Lexicon Announces Positive Results from New Clinical Study of LX4211 in Type 2 Diabetes Patients

THE WOODLANDS, Texas, Jan. 6, 2011 /PRNewswire/ -- Lexicon Pharmaceuticals, Inc. (Nasdaq: LXRX), a biopharmaceutical company focused on discovering breakthrough treatments for human disease, announced data from a recently completed clinical trial and mechanistic study of a solid oral dose formulation for LX4211, a dual inhibitor of sodium-glucose co-transporters 1 and 2 (SGLT1 and SGLT2).

Results from the study demonstrated that administration of a 300 mg solid oral tablet dose of LX4211, administered as two 150 mg tablets, significantly increased total GLP-1 (p=0.001), active GLP-1 (p=0.032) and PYY (p=0.004), important mediators of glycemic and appetite control as well as other metabolic parameters.  Notably, single doses of LX4211 produced rapid and significant improvement in post-prandial glucose (PPG) and fasting plasma glucose (FPG), consistent with results seen in the previous Phase 2 study. Pharmacokinetic and pharmacodynamic data from the study indicated that the solid oral formulation worked as well as or better than the liquid formulation on key parameters of hormonal release, PPG and FPG.  Lexicon plans to move the tablet formulation forward into a Phase 2b study in the second quarter of 2011.

"The significant elevations of GLP-1 levels observed in the study are particularly important given its established relevance in the treatment of diabetes," said Brian Zambrowicz, Ph.D., executive vice president and chief scientific officer.  "Newly observed in this study was the effect of LX4211 on increasing circulating levels of PYY.  We believe the rapid reduction in blood sugar levels after meals, the increase in GLP-1 and the increase in PYY are all associated with SGLT1 inhibition by LX4211 in the gastrointestinal tract."

PYY and GLP-1 are gastrointestinal-derived peptide hormones that have been associated with producing satiety and reducing food intake.  PYY has been studied as an anti-obesity agent, and GLP-1 is a mediator of insulin and glucagon secretion.  As nutrients enter the small intestine, PYY and GLP-1 are co-secreted into the circulation by neuroendocrine cells (L cells) of the gastrointestinal tract.

"We have established a solid tablet formulation suitable for further development and will continue to explore LX4211's unique mechanism of action in the treatment of diabetes and the hormonal control of metabolism," said Arthur T. Sands, M.D., Ph.D., president and chief executive officer. "We believe the results of this study provide further evidence that dual inhibition of SGLT1 and SGLT2 may provide enhanced glycemic control over SGLT2 inhibition alone, consistent with the remarkable results observed in our Phase 2a clinical trial of LX4211."

About the Clinical Trial

The clinical trial compared a new solid oral dose formulation of LX4211 to the liquid dose formulation used in prior clinical trials of LX4211.  The trial employed a randomized, triple-cross over design during which 12 patients with type 2 diabetes each received 300 mg of LX4211 in different dose forms.  Patients were administered a single dose of two 150 mg tablets, six 50 mg tablets or a 300 mg liquid dose formulation in varying sequences at 5-day intervals over a total period of 15 days.  Pharmacokinetic and pharmacodynamic measures were monitored at frequent time points at baseline and after administration of each of the three dose forms with baseline measures prior to dosing used as controls.

Additional details regarding the results from this latest clinical study will be presented on Monday, January 10, 2011 at the JP Morgan Healthcare Conference.  A live webcast of the presentation will be available through Lexicon's corporate website at www.lexpharma.com. An archived version of the presentation will be available for 30 days after the event.

About LX4211

LX4211 is an orally-delivered small molecule under development as a potential treatment for diabetes. LX4211 inhibits both sodium-glucose co-transporter type 1 (SGLT1) and sodium-glucose co-transporter type 2 (SGLT2).  SGLT2 is a transporter responsible for most of the glucose reabsorption performed by the kidney.  SGLT1 is a transporter responsible for glucose and galactose absorption in the gastrointestinal tract, and to a lesser extent than SGLT2, glucose reabsorption in the kidney.  For more information on LX4211 please visit www.lexpharma.com.

About Lexicon

Lexicon is a biopharmaceutical company focused on discovering and developing breakthrough treatments for human disease.  Lexicon currently has four drug candidates in development for autoimmune disease, carcinoid syndrome, diabetes, and irritable bowel syndrome, all of which were discovered by Lexicon's research team.  Lexicon has used its proprietary gene knockout technology to identify more than 100 promising drug targets.  Lexicon has focused drug discovery efforts on these biologically-validated targets to create its extensive pipeline of clinical and preclinical programs.  For additional information about Lexicon and its programs, please visit www.lexpharma.com.

Safe Harbor Statement

This press release contains "forward-looking statements," including statements relating to the characterization of the results observed in the referenced clinical trial and prior clinical trials of LX4211 as positive or remarkable, the mechanism of action of LX4211, and the potential therapeutic and commercial potential of LX4211 generally. 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 LX4211 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, 2009, 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.

SOURCE Lexicon Pharmaceuticals, Inc.