THIRD AMENDMENT TO THE SECOND AMENDED AND RESTATED STOCKHOLDERS’ AGREEMENT

EXHIBIT 4.11

THIRD AMENDMENT TO THE

SECOND AMENDED AND RESTATED STOCKHOLDERS’ AGREEMENT

THIS THIRD AMENDMENT (the “Amendment”) TO THE SECOND AMENDED AND RESTATED STOCKHOLDERS’ AGREEMENT dated as of August 4, 2004, as amended (the “Stockholders’ Agreement”), is entered into as of June 1, 2006 by and among Pharmasset, Inc., a Delaware corporation (the “Company”), and the undersigned holders of the Company’s capital stock (collectively, the “Stockholders”). Capitalized terms used but not otherwise defined in this Amendment shall have the meanings set forth in the Stockholders’ Agreement.

RECITALS

WHEREAS, the Board of Directors of the Company has approved an amendment to the Company’s Equity Incentive Plan, which increases the number of shares available for grants by 1,600,000 additional shares of the Company’s Common Stock from 3,675,522 to 5,275,522 shares;

WHEREAS, a same increase is being made concurrently to the number of shares of Common Stock set forth in clause (ii) of the definition of “Excluded Securities” in the Certificate of Incorporation;

WHEREAS, the Company and the Stockholders desire to amend the definition of “New Shares” set forth in Section 1.1 of the Stockholders’ Agreement;

NOW, THEREFORE, in consideration of the mutual promises and covenants hereinafter set forth, the receipt, sufficiency and adequacy of which are hereby acknowledged, the parties hereto agree to amend the Stockholders’ Agreement as follows:

Definition. (a) The definition of the term “New Shares” set forth in Section 1.1 of the Stockholders’ Agreement is hereby amended by deleting clause (iii) thereof and replacing it in its entirety with the following:

“(iii) up to 5,275,522 shares of Common Stock (appropriately adjusted to take account of any stock split, stock dividend, combination of shares, recapitalization or other similar event) issuable to officers, directors, employees and consultants of the Company or a subsidiary pursuant to the exercise of options granted or shares of Common Stock directly issued under the Equity Incentive Plan, subject to vesting, and such options and other rights to acquire Common Stock granted thereunder;”

Governing Law. This Amendment shall be governed by and construed under the laws of the State of Delaware (without giving effect to any conflicts or choice of laws provisions which would cause the application of the domestic substantive laws of any other jurisdiction).

Effective Date. This Amendment shall become effective as of the date first written above (the “Effective Date”) upon receipt by the Company of counterparts of this Amendment duly executed by (i) the Majority Investors and (ii) the Stockholders holding a majority of the outstanding shares of the Common Stock that are subject to this Agreement and the Preferred Stock (on an as-if-converted basis) owned by such Stockholders. Each Stockholder shall be bound by this Amendment whether or not such Stockholder shall have consented to this Amendment.

Miscellaneous. From and after the Effective Date of this Amendment, each reference in the Stockholders’ Agreement to “this Agreement”, “hereof”, “hereunder”, or words of like import in any and all agreements, instruments, documents, notes, certificates and other writings of any kind and nature shall be deemed to refer to the Stockholders’ Agreement as amended by this Amendment. This Amendment may be executed in any number of counterparts, each of which shall be an original, but all of which together constitute one instrument. The headings in this Amendment are for purposes of reference only and shall not limit or otherwise effect the meaning hereof.

[Signatures on Following Pages]

2

IN WITNESS WHEREOF, the parties hereto have executed this Third Amendment to the Second Amended and Restated Stockholders’ Agreement as of the date set forth in the first paragraph hereof.

COMPANY: PHARMASSET, INC.						STOCKHOLDERS:
						/s/ Xxxxxxx X. Xxxxxxxx, Ph.D.
						Xxxxxxx X. Xxxxxxxx, Ph.D.
By:		/s/ X. Xxxxxxxx Price
Name:		X. Xxxxxxxx Price
Title:		President and Chief Executive Officer
						RFS PARTNERS, L.P.
						By:		RFS & Associates, LLC
						By:		/s/ Xxxxxxx X. Xxxxxxxx
						Name:		Xxxxxxx X. Xxxxxxxx
						Title:		Manager
						XXXXXXX X. XXXXXXXX 2005 QUALIFIED ANNUITY TRUST
						By:		/s/ Xxxxxxx X. Xxxxxxxx
						Name:		Xxxxxxx X. Xxxxxxxx
						Title:		Trustee
						/s/ Xxxxx X. Xxx, Ph.X.
						Xxxxx X. Xxx, Ph.D.
						IDENIX PHARMACEUTICALS, INC.
						By:
						Name:
						Title:
						Xxxxxx Xxxxxx, Ph.D.
						/s/ Xxxx-Xxxxxx Sommadossi, Ph.D.
						Xxxx-Xxxxxx Sommadossi, Ph.D.

Signature Page to Third Amendment to

Second Amended and Restated Stockholders’ Agreement

						STOCKHOLDERS (Cont’d):
						XXXX-XXXXXX SOMMADOSSI 2004 QUALIFIED ANNUITY TRUST NO. 2
						By:		/s/ Xxxx-Xxxxxx Sommadossi, Ph.D.
						Name:		Xxxx-Xxxxxx Sommadossi, Ph.D.
						Title:		Trustee
						/s/ Xxxxx Xxxx Xxxxxxxx
						Xxxxx Xxxx Xxxxxxxx
						Xxxxxxx Xxxxxxxxx Xxxxxxxx
						/s/ Xxxxx X. Xxxx
						Xxxxx X. Xxxx
						Xxxxxx X. Xxx
						/s/ Xxxxx Xxx Xxxxxx
						Xxxxx Xxx Xxxxxx
						XXXXXXXX-XX XXXXX INC.
						By:		/s/ Xxxxxxxxx X. Xxxxx, III
						Name:		Xxxxxxxxx X. Xxxxx, III
						Title:		Vice President & General Counsel

Signature Page to Third Amendment to

Second Amended and Restated Stockholders’ Agreement

						STOCKHOLDERS (Cont’d):
						XXXXXXX LIFE SCIENCES CAPITAL FUND, L.P.
						By: Xxxxxxx & Company (Life Sciences GP), LLC, its General Partner
						By:		/s/ G. Xxxxxx Xxxxxxx
						Name:		G. Xxxxxx Xxxxxxx
						Title:		CEO
						XXXXXXX INDIANA LIFE SCIENCES CAPITAL FUND, L.P.
						By: Xxxxxxx and Company (Indiana GP), LLC, its General Partner
						By:		/s/ G. Xxxxxx Xxxxxxx
						Name:		G. Xxxxxx Xxxxxxx
						Title:		CEO
						MPM BIOVENTURES III, L.P.
						By: MPM BioVentures III GP, L.P., its General Partner
						By: MPM BioVentures III LLC, its General Partner
						By:		/s/ Xxxxxxx Xxxxxxx
						Name:
						Title:

Signature Page to Third Amendment to

Second Amended and Restated Stockholders’ Agreement

						STOCKHOLDERS (Cont’d):
						BB BIOVENTURES L.P.
						By:		BAB BioVentures L.P., its General Partner
						By:		BAB BioVentures, N.V., its General Partner
						By:		/s/ Xxxxxxx Xxxxxxx
						Name:
						Title:
						MPM BIOVENTURES PARALLEL FUND, L.P.
						By:		MPM BioVentures I LP, its General Partner
						By:		MPM BioVentures I LLC, its General Partner
						By:		/s/ Xxxxxxx Xxxxxxx
						Name:
						Title:
						MPM ASSET MANAGEMENT INVESTORS 1999 LLC
						By:		/s/ Xxxxxxx Xxxxxxx
						Name:
						Title:
						MPM BIOVENTURES III-QP, L.P.
						By: MPM BioVentures III GP, L.P., its General Partner
						By: MPM BioVentures III LLC, its General Partner
						By:		/s/ Xxxxxxx Xxxxxxx
						Name:
						Title:

Signature Page to Third Amendment to

Second Amended and Restated Stockholders’ Agreement

						STOCKHOLDERS (Cont’d):
						MPM BIOVENTURES III GMBH & CO. BETEILIGUNGS KG
						By: MPM BioVentures III GP, L.P., in its capacity as the Managing Limited Partner
						By: MPM BioVentures III LLC, its General Partner
						By:		/s/ Xxxxxxx Xxxxxxx
						Name:
						Title:
						MPM BIOVENTURES III PARALLEL FUND, L.P.
						By: MPM BioVentures III GP, L.P., its General Partner
						By: MPM BioVentures III LLC, its General Partner
						By:		/s/ Xxxxxxx Xxxxxxx
						Name:
						Title:
						MPM ASSET MANAGEMENT INVESTORS 2004 BVIII LLC
						By:		/s/ Xxxxxxx Xxxxxxx
						Name:
						Title:

Signature Page to Third Amendment to

Second Amended and Restated Stockholders’ Agreement

						STOCKHOLDERS (Cont’d):
						TVM V LIFE SCIENCE VENTURES GMBH & CO. KG
						By:		/s/ Xxxx X. Xxxxxxx
						Name:		Xxxx X. Xxxxxxx
						Title:		Managing Limited Partner
						By:		/s/ Xxxxx Xxxxxxx
						Name:		Xxxxx Xxxxxxx
						Title:		Managing Limited Partner
						TVM IV GMBH & CO. KG
						By:		/s/ Xxxx X. Xxxxxxx
						Name:		Xxxx X. Xxxxxxx
						Title:		Managing Limited Partner
						By:		/s/ Xxxxx Xxxxxxx
						Name:		Xxxxx Xxxxxxx
						Title:		Managing Limited Partner
						MDS LIFE SCIENCES TECHNOLOGY FUND II NC LIMITED PARTNERSHIP
						By: MDS LSTF II (NCGP) Inc., its General Partner
						By:
						Name:
						Title:
						MDS LIFE SCIENCES TECHNOLOGY FUND II QUEBEC LIMITED PARTNERSHIP
						By: MDS LSTF II (QGP) Inc., its General Partner
						By:
						Name:
						Title:

Signature Page to Third Amendment to

Second Amended and Restated Stockholders’ Agreement

						STOCKHOLDERS (Cont’d):
						MLII CO-INVESTMENT FUND NC LIMITED PARTNERSHIP
						By: MLII (NCGP) Inc., its General Partner
						By:
						Name:
						Title:
						CDIB BIOSCIENCE VENTURES I, INC.
						By:		Xxxxx X. Xx
						Name:		Xxxxx X. Xx
						Title:		Chairman

Signature Page to Third Amendment to

Second Amended and Restated Stockholders’ Agreement