CHANGE IN CONTROL AGREEMENT

EXHIBIT 10.5

CHANGE IN CONTROL AGREEMENT

This Change in Control Agreement (the “Agreement”) is made as of October 10, 2006 between Senomyx, Inc., a Delaware corporation (the “Company”), and Nigel R. A. Beeley, Ph.D. (“Employee”).

Whereas, in order to provide an incentive for Employee to participate actively in the affairs and maximize the value of the Company, the Company is willing to provide Employee with certain benefits on the terms and conditions set forth below.

Now Therefore, for good and valuable consideration, the sufficiency of which is hereby acknowledged, Employee and the Company (each, a “Party,” and collectively, the “Parties”) agree as follows:

1.             Benefits in the Event of a Change in Control.  If (i) a Change in Control (defined below) occurs and (ii) during the period beginning one (1) month prior to the effective date of such Change in Control and ending eighteen (18) months after the effective date of such Change in Control, Employee’s employment with the Company is terminated either (A) by the Company without Cause (defined below) (not including death or Disability (as defined below)) or (B) by Employee for Good Reason (defined below) (not including death or Disability), then, without further action by Employee or the Company, Employee shall be entitled to the benefits set forth below:

(a)           The vesting applicable to all options to purchase shares of the Company’s capital stock (“Options”) and all shares of the Company’s capital stock which are subject to the Company’s right to repurchase such shares (“Restricted Stock”) held by Employee as of the effective date of such termination shall be accelerated in full such that Employee shall have the right to exercise in accordance with the terms thereof all or any portion of such Options (notwithstanding any vesting schedule set forth in such Options) and any such Company repurchase rights with respect to such Restricted Stock shall lapse in full; and

(b)           Employee shall be entitled to receive a lump sum cash payment in an amount equal to one hundred percent (100%) of Employee’s Annual Pay (as defined below), payable on the Effective Date specified in the Release (as defined below) delivered by Employee to the Company following such Change in Control.  The foregoing payments shall be subject to standard deductions and withholdings.

(c)           Assuming the Employee timely and accurately elects to continue his health insurance benefits under the Consolidated Omnibus Budget Reconciliation Act of 1985 (“COBRA”), the Company shall reimburse the Employee for the COBRA expenses he pays on behalf of himself and his family until the earliest of (i) the end of the 12 month period following Employee’s termination, (ii) the expiration of the Employee’s continuation coverage under COBRA and any applicable state COBRA-like statute that provides mandated continuation coverage or (iii) the date the Employee becomes eligible for health insurance benefits of a subsequent employer.

1

2.             Release.  Notwithstanding the foregoing, the Employee shall not receive any of the severance payments or benefits set forth under Section 1, unless upon Employee’s termination of employment the Employee furnishes the Company with an effective waiver and release of claims (the “Release”) in a form acceptable to the Company and substantially as attached hereto as Exhibit A.  If a majority of the Board of Directors of the Company (the “Board”) determines in good faith that the Employee has breached any provision of his Proprietary Information and Inventions Agreement with the Company or any provision of this Agreement or the Release, the Company shall be excused from the obligation to provide any severance payment under Section 1 and the Company shall be entitled to full recovery of any severance payment already provided to the Employee under Section 1.

3.             Definitions.  For purposes of this Agreement, capitalized terms used herein shall have the following meanings:

(a)           “Annual Pay” shall mean the sum of the Employee’s (i) base salary in effect on the date of termination and (ii) the last annual bonus paid to the Employee by the Company prior to the date of termination.

(b)           “Cause” means the occurrence of any of the following:  (i) the Employee’s commission of any felony or any crime involving fraud, dishonesty or moral turpitude under the laws of the United States or any state thereof; (ii) the Employee’s attempted commission of, or participation in, a fraud or act of dishonesty against the Company; (iii) the Employee’s intentional and material violation of any contract or agreement between the Employee and the Company or any statutory duty owed to the Company; (iv) the Employee’s unauthorized use or disclosure of the Company’s confidential information or trade secrets or (v) the Employee’s gross misconduct.  The determination that a termination is for Cause shall be made by the Company in its discretion.  Any determination by the Company that the employment of the Employee was terminated by reason of dismissal without Cause for the purposes of determining benefits under this Agreement shall have no impact upon any determination of the rights or obligations of the Company or such Employee for any other purpose.

(c)           “Change in Control” means the occurrence, in a single transaction or in a series of related transactions, of any one or more of the following events:

(i)            any Exchange Act Person (as defined in the Company’s Amended and Restated 2004 Equity Incentive Plan (the “Plan”)) becomes the owner, directly or indirectly, of securities of the Company representing more than fifty percent (50%) of the combined voting power of the Company’s then outstanding securities other than by virtue of a merger, consolidation or similar transaction.  Notwithstanding the foregoing, a Change in Control shall not be deemed to occur (A) on account of the acquisition of securities of the Company by an investor, any affiliate thereof or any other Exchange Act Person from the Company in a transaction or series of related transactions the primary purpose of which is to obtain financing for the Company through the issuance of equity securities or (B) solely because the level of Ownership (as defined in the Plan) held by any Exchange Act Person (the “Subject Person”) exceeds the designated percentage threshold of the outstanding voting securities as a result of a repurchase or other acquisition of voting securities by the Company reducing the number of shares outstanding, provided that if a Change in Control would occur (but for the operation of

2

this sentence) as a result of the acquisition of voting securities by the Company, and after such share acquisition, the Subject Person becomes the Owner of any additional voting securities that, assuming the repurchase or other acquisition had not occurred, increases the percentage of the then outstanding voting securities Owned by the Subject Person over the designated percentage threshold, then a Change in Control shall be deemed to occur;

(ii)           there is consummated a merger, consolidation or similar transaction involving (directly or indirectly) the Company and, immediately after the consummation of such merger, consolidation or similar transaction, the stockholders of the Company immediately prior thereto do not Own, directly or indirectly, either (A) outstanding voting securities representing more than fifty percent (50%) of the combined outstanding voting power of the surviving Entity (as defined in the Plan) in such merger, consolidation or similar transaction or (B) more than fifty percent (50%) of the combined outstanding voting power of the parent of the surviving Entity in such merger, consolidation or similar transaction, in each case in substantially the same proportions as their Ownership of the outstanding voting securities of the Company immediately prior to such transaction;

(iii)         the stockholders of the Company approve or the Board approves a plan of complete dissolution or liquidation of the Company, or a complete dissolution or liquidation of the Company shall otherwise occur;

(iv)          there is consummated a sale, lease, license or other disposition of all or substantially all of the consolidated assets of the Company and its Subsidiaries (as defined in the Plan), other than a sale, lease, license or other disposition of all or substantially all of the consolidated assets of the Company and its Subsidiaries to an Entity, more than fifty percent (50%) of the combined voting power of the voting securities of which are Owned by stockholders of the Company in substantially the same proportions as their Ownership of the outstanding voting securities of the Company immediately prior to such sale, lease, license or other disposition; or

(v)            individuals who, on the date of this Agreement, are members of the Board (the “Incumbent Board”) cease for any reason to constitute at least a majority of the members of the Board; provided, however, that if the appointment or election (or nomination for election) of any new Board member was approved or recommended by a majority vote of the members of the Incumbent Board then still in office, such new member shall, for purposes of this Agreement, be considered as a member of the Incumbent Board.

(d)           “Disability” shall mean Employee’s failure or inability, for reasons of health, to perform Employee’s usual and customary duties on behalf of the Company in the usual and customary manner for a total of more than ninety (90) consecutive business days (excluding Saturdays, Sundays and holidays (days during which the Company is closed due to a recognized holiday)).

(e)           “Good Reason” shall mean the occurrence of any of the following events or conditions:  (i) (A) a change in the Employee’s status, title, position or responsibilities (including reporting responsibilities) which represents an adverse change from the Employee’s status, title, position or responsibilities as in effect at any time within ninety (90) days preceding the date of a

3

Change in Control or at any time thereafter; (B) the assignment to the Employee of any duties or responsibilities which are inconsistent with the Employee’s status, title, position or responsibilities as in effect at any time within ninety (90) days preceding the date of a Change in Control or at any time thereafter; or (C) any removal of the Employee from or failure to reappoint or reelect the Employee to any of such offices or positions (unless such removal or failure to reappoint or reelect is (1) in connection with the termination of the Employee’s employment for Cause, (2) as a result of the Employee’s Disability or death, or (3) by the Employee other than as a result of termination for Good Reason); (ii) a reduction in the Employee’s annual base compensation; or (i