Exhibit
        10.1

      


      OMNIBUS
        AMENDMENT TO JOINT VENTURE AGREEMENT AND ADDITIONAL
        AGREEMENTS

       

      THIS
        OMNIBUS AMENDMENT TO JOINT VENTURE AGREEMENT AND ADDITIONAL AGREEMENTS (this
        “Amendment”)
        is
        entered into as of June 9, 2008
        by and
        among Manhattan Pharmaceuticals, Inc., a Delaware corporation (“MHA”),
        Hedrin Pharmaceuticals K/S,
        a
        Danish limited liability partnership (“Newco”),
        Hedrin
        Pharmaceuticals General Partner ApS, a Danish private limited company
        (“Hedrin
        GP”)
        and
        Nordic
        Biotech Venture Fund II K/S, a Danish limited liability partnership
        (“Nordic”).

       

      WITNESSETH:

       

      WHEREAS,
        MHA and Nordic previously entered into that certain Joint Venture Agreement
        dated as of January 31, 2008 (as previously amended, the “Joint
        Venture Agreement”).
        Capitalized terms not otherwise defined herein shall have the meanings assigned
        to them in the Joint Venture Agreement;

      


      WHEREAS,
        pursuant
        to the Joint Venture Agreement, (i) MHA agreed to assign certain assets to
        Newco
        in accordance with the terms of that certain Assignment and Contribution
        Agreement dated as of February 21, 2008 (as amended from time to time, the
        “Contribution
        Agreement”),
        (ii)
        MHA, Nordic and Hedrin GP entered into a Limited Partnership Agreement dated
        as
        of February 21, 2008 (as amended from time to time, the “Partnership
        Agreement”),
        and
        (iii) MHA and Nordic entered into a Shareholders Agreement dated as of February
        21, 2008 (as amended from time to time, the “Shareholders
        Agreement”)
        with
        respect to Hedrin GP; and

      


      MHA,
        Newco, Hedrin GP and Nordic wish to recognize that substantial progress has
        been
        made toward achieving the Payment Milestone so as to justify a current partial
        Milestone Payment and that more specificity is appropriate in the definition
        of
        the Payment Milestone that will result in the payment of the remaining Milestone
        Payment, all in accordance with the terms hereof, and that the Joint Venture
        Agreement, Contribution Agreement, Partnership Agreement and Shareholders
        Agreement should be appropriately modified, in each case on the terms and
        conditions set forth in this Amendment. 

      


      NOW,
        THEREFORE, for good and valuable consideration, the receipt and sufficiency
        of
        which is hereby acknowledged, the parties hereto hereby agree as
        follows:

      


      1. Amendments
        to Joint Venture Agreement.
        

       

      (a) Section
        1
        of the Joint Venture Agreement is hereby amended by deleting the defined
        term
“Milestone Payment” in its entirety and adding the following two new defined
        terms in alphabetical sequence in Section 1:


      
        
          
          

        

        
          
          

          
            

          

        

        
          
          

        

      


      “Initial
        Milestone Payment” means the payment by Nordic of an additional $1,250,000 to
        Newco after the satisfaction of the Initial Payment Milestone (as defined
        in the
        Contribution Agreement).

       

      “Second
        Milestone Payment” means the payment by Nordic of an additional $1,250,000 to
        Newco after the satisfaction of the Second Payment Milestone (as defined
        in the
        Contribution Agreement).

       

      (b) Section
        1
        of the Joint Venture Agreement is hereby amended by deleting the defined
        term
“Investment Amount” in its entirety and replacing it with the following:


       

      “Investment
        Amount”
means
        (i) $2,500,000 if neither the Initial Milestone Payment nor the Second Milestone
        Payment has occurred, (ii) $3,750,000 if, prior to June 30, 2009, the Initial
        Milestone Payment has occurred but the Second Milestone Payment has not
        occurred, (iii) $3,500,000 if (A) on or after June 30, 2009, the Initial
        Milestone Payment has occurred but the Second Milestone Payment has not
        occurred, or (B) if
        prior
        to June 30, 2009, the U.S.
        Food
        and Drug Administration (“FDA”)
        formally designates the Licensed Products (as defined in the Contribution
        Agreement) as a drug and refers regulation thereof to the FDA Center for
        Drug
        Evaluation and Research, and (iv) $5,000,000 if both the Initial Milestone
        Payment and the Second Milestone Payment have occurred.

       

      2. Amendments
        to Contribution Agreement.

       

      (a) Section
        5.3 of the Contribution Agreement is hereby deleted in its entirety and replaced
        with the following:

       

      “5.3 Definition
        of Initial Payment Milestone and Second Payment Milestone

      


      For
        purposes of this Agreement, (i) the term “Initial
        Payment Milestone”
shall
        mean a preliminary determination from the U.S. Food and Drug Administration
        received prior to September 30, 2008 that the Licensed Products will be
        regulated as a medical device, and (ii) the term “Second
        Payment Milestone”
shall
        mean (A) a determination by the U.S. Food and Drug Administration (“FDA”)
        that a
        Licensed Product is substantially equivalent to a predicate device in accordance
        with Section 513(f)(1) or 510(k) of the Federal Food, Drug, and Cosmetic
        Act (as
        amended, the “FDC
        Act”)
        or any
        other marketing authorization of a Licensed Product by the FDA as a medical
        device, (B) the issuance of a “Classification Decision” as such term is used in
        Attachment 1 of the FDA Guidance for Industry and CDRH Staff titled “New Section
        513(f)(2) - Evaluation of Automatic Class III Designation” issued by the FDA on
        February 19, 1998, with respect to a Licensed Product, or (C) the receipt
        of a
        formal response to a “Request for Designation” from the Office of Combination
        Products that designates a Licensed Product as a device, in each of cases
        (A)
        through (C) prior to June 30, 2009.”


      
        
          
          

        

        
          2

          
            

          

        

        
          
          

        

      


      (b) Section
        5.1(a)(ii) of the Contribution Agreement is hereby deleted in its entirety
        and
        replaced with two new subsections as follows:

      


      “(ii) within
        21
        days after the achievement of the Initial Payment Milestone (as defined below):
        (A) pay to MHA an additional US$1,000,000.00 in cash (the “Second
        Cash Payment”)
        and
        (B) if necessary to maintain MHA’s 50% ownership of outstanding Partnership
        Shares, issue to MHA, and deliver a certificate representing, a number of
        additional Partnership Shares of Newco that will constitute, together with
        the
        Initial Equity Issuance, 50% of all outstanding Partnership Shares (the
“Second
        Equity Issuance”).

      


      (iii) within
        30
        days after the achievement of the Second Payment Milestone (as defined below):
        (A) pay to MHA an additional US$500,000.00 in cash (the “Third
        Cash Payment”
and
        together with the First Cash Payment and the Second Cash Payment, the
“Cash
        Payments”)
        and
        (B) if necessary to maintain MHA’s 50% ownership of outstanding Partnership
        Shares, issue to MHA, and deliver a certificate representing, a number of
        additional Partnership Shares of Newco that will constitute, together with
        the
        Initial Equity Issuance and Second Equity Issuance, 50% of all outstanding
        Partnership Shares (the “Third
        Equity Issuance”)
        and,
        together with the Initial Equity Issuance and Second Equity Issuance, the
        “Equity
        Issuances”).”

      


      (c) Section
        5.1(c) of the Contribution Agreement is hereby deleted in its entirety and
        replaced with the following:

      


      “Upon
        the
        Initial Equity Issuance, MHA shall own 50% of the outstanding Partnership
        Shares
        of Newco. Upon the Second Equity Issuance, MHA shall own 50% of the outstanding
        Partnership Shares of Newco (after giving effect to the issuance of additional
        Partnership Shares, if any, to Nordic pursuant to the Partnership Agreement).
        Upon the Third Equity Issuance, if any, MHA shall own 50% of the outstanding
        Partnership Shares of Newco (after giving effect to the issuance of additional
        Partnership Shares, if any, to Nordic pursuant to the Partnership
        Agreement).”

      


      (d) Section
        5.2(b) of the Contribution Agreement is hereby deleted in its entirety and
        replaced with the following:

      


      “(b) (i)
        The
        authorized capital of Newco, immediately after the Second Equity Issuance,
        if
        any, consists of 2,000 Partnership Shares, 700 of which are owned, beneficially
        and of record, by Nordic, and 700 of which are owned, beneficially and of
        record
        by MHA, and (ii) the authorized capital of Newco, immediately after the Third
        Equity Issuance, if any, consists of 2,000 Partnership Shares, 1,000 of which
        are owned, beneficially and of record, by Nordic, and 1,000 of which are
        owned,
        beneficially and of record by MHA.



      
        
          
          

        

        
          3

          
            

          

        

        
          
          

        

      


      3. Amendments
        to Partnership Agreement.
        

       

      (a) Section
        1.1 of the Partnership Agreement is hereby amended by deleting the defined
        term
“Payment Milestone” in its entirety and adding the following two new defined
        terms in alphabetical sequence in Section 1.1:

       

      “Initial
        Payment Milestone” means such term as defined in the Contribution Agreement.


       

      “Second
        Payment Milestone” means such term as defined in the Contribution Agreement.


       

      (b) Section
        3.6 of the Partnership Agreement is hereby deleted in its entirety and replaced
        with the following:

       

      “(a)
        Not
        later than 21 days after satisfaction, if any, of the Initial Payment Milestone,
        Nordic shall pay to the Partnership an additional $1,250,000 by wire transfer
        to
        a bank account designated by the Partnership as payment for an additional
        200
        Partnership Shares. The satisfaction of the Initial Payment Milestone shall
        constitute payment by MHA for an additional 200 Partnership Shares, subject
        to
        subsection (c) below. Accordingly, after satisfaction of the Initial Payment
        Milestone, the Partnership Shares shall be distributed among the Parties
        as
        follows (all amounts in DKK):

       

      
        	 	 	
                Number of Partnership Shares

              	 
	
                Nordic 

              	 	 	
                700

              	 
	
                MHA

              	 	 	
                700

              	 
	
                General Partner

              	 	 	
                0

              	 
	
                Total

              	 	 	
                1,400

              	 


      

      


      (b)
        Not
        later than 30 days after satisfaction, if any, of the Second Payment Milestone,
        Nordic shall pay to the Partnership an additional $1,250,000 by wire transfer
        to
        a bank account designated by the Partnership as payment for an additional
        300
        Partnership Shares. The satisfaction of the Second Payment Milestone shall
        constitute payment by MHA for an additional 300 Partnership Shares. Accordingly,
        after satisfaction of the Second Payment Milestone, the Partnership Shares
        shall
        be distributed among the Parties as follows (all amounts in DKK):

       

      
        	 	 	
                Number of Partnership Shares

              	 
	
                Nordic 

              	 	 	
                1,000

              	 
	
                MHA

              	 	 	
                1,000

              	 
	
                General
                  Partner

              	 	 	
                0

              	 
	
                Total

              	 	 	
                2,000

              	 


      

      


      (c)
        If
        the Second Payment Milestone is not achieved by June 30, 2009, or if prior
        to
        June 30, 2009, the U.S.
        Food
        and Drug Administration (“FDA”)
        formally designates the Licensed Products (as defined in the Contribution
        Agreement) as a drug and refers regulation thereof to the FDA Center for
        Drug
        Evaluation and Research,
        (i)
        Nordic shall not be obliged to make any payment to the Partnership pursuant
        to
clause
        3.6(b), (ii) MHA shall forfeit to the Partnership 400 Partnership Shares,
        and
        (iii) Nordic shall be entitled to, and the Partnership shall make, a return
        of
        capital of $250,000, with no corresponding reduction in Nordic’s Partnership
        Shares. Accordingly,
        after June 30, 2009, if the Second Payment Milestone has not been achieved,
        or
        if
        prior to June 30, 2009, the FDA
        formally designates the Licensed Products as a drug and refers regulation
        thereof to the FDA Center for Drug Evaluation and Research, the Partnership
        Shares shall be distributed among the Parties as follows (all amounts in
        DKK):


      
        
          
          

        

        
          4

          
            

          

        

        
          
          

        

      

      


      
        	 	 	
                Number of Partnership Shares

              	 
	
                Nordic 

              	 	 	
                700

              	 
	
                MHA

              	 	 	
                300

              	 
	
                General
                  Partner

              	 	 	
                0

              	 
	
                Total

              	 	 	
                1,000

              	 


      

      


      (c) Section
        11.1(ii) of the Partnership Agreement is hereby deleted in its entirety and
        replaced with the following:

      


      From
        any
        amount available for distribution in excess of the amount referred to under
        sub-clause 11.1(i) the holder(s) of the MHA Partnership Shares shall before
        any
        distribution is made to other Limited Partners be entitled to receive an
        amount
        equal to the proceeds distributed to the holders of the Nordic Partnership
        Shares under sub-clause 11.1(i) multiplied by a fraction the numerator of
        which
        is MHA’s number of Partnership Shares at the time of such distribution, and the
        denominator of which is the total number of outstanding Partnership Shares
        at
        the time of such distribution.

      


      4. Amendments
        to Shareholders Agreement.
        

       

      (a) Section
        1.1 of the Shareholders Agreement is hereby amended by deleting the defined
        term
“Payment Milestone” in its entirety and adding the following two new defined
        terms in alphabetical sequence in Section 1.1:

       

      “Initial
        Payment Milestone” means such term as defined in the Contribution Agreement.


       

      “Second
        Payment Milestone” means such term as defined in the Contribution Agreement.


       

      (b) Section
        4.3 of the Shareholders Agreement is hereby deleted in its entirety and replaced
        with the following: 

       

      “Irrespective
        of clause 4.2, if the Second Payment Milestone has not been achieved by 30
        March
        2009, Nordic shall – in addition to any board members appointed by Nordic
        pursuant to clause 4.2 and as long as Nordic is the owner of the Nordic
        Partnership Shares – immediately be entitled to appoint one additional
        board member, in which case the board of directors may consist of up to five
        members elected at the general meeting.”


      
        
          
          

        

        
          5

          
            

          

        

        
          
          

        

      


      5. Satisfaction
        of Initial Payment Milestone.
        The
        parties hereto acknowledge and agree that the Initial Payment Milestone is
        deemed to be achieved as of the date of this Amendment and that payment of
        the
        Nordic capital contribution to Newco pursuant to Section 3.6(a) of the
        Partnership Agreement, as amended hereby, and payment by Newco of the Second
        Cash Payment pursuant to Section 5.1(a)(ii) of the Contribution Agreement,
        as
        amended hereby, will each occur on or before the twenty-first day after the
        date
        of this Amendment.

       

      6. Representations
        and Warranties; Ratification.
        

       

      (a) Each
        of
        MHA, Nordic, Newco and Hedrin GP represents and warrants to the other parties
        hereto that this Amendment has been duly executed and delivered by such party
        and constitutes a legal, valid and binding obligation of such party enforceable
        against it in accordance with its terms, subject to laws of general application
        relating to bankruptcy, insolvency and the relief of debtors and rules of
        law
        governing specific performance, injunctive relief or other equitable remedies,
        and to limitations of public policy. 

       

      (b) Each
        of
        Nordic, MHA, Newco and Hedrin GP represents and warrants to the others that
        each
        of the representations and warranties of such party in each of the Joint
        Venture
        Agreement and the Additional Agreements to which such company is a party
        is true
        and correct in all material respects on the effective date of this Amendment
        (except as set forth on Schedule
        A
        hereto
        and except for representations and warranties limited as to time or with
        respect
        to a specific event, which representations and warranties shall continue
        to be
        limited to such time or event).

      


      (c) Except
        as
        hereby amended, the Joint Venture Agreement and each provision thereof, and
        each
        Additional Agreement (as the same may be amended in connection with this
        Amendment) and each provision thereof, are hereby ratified and confirmed
        in
        every respect and shall continue in full force and effect. 

       

      7. Conditions
        Precedent.
        The
        agreements set forth in this Amendment are conditional and this Amendment
        shall
        not be effective until receipt by each party of a fully-executed counterpart
        of
        this Amendment (which may be a facsimile or .pdf copy thereof).


      
        
          
          

        

        
          6

          
            

          

        

        
          
          

        

      


      8. Miscellaneous.

      


      (a) Entire
        Agreement.
        This
        Amendment, the Joint Venture Agreement and the Additional Agreements, as
        amended
        hereby, contain the entire understanding of the parties hereto and supercedes
        all prior or contemporaneous negotiations, promises, covenants, agreements
        and
        representations of every nature whatsoever with respect to the matters referred
        to in this Amendment, the Joint Venture Agreement and the Additional Agreements.
        

      (b) Headings.
        The
        headings herein are for convenience only, do not constitute a part of this
        Agreement and shall not be deemed to limit or affect any of the provisions
        hereof. The language used in this Agreement will be deemed to be the language
        chosen by the parties to express their mutual intent, and no rules of strict
        construction will be applied against any party.

      (c) Successors
        and Assigns.
        This
        Amendment shall be binding upon and inure to the benefit of the parties and
        their successors and permitted assigns.

      (d) Expenses.
        Notwithstanding any provision to the contrary in the Agreement or the Additional
        Agreements, MHA will reimburse Nordic for all legal, due diligence and advisory
        fees and expenses incurred by Nordic or its advisors in connection with this
        Amendment and the transactions contemplated by this Amendment, the Agreement
        and
        the Additional Agreements. MHA has made on or before the date of this Amendment,
        or shall make within five (5) days of the date of this Amendment, a payment
        to
        Nordic of $30,000, and thereafter shall make additional advances and payments
        to
        Nordic necessary to reimburse Nordic for its fees and expenses in excess
        of
        amounts previously advanced under this Section 8(d). 

      (e) Governing
        Law.
        

      (i) All
        questions concerning the construction, validity, enforcement and interpretation
        of this Amendment, as it relates to the amendments to the Joint Venture
        Agreement and Contribution 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. 

      (ii) All
        questions concerning the construction, validity, enforcement and interpretation
        of this Amendment, as it relates to the amendments to the Partnership Agreement
        and Shareholders Agreement, shall be governed by and construed and enforced
        in
        accordance with Danish law. 

      (iii) Each
        Party 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 Amendment. 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 Amendment, 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. 

      (f) Counterparts.
        This
        Amendment may be executed in two or more counterparts, all of which when
        taken
        together shall be considered one and the same agreement and shall become
        effective when counterparts have been signed by each party and delivered
        to the
        other party, it being understood that both parties need not sign the same
        counterpart. In the event that any signature is delivered by facsimile
        transmission, such signature shall create a valid and binding obligation
        of the
        party executing (or on whose behalf such signature is executed) with the
        same
        force and effect as if such facsimile signature page were an original
        thereof.


      
        
          
          

        

        
          7

          
            

          

        

        
          
          

        

      


      (g) Severability.
        If any
        provision of this Amendment is held to be invalid or unenforceable in any
        respect, the validity and enforceability of the remaining terms and provisions
        of this Amendment shall not in any way be affected or impaired thereby and
        the
        parties will attempt to agree upon a valid and enforceable provision that
        is a
        reasonable substitute therefore, and upon so agreeing, shall incorporate
        such
        substitute provision in this Amendment.

       

      [Signature
        page follows]

       

      IN
        WITNESS WHEREOF, the parties hereto have executed this Amendment under seal
        as
        of the day and year first above written.

       

      
        	
                MHA:

              
	  
	
                MANHATTAN
                  PHARMACEUTICALS, INC.

              
	 	 
	
                By:

              	
                /s/
                  Douglas Abel

              
	
                Name:
                  

              	
                Douglas
                  Abel

              
	
                Title:

              	
                President
                  and Chief Executive Officer

              
	 	 
	
                NORDIC:

              
	  
	
                NORDIC
                  BIOTECH VENTURE FUND II K/S

              
	 
	
                By:

              	
                /s/
                  Florian Schonharting

              
	 	
                Florian
                  Schonharting, Partner

              
	 	 
	
                By:

              	
                /s/
                  Christian Hansen

              
	 	
                Christian
                  Hansen, Partner

              


      

       

      HEDRIN
        PHARMACEUTICALS K/S:

      


      BY: HEDRIN
        PHARMACEUTICALS GENERAL PARTNER APS

      


      
        	
                By:

              	
                /s/
                  Florian Schonharting

              	 	
                By:

              	
                /s/
                  Douglas Abel 

              
	 	
                Florian
                  Schonharting, Director

              	 	 	
                Douglas
                  Abel, Director

              


      

       

      HEDRIN
        PHARMACEUTICALS GENERAL PARTNER APS:

      


      
        	
                By:

              	
                /s/
                  Florian Schonharting 

              	 	
                By:

              	
                /s/
                  Douglas Abel 

              
	 	
                Florian
                  Schonharting, Director

              	 	 	
                Douglas
                  Abel, Director

              


      

       

      
        
          
          

        

        
          8