July 29, 2008

Lexicon Pharmaceuticals’ Drug Candidate for Irritable Bowel Syndrome Completes Phase 1 Clinical Trial Showing Positive Results

THE WOODLANDS, Texas, July 29, 2008 (PRIME NEWSWIRE) -- Lexicon Pharmaceuticals, Inc. (Nasdaq:LXRX), a biopharmaceutical company focused on discovering and developing breakthrough treatments for human disease, announced today that it has successfully completed a Phase 1 multiple-dose escalation study in normal volunteers with LX1031, its oral drug candidate for irritable bowel syndrome (IBS). The company plans to progress the new drug candidate into Phase 2 studies in the fourth quarter. LX1031 is one of four programs in human clinical trials as part of Lexicon's 10TO10 program.

"LX1031 will be our second drug candidate to enter Phase 2 testing," said Arthur T. Sands, M.D., Ph.D., president and chief executive officer. "Our drug discovery strategy is continuing to produce a pipeline of drug candidates working through novel mechanisms that could ultimately enhance the lives of patients worldwide."

The recently completed trial was a randomized, double-blind, ascending multiple-dose study in which all dose levels were well tolerated over 14 days and no dose limiting toxicities were observed. LX1031 is designed to treat symptoms associated with IBS by decreasing the production of serotonin in the gastrointestinal tract. Serotonin is a key regulator of gastrointestinal sensation and motility. Importantly, the study showed that LX1031 decreased urinary 5-hydroxyindoleacetic acid (5-HIAA), a metabolite of serotonin and biomarker for serotonin production, at all dose levels tested as compared to the placebo group. These results are consistent with a significant reduction in gastrointestinal serotonin synthesis. Doses tested in this study were 250 mg, 500 mg, 750 mg, and 1,000 mg, each administered four times daily. Data from this study will be utilized to select a dosing regime for the Phase 2 proof-of-concept clinical trial.

"LX1031 has demonstrated an excellent safety and tolerability profile in Phase 1 clinical studies, consistent with our observations in preclinical studies," said Philip M. Brown, M.D., J.D., senior vice president of clinical development at Lexicon. "We are eager to assess LX1031 in patients suffering from IBS, who have limited treatment options."

Phase 2 Study

Based on the successful outcome of this Phase 1 study, Lexicon expects to initiate a Phase 2 proof-of-concept clinical trial in IBS patients in the fourth quarter of this year. The clinical trial is planned as a four-week, randomized, double-blind, placebo-controlled study designed to evaluate the safety, tolerability, and effects of LX1031 on symptoms associated with IBS.

About LX1031

LX1031 is an oral drug candidate for IBS and other gastrointestinal disorders. LX1031 was generated by Lexicon medicinal chemists, and its target was internally identified as a key control point for the regulation of peripheral serotonin levels. LX1031 is designed to act locally in the gastrointestinal (GI) tract by reducing the serotonin available for receptor activation, without affecting serotonin levels in the brain or its central nervous system functions. In preclinical studies, LX1031 showed a dose-dependent reduction of serotonin levels in the GI tract.

The target of LX1031 is tryptophan hydroxylase (TPH), a key enzyme in the synthesis of serotonin. Lexicon discovered that mice lacking TPH1, the form of this enzyme found predominantly in the gastrointestinal tract, have virtually no peripheral serotonin but normal levels of brain serotonin.

LX1031 is being developed in a product development collaboration with Symphony Capital Partners, L.P. and its co-investors.

About Irritable Bowel Syndrome

Irritable bowel syndrome is a disorder most commonly characterized by cramping, abdominal pain, bloating, constipation or diarrhea. Symptoms of IBS are believed to be mediated through serotonin, a neurotransmitter that is produced primarily in the GI tract, which has been shown to play an important role in modulating motility and signaling feelings of GI discomfort to the brain.

About Lexicon

Lexicon is a biopharmaceutical company focused on discovering and developing breakthrough treatments for human disease. Lexicon currently has five drug candidates in development for autoimmune disease, carcinoid syndrome, cognitive disorders, diabetes and irritable bowel syndrome, all of which were discovered by the company's research team. The company is using its proprietary gene knockout technology to characterize approximately 5,000 genes in its Genome5000(tm) program, and has discovered more than 100 promising drug targets. Lexicon has applied small molecule chemistry and antibody technology to these biologically-validated targets to create its extensive pipeline of clinical and preclinical programs. Lexicon's goal is to advance 10 drug candidates into human clinical trials by the end of 2010, the strategic objective of its 10TO10 program. For additional information about Lexicon and its programs, please visit www.lexpharma.com.

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Safe Harbor Statement

This press release contains "forward-looking statements," including statements relating to Lexicon's clinical development of LX1031, and the potential therapeutic and commercial potential of LX1031. 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 LX1031, 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.

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 CONTACT:  Lexicon Pharmaceuticals, Inc.           Bobbie Faulkner, Manager, Investor             and Public Relations           281/863-3503           [email protected]