Regeneron Receives U.S. Patent Covering Gene Encoding Angiopoietin-2, a Natural Antagonist of Angiogenesis.

TARRYTOWN, N.Y.--(BUSINESS WIRE)--Oct. 7, 1998--Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) announced today that it has received United States Patent No. 5,814,464 covering the gene that encodes human Angiopoietin-2 (Ang2) protein and a method of using the gene to make the Ang2 protein.

Ang2 is a natural antagonist of Angiopoietin-1 (Ang1), Regeneron's proprietary growth factor that promotes blood vessel growth (angiogenesis) and may have a role in the development and growth of blood cells.

All the tissues of the body depend on a robust blood supply for nourishment and sustenance. Disruption of the normal blood supply, for example, can lead to an oxygen-starved heart at risk for myocardial infarction or to painful and ischemic limbs that can cause suffering in diabetics. On the other hand, a growing tumor also depends on its blood supply, and blocking this blood supply can kill a tumor by starvation. Curbing the abnormal blood vessel growth that coats the retina in diabetic retinopathy may also prove beneficial.

Before Regeneron's discovery of the Angiopoietin family, only one family of growth factors specific for blood vessels had been defined and characterized. This family, known as the Vascular Endothelial Growth Factor (VEGF) family, works via receptors specifically expressed on blood vessel cells. Ang1 appears to work in tandem with VEGF to help regulate blood vessel growth. Familial forms of the most common human vascular malformations have been reported to genetically map to mutations in the receptor for Ang1. Expression of Ang1 receptors on primitive hemopoietic stem cells suggests that this factor may also be useful in regenerating blood cells -- as might be beneficial during chemotherapy -- as well as in forming blood vessels.

In two articles published in the December 27, 1996 issue of Cell, Regeneron scientists reported on their discovery of Ang1. In an article published in the July 4, 1997 issue of Science, Regeneron scientists reported on their discovery of Ang2. Ang2 is a natural antagonist of Ang1, blocking Ang1 activation of its receptor on blood vessels. Regeneron scientists have shown that excess Ang2 can disrupt blood vessel formation in laboratory animal experiments. In higher animals, Ang2 provides the first example of a naturally occurring antagonist that can block the ability of a growth factor receptor to transmit a signal.

In May 1996, Regeneron announced that it had received U.S. Patent No. 5,521,073 covering the gene that encodes Ang1 and a method of using the gene to make the Ang1 ligand protein. In July 1997, Regeneron announced that it had received U.S. Patent No. 5,650,490 covering the Ang2 protein.

George D. Yancopoulos, M.D., Ph.D., Senior Vice President, Research, and Chief Scientific Officer at Regeneron noted that, "The cloning of both positive and negative regulators of angiogenesis provides for interesting therapeutic approaches for potential use in clinical situations in which it may be desirable either to promote or block blood vessel growth, such as in ischemic heart disease, diabetic muscular ischemia, diabetic retinopathy, and cancer. We are excited about the possibility that Ang1, the natural agonist, can be very useful in promoting blood vessel formation. Ang2, the antagonist, may have interesting reciprocal actions."

Regeneron is collaborating with The Procter & Gamble Company in the research and development of the Angiopoietins. In May 1997, the Company and Procter & Gamble entered into a broad, ten-year collaboration agreement, pursuant to which Procter & Gamble will provide up to $155 million during the first five years to support Regeneron and its research programs, including the Company's angiogenesis program. Any products resulting from this collaboration are expected to be commercialized jointly worldwide and the profits shared equally.

Regeneron is a leader in the application of molecular and cell biology to the search for novel human therapeutics. Regeneron uses its expertise in growth factors and their mechanisms of action to discover and develop protein-based and small molecule drugs for the treatment of obesity and neurological, inflammatory, and muscle diseases, as well as abnormal bone growth, cancer, and angiogenesis. Amgen-Regeneron Partners is conducting human clinical studies of Regeneron's brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3).

This news release discusses historical information and includes forward looking statements about Regeneron's 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 Form 10-K for the year ended December 31, 1997 and current Form 10-Q, copies of which should be read before making any investment decision regarding Regeneron common stock.

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