AMENDMENT NO. 1 TO LOAN AND SECURITY AGREEMENT

Exhibit 10.21

AMENDMENT NO. 1

TO

LOAN AND SECURITY AGREEMENT

THIS AMENDMENT NO. 1 TO LOAN AND SECURITY AGREEMENT (this “Amendment”) is entered into this 13th day of September, 2007, by and among ELIXIR PHARMACEUTICALS, INC. (“Borrower”), and HERCULES TECHNOLOGY GROWTH CAPITAL, INC., a Maryland corporation and HERCULES TECHNOLOGY II, L.P., a Delaware limited partnership (collectively, the “Lender”). Capitalized terms used herein without definition shall have the same meanings given them in the Loan Agreement (as defined below).

RECITALS

A. Borrower and Lender have entered into that certain Loan and Security Agreement dated as of November 21, 2006 (as may be amended, restated, or otherwise modified, the “Loan Agreement”), pursuant to which the Lender has agreed to extend and make available to Borrower certain advances of money.

B. Borrower and Lender have agreed to amend the Loan Agreement upon the terms and conditions more fully set forth herein.

AGREEMENT

NOW, THEREFORE, in consideration of the foregoing Recitals and intending to be legally bound, the parties hereto agree as follows:

1. AMENDMENTS.

SECTION 2.1. The following is appended to Section 2.1:

Notwithstanding any foregoing terms to the contrary, the date by which the Milestone Event is required to occur, and by which Borrower may request a Tranche B Advance, is extended from June 30, 2007 to September 19, 2007. Any such Tranche B Advance remains subject to the other terms and conditions of this Agreement.

2. AMENDMENT CHARGE

Borrower agrees to pay a $12,500 amendment charge to Lender for entering into this Amendment and Borrower’s ability to draw under Tranche B is contingent upon payment of such charge.

3. BORROWER’S REPRESENTATIONS AND WARRANTIES. Borrower represents and warrants that:

(a) immediately upon giving effect to this Amendment (i) the representations and warranties contained in the Loan Documents and the updates to the Disclosure Schedules attached hereto as Annex A are true, accurate and complete in all material

respects as of the date hereof (except to the extent such representations and warranties relate to an earlier date, in which case they are true and correct as of such date), and (ii) no Event of Default has occurred and is continuing;

(b) Borrower has the corporate power and authority to execute and deliver this Amendment and to perform its obligations under the Loan Agreement, as amended by this Amendment;

(c) the certificate of incorporation, bylaws and other organizational documents of Borrower delivered to Lender on the date hereof remain true, accurate and complete and have not been amended, supplemented or restated and are and continue to be in full force and effect;

(d) the execution and delivery by Borrower of this Amendment and the performance by Borrower of its obligations under the Loan Agreement, as amended by this Amendment, have been duly authorized by all necessary corporate action on the part of Borrower;

(e) this Amendment has been duly executed and delivered by Borrower and is the binding obligation of Borrower, enforceable against it in accordance with its terms, except as such enforceability may be limited by bankruptcy, insolvency, reorganization, liquidation, moratorium or other similar laws of general application and equitable principles relating to or affecting creditors’ rights; and

(f) as of the date hereof, it has no defenses against the obligations to pay any amounts under the Obligations. Borrower acknowledges that Lender has acted in good faith and has conducted in a commercially reasonable manner its relationships with Borrower in connection with this Amendment and in connection with the Loan Documents.

Borrower understands and acknowledges that Lender is entering into this Amendment in reliance upon, and in partial consideration for, the above representations and warranties, and agrees that such reliance is reasonable and appropriate.

4. LIMITATION. The amendments set forth in this Amendment shall be limited precisely as written and shall not be deemed (a) to be a waiver or modification of any other term or condition of the Loan Agreement or of any other instrument or agreement referred to therein or to prejudice any right or remedy which Lender may now have or may have in the future under or in connection with the Loan Agreement or any instrument or agreement referred to therein; or (b) to be a consent to any future amendment or modification or waiver to any instrument or agreement the execution and delivery of which is consented to hereby, or to any waiver of any of the provisions thereof. Except as expressly amended hereby, the Loan Agreement shall continue in full force and effect.

5. EFFECTIVENESS. This Amendment shall become effective upon the satisfaction of all the following conditions precedent:

5.1 Amendment. Borrower and Lender shall have duly executed and delivered this Amendment to Lender.

5.2 Payment of Amendment Charge. Borrower shall have paid to Lender the amendment charge referenced in Section 2 of this Amendment.

6. COUNTERPARTS. This Amendment may be signed in any number of counterparts, and by different parties hereto in separate counterparts, with the same effect as if the signatures to each such counterpart were upon a single instrument. All counterparts shall be deemed an original of this Amendment.

7. INTEGRATION. This Amendment and any documents executed in connection herewith or pursuant hereto contain the entire agreement between the parties with respect to the subject matter hereof and supersede all prior agreements, understandings, offers and negotiations, oral or written, with respect thereto and no extrinsic evidence whatsoever may be introduced in any judicial or arbitration proceeding, if any, involving this Amendment; except that any financing statements or other agreements or instruments filed by Lender with respect to Borrower shall remain in full force and effect.

8. GOVERNING LAW; VENUE. THIS AMENDMENT SHALL BE GOVERNED BY AND SHALL BE CONSTRUED AND ENFORCED IN ACCORDANCE WITH THE LAWS OF THE STATE OF CALIFORNIA. Borrower and Lender each submit to the exclusive jurisdiction of the State and Federal courts in Santa Clara County, California.

[signature page follows]

IN WITNESS WHEREOF, the parties have duly authorized and caused this Amendment to be executed as of the date first written above.

Annex A

Updates to the Disclosure Schedules

Updated Schedule 5.13

Employee Loans

Updated Schedule 5.14

Authorized Capital Stock

The authorized capital stock of the Corporation consists of (i) 200,000,000 shares of common stock, $0.001 par value per share (the “Common Stock”), 8,669,791 of which are issued and outstanding and (ii) 126,065,076 shares of preferred stock, $0.001 par value per share, of which (A) 13,595,558 shares have been designated as Series A Convertible Preferred Stock, 13,479,998 of which are issued and outstanding and 115,560 of which are issuable upon exercise of outstanding warrants, (B) 300,000 shares have been designated as Series A-2 Convertible Preferred Stock, all of which are issued and outstanding, (C) 43,523,745 shares have been designated as Series B Convertible Preferred Stock, all of which are issued or outstanding, (D) 1,000,000 have been designated as Series B-1 Convertible Preferred Stock, all of which are issued and outstanding, (E) 460,933 shares have been designated as Series B-2 Convertible Preferred Stock, all of which are issued and outstanding, (F) 32,184,840 shares have been designated as Series C Convertible Preferred Stock, 31,295,240 of which are issued and outstanding and 889,600 of which are issuable upon exercise of outstanding warrants, and (G) 35,000,000 shares have been designated as Series D Convertible Preferred Stock, 28,030,032 of which are issued or outstanding. The Corporation has reserved an aggregate of 23,406,479 shares of Common Stock for issuance in the future under the Corporation Stock Option Plans.

Stockholders of Record

A revised capitalization table is attached hereto as Annex B and is incorporated by reference into this section in its entirety.

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Annex B

Capitalization Table

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UPDATED EXHIBIT D

BORROWER’S PATENTS, TRADEMARKS, COPYRIGHTS AND LICENSES

Registered Copyrights

None.

Registered Trademarks

Trademark Records By Trademark

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3

4

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Patents and Patent Applications

The Company owns or controls the patent and patent applications listed in the table below and pursuant to the license agreements set forth on Schedule 3.9(m) of the Schedule of Exceptions.

1. Assignee ELIXIR – Elixir owns the listed patent/application.

2. Assignee MIT – Elixir has exclusively licensed the patent/application from the Massachusetts Institute of Technology.

3. Assignee Northwestern – Elixir has exclusively licensed the patent/application from Northwestern University.

4. Assignee UCSF (Kenyon) – Elixir has exclusively licensed the patent/application from UCSF through the Regents of the University of California. The technology was developed in the laboratory of Cynthia Kenyon.

5. Assignee BMS – Elixir has exclusively licensed the patent/application from Bristol-Myers Squibb Company.

6. Assignee MCG – Elixir has exclusively licensed the patent/application from the Medical College of Georgia.

7. Assignee UCSF (Verdin) – Elixir has exclusively licensed the patent/application from UCSF through the Regents of the University of California. The technology was developed in the laboratory of Eric Verdin.

8. Assignee BIDMC/CMCC – Elixir has exclusively licensed the patent/application from co-owners Beth Israel Deaconess Medical Center and Children’s Medical Center.

9. Assignee Kissei- Elixir has exclusively licensed the patent/application form Kissei Pharmaceutical Company.

License Agreements

Non-Exclusive License Agreement by and among Baylor College of Medicine and the Company, dated as of January 6, 2004.

Exclusive License Agreement by and among Beth Israel Deaconess Medical Center, Children’s Medical Center Corporation and Centagenetix, dated as of October 26, 2001.

Restatement and Amendment of Exclusive License Agreement by and among Boston Medical Center Corporation, Trustees of Boston University and the Company, dated as of June 9, 2004.

Exclusive License Agreement by and between BMS and the Company, dated as of April 25, 2005 (the “BMS Agreement”).

Exclusive License Agreement by and between Cancer Research Technology Ltd. and the Company, dated as of October 30, 2003.

Exclusive License Agreement on Mitiglinide by and between Kissei Pharmaceutical Co Ltd and the Company as of dated March 24, 2006 (the “Kissei License Agreement”).

Massachusetts Institute of Technology Exclusive Patent License Agreement by and between the Massachusetts Institute of Technology and the Company, dated as of June 29, 2001.

Exclusive License Agreement by and between the Medical College of Georgia Research Institute, Inc. and the Company, dated as of October 14, 2004.

Exclusive License Agreement by and between Northwestern University and the Company, dated as of June 3, 2005.

The Regents of the University of California Exclusive License Agreement with the Company for “Eukaryotic Genes Involved in Adult Life Span Regulation,” UC Case Nos. SF99-088 and SF03-008, by and between The Regents of the University of California and the Company, dated as of December 17, 2002, as amended on February 1, 2003.

Exclusive License Agreement for Tubulin Acetylation and Mitochondrial Histone Deacetylase, UC Case Nos. 2004-242, by and between the Regents of the University of California and the Company dated as of December 6, 2004.

Exclusive License Agreement for SIRT1 and HIV Transcription, UC Case Nos. 2004-242, by and between the Regents of the University of California and the Company dated as of May 10, 2005.