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 Xxxxxx Xxxx, 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.

	TESARO, INC.
	By:	/s/ Xxxx X. Xxxxxxx, Xx.
	Name:	Xxxx X. Xxxxxxx, Xx.
	Title:	Chief Executive Officer
	Address:		000 Xxxxxxxx Xxxx Xxxx, Xxxxx 000
			Xxxxxxx, XX 00000
			Attn:	Xxxx X. Xxxxxxx, Xx.
			Phone:	000-000-0000
			E-mail:	xxxxxxxx@xxxxxxxxx.xxx
			Fax:	000-000-0000
	With a copy to:
			Xxxxx Lovells US LLP
			000 Xxxxxxxxxxxxx Xxxxx, Xxxxx 0000
			Xxxxxxxxx, XX 00000
			Attn:	Xxxxx X. Xxxxx
			Phone:	000-000-0000
			E-mail:	xxxxx.xxxxx@xxxxxxxxxxxx.xxx
			Fax:	000-000-0000

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.

	INVESTOR AND FOUNDER:
	XXXX X. XXXXXXX, XX.
	/s/ Xxxx X. Xxxxxxx, Xx.
	Address:	00000 Xxx Xxxxxxx Xxxxx
		Xxxxxxx Xxxxx, XX 00000
		Phone:	000-000-0000
		E-mail:	xxxxxxxx@xxxxxxxxx.xxx
		Fax:	000-000-0000

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.

	INVESTOR AND FOUNDER:
	XXXX XXXXX XXXXXX
	/s/ Xxxx Xxxxx Xxxxxx
	Address:	00 Xxxxxx Xxxx
		Xxxxxxxxx, XX 00000
		Phone:	000-000-0000
		E-mail:	xxxxxxxx@xxxxxxxxx.xxx
		Fax:	000-000-0000

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.

	INVESTOR AND FOUNDER:
	XXXXXXX X. XXXXXXX
	/s/ Xxxxxxx X. Xxxxxxx
	Address:	000 Xxxxxx Xxxxxx
		Xxxxxxxxx, XX 00000
		Phone:	000-000-0000
		E-mail:	xxxxxxxx@xxxxxxxxx.xxx
		Fax:	000-000-0000

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.

	INVESTOR:
	NEW ENTERPRISE ASSOCIATES 13, LIMITED PARTNERSHIP
	By:	NEA Partners 13, Limited Partnership
		its general partner
		By:			NEA GP 13, LTD, its general partner
					By:	/s/ Xxxxx X. Xxxxxx
					Name:	Xxxxx X. Xxxxxx
					Title:	Chief Legal Officer
	NEA VENTURES 2010, LIMITED PARTNERSHIP
	By:		/s/ Xxxxx X. Xxxxxx
	Name:		Xxxxx X. Xxxxxx
	Title:		Vice-President
	Address:			0000 Xxxxxxxxx Xxxxxx, Xxxxx 000
				Xxxxx Xxxxx, XX 00000
				Attn:			Xxxxx Xxxxxx
				Phone:			000-000-0000
				E-mail:			xxxxxxx@xxx.xxx
				Fax:			000-000-0000

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.

	INVESTOR:
	XXXX XXXXXX, M.D.
	/s/ Xxxx Xxxxxx, M.D.
	Address:	c/o New Enterprises Associates 13, Limited Partnership
		0000 Xxxxxxxxx Xxxxxx, Xxxxx 000
		Xxxxx Xxxxx, XX 00000
		Attn:	Xxxxx Xxxxxx
		Phone:	000-000-0000
		E-mail:	xxxxxxx@xxx.xxx
		Fax:	000-000-0000

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.

	INVESTOR:
	INTERWEST PARTNERS X, LP
	By:	InterWest Management Partners X, LLC, its general partner
		By:		/s/ Xxxxxx X. Xxxxxxx
		Name:		Xxxxxx X. Xxxxxxx
		Title:		Managing Director
	Address:		InterWest Partners
			0000 Xxxx Xxxx Xxxx, 0xx Xxxxx
			Xxxxx Xxxx, XX 00000
			Attn:		Xxxxx Xxxxxx
			Phone:		000-000-0000
			E-mail:		xxxxxxx@xxxxxxxxx.xxx
			Fax:		000-000-0000
	With a copy to:
			Xxxxxxxxx Xxxxxx Xxxxxx Xxxxxxxxxx
			Xxxxxxxx & Xxxxxxxxx, LLP
			0000 Xxxxxxx Xxxx.
			Xxxxxxx Xxxx, XX 00000
			Attn:		Xxxxxx X. Xxxxx
			Phone:		000-000-0000
			E-mail:		xxxxxx@xxxxxx.xxx
			Fax:		000-000-0000

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.

	INVESTOR:
	KPCB HOLDINGS, INC.,
	as nominee
	By:	/s/ Xxxxx Xxxxx
	Name:	Xxxxx Xxxxx
	Title:	Senior Vice President
	Address:		Xxxxxxx Xxxxxxx Xxxxxxxx & Xxxxx
			0000 Xxxx Xxxx Xxxx
			Xxxxx Xxxx, XX 00000
			Attn:	Xxx Xxxxxxxx
			Phone:	000-000-0000
			E-mail:	xxxxxxxxx@xxxx.xxx
			Fax:	000-000-0000
	With a copy to:
			Xxxxxxxxx Xxxxxx Xxxxxx Xxxxxxxxxx
			Xxxxxxxx & Xxxxxxxxx, LLP
			0000 Xxxxxxx Xxxx.
			Xxxxxxx Xxxx, XX 00000
			Attn:	Xxxxxx X. Xxxxx
			Phone:	000-000-0000
			E-mail:	xxxxxx@xxxxxx.xxx
			Fax:	000-000-0000

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.

	INVESTOR:
	X. XXXX PRICE ASSOCIATES, INC.
	Investment Adviser, for and on behalf of the advisory clients on Attachment A to this signature page and listed below:
		X. Xxxx Price Health Sciences Fund, Inc.
		TD Mutual Funds — TD Health Sciences Fund
		Valic Company I — Health Sciences Fund
		X. Xxxx Price Health Sciences Portfolio
		Xxxx Xxxxxxx Trust — Health Sciences Trust
	By:		/s/ Xxxx X. Xxxxxx
	Name:		Xxxx X. Xxxxxx
	Title:		Vice President
	Address:			X. Xxxx Price Associates, Inc.
				000 Xxxx Xxxxx Xxxxxx
				Xxxxxxxxx, XX 00000
				Attn:	Xxxxxx Xxxx, Vice President
					and Senior Legal Counsel
				Phone:	000-000-0000
				E-mail:	Xxxxxx_xxxx@xxxxxxxxxx.xxx
				Fax:	000-000-0000
	With a copy to:
				Xxxxx Xxxxxx LLP
				000 X. Xxxxxxx Xxxxxx, Xxxxx 0000
				Xxxxxxxxx, XX 00000
				Attn:	Xxxx Xxxxxxxx Xxxxxxxx
				Phone:	000-000-0000
				E-mail:	xxxxxxxxx@xxxxxxxxxxx.xxx
				Fax:	000-000-0000

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.

	INVESTOR:
	A.M. XXXXXX LIFE SCIENCE VENTURES IV, L.P.
	By:	AMP&A Management IV, LLC
	Its:	General Partner
		By:		/s/ Ford S. Worthy
		Name:		Ford S. Worthy
		Title:		Partner & CFO
	PV IV CEO FUND, L.P.
	By:	AMP&A Management IV, LLC
	Its:	General Partner
		By:		/s/ Ford S. Worthy
		Name:		Ford S. Worthy
		Title:		Partner & CFO
	Address:		c/x Xxxxxx Ventures
			P. O. Box 110287
			Research Xxxxxxxx Xxxx, XX 00000
			Attn:		Ford S. Worthy
			Phone:		000-000-0000
			E-mail:		xxxxxxx@xxxxxxxxxxxxxx.xxx
			Fax:		000-000-0000

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.

	INVESTOR:
	LEERINK XXXXX HOLDINGS, LLC
	By:	/s/ Xxxxxxx A.G. Gerhol
	Name:	Xxxxxxx X.X. Xxxxxxx
	Title:	General Counsel
	LEERINK XXXXX CO-INVESTMENT FUND, LLC
	By:	/s/ Xxxxxx X. Xxxxxxx
	Name:	Xxxxxx X. Xxxxxxx
	Title:	CAO
	Address:		Leerink Xxxxx LLC
			Xxx Xxxxxxx Xxxxxx, 00xx Xxxxx
			Xxxxxx, XX 00000
			Attn:	Xxxxxxx Xxxxxxx, Esq.
			Phone:	000-000-0000
			E-mail:	xxx.xxxxxxx@xxxxxxx.xxx
			Fax:	000-000-0000

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.

	INVESTOR:
	DEERFIELD SPECIAL SITUATIONS FUND, L.P.
	By:	Deerfield Capital, L.P.
		General Partner
		By:		X.X. Xxxxx Capital, LLC
				General Partner
				By:	/s/ Xxxxx X. Xxxxx
				Name:	Xxxxx X. Xxxxx
				Title:	Authorized Signatory
	DEERFIELD SPECIAL SITUATIONS FUND INTERNATIONAL, LIMITED
	By:		/s/ Xxxxx X. Xxxxx
	Name:		Xxxxx X. Xxxxx
	Title:		Authorized Signatory
	Address:			c/o Deerfield Management Co.
				000 Xxxxx Xxx., 00xx Xx.
				Xxx Xxxx, XX 00000
				Attn:		Xxxxx X. Xxxxx
				Phone:		000-000-0000
				E-mail:		XXxxxx@xxxxxxxxxxxxxxxxx.xxx
				Fax:		000-000-0000
	With a copy to:
				Xxxxxx Xxxxxx Rosenman LLP
				000 Xxxxxxx Xxxxxx
				Xxx Xxxx, XX 00000-0000
				Attn:		Xxxx X. Xxxxxx
				Phone:		000-000-0000
				E-mail:		xxxx.xxxxxx@xxxxxxxxx.xxx
				Fax:		000-000-0000

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.

	INVESTOR:
	ORACLE PARTNERS, LP
	By:	Oracle Associates, LLC,
		its General Partner
		By:		/s/ Xxxxx X. Xxxxxxxx
		Name:		Xxxxx X. Xxxxxxxx
		Title:		Managing Member
	ORACLE INSTITUTIONAL PARTNERS, LP
	By:	Oracle Associates, LLC,
		its General Partner
		By:		/s/ Xxxxx X. Xxxxxxxx
		Name:		Xxxxx X. Xxxxxxxx
		Title:		Managing Member
	Address:		Oracle Investment Management, Inc.
			000 Xxxxxxxxx Xxxxxx
			Xxxxxxxxx, XX 00000
			Attn:		Xxxxxx Xxxxx
			Phone:		000-000-0000
			E-mail:		xxxxxx@xxxxxxxxxxxxxx.xxx
			Fax:		000-000-0000

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.

	INVESTOR:
	OPKO HEALTH, INC.
	By:	/s/ Xxxxxx X. Xxxxx
	Name:	Xxxxxx X. Xxxxx
	Title:	Exec. V.P.
	Address:		0000 Xxxxxxxx Xxxxxxxxx
			Xxxxx, XX 00000
			Attn:	Xxxx Xxxxx
			Phone:	(000) 000-0000
			E-mail:	xxxxxx@xxxx.xxx
			Fax:

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

RESTATED INVESTORS’ RIGHTS AGREEMENT FOR TESARO, INC.

SCHEDULE A

Investors

Series A Investor:		Shares of Series A Preferred Stock:
New Enterprise Associates 13, Limited Partnership		17,970,000
NEA Ventures 2010, Limited Partnership		25,000
Xxxx Xxxxxx		5,000
Xxxx X. Xxxxxxx, Xx.		1,500,000
Xxxx Xxxx Xxxxxx		250,000
Xxxxxxx X. Xxxxxxx		250,000

Series B Investor:		Shares of Series B Preferred Stock:
New Enterprise Associates 13, Limited Partnership		7,741,199
Xxxx Xxxxxx		2,298
InterWest Partners X, LP		3,871,748
KPCB Holdings, Inc.		2,903,811
X. Xxxx Price Health Sciences Fund, Inc.		972,450
TD Mutual Funds — TD Health Sciences Fund		49,821
VALIC Company I — Health Sciences Fund		68,928
X. Xxxx Price Health Sciences Portfolio		18,322
Xxxx Xxxxxxx Trust — Health Sciences Trust		51,999
A.M. Xxxxxx Life Science Ventures IV, L.P.		923,959
PV IV CEO FUND, L.P.		43,977
Leerink Xxxxx Holdings, LLC		193,587
Leerink Xxxxx Co-Investment Fund, LLC		193,587
Deerfield Special Situations Fund, L.P.		150,998
Deerfield Special Situations Fund International, Limited		236,176
Oracle Partners, LP		792,251
Oracle Institutional Partners, LP		175,685
Venrock Healthcare Capital Partners, L.P.		818,256
VHCP Co-Investment Holdings, LLC		149,680
Frost Gamma Investments Trust		193,587

SCHEDULE C

Major Investors

New Enterprise Associates 13, Limited Partnership

InterWest Partners X, LP

KPCB Holdings, Inc.

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

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

Venrock Healthcare Capital Partners, L.P.