FIRST AMENDMENT TO REGISTRATION RIGHTS AGREEMENT

Exhibit 4

FIRST AMENDMENT TO

REGISTRATION RIGHTS AGREEMENT

This First Amendment to the Registration Rights Agreement (the “Amendment”) is made as of October 9, 2003 by and among Alnylam Holding Co., a Delaware corporation (the “Corporation”), and the Holders, as defined in the Registration Rights Agreement dated as of July 31, 2003 by and among the Corporation and the persons and entities listed on Schedule A thereto (the “Rights Agreement”).

WHEREAS, the Corporation proposes to issue and sell up to 504,825 shares of its Series C Convertible Preferred Stock, $.0001 par value per share, pursuant to and on the terms reflected in that certain Series C Convertible Preferred Stock Purchase Agreement dated as of the date hereof, by and among the Corporation and the entities listed on the Schedule of Investors attached thereto and the Corporation and the Holders wish to add such shares of Series C Preferred Stock to the provisions of the Rights Agreement; and

WHEREAS, in accordance with Section 20(b) of the Rights Agreement, by executing and delivering this Amendment, the Corporation and the Holders of at least 66 ²/3% in voting power of the outstanding Registrable Shares (as defined in the Rights Agreement) have approved this Amendment.

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

1. Certain Defined Terms. All capitalized terms used herein and not defined herein shall have the meanings ascribed to such terms in the Rights Agreement.

2. Amendment of Rights Agreement.

(i) The Rights Agreement is hereby amended by deleting Section 1(e) in its entirety and by substituting in lieu thereof the following Section 1(e):

“(e) The term “Preferred Stock” means the Series A Preferred Stock, the Series B Preferred Stock and the Series C Preferred Stock.”

(ii) The Rights Agreement is hereby further amended by adding the following Section 1(m):

“(m) The term “Series C Preferred Stock” means the Corporation’s Series C Convertible Preferred Stock, $.0001 par value per share.”

(iii) Except as amended hereby, all of the terms and conditions of the Rights Agreement shall remain in full force and effect.

3. Counterparts. This Amendment may be executed in one or more counterparts, each of which shall be deemed an original, but all of which together shall constitute one and the same instrument.

REMAINDER OF PAGE INTENTIONALLY LEFT BLANK

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IN WITNESS WHEREOF, the undersigned have executed this Amendment as of the date first above written.

CORPORATION:
ALNYLAM HOLDING CO.
By:		/s/ Xxxx X. Xxxxxx
Name:		Xxxx X. Xxxxxx
Title:		CFO

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[First Amendment to Registration Rights Agreement, Signature Page, CONTINUED]

HOLDERS:		ENTITIES:
Xxxxx Xxxxxx		/s/ Abingworth Management Ltd*
Printed Name		Name of Entity
/s/ Xxxxx Xxxxxx		By:		/s/ Xxxx Xxxxxxxx
Signature		Name:		Xxxx Xxxxxxxx
		Title:		Director
Xxxx X. Xxxxxx		*Acting in its capacity as Manager of
Printed Name		Abingworth Bioventures III A, B, C and
		Executives LPs
/s/ Xxxx X. Xxxxxx
Signature
		Arch Venture Fund V, LP
		Name of Entity
Xxxxxxxx
Printed Name		By:		/s/ Xxxxx Xxxx
		Name:		Xxxxx Xxxx
/s/ Xxxxxxxx		Title:		Managing Director
Signature
		Arch V Entrepreneurs Fund, L.P.
Xxxxxx Xxxxxx		Name of Entity
Printed Name
		By:		/s/ Xxxxx Xxxx
		Name:		Xxxxx Xxxx
/s/ Xxxxxx Xxxxxx		Title:		Managing Director
Signature
Xxxx Xxxxxxxx		Atlas Venture Fund VI GmbH & Co. KG
Printed Name		Name of Entity
		By:		Atlas Venture Associates VI, L.P.
/s/ Xxxx Xxxxxxxx				its managing limited partner
Signature		By:		Atlas Venture Associates VI, Inc.
				its general partner
Xxxxxxx X. Xxxxx		By:		/s/ Xxxxxx Xxxxxx Xxxxx
Printed Name		Name:		Xxxxxx Xxxxxx Xxxxx
		Title:		Vice President
/s/ Xxxxxxx X. Xxxxx
Signature

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Xxxxxx Xxxxxx		ATLAS VENTURE FUND VI, L.P.
Printed Name		Name of Entity
		By:		Atlas Venture Associates VI, L.P.
/s/ Xxxxxx Xxxxxx				its general partner
Signature		By:		Atlas Venture Associates VI, Inc.
				its general partner
Xxxx Xxxxxx		By:		/s/ Xxxxxx Xxxxxx Xxxxx
Printed Name		Name:		Xxxxxx Xxxxxx Xxxxx
		Title:		Vice President
/s/ Xxxx Xxxxxx
Signature
		ATLAS VENTURE ENTREPRENEURS’
		FUND VI, L.P.
		Name of Entity
		By:		Atlas Venture Associates VI, L.P.,
				its general partner
		By:		Atlas Venture Associates VI, Inc.
				its general partner
		By:		/s/ Xxxxxx Xxxxxx Xxxxx
		Name:		Xxxxxx Xxxxxx Xxxxx
		Title:		Vice President
		ATLAS VENTURE PARALLEL FUND V-A,
		C.V.
		Name of Entity
		By:		Atlas Venture Associates V, L.P.,
				its general partner
		By:		Atlas Venture Associates V, Inc.
				its general partner
		By:		/s/ Xxxxxx Xxxxxx Xxxxx
		Name:		Xxxxxx Xxxxxx Xxxxx
		Title:		Vice President

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ATLAS VENTURE ENTREPRENEURS’ FUND V, L.P.
Name of Entity
By:		Atlas Venture Associates V, L.P.,
		its general partner
By:		Atlas Venture Associates V, L.P.
		its general partner
By:		/s/ Xxxxxx Xxxxxx Xxxxx
Name:		Xxxxxx Xxxxxx Xxxxx
Title:		Vice President
ATLAS VENTURE PARALLEL FUND V-B, C.V.
Name of Entity
By:		Atlas Venture Associates V, L.P.,
		its general partner
By:		Atlas Venture Associates V, Inc.
		its general partner
By:		/s/ Xxxxxx Xxxxxx Xxxxx
		Name: Xxxxxx Xxxxxx Xxxxx
Title:		Vice President
ATLAS VENTURE FUND V, L.P.
Name of Entity
By:		Atlas Venture Associates V, L.P.,
		Its general partner
By:		Atlas Venture Associates V, Inc.
		Its general partner
By:		/s/ Xxxxxx Xxxxxx Xxxxx
Name:		Xxxxxx Xxxxxx Xxxxx
Title:		Vice President

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CHP II, L.P.
Name of Entity
By:		CHP II Management, LLC
		Its General Partner
By:		/s/ Xxxx X. Xxxxxx
Name:		Xxxx X. Xxxxxx
Title:		Managing Member
POLARIS VENTURE PARTNERS III, L.P.
By:		Polaris Venture Management Co. III, L.L.C.,
		Its General Partner
By:		/s/ Xxxxxxx X. Xxxxxxxx
Name:		Xxxxxxx X. Xxxxxxxx
Title:		Attorney-in-fact
POLARIS VENTURE PARTNERS ENTREPRENEURS’ FUND III, L.P.
By:		Polaris Venture Management Co. III, L.L.C.,
		Its General Partner
By:		/s/ Xxxxxxx X. Xxxxxxxx
Name:		Xxxxxxx X. Xxxxxxxx
Title:		Attorney-in-fact
POLARIS VENTURE PARTNERS FOUNDERS III, L.P.
By:		Polaris Venture Management Co. III, L.L.C.,
		Its General Partner
By:		/s/ Xxxxxxx X. Xxxxxxxx
Name:		Xxxxxxx X. Xxxxxxxx
Title:		Attorney-in-fact

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