By Jim Shrine

Senior

Decades of research into the effects of cigarettes by R.J. Reynolds Tobacco Co. led to the signing of a deal to work with Rhone-Poulenc Rorer Inc. (RPR) to develop drugs that work on nicotinic receptors for Alzheimer's and Parkinson's diseases.

Winston-Salem, N.C.-based R.J. Reynolds' wholly owned subsidiary, Targacept Inc., also of Winston-Salem, granted RPR exclusive worldwide rights to certain compounds that have shown promise in treating the neurodegenerative diseases. Financial terms of the deal were not disclosed.

Sibia Neurosciences Inc., of La Jolla, Calif., is the clear front-runner in this field, with its small-molecule subtype-selective nicotinic agonist, SIB-1508Y, in two Phase II studies for Parkinson's disease. It also has a compound in humans for Alzheimer's disease. Abbott Laboratories, of Abbott Park, Ill., also is working on nicotinic receptors. It has conducted an early-stage trial, targeting pain.

Sibia president and CEO William Comer said the field has drawn a lot of interest, due to a January 1997 article in Science from Abbott and a few conferences on the subject in recent years.

"Interest by big pharma has increased rapidly," Comer said, adding that some companies have approached Sibia about possible alliances and others are setting up work in their own shops.

RPR, of Collegeville, Pa., is using the collaboration to bolster its presence in diseases of the central nervous system (CNS). Its product, Rilutek, is approved for treating amyotrophic lateral sclerosis, and is beginning to be tested for Parkinson's disease. But RPR hasn't much else in that area.

"This strengthens our commitment to CNS, to building a CNS product line," said Sheryl Williams, RPR's senior manager for communications. "In particular, we are looking at diseases that will be on the rise due to the aging of the baby boomer population."

Targacept was formed in 1997 to capitalize on research on compounds that interact with nicotinic receptors. The company said that approach also could have utility in treating attention deficit disorder, ulcerative colitis and schizophrenia.

"Reynolds Tobacco, for many decades, has investigated the chemistry and biology of nicotine as it related to understanding our products better," R.J. Reynolds spokesman Nat Walker said. "In the early 1990s, there were some important factors that converged in the area of nicotine research: a discovery that nicotine interacts with several types of receptors within the body, and the finding that biological effects of nicotine could be better understood by developing nicotinic compounds which were selective for specific types of receptors.

"Then, the evidence that a number of chronic debilitating diseases, such as Alzheimer's and Parkinson's, are associated with deficiencies in nicotinic receptors," Walker said. "And the evidence that these diseases could be treated with nicotine and nicotine-like compounds that target the specific receptors associated with the disease.

"Now, we have some nicotinic compounds that might be helpful as therapies for those diseases," Walker said. "We have done some of the basic research and now, with our arrangement with Rhone-Poulenc, they will further develop these compounds as therapeutic vehicles."

The deal also establishes a two-year collaboration for further development of selective nicotinic compounds. The agreement provides potential payments to Targacept in license fees, research funding, milestone payments and royalties. RPR also might make an equity investment in Targacept.

Comer said Sibia's approach was different from others in the field because it identified the various nicotinic receptor subtypes in the human brain, then established a library of recombinant receptor subtypes.

"I think that distinguishes us from companies that come to it with nicotine analogues," Comer said. "We have a lock on the area of recombinant receptors in the nicotinic field."

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