Lexicon Presents Clinical Data for Cognitive Disorder Drug

Lexicon Identifies Transporter in Brain as the Target for LX6171

THE WOODLANDS, Texas -- Lexicon Pharmaceuticals, Inc. (Nasdaq:LXRX), a leader in genomics-based drug discovery, presented data on Tuesday, April 15, 2008 describing the target of LX6171 and initial Phase 1 clinical results at the American Academy of Neurology in Chicago. LX6171 is an internally-developed compound under evaluation by the company as a potential treatment for cognitive disorders. The compound, currently in Phase 2 clinical testing, is one of four programs in human clinical trials as part of Lexicon's 10TO10 program.

LX6171 is an orally-delivered, small molecule inhibitor of SLC6A7, a high-affinity L-proline transporter found in the brain. SLC6A7 is a member of the gamma-aminobutyric acid (GABA) neurotransmitter transporter family, and is expressed in regions of the brain that are known to be involved in learning and memory. In preclinical studies, mice treated with LX6171 displayed improved performance in tests of learning and memory, corroborating observations in knockout mice lacking SLC6A7.

"Until we identified and analyzed SLC6A7 in our Genome5000(tm) program, relatively little was known about this transporter and its role in behavior," said Dr. Brian Zambrowicz, Lexicon's chief scientific officer. "Our results indicate that inhibiting this target may delineate a novel approach to the treatment of cognitive disorders."

"Initial human studies with both young and elderly volunteers have shown that the compound achieves good systemic exposure and is well tolerated at the doses studied," said Philip M. Brown, M.D., J.D., senior vice president of clinical development at Lexicon. "LX6171 may have potential in a broad range of applications involving cognitive disorders, including Alzheimer's disease, attention disorders, and developmental disorders."

Clinical Results

In Phase 1 clinical trials, LX6171 was generally well tolerated at all dose levels and showed good systemic exposure with no significant adverse events or cognitive impairment observed. Preliminary data on attention parameters were encouraging and suggest the appropriateness of proceeding with further studies to determine if LX6171 could have a potential effect on cognitive or attention disorders.

LX6171 is currently under evaluation in a Phase 2 clinical trial to evaluate the safety, tolerability and cognitive effects of LX6171 in approximately 100 elderly subjects with age-associated memory impairment (AAMI). The placebo-controlled trial will include a low dose group receiving 120 mg of the drug candidate once per day, and a higher dose group receiving 240 mg once per day. Both groups will receive the drug candidate for 28 days and will be evaluated regularly for effects on several dimensions of learning and memory. LX6171 is being developed in a product development collaboration with Symphony Capital Partners, L.P. and its co-investors.

About Lexicon
Lexicon is a leader in genomics-based drug discovery. Through its proprietary gene knockout technology, the company is dedicated to discovering and developing breakthrough treatments for human disease. For more information, please visit the Company's Web site.