Document:

Amendment Number One to Exclusive License Agreement

 Exhibit 10.6.1 
 AMENDMENT NUMBER ONE 
 TO

 EXCLUSIVE LICENSE AGREEMENT 
 BETWEEN 
 THE REGENTS
OF THE UNIVERSITY OF CALIFORNIA AND NEUROGESX, INC. 
 THE REGENTS OF THE UNIVERSITY OF CALIFORNIA, a California corporation having its statewide administrative offices at 1111 Franklin Street, Oakland,
California 94607-5200, (“The Regents”), and acting through its Office of Technology Management, University of California San Francisco, 1294 Ninth Avenue - Suite 1, Box 1209, San Francisco, CA 94143-1209 (“UCSF”) and NEUROGESX,
INC., a California corporation having a principal place of business at 969C Industrial Boulevard, San Carlos, California, (the “Licensee”) hereby amend that certain Exclusive License Agreement, dated as of November 1, 2000, by and
between the parties hereto (hereinafter the “Agreement”) effective as of November 1, 2001 (the “Amendment Date”). 
 WITNESSETH 
 WHEREAS, The Regents and Licensee entered into the Agreement; 
 WHEREAS, The Regents has not been able to provide the exclusive rights to Regents’ Patent Rights for which Licensee had bargained for; and

 WHEREAS, The Regents and Licensee wish to continue their relationship regarding the Regents’ Patent Rights but on modified terms
reflecting the changed economic basis of their relationship; 
 NOW, THEREFORE, in and for consideration of the promises and covenants
contained herein and pursuant to Section 30.3 of the Agreement, The Regents and Licensee agree to amend the Agreement as follows: 
  

	1.	Section 4.4 is hereby deleted in its entirety. 

  

	2.	Article 6 is hereby deleted in its entirety. 

  

	3.	Section 7.1 is hereby amended by replacing “one percent (1%)” with “one-half percent (0.5%)”. 

  

	4.	Section 7.6 is hereby deleted in its entirety. 

  

	5.	Section 7.7 is hereby amended by deleting the first sentence and subsections (a) through (d) and by moving the text of subsection (e) to immediately follow the
section number so that there are no subsections in Section 7.7. 

  

	6.	Section 7.7 (after amending as above) is hereby further amended by deleting “In addition,” in the first sentence. 

  

	7.	Section 7.8 is hereby amended by replacing, in clause (ii), “Licensee” with “The Regents”. 

  

	8.	Section 7.8 is hereby further amended by deleting, in clause (iii) “only with respect to the milestone payable under Section 7.7(e),”.

  

	9.	Section 9.1 is hereby amended by replacing “February 28, 2001” with “February 28, 2002”. 

	10.	Section 17.5 is hereby deleted in its entirety and replaced with the following: “The Regents shall bear the costs of preparing, filing, prosecuting and maintaining all
United States and foreign patent applications contemplated by this Agreement incurred after the Effective Date, and as required under Article 5 and Section 17.6.”. 

  

	11.	Section 17.6 is hereby amended by deleting the third sentence of the section and replacing it with “This notice concerning foreign filing must be in writing and must
identify the countries desired.”. 

  

	12.	Section 17.7 is hereby deleted in its entirety and replaced with the following: “Licensee may terminate its obligations with respect to any given patent application or
patent upon three (3) months written notice to The Regents. If such a notice of termination is received from the Licensee, The Regents may continue to prosecute and maintain such application(s) or patent(s) at its sole discretion and expense,
but the Licensee will have no further right or licenses thereunder. If Licensee does not provide such a notice of termination as to any given patent application or patent within The Regents’ patent Rights, then The Regents’ obligation to
underwrite and to pay patent prosecution costs will continue for so long as this Agreement remains in effect.”. 

  

	13.	Section 17.8 is hereby deleted in its entirety. 

  

	14.	A new Section 30.7 is added as follows: 

 30.7 In the
event that, within one (1) year after the Amendment Date, Licensee agrees, at its sole discretion, to accept an assignment or license of rights to US Patent Application Serial No. 08/746,207 from Messrs. Staats and Pappagallo (or their
executors, successors, or assigns), named inventors on such Application, such that Licensee has exclusive rights under such Application, The Regents and Licensee agree that the foregoing paragraphs 1-8, 10-12 of this Amendment shall be rescinded as
of the date such assignment or license is perfected, and the original terms of the Agreement shall apply thereafter. In addition, Licensee shall be entitled to deduct its costs and expenses incurred with respect to such assignment or license, as
well as any on-going royalty obligations, from any amounts due The Regents hereunder after the date such assignment or license is perfected. 
 SIGNATURES
AND AGREEMENT 
 THIS AMENDMENT AND THE LICENSE AS AMENDED BY THIS AMENDMENT SETS FORTH THE ENTIRE AGREEMENT AND UNDERSTANDING OF THE
REGENTS AND LICENSEE WITH RESPECT TO THE SUBJECT MATTER HEREOF, AND SUPERCEDES ALL PRIOR DISCUSSIONS, AGREEMENTS AND WRITINGS IN RELATION THERETO. ALL MATERIAL REPRESENTATIONS AND WARRANTIES ON WHICH THE PARTIES HAVE RELIED IN CONNECTION WITH THE
NEGOTIATION OF THIS AMENDMENT, IF ANY, ARE STATED EXPRESSLY IN THIS AMENDMENT. 
 Except as stated in this Amendment, all other elements of
the original Agreement remain unchanged. In the event of any conflict between the terms of this Amendment and the License, the terms of this Amendment shall prevail. 
 This Amendment may be executed in counterparts, each of which shall be deemed an original, but both of which together shall constitute one and the same instrument. 

 IN WITNESS WHEREOF, the parties hereto have caused their duly authorized representatives to execute this
Amendment. 
  

									
	NEUROGESX, INC. (“LICENSEE”)	 		 	THE REGENTS OF THE UNIVERSITY OF CALIFORNIA
					
	By:	 	 /s/ Gerard Pereira
	 		 	By:	 	 /s/ Joel B. Kirschbaum

	Name:	 	Gerard Pereira	 		 	Name:	 	Joel B. Kirschbaum
	Title:	 	VP, Business Development	 		 	Title:	 	Director - OTM
	Date:	 	Nov. 16, 2001	 		 	Date:	 	11/21/01Amendment Number Two to Exclusive License Agreement

 Exhibit 10.6.2 
 AMENDMENT NUMBER TWO 
 TO

 EXCLUSIVE LICENSE AGREEMENT 
 BETWEEN 
 THE REGENTS
OF THE UNIVERSITY OF CALIFORNIA AND NEUROGESX, INC. 
 This Amendment Number Two is made effective December 2, 2003 (the “Amendment Date”) between THE REGENTS OF THE UNIVERSITY OF CALIFORNIA, a
California corporation having its statewide administrative offices at 1111 Franklin Street, Oakland, California 94607-5200, (“The Regents”), and acting through its Office of Technology Management, University of California San Francisco,
185 Berry Street, Suite 4603, San Francisco, CA 94107 (“UCSF”) and NEUROGESX, INC., a California corporation having a principal place of business at 981F Industrial Boulevard, San Carlos, California, (the “Licensee”) (together
“the Parties”). The Parties hereby amend that certain Exclusive License Agreement, dated as of November 1, 2000 (the “Agreement”) and Amendment Number One dated as of November 1, 2001 (“Amendment One”).

 WITNESSETH 
 WHEREAS,
The Regents and Licensee entered into the Agreement and Amendment One; 
 NOW, THEREFORE, in and for consideration of the promises and
covenants contained herein and pursuant to Section 30.3 of the Agreement, The Regents and Licensee agree to amend the Agreement as follows: 
 1.
Section 26.1 is hereby deleted in its entirety 
 SIGNATURES AND AGREEMENT 
 THIS AMENDMENT NUMBER TWO, AMENDMENT NUMBER ONE, AND THE EXCLUSIVE LICENSE AGREEMENT AS AMENDED BY THIS AMENDMENT NUMBER TWO AND AMENDMENT NUMBER ONE SETS FORTH THE ENTIRE AGREEMENT AND UNDERSTANDING OF THE REGENTS
AND LICENSEE WITH RESPECT TO THE SUBJECT MATTER HEREOF, AND SUPERCEDES ALL PRIOR DISCUSSIONS, AGREEMENTS AND WRITINGS IN RELATION THERETO. ALL MATERIAL REPRESENTATIONS AND WARRANTIES ON WHICH THE PARTIES HAVE RELIED IN CONNECTION WITH THE
NEGOTIATION OF THIS AMENDMENT, IF ANY, ARE STATED EXPRESSLY IN THIS AMENDMENT. 
 Except as stated in this Amendment Number Two, all other elements of the
original Agreement, as previously amended, remain unchanged. In the event of any conflict between the terms of this Amendment Number Two and the License, the terms of this Amendment Number Two shall prevail. 
 This Amendment may be executed in counterparts, each of which shall be deemed an original, but both of which together shall constitute one and the same instrument.

 IN WITNESS WHEREOF, the parties hereto have caused their duly authorized representatives to execute this Amendment.

  

									
	NEUROGESX, INC. (“LICENSEE”)	 		 	THE REGENTS OF THE UNIVERSITY OF CALIFORNIA
					
	By:	 	 /s/ Stephen Ghiglieri
	 		 	By:	 	 /s/ Joel B. Kirschbaum

	Name:	 	Stephen Ghiglieri	 		 	Name:	 	Joel B. Kirschbaum
	Title:	 	Chief Financial Officer	 		 	Title:	 	Director - OTM
	Date:	 	12/3/03	 		 	Date:	 	12/02/03Amendment Number Three to Exclusive License Agreement

 Exhibit 10.6.3 
 AMENDMENT NUMBER THREE 
 TO 
 EXCLUSIVE LICENSE AGREEMENT 
 BETWEEN 
 THE REGENTS OF THE UNIVERSITY OF CALIFORNIA AND NEUROGESX, INC. 
 This Amendment (“Amendment
Number Three”) is made effective July 29, 2004 between THE REGENTS OF THE UNIVERSITY OF CALIFORNIA, a California corporation having its statewide administrative offices at 1111 Franklin Street, Oakland, California 94607 (the
“Regents”), and acting through its Office of Technology Management, University of California San Francisco, 185 Berry Street, Suite 4603, San Francisco, California 94107 (“UCSF”) and NEUROGESX, INC., a California corporation
having a principal place of business at 981F Industrial Boulevard, San Carlos, California 94070 (the “Licensee”) (together, the “Parties”). 
 WHEREAS, the Parties have entered into that certain Exclusive License Agreement, dated as of November 1, 2000 (the “License Agreement”) an Amendment Number One thereto, dated as of November 1, 2001 (“Amendment
Number One”) and an Amendment Number Two thereto, dated as of December 2, 2003 (“Amendment Number Two”), and now desire the amend the foregoing documents. 
 In consideration of the promises and covenants contained herein and pursuant to Section 30.3 of the License Agreement, the Parties hereby agree to amend the License Agreement and Amendment Numbers One and Two as
follows: 
 1. Clause (ii) of Section 8.3 of the License Agreement shall be replaced in its entirety with the following phrase:
“(ii) filing at least one NDA by November 1, 2008”. 
 2. Clause (iii) of Section 8.3 of the License Agreement shall
be replaced in its entirety with the following: “(iii) commencing the marketing of at least one Licensed Product in one country by November 1, 2010”. 
 3. Section 7.7 of the License Agreement, as amended, shall be replaced in its entirety with the following: 
 “7.7
Licensee shall pay The Regents non-creditable milestone payments should either of the following occur while Commercial Sales or commercialization of a Licensed Product by Licensee are continuing: (i) the closing of an Initial Public Offering
(“IPO”) of the Licensee’s common stock pursuant to a registration statement on Form S-1 filed with the U.S. Securities and Exchange Commission; or (ii) the closing of (x) a consolidation or merger of the Licensee with any
other entity, (y) sale of all or substantially all of the assets of Licensee, or (z) sale of all or substantially all of the outstanding stock of the Licensee, pursuant to which the shareholders of the Licensee receive cash or publicly
traded securities. Upon the occurrence of such event, the Licensee shall pay to The Regents total cash payments equal to X times P, where X is equal to 16,400 shares (which number of shares shall be subject to adjustment from time to time for any
stock split, stock dividends, recapitalizations and the like) and P is equal to either the IPO offering price per share of common 

 
stock, or in the case of a merger, acquisition or sale, the average price per share actually received by shareholders of the Licensee’s common stock
from the acquirer. Such payments shall be paid in three (3) installments, with one third (1/3) of the total to be paid twelve (12) months after the closing date of such transaction, one third (1/3) to be paid twenty four
(24) months after such closing date, and the remaining one third (1/3) to be paid thirty six (36) months after such closing date. In the event the transaction contemplated hereunder involves more than one closing date, the due date
for payments owed to The Regents shall be measured from the date of the last closing.” 
 THIS AMENDMENT NUMBER THREE, AND THE LICENSE AGREEMENT AS
AMENDED BY AMENDMENT NUMBERS ONE AND TWO SETS FORTH THE ENTIRE AGREEMENT AND UNDERSTANDING OF THE REGENTS AND LICENSEE WITH RESPECT TO THE SUBJECT MATTER HEREOF, AND SUPERECEDES ALL PRIOR DISCUSSIONS, AGREEMENTS AND WRITINGS IN RELATION THERETO. ALL
MATERIAL REPRESENTATIONS AND WARRANTIES ON WHICH THE PARTIES HAVE RELIED IN CONNECTION WITH THE NEGOTIATION OF THIS AMENDMENT, IF ANY, ARE STATED EXPRESSLY IN THIS AMENDMENT NUMBER THREE. 
 Except as stated in this Amendment Number Three, all other elements of the original License Agreement, as amended by Amendment Numbers One and Two, shall remain
unchanged. In the event of any conflict between the terms of this Amendment Number Three and the License Agreement, as amended by Amendment Numbers One and Two, the terms of this Amendment Number Three shall prevail. 
 This Amendment Number Three may be executed in counterparts, each of which shall be deemed an original, but both of which together shall constitute one and the same
instrument. 
 IN WITNESS WHEREOF, the parties hereto have caused their duly authorized representatives to execute this Amendment Number Three. 

 

									
	NEUROGESX, INC. (“LICENSEE”)	 		 	 THE REGENTS OF THE UNIVERSITY OF
 CALIFORNIA
(“THE REGENTS”)

					
	By:	 	 /s/ Stephen Ghiglieri
	 		 	By:	 	 /s/ Susan Y. Nakashima

	Name:	 	Stephen Ghiglieri	 		 	Name:	 	Susan Y. Nakashima
	Title:	 	CFO	 		 	Title:	 	Business Manager, UCSF OTM
	Date:	 	8/2/04	 		 	Date:	 	July 29, 2004

  

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