The Woodlands, Texas, May 28, 2008 – Lexicon Pharmaceuticals, Inc. (Nasdaq: LXRX) announced today that it is implementing a reorganization designed to reduce costs and increase efficiencies in its research and discovery operations.  This action will further focus the company’s resources on its strategic, business, and clinical development initiatives.  The cost reductions associated with the reorganization will enable the company to continue to invest appropriately in the development of its expanding pipeline of drug candidates, while maintaining a productive and robust drug discovery operation.

“This reorganization is a significant milestone in the process we began in early 2007 to transform ourselves into a biopharmaceutical company with a pipeline of innovative drug products that derive from our unique insights into the human genome,” said Arthur T. Sands, M.D., Ph.D., president and chief executive officer.  “This action will reduce operating expenses associated with our research and discovery efforts and allow us to deploy these resources into key clinical development areas, including our four programs currently in human clinical trials.”

As part of the reorganization, Lexicon is reducing its workforce at the company’s facilities in Texas and New Jersey. Lexicon expects the move to reduce its expenses by approximately $4.0 million, net of severance costs, for the balance of 2008 and approximately $10.0 million on an annualized basis.  Lexicon will conclude the reorganization by early summer with a prioritization initiative of drug targets designed to further streamline its process of moving new drug candidates from discovery to human clinical testing.

“We are thankful for the significant contributions our employees have made, and we recognize the personal and professional impact this transition will have on all those affected,” Sands said.  “Among those departing the company, there are some long-standing employees, including several executives who have contributed greatly to the company’s rapid growth from its early start-up phase.  We are especially indebted to Julia Gregory, who served as our chief financial officer from the time of our successful initial public offering in 2000.  In addition, we want to thank Jim Piggott, who served as senior vice president of pharmaceutical biology in charge of target discovery from the beginning of the Genome5000™ program, and David Boulton, vice president of technology and operations in New Jersey, who designed and implemented our innovative click chemistry platform, which is the foundation of Lexicon’s chemical library collection, for their efforts.”

About Lexicon
Lexicon is a biopharmaceutical company focused on discovering and developing breakthrough treatments for human disease.  Through its proprietary gene knockout technology, the company is dedicated to discovering and developing breakthrough treatments for human disease.  Lexicon currently has development programs underway for such areas of major unmet medical need as irritable bowel syndrome, cognitive disorders, autoimmune diseases, and carcinoid syndrome.  The company has used its proprietary gene knockout technology to discover more than 100 promising drug targets and create an extensive pipeline of clinical and preclinical programs in the therapeutic areas of cardiology, gastroenterology, immunology and oncology, metabolism, neurology and ophthalmology.  To focus its commitment, Lexicon initiated its 10TO10 program to advance 10 new drug candidates into human clinical trials by the end of 2010.  To advance the development and commercialization of its programs, Lexicon is working both independently and through collaborators including Bristol-Myers Squibb Company, Genentech, Inc. and N.V. Organon.  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 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 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 “Factors Affecting Forward-Looking Statements” and “Risk Factors” in Lexicon’s annual report on Form 10-K for the year ended December 31, 2007, 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.