EXHIBIT 99(A)
FOR IMMEDIATE RELEASE
AVENTIS AND REGENERON ENTER GLOBAL PARTNERSHIP TO DEVELOP AND
COMMERICALIZE THE VEGF TRAP
INNOVATIVE ANTI-ANGIOGENESIS COMPOUND WILL BE
DEVELOPED IN ONCOLOGY AND OPHTHALMOLOGY
Strasbourg, France and Tarrytown, NY, September 8, 2003 - Aventis and Regeneron
Pharmaceuticals, Inc. (Nasdaq: REGN) announced today that they have entered into
a global (excluding Japan) agreement under which the companies will jointly
develop and commercialize Vascular Endothelial Growth Factor (VEGF) Trap,
Regeneron's lead anti-angiogenesis compound.
Under the terms of the agreement, Aventis will pay Regeneron $125 million, of
which $45 million is an investment in newly issued Regeneron common stock and
$80 million is an upfront payment. An additional payment of $25 million is
linked to an early clinical milestone. The two companies will share equally
promotion rights and profits globally. Aventis will also pay Regeneron up to
$360 million at identified milestones related to the receipt of marketing
approvals for up to eight indications in Europe and the United States. Aventis
will also fund development costs. The companies will jointly develop VEGF Trap
in oncology, ophthalmology, and possibly in other indications. Should the
collaboration become profitable, Regeneron will pay back to Aventis 50% of the
development costs. Regeneron will continue to manufacture the VEGF Trap at its
plant in Rensselaer, New York, and Aventis will be responsible for providing
commercial scale manufacturing capacity.
"Developing innovative products that provide effective treatment alternatives
for cancer patients is a primary goal for Aventis, and we believe VEGF Trap is
one of the most
promising investigational oncology compounds currently under study," said Frank
Douglas, M.D., Ph.D., Executive Vice President of Drug Innovation and Approval
and Member of the Board of Management at Aventis. "This is a highly significant
partnership for Aventis as blockage of VEGF is at the leading edge of
innovative, targeted cancer therapy."
"We are thrilled to have a partner with such broad expertise, experience, and
resources in the cancer field," said George D. Yancopoulos, M.D., Ph.D.,
Executive Vice President and Chief Scientific Officer of Regeneron. "We believe
that this collaboration should greatly help the VEGF Trap achieve its
potential."
Aventis has one of the industry's leading oncology portfolios, led by
Taxotere(R) (docetaxel), one of the most widely used chemotherapeutic agents
worldwide for the treatment of patients with breast cancer and non-small cell
lung cancer. Taxotere is also being studied extensively for use in treating
patients with other tumor types. Aventis also markets Campto(R) (irinotecan), a
reference treatment for advanced colon cancer, in countries outside of the US,
and Anzemet(R) (dolasetron mesylate), a 5HT3 inhibitor for the treatment of
chemotherapy induced nausea and vomiting in the U.S. In addition, the company
has a rich pipeline of investigational oncology compounds and various innovative
treatment approaches. This includes Genasense(TM), a compound that inhibits
production of Bcl-2, a protein made by cancer cells that is thought to block
chemotherapy-induced cell death. By reducing the amount of Bcl-2 in cancer
cells, Genasense may enhance the effectiveness of current anticancer treatments.
Genasense is currently in multiple, late-stage, randomized clinical trials
including malignant melanoma, multiple myeloma, chronic lymphocytic leukemia
(CLL) and non-small cell lung cancer. In 2002, Aventis entered a global
agreement with Genta Inc. to jointly develop and commercialize Genasense in the
US. Aventis has been granted sole marketing rights outside of the US. Aventis is
also exploring an antibody-based approach to discover and develop new oncology
agents via its recently announced collaboration with ImmunoGen, signed in July
2003.
THE VEGF TRAP: HOW IT MAY PREVENT SOLID TUMOR GROWTH
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Tumors induce abnormal blood vessel growth to support their own continued
maintenance and expansion. They depend on the formation of new blood vessels - a
process termed "angiogenesis" - to support their growth. Abnormal vessel growth
can also occur in the eye, and such growth disrupts normal ocular architecture
and is a leading cause of blindness due to such diseases as diabetic retinopathy
and Age-related Macular Degeneration (AMD). Therapies aimed at blocking abnormal
vessel
growth are referred to as anti-angiogenesis approaches. Blocking
tumor-associated angiogenesis can also prevent tumor growth, and recent exciting
late-stage data on another VEGF antagonist has validated this approach in the
treatment of solid tumors.
Pre-clinical evidence demonstrates that Regeneron's VEGF Trap is an extremely
potent blocker of VEGF. Its activity against cancer and eye diseases suggests
that it may be a more effective VEGF antagonist than other VEGF blockers
currently under development. The higher binding affinity observed in this agent
has resulted in an effect on established tumor vasculature as well as
neovasculature in pre-clinical models. Furthermore, VEGF Trap has demonstrated
an ability to bind to other members of the VEGF family that may play an
important role in tumor progression. In laboratory experiments in many different
tumor types, VEGF Trap has effectively blocked angiogenesis, leaving tumors with
few or no blood vessels feeding them. The VEGF Trap may also have applications
in other therapeutic areas where pathologic vessel growth can cause problems,
such as psoriasis, and corneal neovascularization associated with transplants,
infection, or trauma.
VEGF Trap was developed using Regeneron's proprietary Trap technology platform.
The VEGF Trap is a fusion protein that contains portions of the extracellular
domains of two different VEGF receptors that occur naturally on blood vessels.
By combining key portions of the receptors that bind VEGF, the VEGF Trap blocks
VEGF activity and prevents the formation of the new blood vessels needed to
sustain growth in cancerous tumors. VEGF Trap is currently in phase I clinical
trials to test the safety and tolerability of the compound in patients with
solid-tumor malignancies and with non-Hodgkin's lymphoma.
AUDIO WEBCAST:
Leonard S. Schleifer, M.D., Ph.D., President & CEO of Regeneron Pharmaceuticals,
Inc. invites you to join him and members of senior management from Aventis and
Regeneron in a audio webcast with the investment community to discuss the global
partnership of Aventis and Regeneron to develop
and commercialize VEGF Trap on Monday, September 8, 2003 at 3:00 p.m. Central
European Time; 2:00p.m. UK Time; 9:00 a.m. Eastern; 8:00 a.m. Central; 7:00 a.m.
Mountain; and 6:00 a.m. Pacific.
The audio portion of the conference call will be available by webcast at
www.regeneron.com on the Events page, under the Investor heading. The online
archive will be available for 30 days, and the dial-in replay of the call will
be available for one week beginning approximately two hours after the live call
ends at the following numbers:
Domestic Replay Dial-In: 800-642-1687
International Replay Dial-In: 706-645-9291
Conference Call ID#2698911
ABOUT AVENTIS
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Aventis is dedicated to treating and preventing disease by discovering and
developing innovative prescription drugs and human vaccines. In 2002, Aventis
generated sales of (128) 17.6 billion, invested (128) 3.1 billion in research
and development and employed approximately 71,000 people in its core business.
Aventis corporate headquarters are in Strasbourg, France. For more information,
please visit: www.aventis.com ABOUT REGENERON Regeneron is a biopharmaceutical
company that discovers, develops, and intends to commercialize therapeutic
medicines for the treatment of serious medical conditions. Regeneron has
therapeutic candidates in clinical trials for the potential treatment of
obesity, rheumatoid arthritis, cancer, and asthma and has preclinical programs
in other diseases and disorders. Regeneron corporate headquarters are in
Tarrytown, NY. For more information, please visit www.regn.com FOR REGENERON
This news release discusses historical information and includes forward-looking
statements about Regeneron and its products, programs, finances, and business,
all of which involve a number of risks and uncertainties, such as risks
associated with preclinical and clinical development of drugs and biologics,
determinations by regulatory and administrative governmental authorities,
competitive factors, technological developments, the availability and cost of
capital, the costs of developing, producing, and selling products, the potential
for any collaboration agreement to be canceled or to terminate without any
product success, and other material risks. A more complete description of these
risks can be found in Regeneron's filings with the United States Securities and
Exchange Commission, including its Form 10-K for the year ended December 31,
2002 and the Form 10-Q for the quarter ended June 30, 2003. Regeneron does not
undertake any obligation to update publicly any forward-looking statement,
whether as a result of new information, future events, or otherwise unless
required by law.
FOR AVENTIS
- -----------
Statements in this news release containing projections or estimates of revenues,
income, earnings per share, capital expenditures, capital structure, or other
financial items; plans and objectives relating to future operations, products,
or services; future economic performance; or assumptions underlying or relating
to any such statements, are forward-looking statements subject to risks and
uncertainties. Actual results could differ materially depending on factors such
as the timing and effects of regulatory actions, the results of clinical trials,
the company's relative success developing and gaining market acceptance for new
products, the outcome of
significant litigation, and the effectiveness of patent protection. Additional
information regarding risks and uncertainties is set forth in the current Annual
Report on Form 20-F of Aventis on file with the Securities and Exchange
Commission and in the current Annual Report -"Document de Reference"- on file
with the "Commission des Operations de Bourse" in France.
Aventis Contact:
----------------
Corinne Hoff Kara Smith-Russell
Aventis Global Media Relations DI&A Communications
Tel: +33 (0) 3 88 99 19 16 Tel: +1 908 231 4490
Corinne.Hoff@Aventis.com Kara.Smith-Russell@Aventis.com
Regeneron Contact: Regeneron Media Contact:
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Charles Poole Lauren Tortorete
Vice President, Investor Relations Biosector2
Tel: +1 914 345 7640 Tel: +1 212 414 5647
charles.poole@regn.com ltortorete@biosector2.com