PURCHASE AGREEMENT

Exhibit 10.1

PURCHASE AGREEMENT

October 8, 2009

Invus, L.P.

c/o The Invus Group, L.L.C.

750 Lexington Avenue (30 ^th Floor)

New York, New York 10022

Lexicon Pharmaceuticals, Inc.

8800 Technology Forest Place

The Woodlands, Texas 77381

Attn:  President and Chief Executive Officer

Ladies and Gentlemen:

Reference is made to (a) that certain Stockholders’ Agreement, dated as of June 17, 2007 (as amended, the “ Stockholders’ Agreement ”), by and between Invus, L.P. (the “ Investor ”) and Lexicon Pharmaceuticals, Inc. (the “ Company ”), (b) the Amendment to Securities Purchase Agreement, dated as of October 7, 2009 (the “ Amendment ”), amending that certain Securities Purchase Agreement, dated as of June 17, 2007, by and between the Investor and the Company (the “ Securities Purchase Agreement ”), and (c) that certain Underwriting Agreement being entered into by the Company with the representatives of the underwriters concurrently with this Purchase Agreement (the “ Underwriting Agreement ”) providing for the issuance by the Company to the underwriters of 19,894,076 shares of Company Common Stock (the “ Firm Shares ”), without giving effect to any exercise of the underwriters’ over-allotment option, for sale in a public offering at a price to the public of $1.50 per share (the “ Price to Public ”).  Capitalized terms used but not otherwise defined herein shall have the meanings ascribed to them in the Stockholders’ Agreement.

Pursuant to Section 4.02 of the Stockholders’ Agreement and Section 8 of the Amendment, on the terms and subject to the conditions set forth herein, the Investor hereby agrees to purchase from the Company the number of shares specified below (the “ Invus Shares ”) of Company Common Stock at a price per share equal to the Price to Public, for the total purchase price specified below:

The Company hereby represents and warrants to and agrees with the Investor to all the same representations and warranties contained in Section 1 and the covenant