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:

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“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.”

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(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.

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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):

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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.”

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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).

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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.

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(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

 
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