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

The Woodlands, Texas, February 23, 2010 – 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, 2009. 

“We have now established proof-of-concept for two of our four clinical programs, with positive results in Phase 2 clinical trials for both LX1031 in IBS and LX4211 in type 2 diabetes,” said Dr. Arthur T. Sands, president and chief executive officer of Lexicon.  “We look forward to reporting Phase 2 clinical results from our next two programs, LX2931 for rheumatoid arthritis and LX1032 for carcinoid syndrome.”

Key Developments of 2009

• Lexicon reported positive results from the Phase 2a clinical trial of its drug candidate for non-constipating irritable bowel syndrome (IBS), LX1031, an inhibitor of tryptophan hydroxylase that acts locally to reduce serotonin synthesis in the gastrointestinal tract.  Top-line data demonstrated that the high dose of LX1031 produced statistically-significant improvements in a global assessment of relief of IBS pain and discomfort and in stool consistency as compared to placebo — clinical benefits that correspond with a reduction in serotonin synthesis.
• Lexicon completed Phase 2a studies of its drug candidate for type 2 diabetes, LX4211, an inhibitor of sodium-glucose cotransporter 2 (SGLT2).  Top-line data from the Phase 2a trial, reported in January 2010, showed statistically-significant and rapid improvements in multiple parameters in patients with type 2 diabetes, including improved glycemic control and reduced HbA1c within four weeks. In addition, reductions in weight, blood pressure, and triglyceride levels were observed for both treatment arms relative to placebo.
• Lexicon advanced LX2931, an inhibitor of sphingosine-1-phosphate (S1P) lyase, into a Phase 2a study in patients with rheumatoid arthritis.  The Phase 2 clinical trial is designed as a 12-week, randomized, double-blind, placebo-controlled study to evaluate the safety and tolerability of LX2931 and its effects on symptoms associated with rheumatoid arthritis. With enrollment in the study proceeding ahead of schedule, the Company has filed for regulatory authorization to permit enrollment of up to 200 patients, an increase from the originally-planned enrollment of up to 120 patients, which will increase the likelihood of observing a positive statistical trend. The study is being conducted at multiple centers in the United States and Eastern Europe.  Top-line data from the expanded trial are expected to be available around the end of the year.
• Lexicon continues to enroll patients in a Phase 2a study of its drug candidate for carcinoid syndrome, LX1032, an inhibitor of tryptophan hydroxylase that reduces peripheral serotonin production without affecting brain serotonin levels.  The Phase 2 clinical trial is designed as a randomized, double-blind, placebo-controlled study to evaluate the safety and tolerability of LX1032 and its effects on symptoms associated with carcinoid syndrome.  The study is expected to include up to 28 patients with carcinoid syndrome who are symptomatic despite treatment with currently available therapy.  Top-line data from the trial are expected to be available in the second half of 2010.
• In October 2009, Lexicon completed the public offering and sale of 38.3 million shares of its common stock at $1.50 per share.  The net proceeds of the offering were $55.2 million, after deducting underwriting discounts and offering expenses. 

LX1031 and LX1032 are being developed in a product development collaboration with Symphony Capital Partners, L.P. and its co-investors.

Financial Results

Revenues:  Lexicon’s revenues for the three months ended December 31, 2009 decreased 78 percent to $1.4 million from $6.4 million for the corresponding period in 2008.  The decrease was primarily attributable to reduced revenues under Lexicon’s alliances with N.V. Organon, Bristol-Myers Squibb and Genentech, Inc., partially offset by increases in revenue under the company’s collaboration with Taconic Farms, Inc.  For the year ended December 31, 2009, revenues decreased 67 percent to $10.7 million from $32.3 million for the corresponding period in 2008.

Research and Development Expenses:  Research and development expenses for the three months ended December 31, 2009 decreased 16 percent to $18.8 million from $22.4 million for the corresponding period in 2008.  The decrease was primarily attributable to lower external preclinical research and development expenses as well as lower salary and benefit costs, partially offset by higher external clinical research and development expenses.  For the year ended December 31, 2009, research and development expenses decreased 24 percent to $81.2 million from $107.2 million for the corresponding period in 2008.

General and Administrative Expenses:  General and administrative expenses for the three months ended December 31, 2009 decreased nine percent to $4.4 million from $4.9 million for the corresponding period in 2008.  The decrease was primarily attributable to lower consulting and stock-based compensation expenses.  For the year ended December 31, 2009, general and administrative expenses decreased 10 percent to $19.4 million from $21.6 million for the corresponding period in 2008.

Net Loss Attributable to Lexicon Pharmaceuticals, Inc.:  Net loss for the three months ended December 31, 2009 was $22.0 million, or $0.13 per share, compared to a net loss of $15.4 million, or $0.11 per share, in the corresponding period in 2008.  Net loss for the year ended December 31, 2009 was $82.8 million, or $0.57 per share, compared to a net loss of $76.9 million, or $0.56 per share, for the corresponding period in 2008.  For the three months and year ended December 31, 2009, net loss included non-cash, stock-based compensation expense of $1.2 million and $5.3 million, respectively.  For the three months and year ended December 31, 2008, net loss included non-cash, stock-based compensation expense of $1.7 million and $6.5 million, respectively. 

Cash and Investments:  As of December 31, 2009, Lexicon had $125.1 million in cash and investments net of its obligations under the credit line secured by its auction rate securities, as compared to $87.3 million as of September 30, 2009 and $158.8 million as of December 31, 2008. 

Lexicon Conference Call:
Lexicon management will hold a conference call to discuss its clinical development progress and financial results for 2009 and financial guidance for 2010 at 11:00 a.m. Eastern Time on February 23, 2010.  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 57354686.  Investors can access a live webcast of the call at http://www.lexpharma.com/.  An archived version of the webcast will be available on the website through March 2, 2010.

About Lexicon
Lexicon is a biopharmaceutical company focused on discovering and developing breakthrough treatments for human disease.  Lexicon currently has five drug candidates in development for autoimmune disease, carcinoid syndrome, diabetes, glaucoma and irritable bowel syndrome, 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 http://www.lexpharma.com/.

Safe Harbor Statement
This press release contains “forward-looking statements,” including statements relating to Lexicon’s clinical development of LX1031, LX1032, LX2931, and LX4211 and the potential therapeutic and commercial potential of LX1031, LX1032, 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, 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.  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, 2008, 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

Consolidated Statements of Operations Data
(In thousands, except         Three Months Ended       Year Ended
 per share data)                 December 31,          December 31,
                            --------------------  --------------------
                              2009       2008       2009        2008
                            --------    --------  --------    --------
                                 (unaudited)           (unaudited)
Revenues:                           
    Collaborative research    $1,292      $4,388    $9,334     $27,177
    Subscription and 
     license fees                120       1,962     1,366       5,144
                            --------    --------  --------    --------
       Total revenues          1,412       6,350    10,700      32,321
Operating expenses:                 
    Research and development, 
     including stock-based 
     compensation of $694,
     $1,028, $3,022 and
     $3,941, respectively     18,834      22,364    81,238     107,232
    General and 
     administrative, 
     including stock-based 
     compensation of $502, 
     $691, $2,252 and 
     $2,559, respectively      4,425       4,875    19,418      21,624
                            --------    --------  --------    --------
       Total operating 
        expenses              23,259      27,239   100,656     128,856
                            --------    --------  --------    --------
Loss from operations         (21,847)    (20,889)  (89,956)    (96,535)
Gain (loss) on 
 investments, net                165       2,008     1,173     (1,314)
Interest income                  211         607       880       5,762
Interest expense                (786)       (671)   (2,966)     (2,691)
Other expense, net              (513)       (485)   (2,550)     (2,106)
                            --------    --------  --------    --------
Consolidated loss before 
 income taxes                (22,770)    (19,430)  (93,419)    (96,884)
Income tax benefit                 -           -       102           -
                            --------    --------  --------    --------
Consolidated net loss        (22,770)    (19,430)  (93,317)    (96,884)
Loss attributable to 
 noncontrolling interest 
 in Symphony Icon, Inc.          765       4,013    10,537      20,024
                            --------    --------  --------    --------
Net loss attributable 
 to Lexicon 
 Pharmaceuticals, Inc.      $(22,005)   $(15,417) $(82,780)   $(76,860)
                            ========    ========  ========    ========
Net loss attributable to 
 Lexicon Pharmaceuticals, 
 Inc. per common share, 
 basic and diluted            $(0.13)     $(0.11)   $(0.57)     $(0.56)
                            ========    ========  ========    ========
Shares used in computing 
 net loss  attributable 
 to Lexicon Pharmaceuticals, 
 Inc. per common share, 
 basic and diluted           169,872     136,797   145,465     136,797



Consolidated Balance Sheet Data 
(In thousands)
                                            As of              As of
                                         December 31,      December 31,
                                            2009               2008
                                         ------------      ------------
                                         (unaudited)                  
Cash and investments, including 
 cash and investments held by 
 Symphony Icon, Inc.                       $162,513          $158,798
Obligations under line of credit            (37,435)                -
                                           --------          --------
Cash and investments, net of 
 obligations under line of credit           125,078           158,798
                                                    
Property and equipment, net                  58,754            65,087
Goodwill                                     25,798            25,798
Total assets                                257,761           261,508
Deferred revenue                             15,154            19,884
Current and long-term debt, 
 including line of credit                    66,964            30,492
Noncontrolling interest in 
 Symphony Icon, Inc.                           (290)           10,247
Accumulated deficit                        (570,175)         (487,395)
Total Lexicon Pharmaceuticals, 
 Inc. stockholders' equity                  163,787           185,580