Manhattan
      Pharmaceuticals, Inc.

    810
      Seventh Avenue, 4th
      Floor

    New
      York, New York 10019

    


    September
      17, 2008

    


    Nordic
      Biotech Venture Fund II K/S

    Østergade
      5, 3rd floor

    DK-1100
      Copenhagen K

    Denmark

    Attn:
      Florian Schönharting

    


    
      	Re:	
              Registration
                Rights Agreement Issues

            


    

    


    Gentlemen:

    


    Manhattan
      Pharmaceuticals, Inc. (“Manhattan”) and Nordic
      Biotech Venture Fund II K/S
      (“Nordic”) are parties to that certain Joint Venture Agreement dated January 31,
      2008, as amended (the “Joint Venture Agreement”), and the Registration Rights
      Agreement dated February 25, 2008 (the “Registration Rights Agreement”). For the
      purpose of clarifying with you certain issues that have arisen under the
      Registration Rights Agreement, we agree with you as follows:

    


    Capitalized
      terms used and not otherwise defined herein that are defined in the Registration
      Rights Agreement or the Joint Venture Agreement are used herein with the
      meanings given such terms in the Registration Rights Agreement or Joint Venture
      Agreement, as the case may be.

    


    Manhattan
      filed a Registration Statement on Form S-1 with the SEC (File No.: 333-150580)
      pursuant to the Registration Rights Agreement. Notwithstanding any other
      agreement to the contrary, Nordic and Manhattan agree that the Effectiveness
      Date for this Registration Statement shall be October 17, 2008, unless the
      SEC
      responds with additional comments to the first amendment to the Registration
      Statement that Manhattan soon intends to file, in which case the Effectiveness
      Date shall be November 17, 2008. 

    


    Within
      forty-five (45) days after the Second Payment Milestone Manhattan shall file
      an
      additional Registration Statement registering the additional shares of Common
      Stock that may be issued to Nordic as Put Consideration as a result of Nordic’s
      additional investment of $1,250,000 in Newco under the terms of the Partnership
      Agreement, provided that Manhattan shall have no obligation to file such
      additional Registration Statement until Nordic makes the additional investment
      in Newco required under the terms of the Partnership Agreement as a result
      of
      the Second Payment Milestone.

    


    Within
      sixteen (16) days after Manhattan provides a Call Notice to Nordic, Manhattan
      shall file an additional Registration Statement with the SEC registering the
      shares of Common Stock to be issued to Nordic as Call Consideration as a result
      of such Call Notice, provided that if the Call Consideration is reduced pursuant
      to Section 4.3 of the Joint Venture Agreement the shares of Common Stock to
      be
      registered shall be correspondingly reduced, and if such Call Consideration
      is
      reduced to zero Manhattan shall have no obligation to file such Registration
      Statement.

    


    
      
         

      

      
         

        
          

        

      

      
         

      

    

    The
      term
“Filing Date” shall mean with respect to any Registration Statement required to
      be filed in accordance with this letter agreement the date by which such
      Registration Statement is required to be filed in accordance with this letter
      agreement. 

    


    The
      Registration Rights Agreement shall be deemed to be modified to the extent
      necessary to give effect to this letter agreement. Except
      as
      hereby modified, the Registration Rights Agreement and each provision thereof
      is
      hereby ratified and confirmed in every respect and shall continue in full force
      and effect.

    


    All
      questions concerning the construction, validity, enforcement and interpretation
      of this letter agreement shall be governed by and construed and enforced in
      accordance with the internal laws of the State of New York, without regard
      to
      the principles of conflicts of law thereof, except to the extent that the
      application of the General Corporation Law of the State of Delaware is
      mandatorily applicable. 

    


    Each
      party to this letter agreement hereby irrevocably submits to the exclusive
      jurisdiction of the federal and state courts sitting in the state of New York
      in
      any action or proceeding arising out of or relating to this letter agreement.
      Each party hereby irrevocably agrees, on behalf of itself and on behalf of
      such
      party’s successors and permitted assigns, that all claims in respect of such
      action or proceeding shall be heard and determined in any such court and
      irrevocably waives any objection such person may now or hereafter have as to
      the
      venue of any such suit, action or proceeding brought in such a court or that
      such court is an inconvenient forum. If either party shall commence an action
      or
      proceeding to enforce any provision of this letter agreement, then the
      prevailing party in such action or proceeding shall be reimbursed by the other
      party for its reasonable attorneys’ fees and other costs and expenses incurred
      with the investigation, preparation and prosecution of such action or
      proceeding.

    


    Please
      signify your agreement to the foregoing by signing a copy of this letter
      agreement in the space provided below and returning it to us.

    


    
      	 	
              Very
                truly yours,

            
	 	 
	 	
              MANHATTAN
                PHARMACEUTICALS, INC.

            
	 	 
	 	 
	 	 
	 	
              By:
                /s/ Michael McGuinness

            
	 	
              Its:
                Chief Operating and Financial
                Officer

            


    

    


    
      
         

      

      
        -2-

        
          

        

      

      
         

      

    


     

    
      	
              ACCEPTED
                AND AGREED TO:

            
	 	 
	
              NORDIC
                BIOTECH VENTURE FUND II K/S

            
	 
	
              By:

            	
              /s/
                Christian Hansen

            
	
              Name:

            	
              Christian
                Hansen

            
	
              Title:

            	
              Partner

            
	 	 
	
              By:

            	
              /s/
                Florian Schonharting

            
	
              Name:

            	
              Florian
                Schonharting

            
	
              Title:

            	
              Partner

            


    

    


     

    
      
         

      

      
        -3-