Two companies with complementary technologies in interleukin-1aconverting enzyme (ICE) inhibitors pooled their efforts in what theysaid might be the industry's first research-to-marketing collaborationbetween two pharmaceutical companies.

Warner-Lambert Co. and the BASF Group said Thursday they are ina collaborative agreement in which both the risks and reward will beshared equally. Several units from both companies will participate inthe program, which is intended to involve equal researchcontributions and equal ownership of any resulting products.

ICE is an enzyme that generates the active form of interleukin-1a, acytokine that's a key mediator in the early stages of inflammation andalso is implicated in neurodegenerative and other diseases. Thecollaborators likely will target rheumatoid arthritis, Alzheimer'sdisease and septic shock initially, Peter Wolf, Warner-Lambert'sdirector of media relations, told BioWorld.

Warner-Lambert, based in Morris Plains, N.J., will contribute mostlythrough its Parke-Davis Pharmaceutical Research division. Fourunits, in the U.S. and Germany, will participate for BASF, based inLudwigshafen, Germany.

"We hope to have a clinical candidate in a couple of years," RobertKamen, president of BASF Bioresearch Corp. in Worcester, Mass.,told BioWorld. "We've greatly increased the probability of achievingthat by tying up with our friends at Parke-Davis."

It is the first collaboration between the companies. And this unioncame about only because of a chance connection between officials atthe two companies, both of which had ICE programs ongoing, Wolfsaid.

Others working in the emerging area include Merck & Co. Inc., ofWhitehouse Station, N.J.; Vertex Pharmaceuticals Inc., ofCambridge, Mass., which is in a program with Paris-based RousselUclaf; Immunex Corp., of Seattle; and Sandoz Ltd., of Basel,Switzerland.

Two Against One

Kamen said the pressures of limited resources and developing noveldrugs in the pharmaceutical industry are leading to a variety ofcollaborations. Together, medium-sized companies such as Warner-Lambert and BASF can be more competitive against the likes ofMerck, he said.

"We couldn't think of another situation in which two pharmaceuticalcompanies decided to join forces in the early stages of research andform a joint project team that will discover the drugs," Kamen said."Both companies have been working on this for more than two yearsalready. It's a full-blown drug-discovery effort heavily based inchemistry. It's very much a structure-based drug design effort."

The goal of the partnership, Kamen said, is to develop orallyavailable small molecules that block the action of IL-1a convertingenzyme.

BASF scientists mapped the 3-D structure of ICE using X-raycrystallography, results of which were published last summer. In theFeb. 10 issue of the journal Cell, BASF researchers said ICE-deficient mice are highly resistant to death caused by endotoxicshock, an acute inflammatory disease.

Parke-Davis scientists cloned the ICE gene from rats. The gene hasbeen used to probe the anatomical distribution and regulation of theICE gene expression in the brain and other tissues. n

-- Jim Shrine

(c) 1997 American Health Consultants. All rights reserved.