LEXICON PHARMACEUTICALS PROVIDES CLINICAL PIPELINE UPDATE AND REPORTS 2012 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 2012 FOURTH QUARTER AND FULL YEAR FINANCIAL RESULTS

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

The Woodlands, Texas, February 21, 2013 - 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, 2012.

"We continued to make significant progress in the development of our pipeline in 2012, highlighted by positive results from clinical studies of LX4211 in diabetes and telotristat etiprate in carcinoid syndrome," said Dr. Arthur T. Sands, president and chief executive officer of Lexicon. "We are pleased to have commenced the Phase 3 program for telotristat etiprate in carcinoid syndrome, and continue to progress in our preparations for LX4211 Phase 3 initiation. We also look forward to significant proof-of-concept results in irritable bowel syndrome (IBS) with LX1033, ulcerative colitis with telotristat etiprate, and type 1 diabetes with LX4211 in 2013."

Key Developments in 2012

Revenues: Lexicon's revenues for the three months ended December 31, 2012 decreased 36 percent to $0.2 million from $0.3 million for the corresponding period in 2011. For the year ended December 31, 2012, revenues decreased 41 percent to $1.1 million from $1.8 million for the corresponding period in 2011.

Research and Development Expenses: Research and development expenses for the three months ended December 31, 2012 decreased 25 percent to $21.0 million from $28.1 million for the corresponding period in 2011, primarily due to a decrease in external manufacturing, clinical research and development costs. For the year ended December 31, 2012, research and development expenses decreased 10 percent to $82.6 million from $91.8 million for the corresponding period in 2011.

Increase (Decrease) 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, 2012, the fair value of the Symphony Icon purchase liability decreased by $0.2 million, compared to an increase of $1.6 million in the corresponding period in 2011. For the years ended December 31, 2012 and 2011, the increase in fair value of the Symphony Icon purchase liability was $9.9 million and $6.8 million, respectively.

General and Administrative Expenses: General and administrative expenses for the three months ended December 31, 2012 decreased two percent to $3.9 million from $4.0 million for the corresponding period in 2011. For the year ended December 31, 2012, general and administrative expenses decreased two percent to $17.0 million from $17.4 million for the corresponding period in 2011.

Consolidated Net Loss: Net loss for the three months ended December 31, 2012 was $24.9 million, or $0.05 per share, compared to a net loss of $33.8 million, or $0.10 per share, in the corresponding period in 2011. Net loss for the year ended December 31, 2012 was $110.2 million, or $0.23 per share, compared to a net loss of $116.2 million, or $0.34 per share, for the corresponding period in 2011. For the three months and year ended December 31, 2012, net loss included non-cash, stock-based compensation expense of $1.6 million and $6.5 million, respectively. 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.

Cash and Investments: As of December 31, 2012, Lexicon had $223.2 million in cash and investments, as compared to cash and investments of $206.8 million as of September 30, 2012 and $281.7 million as of December 31, 2011.

Lexicon Conference Call

Lexicon management will hold a conference call to discuss its clinical development progress and financial results for 2012 and financial guidance for 2013 at 11:00 a.m. Eastern Time on February 21, 2013. The dial-in number for the conference call is 888-645-5785 (within the US/Canada) or 970-300-1531 (international). The conference ID for all callers is 12316846. 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 21, 2013.

Lexicon is a biopharmaceutical company focused on discovering breakthrough treatments for human disease. Lexicon currently has multiple drug 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, telotristat etiprate (LX1032), LX1033, LX2931 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 LX4211, telotristat etiprate (LX1032), LX1033, LX2931 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 LX4211, telotristat etiprate (LX1032), LX1033, LX2931 and 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. 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, 2011, 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.

Lexicon Pharmaceuticals, Inc.

Selected Financial Data

Contact for Lexicon:

Vice President, Communications and Alliance Management