By Lisa Seachrist

Washington Editor

WASHINGTON - Aiming to discover small-molecule drugs that can combat asthma and inflammatory bowel disease, LeukoSite Inc. and Warner-Lambert Co. entered into a collaboration that could be worth up to $100 million.

The multiyear deal will fund research at Cambridge, Mass.-based LeukoSite into small-molecule inhibitors of the cell-adhesion molecules known as integrins, which LeukoSite has shown to be associated with inflammatory bowel disease (IBD) and asthma. The move expands a collaboration between Parke-Davis, a division of Morris Plains, N.J.-based Warner-Lambert, and LeukoSite in chemokine research.

"We are delighted the collaboration has expanded to include integrins," said Gus Lawlor, vice president of corporate development and chief financial officer for Leuko Site. "We have had a very productive relationship with Parke-Davis which has helped us to establish the scientific and business respect between the two companies."

The companies will develop small-molecule inhibitors of the specific integrins alphaE-beta7 for the treatment of asthma and alpha4-beta7 for the treatment of IBD. The research will be conducted at LeukoSite as well as at Warner-Lambert's research laboratories in Fresnes, France - the Institut de Recherche Jouveinal/Parke-Davis.

Under the terms of the agreement, Warner-Lambert will pay LeukoSite license fees, research support and milestone payments that could exceed $50 million for each of the two integrin targets, to total more than $100 million. The companies aren't releasing the breakdown of the up-front license fees and other payments.

In addition, LeukoSite will receive royalty payments on any product that comes to market. The collaboration will be reassessed each year according to the progress that is being made.

"Our hope would be to have clinical programs from each target and eventually a drug from each," Lawlor said.

Integrins are a family of cell-adhesion molecules involved in a wide variety of biological events. LeukoSite has been exploring these particular integrins for their role in recruiting and retaining certain leukocytes during the inflammatory process.

The specific integrins covered under this collaboration reside in the cell membrane of certain leukocytes that have been implicated in inflammatory bowel disease and asthma. The companies hope that by very specifically blocking each integrin, they will be able to quell the inflammatory process causing disease without causing overall immune suppression, like with steroids and cyclosporine.

"We are hoping to develop a much more selective, much less toxic drug for these diseases," said Walter Newman, vice president for research and discovery at LeukoSite. "We are aiming to give something systemically that in the end will have a local effect. These integrins look like tractable targets for a small-molecule approach."

LeukoSite currently has a monoclonal antibody, LPD-01, aimed against the alpha4-beta7 integrin in Phase II clinical trials as part of a collaboration with South San Francisco-based Genentech Inc. This Warner-Lambert collaboration extends the integrin program into small-molecule research.

LeukoSite's stock (NASDAQ:LKST) closed Tuesday at $12.50 a share, up $1.50. n