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

LEXICON PHARMACEUTICALS REPORTS ON CLINICAL PROGRAM STATUS

AND 2011 THIRD QUARTER RESULTS

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

The Woodlands, Texas, November 1, 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 and nine months ended September 30, 2011.

"Recent positive results from clinical studies of LX4211 and LX1032 have provided further validation for the unique mechanisms of action of these first-in-class drugs," said Dr. Arthur T. Sands, president and chief executive officer of Lexicon. "We are progressing with plans to partner LX1032 on the strength of our Phase 2 data in carcinoid syndrome, and are engaged in active discussions with multiple parties about the program."

Progress in Clinical Pipeline

LX2931 once daily showed improvement in the primary efficacy endpoint of the study, the percentage of patients achieving an American College of Rheumatology 20 (ACR20) response at week 12.

Revenues: Lexicon's revenues for the three months ended September 30, 2011 decreased 55 percent to $0.4 million from $0.8 million for the corresponding period in 2010. For the nine months ended September 30, 2011, revenues decreased 59 percent to $1.5 million from $3.7 million for the corresponding period in 2010.

Research and Development Expenses: Research and development expenses for the three months ended September 30, 2011 increased 4 percent to $19.7 million from $18.9 million for the corresponding period in 2010, primarily due to an increase in external preclinical and clinical research and development costs offset by a decrease in personnel costs. For the nine months ended September 30, 2011, research and development expenses increased 6 percent to $63.7 million from $60.3 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. The increase in fair value of the Symphony Icon purchase liability was $2.3 million and $1.1 million for the three months ended September 30, 2011 and 2010, respectively, and was $5.2 million and $1.1 million for nine months ended September 30, 2011 and 2010, respectively.

General and Administrative Expenses: General and administrative expenses for the three months ended September 30, 2011 decreased 18 percent to $4.1 million from $4.9 million for the corresponding period in 2010. The decrease was primarily attributable to decreased personnel costs. For the nine months ended September 30, 2011, general and administrative expenses decreased 14 percent to $13.3 million from $15.5 million for the corresponding period in 2010.

Consolidated Net Loss: Net loss for the three months ended September 30, 2011 was $26.1 million, or $0.08 per share, compared to a net loss of $27.5 million, or $0.08 per share, in the corresponding period in 2010. Net loss for the nine months ended September 30, 2011 was $82.4 million, or $0.24 per share, compared to a net loss of $78.8 million, or $0.27 per share, for the corresponding period in 2010. For the three and nine months ended September 30, 2011, net loss included non-cash, stock-based compensation expense of $1.4 million and $4.4 million, respectively. For the three and nine months ended September 30, 2010, net loss included non-cash, stock-based compensation expense of $1.3 million and $4.0 million, respectively.

Cash and Investments: As of September 30, 2011, Lexicon had $144.2 million in cash and investments, as compared to $164.8 million as of June 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 the third quarter of 2011 at 11:00 a.m. Eastern Time today. 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 20122666. Investors can access a live webcast of the call at www.lexpharma.com. An archived version of the webcast will be available on Lexicon's corporate website through November 29, 2011.

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, 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 partnership discussions with third parties with respect to the development and commercialization of LX1032. 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, 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, including with respect to LX1032, 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