MILLENNIUM PHARMACEUTICALS INC
S-4, 2000-08-01
PHARMACEUTICAL PREPARATIONS
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<PAGE>
     AS FILED WITH THE SECURITIES AND EXCHANGE COMMISSION ON AUGUST 1, 2000
                                            REGISTRATION STATEMENT NO. 333-
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--------------------------------------------------------------------------------

                                 UNITED STATES
                       SECURITIES AND EXCHANGE COMMISSION

                             WASHINGTON, D.C. 20549
                           --------------------------
                                    FORM S-4
            REGISTRATION STATEMENT UNDER THE SECURITIES ACT OF 1933
                           --------------------------

                        MILLENNIUM PHARMACEUTICALS, INC.
             (Exact name of registrant as specified in its charter)
                           --------------------------

<TABLE>
<S>                                                   <C>
                      DELAWARE                                             04-3177038
            (State or other jurisdiction                      (I.R.S. Employer Identification No.)
         of incorporation or organization)
</TABLE>

                                75 SIDNEY STREET
                         CAMBRIDGE, MASSACHUSETTS 02139
                                  617-679-7000
  (Address, including zip code, and telephone number, including area code, of
                   registrant's principal executive offices)
                           --------------------------

                           JOHN B. DOUGLAS III, ESQ.
                   SENIOR VICE PRESIDENT AND GENERAL COUNSEL
                        MILLENNIUM PHARMACEUTICALS, INC.
                                75 SIDNEY STREET
                         CAMBRIDGE, MASSACHUSETTS 02139
                                  617-679-7000

 (Name, address, including zip code, and telephone number, including area code,
                             of agent for service)
                           --------------------------

                                    Copy to:

                             DAVID E. REDLICK, ESQ.
                               HALE AND DORR LLP
                                60 STATE STREET
                          BOSTON, MASSACHUSETTS 02109
                                  617-526-6000
                           --------------------------

    APPROXIMATE DATE OF COMMENCEMENT OF PROPOSED SALE TO PUBLIC: As soon as
practicable after this Registration Statement becomes effective.

    If the securities being registered on this form are being offered in
connection with the formation of a holding company and there is compliance with
General Instruction G, 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, check the following box. /X/

    If this form is filed to register additional securities for an offering
pursuant to Rule 462(b) 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 this form is a post-effective amendment filed pursuant to Rule 462(d)
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. / /
                           --------------------------

                        CALCULATION OF REGISTRATION FEE

<TABLE>
<CAPTION>
                                                                       PROPOSED MAXIMUM     PROPOSED MAXIMUM
                                                      AMOUNT TO BE      OFFERING PRICE     AGGREGATE OFFERING      AMOUNT OF
TITLE OF EACH CLASS OF SECURITIES TO BE REGISTERED     REGISTERED        PER SHARE(1)           PRICE(1)        REGISTRATION FEE
<S>                                                 <C>               <C>                  <C>                  <C>
Common stock, $0.001 par value per share.......        5,120,000            $97.625           $499,840,000          $131,958
</TABLE>

(1) Estimated solely for the purpose of calculating the amount of the
    registration fee pursuant to Rule 457(c) under the Securities Act of 1933,
    as amended based on the average of the high and low sale prices per share of
    the common stock on the Nasdaq National Market on July 31, 2000.
                           --------------------------

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

--------------------------------------------------------------------------------
--------------------------------------------------------------------------------
<PAGE>
                  SUBJECT TO COMPLETION, DATED AUGUST 1, 2000
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 THESE SECURITIES AND IT IS NOT SOLICITING AN OFFER TO BUY THESE
SECURITIES IN ANY STATE WHERE THE OFFER OR SALE IS NOT PERMITTED.
<PAGE>
                                5,120,000 SHARES

                        MILLENNIUM PHARMACEUTICALS, INC.
                                  Common Stock

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

    This prospectus covers up to 5,120,000 shares of our common stock that we
may offer and issue from time to time to acquire businesses or assets, including
by acquiring the securities of entities holding those businesses or assets. We
may pay for these securities, businesses or assets with common stock, stock
options, cash, notes, assumption of liabilities or other forms of payment. We
may also issue shares of common stock at a later time, upon the exercise or
conversion of other securities that we may issue or assume in connection with
acquisitions, such as options, warrants, convertible notes or other similar
instruments. Anyone to whom we issue shares of our common stock under this
prospectus, and anyone to whom they give the shares, may also use this
prospectus, subject to obtaining our prior written permission, to resell the
shares. We have not fixed a period of time during which the common stock offered
by this prospectus may be offered or sold.

    We and the owners or controlling persons of the securities, businesses or
assets that we acquire will negotiate the price, structure and other terms of
these transactions. We expect that we will value the shares of common stock that
we issue in these acquisitions at prices reasonably related to the market price
of our common stock, either when we tentatively or finally agree to the
particular acquisition, when we complete the acquisition or during some other
negotiated period.

    We do not expect to pay underwriting discounts or commissions with respect
to the shares covered by this prospectus. However, we may pay finders' fees to
anyone who assists us in finding securities, businesses or assets to acquire.
Anyone to whom we pay a finders' fee may be considered an "underwriter" under
the Securities Act of 1933.

    Our common stock is traded on the Nasdaq National Market under the symbol
"MLNM." On July 31, 2000, the last reported per share sale price of our common
stock was $96.25.

    YOU SHOULD SEE THE "RISK FACTORS" BEGINNING ON PAGE 5 FOR A DISCUSSION OF
FACTORS YOU SHOULD CONSIDER BEFORE BUYING SHARES OF OUR COMMON STOCK.

    NEITHER THE SECURITIES AND EXCHANGE COMMISSION NOR ANY STATE SECURITIES
COMMISSION HAS APPROVED OR DISAPPROVED OF THESE SECURITIES OR PASSED UPON THE
ACCURACY OR ADEQUACY OF THIS PROSPECTUS. ANY REPRESENTATION TO THE CONTRARY IS A
CRIMINAL OFFENSE.

                      Prospectus dated             , 2000
<PAGE>
                               TABLE OF CONTENTS

<TABLE>
<CAPTION>
                                                                PAGE
                                                              --------
<S>                                                           <C>
INCORPORATION OF CERTAIN DOCUMENTS BY REFERENCE.............      1
WHERE YOU CAN FIND MORE INFORMATION.........................      2
ABOUT THIS PROSPECTUS.......................................      3
MILLENNIUM PHARMACEUTICALS, INC.............................      3
RISK FACTORS................................................      5
SPECIAL NOTE REGARDING FORWARD-LOOKING INFORMATION..........     13
USE OF PROCEEDS.............................................     14
SELLING STOCKHOLDERS........................................     14
SELECTED FINANCIAL DATA.....................................     15
VALIDITY OF COMMON STOCK....................................     16
EXPERTS.....................................................     16
</TABLE>

                                       i
<PAGE>
                INCORPORATION OF CERTAIN DOCUMENTS BY REFERENCE

    The SEC allows us to "incorporate" into this prospectus information that we
file with the SEC in other documents. This means that we can disclose important
information to you by referring to other documents that contain that
information. Any information that we incorporate by reference is considered part
of this prospectus. The documents and reports that we list below are
incorporated by reference into this prospectus. In addition, all documents and
reports which we file pursuant to Section 13(a), 13(c), 14 or 15(d) of the
Exchange Act after the date of this prospectus are also incorporated by
reference in this prospectus as of the respective filing dates of those
documents and reports. Statements contained in documents that we file with the
SEC and that are incorporated by reference in this prospectus automatically
update and supersede information contained in this prospectus, including
information in previously filed documents or reports that have been incorporated
by reference in this prospectus, to the extent the new information differs from
or is inconsistent with the old information.

    We have filed the following documents with the SEC. These documents are
incorporated herein by reference as of their respective dates of filing:

    (1) Our Annual Report on Form 10-K for the year ended December 31, 1999;

    (2) Our Current Report on Form 8-K/A filed with the SEC on January 6, 2000;

    (3) Our Current Report on Form 8-K filed with the SEC on January 6, 2000;

    (4) Our Current Report on Form 8-K filed with the SEC on January 11, 2000;

    (5) Our Current Report on Form 8-K filed with the SEC on January 19, 2000;

    (6) Our Current Report on Form 8-K/A filed with the SEC on January 27, 2000;

    (7) Our Current Report on Form 8-K filed with the SEC on February 9, 2000;

    (8) Our Current Report on Form 8-K filed with the SEC on April 13, 2000;

    (9) Our Current Report on Form 8-K filed with the SEC on April 25, 2000;

    (10) Our Current Report on Form 8-K filed with the SEC on June 30, 2000;

    (11) Our Quarterly Report on Form 10-Q for the quarter ended March 31, 2000;

    (12) Our Quarterly Report on Form 10-Q for the quarter ended June 30, 2000;

    (13) All our filings pursuant to the Exchange Act after the date of filing
       the initial registration statement and prior to the effectiveness of the
       registration statement; and

    (14) The description of our common stock contained in our registration
       statement on Form 8-A filed with the SEC on April 26, 1996, including any
       amendments or reports filed for the purpose of updating that description.

    You may request, orally or in writing, a copy of these documents, which will
be provided to you at no cost, by contacting:

           Investor Relations
           Millennium Pharmaceuticals, Inc.
           75 Sidney Street
           Cambridge, MA 02139
           Telephone: (617) 679-7000

                                       1
<PAGE>
    IN ORDER TO OBTAIN TIMELY DELIVERY, YOU MUST REQUEST THIS INFORMATION NO
LATER THAN FIVE BUSINESS DAYS BEFORE THE DATE ON WHICH YOU MUST MAKE YOUR
INVESTMENT DECISION.

    You should rely only on the information that we provide in this prospectus,
including information incorporated by reference as described above, or any
supplement that we have referred you to. We have not authorized anyone else to
provide you with different information. You should not assume that the
information in this prospectus or any prospectus supplement is accurate as of
any date other than the date on the front of those documents or that any
document incorporated by reference is accurate as of any date other than its
filing date. You should not consider this prospectus to be an offer or
solicitation relating to our common stock in any jurisdiction in which such an
offer or solicitation relating to our common stock is not authorized.
Furthermore, you should not consider this prospectus to be an offer or
solicitation relating to our common stock if the person making the offer or
solicitation is not qualified to do so, or if it is unlawful for you to receive
such an offer or solicitation.

                      WHERE YOU CAN FIND MORE INFORMATION

    We file reports, proxy statements and other documents with the Securities
and Exchange Commission. You may read and copy any document we file with the SEC
at the public reference facilities the SEC maintains at:

           Room 1024, Judiciary Plaza
           450 Fifth Street, N.W.
           Washington, D.C. 20549

    and at the SEC's Regional Offices located at:

           Northwestern Atrium Center
           Suite 1400
           500 West Madison Street
           Chicago, Illinois 60661

    and

           Seven World Trade Center
           13th Floor

           New York, New York 10048

and you may also obtain copies of such material by mail from the Public
Reference Section of the SEC at:

           450 Fifth Street, N.W.
           Washington, D.C. 20549

at prescribed rates. Please call the SEC at 1-800-SEC-0330 for further
information on the public reference rooms.

    The SEC also maintains a web site on the world wide web, the address of
which is http://www.sec.gov. That site also contains our annual, quarterly and
special reports, proxy statements, information statements and other information.

    This prospectus is part of a registration statement that we filed with the
SEC. The registration statement contains more information than this prospectus
regarding us and our common stock, including certain exhibits and schedules. You
can obtain a copy of the registration statement from the SEC at any address
listed above or from the SEC's Internet site.

                                       2
<PAGE>
                             ABOUT THIS PROSPECTUS

    This prospectus is part of a registration statement that we filed with the
Securities and Exchange Commission which will allow us to issue, from time to
time, up to 5,120,000 shares of our common stock in connection with acquisitions
of other businesses or assets, including acquisitions of the securities of
entities holding these businesses or assets. Each time we issue common stock
under the registration statement we will provide a prospectus supplement that
will contain information about the terms of the specific transaction to which
the prospectus supplement relates. We may also add, update or change the
information that is contained in this prospectus in the prospectus supplement.
You should read both this prospectus and any prospectus supplement together with
additional information described under the heading "Where You Can Find More
Information."

    In addition to the shares of common stock that we are offering by this
prospectus, we may offer other consideration, including stock options, cash,
notes or other evidences of debt, assumption of liabilities or a combination of
these types of consideration, as part of the transactions in which we issue
these shares of common stock. In addition, we may lease property from, and enter
into management, employment, consulting and noncompetition agreements with, the
former owners and key executive personnel of the businesses we acquire.

    We and the owners or controlling persons of the assets, businesses or
securities to be acquired will negotiate the price, structure and other terms of
the transactions that involve the issuance of the shares of our common stock
covered by this prospectus. The factors that we may take into account in
negotiating these acquisitions may include:

    - the quality and reputation of the business to be acquired and its
      management;

    - the strategic market position of the business to be acquired;

    - the proprietary assets, earning power, cash flow and growth potential of
      the business to be acquired; and

    - the market value of the common stock of the business to be acquired, when
      relevant.

    In an effort to maintain an orderly market in our common stock, we may
negotiate agreements with persons receiving our common stock covered by this
prospectus that will limit the number of shares that these persons may sell
during specified intervals. These agreements may contain more restrictive
limitations on sales than those imposed in connection with sales under
applicable exemptions from the registration requirements of the Securities Act.
Moreover, the persons who are parties to these agreements may not otherwise be
subject to these Securities Act requirements. We anticipate that, in general,
these negotiated agreements will be of limited duration and will permit the
recipients of common stock issued in connection with acquisitions to sell up to
a specified number of shares per business day or days.

                        MILLENNIUM PHARMACEUTICALS, INC.

    Our goal is to become the biopharmaceutical company of the future by
building on our broad scientific and technological capabilities and methods,
which we call our "technology platform," to develop breakthrough drugs and
predictive medicine products and services. Predictive medicine involves
identifying information that enables healthcare professionals to make better
informed decisions about drug treatment and other aspects of patient care.

    We use many of the same elements of our technology platform throughout our
business, from the discovery of disease-related genes, to the development of
drugs to specifically address these diseases, to the management of patients
affected by these diseases. As a result, we speak of our technological approach
as being applicable from "gene to patient." We continually seek to expand our
technology

                                       3
<PAGE>
platform in an effort to increase the speed of drug discovery and development
and improve the resulting drugs.

    We have entered into research, development and commercialization
arrangements, which we call "strategic alliances," with major pharmaceutical and
biotechnology companies relating to a broad range of therapeutic and predictive
medicine products and services. These alliances provide us with the opportunity
to receive royalties and profit sharing, if we and our alliance partners are
successful in developing and commercializing products. In addition, these
alliances provide substantial funding for our research and development and the
continued enhancement of our technology platform.

    We were incorporated in Delaware in 1993. Our principal executive offices
are located at 75 Sidney Street, Cambridge, MA 02139 and our telephone number is
(617) 679-7000. Our world wide web address is www.mlnm.com. We have not
incorporated by reference into this prospectus the information on our website
and, therefore, the information in our website should not be considered to be a
part of this document. Our web site address is included in this document as an
inactive textual reference only.

    The Millennium Pharmaceuticals name and logo and the names of products and
services offered by Millennium Pharmaceuticals are trademarks, registered
trademarks, service marks or registered service marks of Millennium
Pharmaceuticals. Unless the context otherwise requires, the terms "Millennium,"
"we," "us" and "our" refer to Millennium Pharmaceuticals, Inc. and its
subsidiaries.

                                       4
<PAGE>
                                  RISK FACTORS

    IF YOU PURCHASE SHARES OF OUR COMMON STOCK, YOU WILL TAKE ON FINANCIAL RISK.
IN DECIDING WHETHER TO INVEST, YOU SHOULD CAREFULLY CONSIDER THE FOLLOWING
FACTORS, THE INFORMATION CONTAINED IN THIS PROSPECTUS AND THE ADDITIONAL
INFORMATION IN OUR OTHER REPORTS ON FILE WITH THE SECURITIES AND EXCHANGE
COMMISSION AND IN OTHER DOCUMENTS WE INCORPORATE BY REFERENCE IN THIS
PROSPECTUS.

REGULATORY RISKS

WE HAVE NOT YET RECEIVED MARKETING APPROVAL FOR ANY PRODUCT OR SERVICE RESULTING
FROM OUR DEVELOPMENT EFFORTS AND MAY NOT BE ABLE TO OBTAIN ANY SUCH APPROVAL

    We have completed development of only one product candidate,
CAMPATH-Registered Trademark- monoclonal antibody, which we developed in our
partnership with Ilex Oncology, Inc. This partnership only recently applied to
the U.S. Food and Drug Administration for approval to market this product. It is
possible that the FDA will not grant this marketing approval. As of July 31,
2000, we and our alliance partners were conducting clinical trials of six
product candidates resulting from our research and development programs,
including clinical trials of CAMPATH-Registered Trademark- monoclonal antibody,
and preclinical testing of approximately ten product candidates resulting from
these programs.

    All of the products that we are developing will require additional research
and development, extensive preclinical studies and clinical trials and
regulatory approval prior to any commercial sales. This process is lengthy,
often taking a number of years, and expensive. In some cases, the length of time
that it takes for us to achieve various regulatory approval milestones affects
the payments that we are eligible to receive under our strategic alliance
agreements.

    We may need to successfully address a number of technological challenges in
order to complete development of our products. Moreover, these products may not
be effective in treating any disease or may prove to have undesirable or
unintended side effects, toxicities or other characteristics that may preclude
our obtaining regulatory approval or prevent or limit commercial use.

WE HAVE ONLY LIMITED EXPERIENCE IN REGULATORY AFFAIRS, AND SOME OF OUR PRODUCTS
MAY BE BASED ON NEW TECHNOLOGIES; THESE FACTORS MAY AFFECT OUR ABILITY OR THE
TIME WE REQUIRE TO OBTAIN NECESSARY REGULATORY APPROVALS

    We have only limited experience in filing and prosecuting applications
necessary to gain regulatory approvals which may affect our ability to obtain
these approvals. Moreover, certain of the products that are likely to result
from our research and development programs may be based on new technologies and
new therapeutic approaches that have not been extensively tested in humans. The
regulatory requirements governing these types of products may be more rigorous
than for conventional products. As a result, we may experience a longer
regulatory process in connection with any products that we develop based on
these new technologies or new therapeutic approaches.

RISKS RELATING TO OUR INDUSTRY, BUSINESS AND STRATEGY

BECAUSE THE GENOMICS INDUSTRY IS NEW, IT IS POSSIBLE THAT THE DISCOVERIES AND
TECHNOLOGY ON WHICH THIS INDUSTRY IS BASED WILL NOT RESULT IN COMMERCIAL
PRODUCTS OR SERVICES

    The genomics industry is new and evolving rapidly. We focus our genomics
research primarily on diseases that may be linked to several or many genes
working in combination. Both we and the general scientific and medical
communities have only a limited understanding relating to the role of genes and
their products in these diseases. To date, we have not commercialized any
products or services, and we may not be successful in doing so in the future. In
addition, relatively few products based on gene discoveries have been developed
and commercialized by others. Rapid technological development by us

                                       5
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or others may result in compounds, products or processes becoming obsolete
before we recover our development expenses.

    OUR PLAN TO GROW THROUGH ACQUISITIONS OF OTHER COMPANIES WILL NOT BE
SUCCESSFUL IF WE ARE UNABLE TO INTEGRATE ACQUIRED COMPANIES WITH OUR OTHER
OPERATIONS OR IF THE TECHNOLOGY OR PERSONNEL OF ACQUIRED COMPANIES DO NOT MEET
OUR EXPECTATIONS

    We completed our merger with LeukoSite, Inc. on December 22, 1999. In
addition, on July 27, 2000, we acquired Cambridge Discovery Chemistry Limited, a
subsidiary of Oxford Molecular Group plc. We may not be able to successfully
integrate or profitably manage these businesses. In addition, the combination of
our business with these businesses may not achieve revenues, net income or loss
levels, efficiencies or synergies that justify the merger. The combined company
may experience slower rates of growth as compared to the historical rates of
growth of Millennium and these businesses independently. We plan to make
additional acquisitions in the future, which will entail similar risks.

COMPETITION FOR SCIENTIFIC AND MANAGERIAL PERSONNEL IN OUR INDUSTRY IS INTENSE;
WE WILL NOT BE ABLE TO SUSTAIN OUR OPERATIONS AND GROW IF WE ARE NOT ABLE TO
ATTRACT AND RETAIN KEY PERSONNEL

    Our success substantially depends on the ability, experience and performance
of our senior management and other key personnel. If we lose one or more of the
members of our senior management or other key employees, our business and
operating results could be seriously harmed.

    In addition, our future success will depend heavily on our ability to
continue to hire, train, retain and motivate additional skilled managerial and
scientific personnel. The pool of personnel with the skills that we require is
limited. Competition to hire from this limited pool is intense.

    The stock options held by LeukoSite employees became fully vested upon the
closing of our acquisition of LeukoSite. This acceleration may adversely affect
our ability to retain former LeukoSite employees.

WE FACE SUBSTANTIAL COMPETITION, WHICH MAY RESULT IN OTHERS DISCOVERING,
DEVELOPING OR COMMERCIALIZING PRODUCTS AND SERVICES BEFORE OR MORE SUCCESSFULLY
THAN WE DO

    The fields of genomics, biotechnology and pharmaceuticals are highly
competitive. Many of our competitors are substantially larger than we are and
have substantially greater capital resources, research and development staffs
and facilities than we have. Furthermore, many of our competitors are more
experienced than we are in drug discovery, development and commercialization,
obtaining regulatory approvals and product manufacturing and marketing. As a
result, our competitors may identify genes associated with diseases or discover,
develop and commercialize products or services based on such genes before we do.
In addition, our competitors may discover, develop and commercialize products or
services which render non-competitive or obsolete the products or services that
we or our strategic alliance partners are seeking to develop and commercialize.

WE MAY NOT BE ABLE TO OBTAIN BIOLOGICAL MATERIAL, INCLUDING HUMAN AND ANIMAL DNA
SAMPLES, REQUIRED FOR OUR GENETIC STUDIES, WHICH COULD DELAY OR IMPEDE OUR DRUG
DISCOVERY EFFORTS

    Our gene identification strategy includes genetic studies of families and
populations prone to particular diseases. These studies require the collection
of large numbers of DNA samples from affected individuals, their families and
other suitable populations as well as animal models. The availability of DNA
samples and other biological material is important to our ability to discover
the genes responsible for human diseases through human genetic approaches and
other studies. Competition for these resources is intense. Access to suitable
populations, materials and samples could be limited by forces beyond our
control, including governmental actions. Some of our competitors may

                                       6
<PAGE>
have obtained access to significantly more family and population resources and
biological materials than we have obtained. As a result, we may not be able to
obtain access to DNA samples necessary to support our human gene discovery
programs.

RISKS RELATING TO OUR FINANCIAL RESULTS AND STRUCTURE AND NEED FOR FINANCING

WE HAVE INCURRED SUBSTANTIAL LOSSES, WE EXPECT TO CONTINUE TO INCUR LOSSES AND
WE WILL NOT BE SUCCESSFUL UNLESS WE REVERSE THIS TREND

    We have incurred losses in four of the last six years, including the year
ended December 31, 1999. We expect to continue to incur substantial operating
losses in future periods. To date, substantially all of our revenues have
resulted from payments from strategic alliance partners. We have not received
any revenues from the sale of products or clinical or diagnostic services.

    We expect to increase our spending significantly as we continue to expand
our infrastructure, research and development programs and commercialization
activities. As a result, we will need to generate significant revenues to pay
these costs and achieve profitability. We cannot be certain whether or when we
will become profitable because of the significant uncertainties with respect to
our ability to generate revenues from the sale of products and services and from
existing and potential future strategic alliances.

OUR SUBSTANTIAL INDEBTEDNESS MAY ADVERSELY AFFECT OUR CASH FLOW AND OPERATIONS
AND BE DIFFICULT FOR US TO REPAY, WHICH COULD ADVERSELY AFFECT THE VALUE OF YOUR
INVESTMENT IN US

    We have substantial amounts of outstanding indebtedness, primarily our 5.50%
convertible subordinated notes due January 15, 2007. We also may obtain
additional long term debt and working capital lines of credit. As a result of
this indebtedness, we have substantial principal and interest payment
obligations. There is the possibility that we may be unable to generate cash
sufficient to pay the principal of, interest on and other amounts due in respect
of our indebtedness when due.

    Our substantial leverage could have significant negative consequences,
including:

    - increasing our vulnerability to general adverse economic and industry
      conditions.

    - limiting our ability to obtain additional financing;

    - requiring the dedication of a substantial portion of our cash from
      operations to service our indebtedness, thereby reducing the amount of our
      cash available for other purposes, including capital expenditures;

    - limiting our flexibility in planning for, or reacting to, changes in our
      business and the industry in which we compete; and

    - placing us at a possible competitive disadvantage vis-a-vis less leveraged
      competitors and competitors that have better access to capital resources.

WE MAY NEED ADDITIONAL FINANCING, WHICH MAY BE DIFFICULT TO OBTAIN; OUR FAILURE
TO OBTAIN NECESSARY FINANCING OR DOING SO ON UNATTRACTIVE TERMS COULD AVERSELY
AFFECT OUR DISCOVERY AND DEVELOPMENT PROGRAMS AND OTHER OPERATIONS

    We will require substantial funds to conduct research and development,
including preclinical testing and clinical trials of our potential products,
meet our obligations to our strategic alliance partners, manufacture and market
any products and services that are approved for commercial sale and meet our
debt service obligations. Additional financing may not be available when we need
it or may not be available on terms that are favorable to us.

                                       7
<PAGE>
    If we are unable to obtain adequate funding on a timely basis, we may be
required to significantly curtail one or more of our discovery or development
programs. We could be required to seek funds through arrangements with
collaborative partners or others that may require us to relinquish rights to
certain of our technologies, product candidates or products which we would
otherwise pursue on our own.

RISKS RELATING TO STRATEGIC ALLIANCE PARTNERS

WE DEPEND SIGNIFICANTLY ON OUR STRATEGIC ALLIANCE PARTNERS TO DEVELOP AND
COMMERCIALIZE PRODUCTS AND SERVICES BASED ON OUR WORK; OUR BUSINESS MAY SUFFER
IF ANY OF OUR STRATEGIC ALLIANCE PARTNERS BREACHES THEIR AGREEMENT OR FAILS TO
SUPPORT OR TERMINATES THEIR ALLIANCE WITH US

    We conduct most of our discovery and development activities through
strategic alliances. The success of these programs depends heavily on the
efforts and activities of our strategic alliance partners. Each of our alliance
partners has significant discretion in determining the efforts and resources
that they will apply to the alliance. Our existing and any future alliances may
not be scientifically or commercially successful.

    The risks that we face in connection with these alliances include:

    - All of our strategic alliance agreements are subject to termination under
      various circumstances, including in many cases on short notice without
      cause.

    - In our strategic alliance agreements, we generally agree not to conduct
      specified types of research and development in the field that is the
      subject of the alliance. These agreements may have the effect of limiting
      the areas of research and development we may pursue, either alone or in
      collaboration with third parties.

    - Our alliance partners may develop and commercialize, either alone or with
      others, products and services that are similar to or competitive with the
      products and services that are the subject of the alliance with us.

    - Our alliance partners may change the focus of their development and
      commercialization efforts. Pharmaceutical and biotechnology companies
      historically have re-evaluated their priorities following mergers and
      consolidations, which have been common in recent years in these
      industries.

    - We will rely on our alliance partners to manufacture most products covered
      by our alliances. For example, Becton Dickinson has the sole right to
      manufacture our Melastatin-TM- gene detection product.

WE MAY NOT BE SUCCESSFUL IN ESTABLISHING ADDITIONAL STRATEGIC ALLIANCES, WHICH
COULD ADVERSELY AFFECT OUR ABILITY TO DEVELOP AND COMMERCIALIZE PRODUCTS

    An important element of our business strategy is entering into strategic
alliances for the development and commercialization of products and services
based on our discoveries. We face significant competition in seeking appropriate
alliance partners. Moreover, these alliance arrangements are complex to
negotiate and time-consuming to document. We may not be successful in our
efforts to establish additional strategic alliances or other alternative
arrangements. The terms of any additional strategic alliances or other
arrangements that we establish may not be favorable to us. Moreover, such
strategic alliances or other arrangements may not be successful.

                                       8
<PAGE>
RISKS RELATING TO INTELLECTUAL PROPERTY

IF WE ARE UNABLE TO OBTAIN PATENT PROTECTION FOR OUR DISCOVERIES, THE VALUE OF
OUR TECHNOLOGY AND PRODUCTS WILL BE ADVERSELY AFFECTED; IF WE INFRINGE PATENT OR
OTHER INTELLECTUAL PROPERTY RIGHTS OF THIRD PARTIES, WE MAY NOT BE ABLE TO
DEVELOP AND COMMERCIALIZE OUR PRODUCTS AND SERVICES OR THE COST OF DOING SO MAY
INCREASE

    Our patent positions, and those of other pharmaceutical and biotechnology
companies, are generally uncertain and involve complex legal, scientific and
factual questions.

    Our ability to develop and commercialize products and services depends in
significant part on our ability to:

    - Obtain patents;

    - Obtain licenses to the proprietary rights of others on commercially
      reasonable terms;

    - Operate without infringing upon the proprietary rights of others;

    - Prevent others from infringing on our proprietary rights; and

    - Protect trade secrets.

THERE IS SIGNIFICANT UNCERTAINTY ABOUT THE VALIDITY AND PERMISSIBLE SCOPE OF
GENOMICS PATENTS IN OUR INDUSTRY, WHICH MAY MAKE IT DIFFICULT FOR US TO OBTAIN
PATENT PROTECTION FOR OUR DISCOVERIES

    The validity and permissible scope of patent claims in the pharmaceutical
and biotechnology fields, including the genomics field, involve important
unresolved legal principles and are the subject of public policy debate in the
United States and abroad. For example, there is significant uncertainty both in
the United States and abroad regarding the patentability of gene sequences in
the absence of functional data and the scope of patent protection available for
full-length genes and partial gene sequences. Moreover, certain groups have made
certain gene sequences available in publicly accessible databases. These and
other disclosures may adversely affect our ability to obtain patent protection
for gene sequences claimed by us in patent applications that we file subsequent
to such disclosures. There is also some uncertainty as to whether human clinical
data will be required for issuance of patents for human therapeutics. If such
data are required, our ability to obtain patent protection could be delayed or
otherwise adversely affected.

THIRD PARTIES MAY OWN OR CONTROL PATENTS OR PATENT APPLICATIONS AND REQUIRE US
TO SEEK LICENSES, WHICH COULD INCREASE OUR DEVELOPMENT AND COMMERCIALIZATION
COSTS, OR PREVENT US FROM DEVELOPING OR MARKETING PRODUCT OR SERVICE CANDIDATES

    We may not have rights under some patents or patent applications related to
our proposed products, processes or services. Third parties may own or control
these patents and patent applications in the United States and abroad.
Therefore, in some cases, such as those described below, to develop,
manufacture, sell or import certain of our proposed products, processes or
services, we or our alliance partners may choose to seek, or be required to
seek, licenses under third-party patents issued in the United States and abroad
or those which might issue from United States and foreign patent applications.
In such event, we would be required to pay license fees or royalties or both to
the licensor. If licenses are not available to us on acceptable terms, we or our
alliance partners may not be able to develop, manufacture, sell or import these
products, processes or services.

    With respect to our product candidate LDP-01, we are aware of third-party
patents and patent applications which relate to certain anti-CD18 antibodies and
their use in various methods of treatment including methods of reperfusion
therapy and methods of treating focal ischemic stroke. In addition, our LDP-01,
LDP-02, and CAMPATH-Registered Trademark- product candidates are humanized
monoclonal antibodies. We

                                       9
<PAGE>
are aware of third-party patents and patent applications which relate to certain
humanized or modified antibodies, products useful for making humanized or
modified antibodies, and processes for making and using humanized or modified
antibodies. We are also aware of third-party patents and patent applications
relating to certain manufacturing processes, products thereof and materials
useful in such processes.

    Our product candidates LDP-977, LDP-341, and LDP-519 are all small molecule
drug candidates. With respect to LDP-341, we are aware of third-party patents or
patent applications which relate to either intermediates or synthetic processes
used in the synthesis of these compounds. Additionally, for the use of LDP-341
and LDP-519 in the treatment of infarctions we are aware of the existence of a
potentially interfering patent application filed by one of our former
consultants.

WE MAY BECOME INVOLVED IN EXPENSIVE PATENT LITIGATION OR OTHER PROCEEDINGS,
WHICH COULD RESULT IN OUR INCURRING SUBSTANTIAL COSTS AND EXPENSES OR
SUBSTANTIAL LIABILITY FOR DAMAGES OR REQUIRE US TO STOP OUR DEVELOPMENT AND
COMMERCIALIZATION EFFORTS

    There has been substantial litigation and other proceedings regarding the
patent and other intellectual property rights in the pharmaceutical and
biotechnology industries. We may become a party to patent litigation or other
proceedings regarding intellectual property rights. For example, we believe that
we hold patent applications that cover genes that are also claimed in patent
applications filed by others. Interference proceedings before the United States
Patent and Trademark Office may be necessary to establish which party was the
first to invent these genes.

    The cost to us of any patent litigation or other proceeding, even if
resolved in our favor, could be substantial. Some of our competitors may be able
to sustain the cost of such litigation or proceedings more effectively than we
can because of their substantially greater financial resources. If a patent
litigation or other proceeding is resolved against us, we or our alliance
partners may be enjoined from developing, manufacturing, selling or importing
our products, processes or services without a license from the other party and
we may be held liable for significant damages. We may not be able to obtain any
required license on commercially acceptable terms or at all.

    Uncertainties resulting from the initiation and continuation of patent
litigation or other proceedings could have a material adverse effect on our
ability to compete in the marketplace. Patent litigation and other proceedings
may also absorb significant management time.

RISKS RELATING TO PRODUCT MANUFACTURING, MARKETING AND SALES

BECAUSE MANY OF THE PRODUCTS AND SERVICES THAT WE DEVELOP WILL BE BASED ON NEW
TECHNOLOGIES AND THERAPEUTIC APPROACHES, THE MARKET MAY NOT BE RECEPTIVE TO
THESE PRODUCTS AND SERVICES UPON THEIR INTRODUCTION

    The commercial success of our products and services that are approved for
marketing will depend upon their acceptance by the medical community and
third-party payors as clinically useful, cost effective and safe. Many of the
products and services that we are developing are based upon new technologies or
therapeutic approaches. As a result, it may be more difficult for us to achieve
market acceptance of our products and services, particularly the first products
and services that we introduce to the market based on new technologies and
therapeutic approaches.

BECAUSE WE HAVE NO SALES, MARKETING OR DISTRIBUTION EXPERIENCE AND CAPABILITIES,
WE WILL BE DEPENDENT ON THIRD PARTIES TO SUCCESSFULLY PERFORM THESE FUNCTIONS OR
WILL BE REQUIRED TO INCUR SIGNIFICANT COSTS AND DEVOTE SIGNIFICANT EFFORTS TO
DEVELOP THESE CAPABILITIES

    We have no sales, marketing or distribution experience and capabilities. We
plan to rely significantly on sales, marketing and distribution arrangements
with our strategic alliance partners and

                                       10
<PAGE>
other third parties for the products and services that we are developing. For
example, our partnership that holds CAMPATH-Registered Trademark- monoclonal
antibody will rely solely upon Schering AG and its U.S. affiliate, Berlex
Laboratories, for the marketing, distribution and sale of the
CAMPATH-Registered Trademark- product throughout the world other than the Far
East. If in the future we determine to perform sales, marketing and distribution
functions ourselves, we would face a number of additional risks, including the
need to recruit experienced marketing and sales personnel.

BECAUSE WE HAVE LIMITED MANUFACTURING CAPABILITIES, WE WILL BE DEPENDENT ON
THIRD-PARTY MANUFACTURERS TO MANUFACTURE PRODUCTS FOR US OR WILL BE REQUIRED TO
INCUR SIGNIFICANT COSTS AND DEVOTE SIGNIFICANT EFFORTS TO ESTABLISH OUR OWN
MANUFACTURING FACILITIES AND CAPABILITIES

    We have limited manufacturing experience and no commercial scale
manufacturing capabilities. In order to continue to develop products and
services, apply for regulatory approvals and, ultimately, commercialize any
products and services, we will need to develop, contract for or otherwise
arrange for the necessary manufacturing capabilities.

    We currently rely upon third parties to produce material for preclinical
testing purposes and expect to continue to do so in the future. We also expect
to rely upon other third parties, including our strategic alliance partners, to
produce materials required for clinical trials and for the commercial production
of certain of our products if we succeed in obtaining necessary regulatory
approvals. Our partnership with ILEX Oncology relies on Boehringer Ingleheim as
the sole source manufacturer of CAMPATH-Registered Trademark- monoclonal
antibody.

    There are a limited number of manufacturers that operate under the FDA's
good manufacturing practices regulations capable of manufacturing for us. As a
result, we have experienced some difficulty finding manufacturers for our
products with adequate capacity for our anticipated future needs. If we are
unable to arrange for third-party manufacturing of our products, or to do so on
commercially reasonable terms, we may not be able to complete development of our
products or market them.

    Reliance on third-party manufacturers entails risks to which we would not be
subject if we manufactured products ourselves, including reliance on the third
party for regulatory compliance and quality assurance, the possibility of breach
of the manufacturing agreement by the third party because of factors beyond our
control and the possibility of termination or nonrenewal of the agreement by the
third party, based on its own business priorities, at a time that is costly or
inconvenient for us.

    We may in the future determine to manufacture certain of our products in our
own manufacturing facilities. We will require substantial additional funds and
need to recruit qualified personnel in order to build or lease and operate any
manufacturing facilities.

IF WE FAIL TO OBTAIN AN ADEQUATE LEVEL OF REIMBURSEMENT FOR OUR FUTURE PRODUCTS
OR SERVICES BY THIRD-PARTY PAYORS, THERE MAY BE NO COMMERCIALLY VIABLE MARKETS
FOR OUR PRODUCTS OR SERVICES

    The availability and levels of reimbursement by governmental and other
third-party payors affects the market for any pharmaceutical product or
healthcare service. These third-party payors continually attempt to contain or
reduce the costs of healthcare by challenging the prices charged for medical
products and services. In certain foreign countries, particularly the countries
of the European Union, the pricing of prescription pharmaceuticals is subject to
governmental control. We may not be able to sell our products and services
profitably if reimbursement is unavailable or limited in scope or amount.

    In both the United States and certain foreign jurisdictions, there have been
a number of legislative and regulatory proposals to change the healthcare
system. Further proposals are likely. The potential for adoption of these
proposals affects or will affect our ability to raise capital, obtain additional
collaborative partners and market our products.

                                       11
<PAGE>
    If we or our alliance partners obtain marketing approvals for our products
and services, we expect to experience pricing pressure due to the trend toward
managed health care, the increasing influence of health maintenance
organizations and additional legislative proposals.

ETHICAL, LEGAL AND SOCIAL ISSUES RELATED TO GENETIC TESTING MAY CAUSE OUR
DIAGNOSTIC PRODUCTS TO BE REJECTED BY CUSTOMERS OR PROHIBITED OR CURTAILED BY
GOVERNMENTAL AUTHORITIES

    Diagnostic tests that evaluate genetic predisposition to disease raise
issues regarding the use and confidentiality of the information provided by such
tests. Insurance carriers and employers might discriminate on the basis of such
information, resulting in a significant barrier to the acceptance of such tests
by customers. This type of discrimination could cause governmental authorities
to prohibit or limit the use of such tests.

                                       12
<PAGE>
               SPECIAL NOTE REGARDING FORWARD-LOOKING INFORMATION

    This prospectus and the documents incorporated by reference in this
prospectus contain "forward-looking statements" within the meaning of
Section 27A of the Securities Act and Section 21E of the Exchange Act that
involve risks and uncertainties, such as statements concerning:

    - our growth and future operating results;

    - the discovery and development of products;

    - developments in our markets and strategic focus;

    - new products;

    - potential acquisitions and our integration of acquired businesses,
      products and technologies;

    - our strategic alliances;

    - our intellectual property;

    - our manufacturing, marketing, sales and distribution capabilities; and

    - future economic, business and regulatory conditions.

    We may, in some cases, use words such as "project," "believe," "anticipate,"
"plan," "expect," "estimate," "intend," "should," "would," "could" or "may," or
other words that convey uncertainty of future events or outcomes to identify
these forward-looking statements. There are a number of important factors that
could cause actual results to differ materially from the results anticipated by
these forward-looking statements. These important factors include those that we
discuss under the caption "Risk Factors" and in the documents that we
incorporate herein by reference. You should read these factors and the other
cautionary statements made in this prospectus and in the documents we
incorporate by reference as being applicable to all related forward-looking
statements wherever they appear in this prospectus and in the documents
incorporated by reference.

                                       13
<PAGE>
                                USE OF PROCEEDS

    Other than the businesses, assets or securities that we acquire, we will not
receive proceeds from acquisitions in connection with which we issue shares of
our common stock pursuant to this prospectus.

                              SELLING STOCKHOLDERS

    We have also prepared this prospectus, as we may amend or supplement it if
appropriate, for use by persons, and their pledgees, donees, transferees or
other successors in interest, who receive shares of our common stock in
acquisitions covered by this prospectus. We refer to these persons as selling
stockholders. We have not authorized any selling stockholder to use this
prospectus to reoffer any shares without obtaining our prior written consent. We
may condition our consent on our request of the selling stockholders that they
not offer or sell more than a specified number of shares and that they only do
so following the filing of any required supplements or amendments to this
prospectus. We will not receive any proceeds from sales by selling stockholders.

    The selling stockholders will act independently of us in making decisions
with respect to the timing, manner and size of each sale. The selling
stockholders may make these sales at prices and under terms then prevailing in,
or at prices related to, the then current market price of our common stock. The
selling stockholders may use broker-dealers to effect these transactions.
Broker-dealers or agents may receive commissions, discounts or concessions from
the selling stockholders in amounts to be negotiated prior to the sale.

    In offering shares covered by this prospectus, the selling stockholders, and
any broker-dealers and any other participating broker-dealers who execute sales
for the selling stockholders, may be deemed to be "underwriters" within the
meaning of the Securities Act in connection with these sales. Any profits that
the selling stockholders realize and the compensation they pay to any
broker-dealer may be deemed to be underwriting discounts and commissions.

    We will advise any selling stockholder that the anti-manipulation rules of
Regulation M under the Exchange Act may apply to sales of shares in the market
and to the activities of the selling stockholders and their affiliates. In
addition, we will make copies of this prospectus available to the selling
stockholders for the purpose of satisfying the prospectus delivery requirements
of the Securities Act. The selling stockholders may indemnify any broker-dealer
that participates in transactions involving the sale of the shares against
certain liabilities, including liabilities arising under the Securities Act.

    If required under the Securities Act, we will file a supplemental prospectus
disclosing the name of any selling stockholder, the name of any broker-dealers
involved in the sale, the number of shares involved, the price at which such
shares are to be sold, the commissions paid or discounts or concessions allowed,
and other facts material to the transaction.

    Selling stockholders may also offer shares of stock covered by this
prospectus by means of prospectuses under other registration statements or
pursuant to exemptions from the registration requirements of the Securities Act,
including sales which meet the requirements of Rule 144 or Rule 145(d) under the
Securities Act.

    We may agree to pay certain costs and expenses incurred in connection with
the registration of the shares of common stock offered pursuant to this
prospectus. However, in all cases the selling stockholders will be responsible
for all selling commissions, transfer taxes and related charges in connection
with the offer and sale of such shares.

                                       14
<PAGE>
                            SELECTED FINANCIAL DATA

    In the table below, we provide you with our summary historical financial
data. We have prepared this information using our consolidated financial
statements for the five years ended December 31, 1999 and the six-month periods
ended June 30, 2000 and 1999. The financial statements for the five fiscal years
ended December 31, 1999 have been audited by Ernst & Young LLP, independent
auditors. The financial statements for the six-month periods ended June 30, 2000
and 1999 have not been audited.

    When you read this summary historical financial data, it is important that
you read along with it the historical financial statements and related notes in
our annual and quarterly reports filed with the SEC, as well as the section of
our annual and quarterly reports titled "Management's Discussion and Analysis of
Financial Condition and Results of Operations."

<TABLE>
<CAPTION>
                                                                                                       SIX MONTHS
                                                        YEAR ENDED DECEMBER 31,                      ENDED JUNE 30,
                                        -------------------------------------------------------   ---------------------
                                          1995       1996       1997        1998        1999        1999        2000
                                        --------   --------   ---------   ---------   ---------   ---------   ---------
                                                           (IN THOUSANDS, EXCEPT PER SHARE AMOUNTS)
<S>                                     <C>        <C>        <C>         <C>         <C>         <C>         <C>
CONSOLIDATED STATEMENTS OF OPERATIONS
  DATA:
Revenue under strategic alliances.....  $22,880    $ 31,764   $  89,933   $ 133,682   $ 183,679   $  88,265   $  93,646
Costs and expenses:
  Research and development............   17,838      34,803      74,828     114,190     159,877      74,917     122,111
  General and administrative..........    3,292       7,973      16,517      24,419      32,896      15,628      21,880
  Acquired in-process R&D.............       --          --      83,800          --     350,503          --          --
  Amortization of intangible assets...       --          --       2,397       2,702       3,816       1,351      24,131
                                        -------    --------   ---------   ---------   ---------   ---------   ---------
                                         21,130      42,776     177,542     141,311     547,092      91,896     168,122
                                        -------    --------   ---------   ---------   ---------   ---------   ---------
Income (loss) from operations.........    1,750     (11,012)    (87,609)     (7,629)   (363,413)     (3,631)    (74,476)
Interest income (expense), net........     (466)      2,244       2,977       3,788       9,473       4,420       7,126
Equity in operations of joint
  venture.............................       --          --          --          --          --          --      (1,400)
Minority interest.....................       --          --       3,410      14,179       1,980       2,287         (63)
                                        -------    --------   ---------   ---------   ---------   ---------   ---------
Net Income (loss).....................    1,284      (8,768)    (81,222)     10,338    (351,960)      3,076     (68,813)
Deemed preferred stock dividend.......       --          --          --          --     (27,944)         --     (45,668)
Net income (loss) attributable to
  common stockholders.................  $ 1,284    $ (8,768)  $ (81,222)  $  10,338   $(379,904)  $   3,076   $(114,481)
                                        =======    ========   =========   =========   =========   =========   =========
Basic net income (loss) per share (pro
  forma in 1995 and 1996).............  $  0.05    $  (0.20)  $   (1.43)  $    0.17   $   (5.23)  $    0.04   $   (1.25)
                                        =======    ========   =========   =========   =========   =========   =========
Shares used in computing basic net
  income (loss) per share.............   27,704      43,394      56,646      60,638      72,706      71,140      91,332
                                        =======    ========   =========   =========   =========   =========   =========
Diluted net income (loss) per share
  (pro forma in 1995 and 1996)........  $  0.04    $  (0.20)  $   (1.43)  $    0.16   $   (5.23)  $    0.04   $   (1.25)
                                        =======    ========   =========   =========   =========   =========   =========
Shares used in computing diluted net
  income (loss) per share.............   35,708      43,394      56,646      63,016      72,706      76,376      91,332
                                        =======    ========   =========   =========   =========   =========   =========
</TABLE>

                                       15
<PAGE>

<TABLE>
<CAPTION>
                                                               DECEMBER 31,                             JUNE 30,
                                           -----------------------------------------------------   -------------------
                                             1995       1996       1997       1998       1999        1999       2000
                                           --------   --------   --------   --------   ---------   --------   --------
                                                                         (IN THOUSANDS)
<S>                                        <C>        <C>        <C>        <C>        <C>         <C>        <C>
CONSOLIDATED BALANCE SHEET DATA:
Cash, cash equivalents and marketable
  securities.............................  $17,847    $ 63,848   $ 96,557   $190,964   $ 261,716   $215,912   $644,750
Working capital..........................   10,498      60,273     85,571    178,395     227,347    198,290    597,042
Total assets.............................   25,105      87,744    144,513    257,954     541,625    302,741    938,350
Long-term debt, net of current portion...    1,467          --         --         --          --         --    400,000
Capital lease obligations, net of current
  portion................................    2,499       9,308     19,809     24,827      27,488     25,466     28,053
Stockholders' equity.....................   13,096      66,639     91,755    206,362     439,406    223,375    430,491
</TABLE>

                            VALIDITY OF COMMON STOCK

    The validity of the common stock offered hereby will be passed upon for us
by Hale and Dorr LLP, Boston, Massachusetts.

                                    EXPERTS

    The consolidated financial statements of Millennium Pharmaceuticals, Inc.
appearing in our Annual Report (Form 10-K) for the year ended December 31, 1999,
have been audited by Ernst & Young LLP, independent auditors, as set forth in
their report thereon included therein and incorporated herein by reference. The
information under the caption "Selected Financial Data" for each of the five
years in the period ended December 31, 1999, included elsewhere herein, have
been derived from consolidated financial statements audited by Ernst &
Young LLP, as set forth in their report appearing elsewhere herein. Such
financial statements and selected financial data have been incorporated herein
by reference and included herein, respectively, in reliance upon such reports
given on the authority of such firm as experts in accounting and auditing.

    The consolidated financial statements of LeukoSite, Inc. as of December 31,
1997 and 1998 and for each of the three years in the period ended December 31,
1998 and the financial statements of L&I Partners, L.P. as of December 31, 1997
and 1998 and for the period from inception through December 31, 1997, the year
ended December 31, 1998 and the period from inception through December 31, 1998
incorporated by reference in this prospectus and elsewhere in the Registration
Statement have been audited by Arthur Andersen LLP, independent public
accountants, as indicated in their reports with respect thereto, and are
included herein in reliance upon the authority of said firm as experts in giving
said reports.

    The financial statements of CytoMed, Inc. as of December 31, 1998 and 1997
and for each of the three years in the period ended December 31, 1998
incorporated in this Prospectus by reference to the Millennium Pharmaceuticals
Form 8-K/A dated January 6, 2000, have been so incorporated in reliance on the
report of PricewaterhouseCoopers LLP, independent accountants, given on the
authority of said firm as experts in auditing and accounting.

                                       16
<PAGE>
                                    PART II
                     INFORMATION NOT REQUIRED IN PROSPECTUS

ITEM 20. INDEMNIFICATION OF DIRECTORS AND OFFICERS.

    Article Nine of the Registrant's Amended and Restated Certificate of
Incorporation (the "Restated Certificate of Incorporation") provides that no
director of the Registrant shall be personally liable for any monetary damages
for any breach of fiduciary duty as a director, except to the extent that the
Delaware General Corporation Law prohibits the elimination or limitation of
liability of directors for breach of fiduciary duty.

    Article Nine of the Restated Certificate of Incorporation provides that a
director or officer of the Registrant (a) shall be indemnified by the Registrant
against all expenses (including attorneys' fees), judgments, fines and amounts
paid in settlement incurred in connection with any litigation or other legal
proceeding (other than an action by or in the right of the Registrant) brought
against him by virtue of his position as a director or officer of the Registrant
if he acted in good faith and in a manner he reasonably believed to be in, or
not opposed to, the best interests of the Registrant, and, with respect to any
criminal action or proceeding, had no reasonable cause to believe his conduct
was unlawful and (b) shall be indemnified by the Registrant against all expenses
(including attorneys' fees) and amounts paid in settlement incurred in
connection with any action by or in the right of the Registrant brought against
him by virtue of his position as a director or officer of the Registrant if he
acted in good faith and in a manner he reasonably believed to be in, or not
opposed to, the best interests of the Registrant, except that no indemnification
shall be made with respect to any matter as to which such person shall have been
adjudged to be liable to the Registrant, unless a court determines that, despite
such adjudication but in view of all of the circumstances, he is entitled to
indemnification of such expenses. Notwithstanding the foregoing, to the extent
that a director or officer has been successful, on the merits or otherwise,
including, without limitation, the dismissal of an action without prejudice, he
is required to be indemnified by the Registrant against all expenses (including
attorneys' fees) incurred in connection therewith. Expenses shall be advanced to
a Director or officer at his request, provided that he undertakes to repay the
amount advanced if it is ultimately determined that he is not entitled to
indemnification for such expenses.

    Indemnification is required to be made unless the Registrant determines that
the applicable standard of conduct required for indemnification has not been
met. In the event of a determination by the Registrant that the director or
officer did not meet the applicable standard of conduct required for
indemnification, or if the Registrant fails to make an indemnification payment
within 60 days after such payment is claimed by such person, such person is
permitted to petition the court to make an independent determination as to
whether such person is entitled to indemnification. As a condition precedent to
the right of indemnification, the director or officer must give the Registrant
notice of the action for which indemnity is sought and the Registrant has the
right to participate in such action or assume the defense thereof.

    Section 145 of the General Corporation Law of Delaware provides that a
corporation has the power to indemnify a director, officer, employee or agent of
the corporation and certain other persons serving at the request of the
corporation in related capacities against amounts paid and expenses incurred in
connection with an action or proceeding to which he is or is threatened to be
made a party by reason of such position, if such person shall have acted in good
faith and in a manner he reasonably believed to be in or not opposed to the best
interests of the corporation, and, in any criminal proceeding, if such person
had no reasonable cause to believe his conduct was unlawful; provided that, in
the case of actions brought by or in the right of the corporation, no
indemnification shall be made with respect to any matter as to which such person
shall have been adjudged to be liable to the corporation unless and only to the
extent that the adjudicating court determines that such indemnification is
proper under the circumstances.

                                      II-1
<PAGE>
    The Registrant has purchased directors' and officers' liability insurance
which would indemnify its directors and officers against damages arising out of
certain kinds of claims which might be made against them based on their
negligent acts or omissions while acting in their capacity as such.

ITEM 21. EXHIBITS

<TABLE>
<CAPTION>
EXHIBIT
NUMBER                                          DESCRIPTION
-------                 ------------------------------------------------------------
<C>                     <S>
         4.1*           Amended and Restated Certificate of Incorporation of the
                        Registrant, as amended
         4.2*           Amended and Restated By-Laws of the Registrant, as amended
         4.3**          Specimen stock certificate representing common stock, $0.001
                        par value per share, of Registrant
         5.1            Opinion of Hale and Dorr LLP
        23.1            Consent of Ernst & Young LLP
        23.2            Consent of Arthur Andersen LLP
        23.3            Consent of PricewaterhouseCoopers LLP
        23.4            Consent of Hale and Dorr LLP, included in Exhibit 5.1 filed
                        herewith
        24.1            Power of Attorney (See page II-5 of this Registration
                        Statement)
</TABLE>

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

  * Incorporated by reference to the Registrant's Quarterly Report on Form 10-Q
    filed with the SEC on June 20, 1996, the Registrant's Current Report on
    Form 8-K filed with the SEC on April 13, 2000 and the Registrant's Quarterly
    Report on Form 10-Q filed with the SEC on May 2, 2000.

 ** Incorporated by reference to the Registrant's Registration Statement on
    Form S-1 (File No. 333-02490).

ITEM 22. 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;

        (ii) To reflect in the prospectus any facts or events arising after the
    effective date of this 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 this
    Registration Statement. Notwithstanding the foregoing, any increase or
    decrease in the 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 Commission
    pursuant to Rule 424(b) if, in the aggregate, the changes in volume and
    price represent no more than 20 percent change in the maximum aggregate
    offering price set forth in the "Calculation of Registration Fee" table in
    the effective Registration Statement; and

       (iii) To include any material information with respect to the plan of
    distribution not previously disclosed in this Registration Statement or any
    material change to such information in this Registration Statement;

PROVIDED, HOWEVER, that paragraphs (1)(i) and (1)(ii) do not apply if the
information required to be included in a post-effective amendment by those
paragraphs is contained in periodic reports filed with or furnished to the
Commission by the Registrant pursuant to Section 13 or Section 15(d) of the
Exchange Act, that are incorporated by reference in this Registration Statement.

                                      II-2
<PAGE>
    (2) That, for the purposes of determining any liability under the Securities
Act, each post-effective amendment that contains a form of prospectus shall be
deemed to be a new registration statement relating to the securities offered
therein, and the offering of such securities at the time shall be deemed to be
the initial BONA FIDE offering thereof.

    (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.

    The Registrant hereby undertakes that, for purposes of determining any
liability under the Securities Act, each filing of the Registrant's annual
report pursuant to Section 13(a) or 15(d) of the Exchange Act (and, where
applicable, each filing of an employee benefit plan's annual report pursuant to
Section 15(d) of the Exchange Act) that is incorporated by reference in this
Registration Statement shall be deemed to be a new registration statement
relating to the securities offered therein and the offering of such securities
at the time shall be deemed to be the initial BONA FIDE offering thereof.

    The undersigned Registrant hereby undertakes as follows: that, prior to any
public reoffering of the securities registered hereunder through use of a
prospectus which is a part of this Registration Statement, by any person or
party who is deemed to be an underwriter within the meaning of Rule 145(c), the
issuer undertakes that such reoffering prospectus will contain the information
called for by the applicable registration form with respect to reofferings by
persons who may be deemed underwriters, in addition to the information called
for by the other items of the applicable form.

    The Registrant undertakes that every prospectus (i) that is filed pursuant
to the immediately preceding paragraph, or (ii) that purports to meet the
requirements of Section 10(a)(3) of the Act and is used in connection with an
offering of securities subject to Rule 415, will be filed as a part of an
amendment to the Registration Statement and will not be used until such
amendment is effective, and that, for purposes of determining any liability
under the Securities Act, 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.

    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 indemnification provisions described herein, or
otherwise, the Registrant has been informed that in the opinion of the
Securities and Exchange Commission such indemnification is against public policy
as expressed in the Securities Act and is, therefore, unenforceable. In the
event that a claim for indemnification against such liabilities (other than the
payment by the 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.

    The undersigned registrant hereby undertakes to respond to requests for
information that is incorporated by reference into the prospectus pursuant to
Item 4, 10(b), 11, or 13 of this form, within one business day of receipt of
such request, and to send the incorporated documents by first class mail or
other equally prompt means. This includes information contained in documents
filed subsequent to the effective date of the registration statement through the
date of responding to the request.

    The undersigned registrant hereby undertakes to supply by means of a
post-effective amendment all information concerning a transaction, and the
company being acquired involved therein, that was not the subject of and
included in the registration statement when it became effective.

                                      II-3
<PAGE>
                                 EXHIBIT INDEX

<TABLE>
<CAPTION>
EXHIBIT
NUMBER                                          DESCRIPTION
-------                 ------------------------------------------------------------
<C>                     <S>
         4.1*           Amended and Restated Certificate of Incorporation of the
                        Registrant, as amended
         4.2*           Amended and Restated By-Laws of the Registrant, as amended
         4.3**          Specimen stock certificate representing common stock, $0.001
                        par value per share, of Registrant
         5.1            Opinion of Hale and Dorr LLP
        23.1            Consent of Ernst & Young LLP
        23.2            Consent of Arthur Andersen LLP
        23.3            Consent of PricewaterhouseCoopers LLP
        23.4            Consent of Hale and Dorr LLP, included in Exhibit 5.1 filed
                        herewith
        24.1            Power of Attorney (See page II-5 of this Registration
                        Statement)
</TABLE>

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

  * Incorporated by reference to the Registrant's Quarterly Report on Form 10-Q
    filed with the SEC on June 20, 1996, the Registrant's Current Report on
    Form 8-K filed with the SEC on April 13, 2000 and the Registrant's Quarterly
    Report on Form 10-Q filed with the SEC on May 2, 2000.

 ** Incorporated by reference to the Registrant's Registration Statement on
    Form S-1 (File No. 333-02490).

                                      II-4
<PAGE>
                                   SIGNATURES

    Pursuant to the requirements of the Securities Act of 1933, as amended, the
Registrant has duly caused this Registration Statement to be signed on its
behalf by the undersigned, thereunto duly authorized, in the City of Cambridge,
Commonwealth of Massachusetts, on July 31, 2000.

<TABLE>
<S>                                                    <C>  <C>
                                                       MILLENNIUM PHARMACEUTICALS, INC.

                                                       By:  /s/ JOHN B. DOUGLAS III
                                                            -----------------------------------------
                                                            John B. Douglas III
                                                            Senior Vice President,
                                                            General Counsel and Secretary
</TABLE>

                        SIGNATURES AND POWER OF ATTORNEY

    We, the undersigned officers and directors of Millennium Pharmaceuticals,
hereby severally constitute and appoint Mark J. Levin, Steven H. Holtzman, Kevin
P. Starr and John B. Douglas III and each of them singly, our true and lawful
attorneys with full power to any of them, and to each of them singly, to sign
for us and in our names in the capacities indicated below the Registration
Statement on Form S-4 filed herewith and any and all pre-effective and
post-effective amendments to said Registration Statement and any subsequent
registration statement filed pursuant to Rule 462(b) under the Securities Act of
1933, as amended, and to file the same with all exhibits thereto, and the other
documents in connection therewith, with the Securities and Exchange Commission,
and generally to do all such things in our name and behalf in our capacities as
officers and directors to enable Millennium Pharmaceuticals to comply with the
provisions of the Securities Act of 1933, as amended, and all requirements of
the Securities and Exchange Commission, hereby ratifying and confirming our
signatures as they may be signed by our said attorneys, or any of them, to said
Registration Statement and any and all amendments thereto.

                                      II-5
<PAGE>
    Pursuant to the requirements of the Securities Act of 1933, as amended, this
Registration Statement has been signed by the following persons in the
capacities and on the dates indicated.

<TABLE>
<CAPTION>
                      SIGNATURE                                      TITLE                   DATE
                      ---------                                      -----                   ----
<C>                                                        <S>                        <C>
                  /s/ MARK J. LEVIN
     -------------------------------------------           Chairman of the Board of     July 31, 2000
                    Mark J. Levin                            Directors, Chief
                                                             Executive Officer and
                                                             President (Principal
                                                             Executive Officer)

                 /s/ KEVIN P. STARR
     -------------------------------------------           Chief Financial Officer      July 31, 2000
                   Kevin P. Starr                            (Principal Financial
                                                             and Accounting Officer)

               /s/ JOSHUA BOGER, PH.D.
     -------------------------------------------           Director                     July 31, 2000
                 Joshua Boger, Ph.D.

              /s/ EUGENE CORDES, PH.D.
     -------------------------------------------           Director                     July 31, 2000
                Eugene Cordes, Ph.D.

              /s/ A. GRANT HEIDRICH III
     -------------------------------------------           Director                     July 31, 2000
                A. Grant Heidrich III

           /s/ RAJU S. KUCHERLAPATI, PH.D.
     -------------------------------------------           Director                     July 31, 2000
             Raju S. Kucherlapati, Ph.D.

              /s/ ERIC S. LANDER, PH.D.
     -------------------------------------------           Director                     July 31, 2000
                Eric S. Lander, Ph.D.

                 /s/ NORMAN C. SELBY
     -------------------------------------------           Director                     July 31, 2000
                   Norman C. Selby
</TABLE>

                                      II-6


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