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Lexicon Develops Antibodies That Lower Triglycerides and,Cholesterol as Potential New Therapy for Heart Disease

- Publication of New Cardiovascular Target from Lexicon's Genetic Research -

THE WOODLANDS, Texas, July 02, 2007 /PRNewswire-FirstCall/ -- Lexicon Pharmaceuticals, Inc. today reported results from preclinical research demonstrating that antibodies directed to a potential new target, angiopoietin-like protein 4 (ANGPTL4), rapidly lower triglycerides and cholesterol. Research suggests that a monoclonal antibody (mAb) targeting ANGPTL4 may have therapeutic application in the treatment of cardiovascular disease. The results appeared in an article, entitled "Lipid-lowering effects of anti-angiopoietin-like 4 antibody recapitulate the lipid phenotype found in angiopoietin-like 4 knockout mice," published in the July 10, 2007 edition of the journal Proceedings of the National Academy of Sciences.

Lexicon scientists first identified ANGPTL4 as a potential target for cardiovascular disease using the company's proprietary gene knockout technology. Lexicon scientists create animal models that have alterations in specific genes in order to discover the physiological and behavioral effects that result from the loss of the protein encoded by the gene. Researchers found that animal models in which the ANGPTL4 gene was knocked out had lower triglyceride and cholesterol levels than normal animals. The ANGPTL4 gene encodes a protein that is secreted into the bloodstream and is now believed to play an important role in triglyceride and cholesterol metabolism. Lexicon's biotherapeutics group developed a monoclonal antibody as an injectable agent targeting the ANGPTL4 protein to reproduce the triglyceride and cholesterol- lowering effects identified in the animal models. Notably, this appears to be the first successful production of a monoclonal antibody to this target.

"High triglycerides and cholesterol are correlated with an increased risk of heart disease," commented Dr. Brian P. Zambrowicz, executive vice preside nt and chief scientific officer at Lexicon and an author on the paper. "The research our team published today may be an important first step in the development of a new treatment for severe cardiovascular disease, which continues to be the leading cause of death in the United States."

Earlier this year, researchers at the University of Texas Southwestern Medical Center in Dallas, the Institute of Molecular Medicine at the University of Texas Health Science Center in Houston, and other collaborating institutions found that individuals with a mutated ANGPTL4 gene have significantly lower triglyceride levels and higher levels of HDL cholesterol (or "good" cholesterol).(1) These results from human genetic studies further support Lexicon's therapeutic strategy based on original observations made using animal models.

Lexicon scientists discovered ANGPTL4's utility as a potential cardiovascular disease target as part of its Genome5000(TM) program, and the discovery was selected for inclusion in its collaboration with Genentech, Inc. The collaboration with Genentech was initiated in December 2002 to discover the functions of secreted proteins and potential antibody targets identified through Genentech's Secreted Protein Discovery Initiative (also referred to as the SPDI program), and was expanded in November 2005 to include the advanced research, development and commercialization of new biologic drugs. Under the collaboration, Lexicon has the right to develop and commercialize biotherapeutic drugs for up to six targets. Genentech retains an option on the potential development and commercialization of the biotherapeutic drugs that Lexicon develops from the collaboration under a cost and profit sharing arrangement. ANGPTL4, referred to internally as LG842, is one of two targets already chosen by Lexicon for internal development. Lexicon has already generated versions of ANGPTL4 monoclonal antibodies that are currently in preclinical evaluation to identify a pote ntial clinical development candidate.

    Editor's Notes:

    -- The article, "Lipid-lowering effects of anti-angiopoietin-like 4

       antibody recapitulate the lipid phenotype found in angiopoietin-like 4

       knockout mice," may be found on the PNAS website at

       and downloaded by subscribers or purchased through the Academy's short-

       term access program.

    -- For more information on Lexicon's alliance with Genentech, please visit

       the Lexicon website at and select the tab,


About Lexicon

Lexicon is a biopharmaceutical company focused on the discovery and development of breakthrough treatments for human disease. Lexicon currently has clinical 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., N.V. Organon and Takeda Pharmaceutical Company Limited. For additional information about Lexicon and its programs, please visit

Safe Harbor Statement

This press release contains "forward-looking statements," including statements relating to Lexicon's research and development of ANGPTL4 mAbs and the potential therapeutic and commercial potential of ANGPTL4 mAbs. This p ress 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 preclinical and clinical development of ANGPTL4 mAbs and 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.

    (1)Stefano Romeo et al., "Population-based resequencing of ANGPTL4

       uncovers variations that reduce triglycerides and increase HDL,"

       Nature Genetics, April 2007.

    Contact for Lexicon:

    Bobbie Faulkner

    Manager, Investor Relations


CONTACT: Bobbie Faulkner, Manager, Investor Relations o f Lexicon,+1-281-863-3503,

Web site:

Ticker Symbol: (NASDAQ-NMS:LXRX)

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