(LXRX) Achieves Positive Results in Type 2 Diabetes Patients with Renal Impairment

THE WOODLANDS, Texas, Oct. 1, 2013 — Lexicon Pharmaceuticals, Inc. (Nasdaq: LXRX) announced today that LX4211, a first-in-class, dual inhibitor of sodium glucose transporters 1 and 2 (SGLT1 and SGLT2), successfully met the primary endpoint of reducing post-prandial glucose, in a study of patients with type 2 diabetes and moderate to severe renal impairment.  Reducing elevated post-prandial glucose, high blood sugar levels after meals, is a key objective of diabetes therapy.

In a placebo-controlled, proof-of-concept study, LX4211 provided clinically meaningful and statistically significant reductions (p<0.05) in post-prandial glucose in diabetes patients with moderate to severe renal impairment (Stage 3 and 4 kidney disease). Importantly, these effects were maintained in a sub-group with the most advanced renal impairment, pre-defined as those with glomerular filtration rate (GFR) less than 45 ml/min/1.73 m². LX4211 also produced significant elevations in GLP-1, a hormone involved in control of glucose and appetite.

Renal impairment occurs in approximately 30% of patients with type 2 diabetes and represents a major unmet medical need with limited treatment options.  LX4211’s inhibition of SGLT1 in the gastrointestinal (GI) tract, reducing glucose absorption and triggering GLP-1 secretion, offers the potential for treating this medically challenging population with compromised kidney function.  In previous Phase 2 studies, LX4211 improved glycemic control in patients with type 2 diabetes with normal renal function.

“Our hypothesis was that LX4211 would improve glycemic control even in patients with the greatest degree of renal impairment due to its inhibition of SGLT1 in the GI tract,” said Pablo Lapuerta, M.D., Lexicon’s chief medical officer.  “The post-prandial glucose reductions and GLP-1 elevations observed in this study population support the rationale for demonstrating effective HbA1c reduction in a larger, longer-term Phase 3 trial, and provide further support for the clinical differentiation of LX4211 as a first-in-class dual SGLT1 and SGLT2 inhibitor.”

In this multicenter study, 30 patients with poorly controlled type 2 diabetes and moderate to severe renal impairment were randomized to either placebo or a 400 mg dose of investigational drug LX4211 taken orally once per day before breakfast. Patients’ post-prandial glucose was measured after a standardized meal both at baseline before treatment and after one week of therapy. In addition to achieving the primary efficacy objective of post-prandial glucose reduction, there were no serious adverse events observed in the study and no discontinuations of LX4211 due to adverse events. Lexicon plans to present full results of the study at scientific congresses in 2014.

About Lexicon

Lexicon is a biopharmaceutical company focused on discovering breakthrough treatments for human disease.  Lexicon currently has multiple programs in clinical development for diabetes, irritable bowel syndrome, carcinoid syndrome and other indications, 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 Lexicon’s clinical development of LX4211, characterizations of the results of and projected timing of clinical trials of LX4211, and the potential therapeutic and commercial potential of LX4211.  The 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 “Risk Factors” in Lexicon’s annual report on Form 10-K for the year ended December 31, 2012, 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.