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Lexicon's Drug Candidate LX1032 for Carcinoid Syndrome Successfully Completes Phase 1 Clinical Trials

 * Drug Candidate Will Advance to Phase 2 Clinical Trial in Carcinoid  Patients

* Potent Reduction in Serotonin Achieved

*Drug Candidate Being Developed Under Fast Track Status From FDA

THE WOODLANDS, Texas, Nov. 13, 2008 (GLOBE NEWSWIRE) -- LexiconPharmaceuticals, Inc. (Nasdaq:LXRX), a biopharmaceutical companyfocused on discovering and developing breakthrough treatments for humandisease, announced today that it has successfully completed a second Phase 1 clinical trial of LX1032, an orally-delivered small moleculedrug candidate for managing gastrointestinal symptoms associated withcarcinoid syndrome. Based on the results from this study, Lexicon isplanning to initiate a Phase 2 study in patients with carcinoidsyndrome. LX1032 will be Lexicon's third drug candidate to progress toPhase 2 clinical trials.

In the recently-completed Phase 1b multiple ascending-dose trial,LX1032 was well tolerated at all doses, including the maximum dailydose of 1,500 mg over the 14-day dosing period. Results from this trialdemonstrated a potent reduction in both blood serotonin levels andurinary 5-HIAA, a marker of serotonin biosynthesis, at doses from 500mg to the maximum dose of 1,500 mg, indicating that the target ofLX1032 represents a new mechanism for regulating peripheral serotoninsynthesis. The reduction in blood serotonin and urinary 5-HIAA levelsobserved in the multiple-dose study in normal healthy volunteers isconsistent with the reduction in serotonin levels observed inpreclinical animal models -- demonstrating conservation of themechanism of action from mouse to man.

"The substantial reduction in serotonin observed in this study confirmsour preclinical observations and suggests potent inhibition ofperipheral serotonin production," said Philip M. Brown, M.D., J.D.,senior vice president of clinical development at Lexicon. "We are eagerto test the compound in patients with carcinoid syndrome who sufferfrom significant gastrointestinal symptoms relating to theoverproduction of serotonin."

In June 2008, Lexicon received Fast Track designation from the FDA fordevelopment of LX1032. Fast Track status facilitates the development ofpotential new drugs and expedites the review of new drugs intended toserve unmet medical needs in serious or life-threatening conditions.

Clinical development of LX1032 is being funded through a productdevelopment collaboration with Symphony Capital Partners, L.P. and itsco-investors.

About the Clinical Trial

The Phase 1b trial was a randomized, double-blind, placebo-controlled,multiple ascending-dose study assessing the safety, tolerability, andpharmacokinetics of LX1032 in 40 healthy volunteers. Five dose levelsof LX1032, ranging from 100 mg to 1,500 mg daily, were assessed. LX1032was well tolerated at all dose levels and produced a dose-dependentreduction in blood serotonin and urinary 5-HIAA levels, with maximal,statistically-significant reductions observed at doses at or above 500mg. A dose-dependent, mild increase in hepatic transaminase levels wasobserved, a finding that will be monitored in future trials. No seriousadverse events were reported. In a prior Phase 1a clinical trial, adose-dependent decrease in urinary 5-HIAA levels was observed withsingle doses of LX1032.

About the Target

The target for LX1032 was identified through the Genome5000(tm)program, Lexicon's initiative to identify the functions of 5,000druggable genes in the human genome. LX1032 was discovered anddeveloped at Lexicon as a potent inhibitor of tryptophan hydroxylase(TPH), a rate-limiting enzyme in the synthesis of serotonin. Excessivelevels of serotonin have been implicated in symptoms associated withcarcinoid syndrome. Serotonin's breakdown product, 5-HIAA, is abiomarker used in the diagnosis of the condition. In preclinicalstudies, LX1032 was able to reduce peripheral serotonin and urinary5-HIAA levels in several different species without affecting serotoninlevels in the brain.

About the Disease

Carcinoid syndrome is a chronic condition that is the result ofmetastatic neuroendocrine tumors that usually originate fromenterochromaffin cells in the gastrointestinal tract. These tumorssecrete large amounts of serotonin, which can cause a variety ofsymptoms including severe diarrhea and abdominal discomfort. Accordingto the American Cancer Society, about 11,000 to 12,000 neuroendocrinetumors and neuroendocrine cancers are diagnosed each year in the UnitedStates. Patients with carcinoid syndrome currently have limitedtherapeutic options, and the standard of care includes chronic therapywith somatostatin analogues, which are delivered by injection. Withcurrent therapy, the gastrointestinal symptoms return over time in thevast majority of patients, hence the need for new agents. Lexicon wasgranted Fast Track designation from the FDA to specifically developLX1032 for the treatment of gastrointestinal symptoms associated withcarcinoid syndrome in patients who no longer respond to the standard ofcare.

About Lexicon

Lexicon is a biopharmaceutical company focused on discovering anddeveloping breakthrough treatments for human disease. Lexicon currentlyhas six drug candidates in development for autoimmune disease,carcinoid syndrome, cognitive disorders, diabetes, glaucoma andirritable bowel syndrome, all of which were discovered by the company'sresearch team. Lexicon's goal is to advance 10 drug candidates intohuman clinical trials by the end of 2010, the strategic objective ofits 10TO10 program. The company's pipeline derives from its use of itsproprietary gene knockout technology to identify more than 100promising drug targets. Lexicon has applied small molecule chemistryand antibody technology to these biologically-validated targets tocreate its extensive pipeline of clinical and preclinical programs.

Safe Harbor Statement

This press release contains "forward-looking statements," includingstatements relating to Lexicon's clinical development of LX1032 and thepotential therapeutic and commercial potential of LX1032. This pressrelease also contains forward-looking statements relating to Lexicon'sgrowth and future operating results, discovery and development ofproducts, strategic alliances and intellectual property, as well asother matters that are not historical facts or information. Allforward-looking statements are based on management's currentassumptions and expectations and involve risks, uncertainties and otherimportant factors, specifically including those relating to Lexicon'sability to successfully conduct clinical development of LX1032 andpreclinical and clinical development of its other potential drugcandidates, advance additional candidates into preclinical and clinicaldevelopment, obtain necessary regulatory approvals, achieve itsoperational objectives, obtain patent protection for its discoveriesand establish strategic alliances, as well as additional factorsrelating to manufacturing, intellectual property rights, and thetherapeutic or commercial value of its drug candidates, that may causeLexicon's actual results to be materially different from any futureresults expressed or implied by such forward-looking statements.Information identifying such important factors is contained under"Factors Affecting Forward-Looking Statements" and "Risk Factors" inLexicon's annual report on Form 10-K for the year ended December 31,2007, as filed with the Securities and Exchange Commission. Lexiconundertakes no obligation to update or revise any such forward-lookingstatements, whether as a result of new information, future events orotherwise.

Posted: November 2008