LEXICON PHARMACEUTICALS PROVIDES CLINICAL PIPELINE UPDATE AND REPORTS 2011 FOURTH QUARTER AND FULL YEAR FINANCIAL RESULTS Conference Call and Webcast at 11:00 a.m. Eastern Time The Woodlands, Texas

LEXICON PHARMACEUTICALS PROVIDES CLINICAL PIPELINE UPDATE AND

REPORTS 2011 FOURTH QUARTER AND FULL YEAR FINANCIAL RESULTS

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

The Woodlands, Texas, February 22, 2012 - 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 and year ended December 31, 2011.

"We made substantial progress with our drug pipeline in 2011, highlighted by the positive results obtained from clinical studies of LX4211 in diabetes and LX1032 in carcinoid syndrome," said Dr. Arthur T. Sands, president and chief executive officer of Lexicon." "Our research has continued to reveal the favorable physiological effects that are triggered by therapy with these investigational drug candidates."

Revenues: Lexicon's revenues for the three months ended December 31, 2011 decreased 73 percent to $0.3 million from $1.3 million for the corresponding period in 2010. For the year ended December 31, 2011, revenues decreased 62 percent to $1.8 million from $4.9 million for the corresponding period in 2010.

Research and Development Expenses: Research and development expenses for the three months ended December 31, 2011 increased 54 percent to $28.1 million from $18.3 million for the corresponding period in 2010, primarily due to an increase in external manufacturing, clinical research and development costs. For the year ended December 31, 2011, research and development expenses increased 17 percent to $91.8 million from $78.5 million for the corresponding period in 2010.

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. For the three months ended December 31, 2011, the increase in fair value of the Symphony Icon purchase liability was $1.6 million, consistent with the corresponding period in 2010. For the years ended December 31, 2011 and 2010, the increase in fair value of the Symphony Icon purchase liability was $6.8 million and $2.7 million, respectively.

General and Administrative Expenses: General and administrative expenses for the three months ended December 31, 2011 increased four percent to $4.0 million from $3.9 million for the corresponding period in 2010. For the year ended December 31, 2011, general and administrative expenses decreased 11 percent to $17.4 million from $19.4 million for the corresponding period in 2010.

Consolidated Net Loss: Net loss for the three months ended December 31, 2011 was $33.8 million, or $0.10 per share, compared to a net loss of $23.0 million, or $0.07 per share, in the corresponding period in 2010. Net loss for the year ended December 31, 2011 was $116.2 million, or $0.34 per share, compared to a net loss of $101.8 million, or $0.34 per share, for the corresponding period in 2010. For the three months and year ended December 31, 2011, net loss included non-cash, stock-based compensation expense of $1.4 million and $5.7 million, respectively. For the three months and year ended December 31, 2010, net loss included non-cash, stock-based compensation expense of $1.5 million and $5.5 million, respectively.

Cash and Investments: As of December 31, 2011, Lexicon had $281.7 million in cash and investments, as compared to cash and investments of $144.2 million as of September 30, 2011 and $211.1 million as of December 31, 2010.

Lexicon Conference Call

Lexicon management will hold a conference call to discuss its clinical development progress and financial results for 2011 and financial guidance for 2012 at 11:00 a.m. Eastern Time on February 22, 2012. 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 53392469. Investors can access a live webcast of the call at www.lexpharma.com. An archived version of the webcast will be available on the website through March 23, 2012.

Lexicon is a biopharmaceutical company focused on discovering breakthrough treatments for human disease. Lexicon currently has four drug programs 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, LX4211 and LX7101, 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, LX4211 and LX7101. 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 those relating to Lexicon's ability to successfully conduct clinical development of LX1031, LX1032, LX1033, LX2931, LX4211and LX7101 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.

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