Article in leading scientific journal details Regeneron success in identifying protein factors.

TARRYTOWN, N.Y.--(BUSINESS WIRE)--November 4, 1994--In an article published today in the journal Science, scientists from Regeneron Pharmaceuticals Inc. (NASDAQ:REGN) and Mount Sinai Hospital in Toronto describe their success in identifying a family of protein factors that are likely to act in important ways on the nervous system as well as in other parts of the body.

Regeneron has actively pursued the discovery and acquisition of novel receptor tyrosine kinases, known as "orphan receptors" because their ligands -- or growth factors that bind to them -- have yet to be identified. The company has had success in using these "orphan receptors" to identify novel growth factors, which are compounds that have been found to aid in cell growth and development. All previously identified growth factors (including insulin and nerve growth factor) that bind to receptor tyrosine kinases have been found to have important physiological roles.

Leonard S. Schleifer, M.D., Ph.D., chairman, president and chief executive officer of Regeneron, commented, "The publication of the article is another milestone in the continuing progress of the Regeneron research program. Our ability to identify and understand a new family of protein ligands is a key to Regeneron's strategy to develop and ultimately commercialize proteins with therapeutic benefit."

The article, entitled "Ligands for EPH-Related Receptor Tyrosine Kinases that Require Membrane-Attachment or Clustering for Activity," describes how Regeneron and Mt. Sinai scientists identified and molecularly cloned the factors based on their ability to bind to members of the largest known family of previously "orphan" receptor tyrosine kinases, the EPH-related receptors (named after the EPH-receptor, the first in this family to be identified).

Members of this receptor family are found on an assortment of critical cell types throughout the body, and particularly within the developing and adult nervous system, suggesting an important role for ligands to these receptors. The ligands described by Regeneron scientists have been termed the EFLs (for EPH-family ligands).

While some of these ligands have also been described in recent manuscripts from Amgen and Immunex, the Regeneron manuscript is the first to report the specialized and unconventional manner in which these ligands can activate their receptors. The EFL ligands are normally linked to the cell surface and soluble forms of these ligands -- unlike soluble forms of other growth factors such as stem cell factor or nerve growth factor -- cannot activate their receptors. Thus membrane-linkage seems to provide a specialized mechanism for coupling receptor activation to direct cell-to-cell contact. Regeneron scientists describe a manner in which soluble forms of the EFLs can be activated by deliberate clustering, for the first time allowing soluble forms of these ligands to be evaluated for their biological actions and potential therapeutic applications.

Based on sites of receptor expression a number of diverse cell types -- such as dopaminergic neurons and endothelial cells -- may prove to be important targets of the EFLs.

Regeneron is a leader in the discovery and development of biotechnology-based compounds focused on the treatment of neurodegenerative diseases, peripheral neuropathies, and nerve injuries, including such conditions as Parkinson's disease, Alzheimer's disease, ALS and spinal cord injuries.

CONTACT: Regeneron Pharmaceuticals Inc.

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