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Lexicon's Arthritis Drug Shows Positive Results in Clinical Trial

Published 04/17/2008

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Dose-Dependent Decrease in Circulating Lymphocytes Observed

THE WOODLANDS, Texas -- Lexicon Pharmaceuticals, Inc. (Nasdaq:LXRX) has announced that it has obtained positive results from its initial Phase 1 clinical trial of LX2931, an orally-delivered drug candidate for the treatment of rheumatoid arthritis and other autoimmune conditions. LX2931 is one of four programs in human clinical trials as part of Lexicon's 10TO10 program.

Initial results from this single ascending-dose trial in healthy volunteers demonstrated a potent, dose-dependent reduction in circulating lymphocytes, suggesting that the target of LX2931 may represent a new mechanism for regulating the immune response. Lymphocytes are a type of white blood cell that play an important role in the immune system. Inappropriate activation of lymphocytes is often associated with autoimmune diseases, a spectrum of disorders in which the immune system malfunctions and causes the body to attack its own organs, tissues and cells.

"We are very encouraged by these early but clear results, which reinforce the company's overall drug discovery strategy," said Dr. Arthur Sands, president and chief executive officer. "The immune system regulation we originally observed in animal models was reproduced in humans with the administration of single doses of our drug candidate."

Lexicon has shown previously that genetically "knocking out" or "knocking down" the target of LX2931, sphingosine-1-phosphate (S1P) lyase, substantially reduces the number of circulating lymphocytes, modulating the immune response in multiple animal models of autoimmune disease. Importantly, LX2931 has demonstrated significant pharmacology in preclinical and now clinical studies consistent with the original observations in knockout animals.

"This initial Phase 1 trial demonstrated that single, well-tolerated doses of LX2931 can produce a meaningful reduction in lymphocytes," said Philip M. Brown, M.D., J.D., senior vice president of clinical development at Lexicon. "We are encouraged not only by the rapid onset of action, but also by the timely recovery of lymphocyte counts as the drug candidate is cleared from the system. Based on these results, we are actively pursuing a multidose trial with LX2931." For additional information about the results of this study, Lexicon has posted a video presentation on the company's Web site.

The Clinical Trial

The Phase 1a trial was a single ascending-dose tolerance study assessing the safety, tolerability, and pharmacokinetics of LX2931 in healthy volunteers. Seven dose levels of LX2931, ranging from 10 to 180 mg, were assessed in a double-blind, randomized fashion. A dose-dependent decrease in absolute lymphocyte counts was observed, with a maximal effect noted at approximately 24 hours post dose. Importantly, lymphocyte counts were approaching baseline values by 48 hours post dose. Adverse events were distributed across subjects in each dose group and the placebo group. Adverse events included mild gastrointestinal upset, headache and mild leukocytosis. One subject experienced asymptomatic mild elevations of liver function tests (LFTs) to less than one and one-half times the upper limit of normal and another subject experienced biliary colic with abnormal LFTs. No significant changes in vital signs (including pulse rate) or ECG changes were noted after administration of LX2931.

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. Lexicon currently has development programs underway for such areas of major unmet medical need as irritable bowel syndrome, cognitive disorders, autoimmune diseases, and carcinoid syndrome. The company has used its proprietary gene knockout technology to discover more than 100 promising drug targets and create an extensive pipeline of clinical and preclinical programs in the therapeutic areas of cardiology, gastroenterology, immunology and oncology, metabolism, neurology and ophthalmology. To focus its commitment, Lexicon initiated its 10TO10 program to advance 10 new drug candidates into human clinical trials by the end of 2010. To advance the development and commercialization of its programs, Lexicon is working both independently and through collaborators including Bristol-Myers Squibb Co., Genentech, Inc. and N.V. Organon.

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