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Lexicon's Drug Candidate for Rheumatoid Arthritis, LX2931, Shows Positive Results in Phase 1 Clinical Trial

Lexicon's Drug Candidate for Rheumatoid Arthritis, LX2931, Shows Positive Results in Phase 1 Clinical Trial

Dose-Dependent Decrease in Circulating Lymphocytes Observed

THE WOODLANDS, Texas, April 17, 2008 (PRIME NEWSWIRE) -- Lexicon Pharmaceuticals, Inc. (Nasdaq:LXRX), a leader in genomics-based drug discovery, announced today that it has obtained positive results from its initial Phase 1 clinical trial of LX2931, an orally-delivered, small molecule 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, please view our video presentation on Lexicon's website,

About 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 the Disease

Rheumatoid arthritis is an autoimmune disorder characterized by stiffness, pain, swelling, and limitation of motion in multiple joints. More than 2 million Americans suffer from rheumatoid arthritis, which, if left untreated, can result in disfigurement and disability from irreversible joint damage. According to the National Institutes of Health, autoimmune disorders affect between 14.7 and 23.5 million people in the United States.

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. For additional information about Lexicon and its programs, please visit

The Lexicon Pharmaceuticals, Inc. logo is available at

Safe Harbor Statement

This press release contains "forward-looking statements," including statements relating to Lexicon's clinical development of LX2931 and the potential therapeutic and commercial potential of LX2931. This press release also contains forward-looking statements relating to Lexicon's growth and future operating results, discovery and development of products, strategic alliances and intellectual property, as well as other matters that are not historical facts or information. All forward-looking statements are based on management's current assumptions and expectations and involve risks, uncertainties and other important factors, specifically including those relating to Lexicon's ability to successfully conduct clinical development of LX2931 and preclinical and clinical development of its other potential drug candidates, advance additional candidates into preclinical and clinical development, obtain necessary regulatory approvals, achieve its operational objectives, obtain patent protection for its discoveries and establish strategic alliances, as well as additional factors relating to manufacturing, intellectual property rights, and the therapeutic or commercial value of its drug candidates, that may cause Lexicon's actual results to be materially different from any future results expressed or implied by such forward-looking statements. Information identifying such important factors is contained under "Factors Affecting Forward-Looking Statements" and "Risk Factors" in Lexicon's annual report on Form 10-K for the year ended December 31, 2007, as filed with the Securities and Exchange Commission. Lexicon undertakes no obligation to update or revise any such forward-looking statements, whether as a result of new information, future events or otherwise.

Contact for Lexicon: Bobbie Faulkner Manager, Investor and Public Relations 281/863-3503

Posted: April 2008