LEXICON PHARMACEUTICALS REPORTS ON CLINCIAL PROGRAM STATUS AND 2011 FIRST QUARTER RESULTS Conference Call at 11:00 a.m. Eastern Time The Woodlands, Texas

LEXICON PHARMACEUTICALS REPORTS ON CLINCIAL PROGRAM STATUS

AND 2011 FIRST QUARTER RESULTS

Conference Call at 11:00 a.m. Eastern Time

The Woodlands, Texas, May 3, 2011 - Lexicon Pharmaceuticals, Inc. (Nasdaq: LXRX), a biopharmaceutical company focused on discovering and developing breakthrough treatments for human disease, today updated its drug development progress and reported financial results for the three months ended March 31, 2011.

"Our pipeline of first-in-class drugs continues to make significant progress. Results from a mechanistic study of a tablet formulation of LX4211 in diabetes patients provided further confirmation of the drug's unique dual mechanism of action, and preparations to initiate a Phase 2b study of LX4211 in the second quarter are on track," said Dr. Arthur T. Sands, president and chief executive officer of Lexicon. "In addition, we anticipate completing enrollment in the U.S. Phase 2a clinical trial of LX1032 in patients with carcinoid syndrome in the second quarter, with results expected shortly thereafter."

Key Progress in Clinical Pipeline

Revenues: Lexicon's revenues for the three months ended March 31, 2011 decreased 64 percent to $0.6 million from $1.6 million for the corresponding period in 2010. The decrease for the three months ended March 31, 2011 was primarily attributable to reduced revenues under Lexicon's alliance with Taconic Farms.

Research and Development Expenses: Research and development expenses for the three months ended March 31, 2011 increased 13 percent to $23.9 million from $21.1 million for the corresponding period in 2010. The increase was primarily attributable to increased external clinical and preclinical research and development costs and increased severance costs resulting from Lexicon's continued reallocation of resources from earlier-stage research towards its most advanced drug discovery and development programs.

Increase in Fair Value of Symphony Icon Purchase Liability: In connection with the acquisition of Symphony Icon, Lexicon made an initial estimate of the fair value of the liability for the associated base and contingent payments. Changes in this liability, based on the development of the programs and the time until such payments are expected to be made, are recorded in Lexicon's consolidated statements of operations. The increase in fair value of the Symphony Icon purchase liability was $1.1 million for the three months ended March 31, 2011.

General and Administrative Expenses: General and administrative expenses for the three months ended March 31, 2011 decreased 14 percent to $4.8 million from $5.5 million for the corresponding period in 2010. The decrease was primarily attributable to decreased legal and patent fees.

Consolidated Net Loss: Net loss for the three months ended March 31, 2011 was $29.6 million, or $0.09 per share, compared to a net loss of $26.1 million, or $0.13 per share, in the corresponding period in 2010. For the three months ended March 31, 2011, net loss included non-cash, stock-based compensation expense of $1.5 million, compared to $1.3 million in the corresponding period in 2010.

Cash and Investments: As of March 31, 2011, Lexicon had $188.9 million in cash and investments, as compared to $211.1 million as of December 31, 2010.

Lexicon Conference Call:

Lexicon management will hold a conference call to discuss financial results for the first quarter of 2011 and program status at 11:00 a.m. Eastern Time on May 3, 2011. The dial-in number for the conference call is 888-220-1244 (within the US/Canada) or 706-679-5615 (international). The conference ID for all callers is 62216935. An archived version of the conference call will be available on Lexicon's corporate website at www.lexpharma.com through May 31, 2011.

Lexicon is a biopharmaceutical company focused on discovering breakthrough treatments for human disease. Lexicon currently has four drug candidates in mid-stage development for diabetes, irritable bowel syndrome, carcinoid syndrome and rheumatoid arthritis, 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 LX1031, LX1032, LX1033, LX2931, and LX4211, including characterizations of the results of and projected timing of clinical trials of such compounds, and the potential therapeutic and commercial potential of LX1031, LX1032, LX1033, LX2931, and LX4211. 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 LX1031, LX1032, LX1033, LX2931, and 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. Unless specifically indicated otherwise, results reported as trends

were not statistically significant. 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, 2010, 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.

Contact for Lexicon:

Senior Director, Corporate Communications and Investor Relations

Lexicon Pharmaceuticals, Inc.

Selected Financial Data