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Lexicon Presents Class of Compounds Modulating TPH1, the Target for its LX1031 Investigational Drug for Irritable Bowel Syndrome
Date:8/21/2007

BOSTON and THE WOODLANDS, Texas, Aug. 21 /PRNewswire-FirstCall/ -- Lexicon Pharmaceuticals, Inc. (Nasdaq: LXRX) presented data today describing the structure-activity relationship (SAR) of a class of internally-developed compounds that includes LX1031 and other compounds under evaluation by the company as potential treatments for irritable bowel syndrome (IBS) and other gastrointestinal disorders. LX1031 is currently under evaluation in a Phase 1b clinical trial in healthy volunteers.

Employing high-throughput screening of its proprietary chemical libraries, x-ray crystallography and medicinal chemistry, Lexicon scientists discovered and optimized a series of orally-administered, peripherally-acting small molecule inhibitors of the key enzyme responsible for producing serotonin in the gastrointestinal tract, tryptophan hydroxylase 1 (TPH1). In preclinical studies with these molecules, including LX1031, Lexicon scientists confirmed that serotonin levels could be predictably reduced in the intestine without affecting levels of the neurotransmitter in the brain, where it mediates mood and other behaviors. The data were presented here today at the American Chemical Society National Meeting and Exposition in Boston.

"Our genetic insights and chemistry expertise enabled us to discover a class of potent molecules that can inhibit TPH activity in the gastrointestinal tract while preserving normal levels of serotonin in the brain, an accomplishment we believe represents a significant advance for the field," commented Arthur T. Sands, M.D., Ph.D., president and chief executive officer of Lexicon Pharmaceuticals. "Given serotonin's established role as a neurotransmitter modulating gastrointestinal function, these findings have allowed us to pursue a potential new mechanism for treating conditions, such as IBS, that are not well-served by current therapies."

Using Lexicon's proprietary knock-out mouse technology, company scientists established that serotonin in the brain and neurons is synthesized by TPH2, an enzyme related to but distinct from TPH1, which is responsible for the synthesis of almost all peripheral serotonin. Knock-out studies showed that mice lacking a functional TPH1 gene exhibited normal brain levels of serotonin with no detectable levels in the periphery. Importantly, the TPH1 knockout mice were healthy and exhibited no significant adverse effects.

Top-line Phase 1 clinical results for LX1031 are expected to be presented at the American College of Gastroenterology's Annual Scientific Meeting in Philadelphia in October.

About Lexicon

Lexicon is a biopharmaceutical company focused on the discovery and development of breakthrough treatments for human disease. Lexicon currently has development programs underway for such areas of major unmet medical need as irritable bowel syndrome and cognitive disorders. 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 diabetes and obesity, cardiovascular disease, psychiatric and neurological disorders, cancer, immune system disorders and ophthalmic disease. To advance the development and commercialization of its programs, Lexicon is working both independently and through collaborators including Bristol-Myers Squibb Company, Genentech, Inc. and N.V. Organon. For additional information about Lexicon and its programs, please visit http://www.lexpharma.com.

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, 2006, 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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SOURCE Lexicon Pharmaceuticals, Inc.
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