P. Roy Vagelos recently let Regeneron Pharmaceuticals Inc.shareholders in on the company's pipeline in his first address to themsince becoming chairman in January.

Company officials for the first time disclosed three research areas thatstemmed from their work that has focused on neurological disorders.What seemed surprising was that the research is in the areas of cancer,muscle disorders and inflammation. But Vagelos _ formerly chairmanand CEO of Merck & Co. _ said it was natural evolution of thescience.

"You have to recognize," Vagelos told BioWorld, "that Regeneron andits scientists are the world leaders in receptors and growth factors ofthe nervous system. They have established this reputation onunderstanding how these ligands, or factors, react with their receptorsand turn on the biological activity of a cell.

"While we have two of these nervous system factors in the clinic, itwas quite natural that our scientists extended their work with receptorsto other cells that might be implicated in diseases.

"They have looked around the body, and that's what led us to theblood vessel-specific receptors, and a new family of ligands, and amuscle-specific receptor and its ligand. When these receptors werediscovered they were found to be enormously up-regulated in certaininstances."

The three areas are a class of cytokine antagonists, focused oninterleukin-6 (IL-6); a family of ligands involved in angiogenesis(blood vessel growth); and a ligand for a muscle-specific growth factor."They are all very early," Vagelos said. "Hopefully, in due time, wewill have product candidates, but I would not call these productcandidates at this time."

Regeneron, through its partnership with Thousand Oaks, Calif.-basedAmgen Inc., has two products in the clinic. Encouraging results of aPhase I/II trial of brain-derived neurotrophic factor (BDNF) led to theannouncement that a pivotal Phase III trial of the product inamyotrophic lateral sclerosis will begin in the third quarter. Thepartners also have neurotrophin-3 in a Phase I trial in peripheralneuropathies.

Last year Regeneron discontinued development of ciliary neurotrophicfactor (CNTF) for amyotrophic lateral sclerosis. The news resulted in asignificant drop of the company's stock price, which didn't head backup until Vagelos was named chairman in January. Since then it's gonefrom around $3.50 to $9 per share. On Monday, the stock(NASDAQ:REGN) closed down 13 cents at $8.88.

While one never knows fully about the competition, Vagelos said, thecompany believes it has a very good position on all three projects.

In the angiogenesis program, Regeneron researchers found bloodvessel-specific factors and receptors were up-regulated in tumors andtissue undergoing repair. "It becomes immediately interesting inpotential anti-tumor therapy if one could interrupt the growth of ablood vessel into a tumor," Vagelos said.

The company said it has cloned a new family of naturally occurringprotein ligands important in angiogenesis.

In muscle receptors, it was discovered that they are up-regulated undertwo circumstances: when there is nerve damage, or when the muscle isinactivated by immobilization. "It would appear the muscle atrophy,when inactive from disease, would be a reaction by up-regulating thereceptors," Vagelos said, adding that researchers saw up-regulation ineither nerve damage or inactivity.

The muscle, he said, is seeking a factor that would try to correct thesituation. "Our scientists have isolated that factor," Vagelos said.

The IL-6 antagonist program came from the work in understanding theCNTF receptor, which is related to the specific receptor for IL-6.

"Our scientists have constructed a specific antagonist that willneutralize interleukin-6," Vagelos said. "IL-6 levels are very high in thepresence of certain tumors _ lymphoma, renal cell carcinoma, multiplemyeloma and others _ as well as AIDS, chronic infections andinflammatory conditions. It's believed interleukin-6 causes the weightloss and fever associated with these conditions.

"If one were to lower the interleukin-6 levels," he continued, "onecould treat these symptoms."

The work, Vagelos said, "demonstrates this group is so capable inreceptors and ligands that it will continue to lead the pack." n

-- Jim Shrine

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