus achieving a significant competitive advantage.
Academic institutions, governmental agencies and other public and private
research organizations also conduct research, seek patent protection and
establish collaborative arrangements for products and clinical development and
marketing. These companies and institutions compete with us in recruiting and
retaining highly qualified scientific and management personnel.
Our patents and proprietary technology
Protecting patents and other proprietary rights is crucial to developing our
business. In addition to patents, we rely upon trade secrets, know-how and
continuing technological innovations in the design, synthesis, and purification
of ribozymes and in nucleic acid chemistry. We also rely on licensing
opportunities to develop and maintain our competitive position. It is our
policy to file patent applications when appropriate to protect technology,
inventions, and improvements that are considered important in the development
of our business.
At the core of our technology are inventions and patents of the University
of Colorado developed by Dr. Thomas R. Cech and various of his associates.
Pursuant to the University's policies, these inventions and the related patents
became the property of the University. The Cech technology was assigned to the
University's affiliate, University Research Corporation, or URC, which in turn
assigned the rights to license parts of the Cech technology to Competitive
Technologies, Inc. United States Biochemical Corporation, or USB, licensed the
Cech technology pursuant to two sublicenses. We have entered into a license
with URC and sublicenses with USB and Competitive Technologies pursuant to
which we have obtained the exclusive (except for non-commercial academic
research) worldwide right to the Cech technology to, among other things, make,
use and sell ribozymes and ribozyme products covered by the licensed patents.
The URC license and USB sublicense are fully paid. The Competitive Technologies
license provides for the payment of a royalty on sales
31
<PAGE>
of ribozyme products covered by the licensed patents. We may grant sublicenses
to the licensed technology subject to the payment to Competitive Technologies
of a share of royalty income from such sublicenses or a royalty on sales from
sublicensed products, methods or services, depending on the particular licensed
patents involved. In addition, we must pay Competitive Technologies a share of
any option fee, license fee, prepaid royalty or other "front-end" fee other
than equity or research and development funding paid in connection with such
sublicense.
In August 1999, we acquired all of the non-external guide sequence ribozyme-
based intellectual property assets of Innovir Laboratories, a subsidiary of
NEXELL Therapeutics, Inc. The acquisition included 28 patents and patent
applications plus two trademarks. The intellectual property included ribozyme
motifs, uses of oligonucleotides for therapeutics, target validation and
diagnostics, chemical modifications of oligonucleotides and oligonucleotide
delivery, detection, manufacturing and purification. We acquired these assets
from Innovir in exchange for our common stock, warrants for our common stock
and a small amount of cash.
As part of our overall intellectual property strategy, we selectively enter
into agreements with academic institutions either to license pre-existing
technology or to support the development of new technologies and gain the
commercial rights to such new technologies.
As a result of these licenses and sublicenses, and our own internal
research, we currently have certain rights to more than 110 issued or allowed
patents, and more than 100 patent applications under consideration worldwide.
This includes exclusive worldwide rights to 89 patents issued in the United
States, 4 patents issued in Europe, 1 patent issued in Japan and 14 patents
issued in Australia. In addition, Notices of Allowance have been received for
at least 9 patents from the United States Patent and Trademark Office. Six of
the 89 United States issued patents, 1 European patent and 1 Japanese patent
cover enzymatic RNA and the use of an enzymatic RNA to cleave a single stranded
RNA (collectively the "Cech Patents"). We believe that the Cech Patents grant
us the right to exclude others from practicing ribozyme technology as it is
currently known to us in the United States, Europe and Japan irrespective of
the application, the method of production, the method of purification, or the
ribozyme motif used. Unless extended, the Cech Patents will expire in December
2008 in the United States and December 2007 in Europe and in Japan. The
additional issued patents cover both ribozyme technology (e.g., ribozyme
design, synthesis, chemical modifications, delivery, ribozyme motifs, vector
production, target site selection) as well as application to specific
therapeutic targets. None of our other material patents expire before 2013.
In addition, we have filed or hold exclusive licenses to more than 100
pending United States and related foreign applications. Our patent portfolio
includes approximately 40 United States applications for various areas of
interest in human therapeutics and diagnostics and agricultural uses. The
portfolio also includes approximately 80 United States applications related to
the chemistry, design, optimization, manufacture and delivery of ribozyme
products. These patents collectively extend our ribozyme patent coverage well
beyond the life of the Cech Patents.
We have filed opposition documents against two patents granted to a
competitor in Europe. In one of the opposition proceedings in Europe, we were
successful in invalidating various claims relating to the hammerhead ribozyme
composition. The European patent office found that the claims of the granted
patent drawn to the so-called Non-GUX (where X is U, A, C or G) ribozymes were
not patentable. We do not believe this European-granted patent covers those
ribozymes that we have in clinical trials. Opposition proceedings against two
of our European and Japanese patents have been initiated by our competitors.
The Japanese Opposition Division has rejected competitor oppositions and has
issued a notification that it will maintain our Japanese patent without change.
The opposition proceedings against our European patent are still ongoing. In
addition, we anticipate interference proceedings against some of our patents
and patent applications in the United States.
32
<PAGE>
Government regulation of our drug development activities
The development, manufacture and potential sale of therapeutics is subject
to extensive regulation by United States and foreign governmental authorities.
In particular, pharmaceutical products undergo rigorous preclinical and
clinical testing and other approval requirements by the FDA in the United
States under the federal Food, Drug and Cosmetic Act and the Public Health
Service Act and by comparable agencies in most foreign countries.
Before testing agents with potential therapeutic value in healthy human test
subjects or patients may begin, stringent government requirements for
preclinical data must be satisfied. The data, obtained from studies in several
animal species, as well as from laboratory studies, are submitted in an IND
application or its equivalent in countries outside the United States where
clinical studies are to be conducted. Preclinical data must provide an adequate
basis for evaluating both the safety and the scientific rationale for the
initiation of clinical trials.
Clinical trials are typically conducted in three sequential phases, although
these phases may overlap. In Phase I, which frequently begins with initial
introduction of the compound into healthy human subjects prior to introduction
into patients, the product is tested for safety, adverse affects, dosage,
tolerance, absorption, metabolism, excretion and clinical pharmacology. Phase
II typically involves studies in a small sample of the intended patient
population to assess the efficacy of the compound for a specific indication to
determine dose tolerance and the optimal dose range as well as to gather
additional information relating to safety and potential adverse effects. Phase
III trials are undertaken to further evaluate clinical safety and efficacy in
an expanded patient population at geographically dispersed study sites to
determine the overall risk-benefit ratio of the compound and to provide an
adequate basis for product labeling. Each trial is conducted in accordance with
certain standards under protocols that detail the objectives of the study, the
parameters to be used to monitor safety and the efficacy criteria to be
evaluated. Each protocol must be submitted to the FDA as part of the IND.
Data from preclinical and clinical trials are submitted to the FDA as an NDA
for marketing approval and to other health authorities as a marketing
authorization application. The process of completing clinical trials for a new
drug is likely to take a number of years and requires the expenditure of
substantial resources. Preparing an NDA or marketing authorization application
involves considerable data collection, verification, analysis and expense.
There can be no assurance that FDA or any other health authority approval will
be granted on a timely basis, if at all. The approval process is affected by a
number of factors, primarily the risks and benefits demonstrated in clinical
trials as well as the severity of the disease and the availability of
alternative treatments. The FDA or other health authorities may deny an NDA or
marketing authorization application if the authority's regulatory criteria are
not satisfied or may require additional testing or information.
Even after initial FDA or other health authority approval has been obtained,
further studies, including Phase IV post-marketing studies, may be required to
provide additional data on safety and will be required to gain approval for the
use of a product as a treatment for clinical indications other than those for
which the product was initially tested. Also, the FDA or other regulatory
authorities may require post-marketing reporting to monitor the side effects of
the drug. Results of post-marketing programs may limit or expand the further
marketing of the products. Further, if there are any modifications to the drug,
including changes in indication, manufacturing process or labeling or a change
in manufacturing facility, an application seeking approval of such changes will
be required to be submitted to the FDA or other regulatory authority.
Whether or not FDA approval has been obtained, approval of a product by
regulatory authorities in foreign countries must be obtained prior to
commencing commercial sales of the product in such countries. The requirements
governing the conduct of clinical trials and product approvals vary widely from
country to country, and the time required for approval may be longer or shorter
than that required for FDA approval. Although there are some procedures for
unified filings for certain European countries, in general, each country at
this time has its own procedures and requirements. Further, the FDA regulates
the export of products produced in the United States and may prohibit the
export of such products even if they are approved for sale in other countries.
33
<PAGE>
We are also subject to regulation under the Occupational Safety and Health
Act, the Environmental Protection Act, the Toxic Substances Control Act, the
Resources Conservation and Recovery Act and other present and potential future
federal, state and local regulations.
Completing the multitude of steps necessary before marketing can begin
requires the expenditure of considerable resources and a lengthy period of
time. Delay or failure in obtaining the required approvals, clearances or
permits by us, our corporate partners or our licensees would have a material
adverse affect on our ability to generate sales or royalty revenue. The impact
of new or changed laws or regulations cannot be predicted with any accuracy.
Our manufacturing and marketing strategies
To support our preclinical and clinical trial manufacturing requirements, we
constructed manufacturing facilities that we believe comply with applicable
regulatory requirements. We have also established operational quality assurance
and quality control procedures. We believe that our existing facilities and
those available from contract manufacturers will be satisfactory for production
of ribozymes needed through clinical trials for our products currently in
development.
We do not currently have the internal facilities or means to manufacture,
market, distribute or sell on a commercial scale any of products we may
develop. We have expanded our quality control and quality assurance program
internally, including adopting a set of standard operating procedures designed
to assure that any products manufactured by or for us are made in accordance
with cGMP and other applicable domestic and foreign regulations. In addition,
we signed an agreement with Avecia in January 2000 providing for the transfer
of our proprietary manufacturing processes and intellectual property to enable
Avecia to manufacture ribozyme products. Pursuant to this agreement, we must
purchase minimum quantities of ribozymes over the next three years.
We expect to market and sell most products developed, at least initially,
directly and through co-promotion or other licensing arrangements with third
parties, including our collaborators. In some markets, we may enter into
distribution or partnership agreements with pharmaceutical or biotechnology
companies that have large, established sales organizations.
Our employees
As of December 31, 1999, we had 84 full-time employees, including a
technical scientific staff of 61. Our future performance depends significantly
on the continued service of our key personnel. None of our employees are
covered by collective bargaining arrangements. We believe our employee
relations are good.
Legal proceedings
We, along with our chief executive officer, are defendants in several
related lawsuits which purport to be class actions on behalf of purchasers of
common stock of the Company on November 16 and 17, 1999. The lawsuits, which
are substantially identical, allege the defendants violated certain federal
securities laws based upon an allegedly misleading announcement made on
November 15, 1999. The cases have been consolidated in the United States
District Court, District of Colorado. No discovery has occurred, and only
limited discovery is expected to occur pending ruling on preliminary motions.
Based on current information, we believe the suits are without merit. We intend
to defend ourselves and our chief executive officer vigorously.
Properties
We lease approximately 30,000 square feet of laboratory, manufacturing and
office space at 2950 Wilderness Place, Boulder, Colorado, under an operating
lease that lasts through June 2007. We intend to lease approximately 2,000
square feet of additional office space during 2000. With this addition, our
facility will be sufficient to meet our needs at least through 2001.
34
<PAGE>
Our Scientific Advisory Board
We are assisted in our research and development activities by our
Scientific Advisory Board composed of leading scientists to review our
research and development activities and to discuss technological advances and
our business. Our current Scientific Advisory Board members are:
Gerald Joyce, M.D., Ph.D. Professor, Department of Molecular Biology,
Scripps Research Institute
Edward Mocarski, Ph.D. Professor and Chairman, Departments of Microbiology
& Immunology, Stanford University
Bruce Sullenger, Ph.D. Vice Chairman, Department of Surgery, Duke
University Medical Center
Olke C. Uhlenbeck, Ph.D. Professor, Department of Chemistry and
Biochemistry, University of
Colorado
Each member has entered into an exclusive consulting agreement with
Ribozyme Pharmaceuticals in the field of ribozymes and signed confidentiality
and non-disclosure agreements.
We also have collaborative relationships with several board members that
further advance our product development.
35
<PAGE>
MANAGEMENT
Directors, Executive Officers and Key Employees
The directors, executive officers and key employees of Ribozyme
Pharmaceuticals are as follows:
<TABLE>
<CAPTION>
Name Age Position
---- --- --------
<C> <C> <S>
Chief Executive Officer, President
Ralph E. Christoffersen, Ph.D. (1).. 62 and Director
Lawrence E. Bullock................. 44 Vice President of Administration and
Finance, Chief
Financial Officer and Secretary
Vice President of Clinical and
J. Wayne Cowens, M.D................ 51 Regulatory Affairs
Vice President of Corporate
Alene A. Holzman.................... 43 Development
Nassim Usman, Ph.D.................. 40 Senior Vice President of Research
David T. Morgenthaler (1) (2)....... 80 Chairman of the Board
Jeremy L. Curnock Cook (1) (3)...... 50 Director
Anthony B. Evnin, Ph.D. (1) (2)..... 59 Director
David Ichikawa (3).................. 47 Director
Anders P. Wiklund (2) (3)........... 59 Director
</TABLE>
- --------
(1)Member of the Executive Committee.
(2)Member of the Compensation Committee.
(3)Member of the Audit Committee.
Ralph E. Christoffersen, Ph.D., has served as Chief Executive Officer,
President and Director of Ribozyme Pharmaceuticals since June 1992. From 1989
to June 1992, Dr. Christoffersen was Senior Vice President and Director of U.S.
Research at SmithKline Beecham Pharmaceuticals, a pharmaceutical company. From
1983 to 1989, he held senior management positions in research at The Upjohn
Company, a pharmaceutical company. Prior to joining The Upjohn Company, Dr.
Christoffersen served as a Professor of Chemistry and Vice Chancellor for
Academic Affairs at the University of Kansas and as President of Colorado State
University. He received his Ph.D. in Physical Chemistry from Indiana
University.
Lawrence E. Bullock has served as Vice President of Administration and
Finance, Chief Financial Officer and Secretary since January 1996. From
December 1990 to January 1996, Mr. Bullock was Chief Financial Officer,
Director of Finance and Administration and Secretary of La Jolla Pharmaceutical
Company, a biopharmaceutical company. Mr. Bullock received his M.B.A. from the
University of Utah.
J. Wayne Cowens, M.D., has served as Vice President of Clinical and
Regulatory Affairs since July 1999. From 1992 until July 1999, Dr. Cowens
served as Division Vice President of Product Development for Chiron
Corporation, a biotechnology company. During that time he served as Chiron's
commercial representative on the Ribozyme Pharmaceuticals/Chiron joint project
team for the development of ANGIOZYME. From 1990 until 1992, Dr. Cowens served
as Director of Clinical Oncology at Sterling-Winthrop, a pharmaceutical
company, and from 1980 until 1990 as a Cancer Research Clinician in the Grace
Cancer Drug Center at the Roswell Park Cancer Center. Dr. Cowens received his
M.D. degree from The Johns Hopkins University.
Alene A. Holzman has served as Vice President of Corporate Development since
December 1999. Ms. Holzman served as Business Development and General Manager
of Target Validation and Discovery Business from April 1997 to December 1999.
From January 1990 to March 1997, Ms. Holzman was Vice President of ChemTrak
Corporation, a medical technology firm, where she was responsible for finance,
business development and marketing and sales. From 1987 to 1990, she was Vice
President of CytoSciences, Inc., a biomedical company, and from 1981 to 1987
she was Vice President of Marketing and Sales for Hana Biologics, Inc, a
biotechnology firm. Ms. Holzman received her M.B.A. from the University of
California at Berkeley.
36
<PAGE>
Nassim Usman, Ph.D., has served as Senior Vice President of Research since
December 1999. From May 1996 to December 1999, Dr. Usman served as Vice
President of Research at Ribozyme Pharmaceuticals. From April 1994 until May
1996, Dr. Usman served as Director of Chemistry and Biochemistry Research and
from September 1992 until April 1994 Dr. Usman served as Senior Scientist in
Chemistry and Biochemistry. From January 1987 to September 1992, Dr. Usman was
a Postdoctoral Fellow and Scientist in the Departments of Biology and Chemistry
at the Massachusetts Institute of Technology. Dr. Usman received his Ph.D. in
Chemistry from McGill University.
David T. Morgenthaler has served as a director since February 1992 and was
elected Chairman of the Board in December 1995. Mr. Morgenthaler was a founder
of and has been Managing Partner of Morgenthaler Ventures, a private venture
capital firm, since 1968. He has been a director of a number of public and
private companies. Mr. Morgenthaler received his M.S. degree from the
Massachusetts Institute of Technology.
Jeremy L. Curnock Cook has served as a director since July 1995. Mr. Cook is
a director of Rothschild Asset Management, an investment fund, and has been
responsible for the Rothschild Bioscience Unit since 1987. Mr. Cook founded the
International Biochemicals Group in 1975 which he subsequently sold to Royal
Dutch Shell in 1985, remaining as Managing Director until 1987. He is also a
director of the International Biotechnology Trust plc, Creative BioMolecules
Inc., Targeted Genetics Inc., Cantab Pharmaceuticals plc, Cell Therapeutics,
Inc., Amrad Corporation, Vanguard Medica plc, Angiotech Pharmaceuticals, Inc.,
Inflazyme Pharmaceuticals, Inc. and Biocompatibles International plc. Mr. Cook
received an M.A. in Natural Sciences from Trinity College Dublin.
Anthony B. Evnin, Ph.D., has served as a director since February 1992. Dr.
Evnin has been a General Partner of Venrock Associates, a venture capital
partnership, since 1975. He is also a director of Caliper Technologies Corp.
and Triangle Pharmaceuticals, Incorporated. Dr. Evnin received his Ph.D. from
the Massachusetts Institute of Technology.
David Ichikawa has served as a director since May 1998. Mr. Ichikawa has
been employed by Chiron Corporation, a biotechnology company, since September
1994 and is currently Vice President of Finance and Operations. He has also
held management positions at Boehringer Mannhiem Corporation and Chiron (Cetus)
Corporation. Mr. Ichikawa received his M.B.A. from the University of California
at Berkeley.
Anders P. Wiklund has served as a director since August 1994. Since January
1997, Mr. Wiklund has been the principal of Wiklund International, an advisory
firm to the biotechnology and pharmaceutical industries. From 1967 through
1996, Mr. Wiklund served in numerous executive positions for the Kabi and
Pharmacia group of companies, including President and CEO of Kabi Vitrum Inc.
and Kabi Pharmacia, Incorporated. Mr. Wiklund is also a director of Medivir,
A.B. and InSite Vision, Inc., as well as serving on private company boards. Mr.
Wiklund received a Master of Pharmacy degree from the Pharmaceutical Institute
in Stockholm.
37
<PAGE>
PRINCIPAL AND SELLING STOCKHOLDERS
The following table summarizes information regarding the beneficial
ownership of our outstanding securities as of March 9, 2000 by:
. each person or group that we know owns more than 5% of the outstanding
shares of common stock,
. each of our directors;
. each of our executive officers;
. all of our directors and executive officers as a group; and
. each selling stockholder.
<TABLE>
<CAPTION>
Percent of
Common Stock(1)
Amount and -----------------
Nature of Beneficial Before After
Name and Address Ownership(1) Offering Offering
---------------- -------------------- -------- --------
<S> <C> <C> <C>
Elan International Services, Ltd....... 2,142,276(2) 15.9% 12.9%
Chiron Corporation..................... 1,063,868(3) 8.6% 6.8%
Jeremy L. Curnock Cook................. 1,022,633(4) 8.5% 6.7%
International Biotechnology Trust plc.. 1,012,633(5) 8.4% 6.7%
Schering Berlin Venture Corporation.... 819,988(6) 6.8% 5.4%
Anthony B. Evnin, Ph.D................. 325,773(7) 2.7% 2.1%
Ralph E. Christoffersen, Ph.D.......... 209,867(8) 1.7% 1.4%
David T. Morgenthaler.................. 95,563(9) * *
Nassim Usman, Ph.D..................... 64,186(10) * *
Lawrence E. Bullock.................... 63,455(11) * *
Alene Holzman.......................... 39,778(12) * *
Anders P. Wiklund...................... 14,444(13) * *
Bradley Resources Company ............. 10,751(14) * *
J. Wayne Cowens........................ 10,000(15) * *
David Ichikawa......................... 5,000(16) * *
Executive officers and directors as a
group (10 persons).................... 1,850,699(17) 15.0% 12.0%
</TABLE>
- --------
*Less than 1%.
(1) Beneficial ownership is determined in accordance with rules of the SEC and
includes shares over which the indicated beneficial owner exercises voting
and/or investment power. Shares of common stock subject to options or
warrants currently exercisable or exercisable within 60 days are deemed
outstanding for computing the percentage ownership of the person holding
the options but are not deemed outstanding for computing the percentage
ownership of any other person. Except as otherwise indicated in the
footnotes to this table, we believe that each stockholder identified in
the table has sole voting and investment power with respect to all shares
listed opposite their names. Unless otherwise indicated, the officers,
directors and stockholders can be reached at the principal offices of
Ribozyme Pharmaceuticals.
(2) Includes 1,001,250 shares convertible from our Series A preferred stock
assuming a conversion price of $12.00 per share and 500,000 shares
issuable upon exercise of warrants. Additionally, Elan has the right to
designate a director to our board. Elan's offices are located at 102 St.
James Court, Flatts, Smiths Parish, FL 04, Bermuda.
(3) Includes 444,444 shares issuable upon exercise of warrants. Chiron's
offices are located at 4560 Horton Street, Emeryville, California 94608.
(4) Includes options to purchase 10,000 shares and 1,012,633 shares held by
the International Biotechnology Trust plc, for which Rothschild Asset
Management, Ltd. ("Rothschild") acts as investment advisor. Mr. Cook is a
director of Rothschild but disclaims beneficial ownership of these shares.
38
<PAGE>
(5) International Biotechnology Trust plc's offices are located c/o Rothschild
Asset Management, Ltd. at Five Arrows House, St. Swithin's Lane, London EC
4N 8NR England.
(6) Includes 142,105 shares convertible from outstanding debt assuming a
conversion price of $55.88 per share. Schering Berlin Venture
Corporation's offices are located at 3400 Changebridge Road, Monteville,
New Jersey 07045. If the underwriters' over-allotment option is exercised
in full, Schering Berlin Venture Corporation will sell 318,894 shares in
the offering, in which case it would own 501,094 shares or 3.3% of the
common stock after the offering.
(7) Includes options to purchase 10,000 shares, 218,022 shares held by Venrock
Associates and 97,751 shares held by Venrock Associates II, L.P. Mr. Evnin
is a general partner of both partnerships and disclaims beneficial
ownership of these shares except to the extent of his general partnership
interests. If the underwriters' over-allotment option is exercised in
full, Venrock Associates will sell 102,563 shares and Venrock Associates
II, L.P. will sell 45,985 shares in the offering, in which case Venrock
Associates, Venrock Associates II, L.P. and Mr. Evnin would together own
177,225 shares or 1.2% of the common stock after the offering.
(8) Includes options to purchase 119,583 shares.
(9) Includes options to purchase 10,000 shares, 75,563 shares held by
Morgenthaler Management Partners III and 10,000 shares held by
Morgenthaler Family Partnership. Mr. Morgenthaler is a general partner of
both partnerships and disclaims beneficial ownership of these shares
except to the extent of his general partnership interests.
(10) Includes options to purchase 62,158 shares.
(11) Includes options to purchase 47,394 shares.
(12) Includes options to purchase 33,000 shares.
(13) Includes options to purchase 14,444 shares.
(14) If the underwriters' over-allotment option is exercised in full, Bradley
Resources Company will sell 5,058 shares in the offering, in which case it
would own 5,693 shares or .04% of the common stock after the offering.
Bradley's offices are located at 1151 S.W. 30th Street, Suite E, Palm
City, Florida 34991.
(15) Includes options to purchase 10,000 shares.
(16) Excludes 1,063,868 shares held by Chiron. Mr. Ichikawa is employed by
Chiron and disclaims beneficial ownership of those shares. Includes
options to purchase 5,000 shares.
(17) Includes options to purchase 321,579 shares.
39
<PAGE>
UNDERWRITING
Subject to the terms and conditions of the underwriting agreement, the
underwriters named below, who are represented by ING Barings LLC and Chase
Securities Inc., have severally agreed to purchase from us the following
respective number of shares of common stock at the public offering price less
the underwriting discounts and commissions set forth on the cover page of this
prospectus:
<TABLE>
<CAPTION>
Number of
Underwriters Shares
------------ ---------
<S> <C>
ING Barings LLC.................................................
Chase Securities Inc............................................
---------
Total......................................................... 3,150,000
=========
</TABLE>
The underwriting agreement provides that the obligations of the underwriters
are subject to certain conditions precedent and that the underwriters will
purchase all shares of the common stock offered hereby if any of such shares
are purchased.
We have been advised by the underwriters that the underwriters propose to
offer the shares of common stock to the public at the public offering price set
forth on the cover page of this prospectus and to certain dealers at such price
less a concession not in excess of $ per share. The underwriters may allow,
and such dealers may reallow, a concession not in excess of $ per share to
certain other dealers. After the public offering, the public offering price and
other selling terms may be changed by the underwriters.
The following table shows the fees to be paid to the underwriters by us and,
if the over-allotment option is exercised, the selling stockholders in
connection with this offering. These amounts are shown assuming both no
exercise and full exercise of the underwriters' option to purchase additional
shares of common stock:
<TABLE>
<CAPTION>
Per No Full
Share Exercise Exercise
----- -------- --------
<S> <C> <C> <C>
Payable by Ribozyme Pharmaceuticals............... $ $ $
Payable by the selling stockholders............... $ $ $
</TABLE>
Other expenses of this offering (including the registration fees and the
fees of financial printers, counsel and accountants) to be paid by us are
expected to be approximately $617,000.
The selling stockholders have granted the several underwriters an option,
exercisable not later than 30 days after the date of this prospectus, to
purchase up to 472,500 additional shares of common stock at the public offering
price less the underwriting discounts and commissions set forth on the cover
page of this prospectus. 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 the additional shares that the number of
shares of common stock to be purchased by it shown in the table above bears to
3,150,000. To the extent the underwriters exercise such option, the selling
stockholders will be obligated, pursuant to the option, to sell the additional
shares to the underwriters. The underwriters may exercise such option only to
cover over-allotments, if any, made in connection with the sale of the common
stock offered hereby. If purchased, the underwriters will offer such additional
shares on the same terms as those on which the 3,150,000 shares of common stock
are being offered.
In connection with this offering, certain underwriters may engage in passive
market making transactions in the common stock on Nasdaq immediately prior to
the commencement of sales in this offering in accordance with Rule 103 of
Regulation M. Passive market making consists of displaying bids on Nasdaq
limited by the bid prices of independent market makers and making purchases
limited by such prices and effected in response to order flow. Net purchases by
a passive market maker on each day are limited to a specified percentage of the
passive market maker's average daily trading volume in the common stock during
a specified period and must be discontinued when such limit is reached. Passive
market making may stabilize the market price of the
40
<PAGE>
common stock at a level above that which might otherwise prevail and, if
commenced, may be discontinued at any time.
Subject to applicable limitations, the underwriters, in connection with this
offering, may place bids for or make purchases of the common stock in the open
market or otherwise, for long or short account, or cover short positions
incurred, to stabilize, maintain or otherwise affect the price of the common
stock, which may be higher than the price that might otherwise prevail in the
open market. We cannot assure you that the price of the common stock will be
stabilized, or that stabilizing, if commenced, will not be discontinued at any
time. Subject to applicable limitations, the underwriters may also place bids,
or make purchases on behalf of the underwriting syndicate to reduce a short
position created in connection with this offering. The underwriters are not
required to engage in these activities and may end these activities at any
time.
The shares of common stock offered hereby may not be offered or sold,
directly or indirectly, nor may this prospectus or any other offering material
or advertisements in connection with the offer and sale of any such shares of
common stock be distributed or published in any jurisdiction, except under
circumstances that will result in compliance with the applicable rules and
regulations of such jurisdiction. Persons into whose possession this prospectus
comes are advised to inform themselves about, and to observe, any restrictions
relating to the offering of the common stock and the distribution of this
prospectus. This prospectus is not an offer to sell or a solicitation of an
offer to buy any shares of common stock offered hereby in any jurisdiction in
which such an offer or solicitation is unlawful.
The underwriting agreement contains covenants of indemnity among the
underwriters, us and the selling stockholders against certain civil
liabilities, including liabilities under the Securities Act of 1933, as
amended.
We and each of our directors and executive officers and certain of our
security holders, who in the aggregate will beneficially own, following this
offering (assuming no exercise of the underwriters' over-allotment option),
3,620,309 shares of common stock, preferred shares convertible into 1,001,250
shares of common stock, and options or warrants to purchase 1,266,023 shares of
common stock exercisable within 60 days of March 9, 2000, have agreed that they
will not directly or indirectly, without the prior written consent of ING
Barings LLC, offer, sell, offer to sell, contract to sell, or otherwise dispose
of any shares of common stock or securities exchangeable for or convertible
into common stock for a period of 90 days after the date of this prospectus,
except that we may issue, and grant options to purchase, shares of common stock
under our current stock option and purchase plans and other currently
outstanding options and warrants.
Affiliates of Chase Securities Inc. own 16,666 warrants to purchase our
common stock at an exercise price of $9.00.
41
<PAGE>
LEGAL MATTERS
The validity of the shares of common stock offered by this prospectus will
be passed upon for Ribozyme Pharmaceuticals by Rothgerber Johnson & Lyons, LLP,
Denver, Colorado. Legal matters in connection with this offering will be passed
upon for the underwriters by Stroock & Stroock & Lavan LLP, New York, New York.
EXPERTS
Ernst & Young LLP, independent auditors, have audited our financial
statements at December 31, 1999 and 1998, and for each of the three years in
the period ended December 31, 1999, as set forth in their report. We have
included our financial statements in the prospectus and elsewhere in the
registration statement in reliance on Ernst & Young LLP's report, given on
their authority as experts in accounting and auditing.
WHERE YOU CAN FIND MORE INFORMATION
This prospectus is part of a registration statement on Form S-3 that we
filed with the SEC. Certain information in the registration statement has been
omitted from this prospectus in accordance with the rules of the SEC. We file
proxy statements and annual, quarterly and special reports and other
information with the SEC. You can inspect and copy the registration statement
as well as the reports, proxy statements and other information we have filed
with the SEC at the public reference room maintained by the SEC at 450 Fifth
Street, N.W., Washington, D.C. 20549. You can call the SEC at 1-800-SEC-0330
for further information about the public reference rooms. We are also required
to file electronic versions of these documents with the SEC, which may be
accessed from the SEC's World Wide Web site at http://www.sec.gov. Reports,
proxy and information statements and other information concerning Ribozyme
Pharmaceuticals, Inc. may be inspected at The Nasdaq Stock Market at 1735 K
Street, N.W., Washington, D.C. 20006.
The SEC requires us to "incorporate by reference" certain of our publicly-
filed documents into this prospectus, which means that information included in
those documents is considered part of this prospectus. Information that we file
with the SEC after the effective date of this prospectus will automatically
update and supersede this information. We incorporate by reference the
documents listed below and any future filings made with the SEC under Sections
13(a), 13(c), 14 or 15(d) of the Exchange Act until we terminate the
effectiveness of this registration statement.
The following documents filed with the SEC are incorporated by reference in
this prospectus:
1. Our Annual Report on Form 10-K for the year ended December 31, 1999.
2. Our Form 8-K dated February 8, 2000.
3. The description of our common stock in our Registration Statement on
Form 8-A dated April 11, 1996, including any amendments or reports filed
for the purpose of updating such description.
4. All of the filings pursuant to the Exchange Act after the date of filing
the original Registration Statement and prior to the effectiveness of
the Registration Statement.
We will furnish without charge to you, on written or oral request, a copy of
any or all of the documents incorporated by reference, other than exhibits to
those documents. You should direct any requests for documents to the following
address: Ribozyme Pharmaceuticals, 2950 Wilderness Place, Boulder, CO 80301
Attention: Lawrence E. Bullock, Vice President of Administration & Finance, CFO
and Secretary.
42
<PAGE>
INDEX TO FINANCIAL STATEMENTS
<TABLE>
<CAPTION>
Page
----
<S> <C>
Report of Independent Auditors............................................. F-2
Balance Sheets............................................................. F-3
Statements of Operations................................................... F-4
Statements of Stockholders' Equity......................................... F-5
Statements of Cash Flows................................................... F-6
Notes to Financial Statements.............................................. F-7
</TABLE>
F-1
<PAGE>
REPORT OF INDEPENDENT AUDITORS
To the Stockholders and Board of Directors
Ribozyme Pharmaceuticals, Inc.
We have audited the accompanying balance sheets of Ribozyme Pharmaceuticals,
Inc., as of December 31, 1999 and 1998, and the related statements of
operations, stockholders' equity, and cashflows for each of the three years in
the period ended December 31, 1999. 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 auditing standards generally
accepted in the United States. 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 Ribozyme Pharmaceuticals,
Inc. at December 31, 1999 and 1998, and the results of its operations and its
cash flows for each of the three years in the period ended December 31, 1999 in
conformity with accounting principles generally accepted in the United States.
/s/ Ernst & Young LLP
Denver, Colorado
February 9, 2000
F-2
<PAGE>
RIBOZYME PHARMACEUTICALS, INC.
BALANCE SHEETS
<TABLE>
<CAPTION>
Pro Forma
Stockholders'
Equity at
December 31 December 31
-------------------------- ------------------
1998 1999 1999
------------ ------------ -------------
(see Note 14)
(unaudited)
<S> <C> <C> <C> <C>
ASSETS
Current assets:
Cash and cash equivalents..... $ 6,511,512 $ 9,749,822
Securities available-for-
sale......................... -- 4,250,259
Accounts receivable........... 1,163,388 1,545,164
Accounts receivable--related
parties...................... 2,735,193 484,729
Notes receivable--related
parties...................... 118,466 138,903
Prepaid expenses and other.... 84,766 117,668
------------ ------------
Total current assets........ 10,613,325 16,286,545
Property, plant, and
equipment:
Machinery and equipment....... 6,478,223 7,330,368
Leasehold improvements........ 3,582,664 3,763,515
Office furniture and
equipment.................... 1,065,049 1,157,907
------------ ------------
11,125,936 12,251,790
Accumulated depreciation...... (6,903,742) (8,447,884)
------------ ------------
4,222,194 3,803,906
Notes receivable--related
parties...................... 162,466 313,750
Deferred patent costs, net of
accumulated amortization
(1998--$271,328; 1999--
$379,588).................... 2,905,575 4,231,307
Investment in Atugen AG....... 860,216 --
Other assets.................. 460,515 456,591
------------ ------------
Total assets................ $ 19,224,291 $ 25,092,099
============ ============
LIABILITIES AND STOCKHOLDERS'
EQUITY
Current liabilities:
Accounts payable--trade....... $ 750,514 $ 974,309
Accrued liabilities........... 396,143 626,153
Deferred revenue, current
portion--related parties..... 400,000 400,000
Current portion of long-term
debt......................... 498,179 200,455
------------ ------------
Total current liabilities... 2,044,836 2,200,917
Deferred revenue, long-term
portion--related parties..... 1,600,000 1,200,001
Long-term debt................ 200,455 --
Convertible debt--related
parties...................... 4,344,612 6,810,537
Commitments
Stockholders' equity:
Preferred stock, $.01 par
value; 5,000,000 shares
authorized;
Series A convertible
exchangeable, no shares
issued and outstanding at
December 31, 1999, 12,015
shares outstanding pro
forma (preference in
liquidation of $12,015,000)
........................... -- -- $120
Series L convertible, 5
shares issued and
outstanding at December 31,
1999 and proforma,
(preference in liquidation
of $7,500,000)............. -- --
Common stock, $.01 par
value; 20,000,000 shares
authorized; 9,181,455,
11,263,252 and 11,904,278
shares issued and
outstanding at December 31,
1998 and 1999, and
proforma, respectively...... 91,815 112,633 119,043
Additional paid-in capital.... 84,434,213 98,894,100 115,902,570
Accumulated deficit........... (73,422,491) (84,083,072) (84,083,072)
Unrealized loss on securities
available-for-sale........... -- (2,399) (2,399)
Deferred compensation......... (69,149) (40,618) (40,618)
------------ ------------ ------------
Total stockholders' equity.. 11,034,388 14,880,644 $ 31,895,644
------------ ------------ ============
Total liabilities and
stockholders' equity........ $ 19,224,291 $ 25,092,099
============ ============
</TABLE>
See accompanying notes.
F-3
<PAGE>
RIBOZYME PHARMACEUTICALS, INC.
STATEMENTS OF OPERATIONS
<TABLE>
<CAPTION>
Year ended December 31
----------------------------------------
1997 1998 1999
------------ ------------ ------------
<S> <C> <C> <C>
Revenues:
Collaborative agreements........... $ 1,976,500 $ 8,962,813 $ 5,797,456
Collaborative agreements-related
parties........................... -- -- 1,866,942
Grant and other income............. 6,642 25,045 --
------------ ------------ ------------
Total revenues................... 1,983,14 8,987,858 7,664,398
Expenses:
Research and development........... 15,169,731 16,941,652 15,394,602
General and administrative......... 1,886,108 1,812,860 2,132,252
------------ ------------ ------------
Total expenses................... 17,055,839 18,754,512 17,526,854
Operating loss....................... (15,072,697) (9,766,654) (9,862,456)
Other income (expense):
Interest income.................... 794,968 634,569 614,045
Interest expense................... (844,365) (703,711) (551,954)
Equity in loss of unconsolidated
affiliate......................... -- (1,081,771) (860,216)
------------ ------------ ------------
Total other expense.............. (49,397) (1,150,913) (798,125)
------------ ------------ ------------
Net loss............................. $(15,122,094) $(10,917,567) $(10,660,581)
============ ============ ============
Net loss per share (basic and
diluted)............................ $ (2.04) $ (1.22) $ (1.05)
Shares used in computing net loss per
share............................... 7,419,650 8,978,355 10,158,244
</TABLE>
See accompanying notes.
F-4
<PAGE>
RIBOZYME PHARMACEUTICALS, INC.
STATEMENTS OF STOCKHOLDERS' EQUITY
<TABLE>
<CAPTION>
Preferred
Common Stock Stock Additional Unrealized
-------------------- ------------- Paid-In Accumulated Loss on Deferred
Shares Amount Shares Amount Capital Deficit Securities Compensation Total
---------- -------- ------ ------ ----------- ------------ ---------- ------------ -----------
<S> <C> <C> <C> <C> <C> <C> <C> <C> <C>
Balance at
December 31, 1996.... 6,948,304 $ 69,483 -- -- $67,873,284 $(47,382,830) $(9,214) $(188,902) $20,361,821
Issuance of common
stock for cash--
public offering, net
of issuance costs of
$634,796............. 1,400,000 14,000 -- -- 10,551,204 -- -- -- 10,565,204
Issuance of common
stock for cash....... 212,766 2,128 -- -- 2,497,872 -- -- -- 2,500,000
Issuance of common
stock for cash under
stock option plan.... 30,001 300 -- -- 51,404 -- -- -- 51,704
Issuance of common
stock under employee
stock purchase plan.. 29,875 298 -- -- 310,303 -- -- -- 310,601
Issuance of common
stock under 401(k)
plan-stock match .... 19,409 194 -- -- 155,078 -- -- -- 155,272
Cancellation of common
stock relating to
license agreement ... (33,333) (333) -- -- 333 -- -- -- --
Compensation for
issuance of common
stock and options ... -- -- -- -- (15,137) -- -- 58,590 43,453
Net loss.............. -- -- -- -- -- (15,122,094) -- -- (15,122,094)
Change in unrealized
loss on securities
available-for-sale... -- -- -- -- -- -- 4,150 -- 4,150
-----------
Comprehensive
income/(loss)........ (15,117,944)
---------- -------- --- ---- ----------- ------------ ------- --------- -----------
Balance at
December 31, 1997.... 8,607,022 86,070 -- -- 81,424,341 (62,504,924) (5,064) (130,312) 18,870,111
Issuance of common
stock for cash....... 465,117 4,651 -- -- 2,495,349 -- -- -- 2,500,000
Issuance of common
stock for cash--under
stock option plan.... 21,689 217 -- -- 45,545 -- -- -- 45,762
Issuance of common
stock under employee
stock purchase plan.. 54,115 542 -- -- 307,608 -- -- -- 308,150
Issuance of common
stock under 401(k)
plan-stock match..... 33,512 335 -- -- 190,371 -- -- -- 190,706
Compensation for
issuance of common
stock and options ... -- -- -- -- (29,001) -- -- 61,163 32,162
Net loss.............. -- -- -- -- -- (10,917,567) -- -- (10,917,567)
Change in unrealized
loss on securities
available-for-sale... -- -- -- -- -- -- 5,064 -- 5,064
-----------
Comprehensive
income/(loss)........ (10,912,503)
---------- -------- --- ---- ----------- ------------ ------- --------- -----------
Balance at
December 31, 1998.... 9,181,455 91,815 -- -- 84,434,213 (73,422,491) -- (69,149) 11,034,388
Issuance of common
stock for cash--
public offering, net
of issuance costs of
$976,588............. 1,800,000 18,000 -- -- 5,305,412 -- -- -- 5,323,412
Issuance of preferred
stock for cash....... -- -- 5 -- 7,500,000 -- -- -- 7,500,000
Issuance of common
stock and warrants in
exchange for
patents.............. 160,000 1,600 -- -- 1,039,140 -- -- -- 1,040,740
Issuance of common
stock for cash under
stock option plan ... 40,270 403 -- -- 128,256 -- -- -- 128,659
Issuance of common
stock under employee
stock purchase plan.. 64,407 644 -- -- 294,159 -- -- -- 294,803
Issuance of common
stock under 401(k)
plan-stock match..... 17,120 171 -- -- 153,566 -- -- -- 153,737
Expense for repricing
warrants............. -- -- -- -- 42,222 -- -- -- 42,222
Compensation for
issuance of common
stock and options.... -- -- -- -- (2,868) -- -- 28,531 25,663
Net loss.............. -- -- -- -- -- (10,660,581) -- -- (10,660,581)
Change in unrealized
loss on securities
available-for-sale... -- -- -- -- -- -- (2,399) -- (2,399)
-----------
Comprehensive
income/(loss)........ (10,662,980)
---------- -------- --- ---- ----------- ------------ ------- --------- -----------
Balance at December
31, 1999............. 11,263,252 $112,633 5 $-- $98,894,100 $(84,083,072) $(2,399) $ (40,618) $14,880,644
========== ======== === ==== =========== ============ ======= ========= ===========
</TABLE>
See accompanying notes.
F-5
<PAGE>
RIBOZYME PHARMACEUTICALS, INC.
STATEMENTS OF CASH FLOWS
<TABLE>
<CAPTION>
Year ended December 31
----------------------------------------
1997 1998 1999
------------ ------------ ------------
<S> <C> <C> <C>
Operating activities
Net loss............................. $(15,122,094) $(10,917,567) $(10,660,581)
Adjustments to reconcile net loss to
net cash used by
operating activities:
Depreciation....................... 1,665,044 1,670,825 1,544,142
Amortization....................... 74,051 92,107 108,230
Equity in loss of unconsolidated
affiliate......................... -- 1,081,771 860,216
Write-off of deferred patent
costs............................. 93,557 11,836 50,232
Compensation related to common
stock and options 280,177 278,150 223,337
Compensation related to issuance of
affiliate's stock -- 81,000 --
Compensation for forgiveness of
notes receivable--related parties 92,466 126,466 102,466
Expense related to warrant
repricing......................... -- -- 42,222
Gain on sale of investment in
corporate partner................. -- (25,045) --
Loss (gain) on disposal of
equipment......................... (1,126) 541 --
Accrued interest included in
convertible debt-related parties.. 52,889 291,723 465,925
Recognition of deferred revenue-
related parties................... -- -- (399,999)
Changes in operating assets and
liabilities:
Accounts receivable.............. 65,978 (3,890,537) 1,868,688
Prepaid expenses and other....... 38,168 90,783 (32,902)
Other assets..................... (277,807) (18,087) 3,924
Accounts payable--trade.......... 351,777 (154,167) 223,795
Accrued liabilities.............. 29,340 150,186 230,010
Deferred revenue--related
parties......................... -- 2,000,000 --
Deferred gain.................... (5,515) -- --
------------ ------------ ------------
Net cash used by operating
activities.......................... (12,663,095) (9,130,015) (5,370,295)
Investing activities
Additions to property, plant, and
equipment........................... (2,213,311) (936,395) (1,125,854)
Additions to deferred patent costs... (660,581) (506,994) (415,254)
Purchase of Innovir patents.......... -- -- (28,200)
Sale of investment in corporate
partner............................. -- 275,045 --
Proceeds from sale of equipment...... 2,600 -- --
Net (purchases) sales of securities
available-for-sale.................. 3,748,005 804,680 (4,252,657)
Investment in unconsolidated
affiliate........................... -- (2,022,987) --
Transfer of restricted cash.......... 242,733 52,669 --
Loan repayments--related parties..... 3,000 1,875 33,000
Loan advances--related parties....... (175,000) (50,000) (307,187)
------------ ------------ ------------
Net cash (used) provided by investing
activities.......................... 947,446 (2,382,107) (6,096,152)
Financing activities
Net proceeds from sale of shares of
common stock and warrants........... 13,346,056 2,798,630 13,202,936
Payments under loan facilities....... (1,480,677) (2,077,771) (498,179)
Borrowings under loan facilities..... 2,254,460 2,000,000 2,000,000
Payments on capital lease
obligations......................... (152,093) -- --
------------ ------------ ------------
Net cash provided by financing
activities.......................... 13,967,746 2,720,859 14,704,757
------------ ------------ ------------
Net increase (decrease) in cash and
cash equivalents.................... 2,252,097 (8,791,263) 3,238,310
Cash and cash equivalents at
beginning of year................... 13,050,678 15,302,775 6,511,512
------------ ------------ ------------
Cash and cash equivalents at end of
year................................ $ 15,302,775 $ 6,511,512 $ 9,749,822
============ ============ ============
</TABLE>
See accompanying notes.
F-6
<PAGE>
RIBOZYME PHARMACEUTICALS, INC.
NOTES TO FINANCIAL STATEMENTS
December 31, 1999
1. Summary of Significant Accounting Policies
Description of Business
Ribozyme Pharmaceuticals, Inc. (RPI or the Company) was founded in 1992 to
capitalize on the broad potential of ribozymes for use in the development of
human therapeutics and therapeutic target validation services. To date, the
Company has engaged in the research and development of its ribozyme technology
and has experienced significant operating losses in each fiscal year since
inception. The Company has not generated any revenue from the commercialization
of its ribozyme technology and it expects to continue to incur significant
operating losses over at least the next several years.
Capital Requirements and Management's Plans
The Company incurred a net loss of $10,660,581 for the year ended December
31, 1999 and has an accumulated deficit of $84,083,072 at December 31, 1999.
Development of the Company's products will require a commitment of
substantial additional funds to conduct the costly and time-consuming research,
preclinical and clinical testing necessary to bring its proposed products to
market and to establish manufacturing and marketing capabilities. The Company's
future capital requirements will depend on many factors, including, among
others, the progress of the Company's research, development and drug discovery
efforts, the ability of the Company to establish collaborative arrangements for
clinical testing, progress with preclinical studies and clinical trials, the
time and costs involved in obtaining regulatory approvals, the costs involved
in preparing, filing, prosecuting, maintaining, defending and enforcing patent
claims, competing technological and market developments, changes in the
Company's existing research relationships, determination as to the commercial
potential of the Company's potential products, effective commercialization
activities and arrangements, and the cost and availability of third-party
financing for capital expenditures.
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.
Cash and Cash Equivalents
The Company considers all highly liquid investments purchased with a
maturity of three months or less to be cash equivalents. The Company's cash
equivalents are comprised of certificates of deposit, money market funds, and
investment securities.
Property, Plant, and Equipment
Property, plant, and equipment is stated at cost. Depreciation is computed
by the straight-line method over the estimated useful lives of the assets.
Useful lives of laboratory equipment and furniture are estimated at five years
and all computer equipment is estimated at three years. Leasehold improvements
and equipment subject to financing obligations are amortized on a straight-line
basis over the shorter of their estimated useful lives or the term of the
lease.
F-7
<PAGE>
RIBOZYME PHARMACEUTICALS, INC
NOTES TO FINANCIAL STATEMENTS--(Continued)
Deferred Patent Costs
The Company capitalizes legal costs directly incurred in pursuing patent
applications as deferred patent costs. When such applications result in an
issued patent, the related costs are amortized over the remaining legal life of
the patents, using the straight-line method. On a quarterly basis, the Company
reviews its issued patents and pending patent applications, and if it
determines to abandon a patent application or that an issued patent no longer
has economic value, the unamortized balance in deferred patent costs relating
to that patent is immediately expensed.
During 1999, the Company acquired certain pending and issued patents through
the issuance of common stock and warrants, valued at approximately $1.0
million. The cost of these patents has been capitalized and is being treated
consistent with the policies discussed above.
It is possible the above estimates of future economic life of the Company's
commercialization revenues, the amount of anticipated future commercialization
revenues, or both, will be reduced significantly in the near term due to
alternative technologies developed by other biotechnology or pharmaceutical
companies. As a result, the carrying amount of deferred patent costs may be
reduced in the future.
Revenue Recognition and Accounts Receivable
Revenue from collaborative agreements typically consists of nonrefundable
up-front fees, ongoing research and development funding and milestone, license
fees and other payments. Revenue from nonrefundable up-front fees is recognized
upon signing of the agreement. Revenue from ongoing research and development
funding is recorded as the expenses are incurred. Revenue from milestone,
license fees and other payments will be recognized when earned. Payments
received in advance under these agreements are recorded as deferred revenue
until earned. The Company has no further research commitments from our
collaborators for any revenue recognized. The Company's accounts receivable are
predominately collaborative agreement receivables, and to date, the Company has
not experienced any losses with respect to the collection of its accounts
receivables.
In 1999 and 1998, Chiron accounted for approximately 52% and 70% of
collaborative revenues, respectively. In 1999, 1998 and 1997, Schering AG
accounted for approximately 0%, 22% and 76% of collaborative revenues,
respectively. Revenues from Schering AG and Chiron were for nonrefundable,
ongoing research and development fees.
Research and Development Expenses
Research and development costs are expensed as incurred.
Reclassifications
Certain amounts in the December 31, 1997 and 1998 financial statements were
reclassified to conform with the December 31, 1999 presentation. These
reclassifications had no impact on the reported results of operations.
2. Securities Available-for-Sale
At December 31, 1999 management determined that certain marketable
securities held by the Company at December 31, 1999 were available-for-sale.
Securities available-for-sale are carried at fair value, with
F-8
<PAGE>
RIBOZYME PHARMACEUTICALS, INC
NOTES TO FINANCIAL STATEMENTS--(Continued)
unrealized gains and losses reported as a component of stockholders' equity.
The amortized cost of debt securities in this category is adjusted for
amortization of premiums and accretion of discounts to maturity. Such
amortization is included in investment income. Realized gains and losses and
declines in value judged to be other-than-temporary on securities available-
for-sale are included in investment income. Interest and dividends on
securities available-for-sale are included in investment income. The cost of
securities sold is based on the specific identification method. There were no
gross realized gains or losses on sales of securities available-for-sale in
1999 or 1998.
3. Long-Term Debt
Long-term debt as of December 31, 1998 and 1999, consists of the following:
<TABLE>
<CAPTION>
1998 1999
---------- -----------
<S> <C> <C>
Equipment loan (I)................................ $ 698,634 $ 200,455
Convertible debt--related parties (II)............ 4,344,612 6,810,537
---------- -----------
$5,043,246 $ 7,010,992
========== ===========
</TABLE>
- --------
I. In December 1995, the Company negotiated an equipment credit facility of
$2,000,000 with a financial institution. The facility commitment was
terminated on June 30, 1997. The agreement requires monthly principal and
interest payments through November, 2000. The interest rate on these
borrowings was 12% at December 31, 1999 and 1998.
II. In April 1997, the Company entered into a collaboration agreement with a
corporate partner whereby, among other items, the Company may borrow from
the partner up to $2.0 million annually through 2001. The loans are
collaterallized 50% by equipment purchases. The loans carry an interest
rate of 8% per annum and under certain circumstances are convertible into
equity at the option of the corporate partner. Principal and interest
payments on the loans are deferred until maturity of the loans which is in
April 2004. The collaboration and loan facility may be terminated at the
option of the partner any time.
Cash paid for interest for the years ended December 31, 1999, 1998 and 1997
was $84,029, $411,988, and $791,476, respectively. At December 31, 1999 the
carrying amounts of the Company's long-term debt approximates the fair value as
all borrowings bear interest rates which are comparable to the current market
rate for such borrowings.
As of December 31, 1999, maturities of long-term debt are as follows:
<TABLE>
<CAPTION>
Amount
-----------
<S> <C>
2000.......................................................... $ 200,455
2001.......................................................... --
2002.......................................................... --
2003.......................................................... --
2004.......................................................... --
Thereafter.................................................. 6,810,537
-----------
$ 7,010,992
===========
</TABLE>
4. Leases
The Company leases office space under a noncancelable operating lease which
was extended until June 2007. Total rent expense, including miscellaneous
laboratory equipment rentals, was $398,452, $493,188, and $443,796 in 1999,
1998 and 1997 respectively.
F-9
<PAGE>
RIBOZYME PHARMACEUTICALS, INC
NOTES TO FINANCIAL STATEMENTS--(Continued)
The Company's operating lease commitments at December 31, 1999 are as
follows:
<TABLE>
<S> <C>
2000........................................................... $ 385,200
2001........................................................... 385,200
2002........................................................... 385,200
2003........................................................... 374,796
2004........................................................... 373,764
2005 and thereafter............................................ 933,120
----------
$2,837,280
==========
</TABLE>
5. Stockholders' Equity
The Company adopted an Employee Stock Purchase Plan (the Purchase Plan),
authorizing the issuance of 300,000 shares pursuant to purchase rights granted
to employees of the Company. The Purchase Plan provides a means by which
employees purchase common stock of the Company through payroll deductions. The
Purchase Plan is implemented by offerings of rights to eligible employees.
Generally, each offering is twenty-four months' duration with purchases
occurring on each October 31 and April 30 during each offering (except that
April 30, 1996 was not a purchase date). Common stock is purchased for accounts
of employees participating in the Purchase Plan at a price per share equal to
the lower of (i) 85% of the fair market value of a share of common stock on the
date of commencement of participation in the offering or (ii) 85% of the fair
market value of a share of common stock on the date of purchase. Generally all
regular employees, including executive officers, may participate in the
Purchase Plan and may authorize payroll deduction of up to 15% of their base
compensation for the purchase of stock under the plan. The Company's Board of
Directors has the authority to terminate the Purchase Plan at its discretion.
Shares are deemed issued for accounting purposes in the year the shares are
purchased.
Below is a summary of common stock reserved by the Company at December 31,
1999 for issuance upon the exercise of the various options, warrants and the
401(k) and purchase plans.
<TABLE>
<CAPTION>
Shares
---------
<S> <C>
Stock option plans.............................................. 1,788,903
Employee stock purchase plan.................................... 135,761
Employee 401(k) stock match..................................... 229,959
Warrants at $9.00 per share..................................... 16,666
Warrants at $12.00 per share.................................... 350,000
Warrants at $15.75 per share.................................... 10,793
Warrants at $22.50 per share.................................... 448,888
Warrants at $40.50 per share.................................... 11,111
---------
2,992,081
=========
</TABLE>
In connection with a loan payoff, in 1999 the Company repriced 16,666 of its
outstanding warrants. The exercise price on those warrants was reduced from
$22.50 per share to $9.00 per share. All warrants are immediately exercisable.
In 1999, expense related to this repricing of $42,222 was recognized.
The Company's ability to pay dividends is restricted by the terms of its
collaborative, convertible debt and equipment loan facility agreements.
F-10
<PAGE>
RIBOZYME PHARMACEUTICALS, INC
NOTES TO FINANCIAL STATEMENTS--(Continued)
6. Stock Option Plans
The Company has established a Non-Qualified Stock Option Plan and an
Incentive Stock Option Plan (collectively, the Plans), under which it is
authorized to grant stock options to purchase up to 1,317,154 shares of the
Company's common stock to eligible employees, consultants, and other
individuals, as defined in the Plans. In each of May 1997 and in May 1999, the
Company's shareholders approved an additional 350,000 shares of the Company's
common stock to be reserved for issuance pursuant to the Plans. Options to
purchase the Company's common stock are exercisable at a price as determined by
the Board of Directors at the time the option is granted, which shall not be
less than 100% of the fair market value (110% in the case of 10 percent
shareholders) at the date of grant. Vesting rights are determined by the Board
of Directors at the time the option is granted and generally the options become
exercisable at twenty percent at the end of each of years one through five. If
not exercised, the options expire after ten years. The Board of Directors has
also granted certain employees options vesting upon achievement of certain
contingent milestone events.
During the third quarter of 1998, the Company offered a repricing of
existing stock options to all of its current employees. Pursuant to the offer,
all non-executive employees were allowed to exchange each existing stock option
for a newly priced stock option one for one, with the new stock options having
an exercise price equal to the current market price of the underlying common
stock. If exchanged, the vesting term would start over beginning on the date of
exchange. A similar offer was given to all executives, except the options were
exchanged at a one for .75 ratio. As a result of the offer, 890,921 options
were canceled and 747,060 options were granted, effective September 18, 1998.
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 because, as
discussed below, the alternative fair value accounting provided for under FASB
Statement of Financial Accounting Standards No. 123, Accounting for Stock-Based
Compensation (SFAS 123), requires use of option valuation models that were not
developed for use in valuing employee stock options. Under APB 25, if the
exercise price of the Company's employee stock options equals the market price
of the underlying stock on the date of grant, no compensation expense is
recognized. During 1999, 1998 and 1997, the Company recorded $25,663, $32,162,
and $43,453, respectively, of compensation relating to the grant of stock
options and the Antidilution Agreement, all of which relates to pre-IPO
issuances which have been deferred until vesting has been completed.
Pro forma information regarding net income and earnings per share is
required by SFAS 123, which also requires that the information be determined as
if the Company has accounted for its employee stock options under the fair
value method of SFAS 123. The fair value for these options was estimated at the
date of grant using a Black-Scholes option pricing model with the following
weighted-average assumptions for 1999, 1998 and 1997, respectively: risk-free
interest rates of 6.1%, 4.7%, and 6.4%; a dividend yield of 0%; volatility
factors of the expected market price of the Company's common stock of .971,
.967, and .638; and a weighted-average expected life of the option of 6 years.
The weighted average fair value of stock options granted during 1999, 1998 and
1997 was $5.42, $4.04, and $5.88, respectively.
The Black-Scholes option valuation model was developed for use in estimating
the fair value of traded options which have no vesting restrictions and are
fully transferable. In addition, option valuation models require the input of
highly subjective assumptions including the expected stock price volatility.
Because the Company's employee stock options have characteristics significantly
different from those of traded options, and because changes in the subjective
input assumptions can materially affect the fair value estimate, in
management's opinion, the existing models do not necessarily provide a reliable
single measure of the fair value of its employee stock options.
F-11
<PAGE>
RIBOZYME PHARMACEUTICALS, INC
NOTES TO FINANCIAL STATEMENTS--(Continued)
For purposes of pro forma disclosures, the estimated fair value of the
options is amortized to expense over the options' vesting period. The Company's
pro forma information follows:
<TABLE>
<CAPTION>
1997 1998 1999
------------ ------------ ------------
<S> <C> <C> <C>
Pro forma net loss............ $(16,153,548) $(11,948,280) $(12,071,278)
Pro forma loss per share
(basic and diluted).......... $ (2.18) $ (1.33) $ (1.19)
</TABLE>
Because the SFAS 123 method of accounting has not been applied to options
granted prior to January 1, 1995, the resulting pro forma net loss may not be
representative of that to be expected in future years.
Changes in stock options for the years ended December 31, 1999, 1998 and
1997 were as follows:
<TABLE>
<CAPTION>
Exercise
Options Price
---------- -------------
<S> <C> <C>
Outstanding at December 31, 1996............... 679,423 $ .45--$19.00
Options granted................................ 604,300 $7.50--$13.50
Options exercised/canceled..................... (64,833) $ .45--$19.00
---------- -------------
Outstanding at December 31, 1997............... 1,218,890 $ .45--$15.25
Options granted................................ 1,174,560 $3.00--$ 8.13
Options exercised/canceled..................... (1,045,878) $ .45--$15.25
---------- -------------
Outstanding at December 31, 1998............... 1,347,572 $ .45--$12.78
Options granted................................ 598,759 $4.13--$11.31
Options exercised/canceled..................... (213,891) $ .45--$12.78
---------- -------------
Outstanding at December 31, 1999............... 1,732,440 $ .45--$12.78
========== =============
</TABLE>
The weighted average exercise price of options outstanding at December 31,
1999, 1998 and 1997 was $6.52, $4.21 and $9.31, respectively.
Stock options vest as follows:
<TABLE>
<CAPTION>
Options
---------
<S> <C>
Currently exercisable........................................... 507,963
2000............................................................ 255,797
2001............................................................ 215,420
2002............................................................ 209,036
2003............................................................ 207,573
2004 and thereafter............................................. 78,651
Contingent vesting.............................................. 258,000
---------
Total......................................................... 1,732,440
=========
</TABLE>
7. Formation of Atugen, an unconsolidated German Affiliate
In 1998, the Company transferred its gene function and target validation
business and technology to Atugen, a separately funded German affiliate.
Financing for Atugen was accomplished through an equity investment of $2.0
million in cash from RPI in 1998, a venture capital investment of $7.0 million
and a commitment by the German government to provide grants and loans of up to
$10.0 million. As a result, at December 31, 1998, RPI retained a 49.5%
ownership in Atugen. In connection with its formation, Atugen
F-12
<PAGE>
RIBOZYME PHARMACEUTICALS, INC
NOTES TO FINANCIAL STATEMENTS--(Continued)
received exclusive royalty-free licenses to RPI patents and technologies for
target validation and discovery in exchange for a one-time $2.0 million payment
which was received by RPI in January 1999. The entire amount of this one-time
payment was deferred at December 31, 1998 and is being amortized over the five-
year term of the license agreement and is reflected in the Company's equity in
earnings.
According to a service agreement executed by both parties, RPI will provide
management support, technologies, facilities and reagents to Atugen for
reasonable fees. RPI will retain rights to develop ribozyme therapeutic agents
against targets validated by Atugen.
In 1998, RPI gave to its officers and certain other employees stock
representing a 5.5% interest in the newly formed Atugen at no personal cost to
the individuals. Atugen is a closely held private company, and accordingly, the
fair value of the share grants was by nature an estimate. The Company estimated
the fair market value of these share grants at the date of such grants to be
$81,000. As a result, the Company's 1998 Statement of Operations includes
$81,000 of compensation related to the share grants.
8. Collaborative Agreements
Chiron
In July 1994, the Company entered into a research and development
collaboration agreement with Chiron to research, develop and market products
directed towards five genetic targets, and all human clinical indications
associated with those targets. The Company and Chiron will share equally in the
costs and profits of any jointly developed products. In addition, Chiron may,
at its option, finance the Company's portion of its Phase II and Phase III drug
development costs for mutually approved programs. The Company retains the
option to reacquire its rights by reimbursing Chiron for such development costs
plus a predetermined risk premium. The term of the research program is five
years, with the terms of the agreement to be extended if products are jointly
developed. As part of this agreement, Chiron made a $10,000,000 equity
investment in the Company.
In 1998, the Company received $5.0 million from Chiron related to the joint
product development of ANGIOZYME. The non recurring payment was a reimbursement
for 50% of past expenses incurred by the Company for the preclinical
development of ANGIOZYME. In addition, the Company recorded revenue from Chiron
of $4,015,010 and $1,048,138, in 1999 and 1998, respectively, for 50% of
ANGIOZYME clinical development expenses incurred by the Company. There are no
future obligations between the Company and Chiron related to revenues which
were fully recognized in 1999 and 1998.
Schering AG, Berlin
On April 9, 1997, the Company entered into a research collaboration with
Schering AG, Berlin, (Schering AG) focusing on the use of ribozymes for
therapeutic target validation, as well as the development of ribozymes as
therapeutic agents. The collaboration will utilize the special selectivity of
ribozymes to validate new molecular therapeutic targets and to discover new
therapeutic agents based on those targets. The Company will provide its
expertise in ribozyme design, synthesis and delivery, and Berlex Laboratories,
Inc., a U.S. subsidiary of Schering AG (Berlex) will provide candidate targets,
cell culture screens, animal models and development and commercialization
expertise to the collaboration. The Company anticipates that hundreds of
potential targets may be examined over a five year period with Berlex having
the option to commercialize products from any validated targets.
Schering AG made an equity investment in the Company in May 1997 of $2.5
million in exchange for 212,766 shares of common stock, and made an additional
equity investment of $2.5 million for 465,117 shares
F-13
<PAGE>
RIBOZYME PHARMACEUTICALS, INC
NOTES TO FINANCIAL STATEMENTS--(Continued)
in April 1998. Separately, Schering AG provided a loan of $2.0 million in each
of years 1997, 1998 and 1999. Schering AG has agreed to provide loans of up to
$2.0 million annually for each of the next two years, provided that the
collaboration is continued in each of those years. Amounts not used in any
calendar year may be carried forward to future years. According to the terms of
the Company's agreement with Schering AG, 50% of any borrowings on the line of
credit must be collateralized by equipment purchases. The loans, which carry an
interest rate of 8% per annum, are convertible into equity at the option of
Schering AG under certain circumstances. At December 31, 1999, the outstanding
borrowings of $6.8 million were convertible into approximately 649,000 shares
of the Company's common stock. Subject to the conversion rights referred to
above, principal and interest payments are deferred until maturity of the loans
which is in April 2004. During 1999, the Company subcontracted the research to
Atugen and therefore all subsequent revenues for work completed has been solely
recognized by Atugen. The Company may earn success fees upon product
development milestones and has the right to manufacture synthetic ribozyme
products and receive royalties on sales of both ribozyme and non-ribozyme
products resulting from the collaboration. All such payments are subject to
some restrictions, including receipt of certain third party consents. Upon
payment of termination fees paid to the Company, the research collaboration may
be terminated at Schering AG's option any time.
Eli Lilly and Company
In March 1999, the Company entered into a collaboration with Eli Lilly and
Company (Eli Lilly) to conduct research, development and commercialization of
the Company's ribozyme for the treatment of Hepatitis C virus infection (the
anti-HCV ribozyme). Under the terms of the agreement, the Company received
approximately $9.2 million in 1999, which included $1.7 million of funding for
research and clinical trial expenses and a $7.5 million equity investment
purchasing five shares of the Company's non-voting convertible Series L
preferred stock which was completed in April 1999. Each share of Series L
convertible preferred stock is convertible into shares of the Company's common
stock based upon milestones related to the development and commercialization of
the anti-HCV ribozyme. Under certain circumstances, if the Company commences
Phase II clinical trials prior to March 17, 2002, each share of Series L
preferred stock will convert into $500,000 of common stock valued at the
average closing price 30 days prior to conversion. If, however, the Company
fails to commence Phase II clinical trials prior to March 17, 2002, each share
of Series L preferred stock will convert into $1.5 million of common stock
valued at the average closing price of the Company's common stock 30 days prior
to conversion. In addition to equity and research funding, the Company may
receive success fees related to various development milestones and royalties on
future sales of products developed related to the collaboration. Eli Lilly will
receive the exclusive worldwide commercialization rights to products that
result from this collaboration, including the anti-HCV ribozyme product. The
Company has retained certain rights to manufacture anti-HCV riboyzme products
resulting from the collaboration.
9. Commitments and Contingency
At the core of the Company's technology are inventions and patents of the
University of Colorado (CU) which were developed by Dr. Thomas R. Cech and
various associates of Dr. Cech. Pursuant to the policies of CU, these
inventions and the patents issued thereon, (the Cech Technology) became the
property of CU. The Cech Technology was assigned to CU's affiliate, University
Research Corporation (URC), which in turn assigned the rights to license
certain of the Cech Technology to Competitive Technologies, Inc. (CTI),
formerly known as University Patents, Inc. United States Biochemical
Corporation (USB) licensed the Cech Technology pursuant to two sublicenses. One
of these sublicenses was for the Cech Technology held by CTI. In November 1996,
USB assigned to the Company its rights under the sublicense from CTI and the
Company entered into an amended and restated license with CTI. The Company also
has obtained a license from URC and a sublicense from USB for other Cech
Technology held by URC. The CTI license, URC license and USB sublicense
together grant the Company the exclusive (except for non-commercial academic
research) worldwide right,
F-14
<PAGE>
RIBOZYME PHARMACEUTICALS, INC
NOTES TO FINANCIAL STATEMENTS--(Continued)
among other things, to make, use and sell RNA enzymes covered by licensed
patents and products incorporating them. The URC license and USB sublicense are
fully paid. The CTI license provides for the payment of a royalty on sales of
products incorporating RNA enzymes, covered by licensed patents, and for
certain minimum annual royalties. The Company may grant sublicenses to the
licensed technology subject to the payment to CTI of a share of royalty income
from such sublicenses or a royalty on sales from sublicensed products, methods
or services, depending on the particular licensed patents involved. In
addition, the Company must pay CTI a share of any option fee, license fee,
prepaid royalty or other front-end fee other than research and development
funding paid in connection with such sublicense. At the Company's discretion,
the payment may be in either cash or equity.
The Company, along with one or more of its officers or directors, are
defendants in several related lawsuits which purport to be class actions on
behalf of purchasers of common stock of the Company on November 16 and 17,
1999. The lawsuits, which are substantially identical, allege the defendants
violated certain federal securities laws based upon an allegedly misleading
announcement made on November 15, 1999. The cases have been consolidated in the
United States District Court, District of Colorado. No discovery has occurred,
and only limited discovery is expected to occur pending ruling on preliminary
motions. Based on current information, the Company believes the suits to be
without merit.
10. Related Party Transactions
At December 31, 1999, 1998 and 1997, the Company had a total of $295,000,
$280,932 and $320,000, respectively, of non-interest bearing loans due from
executive officers. The balances may be forgiven by the Company under certain
employment agreement provisions. The loan balances are forgivable or payable to
the Company under various terms not to exceed 5 years. The Company forgave
$88,000, $126,466 and $80,000 of these loans during each of the years ending
December 31, 1999, 1998 and 1997, respectively.
11. Income Taxes
The Company accounts for income taxes in accordance with Statement of
Financial Accounting Standard No. 109, Accounting for Income Taxes (SFAS 109).
Under the provisions of SFAS 109, a deferred tax liability or asset (net of a
valuation allowance) is provided in the financial statements by applying the
provisions of applicable tax laws to measure the deferred tax consequences of
temporary differences that will result in net taxable or deductible amounts in
future years as a result of events recognized in the financial statements in
the current or preceding years.
F-15
<PAGE>
RIBOZYME PHARMACEUTICALS, INC
NOTES TO FINANCIAL STATEMENTS--(Continued)
At December 31, 1999, the Company has the following net operating loss and
tax credit carryforwards for income tax purposes:
<TABLE>
<CAPTION>
Research
Net and State
Operating Development Investment
Expiration Date Losses Credits Credits
--------------- ----------- ----------- ----------
<S> <C> <C> <C>
2000................................... $ -- $ -- $11,000
2001................................... -- -- 6,000
2007................................... 3,506,000 101,000 --
2008................................... 7,363,000 185,000 --
2009................................... 9,239,000 316,000 --
2010................................... 11,953,000 139,000 --
2011................................... 15,125,000 181,000 --
2012................................... 15,291,000 296,000 --
2018................................... 10,109,000 475,000 --
2019................................... 10,708,000 408,000 --
----------- ---------- -------
Total................................ $83,294,000 $2,101,000 $17,000
=========== ========== =======
</TABLE>
The Tax Reform Act of 1986 contains provisions that limit the utilization of
net operating loss and tax credit carryforwards if there has been a change of
ownership as described in Section 382 of the Internal Revenue Code. Such a
change of ownership may limit the Company's utilization of its net operating
loss and tax credit carryforwards, and could have been triggered by the
Company's initial public offering or by subsequent sales of securities by the
Company or its shareholders.
The components of the Company's deferred tax assets and liabilities, net of
taxes, as of December 31, 1998 and 1999 are as follows:
<TABLE>
<CAPTION>
1998 1999
------------ -------------
<S> <C> <C>
Deferred tax assets:
Net operating loss carryforwards......... $ 27,095,000 $ 31,069,000
Research and development and state
investment credit carryforwards......... 1,548,000 2,118,000
Depreciation............................. 639,000 592,000
Equity in loss of unconsolidated
affiliate............................... 404,000 724,000
Other.................................... 30,000 23,000
------------ -------------
29,716,000 34,526,000
Valuation allowance...................... (28,610,000) (32,716,000)
------------ -------------
Net deferred tax assets.................. 1,106,000 1,810,000
Deferred tax liabilities:
Deferred patent costs.................... 1,084,000 1,178,000
Deferred income.......................... -- 597,000
Other.................................... 22,000 35,000
------------ -------------
Total deferred tax liabilities........... 1,106,000 1,810,000
------------ -------------
$ -- $ --
============ =============
</TABLE>
F-16
<PAGE>
RIBOZYME PHARMACEUTICALS, INC
NOTES TO FINANCIAL STATEMENTS--(Continued)
12. Employee Savings Plan
The Company has a 401(k) plan which allows participants to contribute 1% to
15% of their salary, subject to eligibility requirements and annual limits. The
Board may, at its sole discretion, approve matching contributions with the
Company's common stock. In 1999, 1998 and 1997, the Board approved a 50% common
stock match equal to total participant deferrals made in each respective year.
The Company stock match is subject to vesting restrictions.
13. Subsequent Events
Joint Venture
In January 2000, the Company formed a joint venture with Elan for the
development and commercialization of HERZYME, the Company's product to treat
breast and other cancers. As part of this arrangement, the Company licensed
HERZYME and Elan licensed its MEDIPAD(R) drug delivery technology to the joint
venture, Medizyme Pharmaceuticals, Ltd. (Medizyme). The MEDIPAD(R) system is a
disposable continuous subcutaneous drug delivery system which allows a patient
to administer the drug at home.
Initial funding of Medizyme included $12.0 million from the Company and $3.0
million from Elan. The Company's $12.0 million capital contribution was funded
by the sale to Elan of (i) 12,105 shares of the Company's Series A convertible
exchangeable preferred stock (the Series A Preferred Stock), (ii) a warrant to
purchase up to 200,000 shares of the Company's common stock at an exercise
price of $15.00 per share with a term of two years, and (iii) a warrant to
purchase up to 300,000 shares of the Company's common stock at an exercise
price of $20.00 per share with a term of seven years. The Series A Preferred
Stock has a stated dividend rate of 6.0% which is payable semi-annually through
the issuance of additional shares of Series A Preferred Stock at a nominal
value of $1,000 per share.
As a result of Medizyme's initial capitalization, the Company owns 80.1% of
the outstanding capital stock of Medizyme and Elan owns 19.9%. However, Elan
can exchange, at its option, all of its shares of the Company's Series A
Preferred Stock for 30.1% of RPI's interest in Medizyme. After such redemption,
Elan would own 50% of the then outstanding capital stock of Medizyme. Elan also
has the option of converting its shares of the Company's Series A Preferred
Stock into approximately 1,200,000 shares of RPI's common stock.
Medizyme paid Elan in cash a $15.0 million non-refundable license fee for
the MEDIPAD(R) drug delivery technology. As a result of this licensing
transaction, it is likely that Medizyme will capitalize the entire license fee
and amortize the balance over the three-year term of the agreement. The Company
estimates that funding for Medizyme will require approximately $15.0 million in
additional operating and development costs. In connection with expected funding
requirements, Elan has agreed to provide the Company with a $12.0 million
credit facility to fund the Company's pro rata portion of Medizyme's operating
costs over the development period, which is expected to be 30 months. The debt
has a 12% rate and may be converted into shares of the Company's Series B
convertible preferred stock (the Series B Preferred Stock), which ultimately is
convertible into shares of the Company's common stock at a 50% premium to the
average price of its common stock for the 60 days prior to the time of the
applicable draw down on the credit facility. The Series B Preferred Stock has a
stated dividend rate of 12%, which is payable semi-annually through the
issuance of additional shares of Series A Preferred Stock at a nominal value of
$1,000 per share.
Also in connection with the Medizyme joint venture, Elan purchased 641,026
shares of the Company's common stock for a purchase price of $5.0 million. Elan
has committed to purchase an additional $5.0 million of common stock in 15
months at a share price that is at a premium to the average closing price for
the 45 trading days preceding the purchase, but not less than such 45 trading
day average. The price is also based on the achievement of certain milestones.
F-17
<PAGE>
RIBOZYME PHARMACEUTICALS, INC
NOTES TO FINANCIAL STATEMENTS--(Continued)
The joint venture agreement provides for equal representation by the Company
and Elan in the operating and management decisions of Medizyme. The Company
will account for its investment in Medizyme under the equity method.
Purchase Commitment
In January 2000, the Company entered into a manufacturing agreement whereby
the Company transferred its proprietary manufacturing processes and
intellectual property to enable the manufacturing of its ribozyme products.
Pursuant to this agreement, the Company must purchase minimum quantities of
ribozymes over the next three years, which represents a significant majority of
the expected usage during that time.
14. Pro Forma Stockholders' Equity (Unaudited)
Pro forma stockholders' equity as of December 31, 1999 reflects the
following transactions with Elan in January 2000: (i) the sale of 641,026
shares of our common stock to Elan for $5.0 million; and (ii) the sale of
12,015 shares of our Series A Preferred Stock to Elan for $12.0 million.
F-18
<PAGE>
- -------------------------------------------------------------------------------
- -------------------------------------------------------------------------------
You should rely on the information contained in this document to which we
have referred you. We have not authorized anyone to provide you with
information that is different. The information in this document may only be
accurate on the date of this document. This document may be used only where it
is legal to sell these securities.
-----------------
TABLE OF CONTENTS
<TABLE>
<CAPTION>
Page
----
<S> <C>
Prospectus Summary....................................................... 3
Risk Factors............................................................. 7
Use of Proceeds.......................................................... 13
Price Range of Common Stock and Dividends................................ 14
Capitalization........................................................... 15
Dilution................................................................. 16
Selected Financial Data.................................................. 17
Management's Discussion and Analysis of Financial Condition and Results
of Operations........................................................... 18
Business................................................................. 24
Management............................................................... 36
Principal and Selling Stockholders....................................... 38
Underwriting............................................................. 40
Legal Matters............................................................ 42
Experts.................................................................. 42
Where You Can Find More Information...................................... 42
Index to Financial Statements............................................ F-1
</TABLE>
-----------------
Through and including , 2000 (the 25th day after the date of this
prospectus), all dealers effecting transactions in these securities, whether
or not participating in this offering, may be required to deliver a
prospectus. This is in addition to a dealer's obligation to deliver a
prospectus when acting as an underwriter and with respect to an unsold
allotment or subscription.
- -------------------------------------------------------------------------------
- -------------------------------------------------------------------------------
- -------------------------------------------------------------------------------
- -------------------------------------------------------------------------------
3,150,000 Shares
[LOGO OF RPI]
Common Stock
--------------
PROSPECTUS
--------------
ING Barings
Chase H&Q
, 2000
- -------------------------------------------------------------------------------
- -------------------------------------------------------------------------------
<PAGE>
PART II
INFORMATION NOT REQUIRED IN PROSPECTUS
Item 13. Other Expenses Of Issuance And Distribution
The following table sets forth the various expenses in connection with the
distribution and sale of the securities being registered which will be paid by
us. All amounts are estimates except for the SEC registration fee:
<TABLE>
<S> <C>
SEC registration fee............................................ $ 47,578
NASD Fee........................................................ $ 18,522
Printing and mailing expenses................................... $150,000
Nasdaq listing fee.............................................. $ 17,500
Legal fees and expenses......................................... $300,000
Accounting fees and expenses.................................... $ 83,400
--------
Total......................................................... $617,000
========
</TABLE>
Item 14. Indemnification Of Directors And Officers
Article XI of our Bylaws provides for indemnification of our directors to
the fullest extent permitted by law, as now in effect or later amended. Article
XI of our Bylaws also permits the indemnification to the same extent of our
officers, employees or agents if, and to the extent, authorized by the Board of
Directors. In addition, the Bylaws provide for indemnification against expenses
incurred by a director to be paid by us at reasonable intervals in advance of
the final disposition of such action, suit or proceeding upon receipt of an
undertaking by or on behalf of the director or officer to repay such amount if
it shall be ultimately determined that he is not entitled to be indemnified by
us. The Bylaws further provide for a contractual cause of action on the part of
our directors for indemnification claims that have not been paid by us.
Article VI of our Certificate of Incorporation, as amended, limits under
certain circumstances the liability of our directors for a breach of their
fiduciary duty as directors. These provisions do not eliminate the liability of
a director (1) for a breach of the director's duty of loyalty to us or our
stockholders, (2) for acts or omissions not in good faith or that involve
intentional misconduct or a knowing violation of law, (3) under Section 174 of
the General Corporate Law of the State of Delaware ("DGCL") (relating to the
declaration of dividends and purchase or redemption of shares in violation of
the DGCL) or (4) for any transaction from which the director derived an
improper personal benefit.
Section 145 of the DGCL contains provisions regarding indemnification, among
others, of officers and directors. Section 145 of the DGCL provides in relevant
part:
(a) A corporation shall have power to indemnify any person who was or is
a party or is threatened to be made a party to any threatened, pending or
completed action, suit or proceeding, whether civil, criminal,
administrative or investigative (other than an action by or in the right of
the corporation) by reason of the fact that the person is or was a
director, officer, employee or agent of the corporation, or is or was
serving at the request of the corporation as a director, officer, employee
or agent of another corporation, partnership, joint venture, trust or other
enterprise, against expenses (including attorneys' fees), judgments, fines
and amounts paid in settlement actually and reasonably incurred by the
person in connection with such action, suit or proceeding if the person
acted in good faith and in a manner the person reasonably believed to be in
or not opposed to the best interests of the corporation, and, with respect
to any criminal action or proceeding, had no reasonable cause to believe
the person's conduct was unlawful. The termination of any action, suit or
proceeding by judgment, order, settlement, conviction, or upon a plea of
nolo contendere or its equivalent, shall not, of itself, create a
presumption that the person did not act in good faith and in a manner which
the person reasonably believed to be in or not opposed to the best
interests of the corporation, and, with respect to any criminal action or
proceeding, had reasonable cause to believe that the person's conduct was
unlawful.
II-1
<PAGE>
(b) A corporation shall have power to indemnify any person who was or is
a party or is threatened to be made a party to any threatened, pending or
completed action or suit by or in the right of the corporation to procure a
judgment in its favor by reason of the fact that the person is or was a
director, officer, employee or agent of the corporation, or is or was
serving at the request of the corporation as a director, officer, employee
or agent of another corporation, partnership, joint venture, trust or other
enterprise against expenses (including attorneys' fees) actually and
reasonably incurred by the person in connection with the defense or
settlement of such action or suit if the person acted in good faith and in
a manner the person reasonably believed to be in or not opposed to the best
interests of the corporation and except that no indemnification shall be
made in respect of any claim, issue or matter as to which such person shall
have been adjudged to be liable to the corporation unless and only to the
extent that the Court of Chancery or the court in which such action or suit
was brought shall determine upon application that, despite the adjudication
of liability but in view of all the circumstances of the case, such person
is fairly and reasonably entitled to indemnity for such expenses which the
Court of Chancery or such other court shall deem proper.
(c) To the extent that a present or former director or officer of a
corporation has been successful on the merits or otherwise in defense of
any action, suit or proceeding referred to in subsections (a) and (b) of
this section, or in defense of any claim, issue or matter therein, such
person shall be indemnified against expenses (including attorneys' fees)
actually and reasonably incurred by such person in connection therewith.
(d) Any indemnification under subsections (a) and (b) of this section
(unless ordered by a court) shall be made by the corporation only as
authorized in the specific case upon a determination that indemnification
of the present or former director, officer, employee or agent is proper in
the circumstances because the person has met the applicable standard of
conduct set forth in subsections (a) and (b) of this section. Such
determination shall be made, with respect to a person who is a director or
officer at the time of such determination, (1) by a majority vote of the
directors who are not parties to such action, suit or proceeding, even
though less than a quorum, or (2) by a committee of such directors
designated by majority vote of such directors, even though less than a
quorum, or (3) if there are no such directors, or if such directors so
direct, by independent legal counsel in a written opinion, or (4) by the
stockholders.
Delaware law also permits a corporation to purchase and maintain insurance
on behalf of any person who is or was a director or officer against any
liability asserted against him and incurred by him in such capacity or arising
out of his status as such, whether or not the corporation has the power to
indemnify him against that liability under Section 145 of the DGCL.
We also have provided liability insurance for each director and officer for
losses arising from claims or charges made against them while acting in their
capacities as our directors or officers.
The above discussion of our corporate documents is not intended to be
exhaustive and is respectively qualified in its entirety by our corporate
documents.
II-2
<PAGE>
Item 15. Recent Sale Of Unregistered Securities
The following table sets forth Ribozyme Pharmaceuticals' sales of
unregistered securities for the past three years. All transactions listed below
involved the issuance of common stock, preferred stock convertible into shares
of common stock or options to acquire shares of common stock prior to
commencement of the offering described in the foregoing prospectus. No
underwriters were employed with respect to the sale of any of the securities
listed below. All shares were issued in reliance upon Section 4(2) and/or 3(b)
of the Securities Act.
<TABLE>
<CAPTION>
Date
Securities Issued Purchaser Acquired Consideration
- ----------------- ----------------------------------- ------------ -------------
<S> <C> <C> <C>
212,776 shares of common
stock.................. Schering AG May 1997 $ 2,500,000
465,117 shares of common
stock.................. Schering AG May 1998 $ 2,500,000
5 shares of Series L
convertible preferred
stock.................. Eli Lilly and Company April 1999 $ 7,500,000
160,000 shares of common
stock.................. Innovir Laboratories, Inc. August 1999 $ 664,000
641,026 shares of common
stock.................. Elan International Securities, Ltd. January 2000 $ 5,000,000
12,025 shares of Series
A convertible
exchangeable preferred
stock.................. Elan International Securities, Ltd. January 2000 $12,015,000
</TABLE>
Item 16. Exhibits And Financial Statement Schedules
(a) Exhibits
<TABLE>
<CAPTION>
Number Description
------ -----------
<C> <S>
1.1+ Form of Underwriting Agreement among Ribozyme Pharmaceuticals, ING
Barings LLC and Chase Securities Inc.
3.1 Amended and Restated Certificate of Incorporation of Ribozyme
Pharmaceuticals dated April 17, 1996(5)
3.2 Bylaws of Ribozyme Pharmaceuticals, as amended(1)
4.1 Specimen Stock Certificate(1)
4.2 Certificate of Designation, Preferences and Rights of Series L
Preferred Shares (10)
4.3 Certificate of Designations, Preferences and Rights of Series A
Preferred Stock and Series B Preferred Stock (11)
5.1 Opinion of Rothgerber Johnson & Lyons LLP
10.1 Form of Indemnity Agreement entered into between Ribozyme
Pharmaceuticals and its directors and officers, with related
schedule(1)
10.2 Ribozyme Pharmaceuticals' Incentive Stock Option Plan, including form
of Incentive Stock Option Agreement(1)
10.3 Ribozyme Pharmaceuticals' Non-Qualified Stock Option Plan, including
form of Non-Qualified Stock Option Agreement(1)
10.4 Ribozyme Pharmaceuticals' 1996 Stock Option Plan, including forms of
Incentive Stock Option and Nonstatutory Stock Option Agreements(1)
10.5 Ribozyme Pharmaceuticals' 1996 Employee Stock Purchase Plan(1)
10.6 Employment Agreement dated January 1, 1997, between Ribozyme
Pharmaceuticals and Ralph E. Christoffersen(5)
10.7 Incentive Stock Option Agreement between Ribozyme Pharmaceuticals and
Ralph E. Christoffersen dated December 23, 1992(1)
10.8 Incentive Stock Option Agreement between Ribozyme Pharmaceuticals and
Ralph E. Christoffersen dated September 23, 1994(1)
10.9 Warrant Purchase Agreement dated March 15, 1995, between Ribozyme
Pharmaceuticals and Hambrecht & Quist Guaranty Finance(1)
10.10 Warrant to Purchase Common Stock dated March 15, 1995, issued to
Hambrecht & Quist Guaranty Finance(1)
</TABLE>
II-3
<PAGE>
<TABLE>
<CAPTION>
Number Description
------ -----------
<C> <S>
10.11 Warrant to Purchase Common Stock dated February 22, 1993, issued to
LINC Scientific Leasing(1)
10.12 Warrant to Purchase Common Stock dated July 30, 1993, issued to
Douglas E. Olson(1)
10.13 Warrant to Purchase Common Stock dated July 30, 1993, issued to
Richard J. Warburg and Ruth P. Warburg(1)
10.14 Warrant to Purchase Common Stock dated December 28, 1994, issued to
Competitive Technologies, Inc.(1)
10.15 Warrant to Purchase Common Stock dated December 29, 1995, issued to
Silicon Valley Bank(1)
10.16 Warrant to Purchase Common Stock dated July 26, 1996, issued to
Silicon Valley Bank(1)
10.17 Warrant to Purchase Common Stock dated April 17, 1996, issued to
Chiron Corporation(1)
10.18 Collaborative Research, Development and Commercialization Agreement
dated July 15, 1994, between Ribozyme Pharmaceuticals and Chiron
Corporation(1)
10.19 Research Collaboration and Licensing Agreement dated November 1,
1995, between Ribozyme Pharmaceuticals and Pharmacia Biotech, AB(1)
10.20 Research and Development Collaboration Agreement dated April 19,
1993, between Ribozyme Pharmaceuticals and Parke-Davis Division of
Warner-Lambert Company(1)
10.21 First Amendment to the Research and Development Collaboration
Agreement dated April 17, 1995, between Ribozyme Pharmaceuticals and
Parke-Davis Division of Warner-Lambert Company(1)
10.22 Second Amendment to the Research and Development Collaboration
Agreement dated February 8, 1996, between Ribozyme Pharmaceuticals
and Parke-Davis Division of Warner-Lambert Company(1)
10.23 Financing Agreement dated March 16, 1995, among Wilderness Place
Holdings L.L.C., Hambrecht & Quist Guaranty Finance, L.P. and
Ribozyme Pharmaceuticals(1)
10.24 Negotiable Promissory Note dated October 7, 1992, between Ribozyme
Pharmaceuticals and Ralph Christoffersen and Addendum dated June 25,
1993(1)
10.25 Employment Agreement dated January 8, 1996, between Ribozyme
Pharmaceuticals and Lawrence E. Bullock(1)
10.26 Promissory Note dated February 8, 1996, between Ribozyme
Pharmaceuticals and Lawrence E. Bullock(1)
10.27 Lease for Real Property dated May 20, 1992, between Aero-Tech
Investments and Ribozyme Pharmaceuticals(1)
10.28 Non-Disturbance and Attornment Agreement dated March 31, 1995, among
General American Life Insurance Company, Aero-Tech Investments,
Wilderness Place Holdings L.L.C. and Ribozyme Pharmaceuticals(1)
10.29 Master Lease Agreement dated September 2, 1992, between Ribozyme
Pharmaceuticals and LINC Scientific Leasing(1)
10.30 Loan and Security Agreement dated February 28, 1994, between Ribozyme
Pharmaceuticals and Silicon Valley Bank(1)
10.31 Loan Modification Agreement dated December 21, 1994, between Ribozyme
Pharmaceuticals and Silicon Valley Bank(1)
10.32 Loan and Security Agreement dated December 29, 1995, between Ribozyme
Pharmaceuticals and Silicon Valley Bank and MMC/GATX Partnership No.
1(1)
10.33 Warrant to Purchase Common Stock dated December 29, 1995, issued to
MMC/GATX Partnership No. 1(1)
10.34 Agreement dated February 29, 1996, between Ribozyme Pharmaceuticals
and Chiron Corporation relating to research and development
funding(1)
</TABLE>
II-4
<PAGE>
<TABLE>
<CAPTION>
Number Description
------ -----------
<C> <S>
10.35 Amendments to original Employment Agreements between Ribozyme
Pharmaceuticals and Ralph E. Christoffersen, Lawrence E. Bullock and
Nassim Usman, pursuant to letters dated November 14, 1996, November
22, 1996, and December 15, 1996(3)
10.36 Promissory Note dated June 4, 1996, between Ribozyme Pharmaceuticals
and Nassim Usman(3)
10.37 Amendment to Lease for Real Property dated March 13, 1997, between
Aero-Tech Investments and Ribozyme Pharmaceuticals(3)
10.38 Employment Agreement dated May 2, 1996, between Ribozyme
Pharmaceuticals and Nassim Usman(2)
10.39 Collaboration Agreement Regarding Use of Ribozymes to Determine Gene
Function dated May 13, 1996, between Ribozyme Pharmaceuticals and
Chiron Corporation(2)
10.40 Amended and Restated License Agreement dated November 20, 1996,
between Ribozyme Pharmaceuticals, University Research Corporation,
University of Colorado and United States Biochemical Corporation(3)*
10.41 Amended and Restated Sublicense Agreement dated November 20, 1996,
between Ribozyme Pharmaceuticals and United States Biochemical
Corporation(3)*
10.42 Amended and Restated License Agreement dated November 20, 1996,
between Ribozyme Pharmaceuticals and Competitive Technologies,
Incorporated(3)*
10.43 Memorandum of Understanding dated March 1, 1996, between Ribozyme
Pharmaceuticals and DowElanco(1)
10.44 Stock Subscription Agreement dated September 1996 between Ribozyme
Pharmaceuticals and University of Research Corporation(3)*
10.45 Stock Subscription Agreement dated November 20, 1996, between
Ribozyme Pharmaceuticals and United States Biochemical
Corporation(3)*
10.46 Assignment of License and Restated License Agreement dated November
20, 1996, among Ribozyme Pharmaceuticals, United States Biochemical
Corporation and Competitive Technologies(3)*
10.47 Letter Agreement dated May 22, 1996, between Ribozyme Pharmaceuticals
and ALZA Corporation(3)*
10.48 Research and Development Collaboration Agreement dated December 2,
1996, between Ribozyme Pharmaceuticals and Protogene Laboratories(3)*
10.49 License Agreement dated February 14, 1997, between Ribozyme
Pharmaceuticals and IntelliGene, Ltd.(3)*
10.50 Subscription Agreement dated April 17, 1995, between Ribozyme
Pharmaceuticals and Parke-Davis Division of Warner-Lambert Company(1)
10.51 Stock Purchase Agreement dated June 28, 1995, among Ribozyme
Pharmaceuticals and investors(1)
10.52 Agreement dated March 1, 1996, between Ribozyme Pharmaceuticals and
DowElanco Corporation relating to the conversion of preferred
stock(1)
10.53 Stock Subscription Agreement dated October 30, 1995, between Ribozyme
Pharmaceuticals and Gewestelijke Investeringsmaatschappij voor
Vlaanderon n.v.(1)
10.54 Research, License, Supply and Royalty Agreement between Schering
Aktiengesellschaft and Ribozyme Pharmaceuticals dated April 9,
1997(4)*
10.55 Purchase Agreement dated April 9, 1997, among Ribozyme
Pharmaceuticals, Schering Berlin Venture Corporation and Schering
Aktiengesellschaft(4)*
10.56 Employment Agreement dated February 27, 1997, between Ribozyme
Pharmaceuticals and Alene Holzman(5)
</TABLE>
II-5
<PAGE>
<TABLE>
<CAPTION>
Number Description
------ -----------
<C> <S>
10.57 Employment Agreement dated July 5, 1997, between Ribozyme
Pharmaceuticals and Thomas Rossing(5)
10.58 Executive Bonus Plan dated March 27, 1998(6)
10.59 Research, Collaboration and License Agreement dated May 19, 1998,
between Ribozyme Pharmaceuticals and Roche Bioscience, a division of
Syntex (U.S.A.) Inc.(7)*
10.60 Employment Agreement dated September 8, 1998, between Ribozyme
Pharmaceuticals and Nassim Usman(8)
10.61 Participation Agreement dated August 31, 1998, as amended, and
related documents between Ribozyme Pharmaceuticals and Atugen
Biotechnology GmbH(9)*
10.62 Research Collaboration and License Agreement dated March 17, 1999,
between Ribozyme Pharmaceuticals and Eli Lilly and Company* (10)
10.63 Stock Purchase Agreement dated April 30, 1999, between Ribozyme
Pharmaceuticals and Eli Lilly and and Company (10)
10.64 Employment Agreement dated May 10, 1999 between Ribozyme
Pharmaceuticals and Dr. Wayne Cowens (10)
10.65 Securities Purchase Agreement dated January 7, 2000, among Ribozyme
Pharmaceuticals, Elan International Services, Ltd. and Elan
Corporation, plc (11)
10.66** License Agreement dated January 7, 2000 among Elan Pharmaceutical
Technologies (a division of Elan Corporation, plc), Elan Pharma
International Limited and Medizyme Pharmaceuticals, Ltd. (11)
10.67 Warrant dated January 7, 2000, issued to Elan International
Services, Ltd. to purchase up to 200,000 shares of Ribozyme
Pharmaceuticals' common stock (11)
10.68 Warrant dated January 7, 2000 issued to Elan International Services
Ltd. to purchase up to 300,000 shares of Ribozyme Pharmaceuticals'
common stock (11)
10.69 Convertible Promissory Note dated January 7, 2000, from Ribozyme
Pharmaceuticals to Elan International Services, Ltd. (11)
10.70** Subscription, Joint Development and Operating Agreement dated
January 7, 2000, among Ribozyme Pharmaceuticals, Elan Corporation,
plc, Elan Pharma International Limited, Elan International Services,
Ltd. and Medizyme Pharmaceuticals, Ltd. (11)
10.71 Funding Agreement dated January 7, 2000 among Ribozyme
Pharmaceuticals, Elan Pharmaceutical Technologies (a division of
Elan Corporation, plc), Elan Pharma International Limited and Elan
International Services, Ltd. (11)
10.72** License Agreement dated January 7, 2000, among Ribozyme
Pharmaceuticals and Medizyme Pharmaceuticals, Ltd. (11)
10.73 Registration Rights Agreement dated January 7, 2000, between
Ribozyme Pharmaceuticals and Elan International Services, Ltd. (11)
10.74 Registration Rights Agreement dated January 7, 2000 among Ribozyme
Pharmaceuticals, Elan International Services, Ltd. and Medizyme
Pharmaceuticals Ltd. (11)
10.75** Agreement dated January 31, 2000, between Ribozyme Pharmaceuticals
and Avecia Limited (11)
23.1 Consent of Ernst & Young LLP, Independent Auditors
23.2+ Consent of Rothgerber Johnson & Lyons LLP (included in Exhibit 5.1)
24.1+ Power of Attorney (included on the signature page of this
Registration Statement)
</TABLE>
- --------
+ Previously filed
* Ribozyme Pharmaceuticals has applied for and received confidential
treatment with respect to portions of these exhibits.
II-6
<PAGE>
** Ribozyme Pharmaceuticals has applied for confidential treatment with
respect to portions of these exhibits.
(1) Documents incorporated by reference herein to certain exhibits to
Ribozyme Pharmaceuticals' Form SB-2 Registration Statement, File No.
333-1908-D.
(2) Documents incorporated by reference herein to certain exhibits to
Ribozyme Pharmaceuticals' Form 10-QSB for the quarter ended June 30,
1996.
(3) Documents incorporated by reference herein to certain exhibits to
Ribozyme Pharmaceuticals' Form 10-KSB for the year ended December 31,
1996.
(4) Documents incorporated by reference herein to certain exhibits to
Ribozyme Pharmaceuticals' Form 8-K dated June 12, 1997.
(5) Documents incorporated by reference herein to certain exhibits to
Ribozyme Pharmaceuticals' Form SB-2 Registration Statement, File No.
333-34981.
(6) Documents incorporated by reference herein to certain exhibits to
Ribozyme Pharmaceuticals' Form 10-K for the year ended December 31,
1997.
(7) Documents incorporated by reference herein to certain exhibits to
Ribozyme Pharmaceuticals' Form 10-Q/A for the quarter ended June 30,
1998.
(8) Documents incorporated by reference herein to certain exhibits to
Ribozyme Pharmaceuticals' Form 10-Q for the quarter ended September 30,
1998.
(9) Documents incorporated by reference herein to certain exhibits to
Ribozyme Pharmaceuticals' Form 8-K/A dated June 16, 1999.
(10) Documents incorporated by reference herein to certain exhibits to
Ribozyme Pharmaceuticals' Form S-1 Registration Statement, File No.
333-75079.
(11) Documents incorporated by reference herein to certain exhibits to
Ribozyme Pharmaceuticals' Form 8-K dated February 8, 2000.
(b) Financial Statement Schedules
All schedules have been omitted because they are not applicable or not
required or the required information is included in the financial statements
or notes thereto.
Item 17. Undertakings
The undersigned registrant hereby undertakes:
(1) To file, during any period in which offers or sales are being made,
a post-effective amendment
to this registration statement:
(i) To include any prospectus required by Section 10(a)(3) of the
Securities Act of 1933;
(ii) To reflect in the prospectus any facts or events arising after
the effective date of the registration statement (or the most recent
post-effective amendment thereof) which, individually or in the
aggregate, represent a fundamental change in the information set forth
in the registration statement. Notwithstanding the foregoing, any
increase or decrease in volume of securities offered (if the total
dollar value of securities offered would not exceed that which was
registered) and any deviation from the low or high end of the estimated
maximum offering range may be reflected in the form of prospectus filed
with the SEC pursuant to Rule 424(b) if, in the aggregate, the changes
in volume and price represent no more than 20% change in the maximum
aggregate offering price set forth in the "Calculation of Registration
Fee" table in the effective registration statement.
(iii) To include any material with respect to the plan of
distribution not previously disclosed in the registration statement or
any material change to such information in the registration statement;
(2) That, for the purpose of determining any liability under the
Securities Act of 1933, each such post-effective amendment 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>
(3) To remove from registration by means of a post-effective amendment
any of the securities being registered which remain unsold at the
termination of the offering.
Insofar as indemnification for liabilities arising under the Securities Act
may be permitted to directors, officers and controlling persons of the
registrant pursuant to the provision described under Item 20 or otherwise, the
registrant has been advised that in the opinion of the SEC 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 registrant of expenses incurred or
paid by a director, officer or controlling person of the registrant 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 registrant 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.
II-8
<PAGE>
SIGNATURES
Pursuant to the requirements of the Securities Act of 1933, the registrant
certifies that it has reasonable grounds to believe that it meets all the
requirements for filing on Form S-3 and has duly caused this Amendment No. 1 to
Form S-3 Registration Statement to be signed on its behalf by the undersigned,
thereunto duly authorized in Boulder, Colorado, on March 10, 1999.
Ribozyme Pharmaceuticals, Inc.
/s/ Ralph E. Christoffersen
By: _________________________________
Ralph E. Christoffersen, Ph.D.
Chief Executive Officer and
President
In accordance with the requirements of the Securities Act of 1933, as
amended, this Form S-3 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/ Ralph E. Christoffersen Chief Executive Officer and March 10, 2000
______________________________________ President (Principal Executive
Ralph E. Christoffersen, Ph.D. Officer)
/s/ Lawerence E. Bullock Vice President, Administration March 10, 2000
______________________________________ Finance, Chief Financial
Lawrence E. Bullock Officer and Secretary
(Principal Financial and
Accounting Officer)
/s/ Lawerence E. Bullock Chairman of the Board of March 10, 2000
at attorney-in-fact for Directors
______________________________________
David T. Morgenthaler
/s/ Lawerence E. Bullock Director March 10, 2000
at attorney-in-fact for
______________________________________
Jeremy C. Cook
/s/ Lawerence E. Bullock Director March 10, 2000
at attorney-in-fact for
______________________________________
Anthony B. Evnin, Ph.D.
/s/ Lawerence E. Bullock Director March 10, 2000
at attorney-in-fact for
______________________________________
David Ichikawa
/s/ Lawerence E. Bullock Director March 10, 2000
at attorney-in-fact for
______________________________________
Anders Wiklund
</TABLE>
II-9
<PAGE>
EXHIBIT INDEX
<TABLE>
<CAPTION>
Number Description
------ -----------
<C> <S>
1.1 Form of Underwriting Agreement among Ribozyme Pharmaceuticals, ING
Barings LLC and Chase Securities LLC
3.1 Amended and Restated Certificate of Incorporation of Ribozyme
Pharmaceuticals dated April 17, 1996(5)
3.2 Bylaws of Ribozyme Pharmaceuticals, as amended(1)
4.1 Specimen Stock Certificate(1)
4.2 Certificate of Designation, Preferences and Rights of Series L
Preferred Shares (10)
4.3 Certificate of Designations, Preferences & Rights of Series A Preferred
Stock and Series B Preferred Stock (11)
5.1 Opinion of Rothgerber Johnson & Lyons LLP
10.1 Form of Indemnity Agreement entered into between Ribozyme
Pharmaceuticals and its directors and officers, with related
schedule(1)
10.2 Ribozyme Pharmaceuticals' Incentive Stock Option Plan, including form
of Incentive Stock Option Agreement(1)
10.3 Ribozyme Pharmaceuticals' Non-Qualified Stock Option Plan, including
form of Non-Qualified Stock Option Agreement(1)
10.4 Ribozyme Pharmaceuticals' 1996 Stock Option Plan, including forms of
Incentive Stock Option and Nonstatutory Stock Option Agreements(1)
10.5 Ribozyme Pharmaceuticals' 1996 Employee Stock Purchase Plan(1)
10.6 Employment Agreement dated January 1, 1997, between Ribozyme
Pharmaceuticals and Ralph E. Christoffersen(5)
10.7 Incentive Stock Option Agreement between Ribozyme Pharmaceuticals and
Ralph E. Christoffersen dated December 23, 1992(1)
10.8 Incentive Stock Option Agreement between Ribozyme Pharmaceuticals and
Ralph E. Christoffersen dated September 23, 1994(1)
10.9 Warrant Purchase Agreement dated March 15, 1995, between Ribozyme
Pharmaceuticals and Hambrecht & Quist Guaranty Finance(1)
10.10 Warrant to Purchase Common Stock dated March 15, 1995, issued to
Hambrecht & Quist Guaranty Finance(1)
10.11 Warrant to Purchase Common Stock dated February 22, 1993, issued to
LINC Scientific Leasing(1)
10.12 Warrant to Purchase Common Stock dated July 30, 1993, issued to Douglas
E. Olson(1)
10.13 Warrant to Purchase Common Stock dated July 30, 1993, issued to Richard
J. Warburg and Ruth P. Warburg(1)
10.14 Warrant to Purchase Common Stock dated December 28, 1994, issued to
Competitive Technologies, Inc.(1)
10.15 Warrant to Purchase Common Stock dated December 29, 1995, issued to
Silicon Valley Bank(1)
10.16 Warrant to Purchase Common Stock dated July 26, 1996, issued to Silicon
Valley Bank(1)
10.17 Warrant to Purchase Common Stock dated April 17, 1996, issued to Chiron
Corporation(1)
10.18 Collaborative Research, Development and Commercialization Agreement
dated July 15, 1994, between Ribozyme Pharmaceuticals and Chiron
Corporation(1)
10.19 Research Collaboration and Licensing Agreement dated November 1, 1995,
between Ribozyme Pharmaceuticals and Pharmacia Biotech, AB(1)
</TABLE>
<PAGE>
<TABLE>
<CAPTION>
Number Description
------ -----------
<C> <S>
10.20 Research and Development Collaboration Agreement dated April 19, 1993,
between Ribozyme Pharmaceuticals and Parke-Davis Division of Warner-
Lambert Company(1)
10.21 First Amendment to the Research and Development Collaboration Agreement
dated April 17, 1995, between Ribozyme Pharmaceuticals and Parke-Davis
Division of Warner-Lambert Company(1)
10.22 Second Amendment to the Research and Development Collaboration
Agreement dated February 8, 1996, between Ribozyme Pharmaceuticals and
Parke-Davis Division of Warner-Lambert Company(1)
10.23 Financing Agreement dated March 16, 1995, among Wilderness Place
Holdings L.L.C., Hambrecht & Quist Guaranty Finance, L.P. and Ribozyme
Pharmaceuticals(1)
10.24 Negotiable Promissory Note dated October 7, 1992, between Ribozyme
Pharmaceuticals and Ralph Christoffersen and Addendum dated June 25,
1993(1)
10.25 Employment Agreement dated January 8, 1996, between Ribozyme
Pharmaceuticals and Lawrence E. Bullock(1)
10.26 Promissory Note dated February 8, 1996, between Ribozyme
Pharmaceuticals and Lawrence E. Bullock(1)
10.27 Lease for Real Property dated May 20, 1992, between Aero-Tech
Investments and Ribozyme Pharmaceuticals(1)
10.28 Non-Disturbance and Attornment Agreement dated March 31, 1995, among
General American Life Insurance Company, Aero-Tech Investments,
Wilderness Place Holdings L.L.C. and Ribozyme Pharmaceuticals(1)
10.29 Master Lease Agreement dated September 2, 1992, between Ribozyme
Pharmaceuticals and LINC Scientific Leasing(1)
10.30 Loan and Security Agreement dated February 28, 1994, between Ribozyme
Pharmaceuticals and Silicon Valley Bank(1)
10.31 Loan Modification Agreement dated December 21, 1994, between Ribozyme
Pharmaceuticals and Silicon Valley Bank(1)
10.32 Loan and Security Agreement dated December 29, 1995, between Ribozyme
Pharmaceuticals and Silicon Valley Bank and MMC/GATX Partnership No.
1(1)
10.33 Warrant to Purchase Common Stock dated December 29, 1995, issued to
MMC/GATX Partnership No. 1(1)
10.34 Agreement dated February 29, 1996, between Ribozyme Pharmaceuticals and
Chiron Corporation relating to research and development funding(1)
10.35 Amendments to original Employment Agreements between Ribozyme
Pharmaceuticals and Ralph E. Christoffersen, Lawrence E. Bullock and
Nassim Usman, pursuant to letters dated November 14, 1996, November 22,
1996, and December 15, 1996(3)
10.36 Promissory Note dated June 4, 1996, between Ribozyme Pharmaceuticals
and Nassim Usman(3)
10.37 Amendment to Lease for Real Property dated March 13, 1997, between
Aero-Tech Investments and Ribozyme Pharmaceuticals(3)
10.38 Employment Agreement dated May 2, 1996, between Ribozyme
Pharmaceuticals and Nassim Usman(2)
10.39 Collaboration Agreement Regarding Use of Ribozymes to Determine Gene
Function dated May 13, 1996, between Ribozyme Pharmaceuticals and
Chiron Corporation(2)
10.40 Amended and Restated License Agreement dated November 20, 1996, between
Ribozyme Pharmaceuticals, University Research Corporation, University of
Colorado and United States Biochemical Corporation(3)*
</TABLE>
<PAGE>
<TABLE>
<CAPTION>
Number Description
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<C> <S>
10.41 Amended and Restated Sublicense Agreement dated November 20, 1996,
between Ribozyme Pharmaceuticals and United States Biochemical
Corporation(3)*
10.42 Amended and Restated License Agreement dated November 20, 1996, between
Ribozyme Pharmaceuticals and Competitive Technologies, Incorporated(3)*
10.43 Memorandum of Understanding dated March 1, 1996, between Ribozyme
Pharmaceuticals and DowElanco(1)
10.44 Stock Subscription Agreement dated September 1996 between Ribozyme
Pharmaceuticals and University of Research Corporation(3)*
10.45 Stock Subscription Agreement dated November 20, 1996, between Ribozyme
Pharmaceuticals and United States Biochemical Corporation(3)*
10.46 Assignment of License and Restated License Agreement dated November 20,
1996, among Ribozyme Pharmaceuticals, United States Biochemical
Corporation and Competitive Technologies(3)*
10.47 Letter Agreement dated May 22, 1996, between Ribozyme Pharmaceuticals
and ALZA Corporation(3)*
10.48 Research and Development Collaboration Agreement dated December 2,
1996, between Ribozyme Pharmaceuticals and Protogene Laboratories(3)*
10.49 License Agreement dated February 14, 1997, between Ribozyme
Pharmaceuticals and IntelliGene, Ltd.(3)*
10.50 Subscription Agreement dated April 17, 1995, between Ribozyme
Pharmaceuticals and Parke-Davis Division of Warner-Lambert Company(1)
10.51 Stock Purchase Agreement dated June 28, 1995, among Ribozyme
Pharmaceuticals and investors(1)
10.52 Agreement dated March 1, 1996, between Ribozyme Pharmaceuticals and
DowElanco Corporation relating to the conversion of preferred stock(1)
10.53 Stock Subscription Agreement dated October 30, 1995, between Ribozyme
Pharmaceuticals and Gewestelijke Investeringsmaatschappij voor
Vlaanderon n.v.(1)
10.54 Research, License, Supply and Royalty Agreement between Schering
Aktiengesellschaft and Ribozyme Pharmaceuticals dated April 9, 1997(4)*
10.55 Purchase Agreement dated April 9, 1997, among Ribozyme Pharmaceuticals,
Schering Berlin Venture Corporation and Schering Aktiengesellschaft(4)*
10.56 Employment Agreement dated February 27, 1997, between Ribozyme
Pharmaceuticals and Alene Holzman(5)
10.57 Employment Agreement dated July 5, 1997, between Ribozyme
Pharmaceuticals and Thomas Rossing(5)
10.58 Executive Bonus Plan dated March 27, 1998(6)
10.59 Research, Collaboration and License Agreement dated May 19, 1998,
between Ribozyme Pharmaceuticals and Roche Bioscience, a division of
Syntex (U.S.A.) Inc.(7)*
10.60 Employment Agreement dated September 8, 1998, between Ribozyme
Pharmaceuticals and Nassim Usman(8)
10.61 Participation Agreement dated August 31, 1998, as amended, and related
documents between Ribozyme Pharmaceuticals and Atugen Biotechnology
GmbH(9)*
10.62 Research Collaboration and License Agreement dated March 17, 1999,
between Ribozyme
Pharmaceuticals and Eli Lilly and Company* (10)
</TABLE>
<PAGE>
<TABLE>
<CAPTION>
Number Description
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<C> <S>
10.63 Stock Purchase Agreement dated April 30, 1999, between Ribozyme
Pharmaceuticals and Eli Lilly and Company (10)
10.64 Employment Agreement dated May 10, 1999 between Ribozyme
Pharmaceuticals and Dr. Wayne Cowens (10)
10.65 Securities Purchase Agreement dated January 7, 2000, among Ribozyme
Pharmaceuticals, Elan International Services, Ltd. and Elan
Corporation, plc (11)
10.66** License Agreement dated January 7, 2000 among Elan Pharmaceutical
Technologies (a division of Elan Corporation, plc), Elan Pharma
International Limited and Medizyme Pharmaceuticals, Ltd. (11)
10.67 Warrant dated January 7, 2000, issued to Elan International Services,
Ltd. to purchase up to 200,000 shares of Ribozyme Pharmaceuticals'
common stock (11)
10.68 Warrant dated January 7, 2000 issued to Elan International Services
Ltd. to purchase up to 300,000 shares of Ribozyme Pharmaceuticals'
common stock (11)
10.69 Convertible Promissory Note dated January 7, 2000, from Ribozyme
Pharmaceuticals to Elan International Services, Ltd. (11)
10.70** Subscription, Joint Development and Operating Agreement dated January
7, 2000, among Ribozyme Pharmaceuticals, Elan Corporation, plc, Elan
Pharma International Limited, Elan International Services, Ltd. and
Medizyme Pharmaceuticals, Ltd. (11)
10.71 Funding Agreement dated January 7, 2000 among Ribozyme
Pharmaceuticals, Elan Pharmaceutical Technologies (a division of Elan
Corporation, plc), Elan Pharma International Limited and Elan
International Services, Ltd. (11)
10.72** License Agreement dated January 7, 2000, among Ribozyme
Pharmaceuticals and Medizyme Pharmaceuticals, Ltd. (11)
10.73 Registration Rights Agreement dated January 7, 2000, between Ribozyme
Pharmaceuticals and Elan International Services, Ltd. (11)
10.74 Registration Rights Agreement dated January 7, 2000 among Ribozyme
Pharmaceuticals, Elan International Services, Ltd. and Medizyme
Pharmaceuticals Ltd. (11)
10.75** Agreement dated January 31, 2000, between Ribozyme Pharmaceuticals and
Avecia Limited (11)
23.1 Consent of Ernst & Young LLP, Independent Auditors
23.2+ Consent of Rothgerber Johnson & Lyons LLP (included in Exhibit 5.1)
24.1+ Power of Attorney (included on the signature page of this Registration
Statement)
</TABLE>
- --------
+ Previously filed.
* Ribozyme Pharmaceuticals has applied for and received confidential treatment
with respect to portions of these exhibits.
** Ribozyme Pharmaceuticals has applied for confidential treatment with respect
to portions of these exhibits.
(1) Documents incorporated by reference herein to certain exhibits to Ribozyme
Pharmaceuticals' Form SB-2 Registration Statement, File No. 333-1908-D.
(2) Documents incorporated by reference herein to certain exhibits to Ribozyme
Pharmaceuticals' Form 10-QSB for the quarter ended June 30, 1996.
(3) Documents incorporated by reference herein to certain exhibits to Ribozyme
Pharmaceuticals' Form 10-KSB for the year ended December 31, 1996.
(4) Documents incorporated by reference herein to certain exhibits to Ribozyme
Pharmaceuticals' Form 8-K dated June 12, 1997.
(5) Documents incorporated by reference herein to certain exhibits to Ribozyme
Pharmaceuticals' Form SB-2 Registration Statement, File No. 333-34981.
(6) Documents incorporated by reference herein to certain exhibits to Ribozyme
Pharmaceuticals' Form 10-K for the year ended December 31, 1997.
<PAGE>
(7) Documents incorporated by reference herein to certain exhibits to Ribozyme
Pharmaceuticals' Form 10-Q/A for the quarter ended June 30, 1998.
(8) Documents incorporated by reference herein to certain exhibits to Ribozyme
Pharmaceuticals' Form 10-Q for the quarter ended September 30, 1998.
(9) Documents incorporated by reference herein to certain exhibits to Ribozyme
Pharmaceuticals' Form 8-K/A dated June 16, 1999.
(10) Documents incorporated by reference herein to certain exhibits to Ribozyme
Pharmaceuticals' Form S-1 Registration Statement, File No. 333-75079
(11) Documents incorporated by reference herein to certain exhibits to Ribozyme
Pharmaceuticals' Form 8-K dated February 8, 2000.
(b) Financial Statement Schedules
All schedules have been omitted because they are not applicable or not
required or the required information is included in the financial statements or
notes thereto.
<PAGE>
EXHIBIT 23.1
CONSENT OF INDEPENDENT AUDITORS
We consent to the reference to our firm under the captions "Summary
Financial Data", "Selected Financial Data" and "Experts" and to the use of our
report dated February 9, 2000, in the Registration Statement on Form S-3 and
related prospectus of Ribozyme Pharmaceuticals, Inc. for the registration of
3,622,500 shares of its common stock.
Denver, Colorado
March 10, 2000
