PERLEGEN SCIENCES, INC. AMENDMENT NO. 1 TO SECOND AMENDED AND RESTATED REGISTRATION RIGHTS AGREEMENT

Exhibit 4.3

PERLEGEN SCIENCES, INC.

AMENDMENT NO. 1 TO

SECOND AMENDED AND RESTATED REGISTRATION RIGHTS AGREEMENT

     THIS AMENDMENT NO. 1 to the Second Amended and Restated Registration Rights Agreement is made as of December 22, 2005 (the “Effective Date”), between Perlegen Sciences, Inc. a Delaware corporation (the “Company”), and the holders of the Company’s Preferred Stock (each an “Prior Purchaser” and collectively the “Prior Purchasers”).

     WHEREAS, the Company is entering into a Series D-1 Preferred Stock Purchase Agreement dated as of even date herewith (the “Series D-1 Purchase Agreement”), by and among the Company and Pfizer Overseas Pharmaceuticals (the “Purchaser”), that provides for, among other things, the sale by the Company and the purchase by the Purchaser of the Series D-1 Preferred Stock.

     WHEREAS, the obligations in the Series D-1 Purchase Agreement are conditioned upon the execution and delivery of this Amendment;

     WHEREAS, the Company and the Prior Purchasers are parties to that certain Second Amended and Restated Registration Rights Agreement, dated as of February 1, 2005 (the “Rights Agreement”);

     WHEREAS, the Company and the Prior Purchasers desire to amend the Rights Agreement pursuant to Section 9(j) of the Rights Agreement to add the Purchaser as a party, to provide the Purchaser with the rights and obligations thereunder and to include the Series D-1 Preferred Stock (and the Common Stock resulting from conversion thereof) under the definition of Registrable Securities.

     NOW, THEREFORE, in consideration of the mutual covenants contained herein and other good and valuable consideration, the receipt and sufficiency of which are hereby acknowledged, the parties hereto agree as follows:

     1. The Company and the Prior Purchasers holding a majority of the Registrable Securities (as defined in the Rights Agreement) hereby amend the Rights Agreement to include Pfizer Overseas Pharmaceuticals as a “Holder” thereunder and to include the Series D-1 Preferred Stock and the Common Stock issuable upon conversion of the Series D-1 Preferred Stock as “Registrable Securities” thereunder.

     2. The definition of “Holder” set forth in Section 1(e) of the Rights Agreement shall be amended in its entirety as set forth below:

          “‘Holder’ shall mean any person owning Registrable Securities and each of its respective successors and assigns who acquire Registrable Securities, in accordance with the terms of this Agreement.”

     3. The definition of “Registrable Securities” set forth in Section 1(g) of the Rights Agreement shall be amended in its entirety as set forth below:

“‘Registrable Securities’ shall mean the Common Stock issued or issuable upon conversion of the Series A Stock, the Series B Stock, the Series C Stock, the Series D Stock, or Series D-1 Stock; and any securities issued successively in exchange for or in respect of any of the foregoing, whether pursuant to a merger or consolidation, as a result of any successive stock split or reclassification of, or stock dividend on, any of the foregoing or otherwise; provided, however, that such shares of Common Stock or securities shall cease to be Registrable Securities when (i) a registration statement registering such shares of Common Stock or securities, as the case may be, under the Securities Act has been declared effective and such shares of Common Stock or securities, as the case may be, have been sold or otherwise transferred by the Holder thereof pursuant to such effective registration statement, (ii) such shares of Common Stock or securities, as the case may be, are sold pursuant to Rule 144 (or any successor provision) promulgated under the Securities Act under circumstances in which any legend borne by such shares of Common Stock or securities relating to restrictions on transferability thereof, under the Securities Act or otherwise, is removed by the Company, or (iii) such shares of Common Stock or securities, as the case may be, are eligible for sale pursuant to subparagraph (k) of Rule 144 under the Securities Act.”

     4. All notices and other communications under the Rights Agreement shall be made to Pfizer Overseas Pharmaceuticals at the address specified below and thereafter at such other address, notice of which is given in accordance with Section 9(e) of the Rights Agreement:

Pfizer Overseas Pharmaceuticals
0000 Xxxx Xxxxxxx Xxxxxxxx Xxxx
Xxxxxxx Xxxx
Xxxx, Xxxxxxx
Attn: Legal Director

     with copies to:

Pfizer Inc.
000 Xxxx 00^xx Xxxxxx
Xxx Xxxx, XX 00000
Attn: General Counsel

Pfizer Global Research and Development
00 Xxxxxx Xxxxxx
Xxx Xxxxxx, XX 00000
Attn: General Counsel

     5. The Rights Agreement as modified herein shall remain in full force and effect as so modified.

[REMAINDER OF THIS PAGE INTENTIONALLY LEFT BLANK]

     The Parties have executed this Amendment No. 1 to the Second Amended and Restated Registration Rights Agreement as of the Effective Date.

		PERLEGEN SCIENCES, INC.
		By:		/s/ Xxxx X. Xxxxxx
		Name:		Xxxx X. Xxxxxx
		Title:		President and Chief Executive Officer
		Address:
		Perlegen Sciences, Inc.
		0000 Xxxxxxxx Xxxxx
		Xxxxxxxx Xxxx, Xxxxxxxxxx 00000

Signature Page to Perlegen Sciences, Inc.
Amendment No. 1 to the Second Amended and Restated Registration Rights Agreement

		MAVERICK FUND LDC
		By:		/s/ Xxxx XxXxxxxxxx
		Name:
		Title:
		Address:
		Maverick Capital
		000 Xxxxxxxx Xxxxx, 00xx Xxxxx
		Xxxxxx, XX 00000
		Attn:	Xxxx XxXxxxxxxx, General Counsel

Signature Page to Perlegen Sciences, Inc.
Amendment No. 1 to the Second Amended and Restated Registration Rights Agreement

		MAVERICK FUND USA, LTD.
		By:		/s/ Xxxx XxXxxxxxxx
		Name:
		Title:
		Address: Maverick Capital
		000 Xxxxxxxx Xxxxx, 00xx Xxxxx
		Xxxxxx, XX 00000
		Attn:	Xxxx XxXxxxxxxx, General Counsel

Signature Page to Perlegen Sciences, Inc.
Amendment No. 1 to the Second Amended and Restated Registration Rights Agreement

		MAVERICK FUND II, LTD.
		By:		/s/ Xxxx XxXxxxxxxx
		Name:
		Title:
		Address Maverick Capital
		000 Xxxxxxxx Xxxxx, 00xx Xxxxx
		Xxxxxx, XX 00000
		Attn:	Xxxx XxXxxxxxxx, General Counsel

Signature Page to Perlegen Sciences, Inc.
Amendment No. 1 to the Second Amended and Restated Registration Rights Agreement

		VULCAN VENTURES INC.
		By:		/s/ W. Xxxxx Xxxx
		Name:		W. Xxxxx Xxxx
		Title:		Executive Vice President
		Address:
		Xxxxxxx Xxxxxx
		000 0xx Xxxxxx Xxxxx, Xxxxx 000
		Xxxxxxx, XX 00000

Signature Page to Perlegen Sciences, Inc.
Amendment No. 1 to the Second Amended and Restated Registration Rights Agreement

		UNILEVER TECHNOLOGY VENTURES FUND B.V.
		By:		/s/ Xxxx Xxxxxxxxx
		Name:		Xxxx Xxxxxxxxx
		Title:
		By:		/s/ W. G. M. Mulders
		Name:		W. G. M. Mulders
		Title:		Director
		Address:
		455 Weena
		3013 AL Rotterdam The Netherlands

Signature Page to Perlegen Sciences, Inc.
Amendment No. 1 to the Second Amended and Restated Registration Rights Agreement

		BIOMEDICAL SCIENCES INVESTMENT FUND PTE LTD
		By:		/s/ Xxx Xxxx Yeok
		Name:		Xxx Xxxx Yeok
		Title:		Director
		Address:
		00 Xxxxxxxx Xxx
		#00-00 Xxxxxxx
		Xxxxxxxxx 000000
		Attention:  Sim Xxx Xxxx

Signature Page to Perlegen Sciences, Inc.
Amendment No. 1 to the Second Amended and Restated Registration Rights Agreement

		SB LIFE SCIENCE VENTURES I, L.P. Xx. Xxxxxxxx Xxxxx, Director SB Life Science Pte. Ltd. as general partner of SB Life Science Partners, L.P. as general partner of SB Life Ventures I, L.P.
		By:		/s/ Xxxxxxxx Xxxxx
		Name:		Xxxxxxxx Xxxxx
		Title:		Director
		Address:
		00X, Xxxxx Shiodone Building
		0-0-0 Xxxxxxx-xxxxxxxxx Xxxxxx-xx Xxxxx, 000-0000 Xxxxx
		Attention:  Mayo Hotta

Signature Page to Perlegen Sciences, Inc.
Amendment No. 1 to the Second Amended and Restated Registration Rights Agreement

		CMEA VENTURES LIFE SCIENCES 2000, L.P.
		By:		/s/ Xxx Xxxxxx
		Name:		Xxx Xxxxxx
		Title:		General Partner
		Address:
		CMEA Ventures Life Sciences 2000 Limited
		Partnership
		Xxx Xxxxxxxxxxx Xxxxxx, Xxxxx 0000
		Xxx Xxxxxxxxx, XX 00000-0000
		Attn:		Xxx Xxxxxx

Signature Page to Perlegen Sciences, Inc.
Amendment No. 1 to the Second Amended and Restated Registration Rights Agreement

		CMEA VENTURES LIFE SCIENCES 2000, CIVIL LAW PARTNERSHIP
		By:		/s/ Xxx Xxxxxx
		Name:		Xxx Xxxxxx
		Title:		General Partner
		Address:
		CMEA Ventures Life Sciences 2000 Civil Law
		Partnership
		Xxx Xxxxxxxxxxx Xxxxxx, Xxxxx 0000
		Xxx Xxxxxxxxx, XX 00000-0000
		Attn:		Xxx Xxxxxx

Signature Page to Perlegen Sciences, Inc.
Amendment No. 1 to the Second Amended and Restated Registration Rights Agreement

		BSI SA.
		By:		/s/ Xxxxxx Xxxxxxx
		Name:		Xxxxxx Xxxxxxx
		Title:		Assistant Vice President
		By:		/s/ Xxxxxxxx Xxxxxx
		Name:		Xxxxxxxx Xxxxxx
		Title:		Vice President
		Address:
		BSI SA
		Xxxxxx Xxxxxxx
		Assistant Vice President
		Securities Administration
		Xxx Xxxxxxx 0
		0000 Xxxxxx
		Xxxxxxxxxxx

Signature Page to Perlegen Sciences, Inc.
Amendment No. 1 to the Second Amended and Restated Registration Rights Agreement

		BSI — NEW BIOMEDICAL FRONTIER (SICAV)
		By:		/s/ Xxxxx Xxxxxx
		Name:		Xxxxx Xxxxxx
		Title:		Manager
		Address:		BSI-New BioMedical Frontier
		(SICAV)
		Xxx Xxxx 00
		0000 Xxxxxx
		Xxxxxxxxxxx
		Attn:  Xxxxxxxxx Xxxxxxxxx

Signature Page to Perlegen Sciences, Inc.
Amendment No. 1 to the Second Amended and Restated Registration Rights Agreement

		ZAFFARONI REVOCABLE TRUST 1/24/86
		By:		/s/ Xxxxxxxxx Xxxxxxxxx
		Name:		Xxxxxxxxx Xxxxxxxxx
		Title:		Trustee
		Address:
		Xxxxxxx X. Xxxxxxxx
		c/o Technofyn Associates, LLC
		0000 Xxxxxxx Xxxxxx, Xxxxx 000
		Xxxx Xxxx, XX 00000-0000

Signature Page to Perlegen Sciences, Inc.
Amendment No. 1 to the Second Amended and Restated Registration Rights Agreement

		CSK VENTURE CAPITAL CO., LTD. as Investment Manager for Hitachi — CSK Internet Business Fund
		By:		/s/ Xxxxxxxx Xxxxxxxx
		Name:		Xxxxxxxx Xxxxxxxx
		Title:		President
		Address:
		5th Floor, Reviera Xxxxxx Xxxxxx Xxxx.
		0-0-0 Xxxxx-Xxxxxx, Xxxxxx-xx
		Xxxxx 000-0000
		Xxxxx
		Attn:  Xxxxxx Xxxxxxxxx

Signature Page to Perlegen Sciences, Inc.
Amendment No. 1 to the Second Amended and Restated Registration Rights Agreement

		CSK VENTURE CAPITAL CO., LTD. as Investment Manager CSK-4 Investment Fund
		By:		/s/ Xxxxxxxx Xxxxxxxx
		Name:		Xxxxxxxx Xxxxxxxx
		Title:		President
		Address:
		5th Floor, Reviera Xxxxxx Xxxxxx Xxxx.
		0-0-0 Xxxxx-Xxxxxx, Xxxxxx-xx
		Xxxxx 000-0000
		Xxxxx
		Attn:	Xxxxxx Xxxxxxxxx

Signature Page to Perlegen Sciences, Inc.
Amendment No. 1 to the Second Amended and Restated Registration Rights Agreement

/s/ Xxxxx X. Xx Xxxxxxx

XXXXX X. XX XXXXXXX

Address:

0000 Xxxx Xxxxx Xxxx

Xxxxxxx Xxxx, XX 00000

Signature Page to Perlegen Sciences, Inc.
Amendment No. 1 to the Second Amended and Restated Registration Rights Agreement

		THE 1989 LEECH LIVING TRUST
		By:		/s/ Xxx X. Xxxxx
		Name:		Xxx X. Xxxxx
		Title:		Trustee
		Address: The 1989 Leech Living Trust
		0000 Xxxxxx Xxxx Xxx
		Xxxxxxx Xxxx, XX 00000
		Attn:		Xxx Xxxxx

Signature Page to Perlegen Sciences, Inc.
Amendment No. 1 to the Second Amended and Restated Registration Rights Agreement

/s/ Xxxxxxx Xxxxx

XXXXXXX XXXXX

Address: Xxxxxxx Xxxxx

c/o Technofyn Associates L.L.C.

0000 Xxxxxxx Xxxxxx

Xxxxx 000

Xxxx Xxxx, XX 00000

Signature Page to Perlegen Sciences, Inc.
Amendment No. 1 to the Second Amended and Restated Registration Rights Agreement

/s/ Xxxxxxxxx X. Xxxxxxxxx

XXXXXXXXX X. XXXXXXXXX

Address:

Xxxxxxx X. Xxxxxxxx

c/o Technofyn Associates, LLC

0000 Xxxxxxx Xxxxxx, Xxxxx 000

Xxxx Xxxx, XX 00000-0000

Signature Page to Perlegen Sciences, Inc.
Amendment No. 1 to the Second Amended and Restated Registration Rights Agreement

		ALEXANDER XXXXX XXXXXXXXX 12/29/88 TRUST
		By:		/s/ Xxxxxxx Xxxxx
		Name:		Xxxxxxx Xxxxx
		Title:		Trustee
		Address:
		Xxxxxxxxx X. Xxxxxxx
		c/o Technofyn Associates L.L.C.
		0000 Xxxxxxx Xxxxxx
		Xxxxx 000
		Xxxx Xxxx, XX 00000

Signature Page to Perlegen Sciences, Inc.
Amendment No. 1 to the Second Amended and Restated Registration Rights Agreement

		XXXXXXX XXXX XXXXXXXXX 12/29/88 TRUST
		By:		/s/ Xxxxxxx Xxxxx
		Name:		Xxxxxxx Xxxxx
		Title:		Trustee
		Address:
		Xxxxxxxxx X. Xxxxxxx
		c/o Technofyn Associates L.L.C.
		0000 Xxxxxxx Xxxxxx
		Xxxxx 000
		Xxxx Xxxx, XX 00000

Signature Page to Perlegen Sciences, Inc.
Amendment No. 1 to the Second Amended and Restated Registration Rights Agreement

/s/ Xxxxx Xxxxxxxxx

XXXXX XXXXXXXXX

Address:

Xxxxxxxxx X. Xxxxxxx

c/o Technofyn Associates L.L.C.

0000 Xxxxxxx Xxxxxx

Xxxxx 000

Xxxx Xxxx, XX 00000

Signature Page to Perlegen Sciences, Inc.
Amendment No. 1 to the Second Amended and Restated Registration Rights Agreement

/s/ Xxxx Xxxxxxxxx

XXXX XXXXXXXXX

Address:

Xxxxxxxxx X. Xxxxxxx

c/o Technofyn Associates L.L.C.

0000 Xxxxxxx Xxxxxx

Xxxxx 000
Xxxx Xxxx, XX 00000

Signature Page to Perlegen Sciences, Inc.
Amendment No. 1 to the Second Amended and Restated Registration Rights Agreement

/s/ Xxxxx X. Xxxxxxx

XXXXX X. XXXXXXX

Address: Xxxxx Xxxxxxx

c/o Technofyn Associates L.C.

0000 Xxxxxxx Xxxxxx

Xxxxx 000

Xxxx Xxxx, XX 00000

Signature Page to Perlegen Sciences, Inc.
Amendment No. 1 to the Second Amended and Restated Registration Rights Agreement

		AFFYMETRIX, INC.
		By:		/s/ Xxxxxxx X. Xxxxxxxx/mcs
		Name:		Xxxxxxx X. Xxxxxxxx
		Title:		Executive Vice President & General Counsel
		Address:
		Affymetrix, Inc.
		0000 Xxxxxxx Xxxxxxxxxx
		Xxxxx Xxxxx, XX 00000
		Attn: Xxxx Xxxxxxxxx

Signature Page to Perlegen Sciences, Inc.
Amendment No. 1 to the Second Amended and Restated Registration Rights Agreement

		SCHWEIZERHALL HOLDING AG SCHWEIZERHALI MANAGEMENT
		By:		/s/ L. Von Bidder
		Name:		L. Von Bidder
		Title:		Chief Executive Officer
		By:		/s/ X. Xxxx
		Name:		X. Xxxx
		Title:		Investment Analyst
		Address:
		c/o Xx. Xxxx von Bidder
		Xxxxxxxxxxxxxxxx 00
		0000 Xxxxxx
		Xxxxxxxxxxx

Signature Page to Perlegen Sciences, Inc.
Amendment No. 1 to the Second Amended and Restated Registration Rights Agreement

		ZAFFARONI FAMILY PARTNERSHIP, LP
		By:		/s/ Xxxxxxxxx Xxxxxxxxx
		Name:		Xxxxxxxxx Xxxxxxxxx
		Title:		General and Limited Partner
		Address:
		Xxxxxxx X. Xxxxxxxx
		c/o Technofyn Associates, LLC
		0000 Xxxxxxx Xxxxxx, Xxxxx 000
		Xxxx Xxxx, XX 00000-0000

Signature Page to Perlegen Sciences, Inc.
Amendment No. 1 to the Second Amended and Restated Registration Rights Agreement

		COLUMBIA ACORN TRUST (f.k.a.
		LIBERTY ACORN TRUST
		By: /s/ Xxxxx X. Xxxxx
		Name:		Xxxxx X. Xxxxx
		Title:         Treasurer
		Address:
		000 Xxxx Xxxxxx, Xxxxx 0000
		Xxxxxxx, XX 00000
		Attention: Xxxxx Xxxxxx

Signature Page to Perlegen Sciences, Inc.
Amendment No. 1 to the Second Amended and Restated Registration Rights Agreement

		CALIFORNIA EMERGING VENTURES, LLC
		By: GSA Partners, LLC, its Manager
		By: Grove Street Advisors, LLC, its Manager
		By:      /s/ Xxx St. German
		Name:		Xxx St. German
		Title:		Member & CFO
		Address:
		Grove Street Advisors
		00 Xxxxxxx Xxxxxx, Xxxxx 000
		Xxxxxxxxx, XX 000000
		Attention: Xxx St. German

Signature Page to Perlegen Sciences, Inc.
Amendment No. 1 to the Second Amended and Restated Registration Rights Agreement

CSK FINANCE CO., LTD.

By:      /s/ Syoji Wakita

Name:          Syoji Wakita

Title:         President

Address:

5th Floor, Reviera Xxxxxx Xxxxxx Xxxx.

0-0-0 Xxxxx-Xxxxxx, Xxxxxx-xx

Xxxxx 000-0000

Xxxxx

Attn: Xxxxxx Xxxxxxxxx

Signature Page to Perlegen Sciences, Inc.
Amendment No. 1 to the Second Amended and Restated Registration Rights Agreement

CSK VENTURE CAPITAL CO., LTD.,

As Investment Manager for CSK-VC Life

Science Investment Fund

By:          /s/ Xxxxxxxx Xxxxxxxx

Name:         Xxxxxxxx Xxxxxxxx

Title:         President

Address:

5th Floor, Reviera Xxxxxx Xxxxxx Xxxx.

0-0-0 Xxxxx-Xxxxxx, Xxxxxx-xx

Xxxxx 000-0000

Xxxxx

Attn: Xxxxxx Xxxxxxxxx

Signature Page to Perlegen Sciences, Inc.
Amendment No. 1 to the Second Amended and Restated Registration Rights Agreement

/s/ Xxxxxxxxx Xxxxxxx

XXXXXXXXX XXXXXXX

Signature Page to Perlegen Sciences, Inc.
Amendment No. 1 to the Second Amended and Restated Registration Rights Agreement

		XXXXXXXXX XXXXXXXXX, TRUSTEE
		OF ZAFFARONI RETIREMENT TRUST FBO
		XXXXXXX X. XXXXXXXX, U/A/D 1/1/02
		By:		/s/ Xxxxxxxxx Xxxxxxxxx
		Name:         Xxxxxxxxx Xxxxxxxxx
		Title:           Trustee
		Address:
		Xxxxxxx X. Xxxxxxxx
		c/o Technofyn Associates, LLC
		0000 Xxxxxxx Xxxxxx, Xxxxx 000
		Xxxx Xxxx, XX 00000-0000

Signature Page to Perlegen Sciences, Inc.
Amendment No. 1 to the Second Amended and Restated Registration Rights Agreement

		XXXXXXXXX XXXXXXXXX, TRUSTEE OF
		ZAFFARONI RETIREMENT TRUST FBO M.
		XXXXXXX XXXXX, U/A/D 1/1/02
		By:		/s/ Xxxxxxxxx Xxxxxxxxx
		Name:       Xxxxxxxxx Xxxxxxxxx
		Title:         Trustee
		Address:
		Xxxxxxx X. Xxxxxxxx
		c/o Technofyn Associates, LLC
		0000 Xxxxxxx Xxxxxx, Xxxxx 000
		Xxxx Xxxx, XX 00000-0000

Signature Page to Perlegen Sciences, Inc.
Amendment No. 1 to the Second Amended and Restated Registration Rights Agreement

		ALSTERTOR PRIVATE LIFE GMBH & CO.
		KG
		By:		/s/ Xxxxx Xxxxxx / Xxxxxx Xxxxxxxxx
		Name: Xxxxxx/Xxxxxxxxx
		Title: Managing Partners

Signature Page to Perlegen Sciences, Inc.
Amendment No. 1 to the Second Amended and Restated Registration Rights Agreement

		MPM BIOEQUITIES MASTER FUND, LP
		By:		MPM BioEquities GP, LP, its General Partner
		By:		MPM BioEquities GP, LLC its General
		Partner
		By:		/s/ Xxxx Xxx Xxxxxx
		Name: Xxxx Xxx Xxxxxx
		Title: Manager
		Address:
		MPM Capital, LP
		000 Xxxxxxx Xxxx. #000
		Xxxxx Xxx Xxxxxxxxx, XX 00000
		Attention: Xxxx X. Xxx Xxxxxx

Signature Page to Perlegen Sciences, Inc.
Amendment No. 1 to the Second Amended and Restated Registration Rights Agreement

		PRIVATE LIFE BIOMED AG
		By:		/s/ Xxxxx X. Xxxxxxx / /s/ X. Xxxxxxxxx
		Name: Xxxxx X. Xxxxxxx/X. Xxxxxxxxx
		Title: Managing Director
		Address:
		Xxxxx Xxxxxxx
		M.M. Warburrg & CO Schiffahrtstreuhand
		Gesellschaft mit beschränkter Haftung
		Xxxxxxxxxxxxxxx 00-00
		X00000 Xxxxxxx, Xxxxxxx

Signature Page to Perlegen Sciences, Inc.
Amendment No. 1 to the Second Amended and Restated Registration Rights Agreement