$LXRX Reports Positive Top-Line Results In Phase 3 inTandem3 Study

Sotagliflozin Demonstrates Statistically Significant Benefit in Primary Endpoint Results Support a Unique Drug Profile as an SGLT1 and SGLT2 Inhibitor

THE WOODLANDS, Texas, June 9, 2017 — Lexicon Pharmaceuticals, Inc. (Nasdaq: LXRX) today announced positive top-line results from its Phase 3 inTandem3 study of sotagliflozin, an investigational dual SGLT1 and SGLT2 inhibitor, for the treatment of patients with type 1 diabetes on any background insulin therapy. The study met its primary endpoint, demonstrating the superiority of sotagliflozin 400 mg compared to placebo in the proportion of patients with A1C <7.0% at Week 24 and no episode of severe hypoglycemia and no episode of diabetic ketoacidosis (DKA) after randomization.

Sotagliflozin demonstrated a generally well tolerated safety profile during a 24-week treatment period, with rates of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and discontinuations due to AEs that were consistent with rates seen in two prior pivotal Phase 3 studies, inTandem1 and inTandem2, including a similar rate of severe hypoglycemia for the sotagliflozin arm compared to placebo during the 24-week treatment period (2.4% for placebo compared to 3.0% for sotagliflozin 400 mg) and a slightly higher rate of DKA during the 24-week treatment period for sotagliflozin 400 mg (3.0%) than placebo (0.6%).

A full analysis of the results from inTandem3, including safety data, will be submitted for publication in a peer-reviewed journal.

“The results achieved with sotagliflozin in the inTandem3 study are scientifically and clinically important and significant,” said Satish Garg, M.D., lead investigator of inTandem3 and Professor of Medicine and Pediatrics, and Director Adult Program at the Barbara Davis Center for Diabetes, University of Colorado Denver and Editor-in-Chief, Diabetes Technology and Therapeutics. “If approved, sotagliflozin may potentially be the first option as an adjunct to insulin to improve glycemic control for patients with type 1 diabetes.”

“These positive results represent an important milestone, further supporting sotagliflozin’s differentiated profile as a novel, oral anti-diabetic agent with potential to benefit people with type 1 diabetes,” said Lonnel Coats, Lexicon’s president and chief executive officer. “Sotagliflozin is the first-ever oral anti-diabetic drug candidate to have achieved success in now three consecutive Phase 3 clinical trials in this population.”

“These compelling results speak to the potential long-term benefits that sotagliflozin may bring to people with type 1 diabetes,” said Jorge Insuasty, senior vice president, head of global development, Sanofi. “There are more than 1 million adults with type 1 diabetes in the United States alone, and the majority of these are not at their A1C goal of 7 percent. The need for diabetes therapies that help adults with type 1 diabetes control their blood sugar with fewer complications is clear, and sotagliflozin added to insulin therapy can potentially help meet that need. We look forward to pursuing regulatory submissions for the treatment of type 1 worldwide and to continuing to study the use of sotagliflozin in adults with type 2 diabetes.”

About inTandem3

The Phase 3 study known as inTandem3 was a global, randomized, double-blind, placebo-controlled, parallel-group, multicenter study of 1,402 patients with type 1 diabetes on continuous subcutaneous insulin infusion or multiple daily injection therapy who had an A1C level entering the study between 7.0% and 11.0%. Patients had a confirmed diagnosis of type 1 diabetes and inadequate glycemic control on insulin therapy alone. The study evaluated 400 mg of sotagliflozin taken once daily before the first meal of the day, against placebo. The primary objective of the study was to demonstrate the superiority of sotagliflozin 400 mg versus placebo in the proportion of patients with glycosylated A1C <7.0% at Week 24 and no episode of severe hypoglycemia and no episode of DKA after randomization.

About Sotagliflozin

Discovered using Lexicon’s unique approach to gene science, sotagliflozin is a first-in-class, oral dual inhibitor of two proteins responsible for glucose regulation known as sodium-glucose co-transporter types 1 and 2 (SGLT1 and SGLT2). SGLT1 is responsible for glucose absorption in the gastrointestinal tract, and SGLT2 is responsible for glucose reabsorption by the kidney.

Lexicon entered into a collaboration and license agreement with Sanofi in November 2015 under which Lexicon granted Sanofi an exclusive, worldwide (excluding Japan), royalty-bearing right and license to develop, manufacture and commercialize sotagliflozin. Lexicon is responsible for all clinical development activities relating to type 1 diabetes and retains an exclusive option to co-promote and have a significant role, in collaboration with Sanofi, in the commercialization of sotagliflozin for the treatment of type 1 diabetes in the U.S. Sanofi is responsible for all clinical development and commercialization of sotagliflozin for the treatment of type 2 diabetes worldwide (excluding Japan) and is solely responsible for the commercialization of sotagliflozin for the treatment of type 1 diabetes outside the U.S. (excluding Japan).

About Lexicon Pharmaceuticals

Lexicon is a fully integrated biopharmaceutical company that is applying a unique approach to gene science based on Nobel Prize-winning technology to discover and develop precise medicines for patients with serious, chronic conditions. Through its Genome5000™ program, Lexicon scientists have studied the role and function of nearly 5,000 genes over the last 20 years and have identified more than 100 protein targets with significant therapeutic potential in a range of diseases. Through the precise targeting of these proteins, Lexicon is pioneering the discovery and development of innovative medicines to safely and effectively treat disease. In addition to its recently-launched product for carcinoid syndrome diarrhea, XERMELO™ (telotristat ethyl), Lexicon has a pipeline of promising drug candidates in clinical and pre-clinical development in diabetes and metabolism and neuropathic pain. For additional information please visit www.lexpharma.com.

Safe Harbor Statement

This press release contains “forward-looking statements,” including statements relating to Lexicon’s and its licensees’ clinical development of and regulatory filings for sotagliflozin and the results and projected timing of clinical trials and the potential therapeutic and commercial potential of sotagliflozin. In addition, 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 the risk that clinical studies of sotagliflozin may be halted, delayed or otherwise not demonstrate safety or efficacy, the risk that the FDA and other regulatory authorities may not grant regulatory approval of sotagliflozin in accordance with Lexicon’s currently anticipated timelines or at all, and the risk that such regulatory approvals, if granted, may have significant limitations on the approved use of sotagliflozin. As a result, sotagliflozin may never be successfully commercialized. Other risks include Lexicon’s ability to meet its capital requirements, successfully conduct preclinical and clinical development and obtain necessary regulatory approvals of its other potential drug candidates, 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. Any of these risks, uncertainties and other factors 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, 2016, 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.