AMENDMENT NO. 1 TO SECOND AMENDED AND RESTATED INVESTORS RIGHTS AGREEMENT

Exhibit 4.3

EXECUTION COPY

AMENDMENT NO. 1

TO

SECOND AMENDED AND RESTATED INVESTORS’ RIGHTS AGREEMENT

The Second Amended and Restated Investors’ Rights Agreement (the “Investors’ Rights Agreement”), dated as of June 6, 2011, by and among TESARO, INC., a Delaware corporation (the “Company”), and the other parties thereto, is hereby amended as of July 7, 2011.

WHEREAS, the Company is party to that certain Series B Preferred Stock Purchase Agreement, dated as of June 6, 2011, by and among the Company and the Investors party thereto (as amended, the “Purchase Agreement”);

WHEREAS, pursuant to Section 4.7 of the Investors’ Rights Agreement, the Company may amend the Investors’ Rights Agreement only with the written consent of the holders of (i) a majority of the then-outstanding shares of Series A Preferred Stock, (ii) at least sixty percent (60%) of the then-outstanding shares of Series B Preferred Stock, including either InterWest Partners X, LP or KPCB Holdings, Inc., so long as InterWest Partners X, LP and KPCB Holdings, Inc. are Major Investors, and (iii) with respect to Section 3.5 of the Investors’ Rights Agreement, a majority of Registrable Securities that are held by Major Investors (collectively, a “Requisite Majority”); and

WHEREAS, in connection with entering into an amendment to the Purchase Agreement and the issuance and sale by the Company of Additional Shares to Additional Purchasers (as such terms are defined in the Purchase Agreement), including to Venrock Healthcare Capital Partners, L.P., the Company and the undersigned parties to the Investors’ Rights Agreement, constituting a Requisite Majority, have agreed to amend the Investors’ Rights Agreement as set forth herein.

NOW, THEREFORE, in consideration of the foregoing and for good and valuable consideration, the receipt and sufficiency of which are hereby acknowledged, the Investors’ Rights Agreement is hereby amended as follows:

1.             Definitions.

Capitalized terms appearing herein and not otherwise defined herein shall have the meanings ascribed to such terms in the Investors’ Rights Agreement.

2.             Amendments.

2.1          Section 3.5 of the Investors’ Rights Agreement is hereby amended by adding a new clause (e) immediately following clause (d) and immediately prior to the ultimate paragraph thereof.  The new clause (e) shall read as follows:

“(e)         Venrock Healthcare Capital Partners, L.P. (“Venrock”) is a Major Investor, the Company shall invite a representative of Venrock, who initially shall be Anders Hove, to attend all meetings of the Board of Directors in a nonvoting observer

capacity and, in this respect, shall give such representative copies of all notices, minutes, consents and other materials that it provides to its directors; provided, however, that such representative shall agree to hold in confidence and trust all information provided and; provided, further, that the Company reserves the right to withhold any information and to exclude such representative from any meeting or portion thereof if access to such information or attendance at such meeting could adversely affect the attorney-client privilege between the Company and its counsel or result in disclosure of trade secrets or a conflict of interest, or if such Major Investor or its representative is a Competitor of the Company.”

2.2          Section 4.7 of the Investors’ Rights Agreement is hereby amended by (i) deleting the word “and” from immediately prior to clause (d) in the text of the proviso to the third sentence thereof and (ii) adding a new clause (e) the text of such proviso, immediately following clause (d) thereof.  The new clause (e) shall read as follows:

“and (e) any amendment or waiver of Section 3.5(e) shall require the consent of Venrock (for such time and for so long as Venrock is a Major Investor)”

2.3          Schedule A to the Investors’ Rights Agreement is hereby amended by deleting it and replacing it in its entirety with Schedule A hereto.

2.4          Schedule C to the Investors’ Rights Agreement is hereby amended by deleting it and replacing it in its entirety with Schedule C hereto.

3.             General.

Except as modified by this amendment, which shall be effective as of the first date written above, the Investors’ Rights Agreement shall remain in full force and effect, enforceable in accordance with its terms.

[signature page follows]

2

IN WITNESS WHEREOF, the parties have duly executed this Amendment No. 1 to the Second Amended and Restated Investors’ Rights Agreement as of the date first written above.

SIGNATURE PAGE TO AMENDMENT NO. 1 TO THE SERIES B PREFERRED SECOND AMENDED AND

RESTATED INVESTORS’ RIGHTS AGREEMENT FOR TESARO, INC.

IN WITNESS WHEREOF, the parties have duly executed this Amendment No. 1 to the Second Amended and Restated Investors’ Rights Agreement as of the date first written above.

SIGNATURE PAGE TO AMENDMENT NO. 1 TO THE SERIES B PREFERRED SECOND AMENDED AND

RESTATED INVESTORS’ RIGHTS AGREEMENT FOR TESARO, INC.

IN WITNESS WHEREOF, the parties have duly executed this Amendment No. 1 to the Second Amended and Restated Investors’ Rights Agreement as of the date first written above.

SIGNATURE PAGE TO AMENDMENT NO. 1 TO THE SERIES B PREFERRED SECOND AMENDED AND

RESTATED INVESTORS’ RIGHTS AGREEMENT FOR TESARO, INC.

IN WITNESS WHEREOF, the parties have duly executed this Amendment No. 1 to the Second Amended and Restated Investors’ Rights Agreement as of the date first written above.

SIGNATURE PAGE TO AMENDMENT NO. 1 TO THE SERIES B PREFERRED SECOND AMENDED AND

RESTATED INVESTORS’ RIGHTS AGREEMENT FOR TESARO, INC.

IN WITNESS WHEREOF, the parties have duly executed this Amendment No. 1 to the Second Amended and Restated Investors’ Rights Agreement as of the date first written above.

SIGNATURE PAGE TO AMENDMENT NO. 1 TO THE SERIES B PREFERRED SECOND AMENDED AND

RESTATED INVESTORS’ RIGHTS AGREEMENT FOR TESARO, INC.

IN WITNESS WHEREOF, the parties have duly executed this Amendment No. 1 to the Second Amended and Restated Investors’ Rights Agreement as of the date first written above.

SIGNATURE PAGE TO AMENDMENT NO. 1 TO THE SERIES B PREFERRED SECOND AMENDED AND

RESTATED INVESTORS’ RIGHTS AGREEMENT FOR TESARO, INC.

IN WITNESS WHEREOF, the parties have duly executed this Amendment No. 1 to the Second Amended and Restated Investors’ Rights Agreement as of the date first written above.

SIGNATURE PAGE TO AMENDMENT NO. 1 TO THE SERIES B PREFERRED SECOND AMENDED AND

RESTATED INVESTORS’ RIGHTS AGREEMENT FOR TESARO, INC.

IN WITNESS WHEREOF, the parties have duly executed this Amendment No. 1 to the Second Amended and Restated Investors’ Rights Agreement as of the date first written above.

SIGNATURE PAGE TO AMENDMENT NO. 1 TO THE SERIES B PREFERRED SECOND AMENDED AND

RESTATED INVESTORS’ RIGHTS AGREEMENT FOR TESARO, INC.

IN WITNESS WHEREOF, the parties have duly executed this Amendment No. 1 to the Second Amended and Restated Investors’ Rights Agreement as of the date first written above.

SIGNATURE PAGE TO AMENDMENT NO. 1 TO THE SERIES B PREFERRED SECOND AMENDED AND

RESTATED INVESTORS’ RIGHTS AGREEMENT FOR TESARO, INC.

IN WITNESS WHEREOF, the parties have duly executed this Amendment No. 1 to the Second Amended and Restated Investors’ Rights Agreement as of the date first written above.

SIGNATURE PAGE TO AMENDMENT NO. 1 TO THE SERIES B PREFERRED SECOND AMENDED AND

RESTATED INVESTORS’ RIGHTS AGREEMENT FOR TESARO, INC.

IN WITNESS WHEREOF, the parties have duly executed this Amendment No. 1 to the Second Amended and Restated Investors’ Rights Agreement as of the date first written above.

SIGNATURE PAGE TO AMENDMENT NO. 1 TO THE SERIES B PREFERRED SECOND AMENDED AND

RESTATED INVESTORS’ RIGHTS AGREEMENT FOR TESARO, INC.

IN WITNESS WHEREOF, the parties have duly executed this Amendment No. 1 to the Second Amended and Restated Investors’ Rights Agreement as of the date first written above.

SIGNATURE PAGE TO AMENDMENT NO. 1 TO THE SERIES B PREFERRED SECOND AMENDED AND

RESTATED INVESTORS’ RIGHTS AGREEMENT FOR TESARO, INC.

IN WITNESS WHEREOF, the parties have duly executed this Amendment No. 1 to the Second Amended and Restated Investors’ Rights Agreement as of the date first written above.

SIGNATURE PAGE TO AMENDMENT NO. 1 TO THE SERIES B PREFERRED SECOND AMENDED AND

RESTATED INVESTORS’ RIGHTS AGREEMENT FOR TESARO, INC.

IN WITNESS WHEREOF, the parties have duly executed this Amendment No. 1 to the Second Amended and Restated Investors’ Rights Agreement as of the date first written above.

SIGNATURE PAGE TO AMENDMENT NO. 1 TO THE SERIES B PREFERRED SECOND AMENDED AND

RESTATED INVESTORS’ RIGHTS AGREEMENT FOR TESARO, INC.

SCHEDULE A

Investors

SCHEDULE C

Major Investors

New Enterprise Associates 13, Limited Partnership

InterWest Partners X, LP

KPCB Holdings, Inc.

T. Rowe Price Associates, Inc. (Investment Adviser, for and on behalf of the following advisory clients and their nominees: T. Rowe Price Health Sciences Fund, Inc., TD Mutual Funds — TD Health Sciences Fund, VALIC Company I — Health Sciences Fund, T. Rowe Price Health Sciences Portfolio, John Hancock Trust — Health Sciences Trust)

A.M. Pappas Life Science Ventures IV, L.P.

Venrock Healthcare Capital Partners, L.P.