SC 13D/A

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

SCHEDULE 13D

Under the Securities Exchange Act of 1934

(Amendment No. 9)

Lexicon Pharmaceuticals, Inc.

(Name of Issuer)

Common Stock, par value $0.001 per share

(Title of Class of Securities)

528872104

(CUSIP Number)

Raymond Debbane

c/o The Invus Group, LLC

750 Lexington Avenue

30^th Floor

New York, New York 10022

(212) 371-1717

Copies to:

Robert Spatt, Esq.

Peter Malloy, Esq.

Simpson Thacher & Bartlett LLP

425 Lexington Avenue

New York, New York 10017

(212) 455-2000

(Name, Address and Telephone Number of Person Authorized to Receive Notices and Communications)

February 16, 2012

(Date of Event which Requires Filing of this Statement)

If the filing person has previously filed a statement on Schedule 13G to report the acquisition that is the subject of this Schedule 13D, and is filing this schedule because of §§240.13d-1(e), 240.13d-1(f) or 240.13d-1(g), check the following box.  ¨

Note: Schedules filed in paper format shall include a signed original and five copies of the schedule, including all exhibits. See §240.13d-7 for other parties to whom copies are to be sent.

* The remainder of this cover page shall be filled out for a reporting person’s initial filing on this form with respect to the subject class of securities, and for any subsequent amendment containing information which would alter disclosures provided in a prior cover page.

The information required on the remainder of this cover page shall not be deemed to be “filed” for the purpose of Section 18 of the Securities Exchange Act of 1934 (“Act”) or otherwise subject to the liabilities of that section of the Act but shall be subject to all other provisions of the Act (however, see the Notes).

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This Amendment No. 9 hereby amends and supplements the statement of beneficial ownership on Schedule 13D, relating to the common stock, $0.001 par value per share (the “Issuer Common Stock”), of Lexicon Pharmaceuticals, Inc., a Delaware corporation (the “Issuer” or “Lexicon”), initially filed on June 27, 2007, as amended by Amendment No. 1 thereto filed on August 24, 2007, Amendment No. 2 thereto filed on August 29, 2007, Amendment No. 3 thereto filed on October 8, 2009, Amendment No. 4 thereto filed on October 15, 2009, Amendment No. 5 thereto filed on March 15, 2010, Amendment No. 6 thereto filed on August 15, 2011, Amendment No. 7 thereto filed on November 14, 2011 and Amendment No. 8 thereto filed on December 22, 2011 (as so amended, the “Statement”). All capitalized terms not otherwise defined herein have the meaning assigned to them in the Statement. (as so amended, the “Statement”). All capitalized terms not otherwise defined herein have the meaning assigned to them in the Statement.

Item 4. Purpose of Transaction

Item 4 is hereby amended and supplemented by replacing the last two paragraphs thereof with the following new paragraphs:

On February 16, 2012, Mr. Raymond Debbane, one of the members of Lexicon’s board of directors designated by the Invus Parties, was appointed Chairman of Lexicon’s board of directors, replacing Dr. Samuel L. Barker, who will continue to serve as a member of the board and as the chairman of the audit committee.

On February 23, 2012, Invus, L.P., Invus C.V. and Lexicon entered into a Supplement No. 2 to Transaction Agreements (the “Supplement No. 2 to Transaction Agreements”), pursuant to which, among other things, Invus, L.P. and Lexicon agreed to supplement certain provisions of the Stockholders’ Agreement. The Supplement No. 2 to Transaction Agreements is summarized in Item 6 below and is filed as an exhibit to the Statement. The Supplement No. 2 to Transaction Agreements, and the description thereof included in Item 6 below, are incorporated by reference into this Item 4.

Other than as described in this Statement, the Invus Parties do not have any present plans or proposals (1) to exercise their rights under the Stockholders’ Agreement to designate additional directors to Lexicon’s board of directors or to otherwise modify the current composition of Lexicon’s board of directors or Lexicon’s certificate of incorporation, bylaws or other governance arrangements or (2) that relate to or would otherwise result in any of the actions described in subparagraphs (a) through (j) of Item 4 of Schedule 13D; provided, that the Invus Parties may, at any time, review or reconsider their position with respect to Lexicon and reserve the right to develop such plans or proposals.

Item 6. Contracts, Arrangements, Understandings or Relationships with Respect to Securities of the Issuer

Item 6 is hereby amended and supplemented by adding the following immediately after the last paragraph thereof:

l. Supplement No. 2 to Transaction Agreements

On February 23, 2012, Invus, L.P., Invus C.V. and Lexicon entered into a Supplement No. 2 to Transaction Agreements, pursuant to which, among other things, Lexicon agreed, in accordance with its obligations under Sections 2.01 and 2.04 of the Stockholders’ Agreement, to amend its certificate of incorporation and bylaws and take certain other actions to facilitate the right of Invus, L.P. and Invus C.V. to designate a number of directors (the “Investor Designated Directors”) to Lexicon’s board of directors equal to Invus, L.P.’s ownership percentage of Issuer Common Stock (rounded up to the nearest whole number of directors) (the “Required Director Number”), which right Invus, L.P. and Invus C.V. have determined not to exercise presently, but may exercise at any time in the future in their sole discretion. The following is a summary of selected provisions of the Supplement No. 2 to Transaction Agreements. While the Invus Parties believe this description covers the material terms of the Supplement No. 2 to Transaction Agreements, it is qualified in its entirety by reference to the Supplement No. 2 to Transaction Agreements, a copy of which is included as Exhibit 15 to this Statement and is incorporated herein by reference.

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Amendment to Lexicon’s Certificate of Incorporation

Lexicon acknowledged that its board of directors has, in accordance with its obligations under Section 2.04 of the Stockholders’ Agreement, (1) approved an amendment to Section 5.01 of Lexicon’s certificate of incorporation to increase the maximum number of directors of which the board may consist from 12 to 13 directors or such greater number of directors as is necessary to permit the election or appointment to the board of the Required Director Number of Investor Designated Directors and (2) recommended such amendment for approval by Lexicon’s stockholders.

In advance of the next annual meeting of its stockholders and in accordance with Section 2.01 of the Stockholders’ Agreement, Lexicon agreed to (1) include such amendment as a matter to be considered and acted upon by its stockholders in the proxy statement to be sent to stockholders in advance of such meeting, (2) solicit from stockholders eligible to vote at such meeting proxies in favor of such amendment and (3) use its reasonable efforts to obtain the approval of any significant stockholder advisory firms or other similar third-party agencies in favor of such amendment.

Amendments to Lexicon’s Bylaws

Lexicon acknowledged that its board of directors has, in accordance with its obligations under Section 2.04 of the Stockholders’ Agreement, approved (1) an amendment to Section 2.2 of Lexicon’s bylaws providing that special meetings of the stockholders may be called at any time by any Investor Designated Director, (2) an amendment to Section 3.2 of the bylaws increasing the maximum number of directors of which the board may consist from 12 to 13 directors or such greater number of directors as is necessary to permit the election or appointment to Lexicon’s board of directors of the Required Director Number of Investor Designated Directors and (3) an amendment to Section 3.4(b) of the bylaws providing that Investor Designated Directors may be elected at special meetings of stockholders, which amendments will take effect upon the approval of the amendment to the certificate of incorporation by the requisite number of stockholders.

Procedure for Appointing Investor Designated Directors to Newly-Created Directorships

Upon the delivery of a written notice from Invus, L.P. and Invus C.V. to Lexicon, Lexicon and its board of directors agreed, in accordance with Section 2.01 of the Stockholders’ Agreement, to promptly (1) increase the number of directors of which the board shall consist to the number set forth in such notice (which number shall be no greater than reasonably necessary to seat the Required Director Number of Investor Designated Directors on the board) and (2) cause the appointment of the Investor Designated Directors set forth in such notice to the newly-created directorships resulting from such increase.

Item 7. Material to be Filed as Exhibits

Item 7 is hereby amended and supplemented by inserting the following at the end thereof:

15. Supplement No. 2 to Transaction Agreements, dated as of February 23, 2012.

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SIGNATURE

After reasonable inquiry and to the best of my knowledge and belief, I certify that the information set forth in this Statement is true, complete and correct.

INVUS, L.P.
By: INVUS ADVISORS, L.L.C., its general partner
By:	/s/ Raymond Debbane
Name:	Raymond Debbane
Title:	President
INVUS PUBLIC EQUITIES, L.P.
By: INVUS PUBLIC EQUITIES ADVISORS, LLC, its general partner
By:	/s/ Raymond Debbane
Name:	Raymond Debbane
Title:	President
INVUS ADVISORS, L.L.C.
By:	/s/ Raymond Debbane
Name:	Raymond Debbane
Title:	President
INVUS PUBLIC EQUITIES ADVISORS, LLC
By:	/s/ Raymond Debbane
Name:	Raymond Debbane
Title:	President
INVUS C.V.
By: ULYS, L.L.C., its general partner
By:	/s/ Raymond Debbane
Name:	Raymond Debbane
Title:	President

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ULYS, L.L.C.
By:	/s/ Raymond Debbane
Name:	Raymond Debbane
Title:	President
RAYMOND DEBBANE
/s/ Raymond Debbane
Dated: February 24, 2012

EX-99.15

EXHIBIT 15

SUPPLEMENT NO. 2 TO

TRANSACTION AGREEMENTS

This Supplement No. 2 to Transaction Agreements (this “Supplement”) is entered into as of February 23, 2012 by and among Invus, L.P., a Bermuda limited partnership (“Invus, L.P.”), Invus C.V., a Netherlands limited partnership (“Invus C.V.”, and, together with Invus, L.P., the “Investors”), and Lexicon Pharmaceuticals, Inc., a Delaware corporation (the “Company”). Capitalized terms used but not otherwise defined herein shall have the meanings ascribed to them in the Securities Purchase Agreement (as defined below).

W I T N E S S E T H :

WHEREAS, Invus, L.P. and the Company entered into the Securities Purchase Agreement, dated as of June 17, 2007, by and between Invus, L.P. and the Company (as amended, supplemented or otherwise modified, the “Securities Purchase Agreement”), the Stockholders’ Agreement, dated as of June 17, 2007 (as amended, supplemented or otherwise modified, the “Stockholders’ Agreement”) and the Registration Rights Agreement, dated as of June 17, 2007 (as amended, supplemented or otherwise modified, the “Registration Rights Agreement”, and, together with the Securities Purchase Agreement and the Stockholders’ Agreement, the “Transaction Agreements”);

WHEREAS, pursuant to the exercise of subscription rights issued to the Investors in the Second Rights Offering, the Investors have increased their beneficial ownership of Company Common Stock to approximately 58.3% of the outstanding shares of Company Common Stock, from approximately 48.9% of the shares of Company Common Stock outstanding before completion of the Second Rights Offering;

WHEREAS, as a result of the increase in the Investors’ beneficial ownership of Company Common Stock to over 50% of the outstanding shares of Company Common Stock, the Investors’ rights under the Stockholders’ Agreement have been altered as provided in Articles II, III, IV and V thereof, including, among other things, increasing the number of directors to the Board that the Investors are entitled to designate pursuant to Section 2.01 of the Stockholders’ Agreement (the “Appointment Right”);

WHEREAS, pursuant to Section 2.01(c) of the Stockholders’ Agreement, the Company, subject to the Board’s fiduciary duties, has agreed to take all necessary and desirable actions within its control (including calling special meetings of the Board and stockholders) to effectuate the provisions of Section 2.01, and pursuant to Section 2.04 of the Stockholders’ Agreement, the Board shall take or cause to be taken all lawful action necessary or appropriate to ensure that none of the Certificate of Incorporation or the By-Laws contains any provisions inconsistent with the Stockholders’ Agreement or that would in any way nullify or impair the terms of the Stockholders’ Agreement or the rights of the Investors thereunder; and

WHEREAS, in consideration of the Investors’ Appointment Right, which right the Investors have determined not to exercise presently, but may exercise at any time in the future in their sole discretion, the Investors and the Company desire to take certain actions to facilitate the potential future exercise of the Investors’ Appointment Right.

NOW, THEREFORE, intending to be legally bound hereby, the parties hereto hereby agree as follows:

Section 1. Amendment to the Certification of Incorporation

(a) The Company acknowledges that on or before the date hereof the Board has approved, by the affirmative vote of a majority of the Whole Board (as defined in the By-Laws), the following amendment to Section 5.01 of the Certificate of Incorporation in accordance with the Board’s obligations under Section 2.04 of the Stockholders’ Agreement and has recommended such amendment for approval by the Company’s stockholders, which amendment (the “Charter Amendment”) will amend and restate such section in its entirety so that it reads substantially as follows:

Section 5.01. Number and Term. The number of directors of the Corporation shall from time to time be fixed exclusively by the Board of Directors in accordance with, and subject to the limitations set forth in, the bylaws of the Corporation (the “Bylaws”); provided, however, that the Board of Directors shall at all times consist of a minimum of three and a maximum of 13 directors, subject, however, to increases above 13 directors as may be required in order to permit the holders of any series of Preferred Stock to exercise their right (if any) to elect additional directors under specified circumstances or to permit the election or appointment to the Board of Directors of the Required Director Number of Investor Designated Directors (each as defined in the Stockholders’ Agreement, dated as of June 17, 2007, between Invus, L.P. and the Corporation (as amended, supplemented or otherwise modified, the “Stockholders’ Agreement”)) pursuant to the Stockholders’ Agreement. No decrease in the number of directors shall have the effect of shortening the term of any incumbent director. Anything in this Certificate of Incorporation or the Bylaws to the contrary notwithstanding, each director shall hold office until his successor is elected and qualified or until his earlier death, resignation or removal.

(b) In advance of the next annual meeting of its stockholders and in accordance with Section 2.01 of the Stockholders’ Agreement, the Company shall take all necessary actions to (i) include the Charter Amendment as a matter to be considered and acted upon by its stockholders in the applicable proxy statement to be sent to stockholders in advance of such meeting, which proxy statement shall include the Board’s recommendation that the stockholders of the Company vote in favor of such amendment, (ii) solicit from stockholders eligible to vote at such meeting proxies in favor of the Charter Amendment and (iii) use its reasonable efforts to obtain the approval of any significant stockholder advisory firms or other similar third-party agencies in favor of the Charter Amendment.

(c) In the event that the Charter Amendment is not approved by the requisite number of stockholders eligible to vote at such meeting pursuant to Article X of the Certificate of Incorporation, the Company shall, in advance of subsequent annual or

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special meetings of its stockholders, take all necessary actions to (i) include the Charter Amendment as a matter to be considered and acted upon by its stockholders in the applicable proxy statement to be sent to stockholders in connection with such meeting, which proxy statement shall include the Board’s recommendation that the stockholders of the Company vote in favor of such amendment, (ii) solicit from stockholders eligible to vote at such meetings proxies in favor of the Charter Amendment and (iii) use its reasonable efforts to obtain the approval of any significant stockholder advisory firms or other similar third-party agencies in favor of the Charter Amendment, until the Charter Amendment is approved by the requisite number of stockholders.

Section 2. Amendments to the By-Laws

The Company acknowledges that on or before the date hereof the Board has approved, by the affirmative vote of a majority of the Whole Board, the following amendments to Sections 2.2, 3.2 and 3.4(b) of the By-Laws in accordance with the Board’s obligations under Section 2.04 of the Stockholders’ Agreement, which amendments will automatically take effect on the date on which the Charter Amendment is approved by the requisite number of stockholders and will amend and restate such sections in their entirety so that they read substantially as follows:

Section 2.2. Special Meetings. Special meetings of the Stockholders, for any purpose or purposes, may be called at any time by the Chairman of the Board of Directors (the “Chairman of the Board”) (if any), any Investor Designated Director (as defined in the Stockholders’ Agreement, dated as of June 17, 2007, between Invus, L.P. and the Corporation (as amended, supplemented or otherwise modified, the “Stockholders’ Agreement”)) or the Chief Executive Officer and shall be called by the Secretary at the written request, or by resolution adopted by the affirmative vote, of a majority of the total number of directors that the Corporation would have if there were no vacancies (the “Whole Board”), which request or resolution shall fix the date, time and place, and state the purpose or purposes, of the proposed meeting. Except as provided by applicable law, these Bylaws or the Certificate of Incorporation, Stockholders shall not be entitled to call a special meeting of Stockholders or to require the Board of Directors or any officer to call such a meeting or to propose business at such a meeting. Business transacted at any special meeting of Stockholders shall be limited to the purposes stated in the notice or waivers of notice of such meeting.

Section 3.2. Number and Qualification. The number of directors shall be fixed from time to time exclusively pursuant to resolution adopted by a majority of the Whole Board, but shall consist of not less than three nor more than 13 directors, subject, however, to increases above 13 directors as may be required in order to permit the holders of any series of preferred stock of the Corporation to elect directors under specified circumstances or to permit the election or appointment to the Board of Directors of the Required Director Number (as defined in the Stockholders’ Agreement) of Investor Designated Directors pursuant to the Stockholders’ Agreement. The directors need not be Stockholders or residents of the State of Delaware. Each director must have attained 21 years of age.

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Section 3.4. Election; Term of Office.

(b) Directors shall be elected by Stockholders only at annual meetings of Stockholders; provided, however, that if any such annual meeting is not held or if any director to be elected thereat is not elected, such director may be elected at any special meeting of Stockholders held for that purpose; provided, further, that Investor Designated Directors may be elected at any special meeting of Stockholders held for that purpose.

Section 4. Increase in the Number of Directors; Newly-Created Directorships

(a) Upon the delivery of a written notice from the Investors to the Company, the Company and the Board shall, in accordance with Section 2.01 of the Stockholders’ Agreement, take all necessary actions to promptly (a) increase the number of directors of which the Board shall consist to the number set forth in such notice (which number shall be no greater than reasonably necessary for the exercise of the Investors’ rights under Section 2.01 of the Stockholders’ Agreement) in accordance with Section 5.01 of the Certificate of Incorporation and Section 3.2 of the By-Laws and (b) cause the appointment of the Investor Designated Directors (as defined in the Stockholders’ Agreement) set forth in such notice to the newly-created directorships resulting from such increase in accordance with Section 5.06 of the Certificate of Incorporation and Section 3.9 of the By-Laws.

(b) For the avoidance of doubt, in connection with each annual or special meeting of stockholders held to elect directors to the Board, the Company and the Board shall adhere to their obligations in Sections 2.01(b) and 2.01(c) of the Stockholders’ Agreement with respect to the election to the Board of the Investor Designated Directors, including, without limitation, the Company’s and the Board’s obligation to recommend and use all reasonable efforts to cause the election of such Investor Designated Directors and the Company’s obligation to use its best efforts to solicit from its stockholders eligible to vote in the election of directors proxies in favor of the election of each person designated for election as an Investor Designated Director and against the election of any candidate whose election would adversely impact the election to, or opportunity to serve on, the Board of any such Investor Designated Director.

Section 5. Consent to Further Amendments; Further Assurances

The parties hereto hereby consent to such other amendments and changes to the Certificate of Incorporation, By-Laws and Transaction Agreements as necessary to give effect to the intent of this Supplement and shall execute and deliver or cause to be executed and delivered any additional documents, certificates, consents, waivers and instruments and perform any additional acts that may be reasonably necessary or appropriate to effectuate and perform the provisions of this Supplement and those transactions contemplated herein, including, without limitation, to cause the appointment or election to the Board of any Investor Designated Directors in accordance with the Stockholders’ Agreement.

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Section 6. Ratification and Confirmation

The Transaction Agreements, as hereby amended, supplemented or otherwise modified, are hereby ratified and confirmed in all respects. This Supplement shall be interpreted and construed together with, and as a part of, each of the Transaction Agreements, as applicable. Any reference in any other document to any of the Transaction Agreements shall be deemed to refer to the applicable Transaction Agreement, as modified by this Supplement. The execution, delivery and effectiveness of this Supplement shall not constitute a modification or waiver of any provision of the Transaction Agreements except as expressly provided herein.

Section 7. Governing Law

This Supplement shall be governed by, and construed in accordance with, the laws of the State of New York. All actions and proceedings arising out of or relating to this Supplement shall be heard and determined exclusively in any New York state or federal court, in each case sitting in the Borough of Manhattan. The parties hereto hereby (a) submit to the exclusive jurisdiction of any New York state or federal court, in each case sitting in the Borough of Manhattan, for the purpose of any Action arising out of or relating to this Supplement brought by any party hereto, and (b) irrevocably waive, and agree not to assert by way of motion, defense, or otherwise, in any such Action, any claim that it is not subject personally to the jurisdiction of the above-named courts, that its property is exempt or immune from attachment or execution, that the Action is brought in an inconvenient forum, that the venue of the Action is improper, or that this Supplement may not be enforced in or by any of the above-named courts.

Section 8. Counterparts

This Supplement may be executed and delivered (including by facsimile transmission) in one or more counterparts, and by the different parties hereto in separate counterparts, each of which when executed and delivered shall be deemed to be an original but all of which taken together shall constitute one and the same agreement.

[Signature Page Follows]

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IN WITNESS WHEREOF, the Investors and the Company have caused this Supplement to be executed as of the date first written above by their respective officers thereunto duly authorized.

INVESTORS: INVUS, L.P., a Bermuda limited partnership By: Invus Advisors, L.L.C., its general partner
By:	/s/ Raymond Debbane
Name:	Raymond Debbane
Title:	President

INVUS C.V., a Netherlands limited partnership By: Ulys, L.L.C., its general partner
By:	/s/ Raymond Debbane
Name:	Raymond Debbane
Title:	President

COMPANY: LEXICON PHARMACEUTICALS, INC., a Delaware corporation
By:	/s/ Arthur T. Sands
Name:	Arthur T. Sands
Title:	President and CEO

[Signature Page to Supplement No. 2 to Transaction Agreements]