By Frances Bishopp

In its first such collaboration, apoptosis company LXR Biotechnology Inc. has signed an agreement with Oxford Asymmetry to discover small molecule drug candidates that target specific apoptosis pathways.

Under terms of the agreement, the Richmond, Calif. company will provide its automated screening systems that have been developed for specific gene targets and general mechanisms of apoptosis.

Oxford Diversity, a division of Oxford Asymmetry, of Abingdon, U.K., will provide libraries of diverse, well characterized compounds for screening using technology in the areas of organic chemistry and combinatorial chemistry.

No financial terms were disclosed.

David Tomei, CEO of LXR, said his company, which has adopted a focused discovery program in which drugs were discovered and structures were identified, has now gone to Oxford for diversification of the structures.

LXR has developed an assay system to screen small molecules that may affect apoptosis (programmed cell death). The failure of cells to undergo apoptosis in a timely manner can play a critical role in proliferative diseases such as cancer: conversely, if cells undergo apoptosis prematurely, the result can be severe tissue damage such as evidenced in stroke.

"We started with complex mixtures we knew had the ability to suppress the death of cells and, using the in vitro screen, we identified the molecules," Tomei explained.

This process has led to Lexirin, currently going into Phase II clinical trials, which is being studied for suppression of severe diarrhea associated with AIDS and the effects of chemotherapy and radiation in the treatment of cancer.

Also in the pipeline for LXR is Elirex, currently coming out of preclinical study, which is used to suppress apoptosis in liver transplantation and suppression of acute myocardial infarction following heart attack.

"With all of the programs we have, we have already identified the molecules, we have the mechanism, we have the receptors and the key genes in heart and brain that are modulated by these," Tomei said. "Oxford Diversity's job is to begin looking at variations on the structure rather than just a blind screen, which we don't think is a very productive way of looking for drugs.

"Oxford's compounds will be going into a system that we have already demonstrated is capable of identifying drugs that work, not only in cell cultures, but in animals," Tomei said. "The big question now is 'can we identify increasing numbers of related structures and can we then move from our in vitro screen to animals, improve the behavior and expand the number of applications?'"

In 1993, Tomei and other researchers at LXR identified a suicide gene that, they said, may play a key role in the death of heart muscle cells during a heart attack. The gene, called Bak, for Bcl-1 homologous antagonist/killer, also plays a part in promoting cell death in other clinical situations, such as cardiopulmonary bypass surgery or heart transplantation.

Other drugs in development for LXR are HK-Cardiosol, a preservation solution for use during heart transplantation, which is going into the last clinical trial prior to asking the FDA for permission to market and CP-Cardiosol, used to prevent damage to the heart and other organs during heart/lung bypass, and soon to go into clinical trials

LXR, which raised $19.6 million in two private offerings in 1996, has a burn rate of $700,000 a month. LXR's stock (NASDAQ:LXR) closed Tuesday at $2.25, up $0.25. *