REGENERON PHARMACEUTICALS INC, S-3, 2000-03-06

REGENERON PHARMACEUTICALS INC
S-3, 2000-03-06
PHARMACEUTICAL PREPARATIONS

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<PAGE>

As filed with the Securities and Exchange Commission on March 6, 2000
Registration No. 333-

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

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

FORM S-3
REGISTRATION STATEMENT

UNDER

THE SECURITIES ACT OF 1933

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

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

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

New York 13-3444607
(State or other jurisdiction (I.R.S. Employer
of incorporation or organization) Identification No.)

777 Old Saw Mill River Road
Tarrytown, New York 10591-6707
(914) 347-7000
(Address, including zip code and telephone number,
including area code, of registrant's principal executive offices)

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

Murray A. Goldberg
Chief Financial Officer
Regeneron Pharmaceuticals, Inc.
777 Old Saw Mill River Road
Tarrytown, New York 10591-6707
(914) 347-7000

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

Copies to:

Matthew J. Mallow, Esq. Ji Hoon Hong, Esq.
David J. Goldschmidt, Esq. Shearman & Sterling
Skadden, Arps, Slate, Meagher & Flom LLP 599 Lexington Avenue
Four Times Square New York, New York 10022-6069
New York, New York 10036-6522 (212) 848-4000
(212) 735-3000

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

Approximate date of commencement of proposed sale to the public: As
soon as practicable after this 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, please check the following box. /_/

CALCULATION OF REGISTRATION FEE
<TABLE>
<CAPTION>
====================================================================================================================================
Proposed Proposed
Title of each class of Amount to be maximum offering maximum aggregate Amount of
securities to be registered registered(1) price per unit(2) offering price(2) registration fee(2)
- ------------------------------------------------------------------------------------------------------------------------------------
<S> <C> <C> <C> <C>
Common stock, $0.001 par value (including
the associated rights to purchase Series
A Junior Participating Preferred Stock)(3) 4,600,000 $ 50.40625 $ 231,868,750 $ 60,909.75
====================================================================================================================================
</TABLE>

(1) Includes shares of the common stock of the Registrant which may be sold
pursuant to options granted to the Underwriters from a shareholder of the
Registrant to cover over-allotments.

(2) Estimated solely for the purpose of computing 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 prices reported on the Nasdaq
National Market as of March 2, 2000.

(3) The rights to purchase shares of our Series A Junior Participating Preferred
Stock initially are attached to and trade with the shares of our common
stock being registered hereby. Value attributed to such rights, if any, is
reflected in the market price of our common stock.

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

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 specifically stating that this Registration
Statement shall thereafter become effective in accordance with Section 8(a) of
the Securities Act of such date as the Commission, acting pursuant to said
Section 8(a), may determine.

<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 these securities and it is not soliciting an offer to buy these
securities in any state where the offer or sale is not permitted.

Subject to Completion
Preliminary Prospectus dated March 6, 2000

PROSPECTUS
- ----------
4,000,000 Shares

REGENERON PHARMACEUTICALS, INC.

Common Stock
----------------------

Regeneron is selling 4,000,000 shares.

The shares are quoted on the Nasdaq National Market under the symbol
"REGN." On March 2, 2000, the last sale price of the shares as reported on the
Nasdaq National Market was $50 13/32 per share.

Investing in the common stock involves risks that are described in the
"Risk Factors" section beginning on page 8 of this prospectus.

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

Per Share Total
--------- -----
Public offering price ......................... $ $
Underwriting discount ......................... $ $
Proceeds, before expenses, to Regeneron ....... $ $

The underwriters may also purchase up to an additional 600,000 shares from
a selling shareholder at the public offering price, less the underwriting
discount, within 30 days from the date of this prospectus to cover
over-allotments.

Neither the Securities and Exchange Commission nor any state securities
commission has approved or disapproved of these securities or determined if this
prospectus is truthful or complete. Any representation to the contrary is a
criminal offense.

The shares will be ready for delivery on or about __________, 2000.

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

Merrill Lynch & Co.
Lehman Brothers
J.P. Morgan & Co.
Robertson Stephens

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

The date of this prospectus is , 2000.

<PAGE>

TABLE OF CONTENTS

Page
----

Summary ............................................................3
Risk Factors.........................................................8
Forward-looking Statements..........................................16
Use of Proceeds.....................................................18
Dividend Policy.....................................................18
Capitalization......................................................19
Dilution ...........................................................20
Selected Financial Data.............................................21
Business ...........................................................22
Management..........................................................30
Investment Company Act Considerations...............................34
Description of Capital Stock........................................34
Selling Shareholder.................................................38
Underwriting........................................................39
Legal Matters.......................................................42
Experts ...........................................................42
Where You Can Find More Information.................................42

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

In this prospectus, "Regeneron," "our company," "we," "us" and "our"
refer to Regeneron Pharmaceuticals, Inc. You should rely only on the information
contained or incorporated by reference in this prospectus. We have not, and the
underwriters have not, authorized any other person to provide you with different
information. If anyone provides you with different or inconsistent information,
you should not rely on it. We are not, and the underwriters are not, making an
offer to sell these securities in any jurisdiction where the offer or sale is
not permitted. You should assume that the information appearing in this
prospectus is accurate only as of the date on the front cover of this
prospectus. Our business, financial condition, results of operations and
prospects may have changed since that date.

2
<PAGE>

SUMMARY

The following summary highlights information contained in
other parts of this prospectus or incorporated by reference in this prospectus.
You should read this summary together with the more detailed information
elsewhere in this prospectus and in our financial statements and accompanying
notes and other information incorporated by reference in this prospectus. Unless
otherwise indicated, all information in this prospectus assumes no exercise of
the underwriters' over-allotment option, gives no effect to the exercise of
outstanding options to purchase common stock, and assumes all share numbers set
forth in this prospectus are as of February 25, 2000.

Regeneron Pharmaceuticals, Inc.

We are a biopharmaceutical company that discovers, develops and intends
to commercialize therapeutic drugs for the treatment of serious medical
conditions. Expanding from our initial focus on degenerative neurologic
diseases, we have more recently broadened our product pipeline to include drug
candidates for the treatment of obesity, rheumatoid arthritis, cancer,
allergies, asthma, ischemia and other diseases and disorders.

Our ability to discover and develop product candidates for a wide
variety of serious medical conditions results from the leveraging of several
powerful technology platforms, many of which were developed or enhanced by us.
In contrast to basic genomics approaches, which attempt to identify every gene
in a cell or genome, we use Targeted Genomics(TM) and Functionomics(TM)
(functional cloning) technology platforms that are designed to discover
specific genes of therapeutic interest for a particular disease or cell type.
Using these approaches, we have discovered many new families of growth factors
and receptors, most of which are already protected by issued patents and which
have led to several product candidates. In cases in which the natural gene
product is itself not a product candidate, we utilize our Designer Protein
Therapeutics(TM) platform to genetically engineer product candidates with the
desired properties. This technology platform has already produced more than 10
patented proteins, several of which are in preclinical development.

The sophisticated application of all of these technology platforms,
coupled with our biologic expertise in disease modeling, have allowed us to
discover drug candidates that address a wide variety of important medical needs.
Relative to many participants in the biotechnology and genomics industry, we are
well-positioned with three products in ongoing clinical trials and several
product candidates planned to enter clinical trials over the next one to two
years, including:

o AXOKINE(R) second generation ciliary neurotrophic factor: Acts on
the brain region regulating food intake and energy expenditure.
AXOKINE is being developed for the treatment of obesity and
complications of obesity such as Type II diabetes and is
in clinical trial.

o Cytokine Traps: Antagonists for cytokines such as interleukin-1
(called IL-1), interleukin-4 (IL-4), interleukin-13 (IL-13) and
interleukin-6 (IL-6). These cytokines are thought to play a major
role in diseases such as rheumatoid arthritis and other
inflammatory diseases, asthma, allergic disorders and cancer.
Cytokine Traps are potential treatments for these diseases, and at
least one Cytokine Trap is expected to enter clinical trials by
2001.

o VEGF Trap: An antagonist to Vascular Endothelial Growth Factor
(called VEGF), which is required for the growth of blood vessels
that are needed for tumors to grow. VEGF Trap is a potential
treatment for cancer and is expected to enter clinical trial
in 2001.

3
<PAGE>

vessel growth (to provide blood flow in diseased hearts and other
tissues that have lost their original blood supplies), for
blocking blood vessel growth (for the treatment of cancers),
for fixing leaky blood vessels (that cause swelling and edema in
many different diseases such as stroke, diabetic retinopathy and
inflammatory diseases), and for promoting the growth and
mobilization of certain hemopoietic cells such as stem cells and
platelets.

o Brain-derived neurotrophic factor, or BDNF: Promotes survival of
the spinal cord neurons that die in amyotrophic lateral sclerosis
(or ALS, commonly known as Lou Gehrig's Disease) and is in
clinical trial for ALS.

o Neurotrophin-3, or NT-3: Acts on the neurons of the intestinal
tract and is in clinical trial for the treatment of constipating
disorders associated with spinal cord injury and other neurologic
diseases.

We are currently developing AXOKINE and our Cytokine Traps
independently of any corporate partners. We are developing BDNF in partnership
with Amgen Inc. and Sumitomo Pharmaceuticals Company, Ltd., NT-3 in partnership
with Amgen and our VEGF antagonist, Angiopoietins and other product candidates
in partnership with The Procter & Gamble Company. In all our partnerships, we
retain 50% U.S. commercialization rights. We also have numerous academic
collaborations.

Our GMP manufacturing facility in Tarrytown, New York produces
preclinical and clinical supplies of our products and product candidates. At our
GMP manufacturing facility in Rensselaer, New York, we contract manufacture
products for Sumitomo Pharmaceuticals and Merck & Co., Inc. The Company
continues to upgrade and expand its manufacturing facilities as it advances its
products toward commercialization.

We believe that we possess a strong intellectual property position,
including 42 issued U.S. patents and more than 100 pending applications in all
key areas of our research and development, including angiogenesis, bone and
cartilage formation, Cytokine Traps, muscle atrophy and neurological disorders.
We have a policy to file patent applications to protect technology, inventions
and improvements we consider important to the development of our business. We
also rely on trade secrets, know-how and continuing technological innovation to
maintain and enhance our competitive position.

Each member of our senior management team has at least ten years of
experience in the biopharmaceutical industry. In addition, our Board of
Directors consists of noted business and scientific leaders, including the
former Chairman and CEO of Merck and three Nobel Laureates. According to a 1997
survey by the Institute for Scientific Information, our Chief Scientific Officer
was among the top 11 most highly cited scientists and the only non-academic
scientist in the group. We have been very successful in attracting skilled and
experienced personnel in a highly competitive environment. As of December 31,
1999, we had 437 full-time employees, 82 of whom hold a Ph.D. and/or M.D.
degree.

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

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<PAGE>

Selected Products and Programs

Technology Platforms
Used for Discovery and Commercialization
Development Program and Product Targeted Indication Stage Rights
- ----------- ------------------- ------------------- ----- ------

<S> <C> <C> <C> <C>
TARGETED GENOMICS AXOKINE(R)(Second Obesity and Clinical Regeneron
DESIGNER PROTEIN Generation Ciliary complications of
THERAPEUTICS Neurotrophic Factor) obesity such as Type
II diabetes

TARGETED GENOMICS BDNF (Brain-derived Amyotrophic lateral
Neurotrophic Factor) sclerosis (ALS)
Intrathecal (U.S.) Clinical Regeneron and Amgen
Subcutaneous (U.S.) Clinical Regeneron and Amgen
Subcutaneous (Japan) Clinical Sumitomo Pharmaceuticals

TARGETED GENOMICS NT-3 (Neurotrophin-3) Constipating Clinical Regeneron and Amgen
conditions associated
with spinal cord
injury and other
medical conditions

Cytokine Traps
--------------

DESIGNER PROTEIN IL-1 Rheumatoid arthritis Preclinical Regeneron
THERAPEUTICS and other inflammatory
disorders

DESIGNER PROTEIN IL-4 Asthma and allergic Preclinical Regeneron
THERAPEUTICS disorders

DESIGNER PROTEIN IL-4/13 Asthma and allergic Preclinical Regeneron
THERAPEUTICS disorders

DESIGNER PROTEIN IL-2, IL-3, IL-5, Multiple Research Regeneron
THERAPEUTICS IL-6, IL-15, gamma-
interferon, TGFbeta
and others

Angiogenesis Programs
---------------------

DESIGNER PROTEIN VEGF Trap Cancer Preclinical Regeneron and Procter
THERAPEUTICS & Gamble

TARGETED GENOMICS Angiopoietin-1 Ischemia, vascular Preclinical Regeneron and Procter
FUNCTIONOMICS leak and edema, and & Gamble
DESIGNER PROTEIN hemopoiesis
THERAPEUTICS

TARGETED GENOMICS Ephrins, Angiopoietin-2 Cancer, ischemia, Research Regeneron and Procter
FUNCTIONOMICS hemopoiesis & Gamble
DESIGNER PROTEIN
THERAPEUTICS

TARGETED GENOMICS Muscle Diseases and Muscle atrophy and Research Regeneron and Procter
FUNCTIONOMICS Disorders injury & Gamble
-------------------

Bone and Cartilage
------------------

TARGETED GENOMICS RORs Osteoarthritis Research Regeneron and Procter
FUNCTIONOMICS & Gamble

TARGETED GENOMICS DDRs Fibrosis and cirrhosis Research Regeneron and Procter
FUNCTIONOMICS & Gamble

TARGETED GENOMICS G-Protein Coupled Multiple Research Regeneron and Procter
FUNCTIONOMICS Receptors & Gamble
-----------------

</TABLE>

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

We are a New York corporation organized on January 8, 1988. Our
executive offices are at 777 Old Saw Mill River Road, Tarrytown, New York
10591-6707 and our telephone number is (914) 347-7000.

5
<PAGE>

The Offering

<TABLE>
<S> <C>
Common stock offered by Regeneron ................................ 4,000,000 shares

Shares outstanding after the offering:

Common stock................................................... 32,313,345 shares (1)
Class A stock.................................................. 3,579,277 shares
-----------
Total.......................................................... 35,892,622 shares
==========

Use of proceeds................................................... We estimate that our net proceeds
from this offering will be approxi-
mately $191.0 million. We intend to use these
net proceeds for working capital and general
corporate purposes, including research
and development.

Risk factors...................................................... See "Risk Factors" and other infor-
mation included in this prospectus
for a discussion of factors you should
carefully consider before deciding to
invest in shares of our common stock.

Nasdaq National Market symbol..................................... REGN
</TABLE>

The number of shares outstanding after the offering is derived from our records
and excludes options to purchase 5,248,517 shares of our common stock under our
1990 Long-Term Incentive Plan, of which 2,343,366 were exercisable at February
25, 2000.

6
<PAGE>

Summary Selected Financial Data

<TABLE>
<CAPTION>
Year Ended December 31,
--------------------------------------------------------------------------
1999 1998 1997 1996 1995
------------ ------------ ------------ ------------ ----------
Statement of Operations Data: (in thousands, except per share data)

<S> <C> <C> <C> <C> <C>
Revenues

Contract research and development ......... $ 24,539 $ 19,714 $ 17,400 $ 17,303 $ 23,247
Research progress payments ................ - 9,500 5,000 - -
Contract manufacturing .................... 9,960 9,113 4,458 2,451 1,140
Investment income ......................... 5,207 6,866 6,242 4,360 2,997
--------- --------- --------- --------- ---------
39,706 45,193 33,100 24,114 27,384
--------- --------- --------- --------- ---------
Expenses

Research and development .................. 44,940 37,047 27,770 28,269 23,310
Loss in Amgen-Regeneron Partners .......... 4,159 2,484 3,403 14,250 13,805
General and administrative ................ 6,355 5,838 5,765 5,880 5,764
Depreciation and amortization ............. 3,426 3,019 4,389 6,084 5,886
Contract manufacturing .................... 3,612 5,002 2,617 1,115 72
Interest .................................. 284 428 735 940 1,205
Other ..................................... - - - - 850
--------- --------- --------- --------- ---------
62,776 53,818 44,679 56,538 50,892
--------- --------- --------- --------- ---------
Net loss ..................................... ($ 23,070) ($ 8,625) ($ 11,579) ($ 32,424) ($ 23,508)
========= ========= ========= ========= =========
Weighted average number of Class A and
Common shares outstanding, basic and
diluted ................................... 31,308 30,992 28,702 24,464 19,768
========= ======== ======== ======== ========
Net loss per share, basic and diluted ........ ($0.74) ($0.28) ($0.40) ($1.33) ($1.19)
========= ======== ======== ======== ========

<CAPTION>
December 31,
--------------------------------------------------------------------------
1999 1998 1997 1996 1995
------------ ------------ ------------ ------------ ----------
Balance Sheet Data: (in thousands)
<S> <C> <C> <C> <C> <C>
Cash, cash equivalents and marketable
securities ................................ $ 93,599 $ 113,530 $ 128,041 $ 97,028 $ 59,622
Working capital .............................. 59,725 83,499 88,953 72,960 36,254
Total assets ................................. 136,999 156,915 168,380 137,582 93,811
Capital lease obligations and note payable,
long-term portion ......................... 2,731 3,066 3,752 5,148 5,978
Shareholders' equity ......................... 109,532 131,227 138,897 106,931 67,856

</TABLE>

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<PAGE>

RISK FACTORS

You should carefully consider the following risk factors before you
decide to buy our common stock. If any of these risks actually occur, our
business, financial condition, operating results or cash flows could be
materially adversely affected. This could cause the trading price of our common
stock to decline and you may lose part or all of your investment.

Risks Related to our Business, Industry and Strategy

Most drug research and development programs fail.

Only a small minority of all research and development programs
ultimately result in commercially successful drugs. It is not possible to
predict whether any program will succeed until it actually produces a drug that
is commercially marketed for a significant period of time. We are attempting to
develop drugs for human therapeutic use and we cannot assure you that any of our
research and development activities will be successful or that any of our
current or future potential product candidates will be commercialized. The Phase
III trial of BDNF that Amgen-Regeneron Partners conducted during 1995 and 1996
failed to achieve its expected results. We rely on third-party clinical
investigators to conduct our clinical trials. As a result, we may encounter
delays outside of our control.

There are risks involved in expanding our initial focus and broadening our
product pipeline.

Expanding from our initial focus on degenerative neurologic disease and
broadening our product pipeline to include drug candidates for the treatment of
other diseases involves risks. As we expand our focus to broaden our product
pipeline and as our scientific efforts lead us in new directions into conditions
or diseases outside of our areas of experience and expertise, we will require
additional internal expertise or external collaborations in areas in which we
currently do not have substantial resources and personnel. As we develop and
continue to develop drug candidates independently, we will require additional
resources that may be difficult to obtain and we may have to enter into
collaboration arrangements with others. We cannot assure you that we will be
able to acquire the necessary expertise or enter into collaboration agreements
on acceptable terms to develop additional drug candidates.

We have incurred substantial losses and expect to incur losses over the next
several years.

We have not received revenue from the sale of any commercial product
and have incurred losses in each year since inception of operations in 1988. As
of December 31, 1999, we had an accumulated deficit of $200.3 million.

To date, we have received revenues from (1) our licensees and
collaborators for research and development efforts, (2) Merck for contract
manufacturing and (3) investment income. We cannot assure you that these
revenues will continue or to what extent, if any, our expenses incurred in
connection with our work on BDNF or NT-3 or other programs will be reimbursed by
our licensees or collaborators. In the absence of revenues from commercial
product sales or other sources (the amount, timing, nature, or source of which
we cannot predict), our losses will continue as we conduct our research and
development activities. Our activities may expand over time and may require
additional resources and our operating losses may be substantial over at least
the next several years. Our losses may fluctuate from quarter to quarter and
will depend, among other factors, on the timing of certain expenses and on the
progress of our research and development efforts. We do not know if we will ever
have an approved product or achieve significant revenues or profitable
operations. To date, we have not received any revenues from the commercial sale
of products and we do not expect to receive any such revenues for at least
several years.

We have had negative cash flow from operations in each year since our
inception. We expect that the funding requirements for our activities will
remain substantial and could increase significantly if, among other things, our
development or clinical trial programs are successful or our research is
expanded. In addition, we are required to provide capital from time to time to
fund and remain equal partners with Amgen in Amgen-Regeneron Partners. Our
aggregate capital contributions to Amgen-Regeneron Partners from the
partnership's inception in

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<PAGE>

June 1993 through December 31, 1999 was $51.1 million. We expect that our
capital contributions in 2000 will total at least $4.5 million. These
contributions could increase or decrease, depending upon, among other things,
the nature and cost of ongoing and additional BDNF and NT-3 studies that
Amgen-Regeneron Partners may conduct and the outcomes of those studies. In
addition, the amount needed to fund our operations will also depend on other
factors, including the potential future need to expand our professional and
support staff and facilities to support new areas of research and development,
competitive products, the success of our research and development programs, the
status of patent and other intellectual property right developments and the
extent and success of any collaborative research arrangements.

Our success depends upon obtaining FDA and foreign regulatory approval to market
products currently under development.

The safety, effectiveness, testing, manufacture, distribution,
labeling, storage, record-keeping, approval, advertising and promotion of our
product candidates and the research and development activities associated with
them are subject to extensive federal, state and foreign regulation. If we fail
to obtain the necessary approvals or comply with regulatory requirements, or if
any of our approvals are restricted, suspended or revoked, there could be a
material adverse effect on us. Even if we are able to develop drugs and related
therapies that are approved for sale by the FDA or by foreign regulatory
authorities, we cannot assure you that any such drugs or related therapies will
be commercially successful.

The compounds we are developing will require significant additional
time-consuming and costly research and development, including further
preclinical and clinical testing, before we can file an application for
commercial approval. As an initial step in the FDA regulatory approval process,
preclinical studies are typically conducted in animals to identify potential
safety problems. The results of preclinical studies are submitted to the FDA as
a part of Investigation of New Drugs, or the IND, which is filed to comply with
FDA regulations before beginning human clinical studies. For several of our drug
candidates, no reliably predictive animal model exists. As a result, no
indication of efficacy for human beings is available until these product
candidates progress to human clinical trials.

The extensive regulatory approval process required by the FDA and by
comparable agencies in other countries can take many years and requires the
expenditure of substantial resources. This gives larger companies with greater
financial resources a competitive advantage. Data obtained from preclinical and
clinical activities are subject to different interpretations which could delay,
limit, or prevent FDA regulatory approval. We may encounter delays or
rejections based upon changes in FDA policy for drug approval during the period
of development and FDA regulatory review. We may also encounter similar delays
or rejection of applications in foreign countries. We cannot assure you that
even after such time and expenditures, regulatory approval will be obtained for
any compounds we develop. Moreover, even if approval is granted, such approval
may have limitations on the indicated uses for which compounds may be marketed.

Our compounds may prove to have undesirable and unintended toxic side
effects that may interrupt or delay clinical studies and could ultimately
prevent or limit their commercial use. We or the regulatory authorities may
suspend or terminate clinical trials at any time if the people participating in
such trials are believed to be exposed to unacceptable health risks. Even after
we have undertaken additional research and development and preclinical and
clinical testing, we cannot assure you that the FDA or foreign regulatory
agencies will not require additional preclinical or clinical testing before
considering whether to approve the marketing of these compounds. Subsequent
discovery of previously unknown problems with a product or its manufacturer may
result in restrictions on the product or manufacturer, including withdrawal of
the product from the market.

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<PAGE>

We face substantial competition, which may result in others discovering,
developing or commercializing products before or more successfully than we do.

There is substantial competition in the biotechnology and
pharmaceutical industries from pharmaceutical, biotechnology and chemical
companies. Many of our competitors have substantially greater research,
preclinical and clinical product development and manufacturing capabilities and
financial, marketing and human resources than we do. Our smaller competitors may
also be significant if they acquire or discover patentable inventions or form
collaborative arrangements or merge with large pharmaceutical companies. We also
compete with academic institutions, government agencies and other public and
private research organizations in the development of technologies and processes
and, in some instances, compete with others in acquiring technology from such
institutions, agencies and organizations. We cannot assure you that we will be
able to produce approved compounds that have commercial potential and, even if
we achieve product commercialization, that one or more of our competitors may
not achieve product commercialization earlier than we do or patent protection
that dominates or adversely affects our activities.

There is substantial competition in the discovery and development of
treatments for obesity and obesity-related morbidities, including Type II
diabetes, as well as established and cost-effective and emerging prescription
and over-the-counter treatments for these conditions. For example, Amgen and a
number of other pharmaceutical companies are developing leptin and related
molecules. Clinical trials of leptin are currently under way. Many firms and
entities are engaged in research and development in the areas of cytokines,
interleukins, angiogenesis and muscle conditions. Some of these competitors are
currently conducting advanced preclinical and clinical research programs in
these areas. These and other competitors may have established substantial
intellectual property and other competitive advantages. The treatment of
constipating conditions is highly competitive, with a number of companies
providing over-the-counter remedies and other competitors attempting to discover
and develop improved over-the-counter or prescription treatments. Many
pharmaceutical and biotechnology companies are attempting to discover and
develop small-molecule based therapeutics, similar in at least certain respects
to our program with Procter & Gamble. In these and related areas, intellectual
property rights have been sought and certain rights have been granted to
competitors and potential competitors of ours and we may be at a substantial
competitive disadvantage in such areas as a result of, among other things, our
lack of experience, trained personnel and expertise. A number of corporate and
academic competitors are involved in the discovery and development of novel
therapeutics using tyrosine kinase receptors, orphan receptors and compounds
that are the focus of other research or development programs we are now
conducting. These competitors include Amgen, Genentech, as well as many others.

More specifically, our efforts to develop treatments for neurological
diseases and conditions are being conducted in a highly competitive environment.
Even if BDNF or NT-3 is shown to be safe and effective to treat ALS or other
conditions, other companies have developed or are developing drugs for the
treatment of the same or similar conditions, including Rhone-Poulenc Rorer and
Sanofi Pharmaceuticals, Inc. Amgen is a direct competitor of ours in the field
of neurotrophic factors and possibly other fields. Other potential competitors
include Genentech and Cephalon, Inc., which is in a collaboration with Chiron
Corporation. Amgen, Genentech, Cephalon and others have filed patent
applications and obtained issued patents relating to neurotrophic factors, or
have announced that they are actively pursuing preclinical or clinical
development programs in the area of neurotrophic factors. Other companies have
developed or are developing drugs based on technology other than neurotrophic
factors for the treatment of diseases and injuries relating to the nervous
system (including ALS). We are also aware that several pharmaceutical companies
are conducting clinical trials in ALS with drugs that are orally administered.
Our developments relating to treatments for asthma or other inflammatory
conditions, obesity, diabetes and other conditions are subject to a similarly
competitive environment.

If a competitor announces a successful clinical study involving a
product that may be competitive with one of our product candidates or an
approval by a regulatory agency of the marketing of a competitive product,

10
<PAGE>

such announcement may have a material adverse effect on our operations or future
prospects or the price of our common stock.

We also compete with academic institutions, governmental agencies and
other public or private research organizations which continue to conduct
research, seek patent protection and establish collaborative arrangements for
the development and marketing of products that would provide royalties for use
of their technology. These institutions are becoming more active in seeking
patent protection and licensing arrangements to collect royalties for use of the
technology that they have developed. Products developed in this manner may
compete directly with products we develop. We also compete with others in
acquiring technology from such institutions, agencies and organizations.

Our ability to compete will depend on how fast we can develop safe and
effective product candidates, complete clinical testing and approval processes
and supply commercial quantities of the product to the market. Competition among
product candidates approved for sale will also be based on efficacy, safety,
reliability, availability, price, patent position and other factors.

We depend on the collaborative efforts of our academic and corporate partners
for research, development and commercialization of some of our products.

Our strategy for research, development and commercialization of certain
of our products involves entering into various arrangements with academic and
corporate partners and others. As a result, our strategy depends, in part, upon
the success of these outside parties in performing their responsibilities. Our
collaborators may also be our competitors, such as Amgen. We cannot control the
amount and timing of resources that our collaborators devote to performing their
contractual obligations. We cannot assure you that these parties will perform
their obligations as expected or that any revenue will be derived from these
arrangements. If our collaborators breach or terminate their agreement with us
or otherwise fail to conduct their collaborative activities in a timely manner,
the development or commercialization of the product candidate or research
program under such collaborative arrangement may be delayed. If that is the
case, we may be required to undertake unforeseen additional responsibilities or
to devote unforeseen additional funds or other resources to such development or
commercialization, or such development or commercialization could be terminated.
Our agreement with Procter & Gamble has an early termination provision whereby
either party has the right to terminate the agreement at any time after June
2002 by giving the other party one year's notice. The termination or
cancellation of collaborative arrangements could adversely affect our financial
condition, intellectual property position and operations. In addition,
disagreements between collaborators and us could lead to delays in the
collaborative research, development, or commercialization of certain products or
could require or result in formal legal process or arbitration for resolution.
These consequences could be time-consuming and expensive and could have material
adverse effects on us.

Other than our contractual rights under our license agreements, we may
be limited in our ability to convince our licensees to fulfill their
obligations. The failure of such licensees to act in a prompt and effective
manner, or the existence of a dispute between us and our licensees regarding
this or other matters, could have a material adverse effect on our results of
operations and the price of our common stock.

We rely upon scientific, technical and clinical data supplied by
academic and corporate collaborators, licensors, licensees, independent
contractors and others in the evaluation and development of potential
therapeutic compounds. We cannot assure you that there are no errors or
omissions in this data that would materially adversely affect the development
of these compounds.

We may seek additional collaborative arrangements to develop and
commercialize our products in the future. There can be no assurance that we will
be able to negotiate acceptable collaborative arrangements in the future or that
any collaborative arrangements will be successful. In addition, we cannot assure
you that our col-

11
<PAGE>

laborative partners will not pursue alternative technologies or develop
alternative compounds independently or in collaboration with others as a means
of developing treatments for the diseases targeted by their collaborative
programs with us.

Our ability to conduct timely preclinical and clinical research and
development programs, obtain regulatory approval, commercialize our product
candidates, fulfill our contract manufacturing obligations to others will
depend, in part, upon our ability to manufacture our products, either directly
or through third parties, in accordance with FDA and other regulatory
requirements.

If we are unable to manufacture our products, we would be unable to
proceed with or could experience delays in the regulatory process for our
product candidates under development, suffer potential financial and competitive
consequences and experience delays in the commercialization of our products. We
cannot assure you that we will be able to manufacture products successfully or
in a cost effective manner at our facilities. If we are unable to develop our
own manufacturing facilities or to obtain or retain third-party manufacturing on
acceptable terms, we may not be able to conduct certain future preclinical and
clinical testing or to supply commercial quantities of our product candidates.
Our dependence upon third parties for the manufacture of certain of our products
and related therapies may adversely affect our profit margins and our ability to
develop and deliver products on a timely and competitive basis.

In addition, if our manufacturing facilities fail to comply with FDA
and other regulatory requirements, we will be required to suspend manufacturing.
This will have a material adverse effect on our financial condition, results of
operations and cash flow.

Our programs to attempt to discover and develop orally active, small
molecule drugs may require that we obtain new manufacturing capabilities,
facilities, equipment, personnel and expertise, expand our regulatory and
related organizations and enter into agreements with third parties to provide
some or all of the foregoing. We cannot assure you that we will be successful in
any of these efforts, or that the necessary plant, equipment, people, or
expertise will be available to us or, if available, will be available at a cost
that is acceptable to us.

Our products may not achieve commercial success.

The commercial success of any of our products will depend upon their
acceptance by patients, the medical community and third-party payors, our
ability to successfully develop, manufacture and market our products. Among the
factors that we believe will materially affect acceptance of our products are:

o our ability to manufacture these products successfully;

o our sales, marketing and distribution experience;

o the timing of receipt of marketing approvals and the countries in
which those approvals are obtained;

o the safety and efficacy of our products;

o the success of physician education programs;

o the cost of our products in comparison with conventional or
alternative therapeutic products; and

o the availability of government and third-party payor reimbursement
of our products.

As described above, we cannot assure you that we will be able to
manufacture our products successfully. We have no sales, marketing and
distribution experience and may have to rely significantly on sales, marketing
and distribution arrangements with third parties for the products that we are
developing.

The success of our products will depend, in part, upon the extent to
which a consumer will be willing to pay the price or be able to obtain
reimbursement for the cost of these products from government health
administration authorities, private health insurers and other organizations.

12
<PAGE>

Significant uncertainties exist as to the reimbursement status of newly
approved therapeutic products. Medicare generally does not provide reimbursement
for self-administered prescription therapeutic agents. We cannot assure you that
(1) reimbursement in the United States or foreign countries will be available
for any of our products or, (2) if available, there will be no decrease in the
future or (3) that reimbursement amounts will not reduce the demand for or the
price of our products. The unavailability or inadequacy of third-party
reimbursement for our products could have a material adverse effect on us.

Third-party payors are increasingly challenging the prices charged for
medical services and products and the trend towards managed care in the United
States and the growth of organizations such as health maintenance organizations,
which could control or significantly influence the purchase of health care
services and products, as well as legislative proposals to reform health care or
reduce government insurance programs, may result in lower prices for our
products. The cost containment measures that health care providers are
instituting and the effect of any health care reform could affect our ability to
sell our products and may have a material adverse effect on us. We are unable to
forecast what additional legislation or regulation, if any, relating to the
health care industry or third-party coverage and reimbursement may be enacted in
the future or what effect such legislation or regulation would have on our
business.

Risks Related to Intellectual Property

We may not be able to obtain patent protection for our discoveries and we may
infringe patent rights of others.

We believe that patent protection of products or processes that may
result from our research and development efforts, our licensors, licensees or
collaborators is important to the possible commercialization of our product
candidates. We or our licensors or collaborators have filed patent applications
on products and processes relating to AXOKINE, cytokine traps, angiopoietins,
BDNF, NT-3, as well as other technologies and inventions in the United States
and in certain foreign countries. Although we have obtained a number of U.S.
patents, we cannot assure you that any additional patents will be issued or that
any issued patents will provide adequate protection against competitive products
or otherwise be commercially valuable. In addition, patent law relating to the
patentability and scope of claims in the biotechnology field is evolving and our
patent rights are subject to this additional uncertainty. Others will not
independently develop similar products or processes to those developed by us,
duplicate any of our products or processes or, if patents are issued to us,
design around any products and processes covered by our patents. We expect to
continue to file products or processes covered by our patents. However, there
can be no assurance that any such patents will be filed or, if filed, that they
will be issued. Patents issued to or licensed by us may be infringed by the
products or processes of others.

Defense and enforcement of our rights can be expensive and time
consuming, even if the outcome is favorable to us. It is possible that patents
issued to or licensed to us will be successfully challenged, that a court of
competent jurisdiction may find that we are infringing validly issued patents of
third parties, or that we may have to alter our products or processes or pay
licensing fees or cease certain activities to take into account patent rights of
third parties, causing additional unexpected costs and delays which may have a
material adverse effect on us.

If we are not able to keep our trade secrets confidential, our technology and
information may be used by others to compete against us.

In addition to our reliance on patents, we attempt and will continue to
attempt to protect our proprietary products and processes by relying on trade
secret laws and nondisclosure and confidentiality agreements and exclusive
licensing arrangements with our employees and certain other persons who have
access to our proprietary products or processes or have licensing or research
arrangements exclusive to us. Despite these protections,

13
<PAGE>

no assurance can be given that these agreements or arrangements will provide
meaningful protection for our trade secrets in the event of unauthorized use or
disclosure of such information or that others will not independently develop or
obtain access to such products or processes or that our competitive position
will not be adversely affected thereby. No assurance can be given that others
will not independently develop substantially equivalent proprietary information
and techniques or otherwise gain access to our trade secrets or technology or
that we can meaningfully protect our rights to our trade secrets.

We may become involved in expensive patent litigation or other intellectual
property proceedings which could result in liability for damages or stop our
product development and commercialization efforts.

There has been substantial litigation and other proceedings regarding
the complex 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.

Other types of situations in which we may become involved in patent
litigation or other intellectual property proceedings include:

o we may initiate litigation or other proceedings against third
parties to enforce our patent rights;

o we may initiate litigation or other proceedings against third
parties to seek to invalidate the patents held by these third
parties or to obtain a judgment that our products or services do
not infringe the third parties' patents;

o if our competitors file patent applications that claim technology
also claimed by us, we may participate in interference or
opposition proceedings to determine the priority of invention; and

o if third parties initiate litigation claiming that our processes or
products infringe their patent or other intellectual property
rights, we will need to defend against such claims.

The cost to us of any patent litigation or other proceedings, 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 intellectual property proceeding is resolved
unfavorably to us, we may be enjoined from manufacturing or selling our products
and services without a license from the other party and be held liable for
significant damages. We may not be able to obtain any required license on
commercially acceptable terms or not at all.

Uncertainties resulting from the litigation 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.

If we breach any of the agreements under which we license technology from
others, we could lose license rights that are important to our business.

We are a party to technology licenses that are important to our
business and expect to enter into additional licenses in the future. These
licenses impose commercialization, sublicensing, royalty, insurance and other
obligations on us. If we fail to comply with these requirements, the licensor
will have the right to terminate the license.

14
<PAGE>

Risks Relating to Ongoing Operations

Recruiting and retaining qualified scientific and management personnel to
perform research and development work and to commercialize products is critical
to our success.

Although we believe we have been successful in attracting and retaining
skilled and experienced scientific and management personnel, we cannot assure
you that we will be able to continue to attract and retain such personnel on
acceptable terms. The loss of any of our key personnel, in particular (1) our
Chairman, P. Roy Vagelos, M.D., (2) our President and Chief Executive Officer,
Leonard S. Schleifer, M.D., Ph.D. and (3) our Chief Scientific Officer, George
D. Yancopoulos, M.D., Ph.D., may have an adverse effect on us. In addition, our
anticipated growth and expansion into areas requiring additional expertise are
expected to place increased demands on our resources and require the recruitment
of additional management personnel and the development of additional expertise
by existing management personnel. The failure to acquire such services or to
develop such expertise could have a material adverse effect on us.

We could be exposed to significant liability claims if we are unable to obtain
insurance at acceptable costs or otherwise to protect us against potential
product liability claims.

The testing, manufacturing and marketing of human pharmaceutical
products entail significant inherent risks. Their use in clinical trials and
their sale may expose us to liability claims. These claims might be made
directly by consumers or by pharmaceutical companies or others selling the
products, among others. We are insured by health care product liability
insurance policies, including a policy carried by Amgen-Regeneron Partners, the
purpose of which is to cover certain claims that could arise during the clinical
trials of BDNF and NT-3. Such coverage or the amount and scope of any coverage
obtained in the future for these products or any other products, developed with
collaborators or by ourselves may be inadequate to protect Regeneron in the
event of a successful liability claim and we cannot assure you that the amount
of such insurance can be purchased, increased or renewed. We cannot assure you
that we will avoid a significant product liability claim or recall that could
have a material adverse effect on us.

Risks Relating to our Common Stock

Our stock price could be volatile, which could cause you to lose part or all of
your investment.

There has been a history of significant volatility in the market price
of shares of biotechnology companies, including our shares and it is likely that
the market price of our common stock will continue to be highly volatile. In
1998, the bid price for our common stock fluctuated from a low of $5.75 a share
to $11.00 a share. In 1999, the bid price fluctuated from a low of $5.38 per
share to a high of $13.00 per share. From January 1, 2000 to March 2, 2000, the
bid price fluctuated from a low of $11.50 per share to a high of $56.17 per
share. Factors such as fluctuations in our operating results, clinical trial
results, announcements of technological innovations or new commercial
therapeutic products introduced by us or our competitors, governmental
regulation, regulatory delays, litigation, development in patent or other
proprietary rights, public concern as to the safety or other implications of the
drugs sought to be developed by us or the genetic engineering involved in their
production and general market conditions may have a significant effect on the
market price of our common stock.

Our existing shareholders may be able to influence the outcome of corporate
actions.

Holders of Class A Stock (the shareholders who purchased their stock
from us before our initial public offering) are entitled to ten votes per share
and holders of common stock are entitled to one vote per share. Upon completion
of this offering, holders of Class A Stock will hold 10.0% of our outstanding
common stock and 52.7% of the combined voting power of the common stock and
will be in position to elect all of our directors and to effect or prevent
certain corporate transactions which require majority or super majority approval
of the combined classes, including mergers and other business combinations. Upon
the com-

15
<PAGE>

pletion of this offering, our current officers and directors will own 65.0% of
the outstanding shares of Class A Stock and 4.5% of the shares of our common
stock, constituting 10.6% of our outstanding common stock and 36.4% of the
combined voting power of our common stock. In addition, certain of our
collaborators, including Procter & Gamble and Amgen, hold shares of our common
stock. Upon completion of this offering, Procter & Gamble will hold 14.4% of our
outstanding common stock (7.6% of the combined voting power) and Amgen will hold
12.1% of our outstanding common stock (16.8% of the combined voting power) and
10.4% of our outstanding common stock if the underwriters of this offering
exercise their option to purchase from Amgen 600,000 shares of our common stock
to cover over-allotments. In addition, our Restated Certificate of Incorporation
provides for staggered terms for the members of the Board of Directors. A
staggered board, the existence of Class A Stock, blank-checked preferred stock,
our rights plan and certain provisions of the New York Business Corporation Law
may discourage certain types of transactions involving an actual or potential
change of control.

THIS PROSPECTUS CONTAINS FORWARD LOOKING STATEMENTS

The following important factors, among others, in some cases have
affected and in the future could affect, our actual results and could cause our
actual results to differ materially from those expressed in any forward-looking
statements made by, or on behalf of, us:

o Delay, difficulty, or failure of our research and development
programs to produce product candidates that are scientifically or
commercially appropriate for further development by us or others.

o Cancellation or termination of material collaborative or licensing
agreements (including in particular, but not limited to, those with
Procter & Gamble and Amgen) and the resulting loss of research or
other funding could have a material adverse effect on us and our
operations. A change of control of one or more of our material
collaborators or licensees could also have a material adverse
effect on us.

o Delay, difficulty, or failure of a clinical trial of any of our
product candidates. A clinical trial can fail or be delayed as a
result of many causes, including, among others, failure of the
product candidate to demonstrate safety or efficacy, the
development of serious or life-threatening adverse events (side
effects) caused by or connected with exposure to the product
candidate and the failure of clinical investigators, trial monitors
and other consultants, or trial subjects to comply with the trial
plan or protocol.

o In addition to the safety, efficacy, manufacturing and regulatory
hurdles faced by our drug candidates, the administration of
recombinant proteins frequently causes an immune response,
resulting in the creation of antibodies against the therapeutic
protein. The antibodies can have no effect or can totally
neutralize the effectiveness of the protein, or require that higher
doses be used to obtain a therapeutic effect. In some cases, the
antibody can cross react with the patient's own proteins, resulting
in an "auto-immune type" disease. Whether antibodies will be
created can often not be predicted from preclinical experiments and
their appearance is often delayed, so that there can be no
assurance that neutralizing antibodies will not be created at a
later date -- in some cases even after pivotal clinical trials have
been successfully completed. Patients who have been treated with
AXOKINE, BDNF and NT-3 have developed antibodies, though we have no
information that indicates that these antibodies are neutralizing
antibodies.

o Delay, difficulty, or failure in obtaining regulatory approval
(including approval of our facilities for production) for our
products (including vaccine intermediate for Merck), including
delays or difficulties in development because of insufficient
proof of safety or efficacy.

16
<PAGE>

o Increased and irregular costs of development, manufacture,
regulatory approval, sales and marketing associated with the
introduction of products in the late stage of development.

o Competitive or market factors that may cause use of our products to
be limited or otherwise fail to achieve broad acceptance.

o The ability to obtain, maintain and prosecute intellectual property
rights and the cost of acquiring in-process technology and other
intellectual property rights, either by license, collaboration, or
purchase of another entity.

o Difficulties or high costs of obtaining adequate financing to meet
our obligations under our collaboration and licensing agreements
or to fund 50 percent of the cost of developing product candidates
in order to retain 50 percent of the commercialization rights.

o Amount and rate of growth of our general and administrative
expenses and the impact of unusual charges resulting from our
ongoing evaluation of our business strategies and organizational
structure.

o Failure of corporate partners to successfully develop or
commercialize our products or to retain and expand the markets
served by the commercial collaborations; conflicts of interest,
priorities and commercial strategies which may arise between us and
our corporate partners.

o Delays or difficulties in developing and acquiring production
technology and technical and managerial personnel to manufacture
novel biotechnology products in commercial quantities at reasonable
costs and in compliance with applicable quality assurance and
environmental regulations and governmental permitting
requirements.

o Difficulties in obtaining key raw materials and supplies for the
manufacture of our product candidates.

o The costs and other effects of legal and administrative cases and
proceedings (whether civil, such as product- or employment-related,
or environmental, or criminal); settlements and investigations;
developments or assertions by or against us relating to
intellectual property rights and licenses; the issuance and use of
patents and proprietary technology by us and our competitors,
including the possible negative effect on our ability to develop,
manufacture and sell our products in circumstances where we are
unable to obtain licenses to patents which may be required for such
products.

o Underutilization of our existing or new manufacturing facilities or
of any facility expansions, resulting in inefficiencies and higher
costs; start-up costs, inefficiencies, delays and increased
depreciation costs in connection with the start of production in
new plants and expansions.

o Health care reform, including reductions or changes in
reimbursement available for prescription medications or other
reforms.

o The ability to attract and retain key personnel.

For these statements, we claim the protection of the safe harbor for
forward-looking statements contained in Section 21E of the Securities Act. Our
actual results could differ materially from those anticipated in these
forward-looking statements as a result of various factors, including all of the
risks discussed in "Risk Factors" and elsewhere in this prospectus.

17
<PAGE>

USE OF PROCEEDS

We estimate that the net proceeds we will receive from the sale of
4,000,000 shares of our common stock will be approximately $190,994,000 at an
assumed public offering price of $50.41, after deducting underwriting discounts
and commissions and the estimated expenses of this offering. We will not receive
any proceeds from the sale of shares of our common stock by our selling
shareholder if the underwriters exercise their over-allotment option.

We intend to use the net proceeds from this offering for working
capital and general corporate purposes, including basic research, product
development and clinical testing (including our own programs and programs in
collaboration with partners), regulatory filings and compliance,
commercialization expansion of our facilities and operations, including the
acquisition of equipment and furnishings and for other purposes. Proceeds may
also be used to acquire companies, technologies or products that complement our
business. No such transactions are planned or being negotiated as of the date of
this prospectus.

Pending application of the net proceeds as described above, we intend
to invest the net proceeds of this offering primarily in U.S. Government and
other investment grade obligations, interest bearing money market funds and
other financial instruments. See "Investment Company Act Considerations."

DIVIDEND POLICY

We have never paid cash dividends and do not anticipate paying any in
the foreseeable future. In addition, under the terms of certain of our debt
agreements, we are not permitted to declare or pay cash dividends.

18
<PAGE>

CAPITALIZATION

The following table sets forth our capitalization as of December 31,
1999 and as adjusted to give effect to our sale of 4,000,000 shares of our
common stock in this offering, after deducting underwriting discounts and
commissions and estimated expenses of this offering and the application of the
estimated net proceeds. See "Use of Proceeds."

<TABLE>
<CAPTION>
At December 31, 1999
---------------------------------
Actual As Adjusted
------------- ----------------
(in thousands)
<S> <C> <C>
Cash, cash equivalents and marketable securities........................... $93,599 $284,593
======= ========
Capital lease obligations - long-term portion.............................. 1,204 1,204
----- -----
Note payable - long-term portion........................................... 1,527 1,527
----- -----
Shareholders' equity:
Preferred stock, $.01 par value; 30,000,000 shares
authorized; issued and outstanding - none....................... - -
Class A Stock, $.001 par value; 40,000,000 shares
authorized, 3,605,133 shares issued and
outstanding - actual and as adjusted............................ 4 4
Common stock, $.001 par value; 60,000,000 shares
authorized; 27,817,636 shares issued and outstanding - actual;
31,817,636 shares issued and outstanding - as adjusted.......... 28 32
Additional paid-in capital........................................ 310,296 501,286
Accumulated deficit............................................... (200,303) (200,303)
Net unrealized loss on marketable securities...................... (493) (493)
-------- --------
Total shareholders' equity.................................... 109,532 300,526
------- --------
Total capitalization.......................................... $112,263 $303,257
======== ========
</TABLE>

19
<PAGE>

DILUTION

As of December 31, 1999, our net tangible book value before the
offering was $109.5 million or $3.49 per common stock. "Net tangible book value
per share" is determined by dividing our net tangible book value (total assets
less total liabilities) by the number of common stock outstanding. After giving
effect to the sale of the shares of our common stock in this offering and after
deducting underwriting discounts and commissions and the estimated expenses of
this offering, our pro forma net tangible book value as of December 31, 1999
would have been $300.5 million in the aggregate, or $8.48 per common stock. This
represents an immediate increase in net tangible book value of $4.99 per common
stock to existing holders and immediate dilution of $41.93 per common stock to
new investors purchasing shares of common stock in this offering. The following
table illustrates this per share dilution:

<TABLE>
<S> <C> <C>
Assumed public offering price................................................. $50.41
Net tangible book value per common stock before this offering........ $3.49
Increase attributable to new investors............................... $4.99
-----
Pro forma net tangible book value per common stock after this offering........ 8.48
------

Dilution to new investors(1).................................................. $41.93
======
</TABLE>

- ----------

(1) "Dilution" means the difference between the public offering price per share
of common stock and the pro forma net tangible book value per common stock
after giving effect to this offering.

20
<PAGE>

SELECTED FINANCIAL DATA

We have derived the selected financial data presented below for the
years ended December 31, 1999, 1998 and 1997 and at December 31, 1999 and 1998
from our audited financial statements and notes thereto included in our Annual
Report on Form 10-K for the year ended December 31, 1999 which is incorporated
by reference in this prospectus. We have derived the selected financial data for
the years ended December 31, 1996 and 1995 and at December 31, 1997, 1996 and
1995 from our audited financial statements and notes thereto not included in
this prospectus. You should read the selected financial data together with the
audited financial statements and the section entitled "Management's Discussion
and Analysis of Financial Condition and Results of Operations" in our Annual
Report which is incorporated by reference in this prospectus.

<TABLE>
<CAPTION>
Year Ended December 31,
-------------------------------------------------------------------------
1999 1998 1997 1996 1995
-------- -------- -------- -------- --------
(in thousands, except per share data)
Statement of Operations Data:

Revenues
<S> <C> <C> <C> <C> <C>
Contract research and development......... $ 24,539 $ 19,714 $ 17,400 $ 17,303 $ 23,247
Research progress payments................ - 9,500 5,000 - -
Contract manufacturing ................... 9,960 9,113 4,458 2,451 1,140
Investment income......................... 5,207 6,866 6,242 4,360 2,997
-------- -------- -------- -------- --------
39,706 45,193 33,100 24,114 27,384
-------- -------- -------- -------- --------
Expenses

Weighted average number of Class A and
Common shares outstanding, basic and 31,308 30,992 28,702 24,464 19,768
diluted ======= ====== ====== ====== ======
Net loss per share, basic and diluted ($0.74) ($0.28) ($0.40) ($1.33) ($1.19)
======== ======== ========= ======== ========

</TABLE>

<TABLE>
<CAPTION>
December 31,
-------------------------------------------------------------------------
1999 1998 1997 1996 1995
--------- --------- -------- -------- -------
(in thousands)
Balance Sheet Data:
<S> <C> <C> <C> <C> <C>
Cash, cash equivalents, and marketable
securities................................ $93,599 $113,530 $128,041 $97,028 $59,622
Working capital.............................. 59,725 83,499 88,953 72,960 36,254
Total assets................................. 136,999 156,915 168,380 137,582 93,811
Capital lease obligations and note payable,
long-term portion......................... 2,731 3,066 3,752 5,148 5,978
Shareholders' equity......................... 109,532 131,227 138,897 106,931 67,856

</TABLE>

21
<PAGE>

BUSINESS

General

o Angiopoietins: A new family of growth factors, discovered by us,
that are specific for blood vessels and early hemopoietic stem
cells. The Angiopoietins and engineered forms of these growth
factors that can act as activators and blockers, are in
preclinical testing for promoting blood vessel growth (to provide
blood flow in diseased hearts and other tissues that have lost
their original blood supplies), for blocking blood vessel growth
(for the treatment of cancers), for fixing leaky blood vessels
(that cause swelling and edema in diseases such as stroke,
diabetic retinopathy and inflammatory diseases) and for promoting
the growth and mobilization of certain hemopoietic cells such as
stem cells and platelets.

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<PAGE>

Technology Platforms

Targeted Genomics and Bioinformatics. In contrast to basic genomics
approaches, which attempt to identify every gene in a cell or genome, we use
Targeted Genomics approaches to identify specific genes likely to be of
therapeutic interest. Such approaches include homology cloning using
low-stringency hybridization approaches, homology cloning using degenerate
oligonucleotides in polymerase chain reaction-based amplification searches,
subtractive hybridization approaches and bioinformatics-based algorithms that
search public genomic and expressed sequence tag (EST) databases for genes of
interest. These approaches have resulted in the discovery of a wide variety of
important genes useful for developing drugs in a diverse number of therapeutic
areas, including angiogenesis, cancer, muscle disorders, bone and cartilage
formation, fibrosis and inflammatory diseases. A particular focus of these
efforts is the identification of so-called orphan receptors, as described in the
next section.

Functionomics: Orphan Receptor Technology and Functional Cloning of
Growth Factors for these Orphan Receptors. The therapeutic utility of many
growth factors depends, in part, on the exquisite specificity of their actions.
This specificity is determined largely by the limited distribution of receptors
for these factors on the target cells of interest. Using proprietary technology
initially developed for the discovery and characterization of neurotrophic
factors and their receptors described in the previous section on Targeted
Genomics and Bioinformatics, we have discovered new receptor proteins
specifically expressed on particular cell populations of potentially important
clinical interest. These cell populations include not only additional subsets of
neurons but non-neuronal cells, such as the endothelial cells that constitute
blood vessels, skeletal muscle cells, cartilage cells and hemopoietic cells.
Because these novel receptor proteins initially have no defined growth factor
partner, they are termed orphan receptors. We have also obtained licenses and
established collaborations for additional orphan receptors, including licenses
from The Salk Institute for Biological Studies. Our scientists then define the
growth factor-binding portion of the orphan receptors and engineer it into an
antibody-like reagent, termed a receptor-body. This receptor-body is used to
detect a source of the unknown growth factor and a cDNA library is produced from
this source. The millions of cDNAs in this library are then introduced into
millions of mammalian cells and the rare cell that has taken up the cDNA
encoding the unknown growth factor is detected using the receptor-body. The cell
is then isolated and its cDNA amplified, allowing for the molecular cloning of
the unknown growth factor. These approaches have allowed our scientists to clone
growth factor families such as the Angiopoietins and Ephrins.

Designer Protein Therapeutics and Genetic Engineering. In cases in
which the natural gene product is itself not a product candidate, we utilize our
Designer Protein Therapeutics platform approaches to genetically engineer
product candidates with the desired properties. These technologies allow for the
development of derivatives of the growth factors and their receptors, which can
allow for modified agonistic or antagonistic properties that may prove to be
therapeutically useful. Examples include the generation of AXOKINE as a second
generation version of CNTF and the development of Cytokine Traps and the VEGF
Trap. Traps are derivatives of the receptors for cytokines and VEGF, in which
the binding portions of two different receptor

23
<PAGE>

components are combined to form a very high-affinity and fully human soluble
antagonist. This technology platform has already produced more than 10 patented
proteins, several of which are in preclinical development.

Additional research and development capabilities. These capabilities
include molecular and cellular biology, protein chemistry, transgenics and gene
knockouts, disease modeling, viral gene delivery of proteins, recombinant
expression of proteins and large-scale manufacturing of recombinant proteins.

Our Programs

Selected Products and Programs

Technology Platforms
Used for Discovery and Commercialization
Development Program and Product Targeted Indication Stage Rights
- ----------- ------------------- ------------------- ----- ------

TARGETED GENOMICS NT-3 (Neurotrophin-3) Constipating Clinical Regeneron and Amgen
conditions associated
with spinal cord
injury and other
medical conditions

Cytokine Traps
--------------

DESIGNER PROTEIN IL-1 Rheumatoid arthritis Preclinical Regeneron
THERAPEUTICS and other inflammatory
disorders

DESIGNER PROTEIN IL-4 Asthma and allergic Preclinical Regeneron
THERAPEUTICS disorders

DESIGNER PROTEIN IL-4/13 Asthma and allergic Preclinical Regeneron
THERAPEUTICS disorders

DESIGNER PROTEIN IL-2, IL-3, IL-5, Multiple Research Regeneron
THERAPEUTICS IL-6, IL-15, gamma-
interferon, TTPbeta
and others

Angiogenesis Programs
---------------------

DESIGNER PROTEIN VEGF Trap Cancer Preclinical Regeneron and Procter
THERAPEUTICS & Gamble

TARGETED GENOMICS Angiopoietin-1 Ischemia, vascular Preclinical Regeneron and Procter
FUNCTIONOMICS leak and edema, and & Gamble
DESIGNER PROTEIN hemopoiesis
THERAPEUTICS

TARGETED GENOMICS Ephrins, Angiopoietin-2 Cancer, ischemia, Research Regeneron and Procter
FUNCTIONOMICS hemopoiesis & Gamble
DESIGNER PROTEIN
THERAPEUTICS

TARGETED GENOMICS Muscle Diseases and Muscle atrophy and Research Regeneron and Procter
FUNCTIONOMICS Disorders injury & Gamble
-------------------

Bone and Cartilage:
-------------------

TARGETED GENOMICS RORs Osteoarthritis Research Regeneron and Procter
FUNCTIONOMICS & Gamble

TARGETED GENOMICS DDRs Fibrosis and cirrhosis Research Regeneron and Procter
FUNCTIONOMICS & Gamble

TARGETED GENOMICS G-Protein Coupled Multiple Research Regeneron and Procter
FUNCTIONOMICS Receptors & Gamble
-----------------

</TABLE>

24
<PAGE>

AXOKINE. AXOKINE is our patented second generation ciliary neurotrophic
factor, called CNTF. In an earlier clinical program, CNTF was evaluated as a
potential treatment for patients with ALS. It was discovered that reduced
appetite and weight loss were among the prominent adverse events in these
patients. Later preclinical studies with AXOKINE in animal models of obesity
confirmed the ability of AXOKINE to induce substantial weight loss,
preferentially of fat as opposed to lean body mass. AXOKINE is effective in all
obesity models studied to date, which include diet induced obesity and genetic
obesity rodent models (ob/ob and db/db mice) and causes marked weight loss in
lean animals.

AXOKINE has similarities to and important differences from leptin, a
protein that is secreted by fat cells which another company is currently
evaluating in clinical trials in obese people. AXOKINE and leptin use similar
intracellular signaling pathways but signal through different, but closely
related, receptors; they interact with the CNTF and the leptin receptor,
respectively. AXOKINE causes weight loss comparable to leptin in ob/ob mice;
ob/ob mice are genetically obese mice which lack leptin but have the intact
leptin receptor. Leptin in pharmacological doses does not induce weight loss in
mice made obese with high fat/high calorie diet. In contrast, AXOKINE in this
model produces a 30 percent weight loss in three weeks without causing obvious
signs of toxicity.

The vast majority of obese humans have intact leptin receptors and
increased serum leptin levels. Hence, human obesity does not appear to be a
leptin deficient state but, rather, a condition of leptin resistance. Based on
the animal studies, AXOKINE is anticipated to be pharmacologically active in
patients with obesity, despite their elevated leptin levels and leptin
resistance.

Cytokine Traps. Our widely-cited research on the CNTF class of
neurotrophic factors led to the discovery that CNTF, although it is a
neurotrophic factor, belongs to the "superfamily" of factors referred to as
cytokines. This superfamily includes factors such as erythropoietin,
thrombopoietin, granulocyte-colony stimulating factor and the interleukins (or
ILs). Our research has led to proprietary insights into the receptors and signal
transduction mechanisms used by the entire cytokine superfamily and to novel
approaches to develop both agonists and antagonists for a variety of cytokines.
Our scientists have created protein-based antagonists for IL-1, IL-4, IL-6 and a
single antagonist that blocks both IL-4 and IL-13. These antagonists are more
potent than previously described antagonists, allowing lower levels of these
antagonists to be used; moreover, these antagonists are comprised entirely of
natural human-derived sequences and thus would not be expected to induce an
immune reaction in humans (although no assurance can be given since none have
yet been tested in humans). These cytokine antagonists are termed Cytokine
Traps. Because pathological levels of IL-1, IL-4, IL-6 and IL-13 seem to
contribute to a variety of disease states, these Cytokine Traps have the
potential to be important therapeutic agents. The approach to treating serious
diseases by blocking the action of cytokines has been validated by approved
drugs for the treatment of rheumatoid arthritis.

Our research regarding protein-based cytokine antagonists currently
includes molecular and cellular research to improve or modify our Cytokine Trap
technology, process development efforts to produce experimental and clinical
research quantities of the Cytokine Traps and in vivo and in vitro studies to
further understand and demonstrate the efficacy of the Cytokine Traps. We plan
to commence a clinical study of one of our cytokine traps this year and one next
year. The Company has patents covering additional Cytokine Traps for IL-2, IL-3,
IL-5, IL-15, gamma-interferon, transforming growth factor beta, and others,
which are being pursued at the research level.

BDNF. Brain-derived neurotrophic factor is a naturally occurring human
protein. During 1995 and 1996, Amgen conducted, on behalf of Amgen-Regeneron
Partners, a Phase III BDNF clinical trial to treat ALS. This study involved
1,135 patients, with each patient scheduled to receive subcutaneous treatment
for nine months. ALS is a disease that attacks motor neurons, those nerve cells
that cause muscles to contract. Degeneration of these neurons causes muscle
weakness, leading to death due to respiratory insufficiency. ALS afflicts adults
primarily between the ages of 40 and 70 years old; average survival is three to
five years following diagno-

<PAGE>

sis. It is estimated that approximately 25,000 people in the United States have
ALS. In January 1997, we and Amgen announced that the Phase III study failed to
demonstrate clinical efficacy. As described earlier, additional clinical
development of BDNF for ALS was suggested based on, among other things,
retrospective analyses of the data from that study.

BDNF is being tested in humans by Amgen-Regeneron Partners for
potential use in treating ALS through two routes of administration: intrathecal
(infusion into the spinal fluid through an implanted pump) and subcutaneous
(injection under the skin). In the fourth quarter of 1998, Amgen, on behalf of
the partnership, began an intrathecal study in more than 200 patients with ALS.
Subcutaneous studies conducted by us on behalf of the partnership began in the
first quarter of 1998. The subcutaneous studies are based on an analysis of the
Amgen-Regeneron Partners Phase III trial of BDNF for ALS that was completed in
1996. That trial failed to achieve its predetermined end points, but subsequent
analyses indicated that a retrospectively-defined subset of ALS patients in the
trial may have received a survival benefit from BDNF treatment. A double-blind,
placebo-controlled, multi-center study of more than 300 ALS patients who will
receive BDNF subcutaneously began in August 1999.

NT-3. Neurotrophin-3 is a naturally occurring human protein.
Amgen-Regeneron Partners' clinical development of NT-3 is currently focused on
constipation associated with conditions such as spinal cord injury, use of
narcotic analgesics and severe idiopathic constipation. We and Amgen are
developing NT-3 in the United States under a license from Takeda Chemical
Industries, Ltd.

Angiogenesis and Hemopoiesis. A plentiful blood supply is required to
nourish every tissue and organ of the body. Diseases such as diabetes and
atherosclerosis wreak their havoc, in part, by destroying blood vessels
(arteries, veins and capillaries) and compromising blood flow. Decreases in
blood flow (known as ischemia) can result in non-healing skin ulcers and
gangrene, painful limbs that cannot tolerate exercise, loss of vision and heart
attacks. In other cases, disease processes can damage blood vessels by breaking
down vessel walls, resulting in defective and leaky vessels. Leaking vessels can
lead to swelling and edema, as occurs in brain tumors, following ischemic
stroke, in diabetic retinopathy and in arthritis and other inflammatory
diseases. Finally, some disease processes such as tumor growth depend on the
induction of new blood vessels.

Depending on the clinical situation, positively or negatively
regulating blood vessel growth could have important therapeutic benefits, as
could the repair of damaged and leaky vessels. Thus, building new vessels, by a
process known as angiogenesis, can improve circulation to ischemic limbs and
heart, aid in healing of skin ulcers or other chronic wounds and in establishing
tissue grafts. Reciprocally, blocking tumor-induced angiogenesis can blunt tumor
growth. In addition, repairing leaky vessels can reverse swelling and edema.

Vascular endothelial growth factor (VEGF) was the first growth factor
shown to be specific for blood vessels, by virtue of having its receptor
specifically expressed on blood vessel cells. Our scientists have used their
Targeted Genomics and Functionomics technology platforms to discover a second
family of angiogenic growth factors, termed the Angiopoietins, and received
patents for the members of this family. The Angiopoietins include naturally
occurring positive and negative regulators of angiogenesis, as described in
numerous scientific manuscripts published by our scientists and their
collaborators.

To discover the Angiopoietins, our scientists exploited their platform
technologies. They first used Targeted Genomics approaches to identify a new
family of growth factor receptor proteins expressed on blood vessels. These
proteins were termed orphan receptors because their putative ligands had not yet
been identified. Our scientists then used functional expression cloning
technologies (Functionomics) to discover the growth factors for these orphan
receptors, which they termed the Angiopoietins. Finally, they and their
collaborators performed an assortment of functional studies to define the
biologic roles of the Angiopoietins and their potential applications in disease
processes.

26
<PAGE>

These studies have revealed that VEGF and the Angiopoietins normally
function in a coordinated and collaborative manner during blood vessel growth.
Thus, the growth of new blood vessels to nourish ischemic tissue seemingly
requires use of both these agents. Second, Angiopoietin-1 seems to play a
critical role in stabilizing the vessel wall, and the use of this growth factor
has the ability to prevent or repair leaky vessels. In terms of blocking vessel
growth, both VEGF and Angiopoietin manipulation seem to be of value. Currently,
Regeneron has a highly potent VEGF antagonist, termed the VEGF-Trap, in
preclinical development as an anti-angiogenic agent for cancer. In addition,
Regeneron has Angiopoietin-1 and engineered designer versions in preclinical
studies aimed at evaluating its utility for blocking blood vessel leak, and for
growing blood vessels in ischemia. Finally, as part of its collaboration with
Procter & Gamble, the Company is developing animal models and high-throughput
screens and conducting medicinal chemistry efforts to develop small molecule
regulators of angiogenesis.

Hemopoietic stem cells and blood vessel cells share a common precursor,
termed the hemangioblast. The receptors for the Angiopoietins are thus also
expressed on hemopoietic lineage cells. The Angiopoietins are in preclinical
studies for their abilities to promote growth and mobilization of hemopoietic
stem cells and megakaryocytes.

We and others have identified a family of growth factors termed the
Ephrins and their receptors termed the Ephs. Members of this family have
specific roles in angiogenesis and hemopoiesis, which are being pursued in
preclinical studies.

Muscle Atrophy and Related Disorders. Muscle atrophy occurs in many
neuromuscular diseases and also when muscle is unused, as often occurs during
prolonged hospital stays and during convalescence. Currently, physicians have
few options to prescribe for patients with muscle atrophy or other muscle
conditions which afflict millions of patients globally. Thus, a factor that
might have beneficial effects on skeletal muscle could have significant clinical
benefit. The muscle program is currently focused on conducting in vivo and in
vitro experiments with the objective of demonstrating and further understanding
the molecular mechanisms involved in muscle atrophy. This work is being
conducted in collaboration with scientists at Procter & Gamble as part of the
P&G Agreement.

Other Early Stage Programs: Cartilage Growth Factor Receptor System and
Osteoarthritis, Collagen Receptors and Fibrosis, and G-Protein Coupled
Receptors. Osteoarthritis results from the wearing down of the articular
cartilage surfaces that cover joints. Thus, growth factors that specifically act
on cartilage cells could have utility in osteoarthritis. Using our platform
technologies that utilize Targeted Genomics to discover orphan receptors,
together with our functional biology capabilities, our scientists have
discovered a growth factor receptor system selectively expressed by cartilage
cells, termed Regeneron Orphan Receptor 2 (ROR2). Furthermore, our scientists
have demonstrated that this growth factor receptor system is required for normal
cartilage development in mice as revealed by gene knockout technology. In
addition, together with collaborators, our scientists have proven that mutations
in this growth factor receptor system cause inherited defects in cartilage
development in humans. Thus, this growth factor receptor system is an exciting
new target for cartilage diseases such as osteoarthritis.

We also have an intensive program to discover and characterize
G-Protein Coupled Receptors, which have historically been among the most useful
targets for pharmaceuticals.

Fibrotic diseases, such as cirrhosis, result from the excess production
of fibrous extracellular matrix by certain cell types that are inappropriately
activated in these diseases. We and our collaborators identified orphan
receptors, termed Discoidin Domain Receptors 1 and 2 (DDR1 and DDR2) that are
expressed by the activated cell types in fibrotic disease. We have further shown
that these receptors bind and

27
<PAGE>

are activated by the fibrous matrix they produce. Thus, these receptors are
important new targets in fibrotic disease.

Collaborative Relationships

We currently conduct programs in collaboration with academic and
corporate partners and independently. We have entered into research
collaboration and licensing agreements with various corporate partners,
including Procter & Gamble, Amgen and Sumitomo Pharmaceuticals.

Procter & Gamble. The majority of our scientific resources are devoted
to our collaborative activities with Procter & Gamble in the fields of
angiogenesis, cancer, bone growth and related areas, muscle injury and atrophy
and small molecule (orally active) drugs.

In May 1997, we entered into a ten-year collaboration agreement with
Procter & Gamble to discover, develop and commercialize pharmaceutical products.
Procter & Gamble agreed over the first five years of the various agreements to
purchase up to $60.0 million in our equity, of which, as of December 31, 1999,
it had purchased $42.9 million. In addition, Procter & Gamble purchased $10.0
million of our common stock in 1997. Procter & Gamble agreed over the first five
years of the various agreements to provide up to $94.7 million in support of our
research efforts related to the collaboration, of which we had received $24.0
million as of December 31, 1999.

In September 1997, our ten-year agreement with Procter & Gamble was
expanded to include AXOKINE and related molecules, and we agreed to develop
AXOKINE initially to treat obesity associated with Type II diabetes. In the
first quarter of 1999, we and Procter & Gamble commenced a Phase I clinical
study to determine the safety of AXOKINE administered subcutaneously for a short
duration to mildly to moderately obese healthy volunteers. After examining the
interim data from the Phase I study (including the possibility that the market
for AXOKINE might be limited to herpes simplex virus (commonly called
HSV)-negative patients) as part of an internal review of drug development
programs and budgets, Procter & Gamble decided to return to us the product
rights to AXOKINE. We and Procter & Gamble completed the Phase I study in
HSV-negative patients. Based on the final results of the Phase I study, we
expect to start in March 2000 a double-blind, placebo-controlled Phase II
dose-ranging trial to study the safety and efficacy of AXOKINE in severely obese
patients. Under certain circumstances, Procter & Gamble will continue to be
entitled to receive a small royalty on any sales of AXOKINE. Procter & Gamble's
decision to return to us product rights to AXOKINE has no impact on our broader
relationship with Procter & Gamble.

Amgen. We and Amgen are conducting clinical trials of BDNF and NT-3 on
behalf of Amgen-Regeneron Partners, a general partnership owned equally by us
and Amgen. We are required to fund 50 percent of the development costs of
Amgen-Regeneron Partners to maintain 50 percent of the commercialization
rights. BDNF is currently being developed by Amgen-Regeneron Partners for
potential use in treating ALS through two routes of administration: intrathecal
(infusion into the spinal fluid through an implanted pump, supplied by
Medtronic, Inc.) and subcutaneous (injection under the skin). The
Amgen-Regeneron Partners Phase III trial of BDNF for ALS, completed in 1996,
failed to achieve its predetermined end points, but subsequent analyses
indicated that a retrospectively defined subset of ALS patients in the trial may
have received a survival benefit from BDNF treatment.

Sumitomo Pharmaceuticals. We and Sumitomo Pharmaceuticals are
collaborating in the development of BDNF in Japan, initially for the treatment
of ALS. Pursuant to our license agreement with Sumitomo Pharmaceuticals,
Sumitomo Pharmaceuticals made a $5.0 million research progress payment (reduced
by $0.5 million of Japanese withholding tax) to our company in 1998 and will be
required to make additional payments upon the achievement of specified
milestones. Sumitomo Pharmaceuticals will also pay a royalty on sales of BDNF in
Japan.

28
<PAGE>

Other Agreements. We have agreements with individual researchers and
universities to conduct sponsored research and development programs. The goal
of these agreements is to extend our capabilities and to acquire proprietary
rights to the results of sponsored research. We are a party to a number of
sponsored research agreements which include grants to us of exclusive licenses
to certain discoveries and technologies developed at, among other places, the
Max Planck Institute and the University of California at San Francisco. We have
also collaborated with Glaxo Wellcome plc to discover and develop small
molecule-based treatments for neurodegenerative diseases. In addition to these
sponsored research agreements, we (individually or in partnership with our
collaborators) provide resource material and information that relate to its
product candidates and research programs to over 400 investigators at private
and public institutions throughout the world. We supply supplies, materials and
know-how to these investigators on a confidential basis in exchange for access
to additional research and ownership of certain proprietary rights resulting
from the work of the investigators.

Manufacturing

We maintain a manufacturing facility in Tarrytown, New York. This
facility, which was designed to comply with FDA current good manufacturing
practices (called GMP), is intended to produce preclinical and clinical supplies
of compounds. Depending on the dosage of its drugs, the facility could also
produce either bulk compounds or the final dosage form of certain product
candidates.

In 1993, we purchased our Rensselaer, New York manufacturing facility,
which is being used to produce BDNF for use by Sumitomo Pharmaceuticals and a
vaccine intermediate for Merck. We may use the facility to produce other product
candidates and materials in the future.

Patents, Trademarks and Trade Secrets

Our success depends, in part, on our ability to obtain patents,
maintain trade secret protection and operate without infringing on the
proprietary rights of third parties. Our policy is to file patent applications
to protect technology, inventions and improvements that are considered important
to the development of our business. We have been granted a number of U.S.
patents and we are the exclusive or nonexclusive licensee of a number of
additional U.S. patents and patent applications. We also rely upon trade
secrets, know-how and continuing technological innovation to develop and
maintain its competitive position. We or our licensors or collaborators have
filed patent applications on products and processes relating to neurotrophic
factors and other technologies and inventions in the United States and in
certain foreign countries. We intend to file additional patent applications,
when appropriate, relating to improvements in these technologies and other
specific products and processes. We plan to aggressively prosecute, enforce and
defend our patents and other proprietary technology.

Employees

As of December 31, 1999, we had 437 full-time employees, 82 of whom
hold a Ph.D. and/or M.D. degree. We believe that we have been highly successful
in attracting skilled and experienced personnel; however, competition for such
personnel is intense.

29
<PAGE>

MANAGEMENT

Directors and Executive Officers

The following table provides information with respect to our directors
and executive officers as of February 29, 2000:

<S> <C> <C>
P. Roy Vagelos, M.D. 70 Chairman of the Board of Directors (Class II)
Leonard S. Schleifer, M.D., Ph.D. 47 Director (Class I) President, Chief Executive Officer and
Founder
Charles A. Baker 67 Director(Class III)
Michael S. Brown, M.D. 59 Director (Class III) and Member of Scientific Advisory Board
Alfred G. Gilman, M.D., Ph.D. 58 Director (Class II) Member of Scientific Advisory Board and
Co-Founder
Joseph L. Goldstein, M.D. 60 Director (Class II) and Member of Scientific Advisory Board
Fred A. Middleton 50 Director (Class I)
Eric M. Shooter, Ph.D. 76 Director (Class I) and Chairman of Scientific Advisory Board
George L. Sing 51 Director (Class III)
George D. Yancopoulos, M.D., Ph.D 40 Senior Vice President, Research and Chief Scientific Officer
Jesse M. Cedarbaum, M.D. 48 Vice President, Clinical Affairs
Murray A. Goldberg 55 Vice President, Finance & Administration, Chief
Financial Officer, Treasurer and Assistant Secretary
Hans-Peter Guler, M.D. 51 Vice President, Clinical Sciences
Stephen L. Holst 58 Vice President, Quality Assurance and Regulatory
Affairs
Richard X. Horne 49 Staff Vice President, Human Resources
William G. Roberts, M.D. 42 Vice President, Regulatory Development
Randall G. Rupp, Ph.D. 53 Vice President, Manufacturing and Process Science
Joseph M. Sorrentino, Ph.D. 48 Vice President, Intellectual Property
Neil Stahl, Ph.D. 43 Vice President, Preclinical Development and
Biomolecular Science
David M. Valenzuela, Ph.D. 49 Vice President, Genomics and Bioinformatics
Douglas S. McCorkle 43 Controller and Assistant Treasurer
Beverly C. Dubs 45 Administrative Controller and Assistant Treasurer

</TABLE>

The Board of Directors is divided into three classes, denominated Class
I, Class II and Class III, with members of each class holding office for
staggered three-year terms. Our Scientific Advisory Board consists of
individuals with recognized expertise in neurobiology, clinical neurology,
molecular biology and related fields who advise us about present and long-term
scientific planning, research and development.

P. Roy Vagelos, M.D., 70, has been chairman of the board of our company
and a member of the Scientific Advisory Board since January 1995. He became a
part-time employee of Regeneron in January 1999. Prior to joining Regeneron, Dr.
Vagelos was Chairman of the Board and Chief Executive Officer of Merck & Co.,
Inc. He joined Merck in 1975, became a director in 1984, President and Chief
Executive Officer in 1985 and Chairman in 1986. Dr. Vagelos retired from all
positions with Merck in 1994. He is also currently a member of the Board of
Directors of PepsiCo, Inc., The Prudential Insurance Company of America and
Estee Lauder Companies.

30
<PAGE>

Leonard S. Schleifer, M.D., Ph.D., 47, founded our company in 1988 and
has been its president and chief executive officer since its inception and
served as Chairman of the Board from 1990 through 1994. In 1992, Dr. Schleifer
was appointed Clinical Professor of Neurology at the Cornell University Medical
School and from 1984 to 1988 he was Assistant Professor at the Cornell
University Medical School in the Departments of Neurology and Neurobiology. Dr.
Schleifer received his M.D. and PhD. in Pharmacology from the University of
Virginia. Dr. Schleifer is a licensed physician and is certified in Neurology by
the American Board of Psychiatry and Neurology.

Charles A. Baker, 67, has been a director of our company since February
1989. Since December 1989, he has been the Chairman, President and Chief
Executive Officer of The Liposome Company, Inc., a publicly held company. During
his career, Mr. Baker served in senior management capacities in various
pharmaceutical companies, including the positions of Group Vice President,
Squibb Corporation (now Bristol-Myers Squibb) and President, Squibb
International. He also held various senior executive positions at Abbott
Laboratories and Pfizer, Inc. Mr. Baker is a special limited partner in
Sanderling Ventures, which is a shareholder of the Company.

Michael S. Brown, M.D., 59, has been a director of our company since
June 1991 and a member of our Scientific Advisory Board since January 1988. Dr.
Brown is Professor of Medicine and Genetics and the Director of the Center for
Genetic Diseases at The University of Texas Southwestern Medical Center at
Dallas. He is a member of the National Academy of Sciences. He is a Director of
Pfizer, Inc. His scientific contributions in cholesterol and lipid metabolism
were made in collaboration with Dr. Joseph L. Goldstein. Dr. Brown and Dr.
Goldstein jointly received the Nobel Prize for Physiology or Medicine in 1985.

Alfred G. Gilman, M.D., Ph.D., 58, a co-founder of our company, has
been a director of our company since July 1990 and a member of our Scientific
Advisory Board since 1988. Dr. Gilman has been the Raymond and Ellen Willie
Professor of Molecular Neuropharmacology and Chairman of the Department of
Pharmacology at The University of Texas Southwestern Medical Center at Dallas
since 1981 and was named a Regental Professor in 1995. Dr. Gilman is a member
of the National Academy of Sciences. He is the Consulting Editor of "Goodman and
Gilman's The Pharmacological Basis of Therapeutics," the leading medical
pharmacology textbook. Dr. Gilman received the Nobel Prize for Physiology or
Medicine in 1994. Dr. Gilman is a member of the Board of Directors of Eli Lilly
& Company.

Joseph L. Goldstein, M.D., 60, has been a director of our company
since June 1991 and a member of our Scientific Advisory Board since January
1988. Dr. Goldstein has been the Professor of Medicine and Genetics and Chairman
of the Department of Molecular Genetics at The University of Texas Southwestern
Medical Center at Dallas for more than five years. Dr. Goldstein is a member of
the National Academy of Sciences. Dr. Goldstein and Dr. Brown jointly received
the Nobel Prize for Physiology or Medicine in 1985.

Fred A. Middleton, 50, has been a director of our company since July
1990. Mr. Middleton is a General Partner of Sanderling Ventures, a venture
capital firm he co-founded with Dr. Robert McNeil in December 1987 specializing
in early stage biomedical companies. Sanderling Ventures is a shareholder of the
Company. Between 1984 and 1987, he was Managing General Partner of Morgan
Stanley Ventures and, from 1978 through 1984, was Vice President and Chief
Financial Officer of Genentech, Inc. and President, Genentech Development
Corporation.

Eric M. Shooter, Ph.D., 76, a co-founder of our company, has been a
director of our company and chairman of the Scientific Advisory Board since
1988. Dr. Shooter has been a Professor at Stanford University School of Medicine
since 1968. He was the founding Chairman of the Department of Neurobiology at
Stanford University School of Medicine in 1975 and served as its Chairman until
1987. He is a Fellow of the Royal Society of

31
<PAGE>

England, a Fellow of the American Academy of Arts and Sciences and a Foreign
Associate of the Institute of Medicine of the National Academy of Sciences.

George L. Sing, 51, has been a director of our company since January
1988. From February 1990 until February 14, 1991, Mr. Sing served as a
consultant to Merrill Lynch Venture Capital Inc. with respect to the Company.
From 1982 to February 1990, Mr. Sing was a Vice President and member of the
Board of Directors of Merrill Lynch Venture Capital Inc., a venture capital
firm. Since 1993, Mr. Sing has been a general partner of Zitan Partners, an
investment and advisory firm.

George D. Yancopoulos, M.D., Ph.D., 40, has been senior vice president,
Research since June 1997 and chief scientific officer since January 1998. Dr.
Yancopoulos was Vice President, Discovery from January 1992 until June 1997 and
was employed by us since March 1989 as Senior Staff Scientist and Head of
Discovery from January 1991 to January 1992. He received his Ph.D. in
Biochemistry and Molecular Biophysics and his M.D. from Columbia University.
According to a 1997 survey by the Institute for Scientific Information, our
Chief Scientific Officer was among the top 11 most highly cited scientists and
the only non-academic scientist in that group.

Jesse M. Cedarbaum, MD., 48, has been our vice president, Clinical
Affairs since January 1993 and was Program Director of Clinical Affairs of the
Company from July 1990 until December 1992. He was Associate Professor of
Neurology and Neuroscience at Cornell University Medical College and director of
the Parkinson and Movement Disorders Clinics, New York Hospital and The Burke
Rehabilitation Center from 1983 to 1990 and is currently Clinical Associate
Professor of Neurology at Mt. Sinai Medical School in New York. Dr. Cedarbaum is
a board certified neurologist. Dr. Cedarbaum received his M.D. from the Yale
University School of Medicine.

Murray A. Goldberg, 55, has been our vice president, Finance and
Administration, Treasurer and Chief Financial Officer since March 1995 and
Assistant Secretary since January 2000. Prior to joining us, Mr. Goldberg was
Vice President, Finance, Treasurer and Chief Financial Officer of PharmaGenics,
Inc. from February 1991 and a Director of that company from May 1991. From 1987
to 1990, Mr. Goldberg was Managing Director, Structured Finance Group at the
Chase Manhattan Bank, N.A. and from 1973 to 1987 he served in various managerial
positions in finance and corporate development at American Cyanamid Company.

Hans-Peter Guler, M.D., 51, has been our vice president, Clinical
Affairs since April 1998. From 1994 until joining the Company, Dr. Guler was
employed by Chiron Corporation, most recently as Senior Director of Clinical
Development. From 1989 to 1994, he was Associate Director of Drug Development in
the Pharmaceuticals Divisions of CIBA-GEIGY Corporation. Dr. Guler received his
M.D. from the University of Zurich.

Steven L. Holst, 58, has been our vice president, Quality Assurance and
Regulatory Affairs since October 1997. From 1993 until October 1997, Mr. Holst
was employed by Novo Nordisk A/S, most recently as Senior Regulatory Officer and
Responsible Head of its worldwide Health Care group. From 1990 to 1993, he was
Director of our Regulatory Affairs and Quality Assurance Groups.

Richard X. Horne, 49, has been our Staff Vice President, Human
Resources since August 1998. Immediately prior to joining Regeneron, he was
Vice President, Human Resources at Braintree Hospital in Braintree, MA, serving
in that capacity since 1990. Mr. Horne also was a member of the Board of
Directors of The Rehabilitation Hospital of Rhode Island from October 1997
until April 1998.

William Roberts, M.D., 42, has been our vice president, Regulatory
Development since May 1999. From 1993 until joining us, Dr. Roberts was employed
by Merck & Co., Inc., as Associate Director, Gastroenterology Clinical Research
and subsequently, Director, Regulatory Affairs. He received his M.D. from the
Columbia University College of Physicians & Surgeons.

32
<PAGE>

Randall G. Rupp, Ph.D., 53, has been our vice president, Manufacturing
and Process Science since January 1992 and was our director of manufacturing
from July 1991 until December 1992. He received his Ph.D. in Biomedical Sciences
from the University of Texas, M.D. Anderson Hospital and Tumor Institution,
Houston.

Joseph M. Sorrentino, Ph.D., 48, has been our vice president,
Intellectual Property since September 1999. Immediately before joining us, he
was Vice President and Counsel (Biotechnology Patents) at Bristol-Myers Squibb
Co., which he joined in 1990. Dr. Sorrentino received his Ph.D. in Biochemistry
from the University of Texas and his J.D. from the University of Arizona.

Neil Stahl, Ph.D., 43, has been our vice president, Preclinical
Development and Biomolecular Sciences since January 2000. He joined us in
1991. Before becoming Vice President, Biomolecular Sciences in July 1997, Dr.
Stahl was Director, Cytokines and Signal Transduction. Dr. Stahl received his
Ph.D. in Biochemistry from Brandeis University.

David Valenzuela, Ph.D., 49, has been our vice president, Genomics and
Bioinformatics since January 1998. Dr. Valenzuela joined us in 1990. He received
his Ph.D. in Molecular Biology from the Albert Einstein College of Medicine,
Yeshiva University.

Douglas S. McCorkle, 43, has been our controller since May 1998 and
Assistant Treasurer since June 1998. Before joining us, Mr. McCorkle was the
Controller at Intergen Company from January 1997. He was a manager from 1995 to
1996, Senior Associate from 1992 to 1995 and Associate from 1990 to 1991, with
PricewaterhouseCoopers LLP.

Beverly C. Dubs, 45, has been our administrative controller since May
1998 and Assistant Treasurer since August 1990. Ms. Dubs has served in various
finance and administration capacities at Regeneron since 1989.

33
<PAGE>

INVESTMENT COMPANY ACT CONSIDERATIONS

The Investment Company Act of 1940, as amended, requires the
registration of, and imposes various substantive restrictions on, certain
companies that engage primarily, or propose to engage primarily, in the
business of investing, reinvesting or trading in securities, or fail certain
statistical tests regarding the composition of assets and sources of income and
are not primarily engaged in businesses other than investing, holding, owning,
or trading securities. We presently satisfy these statistical tests and intend
to remain primarily engaged in businesses other than investing, reinvesting,
owning, holding, or trading securities. In addition, we are relying on an SEC
position that biotechnology companies such as our company are not investment
companies required to register under the 1940 Act. We will seek temporarily to
invest the proceeds of this offering, pending their use as described under the
caption "Use of Proceeds." We expect to continue to be able to avoid
registration requirements of the 1940 Act. If we were required to register as
an investment company under the 1940 Act, we would become subject to substantial
regulations with respect to our capital structure, management, operations,
transactions with affiliates described in the Investment Company Act of 1940
and other matters. Application of the provisions of this Act would have a
material adverse effect on our business.

DESCRIPTION OF CAPITAL STOCK

Our authorized capital stock consists of 60,000,000 shares of common
stock, par value $.001 per share, 40,000,000 shares of Class A stock, par value
$.001 per share and 30,000,000 shares of Preferred Stock, par value $.01 per
share. As of February 28, 2000, 28,160,357 shares of our common stock were
outstanding and held by 737 shareholders of record and 3,579,277 shares of our
Class A stock were outstanding and held by 74 shareholders of record. The
following is a summary description of our capital stock. For more information,
see our Restated Certificate of Incorporation. A copy of this certificate is
incorporated by reference to the registration statement of which this prospectus
forms a part.

Common Stock and Class A Stock

General. The rights of holders of common stock and holders of Class A
stock are identical except for voting and conversion rights and restrictions on
transferability.

Voting Rights. The holders of Class A stock are entitled to ten votes
per share and the holders of Common Stock are entitled to one vote per share.
Except as otherwise required by law or as described below, holders of Class A
common stock will vote together as a single class on all matters presented to
the shareholders for their vote or approval, including the election of
directors. Shareholders are not entitled to vote cumulatively for the election
of directors and no class of outstanding common stock acting alone is entitled
to elect any directors.

Transfer Restrictions. Class A stock is subject to certain limitations
on transfer that do not apply to the common stock.

34
<PAGE>

Dividends and Liquidation. Holders of Class A stock and holders of our
common stock have an equal right to receive dividends when and if declared by
our Board of Directors out of funds legally available therefor. If a dividend or
distribution payable in Class A stock is made on the Class A stock, we must also
make a pro rata and simultaneous dividend or distribution on the common stock
payable in shares of common stock. Conversely, if a dividend or distribution
payable in common stock is made on the common stock, we must also make a pro
rata and simultaneous dividend or distribution on the Class A stock payable in
shares of Class A stock. In the event of our liquidation, dissolution, or
winding up, holders of the shares of Class A stock and common stock are entitled
to share equally, share-for-share, in the assets available for distribution
after payment of all creditors and the liquidation preferences of our preferred
stock.

Optional Conversion Rights. Each share of Class A stock may, at any
time and at the option of the holder, be converted into one fully paid and
non-assessable share of common stock. Upon conversion, such shares of common
stock would not be subject to restrictions on transfer that applied to the
shares of Class A stock prior to conversion except to the extent such
restrictions are imposed under applicable securities laws.

The shares of common stock are not convertible into or exchangeable for
shares of Class A stock or any other of our shares or securities.

Other Provisions. Holders of Class A stock and common stock have no
preemptive rights to subscribe to any additional securities of any class which
we may issue and there are no redemption provisions or sinking fund provisions
applicable to either such class, nor is the Class A stock or the common stock
subject to calls or assessments.

Nasdaq National Market Listing. Our common stock is quoted on the
Nasdaq National Market. The current rules of the National Association of
Securities Dealers, Inc. (the "NASD") effectively preclude the trading or
quotation through the Nasdaq National Market of any securities of an issuer
which has issued securities or taken other corporate action that would have the
effect of nullifying, restricting, or disparately reducing the per share voting
of an outstanding class or classes of equity securities registered under Section
12 of the Exchange Act. Certain national securities exchanges have adopted
similar rules or policies. We do not intend to issue any additional shares of
any stock that would make it ineligible for inclusion on the Nasdaq National
Market or any national securities exchange. However, if we issue additional
stock that causes us to become ineligible for continued inclusion on the Nasdaq
National Market, then the ineligibility would be likely to materially reduce the
liquidity of an investment in our common stock and would likely depress its
market value below that which would otherwise prevail.

Transfer Agent and Registrar. The Transfer Agent and Registrar to the
common stock is American Stock Transfer & Trust Company.

<PAGE>

Preferred Stock

Our Restated Certificate of Incorporation allows us to issue up to
30,000,000 shares of preferred stock in one or more series and as may be
determined by our Board of Directors who may establish from time to time the
number of shares to be included in each such series, to fix the designation,
powers, preference and rights of the shares of each such series and any
qualifications, limitations, or restrictions thereof and to increase or decrease
the number of shares of any such series without any further vote or action by
the shareholders. Our Board of Directors may authorize, without shareholder
approval, the issuance of preferred stock with voting and conversion rights that
could adversely affect the voting power and other rights of holders of our
common stock. Preferred stock could thus be issued quickly with terms designed
to delay or prevent a change in control or to make the removal of management
more difficult. In certain circumstances, this could have the effect of
decreasing the market price of our common stock.

Registration Rights of Certain Holders

Certain of our shareholders have registration rights. Under the
agreements between us and the holders of registration rights, certain holders
may under certain circumstances request that we file a registration statement
under the Securities Act and, upon such request and subject to certain minimum
size conditions, we will generally be required to use our best efforts to effect
any such registration. We are not generally required to effect more than two
such registrations. However, we are required under certain circumstances to
effect an unlimited number of Form S-3 or similar short form registrations for
such holders. We are generally obligated to bear the expenses, other than
underwriting discounts and sales commissions, of all of these registrations.

In addition, if we propose to register any of our securities, either
for our own account or for the account of other shareholders, with certain
exceptions, we are required to notify the holders noted above and to include in
such registration all of the shares of our common stock requested to be included
by such holders. In connection with this offering, we have notified each of the
holders who have registration rights and each holder other than the selling
shareholder has waived or intends to waive its rights to exercise its respective
registration rights.

Rights Plan

In September 1996, we adopted a Shareholder Rights Plan. As with most
shareholder rights agreements, the terms of our rights agreement are complex and
not easily summarized. This summary may not contain all of the information that
is important to you. Accordingly, you should carefully read our rights
agreement, which has been filed with the SEC.

Our rights agreement provides that each share of our common stock will
have one right to purchase a unit consisting of one-hundredth of a preferred
share at a purchase price of $120 per unit.

Initially, the rights under our rights agreement are attached to
outstanding certificates representing our common stock and no separate
certificates representing the rights will be distributed. The rights will
separate from our common stock and be represented by separate certificates
approximately 10 days after someone acquires or commences a tender offer for 20%
of our outstanding common stock.

After the rights separate from our common stock, certificates
representing the rights will be mailed to record holders of our common stock.
Once distributed, the rights certificates alone will represent the rights.

All shares of our common stock issued prior to the date the rights
separate from the common stock will be issued with the rights attached. The
rights are not exercisable until the date the rights separate from the common
stock. The rights will expire on October 18, 2006 earlier redeemed or exchanged
by us.

If an acquiror obtains or has the right to obtain 20% or more of our
common stock, then each right will entitle the holder to purchase a number of
shares of our common stock equal to two times the purchase price of each right,
unless the acquisition is made pursuant to a tender or exchange offer for all of
our outstanding shares at a price determined by a majority of our independent
directors. In this event, rights held by the acquiring person shall become null
and void.

In certain circumstances, a right will entitle the holder to purchase a
number of shares of common stock of the acquiror having a then current market
value of twice the right's purchase price.

<PAGE>

Holders of rights will have no rights as our stockholders including the
right to vote or receive dividends, simply by virtue of holding the rights.

Our rights agreement may have anti-takeover effects. The rights may
cause substantial dilution to a person or group that attempts to acquire us.
Accordingly, the existence of the rights may deter acquirors from making
takeover proposals or tender offers. However, the rights are not intended to
prevent a takeover, but rather are designed to enhance the ability of our board
to negotiate with an acquiror on behalf of all the shareholders. In addition,
the rights should not interfere with a proxy contest.

37
<PAGE>

SELLING SHAREHOLDER

The following table sets forth certain information with respect to the
beneficial ownership of our common stock (before and after giving effect to the
issuance and sale of shares pursuant to this prospectus) as of , 2000 of
the selling shareholder.

<TABLE>
<CAPTION>
Shares Beneficially Owned Shares Being Offered if Shares Beneficially Owned
Prior to the Offering the Underwriters Over- After the Offering
------------------------------ Allotment Option is ------------------------------
Name and Address Number (1) Percent (2) Exercised in Full Number (1) Percent (3)
------------- ------------- ----------------------- ------------- --------------
<S> <C> <C> <C> <C> <C>
Amgen, Inc.
Amgen Center
1840 Dehavilland Drive
Thousand Oaks, CA 91320

</TABLE>

<PAGE>

UNDERWRITING

Merrill Lynch, Pierce, Fenner & Smith Incorporated, Lehman Brothers
Inc., J.P. Morgan Securities Inc. and FleetBoston Robertson Stephens Inc. are
acting as representatives of each of the underwriters named below. Subject to
the terms and conditions described in a purchase agreement among us, the selling
shareholder and the underwriters, we have agreed to sell to the underwriters and
the underwriters severally have agreed to purchase from us the number of shares
of common stock listed opposite their names below.

Number
Underwriter of Shares
----------- ---------

Merrill Lynch, Pierce, Fenner & Smith
Incorporated................................
Lehman Brothers Inc.....................................
J.P. Morgan Securities Inc..............................
FleetBoston Robertson Stephens Inc......................
--------------
Total 4,000,000
==============

We and the selling shareholder have agreed to indemnify the
underwriters against certain liabilities, including liabilities under the
Securities Act, or to contribute to payments the underwriters may be required to
make in respect of those liabilities.

The underwriters are offering the shares, subject to prior sale, when,
as and if issued to and accepted by them, subject to approval of legal matters
by their counsel, including the validity of the shares and other conditions
contained in the purchase agreements, such as the receipt by the underwriters of
officer's certificates and legal opinions. The underwriters reserve the right to
withdraw, cancel or modify offers to the public and to reject orders in whole or
in part.

Commissions and Discounts

The underwriters have advised us that the underwriters propose
initially to offer the shares to the public at the initial public offering price
on the cover page of this prospectus and to dealers at the price less a
concession not in excess of $___ per share. The underwriters may allow and the
dealers may reallow, a discount not in

39
<PAGE>

excess of $___ per share to other dealers. After the initial public offering,
the public offering price, concession and discount may be changed.

The following table shows the public offering price, underwriting
discount and proceeds before expenses to our company. The information assumes
either no exercise or full exercise by the underwriters of their over-allotment
options.

<TABLE>
<CAPTION>
Per Share Without Option With Option
--------- -------------- -----------
<S> <C> <C> <C>
Public offering price.......................... $ $ $
Underwriting discount.......................... $ $ $
Proceeds, before expenses, to Regeneron........ $ $ $

</TABLE>

The expenses of the offering, not including the underwriting discount,
are estimated at $550,000 and are payable by our company.

Over-allotment Option

The selling shareholder has granted options to the underwriters to
purchase up to 600,000 additional shares at the public offering price less the
underwriting discount. The underwriters may exercise these options for 30 days
from the date of this prospectus solely to cover any over-allotments. If the
underwriters exercise these options, each will be obligated, subject to
conditions contained in the purchase agreements, to purchase a number of
additional shares proportionate to that underwriters's initial amount reflected
in the above table.

No Sales of Similar Securities

We and our executive officers and directors and certain existing
shareholders have agreed, with exceptions, not to sell or transfer any common
stock for 90 days after the date of this prospectus without first obtaining the
written consent of Merrill Lynch. Specifically, we and these other individuals
or entities have agreed not to directly or indirectly:

o offer, pledge, sell or contract to sell any common stock,

o sell any option or contract to purchase any common stock,

o purchase any option or contract to sell any common stock,

o grant any option, right or warrant for the sale of any common
stock,

o lend or otherwise dispose of or transfer any common stock,

o enter into any swap or other agreement that transfers, in whole or
in part, the economic consequence of ownership of any common stock
whether any such swap or transaction is to be settled by delivery
of shares or other securities, in cash or otherwise.

This lockup provision applies to common stock and to securities
convertible into or exchangeable or exercisable for or repayable with common
stock. It also applies to common stock owned now or acquired later by the person
executing the agreement or for which the person executing the agreement later
acquires the power of disposition.

40
<PAGE>

Procter & Gamble has agreed to a lockup provision for a period not to
exceed the earlier of (1) 90 days after the date of this prospectus and (2) June
30, 2000.

The shares are quoted on the Nasdaq National Market under the symbol
"REGN."

Price Stabilization, Short Positions

Until the distribution of the shares is completed, SEC rules may limit
underwriters and selling group members from bidding for and purchasing our
common stock. However, the underwriters may engage in transactions that
stabilize the price of the common stock, such as bids or purchases to peg, fix
or maintain that price.

If the underwriters create a short position in the common stock in
connection with the offering, i.e., if they sell more shares than are listed on
the cover of this prospectus, the underwriters may reduce that short position
by purchasing shares in the open market. The underwriters may also elect to
reduce any short position by exercising all or part of the over-allotment option
described above. Purchases of the common stock to stabilize its price or to
reduce a short position may cause the price of the common stock to be higher
than it might be in the absence of such purchases.

Neither we nor any of the underwriters make any representation or
prediction as to the direction or magnitude of any effect that the transactions
described above may have on the price of the common stock. In addition, neither
we nor any of the underwriters make any representation that the underwriters or
the lead manager will engage in these transactions or that these transactions,
once commenced, will not be discontinued without notice.

Passive Market Making

In connection with this offering, underwriters and selling group
members may engage in passive market making transactions in the common stock on
the Nasdaq National Market in accordance with Rule 103 of Regulation M under
the Exchange Act during a period before the commencement of offers or sales of
common stock and extending through the completion of distribution. A passive
market maker must display its bid at a price not in excess of the highest
independent bid of that security. However, if all independent bids are lowered
below the passive market maker's bid, that bid must then be lowered when
specified purchase limits are exceeded.

Other Relationships

Some of the underwriters and their affiliates have engaged in and may
in the future engage in, investment banking and other commercial dealings in the
ordinary course of business with us. They have received customary fees and
commissions for these transactions.

41
<PAGE>

LEGAL MATTERS

Skadden, Arps, Slate, Meagher & Flom LLP, New York, New York will pass
upon the validity of our common stock offered by this prospectus for us.
Shearman & Sterling, New York, New York will pass upon certain legal matters in
connection with this offering for the underwriter.

EXPERTS

The financial statements of Regeneron Pharmaceuticals, Inc. which are
incorporated in this Prospectus by reference to the Annual Report on Form 10-K
of Regeneron Pharmaceuticals, Inc. for the year ended December 31, 1999, 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.

The financial statements of Amgen-Regeneron Partners appearing in the
Regeneron Pharmaceuticals, Inc.'s 1999 Form 10-K have been audited by Ernst &
Young LLP, independent auditors, as set forth in their report thereon included
therein and incorporated herein by reference. Such financial statements are
incorporated herein by reference in reliance upon such report given on the
authority of such firm as experts in accounting and auditing.

WHERE YOU CAN FIND MORE INFORMATION

We file annual, quarterly and special reports, proxy statements and
other information with the SEC. You may read and copy any documents we file at
the SEC's Public Reference Room at 450 Fifth Street, N.W., Washington, D.C.
20549 and at the Regional Offices of the SEC at 7 World Trade Center, 13th
Floor, New York, New York 10048 and Citicorp Center, 500 West Madison Street,
Suite 1400, Chicago, Illinois 60601. Please call the SEC at 1-800-SEC-0330 for
further information on the public reference rooms. The SEC maintains a site on
the World Wide Web at http://www.sec.gov that contains our SEC filings and
reports, proxy and information statements and other information regarding
registrants.

The SEC allows us to "incorporate by reference" the information we file
with them, which means that we can disclose important information to you by
referring you to those documents. The information incorporated by reference is
considered to be part of this prospectus and information that we file later with
the SEC will automatically update and supersede this information. We incorporate
by reference the documents listed below and all future filings we make with the
SEC after the date of the initial registration statement and prior to
effectiveness of the registration statement and any filings thereafter and prior
to the termination of this offering with the SEC under Section 13(a), 13(c), 14,
or 15(d) of the Securities Exchange Act of 1934:

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

(2) the description of our common stock contained in Item 1
of our Registration Statement on Form 8-A filed on
February 20, 1991, as amended by a Form 8 filed on
March 27, 1991.

You may request a copy of these filings, at no cost, by writing or telephoning
us at the following address:

Regeneron Pharmaceuticals, Inc.
777 Old Saw Mill River Road,
Tarrytown, New York 10591-6707
(914) 347-7000
Attention: Murray A. Goldberg
Chief Financial Officer

42
<PAGE>

4,000,000 Shares

REGENERON PHARMACEUTICALS, INC.

Common Stock

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

PROSPECTUS

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

Merrill Lynch & Co.
Lehman Brothers
J.P. Morgan & Co.
Robertson Stephens

March ___, 2000

43
<PAGE>

PART II

INFORMATION NOT REQUIRED IN PROSPECTUS

Item 14. Other Expenses of Issuance and Distribution.

The following tables sets forth all fees and expenses payable by the
Registrant in connection with the issuance and distribution of the securities
being registered hereby (other than underwriting discounts and commissions).
All of such expenses, except the Commission registration fee, the National
Association of Securities Dealers, Inc. filing fee and the NASDAQ listing fee
are estimated.

Securities and Exchange Commission registration fee $ 60,909.75

NASDAQ listing fee ................................ 17,500.00

Legal fees and expenses ........................... *

Transfer Agent and Registrar fees and expenses .... *

Accounting fees and expenses ...................... 125,000.00

Blue sky fees and expenses (including counsel fees) *

Printing expenses ................................. *

Miscellaneous ..................................... *
------------
Total .................................... $*
============
- -----------------
* To be filed by amendment.

Item 15. Indemnification of Directors and Officers.

Article Seven of Restated Certificate of Incorporation requires
indemnification of the Registrant's officers and directs that such
indemnification be made to the fullest extent permitted by the New York Business
Corporation Law.

Section 722 of the New York Business Corporation Law permits a
corporation to provide in its Certificate of Incorporation to indemnify members
of its board of directors and officers against actions or proceedings, or the
threat thereof, by or in the right of the corporation. In order to receive
indemnification such director or officer must have (i) acted in good faith for a
purpose which he reasonably believed was in the best interest of the corporation
and, (ii) in the case of a criminal proceeding, also had no reasonable
belief that such conduct was unlawful.

Article IV of the Company's By-Laws provides that the directors and
certain other personnel of the Company shall be indemnified against expenses and
certain other liabilities arising out of legal actions brought or threatened
against them for their conduct on behalf of the Company, subject to certain
qualifications and provided that each such person acted in good faith and in a
manner that they reasonably believed was in the Company's best interest.

Each of the directors has entered into an agreement with the Company
that provides that the Company will indemnify such director to the fullest
extent permitted by the New York Business Corporation Law. The

II-1
<PAGE>

Company maintains directors and officers liability insurance which insures
against liabilities that directors or officers of the Company may incur in such
capacities.

Reference is made to the proposed Underwriting Agreement filed as
Exhibit 1 to this Registration Statement for certain provisions relating to the
indemnification of directors and officers of the Company against certain
liabilities under the Securities Act.

Item 16. Exhibits

<TABLE>
<CAPTION>
Exhibit
Number Description
------ -----------
<S> <C> <C>
1* -- Form of Underwriting Agreement.

4.1 -- Stock Purchase Agreement dated January 13, 1988, by and between the Company,
Leonard S. Schleifer and ML Venture Partners II, L.P. (the "Stock Purchase Agreement").
Incorporated by reference to Exhibit 10.1 to Regeneron's Registration Statement on Form
S-1 (File No. 33-39043)(the "Regeneron S-1").

4.2 Amendment to the Stock Purchase Agreement dated March 3, 1989. Incorporated by
reference to Exhibit 10.2 to the Regeneron S-1.

4.3 -- Letter Agreement dated November 27, 1989, amending the
Stock Purchase Agreement. Incorporated by reference to
Exhibit 10.13 to the Regeneron S-1.

4.4 -- Class B Convertible Preferred Stock Purchase Agreement dated November 22, 1988 by
and between the Company and each purchaser set forth on Exhibit A thereto.
Incorporated by reference to Exhibit 10.3 to the Regeneron S-1.

4.5 -- Class C Convertible Preferred Stock Purchase Agreement dated March 20, 1989, by and
between the Company and Sumitomo Chemical Company, Limited. Incorporated by
reference to Exhibit 10.4 to the Regeneron S-1.

4.6 -- Class D Convertible Preferred Stock Purchase Agreement dated August 31, 1990, by and
between the Company and Amgen Inc. Incorporated by reference to Exhibit 10.9 to the
Regeneron S-1.

4.7 -- Registration Rights Agreement, dated as of July 22, 1993, by and between the Company
and Glaxo Group Limited. Incorporated by reference to Exhibit 4.7 to Regeneron's
Registration Statement on Form S-3 (33-66788).

4.8 -- Registration Rights Agreement, dated as of April 15, 1996, by and between the Company
and Amgen Inc. Incorporated by reference to Exhibit 10.3 to Regeneron's Form 10Q for
the quarter ended June 30, 1996, filed August 14, 1996.

4.9 -- Registration Rights Agreement, dated as of June 27, 1996, by and between the Company
and Medtronic, Inc. Incorporated by reference to Exhibit 10.6 to Regeneron's Form 10Q
for the quarter ended June 30, 1996, filed August 14, 1996.

4.10 -- Registration Rights Agreement, dated as of December 11, 1996, by and between the
Company and Procter & Gamble Pharmaceuticals. Incorporated by reference to Exhibit
10.30 to Regeneron's Form 10K for the fiscal year ended December 1996, filed March 26,
1997.
</TABLE>

II-2

<PAGE>

<TABLE>
<S> <C> <C>
4.11 -- Registration Rights Agreement, dated as of May 13, 1997, by and between the Company
and Procter & Gamble Pharmaceuticals. Incorporated by reference to Exhibit 10.3 to
Regeneron's Form 10Q for the quarter ended June 30, 1997, filed August 12, 1997.

4.12 -- Form of Certificate of shares of common stock. Incorporated by reference to Exhibit (a)
to the Company's Form 8-A filed with the Commission on February 20, 1991.

5* -- Opinion of Skadden, Arps, Slate, Meagher & Flom LLP.

23.1 -- Consent of PricewaterhouseCoopers LLP.

23.2 -- Consent of Ernst & Young LLP, Independent Auditors.

23. -- Consent of Skadden, Arps, Slate, Meagher & Flom LLP. Included in Exhibit 5.

24 -- Powers of Attorney. Included in the signature page of this Registration Statement

</TABLE>

- ---------
* To be filed by amendment.

Item 17. Undertakings

The undersigned registrant hereby undertakes that, for purposes of
determining any liability under the Securities Act of 1933, each filing of the
registrant's annual report pursuant to section 13(a) or section 15(d) of the
Securities Exchange Act of 1934 (and, where applicable, each filing of an
employee benefit plan's annual report pursuant to section 15(d) of the
Securities Exchange Act of 1934) that is incorporated by reference in the
registration statement 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 foregoing provisions, or otherwise, the Registrant
has been advised that in the opinion of the 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 that:

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

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

II-3
<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
of the requirements for filing on Form S-3 and has duly caused this Registration
Statement to be signed on its behalf by the undersigned, thereunto duly
authorized, in the City of Tarrytown, State of New York on March 3, 2000.

REGENERON PHARMACEUTICALS, INC.

By: /s/ Leonard S. Schleifer, M.D., Ph.D.
---------------------------------------
Leonard S. Schleifer, M.D., Ph.D.
President and Chief Executive Officer

Pursuant to the requirements of the Securities Act of 1933, this
Registration Statement has been signed by the following persons in the
capacities indicated on March 3, 2000. Each person whose signature appears below
hereby authorizes Leonard S. Schleifer and Murray A.Goldberg, jointly and
severally, with full power to each, to execute in the name and on behalf of such
person any amendment (including any post-effective amendments) to this
Registration Statement (or any other registration statement for the same
offering that is to be effective upon filing pursuant to Rule 462(b) under the
Securities Act) and to file the same, with exhibits thereto and other documents
in connection therewith, making such changes in this Registration Statement as
the person(s) so acting deems appropriate and appoints each of such persons,
each with full power of substitution, attorney-in-fact to sign any amendment
(including any post-effective amendment) to this Registration Statement (or any
other registration statement for the same offering that is to be effective upon
filing pursuant to Rule 462(b) under the Securities Act) and to file the same,
with exhibits thereto and other documents in connection therein.

<TABLE>
<CAPTION>
Signature Title

<S> <C>
/s/ P. Roy Vagelos, M.D.
- -------------------------------------------------------------- Chairman of the Board
P. Roy Vagelos, M.D.

/s/ Leonard S. Schleifer, M.D., Ph.D
- -------------------------------------------------------------- President, Chief Executive Officer and Director
Leonard S. Schleifer, M.D., Ph.D. (Principal Executive Officer)

/s/ Murray A. Goldberg
- -------------------------------------------------------------- Vice President, Finance & Administration,
Murray A. Goldberg Chief Financial Officer, Treasurer and Assistant Secretary
(Principal Financial Officer)

/s/ Douglas S. McCorkle
- -------------------------------------------------------------- Controller and Assistant Treasurer
Douglas S. McCorkle

/s/ Charles A. Baker
- -------------------------------------------------------------- Director
Charles A. Baker

/s/ Michael S. Brown, M.D.
- -------------------------------------------------------------- Director
Michael S. Brown, M.D.

</TABLE>

II-4
<PAGE>

<TABLE>

<S> <C>
/s/ Alfred G. Gilman, M.D., Ph.D.
- -------------------------------------------------------------- Director
Alfred G. Gilman, M.D., Ph.D.

/s/ Joseph L. Goldstein, M.D.
- -------------------------------------------------------------- Director
Joseph L. Goldstein, M.D.

- -------------------------------------------------------------- Director
Eric M. Shooter, Ph.D.

/s/ George L. Sing
- -------------------------------------------------------------- Director
George L. Sing

</TABLE>

II-5

<PAGE>
EXHIBIT 23.1

CONSENT OF INDEPENDENT ACCOUNTANTS
----------------------------------

We hereby consent to the incorporation by reference in this Registration
Statement on Form S-3 of our report, which is based in part on the report of
other auditors, dated February 8, 2000 relating to the financial statements,
which appears in Regeneron Pharmaceuticals, Inc.'s Annual Report on Form 10-K
for the year ended December 31, 1999. We also consent to the reference to us
under the heading "Experts" in such Registration Statement.

PricewaterhouseCoopers LLP

New York, New York
March 3, 2000

<PAGE>

Exhibit 23.2

CONSENT OF ERNST & YOUNG LLP, INDEPENDENT AUDITORS

We consent to the reference to our firm under the caption "Experts" in
the Registration Statement (Form S-3) and related Prospectus of Regeneron
Pharmaceuticals, Inc. for the registration of 4,000,000 shares of its common
stock and to the incorporation by reference therein of our report dated February
8, 2000, with respect to the financial statements of Amgen Regeneron Partners
included in Regeneron Pharmaceuticals, Inc.'s Annual Report (Form 10-K) for the
year ended December 31, 1999, filed with the Securities and Exchange Commission.

ERNST & YOUNG LLP

Los Angeles, California
March 3, 2000