Lexicon-Genentech reveals potential therapeutic targets

Lexicon Genetics Incorporated has announced that data was presented highlighting potential therapeutic targets related to its collaboration with Genentech, Inc. at the Society for Biomolecular Sciences 13th Annual Conference & Exhibition in Montreal, Canada.

These target discoveries were made in a collaboration between Lexicon and Genentech that was initiated in December 2002 and expanded in November 2005 to advance the research, development and commercialization of new biologic drugs. Lexicon has developed antibodies for one of these targets, designated LG842, which it is now advancing through preclinical research.

Data presented today revealed that the deletion or neutralization of LG842, a circulating protein expressed predominantly in adipose tissue, placenta, pancreas and liver, resulted in lower triglycerides and cholesterol in in vivo models.

"Our in vivo studies, recently corroborated by human genetic data, have defined an important new pathway for potential treatments of dyslipidemia and metabolic disorders related to cardiovascular disease," commented Brian P. Zambrowicz, Ph.D., Lexicon's chief scientific officer. "We believe that our collaboration with Genentech has been enormously fruitful. We have been able to elucidate the function of a number of genes that have shown promise in important areas of medicine."

In preclinical studies, treatment with Lexicon's LG842 antibodies was shown to decrease plasma triglycerides and cholesterol. Lexicon has the option to choose six targets from the collaboration to advance into biotherapeutics drug discovery efforts. LG842 was one of the first two targets selected by Lexicon for internal development.

Gene Knockout Technology

Lexicon's proprietary technology allows scientists to create in vivo models in which certain genes have been altered in order to discover the physiological and behavioral effects that result from the loss of the functioning protein encoded by the disrupted gene. Lexicon's gene knockout technology is being employed in the Company's Genome5000(TM) program to discover the physiological and behavioral functions of proteins encoded by 5,000 genes believed to be pharmaceutically important. To date, Lexicon has completed analysis of approximately 80% of these genes, and has identified and validated more than 100 potential antibody and small molecule targets with promising profiles for drug discovery. Two drug candidates discovered by Lexicon against such targets, LX6171 for cognitive impairment and LX1031 for irritable bowel syndrome, have entered the clinic. LX6171 and LX1031 mark the first two clinical candidates for Lexicon's 10TO10 Program, an initiative to move ten drug candidates into human clinical trials through 2010.

Lexicon's drug discovery collaboration was initiated with Genentech in December 2002 and expanded in November 2005 to include the advanced research, development and commercialization of new biologic drugs. Under the original collaboration, Lexicon used its gene knockout technology to discover the functions of secreted proteins and potential antibody targets identified through Genentech's internal drug discovery research. In the expanded collaboration, Lexicon is conducting additional, advanced research on a broad subset of those proteins and targets. Lexicon may develop and commercialize biotherapeutic drugs for up to six of these targets, with Genentech having exclusive rights to develop and commercialize biotherapeutic drugs for the other targets. Genentech retains an option on the potential development and commercialization of the biotherapeutic drugs that Lexicon develops from the collaboration under a cost and profit sharing arrangement, while Lexicon has certain conditional rights to co-promote drugs on a worldwide basis. Lexicon retains certain other rights to discoveries made in the collaboration, including non-exclusive rights, along with Genentech, for the development and commercialization of small molecule drugs addressing the targets included in the collaboration.

Lexicon received upfront and performance payments in connection with the original collaboration and its expansion and continues to receive research funding for its work in the expanded collaboration. Lexicon is also entitled to receive milestone payments and royalties on sales of therapeutic proteins and antibodies for which Genentech obtains exclusive rights. Genentech is entitled to receive milestone payments and royalties on sales of therapeutic proteins and antibodies for which Lexicon obtains exclusive rights.