EXHIBIT 10.20
Portions of this Exhibit
have been omitted
pursuant to a request
for confidential
treatment. The omitted
portions are marked
***** and have been
filed separately with
the Commission.
AMENDMENT NO. 1 TO THE
COLLABORATION AND LICENSE AGREEMENT
dated as of November 8, 1996
by and between
CELL THERAPEUTICS, INC.
and
ORTHO BIOTECH INC.
and
THE X.X. XXXXXXX PHARMACEUTICAL CORPORATION
THIS AMENDMENT NO. 1 to the COLLABORATION AND LICENSE AGREEMENT (the
"Agreement"), dated as of November 6, 1996, by and between CELL THERAPEUTICS,
INC., a Washington corporation having its principal place of business at 000
Xxxxxxx Xxxxxx Xxxx, Xxxxx 000, Xxxxxxx, Xxxxxxxxxx 00000 (hereinafter
referred to as "CTI") and ORTHO BIOTECH INC., a New Jersey corporation having
its principal place of business at 000 X.X. Xxxxx 000 Xxxxx, Xxxxxxx, Xxx
Xxxxxx 00000 and THE X. X. XXXXXXX PHARMACEUTICAL RESEARCH INSTITUTE, a
division of ORTHO PHARMACEUTICAL CORPORATION, a Delaware corporation having
its principal office at U.S. Xxxxx 000, Xxxxxxx, Xxx Xxxxxx 00000 (hereinafter
collectively referred to as "ORTHO"), is made this 16th day of November, 1998
by and among CTI and ORTHO (each, a "Party" and together, the "Parties").
W I T N E S S E T H:
- - - - - - - - - -
WHEREAS, CTI and ORTHO desire to amend the Agreement as provided
herein:
NOW THEREFORE, in consideration of the foregoing and the
representations, warranties and covenants set forth herein, and other good and
valuable consideration, the receipt and adequacy of which are hereby
acknowledged, and intending to be legally bound hereby, the Parties hereto
hereby agree as follows:
SECTION 1.01. Definitions. The following terms, when capitalized,
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shall have the following meanings as used in this Amendment:
"ALI Recommendation" means the interim analysis recommendation by The
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National Heart, Lung and Blood Institute through the Steering Committee of its
ARDS Network with respect to the Phase II/III ALI Trial (Protocol 1037).
"Certificate of Analysis" means the document that summarizes all final
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release test data as compared to the release specification for each lot of
product, including date of manufacture, expiration or retest date, and is
approved by the appropriate authority.
"Certificate of Conformance" means the document that provides
--------------------------
certification that all documentation for a particular lot, collected during
production and testing, has been reviewed and all deviations, non-conformances
or other quality issues have been satisfactorily resolved to release the lot,
and shall include proof of sterility, endotoxin and environmental testing.
"ORTHO Resumption Date" shall mean that date which is sixty (60) days
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after the later to occur of: (i) the delivery by CTI to ORTHO of the results of
the Phase III AML Trial and (ii) the delivery by CTI to ORTHO of the ALI
Recommendation.
"ORTHO Suspension Date" means July 1, 1998.
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"Phase II/III ALI Trial" means CTI's Phase II/III clinical trial for
----------------------
Lisofylline currently designated under protocol 1036 and includes all
modifications thereto (including a change in protocol number).
"Phase III AML Trial" means CTI's Phase III clinical trial for
-------------------
Lisofylline currently designated under protocol 1031 and includes all
modifications thereto (including a change in protocol number).
(The information below marked by ***** has been omitted by a request for
confidential treatment. The omitted portion has been separately filed with the
Commission.)
"Standard Manufacturing Cost" means the standard manufacturing cost
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using generally accepted accounting principles for one (1) 10 milliliter ampoule
(10.6 milliliter fill), including formulation, filling and bulk packaging
activities, but excluding drug substance and shipping charges. On the date
hereof, such costs are estimated by ORTHO to be as follows: *****.
SECTION 2.01. Development.
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(a) Lead Development Party. Notwithstanding anything in the Agreement
----------------------
to the contrary, effective as of the ORTHO Suspension Date, CTI shall be the
Lead Development Party in all geographic territories. As Lead Development
Party, CTI shall have sole control over all aspects of Development under the
Agreement. ORTHO shall have no obligations for Development after the ORTHO
Suspension Date until the ORTHO Resumption Date.
(b) Development Expenses. Notwithstanding anything in the Agreement
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to the contrary, subject to Section 7.01 of this Amendment, effective as of the
ORTHO Suspension Date, ORTHO shall have no obligations to fund Development
Expenses under the Agreement until the ORTHO Resumption Date.
2.
SECTION 3.01. Commercialization and Marketing. Notwithstanding
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anything in the Agreement to the contrary, effective as of the ORTHO Suspension
Date, ORTHO shall have no obligations for Commercialization or Marketing under
the Agreement until the ORTHO Resumption Date.
SECTION 4.01. Milestone Payments. Notwithstanding anything in the
------------------
Agreement to the contrary, ORTHO shall not be obligated to make Milestone
Payments under Section 3.02 of the Agreement unless and until the occurrence of
the ORTHO Resumption Date. Upon the occurrence of the ORTHO Resumption Date,
ORTHO shall make the Milestone Payment as set forth in Section 5.01(c)(iv) of
this Amendment and Article III of the Agreement.
SECTION 5.01. Termination.
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(a) Termination by ORTHO. Section 14.03 of the Agreement shall be
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amended by adding the following paragraph as subsection (c):
"(c) ORTHO shall have the right to terminate this Agreement by
written notice to CTI, within sixty (60) days following the later of
to occur of (i) delivery to ORTHO of the ALI Recommendation, or (ii)
delivery to ORTHO of the results of CTI's Phase III AML Trial. Such
termination shall be effective immediately upon receipt by CTI of such
written notice."
(b) Effect of Termination by ORTHO.
------------------------------
(i) The title and first sentence of Section 14.04 shall be
amended by adding the language indicated in italics as follows:
"SECTION 14.04. Effect of Termination by ORTHO Pursuant to
------------------------------------------
Section 14.03 (a) or (b). If ORTHO terminates this Agreement pursuant
------------------------
to Section 14.03(a) or (b)".
(ii) The following provision shall be added to Article XIV as
Section 14.08.
"SECTION 14.08. Effect of Termination by ORTHO pursuant to
------------------------------------------
Section 14.03(c). If ORTHO terminates this Agreement pursuant to
----------------
Section 14.03(c), its obligation to perform its obligations under this
Agreement shall terminate immediately. In addition, as a result of
such termination, Sections 14.04(a), (b), (c), (e) and (f) shall apply
to the Parties."
(c) ORTHO Resumption Date. Notwithstanding anything in the Agreement
---------------------
to the contrary, upon the occurrence of the ORTHO Resumption Date the following
provisions will apply:
3.
(i) ORTHO shall resume all Development, Commercialization
and Marketing obligations under the Agreement as if this Amendment had not
been adopted.
(ii) ORTHO shall be solely responsible for all ORTHO internal
ramp-up and similar costs associated with the resumption of ORTHO's
obligations pursuant to Section 6.01(b)(i) above.
(The information below marked by ***** has been omitted by a request for
confidential treatment. The omitted portion has been separately filed with the
Commission.)
(iii) ORTHO shall reimburse CTI ***** of the Development
Expenses incurred by CTI with respect to Development during the period
between December 31, 1998, and the ORTHO Resumption Date.
(iv) ORTHO shall pay CTI all Milestone Payments for milestones
achieved by CTI between the ORTHO Suspension Date and the ORTHO
Resumption Date.
(The information below marked by ***** has been omitted by a request for
confidential treatment. The omitted portion has been separately filed with the
Commission.)
(v) ORTHO shall pay CTI a one-time milestone payment of
*****.
SECTION 6.01. Manufacture.
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(a) Manufacture of Collaboration Products. Notwithstanding anything
-------------------------------------
in the Agreement to the contrary, if ORTHO terminates the Agreement pursuant to
Section 14.03(c), the following provisions shall apply:
(i) CTI shall use commercially reasonable efforts to
identify an alternative party to manufacture and supply Collaboration
Products.
(ii) Upon receipt of bulk raw material from CTI with a
Certificate of Analysis, ORTHO shall provide the following manufacturing
services to CTI for twenty-four (24) months following such termination:
(A) test the bulk raw material;
(B) formulate the suspension-liquid without doing any
further development work;
(C) fill ampoules under aseptic conditions and terminally
sterilize the final product; and
(D) supply unlabelled ampoules to CTI along with a
Certificate of Conformance.
provided, however, CTI shall have sole responsibility for the release of the
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finished product.
4.
(b) Manufacturing Expenses. ORTHO shall provide the Manufacturing
----------------------
services set forth in Section 5.01(a) of this Amendment at Standard
Manufacturing Cost.
SECTION 7.01. Payments.
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(a) Payments by ORTHO.
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(The information below marked by ***** has been omitted by a request
for confidential treatment. The omitted portion has been separately filed with
the Commission.)
(i) As full and complete settlement with respect to its
development and other obligations under the Agreement from the period from
the ORTHO Suspension Date to December 31, 1998, ORTHO shall pay to CTI an
aggregate amount of ***** in connection with the execution of this
Amendment. Such amount shall be paid to CTI in two equal installments as
follows: (A) ***** shall be paid to CTI no later than October 30,
1998; and (B) ***** shall be paid to CTI no later than January 31,
1999, and shall not require the submission of any invoice or documentation
by CTI.
(ii) Notwithstanding anything in the Agreement to the
contrary, with the exception of the amounts described in the foregoing
subsection (i), all amounts that ORTHO might owe to CTI under the
Agreement or otherwise with respect to periods on or prior to Suspension
Date are hereby cancelled in full.
(b) Payments by CTI. Notwithstanding anything in the Agreement to the
---------------
contrary, all amounts that CTI might owe to ORTHO under the Agreement or
otherwise with respect to periods on or prior to the date hereof are hereby
cancelled in full.
SECTION 8.01. Miscellaneous.
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(a) Communications. CTI shall direct any and all communications
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regarding the Agreement or this Amendment to:
Xxxxxx X. Xxxxx, Ph.D
Vice President, Preclinical Development
X.X. Xxxxxxx Pharmaceutical Research Institute
000 X.X. Xxxxxxx 000
Xxxxxxx Xxx Xxxxxx 00000-0000
Telephone: (000) 000-0000
Facsimile: (000) 000-0000
(b) Access to CTI Information. Prior to the ORTHO Resumption Date,
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CTI shall provide ORTHO with full access, from the hours of 8:30 am to 5:00 pm,
Pacific Time, on regular Business Days, to all records and documents relating to
the Phase II/III ALI Trial and the Phase III AML Trial. Such records and
documents shall include, but not be limited to: trial design and protocol
information, patient records, clinical and safety data, statistical analysis and
results, and, with respect to the Phase II/III ALI Trial, joint access with CTI
to
5.
the Steering Committee of the ARDS Network at The National Heart, Lung and Blood
Institute.
SECTION 9.01. Representations and Warranties. Each of the Parties
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hereby represents and warrants to the other Party that this Amendment is a legal
and valid obligation binding upon such Party and enforceable in accordance with
its terms. The execution, delivery and performance of the Amendment by such
Party does not conflict with any agreement, instrument or understanding, oral or
written, to which it is a Party or by which it is bound, nor violate any law or
regulation of any court, governmental body or administrative or other agency
having jurisdiction over it.
6.
IN WITNESS WHEREOF, CTI and ORTHO have caused this Amendment to be
executed as of the date first written above by their respective officers
thereunto duly authorized.
CELL THERAPEUTICS, INC.
By:
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Name: Xxxxx X. Xxxxxx, M.D.
Title: President and Chief Executive
Officer
ORTHO BIOTECH INC.
By:
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Name:
Title:
X. X. XXXXXXX PHARMACEUTICAL
RESEARCH INSTITUTE, a division of
ORTHO PHARMACEUTICAL
CORPORATION
By: ORTHO PHARMACEUTICAL
---------------------------------------
CORPORATION
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By:
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Name:
Title:
7.
