Letter Agreement



 Exhibit 10.3 
 ***Text Omitted and Filed Separately 
 with the Securities and Exchange Commission. 

Confidential Treatment Requested 
 Under 17 C.F.R. Sections 200.80(b)(4) 
 and 240.24b-2. 
 

 
 Metabasis Therapeutics, Inc. 
 11119 North Torrey Pines Road 
 La Jolla, CA 92037 
 USA

 Attention: Chief Executive Officer 
  
 June 1, 2009 
 Re: Fourth Letter
Agreement to Collaboration and License Agreement 
 Ladies and Gentlemen: 
 Reference is made to the Collaboration and License Agreement (“Collaboration Agreement”) dated August 7, 2008 by and between
Hoffmann-La Roche Inc., Roche Palo Alto LLC and F.Hoffmann-La Roche Ltd (collectively, “Roche”), and Metabasis Therapeutics, Inc. (“Metabasis”), as further modified by the letter agreements dated August 7,
2008, November 26, 2008 and February 25, 2009 (respectively, the “1st Letter”, “2nd Letter” and “3rd Letter”). This Fourth Letter Agreement (“4th Letter”) shall be effective as of the date of the last signature below. Capitalized terms used but not otherwise
defined in this 4th Letter shall have the meanings provided in the Collaboration
Agreement. 
 Under the following terms and conditions and upon execution of this 4th Letter by all parties, the parties agree as follows: 
  

	1.	On or before June 1, 2009, Roche shall pay to Metabasis the Development Event Payment I of Section 5.3 of the Collaboration Agreement, specifically $2,000,000 (two million
dollars) for the Initiation of Toxicology Studies of the first Collaboration Compound (the “Milestone Payment”). 

  

	2.	In consideration for Roche’s advance payment of this development event, Metabasis shall [...***...]. Such Transfer shall be 

  
  
  
  
  
 ***Confidential Treatment Requested 

	 	








 

 
  

	 	conducted in accordance with the technology transfer workplan (the “Workplan”) set forth in Appendix A attached hereto. 

  

	3.	In accordance with the Workplan, Metabasis shall assign two senior scientists (the “FTE”) to facilitate the Transfer. The Transfer shall take place in a location of
Roche’s choosing at a time mutually agreeable to both parties, but will be completed within 30 days of receipt by Metabasis of the Milestone Payment. Within 30 days after completion of the Transfer and receipt of an invoice from Metabasis,
Roche shall reimburse Metabasis for the services of the FTEs plus expenses incurred (e.g., travel, lodging and meals). Such payment shall not exceed a total of [...***...] and shall not exceed [...***...] per day for each
FTE plus reasonable documented expenses. 

  

	4.	 This 4th Letter may be executed in two or more counterparts, each of which shall be deemed an original document, and all of which, together with this writing, shall be deemed one instrument. 


  

	5.	 The Collaboration Agreement, as expressly amended by the 1st Letter, 2nd
 Letter, 3rd Letter and this
4th Letter, including all exhibits, schedules and appendices attached thereto and
herewith, are both a final expression of the parties’ agreement and a complete and exclusive statement with respect to all of its terms. Except as specifically provided by this 4th Letter, the Collaboration Agreement and the 1st Letter, 2nd
 Letter and 3rd Letter shall remain in
full force and effect in accordance with their terms. 


 Please indicate your acceptance of these terms by signing in the space provided
below. 
  

			
	Sincerely,	  	
		
	 HOFFMANN-LA ROCHE INC.
	  	ROCHE PALO ALTO LLC
		
	 /s/ Nader Fotouhi
	  	/s/ Kevin A. Marks
		
	 Name:  Nader Fotouhi, Ph.D.
 Title:    Vice President, Discovery Chemistry
              Ctr. Mgr. Pharma Research Nutley
              Head of Discovery Technologies
 Date:    5/29/09
	  	 Name:  Kevin A. Marks
 Title:    Vice President
  
  
 Date:    6/1/09


  
  
  
  
  
  
  
  
  
  
  
  
  
 ***Confidential Treatment Requested 







 

 
  

			
		
	 F.HOFFMANN-LA ROCHE LTD
	  	F.HOFFMANN-LA ROCHE LTD
		
	 /s/ Robin Breckenridge
	  	/s/ Stefan Arnold
		
	 Name:  Robin Breckenridge
 Title:    PP Site Head
  
 Date:    
	  	 Name:  Stefan Arnold
 Title:    Head Corporate Law Pharma
  
 Date:    

		
	  
 AGREED TO AND ACCEPTED BY:
  
 METABASIS THERAPEUTICS, INC.
	  	
		
	 /s/ Mark D. Erion
	  	
		
	 Name:  Mark D. Erion, Ph.D.
 Title:    President, CEO and CSO
  
 Date:    May 28,
2009
	  	








 APPENDIX A 
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 *** Confidential Treatment Requested