Regeneron receives U.S. patent covering novel growth factor for receptor localized to blood vessels and hemopoietic stem cells.

TARRYTOWN, N.Y.--(BUSINESS WIRE)--May 29, 1996--Regeneron Pharmaceuticals Inc. (NASDAQ: REGN) announced today that it has received U.S. Patent No. 5,521,073 covering the gene that encodes the human Tie-2 ligand protein and a method of using the gene to make the Tie-2 ligand protein, a growth factor involved in blood vessel formation whose receptor is also present on hemopoietic stem cells.

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 damaging the blood vessels (arteries, veins, and capillaries). The decreased blood flow that results from such diseases can result in non-healing skin ulcers and gangrene, painful limbs that cannot tolerate exercise, loss of vision, and heart attacks. Building new vessels (a process known as angiogenesis) might not only help in the potential treatment of these disease processes, but could also allow for better recovery following surgery and aid in the acceptance of skin and bone grafts. In some cases, on the other hand, restricting blood flow may be useful in the treatment of disease. For example, cancers subvert the body's blood vessels and recruit them for the purpose of maintaining their own cancerous growth and metastasis; preventing the recruitment of blood vessels to tumors could be used to starve the cancer and prevent its growth. Such therapies are currently unavailable.

Before the discovery of the Tie family, only one family of growth factors specific for blood vessels had been defined and characterized. Vascular endothelial growth factor (VEGF) and its close relatives act specifically to regulate blood vessel growth because the receptors that recognize these factors are found only on blood vessel cells. Extensive ongoing efforts by academic researchers and the pharmaceutical industry are focused on using VEGF, or blockers of the VEGF, either to promote or restrict blood vessel growth, for possible use in the therapeutic applications outlined above.

Regeneron scientists have identified a second family of growth factors specific for blood vessels. The United States Patent and Trademark Office has issued Regeneron a patent for the first member of this second family of growth factors specific for blood vessels. Regeneron scientists exploited a novel class of receptors expressed almost exclusively on blood vessels, known as the Tie receptors, by developing a novel technology that allowed them to molecularly clone the growth factors binding to these receptors. Preclinical genetic evidence has demonstrated that both the VEGF family and the Tie growth factors are required for normal blood vessel formation and that these two families appear to act together in a coordinated fashion.

The Tie receptors are also expressed on the surface of primitive hemopoietic stem cells, the precursors of all the different blood cells. Thus, the Tie growth factors may also be important in regulating blood cell formation by the process known as hemopoiesis. Other hemopoietic growth factors have proven useful in generating different types of blood cells in clinical settings -- such as cancer chemotherapy -- when deficits of red blood cells, white blood cells, and platelets can occur.

George D. Yancopoulos, M.D., Ph.D., Regeneron's Vice President of Discovery, who directed the Tie research, noted that, "Our plans for further research in the Tie area includes comparing the therapeutic roles of the VEGF family and our Tie growth factors, to further understand their individual as well as combined capabilities for blood vessel growth. Similarly, it will be interesting to further explore how the Tie growth factors may interact with other hemopoietic growth factors."

Leonard S. Schleifer, M.D., Ph.D., president and chief executive officer of Regeneron, commented that, "This patent serves to confirm our leading role not only in neurotrophic factor research, but in fundamental growth factor research in general. Following on the heels of our recent publications about our basic research describing a novel muscle-specific receptor and the growth factor which activates it, Regeneron's research in Ties brings to our arena two more cutting-edge areas -- angiogenesis and hemopoiesis -- where Regeneron now has proprietary growth factors as potential therapeutic agents."

Regeneron is a leader in the application of molecular and cell biology to discover novel potential therapeutics for human medical conditions. The company is applying its expertise in protein growth factors, their receptors, and their mechanisms of action to the discovery and development of neurotrophic factors for the potential treatment of neurodegenerative diseases, peripheral neuropathies, and nerve injury. Regeneron is collaborating with Amgen Inc. in the development of two neurotrophic factors, brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) each of which is in human clinical studies. More recently, Regeneron has used its technological expertise to attempt to identify treatments for diseases and conditions outside of the nervous system, such as inflammation and the cachexia that often accompanies cancer, angiogenesis and hemopoiesis, and muscle disease.

This news release discusses historical information and includes forward-looking statements that involve a number of risks and uncertainties, such as risks associated with preclinical and clinical development in the biotechnology industry in general (and of the Tie family in particular), determinations by regulatory and administrative governmental authorities, competitive factors (including the development of VEGF by industrial and academic researchers), technological developments, costs of developing, producing and selling products, intellectual property developments relating to the Tie family and other matters, and the risk factors listed or described from time to time in the company's filings with the Securities and Exchange Commission, including, but not limited to, the reports on Form 10-K for the year ended Dec. 31, 1995 and Form 10-Q for the quarter ended March 31, 1996. -0-

Regeneron's recent news releases can be obtained by dialing

800-311-0841 for fax copies or by accessing the Internet at

http://www.businesswire.com

CONTACT: Regeneron Pharmaceuticals Inc., Tarrytown

Murray A. Goldberg, 914/345-7492

or

Robinson Lerer Sawyer Miller, New York

Michael Gross, 212/484-7721