Amendment No. 1 to the Third Amended and Restated Investors' Rights Agreement



 EXHIBIT 4.2 
 AMENDMENT NO. 1 TO THE THIRD AMENDED AND RESTATED 
 INVESTORS’ RIGHTS AGREEMENT 
 This AMENDMENT NO. 1 THE THIRD AMENDED AND RESTATED INVESTORS’ RIGHTS AGREEMENT is dated as of December 28, 2007 (this “Amendment”)
and is entered into by and among NeurogesX, Inc., a Delaware corporation (the “Company”), the parties defined as “Investors” in the IRA (as defined below) (each a “Prior Investor,” and collectively, the “Prior
Investors”), and the parties listed on Exhibit A to the SPA (as defined below) (each a “Purchaser,” and collectively, the “Purchasers”). The Third Amended and Restated Investors’ Rights Agreement dated as of
November 14, 2005, as amended, shall be hereinafter referred to as the “IRA.” 
 RECITALS 
 WHEREAS, The Purchasers are purchasing shares of Common Stock of the Company (the “Shares”) and warrants to purchase shares of Common Stock of
the Company (the “Warrants”) pursuant to a Securities Purchase Agreement, dated as of December 23, 2007, by and among the Company and the Purchasers (the “SPA”); 
 WHEREAS, the Company and the undersigned Prior Investors (on behalf of all Prior Investors) desire the Purchasers to have certain registration rights
with respect to the Shares and the shares of Common Stock of the Company issuable upon exercise of the Warrants (the “Underlying Shares,” along with the Shares, collectively, the “Securities”) pursuant to Sections 1.1 through 1.4
and Sections 1.6 through 1.14 of the IRA, by and among the Company and the Prior Investors, and that the Purchasers be added to the Rights Agreement as parties thereto for the purpose of granting such registration rights; 
 WHEREAS, Section 4.3 of the IRA allows the amendment or waiver of such IRA with the written consent of the Company and the holders of at least a
majority Registrable Securities, as defined in the IRA, outstanding (the “Majority Holders”); and 
 NOW, THEREFORE,
in consideration of the promises contained herein and for other good and valuable consideration, the receipt and sufficiency of which is hereby mutually acknowledged by the parties hereto, the parties hereby covenant and agree as follows:

 1. The Securities shall constitute “Registrable Securities,” as such term is defined in Section 1.1(g) of the IRA, for all
intents and purposes of the registration rights and related provisions and obligations set forth in Sections 1.1 through 1.4, Sections 1.6 through 1.14 and Section 4 of the IRA. 
 2. The Purchasers shall be treated for all purposes under Sections 1.1 through 1.4, Sections 1.6 through 1.14, and Section 4 of the IRA as
“Holders,” as such term is defined in Section 1.01(d) of the IRA; provided however, that the Purchasers shall not be considered “Initiating Holders” as such term is defined in Section 1.1(e). 







 3. Notwithstanding the foregoing, if the Registration Statement on Form S-3 required to be filed pursuant
to the Registration Rights Agreement, dated as of December 23, 2007, by and among the Company and the Purchasers (the “RRA”), is not declared effective or ceases to be effective, or if Form S-3 is not available to the Company to
register the Securities under Rule I.B.1 of Form S-3, the Purchasers shall have the right to request up to two demand registrations for underwritten public offerings pursuant to the terms of Section 1.2 of the IRA as if the Purchasers were
“Initiating Holders” under such section (without regard, except as set forth below, to the share and dollar threshold requirements set forth in Sections 1.1(e) and 1.2(a)(A), respectively, of the IRA), provided, however, that the Company
shall not be required to carry out any such demand registration unless such registration is requested in writing after June 30, 2008 by Purchasers holding at least 30% of the Securities. The Purchaser’s rights to demand registration
pursuant to this Section 3 shall terminate two years after the Initial Closing Date, as defined in the RRA. 
 4. The Purchasers agree to
be bound by the terms and conditions of Sections 1.1 through 1.4, Sections 1.6 through 1.14 and Section 4 of the Rights Agreement and shall succeed to and assume all of the rights and obligations of Holders of Registrable Securities for all
intents and purposes of such Sections, provided that, the Purchasers shall not be deemed to possess any rights set forth in Sections 2 or 3 of the Rights Agreement. 
 5. All notices and other communications under the IRA shall be made to the Purchasers at the addresses specified in Exhibit A to the SPA, and thereafter at such other address, notice of which is given in accordance
with Section 4.4 of the IRA. 
 6. To facilitate the sale and issuance of the Securities and the proposed registration of the Securities
pursuant to a Registration Statement on Form S-3 under the RRA, the Prior Investors (on their own behalf and on behalf of all Prior Investors for purposes of the IRA) furthermore hereby waive the following as such apply to such Form S-3 registration
of the Securities: (i) any right to prior or other notice of a Form S-3 registration carried out pursuant to the RRA; (ii) the 20 day period, set forth in Section 1.3 of the IRA, in which the Prior Investors may otherwise be able to
respond to notice by the Company of a Form S-3 registration carried out pursuant to the RRA; (iii) any and all registration rights under the IRA that would require the Company to register in a Form S-3 registered pursuant to the RRA any shares
of Company Common Stock held by the Prior Investors; and (iv) any other conflict that may arise between the IRA and the RRA. 
 7. The
Prior Investors hereby (on their own behalf and on behalf of all Prior Investors for purposes of the IRA) consent to the grant to the Purchasers of the piggyback and demand registration rights set forth herein, and hereby waive any conflicts that
may arise between the terms hereof and the terms of the IRA. 
 8. The IRA as modified herein shall remain in full force and effect as so
modified. 
 [Signature Pages Follow] 







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

			
	NEUROGESX, INC.
		
	By:	 	 /s/ Stephen Ghiglieri

	Name:	 	Stephen Ghiglieri
	Title:	 	Chief Financial Officer

 THE PURCHASER’S SIGNATURE TO THE INVESTOR QUESTIONNAIRE DATED OF EVEN DATE HEREWITH SHALL CONSTITUTE THE
PURCHASER’S SIGNATURE TO THIS AMENDMENT NO. 1 THE THIRD AMENDED AND RESTATED INVESTORS’ RIGHTS AGREEMENT. 
  

 [Signature Page to Amendment No. 1 to the Third Amended and Restated Investors’ Rights
Agreement] 








 PRIOR INVESTORS: 
  

			
	Alta California Partners II, L.P.
		
	By:	 	 Alta California Management Partners II,
 LLC

	Its:	 	General Partner
		
	By:	 	 /S/ ALIX MARDUEL

		 	 Member

	
	Alta Embarcadero Partners II, LLC
		
	By:	 	 /S/ ALIX MARDUEL 

		 	 Under Power of Attorney

	
	Alta California Partners II, L.P. – New Pool
		
	By:	 	Alta California Management Partners II, LLC – New Pool, its General Partner
		
	By:	 	 /S/ ALIX MARDUEL

		 	 Managing Director

	
	Alta BioPharma Partners III, L.P.
		
	By:	 	Alta BioPharma Management III, LLC
		
	By:	 	 /S/ ALIX MARDUEL

		 	 Director

	
	Alta BioPharma Partners III GmbH & Co. Beteiligungs KG
		
	By:	 	Alta BioPharma Management III, LLC
		
	By:	 	 /S/ ALIX MARDUEL

		 	 Director

	
	Alta Embarcadero BioPharma Partners III, LLC
		
	By:	 	  

		 	 V.P. of Finance & Admin



  

 [Signature Page to Amendment No. 1 to the Third Amended and Restated Investors’ Rights
Agreement] 








 PRIOR INVESTORS: 
  

					
	ARCH Venture Fund V, L.P.
		
	By:	 	ARCH Venture Partners V, L.P.
	Its:	 	General Partner
			
		 	By:	 	ARCH Venture Partners V, LLC
		 	Its:	 	General Partner
		
	By:	 	 /S/ CLINTON BYBEE

	Its:	 	Managing Director
	
	ARCH V Entrepreneurs Fund, L.P.
		
	By:	 	ARCH Venture Partners V, L.P.
	Its:	 	General Partner
			
		 	By:	 	ARCH Venture Partners V, LLC
		 	Its:	 	General Partner
		
	By:	 	 /S/ CLINTON BYBEE

	Its:	 	Managing Director
	
	Healthcare Focus Fund, L.P.
		
	By:	 	ARCH Venture Partners V, L.P.
	Its:	 	General Partner
			
		 	By:	 	ARCH Venture Partners V, LLC
		 	Its:	 	General Partner
		
	By:	 	 /S/ CLINTON BYBEE

	Its:	 	Managing Director


  

 [Signature Page to Amendment No. 1 to the Third Amended and Restated Investors’ Rights
Agreement] 








 PRIOR INVESTORS: 
  

			
	Montreux Equity Partners II, SBIC, L.P.
		
	By:	 	 Montreux Equity Management II SBIC,
 LLC, its General
Partner

		
	By:	 	 /S/ DANIEL K. TURNER

	Name:	 	Daniel K. Turner III
	Title:	 	Managing Member
	
	Montreux Equity Partners III, SBIC, L.P.
		
	By:	 	 Montreux Equity Management III SBIC,
 LLC, its General
Partner

		
	By:	 	 /S/ DANIEL K. TURNER

	Name:	 	Daniel K. Turner III
	Title:	 	Managing Member


  

 [Signature Page to Amendment No. 1 to the Third Amended and Restated Investors’ Rights
Agreement] 








 PRIOR INVESTORS: 
  

			
	Pacven Walden Ventures V, L.P.
		
	By:	 	  

		 	 Lip-Bu Tan

	Title:	 	 Director
 of Pacven Walden Management V,
Co.,
 Ltd. as General Partner of Pacven
 Walden Ventures V, L.P.


	
	Pacven Walden Ventures Parallel V-A, C.V.
		
	By:	 	  

		 	 Lip-Bu Tan

	Title:	 	 Director
 of Pacven Walden Management V,
Co.,
 Ltd. as General Partner of Pacven
 Walden Ventures Parallel
V-A C.V.

	
	Pacven Walden Ventures Parallel V-B, C.V.
		
	By:	 	  

		 	 Lip-Bu Tan

	Title:	 	 Director
 of Pacven Walden Management V,
Co.,
 Ltd. as General Partner of Pacven
 Walden Ventures Parallel
V-B C.V.

	
	Pacven Walden Ventures V Associates Fund, L.P.
		
	By:	 	  

	Title:	 	 Director
 of Pacven Walden Management V,
Co.,
 Ltd. as General Partner of Pacven
 Walden Ventures V
Associates Fund,
 L.P.



  

 [Signature Page to Amendment No. 1 to the Third Amended and Restated Investors’ Rights
Agreement] 









			
	Pacven Walden Ventures V-OP Associates Fund, L.P.
		
	By:	 	  

		 	 Lip-Bu Tan

	Title:	 	 Director
 of Pacven Walden Management V,
Co.,
 Ltd. as General Partner of Pacven
 Walden Ventures V-QP
Associates
 Fund, L.P.

	
	International Venture Capital Investment III Corporation
		
	By:	 	  

		 	 Lip-Bu Tan

	Title:	 	President
	
	International Venture Capital Investment Corporation
		
	By:	 	  

		 	 Lip-Bu Tan

	Title:	 	President
	
	Asian Venture Capital Investment Corporation
		
	By:	 	  

		 	 Lip-Bu Tan

	Title:	 	President
	
	Seed Ventures III Pte. Ltd.
		
	By:	 	  

		 	 Lip-Bu Tan, Director



  

 [Signature Page to Amendment No. 1 to the Third Amended and Restated Investors’ Rights
Agreement] 








 PRIOR INVESTORS: 
  

			
	Dow Employees’ Pension Plan
		
	By:	 	Diamond Capital Management Inc.
		 	Its Agent
		
	By:	 	  

	Name:	 	Kenneth J. Van Heel
	Title:	 	Sr. Investment Manager
	
	Union Carbide Employees’ Pension Plan
		
	By:	 	Diamond Capital Management Inc.
		 	Its Agent
		
	By:	 	  

	Name:	 	Kenneth J. Van Heel
	Title:	 	Sr. Investment Manager


  

 [Signature Page to Amendment No. 1 to the Third Amended and Restated Investors’ Rights
Agreement] 








 PRIOR INVESTORS: 
  

			
	 The Global Life Sciences Ventures Funds II
 GmbH & Co. KG

	
	Represented by its General Partners
	The Global Life Science Ventures GmbH
		
	By:	 	  

		
	Title:	 	  

	
	The Global Life Sciences Ventures Fund II Limited Partnership
	
	Represented by its General Partner
	Global Life Science Ventures (GP) Limited
		
	By:	 	 /S/ JO BAXTER

		
	Title:	 	 Director



  

 [Signature Page to Amendment No. 1 to the Third Amended and Restated Investors’ Rights
Agreement] 








 PRIOR INVESTORS: 
  

			
	  

	Jean-Jacques Bienaime


  

 [Signature Page to Amendment No. 1 to the Third Amended and Restated Investors’ Rights
Agreement] 








 PRIOR INVESTORS: 
  

			
	MC Life Science Ventures, Inc.
		
	By:	 	  

	Name:	 	Tsunehiko Yanagihara
	Title:	 	President


  

 [Signature Page to Amendment No. 1 to the Third Amended and Restated Investors’ Rights
Agreement] 








 PRIOR INVESTORS: 
  

			
	MunMun International Ltd.
		
	By:	 	  

		
	Name:	 	  

		
	Title:	 	  



  

 [Signature Page to Amendment No. 1 to the Third Amended and Restated Investors’ Rights
Agreement] 








 PRIOR INVESTORS: 
  

			
	Saudi Venture Development Company
		
	By:	 	  

		
	Name:	 	  

		
	Title:	 	  



  

 [Signature Page to Amendment No. 1 to the Third Amended and Restated Investors’ Rights
Agreement] 








 PRIOR INVESTORS: 
  

			
	 Palefsky Children’s Irrevocable Trust fbo
 Alexis Nicole Palefsky

		
	By:	 	  

		
	Title:	 	  

	
	 Palefsky Children’s Irrevocable Trust fbo
 Nicholas Howard Palefsky

		
	By:	 	  

		
	Title:	 	  

	
	 Palefsky Children’s Irrevocable Trust fbo
 Jessica Victoria Baxter

		
	By:	 	  

		
	Title:	 	  



  

 [Signature Page to Amendment No. 1 to the Third Amended and Restated Investors’ Rights
Agreement]