AMENDMENT
EXHIBIT
10.1
***
Confidential treatment has been requested for portions of this exhibit. The
copy
filed herewith omits the information subject to the confidentiality treatment
request, and such omissions are designated as [***]. A complete version of
this
exhibit has been filed separately with the Securities and Exchange Commission
pursuant to the request for confidential treatment.
AMENDMENT
This
Amendment (“Amendment”), dated as of August 5, 2005 (the “Amendment Effective
Date”), is made by and between MSD Warwick (Manufacturing) Ltd. (“Merck”) and
DOV Pharmaceutical, Inc. (“DOV”) with respect to the Exclusive License,
Development and Commercialization Agreement by and between Merck and DOV dated
August 5, 2004 (the “Agreement”)
Whereas
the parties have held discussions on amending the Agreement on an interim basis
such that Merck’s obligations to commence a certain Phase II Clinical Trial on
DOV 21,947 would be transferred to DOV and re-assumed by Merck under certain
conditions;
Now
therefore the parties agree as follows, employing where capitalized terms are
used and not otherwise defined the definitions used in the
Agreement:
| 1. |
IND.
Merck shall transfer, or cause to be transferred, to DOV the current
open
IND for DOV 21,947 to enable DOV to conduct Clinical Trials including
those contemplated by this Amendment. Upon the transfer of the IND
to DOV,
DOV shall be solely responsible for performance of all Clinical Trials
pursuant to the IND and compliance with the conditions of the IND.
The
exclusive license granted to Merck pursuant to Section 3.1 of the
Agreement shall have any and all exceptions (the “License Exceptions”)
sufficient to permit DOV, and one or more third parties engaged by
DOV on
its behalf, to conduct and perform any and all research and development,
Clinical Trials including those required by Paragraphs 3, 4 and 5
below
and any other activities necessary or appropriate to fulfill DOV’s rights
and obligations under this Amendment. Additionally, Merck hereby
grants to
DOV (a) a non-exclusive license under Merck Patent Rights (if any)
and
Merck Know-How (if any) and (b) the right to permit, under Merck
Patent
Rights (if any) and Merck Know-How (if any), one or more third parties
engaged by DOV to make or use, on DOV’s behalf, DOV 21,947 and any Product
containing DOV 21,947 and methods, in the case of either of the foregoing
clauses (a) or (b), sufficient to permit DOV to conduct and perform
any
and all research and development, Clinical Trials including those
required
by Paragraphs 3, 4 and 5 below and any other activities necessary
or
appropriate to fulfill DOV’s rights and obligations under this Amendment.
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| 2. |
Drug
Supply.
Merck shall supply to DOV at Merck’s expense all Merck’s supply existing
as of the Amendment Effective Date of DOV 21,947 that is qualified
as of
the Amendment Effective Date for use in
humans.
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| 3. |
Phase
Ib and R&D.
DOV shall conduct at its expense a Phase Ib Clinical Trial with respect
to
DOV 21,947 (the “Phase Ib”) on normal volunteers in order to form a basis
for a Phase II Clinical Trial with respect to DOV 21,947, as more
fully
described below (the “First Phase II”). DOV shall have the right, during
the Phase Ib, First Phase II and Second Phase II (as defined below),
and
upon consultation with Merck, to conduct at DOV’s expense further
development activities on DOV 21,947 including formulation, longer
term
toxicology, ADME and other pre-clinical development and Clinical
Trials
(collectively, “Further R&D”).
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| 4. |
First
Phase II.
DOV shall conduct at its expense the First Phase II, which shall
be a
dose-response, placebo controlled study. The results of the First
Phase II
shall be taken into account in designing a successive Phase II Clinical
Trial, as more fully described below (the “Second Phase II”).
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| 5. |
Second
Phase II.
DOV shall conduct at its expense the Second Phase II, which shall
have as
its objective determining the superiority of DOV 21,947 over an SSRI
in
the treatment of outpatients with major depressive disorder. No later
than
the commencement of the Second Phase II, the parties shall agree
in
writing on the design of the Second Phase II and what constitutes
successful completion of the Second Phase II (“Successful”). Whether such
study is Successful shall be determined without reference to Section
1.74
of the Agreement.
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| 6. |
DOV
Development Plan and Budget.
Within ninety (90) days following the Amendment Effective Date DOV
shall
present to Merck the development plan and budget for the Phase Ib
and
First Phase II (the “DOV Plan”). The DOV Plan shall include spending caps
for the DOV personnel involved in carrying out the DOV Plan for up
to
$[***] for the Phase Ib and $[***] for the Second Phase II. DOV shall
update the DOV Plan based on new information developed for Further
R&D
and Second Phase II.
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| 7. |
Reimbursement
of DOV.
If the Second Phase II is Successful or if Merck otherwise elects
as
contemplated by this Paragraph 7 or Paragraphs 8 or 11 below, Merck
shall
reimburse DOV as follows (the “Reimbursement Payment): [***]% of DOV’s
actual costs for the Phase Ib and Second Phase II and [***]% of its
actual
costs for the First Phase II and Further R&D, in each case upon
presentation of an itemization of such costs calculated to include
out of
pocket and internal professional time at CRO rates to be agreed upon
by
the parties; provided that Merck shall not be required to reimburse
DOV
for Further R&D expenses that were not approved by Merck prior to
being incurred. If the Second Phase II is not Successful, Merck may
elect
but is not required to make the Reimbursement Payment. The Reimbursement
Payment shall be due (a) forty-five (45) days following the later
of (i)
the date that DOV provides Merck with all Information and Inventions
generated as a result of Phase Ib, First Phase II, Second Phase II
and
Further R&D, and (ii) the date on which DOV delivers to Merck data
demonstrating that the Second Phase II is Successful, (b) in the
event
that the Second Phase II is not Successful and Merck nevertheless
elects
to make the Reimbursement Payment, no later than sixty (60) days
after the
delivery to Merck of data demonstrating that the Second Phase II
was not
Successful or (c) in the event that DOV terminates this Amendment
in
accordance with Paragraph 11 below after the commencement of the
Second
Phase II, and if Merck exercises its rights under Paragraph 11, not
later
than the date specified in Paragraph
11.
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| 8. |
Merck
Payment and Continuing Obligations.
(a) If the Second Phase II is Successful or if Merck otherwise elects
to
make the Reimbursement Payment, it shall re-assume all development
and
other obligations under the Agreement with respect to DOV
21,947.
|
(b) Upon
the
Amendment Effective Date, the penalty payments in respect of Initiation of
a
first Phase II Clinical Trial for DOV 21,947 called for by Section 5.3(d) of
the
Agreement shall be eliminated and replaced by payments in the same amounts
to be
due in the event of Merck’s failure to Initiate a further Phase II Clinical
Trial or Phase III Clinical Trial for DOV 21,947 or such Additional Compound
selected by Merck pursuant to Paragraph 10 within [***] following the
Reimbursement Payment for the initial penalty, [***] thereafter for the second
penalty and [***] after the second penalty for each subsequent penalty, provided
that DOV has promptly transferred the IND for DOV 21,947 and all Information
and
Inventions pursuant to paragraph 13.
| 9. |
Pivotal
Trial Milestone.
If the Second Phase II is Successful, Merck shall, notwithstanding
anything to the contrary in the Agreement (including without limitation
Section 5.3(c) of the Agreement), make the development milestone
payment
called for by Section 5.3(a)(i) of the Agreement.
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| 10. |
Additional
Licenses to Merck.
Within thirty (30) days of the Amendment Effective Date, DOV shall
transfer all Information and Inventions relating to the Additional
Compounds (defined below) (the “Transfer Date”). DOV hereby grants to
Merck, free of charge, for a period commencing on the date of this
Amendment and ending 12 months following the Transfer Date, an exclusive
license in the Territory under the DOV Patent Rights, DOV’s and its
Controlled Affiliates’ rights in the Joint Patent Rights, and DOV
Know-How, but with no right to sublicense, to conduct pre-clinical
testing
on three additional triple reuptake inhibitor compounds of DOV, namely,
[***] (“Additional Compounds”), whereupon Merck shall be entitled to
select (in writing no later than 30 days after the end of such 12-month
period) with no up-front payment to DOV one of such Additional Compounds
for inclusion in the Agreement as a Compound and all references in
the
Agreement to DOV 21,947 shall be deemed to mean DOV 21,947 and/or
the
Additional Compound that has been selected by Merck. Upon such selection,
all know-how, data and related inventions and/or intellectual property
related to such other two Additional Compounds created or developed
by or
on behalf of Merck during such 12 month period (the “Rejected Compound
IP”) shall be returned or transferred to and be owned by DOV. In
furtherance thereof, Merck hereby assigns and transfers, and shall
assign
and transfer, to DOV all ownership and interest in the Rejected Compound
IP and any and all intellectual property rights in and to any Rejected
Compound IP.
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| 11. |
Termination
by DOV.
DOV shall have the right, prior to conclusion of the Second Phase
II and
before clinical results are known, to terminate this Amendment upon
30
days’ written notice provided pursuant to Section 12.4 of the Agreement
in
which case (a) all references in the Agreement to DOV 21,947 including
in
Section 1.15 shall be deleted and the compound selected by Merck
pursuant
to Paragraph 10 shall be substituted therefor and (b) Section 9.4
of the
Agreement shall apply to DOV 21,947 as if the Agreement were terminated
by
Merck pursuant to Section 9.2 of the Agreement; provided that such
termination shall not affect the parties’ rights and obligations under
Paragraph 10 of this Amendment. In the event of such a termination
by DOV,
DOV will provide to Merck copies of all DOV’s Information relating to DOV
21,947 that has not previously been provided to Merck. Merck will
have the
right, no later than sixty (60) days after DOV has provided such
Information to Merck, upon written notice and payment of the Reimbursement
Payment, to re-assume all development and other rights and obligations
under the Agreement with respect to DOV 21,947; provided,
however,
that, in the event that Merck’s election to make a Reimbursement Payment
relates to a termination by DOV prior to the commencement of the
Second
Phase II, the component of the Reimbursement Payment payable pursuant
to
this sentence that is attributable to the First Phase II shall be
[***]%
of DOV’s actual costs for the First Phase II ( rather than [***]% of DOV’s
actual costs for the First Phase II).
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| 12. |
Termination
by Merck.
During the term of this Amendment, in addition to the rights Merck
has
pursuant to Sections 9.2 and 9.3 of the Agreement, Merck shall have
the
right to terminate the Agreement upon 30 days’ written notice (i) within
sixty (60) days of DOV presenting to Merck the DOV Plan, or (ii)
if the
Parties do not agree in writing on the design of the Second Phase
II or
what constitutes Successful completion of the Second Phase II. Termination
pursuant to this Paragraph 12 of the Amendment shall be deemed a
termination by Merck pursuant to Section 9.2 of the Agreement. Merck
shall
not elect to terminate the Agreement pursuant to Section 9.2 prior
to the
date that is ninety (90) days following the Amendment Effective
Date.
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| 13. |
Reversion
of Rights to Merck.
If Merck makes the payments required by Paragraphs 7 and 9 above,
the
License Exceptions shall terminate, and DOV shall promptly transfer
to
Merck under the Agreement all Information and Inventions created
or
developed by DOV during the term of this Amendment relating to DOV
21,947
and any Information and Inventions created or developed during the
period
shall be governed by the Agreement and the IND for DOV 21,947. Thereupon
the parties shall have all rights and obligations set forth in the
Agreement except as expressly amended by this Amendment.
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| 14. |
Joint
Development Committee.
Notwithstanding the provisions of Section 2.3 of the Agreement, during
the
term of this Amendment, and until the reversion of rights to Merck
pursuant to Paragraph 13 of this Amendment, JDC meetings shall be
chaired
by DOV, and Merck shall have the right to waive its participation
in JDC
meetings. DOV shall inform Merck during the JDC meetings of all
correspondence sent to and received from the FDA regarding the
Phase
Ib, First Phase II, and Second Phase II and with respect to the Further
R&D.
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| 15. |
DOV
216,303 Public Communications.
DOV shall be entitled to publish the results of the DOV 216,303 study
entitled “A Multi-Centered, Double-blind Safety, Efficacy and Tolerability
Study Comparing DOV 216,303 BID 50 mg to Citalopram HBr 20 mg BID
for Two
Weeks in Hospitalized and Outpatient Patients with Major Depressive
Disorder” [***].
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| 16. |
Construction.
The parties intend that this Amendment supersede any inconsistent
terms of
the Agreement or, if not directly inconsistent, be construed so as
to
harmonize the two documents to the extent that the intent of this
Amendment is carried out.
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| 17. |
Further
Assurances.
Each party agrees to execute such further papers, agreements, documents,
instruments and the like as may be necessary or desirable to effect
the
purpose of this Amendment and to carry out its
provisions.
|
| 18. |
Counterparts.
This Amendment may be executed in two or more counterparts, each
of which
will be deemed an original, but all of which will constitute one
and the
same instrument.
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remainder of this page has been left blank intentionally.]
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Agreed:
MSD
Warwick (Manufacturing) Ltd.
By:
/s/
Xxxxxxxx Xxxxx
| Name: |
Xxxxxxxx
Xxxxx
|
| Title: |
Treasurer
|
DOV
Pharmaceutical, Inc.
By:
/s/
Xx.
Xxxxxx
Xxxxxx
| Name: |
Xx.
Xxxxxx Xxxxxx
|
| Title: |
President
and Chief Executive
|
Officer
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