Document:

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-Grantee: ________________

    Grant
      Date:  _____________

     

    GENSPERA,
      INC.

    2007
      EQUITY COMPENSATION PLAN

    

    INCENTIVE
      STOCK OPTION GRANT

     

    This
      INCENTIVE STOCK OPTION GRANT (“Grant Instrument”), dated as of ____________
      ____, 20___ (the “Date of Grant”), is delivered by GenSpera, Inc. (the
“Company”) to _____________________________________________________ (the
“Grantee”).

    

    RECITALS

    

    A. The
      GenSpera, Inc., 2007 Equity Compensation Plan (the “Plan”) provides for the
      grant of options to purchase shares of common stock of the Company. The Board
      of
      Directors of the Company (the “Board”) has decided to make a stock option grant
      as an inducement for the Grantee to promote the best interests of the Company
      and its stockholders. A copy of the Plan is attached as Appendix
      A
      to this
      Grant Instrument.

    

    B. The
      Board
      is authorized to appoint a committee to administer the Plan. If a committee
      is
      appointed, all references in this Grant Instrument to the “Board” shall be
      deemed to refer to the committee.

    

    NOW,
      THEREFORE, the parties to this Grant Instrument, intending to be legally bound
      hereby, agree as follows:

    

    1. Grant
      of Option.

    

    (a) Subject
      to the terms and conditions set forth in this Grant Instrument and in the Plan,
      the Company hereby grants to the Grantee an incentive stock option (the
“Option”) to purchase _______ shares of common stock of the Company (“Shares”)
      at an exercise price of $_____ per Share. The Option shall become vested and
      exercisable according to Paragraph 2 below.

    

    (b) The
      Option is designated as an incentive stock option, as described in Paragraph
      6
      below. However, if and to the extent the Option exceeds the limits for an
      incentive stock option, as described in Paragraph 6, the Option shall be a
      nonqualified stock option.

    
      
         

      

      
         

        
          

        

      

      
         

      

    

    

    2. Vesting
      of Option.
      

    

    (a) The
      Option shall become vested on each of the following Vesting Dates, if the
      Grantee has been continuously employed by, or providing service to, the Company
      (as defined in the Plan) from the Date of Grant through to the applicable
      Vesting Date:

    

      
        	
                Vesting Date

              	 	
                Vested Shares

              
	
                ______________________

              	 	
                _______

              
	
                ______________________

              	 	
                _______

              
	
                ______________________

              	 	
                _______

              
	
                ______________________

              	 	
                _______

              

      

    

     

    The
      vesting of the Option is cumulative. 

    

    (b) The
      Grantee may exercise the Option before or after it becomes vested, provided
      that
      if the Grantee exercises any portion of the Option before it has become vested,
      the Shares received upon the exercise of the nonvested Option (“Nonvested
      Shares”) shall be subject to the restrictions described in Subsection (c) below
      until the date on which the applicable portion of the Option would have vested.
      The period before the applicable portion of the Option would have vested is
      referred to as the “Restriction Period.”

    

    (c) During
      the Restriction Period, the Grantee may not sell, assign, encumber or otherwise
      transfer the Nonvested Shares, notwithstanding anything in the Plan to the
      contrary. If the Grantee ceases to be employed by, or provide service to, the
      Company for any reason during the Restriction Period, the Grantee shall
      immediately return the Nonvested Shares to the Company and the Company shall
      pay
      to the Grantee, as consideration for the return of the Nonvested Shares,
      $_________ per share for each returned Share. If the Grantee continues to be
      employed by, or perform service to, the Company through the vesting dates
      described in Subsection (a) above, the restrictions on the Nonvested Shares
      shall lapse according to the vesting schedule.

    

    (d) If
      the
      Grantee exercises the Option and receives Nonvested Shares, the Grantee shall
      have the right to vote any Nonvested Shares and to receive dividends and
      distributions on Nonvested Shares during the Restriction Period, provided that
      all dividends and distributions payable on Nonvested Shares during the
      Restriction Period shall be held by the Company subject to the same restrictions
      as the underlying Nonvested Shares.

    

    (e) Any
      stock
      certificates representing Nonvested Shares shall be held in escrow by the
      Company or by an escrow agent designated by the Company until the Nonvested
      Shares vest. When the Grantee obtains a vested right to the Nonvested Shares,
      a
      certificate representing the vested Shares shall be issued to the Grantee.
      The
      certificate representing the vested Shares shall be duly endorsed (or
      accompanied by an executed stock power) so as to transfer to the Grantee all
      right, title and interest in and to the Shares represented by such
      certificate.

    
      
         

      

      
        -2-

        
          

        

      

      
         

      

    

    

    3. Lock-Up
      Period.
      Notwithstanding the provisions of Paragraph 2, above, Grantee agrees that
      Grantee will not sell, transfer, or otherwise dispose of any securities of
      the
      Company during the period: (i) commencing upon the date that the Company’s
      registration statement filed with the Securities and Exchange Commission with
      respect to Company’s initial public offering (“IPO”) is declared effective (the
“IPO Effective Date”) and, (ii) terminating on the 180th
      day
      following the IPO Effective Date (the “Lock-Up Period”), provided, however, that
      the Lock-Up Period may be shortened to any period less than 180 days from the
      IPO Effective Date if agreed to by the managing underwriter for the
      IPO.

    

    4. Term
      of Option.

    

    (a) The
      Option shall have a term of ten (10) years from the Date of Grant and shall
      terminate at the expiration of that period (____________ ____, 20___), unless
      it
      is terminated at an earlier date pursuant to the provisions of this Grant
      Instrument or the Plan.

    

    (b) The
      Option shall automatically terminate upon the happening of the first of the
      following events:

    

    (i) The
      expiration of the 90-day period after the Grantee ceases to be employed by,
      or
      provide service to, the Company, if the termination is for any reason other
      than
      disability (as defined in the Plan) or death. 

    

    (ii) The
      expiration of the one-year period after the Grantee ceases to be employed by,
      or
      provide service to, the Company on account of the Grantee’s disability (as
      defined in the Plan).

    

    (iii) The
      expiration of the one-year period after the Grantee ceases to be employed by,
      or
      provide service to, the Company, if the Grantee dies while employed by, or
      providing service to, the Company or within 90 days after the Grantee ceases
      to
      be so employed or provide services on account of a termination described in
      Subparagraph (i) above.

    

    Notwithstanding
      the foregoing, in no event may the Option be exercised after the date that
      is
      ten (10) years from the Date of Grant. Any portion of the Option that is not
      vested at the time the Grantee ceases to be employed by, or provide service
      to,
      the Company shall immediately terminate.

    
      
         

      

      
        -3-

        
          

        

      

      
         

      

    

    

    5. Exercise
      Procedures.

    

    (a) Subject
      to the provisions of Paragraphs 2, 3 and 4 above, the Grantee may exercise
      part
      or all of the Option by giving the Board written notice of intent to exercise
      in
      the manner provided in Paragraph 15 below, specifying the number of Shares
      as to
      which the Option is to be exercised. On the delivery date, the Grantee shall
      pay
      the exercise price (i) in cash, (ii) with the approval of the Board, by
      delivering Shares of the Company which shall be valued at their fair market
      value on the date of delivery, or (iii) by such other method as the Board may
      approve, including, after a public offering of the Company’s stock, payment
      through a broker in accordance with procedures permitted by Regulation T of
      the
      Federal Reserve Board. The Board may impose from time to time such limitations
      as it deems appropriate on the use of Shares of the Company to exercise the
      Option.

    

    (b) The
      obligation of the Company to deliver Shares upon exercise of the Option shall
      be
      subject to all applicable laws, rules, and regulations and such approvals by
      governmental agencies as may be deemed appropriate by the Board, including
      such
      actions as Company counsel shall deem necessary or appropriate to comply with
      relevant securities laws and regulations. The Company may require that the
      Grantee (or other person exercising the Option after the Grantee’s death)
      represent that the Grantee is purchasing Shares for the Grantee’s own account
      and not with a view to or for sale in connection with any distribution of the
      Shares, or such other representation as the Board deems appropriate. All
      obligations of the Company under this Grant Instrument shall be subject to
      the
      rights of the Company as set forth in the Plan to withhold amounts required
      to
      be withheld for any taxes, if applicable. Subject to Board approval, the Grantee
      may elect to satisfy any income tax withholding obligation of the Company with
      respect to the Option by having Shares withheld up to an amount that does not
      exceed the applicable withholding tax rate for federal (including FICA), state
      and local tax liabilities.

    

    6. Designation
      as Incentive Stock Option.

    

    (a) This
      Option is designated an incentive stock option under Section 422 of the Internal
      Revenue Code of 1986, as amended (the “Code”). If the aggregate fair market
      value of the stock on the date of the grant with respect to which incentive
      stock options are exercisable for the first time by the Grantee during any
      calendar year, under the Plan or any other stock option plan of the Company
      or a
      parent or subsidiary, exceeds $100,000, then the Option, as to the excess,
      shall
      be treated as a nonqualified stock option that does not meet the requirements
      of
      Section 422. If and to the extent that the Option fails to qualify as an
      incentive stock option under the Code, the Option shall remain outstanding
      according to its terms as a nonqualified stock option.

    

    (b) The
      Grantee understands that favorable incentive stock option tax treatment is
      available only if the Option is exercised while the Grantee is an employee
      of
      the Company or a parent or subsidiary or within a time specified in the Code
      after the Grantee ceases to be an employee. The Grantee should consult with
      his
      or her tax adviser regarding the tax consequences of the
      Option.

    
      
         

      

      
        -4-

        
          

        

      

      
         

      

    

    

    7. Change
      of Control.
      The
      provisions of the Plan applicable to a Change of Control shall apply to the
      Option, and, in the event of a Change of Control, the Board may take such
      actions as it deems appropriate pursuant to the Plan.

    

    8. Stockholder’s
      Agreement.
      As a
      condition of receiving this Option, the Grantee hereby agrees that, if requested
      by the Company prior to a public offering of the Company’s stock, the
Grantee
      (or other person exercising the Option after the Grantee’s death) will execute a
      stockholder’s agreement, on such terms as may be approved by the Company, with
      respect to all Shares issued upon the exercise of the Option.

    

    9. Restrictions
      on Exercise.
      Only
      the Grantee may exercise the Option during the Grantee’s lifetime. After the
      Grantee’s death, the Option shall be exercisable (subject to the limitations
      specified in the Plan) solely by the legal representatives of the Grantee,
      or by
      the person who acquires the right to exercise the Option by will or by the
      laws
      of descent and distribution, to the extent that the Option is exercisable
      pursuant to this Grant Instrument.

    

    10. Grant
      Subject to Plan Provisions.
      This
      grant is made pursuant to the Plan, the terms of which are incorporated herein
      by reference, and in all respects shall be interpreted in accordance with the
      Plan. The grant and exercise of the Option are subject to the provisions of
      the
      Plan and to interpretations, regulations and determinations concerning the
      Plan
      established from time to time by the Board in accordance with the provisions
      of
      the Plan, including, but not limited to, provisions pertaining to (i) rights
      and
      obligations with respect to withholding taxes, (ii) the registration,
      qualification or listing of the Shares, (iii) capital or other changes of the
      Company and (iv) other requirements of applicable law. The Board shall have
      the
      authority to interpret and construe the Option pursuant to the terms of the
      Plan, and its decisions shall be conclusive as to any questions arising
      hereunder.

    

    11. No
      Employment or Other Rights.
      The
      grant of the Option shall not confer upon the Grantee any right to be retained
      by or in the employ or service of the Company and shall not interfere in any
      way
      with the right of the Company to terminate the Grantee’s employment or service
      at any time. The right of the Company to terminate at will the Grantee’s
      employment or service at any time for any reason is specifically
      reserved.

    

    12. No
      Stockholder Rights.
      Neither
      the Grantee, nor any person entitled to exercise the Grantee’s rights in the
      event of the Grantee’s death, shall have any of the rights and privileges of a
      stockholder with respect to the Shares subject to the Option, until Shares
      have
      been issued upon the exercise of the Option.

    
      
         

      

      
        -5-

        
          

        

      

      
         

      

    

    

    13. Assignment
      and Transfers.
      The
      rights and interests of the Grantee under this Grant Instrument may not be
      sold,
      assigned, encumbered or otherwise transferred except, in the event of the death
      of the Grantee, by will or by the laws of descent and distribution. In the
      event
      of any attempt by the Grantee to alienate, assign, pledge, hypothecate, or
      otherwise dispose of the Option or any right hereunder, except as provided
      for
      in this Grant Instrument, or in the event of the levy or any attachment,
      execution or similar process upon the rights or interests hereby conferred,
      the
      Company may terminate the Option by notice to the Grantee, and the Option and
      all rights hereunder shall thereupon become null and void. The rights and
      protections of the Company hereunder shall extend to any successors or assigns
      of the Company and to the Company’s parents, subsidiaries, and affiliates. This
      Grant Instrument may be assigned by the Company without the Grantee’s
      consent.

    

    14. Applicable
      Law; Consent to Jurisdiction.
      The
      validity, construction, interpretation and effect of this instrument shall
      be
      governed by and determined in accordance with the laws of the State of Texas
      without regard for conflict of law principles. GRANTEE HEREBY EXPRESSLY CONSENTS
      TO THE PERSONAL JURISDICTION OF THE STATE AND FEDERAL COURTS LOCATED IN THE
      STATE OF TEXAS FOR ANY LAWSUIT FILED BY OR AGAINST THE GRANTEE ARISING FROM
      OR
      RELATING TO THIS AGREEMENT.

    

    15. Notice.
      Any
      notice to the Company provided for in this instrument shall be addressed to
      the
      Company in care of the CEO at the Company headquarters (with a copy also sent
      to
      the attention of the Secretary at the same address), and any notice to the
      Grantee shall be addressed to such Grantee at the current address shown on
      the
      payroll of the Company, or to such other address as the Grantee may designate
      to
      the Company in writing. Any notice shall be delivered by hand, sent by telecopy
      or enclosed in a properly sealed envelope addressed as stated above, registered
      and deposited, postage prepaid, in a post office regularly maintained by the
      United States Postal Service.

    

    IN
      WITNESS WHEREOF, the Company has caused its duly authorized officers to execute
      and attest this Grant Instrument, and the Grantee has executed this Grant
      Instrument, effective as of the Grant Date.

    

    
      	
              GenSpera,
                Inc.

            	 
	 	 
	
              By:

            	  	 
              	
              Attest:

            	 
	 	 
	
              Accepted:

            	 
	 	 
	 
              	 
	
              Grantee

            	 

    

    

    
      	
              Full
                Name:

            	 
	 	 
	
              Address:

            	 
	 	 
	 
              	 

    

    

    
      
         

      

      
        -6-

        
          

        

      

      
         

      

    

    

    APPENDIX
      A

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