EXHIBIT 10.1
Portions of this Exhibit have been redacted and are the subject of a
confidential treatment request filed with the Secretary of the Securities and
Exchange Commission.
AMENDMENT NO. 1
TO
DEVELOPMENT AND MARKETING COLLABORATION AGREEMENT
THIS AMENDMENT NO. 1 TO DEVELOPMENT AND MARKETING COLLABORATION AGREEMENT
(this "Amendment"), dated as of the 4th day of June 2004 (the "Amendment
Effective Date"), by and between OSI Pharmaceuticals, Inc., a Delaware
corporation ("OSI"), and Genentech, Inc., a Delaware corporation ("Genentech"),
amends the Development and Marketing Collaboration Agreement (the "Collaboration
Agreement"), dated as of January 8, 2001, by and between OSI and Genentech. The
Collaboration Agreement as amended by this Amendment shall be referred to herein
as the "Agreement". Capitalized terms undefined herein shall have the meanings
given to them in the Collaboration Agreement.
WITNESSETH
WHEREAS, the Collaboration Agreement provides, among other things, that
OSI and Genentech have differing roles and obligations with respect to certain
promotion, marketing, and other activities.
WHEREAS, pursuant to the Collaboration Agreement, OSI has the right,
subject to certain conditions and criteria, to co-promote the Licensed Product.
WHEREAS, the Parties now wish to amend the Collaboration Agreement to
modify, clarify and more fully define their rights and responsibilities with
respect to the post-approval development of Licensed Product and co-promotion of
Licensed Product by OSI, all as more fully set forth herein.
NOW, THERFORE, in consideration of the foregoing recitals and the
covenants contained herein, OSI and Genentech hereby agree as follows:
AMENDMENT TO COLLABORATION AGREEMENT
1 JOINT COMMERCIAL INTEGRATION TEAM, JOINT CLINICAL SUBTEAM AND JOINT
CLINICAL TRIALS REVIEW COMMITTEE
A. Section 3.2(b) of the Collaboration Agreement is hereby deleted in its
entirety and replaced with the following:
(b) JOINT PROJECT TEAM RESPONSIBILITIES.
(i) The Joint Project Team shall be responsible for formulating
overall development plans and an annual development budget, for making
overall decisions regarding the priority and design of all clinical trials
for new indications (except for Registry Studies and ISTs, defined below),
for recommending to the JSC which Party will be responsible for
implementing clinical studies for each indication (other than Registry
Studies), for developing a publication strategy and a calendar of key
scientific and clinical meetings and other events for Licensed Product,
for exchanging information and facilitating cooperation and coordination
between the Parties as they exercise their respective rights and meet
their respective obligations under this Agreement, for determining the
priority with respect to seeking Regulatory Approval of Licensed Product,
for approving third party manufacturing and supply agreements, for
recommending to the JSC or the GDC (via the OSI-774 Liaison Team, in the
case of the GDC), as the case might be, new Lifecycle Initiatives
hereunder, and for implementing all activities approved by the JSC or the
GDC, as the case might be.
2
(ii) In addition, the Joint Project Team may designate subteams as
appropriate to facilitate coordination and cooperation in key areas.
Specifically, the Joint Project Team will designate a Joint Regulatory
Subteam to coordinate efforts as may be necessary for NDA filing and other
regulatory activities. The Joint Project Team will also designate a
subteam called the Joint Commercial Integration Team ("JCIT"), which will
be chaired by the Genentech Director of Licensed Product Marketing or
Sales. There shall be two OSI representatives on the JCIT, consisting of
an OSI commercial director assigned to Licensed Product at a level
comparable to the chair of the JCIT and a sales director assigned to
Licensed Product at a level comparable to the OSI commercial director. OSI
shall be permitted to propose that an additional OSI staff member(s)
attend specific portions of JCIT meetings to address particular agenda
items, and such additional staff members may only attend for such agenda
items after good faith consideration by, and agreement of, the Genentech
JCIT chairperson. The functions of the JCIT are as follows:
a. to provide a forum to update OSI on Genentech's
commercial activities with respect to Licensed Product and any issues
related thereto and for OSI to provide feedback with respect thereto for
Genentech's consideration;
b. to provide a forum for OSI to give input to Genentech
with respect to Co-promotion (as defined below) related matters to be
included in the Commercialization Plan;
c. to review and discuss Co-promotion-related matters,
including without limitation, assignment of Physician Call Targets (as
hereinafter defined) in accordance with Section 5.2A(b) below, sales force
bonus criteria alignment, and sales force training, and also to act as a
forum to which a Party may bring up for discussion
3
other Co-promotion related matters listed on Appendix A attached hereto
and incorporated herein and entitled "Licensed Product Commercial Roles
and Responsibilities";
d. to resolve disputes arising from routine "day-to-day"
Co-promotion-related operational matters that cannot be resolved by the
field sales managers of the Parties; and
e. to carry out such other matters assigned to the JCIT by
the JSC. "Co-promotion" and "Co-promote" as used in this Agreement shall
mean performing sales calls by OSI sales representatives to Physician Call
Targets and to medical staff associated with those Physician Call Targets,
and having OSI sales representatives at OSI promotional exhibit booths at
medical meetings and tradeshows, all solely for the purpose of the sale of
Licensed Product under the Trademark, as more specifically described in
and to the extent permitted by Section 5.2A below. Co-promotion shall not
be included within the term marketing as such term is used within the
Agreement.
The JCIT shall meet quarterly either in person or telephonically, or
as otherwise agreed by the JCIT, however the JCIT members of the Parties
with direct responsibility for implementing Co-promotion activities shall
communicate and meet as often as they reasonably deem necessary to achieve
their objectives under the Commercialization Plan.
(iii) The Joint Project Team will also designate a subteam called
the Joint Clinical Subteam, which will be co-chaired by one representative
from each Party. The functions of the Joint Clinical Subteam are as
follows:
a. to review protocols for all clinical trials (other than
ISTs) and to approve protocols for all clinical trials (other than
Registry Studies and ISTs), related to
4
Licensed Product and sponsored by Genentech or OSI (usually under their
respective INDs), whether or not such protocols constitute Lifecycle
Initiatives (as hereinafter defined);
b. to review clinical trial studies related to Licensed
Product (other than ISTs) that are conducted by cooperative groups or
under the Cancer Therapy Evaluation Program (CTEP), and to approve
clinical trial studies related to Licensed Product conducted by
cooperative groups or under CTEP (other than ISTs and Registry Studies,
which are approved as more fully described below) ;
c. to update the Parties on on-going Licensed Product
clinical programs, and
d. to resolve and settle any disagreement of the JCTRC
regarding IST review or approval.
The Joint Clinical Subteam shall meet monthly either in person or
telephonically, or as otherwise agreed by the Joint Clinical Subteam
leaders.
The Joint Clinical Subteam will designate a subteam called the Joint
Clinical Trials Review Committee ("JCTRC"). The sole function of the JCTRC
will be to review and approve all clinical trial proposals, protocols and
clinical trial concept sheets provided by or solicited from external
sponsor-investigators, including, without limitation, sponsoring
cooperative groups and CTEP (to the extent not governed by Section
3.2(b)(iii)(b) above), for clinical trials evaluating Licensed Product
(collectively, "ISTs"), including, without limitation, ISTs within a
Lifecycle Initiative pursued and funded solely by one Party under Section
4.3A(b)(ii) below. For clarity, "ISTs" hereunder are clinical trials
evaluating Licensed Product that are sponsored by third party
5
sponsor-investigators, or cooperative group sponsors, as the terms
"sponsor-investigator" and "sponsor" are defined in Section 312.3(b) of
Title 21 of the U.S. Code of Federal Regulations. The membership of the
JCTRC shall include the heads of clinical teams or their designees from
each Party and Medical Science Liaisons from each Party. The JCTRC shall
meet monthly either in person or telephonically or as otherwise agreed by
the JCTRC. The Parties' respective commercial, marketing and sales groups
shall not vote on or control decisions of the JCTRC regarding any IST or
other matter discussed at any JCTRC meeting. Decisions to approve ISTs
shall be based on medical, scientific, strategic and budgetary
considerations, provided that a Party has not reasonably objected that an
IST could adversely affect the Licensed Product. Only ISTs approved by the
JCTRC can be funded and/or supplied Licensed Product by either Party for
the purpose of such ISTs. In general the JCTRC will operate by consensus.
In the event that the JCTRC members do not reach consensus regarding an
IST decision, the JCTRC representatives of each Party shall collectively
have one vote, with decisions made by unanimous vote. If the JCTRC cannot
agree with respect to an IST decision, such disputed IST may be referred
to the Joint Clinical Subteam by either Party. In the case of such
referral, all decisions regarding ISTs shall be finally decided by the
Joint Clinical Subteam and shall not be subject to further review or
escalation. If the JCTRC approves an IST based on medical, scientific and
strategic considerations but one Party does not wish to fund such IST,
such IST may be funded and/or provided Licensed Product drug by the other
Party at its sole cost. Similarly, if the JCTRC approves an IST based on
medical, scientific and strategic considerations and such IST is solely
within a Lifecycle Initiative pursued and funded solely by one Party under
Section 4.3A(b)(ii) below), then
6
such Party may pursue and fund such IST under such Lifecycle Initiative.
Any adverse event safety data occurring during ISTs funded solely by one
Party shall be part of the Licensed Product SAE database. Data from ISTs
funded solely by one Party or provided Licensed Product at one Party's
sole cost shall be subject to Section 4.3 if such IST is within a
Lifecycle Initiative or a GNE/OSI Initiative for which the Parties are
sharing costs. Data from ISTs funded solely by one Party, or provided
Licensed Product at the cost solely of one Party, under Section
4.3A(b)(ii) below shall not be shared except as provided therein.
(iv) The Joint Project Team will prepare a draft Development
Budget/Plan, and draft an annual development budget by August 15 of the
then-current calendar year, and a final Development Budget/Plan shall be
presented by the Joint Project Team to the JSC for approval by September
15 of the then-current calendar year. The Development Budget/ Plan shall
include specific budgets for OSI/GNE Initiatives (as hereinafter defined).
In addition, the Joint Project Team Leaders will participate in the
OSI-774 Liaison Team, described in Section 3.4 below, to exchange
information, and facilitate cooperation and coordination, between the
Parties and Roche, pursuant to the Tripartite Agreement.
(v) Annually, on or about August 15, the OSI commercial director,
the Genentech marketing director and the heads of OSI's and Genentech's
clinical teams shall meet to discuss and approve the general budget for
ISTs, which budget shall then be included in the Commercialization Budget
(as hereinafter defined) submitted by Genentech to the JSC for approval as
provided in Section 5.1 below.
7
B. Section 3.2(c) of the Collaboration Agreement is hereby amended by adding
the following two sentences immediately after the last sentence of such
subsection:
"The foregoing provisions of this Section 3.2(c) shall also apply to the
Joint Clinical Subteam, which shall be subject to the dispute resolutions
procedures set forth in Article 16 for matters other than the resolution
of disagreements of the JCTRC.
2. POST-APPROVAL DEVELOPMENT ACTIVITIES.
Article 4 of the Collaboration Agreement is hereby amended by inserting
the following new Sections 4.3A, 4.3B and 4.3C immediately after Section 4.3:
"4.3A POST-APPROVAL DEVELOPMENT ACTIVITIES.
(a) As part of the updating of the Global Development Plan under
the Tripartite Agreement, which updating is required by the Tripartite
Agreement, OSI and Genentech shall each use commercially reasonable
efforts to cause the GDC to create a lifecycle plan ("Lifecycle Plan")
which will identify specific Lifecycle Initiatives. "Lifecycle
Initiatives" shall mean development opportunities with estimable
probabilities of technical and commercial success and defined budgets,
that are designed to provide an estimable increase to the overall value of
Licensed Product. Lifecycle Initiatives will include one or more of the
following: a new medical indication (for example, an indication within
**), a new therapy within indications being pursued under the existing
Global Development Plan or Development Plan (for example, studies for **).
The Lifecycle Plan will include the following details with respect to each
Lifecycle Initiative in order to achieve the purposes of such Lifecycle
Initiative: scope of clinical trials
------------
** This portion has been redacted pursuant to a confidential treatment request.
8
(including, without limitation, the size of trials), the purpose of each
trial (for example, **), the number of clinical trials and the phase of
each trial (e.g. Phase I, II, or III), the number of investigators
required to conduct each such trial, whether the trial(s) will be
sponsored and conducted by Genentech, OSI or Roche or by a cooperative
group investigator or through CTEP, and the estimated costs of such
trials. The Lifecycle Plan will be submitted by the OSI-774 Liaison Team
to the GDC for review and approval of the Lifecycle Initiatives by the GDC
in accordance with the procedures set forth under the Tripartite
Agreement. Accordingly, it is expected that the GDC will determine which
Lifecycle Initiatives, if any, or which part of each Lifecycle Initiative,
will be approved and funded under the Global Development Plan as Global
Development Costs. If the GDC approves the funding of a Lifecycle
Initiative, in accordance with the Tripartite Agreement, the GDC is to
determine each company's responsibilities for such Lifecycle Initiative,
which shall be comprised of some or all of the clinical study activities
described in Section 4.3A(b)(i) below. To the extent that Lifecycle
Initiatives put forward by the OSI-774 Liaison Team to the GDC have not
been approved, such Lifecycle Initiatives shall be handled pursuant to
Section 4.3A(b) below. Similarly, if the Tripartite Agreement is
terminated, the Parties shall operate in accordance with Section 4.3A(b)
below.
(b) If the GDC does not approve the funding of a Lifecycle Initiative,
or if Roche opts out pursuant to Section A.4 of Exhibit A to the
Tripartite Agreement (provided that neither Party or Roche
reasonably has objected to such Lifecycle Initiative, and such
Lifecycle Initiative does not adversely affect the goals of the
Global Development Plan, pursuant to Section 10.13 of the Tripartite
Agreement), or if the
------------
** This portion has been redacted pursuant to a confidential treatment request.
9
Tripartite Agreement is terminated, the JSC shall consider such
Lifecycle Initiative (or, in the event that the Tripartite Agreement
is terminated, a Lifecycle Initiative created by Genentech and OSI
as part of their annual lifecycle plan) and determine whether to
fund such Lifecycle Initiative under the Development Budget/Plan,
provided that neither Party reasonably has objected to such
Lifecycle Initiative during JSC review and such Lifecycle Initiative
does not adversely affect the goals of the Development Budget/Plan
under the Agreement.
(i) If such Lifecycle Initiative is approved by the JSC
(thereafter, an "OSI/GNE Initiative"), the JSC shall
determine which Party shall have the lead responsibility
for such OSI/GNE Initiative and the Joint Project Team
shall propose the responsibilities of each Party with
respect to such OSI/GNE Initiative, which proposals
shall be subject to JSC approval. Except as otherwise
agreed by the Parties, activities assigned to a Party
with respect to each such OSI/GNE Initiative shall be:
1) specific clinical studies sponsored and conducted by
such Party to directly further such OSI/GNE Initiative,
2) specific studies conducted by cooperative groups that
directly further such OSI/GNE Initiative, 3) specific
ISTs that directly further such OSI/GNE Initiative, 4)
specific studies conducted by such Party or the Parties
in collaboration with another sponsor that directly
further such OSI/GNE Initiative and/or 5) FDA mandated
Phase IV studies for Licensed Product within such
OSI/GNE Initiative. As used herein, "directly further"
shall mean that the study is designed to show
feasibility, efficacy and/or safety of
10
Licensed Product within the applicable OSI/GNE
Initiative. Studies under OSI/GNE Initiatives, or under
a Lifecycle Initiative above, shall not include: 1)
Registry Studies, as defined herein (which shall only be
conducted by Genentech but which are nonetheless subject
to review by the Joint Clinical Subteam, as described in
Section 4.3A(c) below), 2) ISTs outside the scope of an
OSI/GNE Initiative or Lifecycle Initiative (for example,
unsolicited requests for IST funding for an indication
outside of the OSI/GNE Initiatives), which are subject
to JCTRC approval, or 3) marketing or other
commercialization activities. The costs for any clinical
study activities within OSI/GNE Initiatives shall be
treated as OSI/GNE Development Costs in accordance with
Section 4.6 of this Agreement, except for the costs of
ISTs borne by one Party. The provisions of Section 4.3
above shall apply to any clinical trials conducted by
the Parties or external sponsors as part of such OSI/GNE
Initiatives, except for clinical trials sponsored and
funded solely by one Party within a rejected Lifecycle
Initiative under Section 4.3A(b)(ii) below. Safety
reports and safety data from all clinical trials,
however, shall be shared and centralized, however, in
accordance with Section 4.3. The costs for any Registry
Studies (subject to the last sentence of Section 4.3A(c)
below) and for jointly funded ISTs outside the scope of
an OSI/GNE Initiative or Lifecycle Initiative shall be
treated as **, in accordance with Exhibit B to the
Agreement.
------------
** This portion has been redacted pursuant to a confidential treatment request.
11
(ii) The JSC may reject such Lifecycle Initiative in whole or
in part and/or the corresponding budget for pursuit
under the Agreement. In such case, either Party may
pursue such Lifecycle Initiative or rejected part
thereof at its own expense. Any serious adverse event
safety data occurring during the activities of such
Lifecycle Initiative shall be part of the Licensed
Product SAE database. If such Lifecycle Initiative is
for an additional indication and the Tripartite
Agreement is in effect, then such Lifecycle Initiative
so pursued by only one Party will be subject to the
applicable terms, if any, of the additional indication
opt out-opt back in provisions in Section A.4 of Exhibit
A to the Tripartite Agreement. For Lifecycle Initiatives
other than for an additional indication, or if the
Tripartite Agreement is no longer in effect, then for
such Lifecycle Initiative pursued by only one Party at
its own expense, the following will apply: If the other
Party that did not pursue such Lifecycle Initiative
wishes to regain its rights to such Lifecycle
Initiative, including the use of and access to data and
results (including, without limitation, all data and
results for ISTs within such Lifecycle Initiative), then
it may regain such rights by electing to do so within
ninety (90) days of delivery of a final study report for
the pivotal trial for such Lifecycle Initiative to the
non-participating Party and by paying within thirty days
** of the total costs the non-participating Party would
have incurred had the non-participating Party
participated (i.e.
------------
** This portion has been redacted pursuant to a confidential treatment request.
12
shared costs, and thereafter assuming from the opt back
in date its ongoing obligations as if no opt out had
occurred.
(iii) From time to time, if a Party desires to pursue
Lifecycle Initiatives which have not been evaluated by
the GDC or JSC, as applicable, or included under the
current Lifecycle Plan, such Lifecycle Initiatives shall
be brought to the GDC, or if the Tripartite Agreement
has been terminated, to the JSC, for evaluation pursuant
to this Section 4.3A.
(c) "Registry Study", for purposes of the Agreement, shall mean a
prospective, observational study of the process and outcomes of care
in a population of patients designated by a common condition, status
or treatment, usually descriptive in nature, and usually without a
control or comparator arm, in which treatment is not dictated beyond
"standard of care." The Parties agree that Registry Studies shall
only be conducted by Genentech, but will be nonetheless subject to
review and good faith consideration (but not approval) by the Joint
Clinical Subteam. If the Joint Clinical Subteam does not agree
whether a proposed Registry Study should be supported or conducted,
the final decision regarding such Registry Study shall be made by
Genentech without further review discussion or escalation under the
Agreement. If the OSI members of the Joint Clinical Subteam do not
agree that a Registry Study, which has been approved by Genentech,
should be conducted or supported, then such Registry Study shall be
conducted by Genentech at its sole cost, however, OSI shall not be
entitled to obtain or review the data or results from such Registry
Study prior to publication in a scientific journal or otherwise made
13
available to the public, nor will OSI be allowed to participate in
registry investigator meetings.
4.3B MEDICAL SCIENCE LIAISON (MSL) ACTIVITIES.
"Medical Science Liaisons" or "MSLs" are defined as field-based clinical
research employees of each of the Parties whose main function is to
support clinical investigators in developing and conducting clinical
trials. OSI MSLs may conduct activities with respect to Licensed Product
only for so long as OSI is conducting clinical study activities within a
OSI Lifecycle Initiatives (as defined in Section 4.3B(a) below in
accordance with the following:
(a) With respect to Licensed Product, OSI MSLs may only make calls to
potential or current investigators for the purpose of discussing
clinical studies within: (i) OSI/GNE Initiatives, (ii) Lifecycle
Initiatives under the Tripartite Agreement, (iii) ongoing
development activities under the Global Development Plan for which
OSI is assigned the responsibility of executing or managing the
status of under the Tripartite Agreement, and (iv) Lifecycle
Initiatives which OSI is conducting and funding on its own either as
permitted under the Tripartite Agreement or under Section
4.3A(b)(ii) above (such Initiatives and Global Development Plan
activities collectively hereafter referred to as the "OSI Lifecycle
Initiatives"), but only to the extent reasonably expected to be
necessary in order to execute such OSI Lifecycle Initiatives. In
addition, OSI MSLs may also make calls to investigators for the
purpose of discussing ISTs which have been approved by the JCTRC but
which are not included within OSI/GNE Initiatives and for which OSI
has been assigned responsibility by the JCTRC, but only to the
extent reasonably expected to be
14
necessary in order to execute such ISTs. With respect to such
potential investigators, OSI may make such calls only to a number of
potential investigators that is reasonable, given the total number
of investigators that will be participating in each such clinical
study. For all inquiries with respect to Licensed Product or
clinical studies other than the foregoing, OSI MSLs shall refer such
inquiries to the appropriate Genentech MSL.
(b) With respect to Licensed Product, Genentech MSLs may make call to
potential or current investigators for any purpose, other than for
the purpose of discussing OSI Lifecycle Initiatives. Genentech MSLs
shall respond to inquiries regarding clinical studies within OSI
Lifecycle Initiatives by referring such inquiries to the appropriate
OSI MSL.
(c) With respect to Licensed Product, OSI shall ensure that OSI MSLs are
fully trained by OSI, under guidelines agreed upon by the Parties,
to handle unsolicited queries, to respond to unsolicited study
proposals and to discuss clinical studies within OSI Initiatives in
accordance with applicable law and regulations and the following:
(i) Any clinical study proposals received by OSI MSLs that
are directly within OSI Lifecycle Initiatives will be
reviewed by OSI for potential submission to the JCTRC.
15
(ii) OSI will forward clinical study proposals that are not
directly within OSI Lifecycle Initiatives to a Genentech
MSL for follow-up and review by Genentech for potential
submission to the JCTRC.
(iii) Any clinical study proposals directly within OSI
Lifecycle Initiatives that are forwarded to OSI by
Genentech will be reviewed by OSI for potential
submission to the JCTRC.
(d) With respect to Licensed Product, Genentech shall ensure that
Genentech MSLs are fully trained, under its standard guidelines, to
handle unsolicited queries and to respond to unsolicited proposals
in accordance with applicable law and regulations and the following:
(i) Any clinical study proposals received by Genentech MSLs
that are not directly within OSI Lifecycle Initiatives
will be reviewed by Genentech for potential submission
to the JCTRC.
(ii) Genentech will forward clinical study proposals that are
directly within OSI Lifecycle Initiatives to an OSI MSL
for follow-up and review by OSI for potential submission
to the JCTRC.
(iii) Any clinical study proposals forwarded to Genentech by
OSI will be reviewed by Genentech for potential
submission to the JCTRC.
16
(e) Genentech MSLs will be the primary liaisons for Licensed Product
with cooperative groups and professional societies other than the
Cancer Therapy Evaluation Program (CTEP) for which OSI shall be the
primary liaison as set forth in Section 4.3C. Representatives of OSI
shall jointly participate with Genentech in all significant meetings
and telephone calls (for example, those involving or expected to
involve strategy, clinical trial design and/or safety issues) with
cooperative groups and professional societies relating to Licensed
Product. Genentech shall promptly forward to OSI copies of any
significant cooperative group and professional society
correspondence related to Licensed Product sent or received by
Genentech and any research data sent by a cooperative group or
professional society investigator to Genentech.
(f) Subject to Section 5.3A(b), Genentech MSLs will be responsible for
Licensed Product education and disease state education (including,
without limitation, medical and professional disease state
education), and unrestricted Licensed Product medical education
grants.
4.3C CANCER THERAPY EVALUATION PROGRAM (CTEP). OSI shall be the primary
liaison for the Parties' relationship with CTEP with respect to Licensed
Product. Representatives of Genentech shall jointly participate with OSI
in all meetings and significant telephone calls (for example, those
involving or expected to involve strategy, clinical trial design and/or
safety issues) with CTEP relating to Licensed Product. OSI shall promptly
forward to Genentech copies of any CTEP correspondence relating to
17
Licensed Product sent or received by OSI and any research data sent to OSI
by a CTEP investigator.
3. INDS AND DRUG APPROVAL APPLICATIONS.
Section 4.4 is hereby amended by adding a new subsection 4.4(d) to the end
of Section 4.4 as follows:
4.4 (d) Notwithstanding anything to the contrary herein, the Joint Regulatory
Subteam will develop and agree on the strategy and proposed wording for Licensed
Product labels and package inserts, including, without limitation, strategy for
discussions related thereto with regulatory agencies. Decisions on all such
matters will be made by consensus. In the event that the Joint Regulatory
Subteam does not agree on any such matter, the matter in dispute will be
escalated to the Vice President (or Party officer of similar title) in charge of
the regulatory function of each Party, and notwithstanding any other provision
in this Agreement, the final decision on the matter in dispute will be made by
such two Vice Presidents. Members of the Joint Regulatory Subteam from both
Parties will participate in meetings and teleconferences with regulatory
authorities in which such labels or package inserts are discussed or negotiated,
with the number of members attending such meetings to be determined by the Joint
Regulatory Subteam.
4. COMMERCIALIZATION PLAN/ BUDGET
Article 5 of the Collaboration Agreement is hereby amended by deleting the
last two sentences of Section 5.1 and replacing them with the following:
18
"Within thirty (30) days after NDA submission, the Genentech marketing
director for Licensed Product shall present, for discussion, to the OSI
commercial director for Licensed Product the first detailed annual commercial
budget for the commercialization of Licensed Product in the Territory, which
shall include the budget for activities listed in the definition of Marketing
Costs and Sales Costs under Exhibit B of the Agreement (the "Commercialization
Budget"). The Genentech marketing director and OSI commercial director will
conduct a discussion of such draft Commercialization Budget and attempt to reach
consensus on such budget during that discussion. If consensus has been reached
during that discussion that requires revisions to such draft Commercialization
Budget, the Genentech marketing director will prepare a new draft
Commercialization Budget reflecting such consensus. To the extent that consensus
has not been reached during that discussion, the Genentech marketing director
will take into consideration, in good faith, the comments of the OSI commercial
director to the Commercialization Budget. The Genentech marketing director shall
then prepare the final Commercialization plan and Commercialization Budget
("together, the Commercialization Plan") and submit it to the JSC for approval.
The OSI commercial director may attend the JSC meeting to discuss such
Commercialization Budget. Thereafter, Genentech shall update the
Commercialization Plan (including the Commercialization Budget) on a yearly
basis, in accordance with the procedures set forth in the preceding five (5)
sentences and the following two sentences. Genentech shall provide to OSI, on or
about August 15, a preliminary budget. On or about September 15, Genentech shall
provide a draft of the detailed Commercialization Budget to the OSI commercial
director for comment, and thereafter to the JSC for review and approval on or
about October 15. The timing of submission of the Commercialization Budget to
19
the JSC shall be coordinated with the submissions of the development and
manufacturing budgets, whenever possible.
5. CO-PROMOTION.
A. Article 5 of the Collaboration Agreement is hereby amended by inserting
the following new Sections 5.2A and 5.2B immediately after Section 5.2:
"5.2A CO-PROMOTION. OSI shall be entitled to Co-promote (as defined
hereinabove) Licensed Product as follows:
(a) For so long as OSI is Co-promoting Licensed Product, OSI will be
entitled to Co-promote only as specifically described in Sections
5.2A(a) through 5.2A(i). OSI shall assign certain OSI sales force
representative Full Time Equivalents ("FTEs") to Co-promote Licensed
Product (consisting of a percentage of time, determined by OSI, for
each OSI sales force representative to devote to Licensed Product
Co-promotion but in any case such percentage shall not be less that
an average of sixty-five percent (65%) for such OSI sales force
representatives, unless first approved by the JSC, and provided that
such percentage for each such OSI sales force representative shall
not be less than fifty percent (50%)). Such OSI sales force
representatives shall be employees of OSI. OSI sales force
representatives for Licensed Product will call on a subset of the
physicians also called upon by the Genentech Licensed Product sales
force, as provided in Section 5.2A(b) below. Sales territories for
the OSI sales force FTEs for Licensed Product will be
20
determined by OSI, provided that OSI will assign one representative
to each Genentech Licensed Product sales territory, and further
provided that OSI may assign an additional representative to each
such sales territory with approval of Genentech, such approval not
to be unreasonably withheld. OSI sales territories for Licensed
Product need not be identical to the Genentech sales territories for
Licensed Product. It is expressly understood by the Parties that
Genentech sales representatives may also call on physicians in the
OSI sales territories in which OSI's sales representative are
operating.
(b) OSI sales force FTEs for Licensed Product shall call on specific
customer targets, generally defined as potential high volume
oncology/hematology prescribers for Licensed Product (i.e., within
the top three to four deciles of prescribers within Genentech sales
territories, with criteria of such deciles to be identical for the
determination of such OSI and Genentech call targets) ("Physician
Call Targets") in order to increase sales call frequency on such
customer accounts. Genentech shall determine such Physician Call
Targets after discussion at the JCIT and its good faith
consideration of JCIT comments. If OSI provides in good faith a
reasonable reason to decline a Physician Call Target it may do so
and such customer account will be removed from the list of Physician
Call Targets. In such event, then OSI may propose replacements for
such declined Physician Call Targets to the JCIT, which shall then
discuss the proposed replacements. Final decisions for adding such
replacement Physician Call Targets shall be made by Genentech after
good faith consideration of OSI's proposed replacements. Physician
Call Targets will be
21
updated by Genentech, after review and comment by the JCIT and
Genentech's good faith consideration of such JCIT comments and the
needs of the Licensed Product business, provided, however, that
Genentech may change the list of Physician Call Targets no more than
once per calendar year and by not more than 20 percent for each such
change, unless otherwise agreed by the Parties or unless regulatory
approval is obtained to sell a new Licensed Product or to sell an
existing marketed Licensed Product for a new indication.
(c) Genentech shall determine the total number of FTEs which will
comprise the combined OSI/Genentech sales force for Licensed Product
and the ratio of OSI sales force FTEs to Genentech's sales force
FTEs, provided, however, that the OSI sales force FTEs for Licensed
Product shall not be required to be less than 25% of the combined
OSI/Genentech sales force FTEs. Genentech's proposal shall be made
in good faith based upon a sales force sizing analysis, which shall
be conducted by Genentech by **. Such sizing analysis shall be
conducted by Genentech as frequently as Genentech determines in good
faith is needed. Any proposed adjustment to the total number of FTEs
which will comprise the combined OSI/Genentech sales force for
Licensed Product and the ratio of OSI sales force FTEs to
Genentech's sales force FTEs as a result of such sizing analysis
shall be part of, or a modification to, the Commercialization Plan.
(d) Genentech shall have final decision making authority with respect to
overall sales force activities, except as otherwise expressly
provided in this Amendment
--------
** This portion has been redacted pursuant to a confidential treatment request.
22
or Appendix A hereto. Genentech shall coordinate overall sales force
activities through the JCIT (which shall not require JCIT approval,
however), to ensure a consistent and unified voice to the customer,
including plan of action meetings, call reach and frequency goals,
customer targets and messages. Genentech will determine the
execution of sales training of the OSI and Genentech sales force
representatives pertaining to Licensed Product.
(e) Licensed Product shall be the primary detail by the OSI Licensed
Product sales force FTEs calling upon Physician Call Targets. The
sales force representatives for each Party assigned to Licensed
Product hereunder shall not promote a product competitive with
Licensed Product. A competitive product shall mean a product that is
designed to replace a Licensed Product for treatment of an approved
disease indication. A product that can potentially be used in
combination with such Licensed Product, regardless of whether such
combination is approved by regulatory authorities, shall be deemed
not competitive. In any event, competitive products **.
(f) OSI shall report call activity of OSI sales force FTEs for Licensed
Product to Genentech on a **. OSI shall report in a format
compatible with the Genentech call reporting system as of the
Amendment Effective Date, or as otherwise agreed upon by the
Parties.
--------------
** This portion has been redacted pursuant to a confidential treatment request.
23
(g) The components and criteria for sales force bonus remuneration
directly related to Licensed Product shall be aligned for OSI and
Genentech representatives for Licensed Product, through discussion
at the JCIT.
(h) Genentech shall maintain sole responsibility for Licensed Product
sales data collection and reporting, and shall make such sales data
available to OSI on the following basis. Genentech will provide to
OSI daily reports of Licensed Product shipments (quantities),
monthly reports of Licensed Product sales by geography, and such
other sales data mutually agreed upon by the Parties. Such shipment
and sales reports will be for OSI's internal use only and not for
public disclosure.
(i) The sales force budgets allocated for sales territories for OSI and
Genentech representatives shall be aligned, and will be part of the
Commercialization Budget prepared by Genentech and approved by the
JSC. In accordance with Section 5.2 above, OSI shall be responsible,
for **. Genentech will discuss with OSI the projected dollar amounts
of such OSI share of Sales Costs, during Genentech's preparation of
the Commercialization Budget.
"5.2B. TERMINATION OF CO-PROMOTION. (a) If OSI (i) materially breaches
this Amendment and fails to cure such breach within thirty 30 days following
written notice from Genentech or (ii) fails to cure, within thirty (30) days
following written notice from Genentech, circumstances or conditions which have
resulted in a pattern of several similar breaches of this Amendment, regardless
of materiality of the individual breaches (such as a failure on the part of
--------------
** This portion has been redacted pursuant to a confidential treatment request.
24
an OSI sales representative to spend at least 50% of his or her time on Licensed
Product promotion or the failure of an OSI MSL to refer a matter to a Genentech
MSL as required under this Amendment), for which OSI has also received written
notices thereof, Genentech shall have the right to terminate all of OSI's
Co-promotion rights granted under the Agreement by written notice, subject to
the terms of this Section 5.2B The parties acknowledge and agree that because
the materiality of any specific breach must be measured as of the time of the
breach and is dependent on the performance obligations and conditions at such
time, the examples above are for purposes of reference and are not intended to
change the applicable legal principles governing materiality. OSI will have five
(5) days after its receipt of Genentech's notice of termination to notify
Genentech in writing that it will challenge the termination, and OSI may not
challenge such termination if it does not give such notice to Genentech. If OSI
does challenge the termination, then notwithstanding anything to the contrary in
the Agreement, such dispute shall be resolved through the Expedited Arbitration
Procedure set forth in Section 16.4 below. The termination shall be effective on
the later of (A) ninety (90) days after Genentech's notice of termination, if
OSI fails to challenge the claim upon which the termination has been based, or
(B) sixty (60) days after receipt of an arbitration decision affirming the
termination in the Expedited Arbitration Procedure set forth hereinbelow,
regardless of any pending judicial proceedings related thereto. For purposes of
the "Expedited Arbitration Procedure" set forth in Section 16.4 below, Genentech
and OSI agree (1) that the time periods in Section 16.1 of the Agreement will be
reduced by 50%, and (2) if such dispute cannot be resolved during such reduced
time periods, the dispute shall be resolved as set forth in Section 16.4 below.
The Parties acknowledge that time is of the essence in resolving termination of
Co-promotion. Should OSI be found by the arbitrator to have delayed such
procedures for purposes of delaying
25
a decision on the termination, Genentech shall be entitled to reasonable
attorney fees and, at the sole discretion of the arbitrator, exemplary damages
for the delay. The Parties agree that the Expedited Arbitration Procedure set
forth in Section 16.4 is solely for purposes of affirming or reversing the
Co-promotion termination decision and claims for damages directly related to the
breach resulting in such Co-promotion termination and is not the exclusive
remedy for any breaches or damages contemplated herein. The Expedited
Arbitration Procedure does not apply to any other dispute or claim under the
Agreement.
(b) Such termination of OSI's Co-promotion rights shall also be subject to
OSI's ability to assert, under Section 5.2 of the Agreement, its participation
in Co-promotion again pursuant to the terms of this Amendment, such assertion
not to be made until at least two (2) calendar years after the later of: (i) the
effective date of such termination or (ii) the effective date of the final
arbitration decision upholding such termination, described above.
B. Section 5.3 of the Collaboration Agreement is hereby amended by deleting
the second and third sentences of Section 5.3 in their entirety. A new Section
5.3A is hereby added to the Agreement immediately after Section 5.3 as follows:
"Genentech shall have the responsibility for design of Licensed Product
advertising and promotional materials and sales training materials.
Genentech shall file such advertising and promotional materials with the
FDA as required under applicable law. Genentech will be designated by OSI
as the Party responsible for filing such materials to OSI's NDA. Genentech
will provide, in a timely manner, the draft of such advertising and
promotional materials to OSI, and a senior member of OSI's regulatory
function will be
26
able to attend Genentech's internal regulatory review of such materials
through Genentech's Promotional Review Committee ("PRC") meetings (or
similar successor Genentech regulatory committee review if the PRC ceases
to exist). During such meetings the OSI regulatory representative may
raise any reasonable concern of OSI regarding such materials only with
respect to any particular potential violation of a law or FDA regulation
governing pharmaceutical product promotion, which Genentech has not
addressed. Decisions at the PRC meeting regarding any such OSI regulatory
concern will be made by consensus. In the event that such PRC members and
the OSI regulatory representative do not agree on such regulatory
compliance of any such materials, the materials in dispute will be
reviewed and discussed at Genentech's PRC Oversight Committee (or similar
successor Genentech committee if the PRC Oversight Committee ceases to
exist), which will include participation by the OSI Vice President (or
officer of similar title) in charge of OSI's regulatory function. In the
event that the OSI Vice President and the Genentech members of such PRC
Oversight Committee do not agree and resolve such regulatory dispute for
the materials, the materials and regulatory issue will be referred for
resolution to the Vice President (or Party officer of similar title) in
charge of the regulatory function of each Party. If such two Vice
Presidents together cannot resolve such regulatory issue in dispute, then
notwithstanding anything to the contrary in this Agreement, such dispute
will be finally resolved by the Party which will hold the NDA for the
particular Licensed Product for which such materials are prepared."
C. The following sentence is hereby added to the end of Section 5.3 of the
Collaboration Agreement:
27
"For further clarification, each Party will have the responsibility for
execution of and decision making responsibility for, Licensed Product
commercialization activities as specified on Appendix A hereto."
D. Section 5.3 of the Collaboration Agreement is further amended by deleting
the fourth sentence in its entirety and replacing it with the following
sentence: "Except as otherwise expressly provided in this Amendment or in
Appendix A hereto, Genentech shall have the final decision making authority with
respect to commercialization matters."
6. MARKETING ACTIVITIES OF LICENSED PRODUCT.
A. Article 5 of the Collaboration Agreement is hereby amended by inserting
the following new Section 5.3B immediately after Section 5.3:
"5.3B MARKETING ACTIVITIES.
(a) Except as otherwise stated in Appendix A hereto or otherwise expressly
provided in the Agreement, Genentech shall have the sole responsibility
for setting the overall commercial strategy for Licensed Product and for
designing and implementing all marketing activities related to Licensed
Product, including, without limitation, branding, positioning, advertising
and promotional materials (subject to OSI's regulatory review under
Section 5.3), medical and professional disease state education (subject to
Section 5.3B(b) below), Licensed Product public relations (except as
provided in Appendix A hereto or otherwise expressly provided in the
Agreement), relationships with opinion leaders and professional societies,
medical meeting and tradeshow activities (except as set forth in the
following sentence) and Licensed Product market research, except for
28
those activities expressly assigned to OSI in Appendix A hereto or by
Genentech. Notwithstanding the foregoing, OSI shall be entitled to use at
medical meetings and tradeshows specific Licensed Product promotional
materials and exhibit panels that have been previously approved in writing
by Genentech and, with respect to which, OSI has confirmed through the
JCIT that have not been updated. Except for OSI's role in decision making
with respect to regulatory review under Section 5.3A above and as
otherwise provided in Appendix A hereto or otherwise expressly provided in
the Agreement, all final decision making for all Licensed Product
marketing activities shall reside with Genentech. Genentech shall manage
the Commercialization Budget and will also manage all relationships with
vendors for Licensed Product commercial activities.
(b) Notwithstanding Section 4.3B(f) above, either Party shall be entitled
to make unrestricted medical education grants and to conduct continuing
medical education ("CME") accredited medical and professional disease
state education (and continuing education accredited professional disease
state education for nurses and pharmacists) that: (i) are not designed to
provide but may include education on Licensed Product and (ii) are
designed to provide general education in oncology or another general
disease state area, and (iii) are funded from such Party's own budget
(which shall not be subject to any cost sharing under the Agreement). All
unrestricted medical education grants and CME accredited disease state
education shall be made in accordance with applicable laws and regulations
and the PhRMA Code on Interactions with Healthcare Professionals.
B. Article 5 of the Collaboration Agreement is hereby amended by adding a new
Section 5.6 immediately after Section 5.5 as follows:
29
"5.6 USE OF LOGO. All Licensed Product-related materials, including,
without limitation, marketing, promotional, medical and training materials
for Licensed Product and all sponsorships related to Licensed Product for
or on which the names and/or logo of a Party are to be included shall bear
the names and/or logos of both Genentech and OSI, as provided by the
Parties to each other, in comparable prominence (size, emphasis and
position), to the extent permitted under applicable law and regulations.
Use of a Party's name and/or logo for such purposes shall be in accordance
with all requirements of such Party with respect to such use, and neither
Party shall otherwise use the name or logo of the other Party unless
expressly provided in the Agreement or expressly permitted by such Party.
7. EXPEDITED ARBITRATION
Article 16 of the Collaboration Agreement is hereby amended by adding a
new Section 16.4 immediately after Section 16.3 as follows:
"16.4 EXPEDITED ARBITRATION PROCEDURE. In the event of disputes under
Section 5.2B(a) as to which the Expedited Arbitration Procedure herein applies,
Sections 16.2 and 16.3 shall apply, except as expressly set forth below:
(a) The Parties agree that issues under the Expedited Arbitration
Procedure will be determined by one arbitrator. Within ten (10) days after the
commencement of procedures under Section 16.1, the Parties shall attempt to
agree to and rank in order of preference no fewer than three (3) qualified
arbitrators. In the event the Parties cannot agree on such a list within such
30
ten-day period, either Party may request the American Arbitration Association
("AAA") to appoint for purposes of ranking no fewer the three (3) such
arbitrators (including a request that the AAA do so within fifteen (15) days of
such request) and such appointments shall be final and binding on the Parties.
Whether the arbitrators are chosen by the Parties or the AAA is asked to appoint
such arbitrators, (i) all appointees must have at least ten (10) years
experience as an attorney and experience in the pharmaceuticals industry so as
to better understand the legal, business and scientific issues addressed in the
arbitral proceeding, and (ii) the Parties will separately rank the proposed
arbitrators and the average ranking of the Parties will determine the order for
purposes of subsection (b) below (in the event of a tie, the Parties will rank
the tying arbitrators based on random selection).
(b) Upon such initiation, the Parties will jointly contact the first
ranking arbitrator and determine whether that person is available to serve
within the time frame set forth herein. If that person is not available on those
terms, the next ranking arbitrator will be contacted, and so forth down the
ranking. Upon agreement by an arbitrator to take the case, and upon completion
of the procedures set for in Section 16.1 as expedited, the Expedited
Arbitration Process will be deemed commenced ("Commencement"), and the following
sequence of proceedings will occur:
i. Within ** after Commencement, OSI shall serve a brief on Genentech
and the arbitrator setting forth its factual and legal arguments with regard to
the termination dispute and providing all documents it proposes to use at
hearing in support of its position. Within ** after service of OSI's brief,
Genentech shall serve a brief on OSI and the arbitrator setting forth its
factual and legal arguments with regard to the termination dispute and providing
all documents it proposes to use at hearing in support of its position. Within
** after service of Genentech's brief,
--------------
** This portion has been redacted pursuant to a confidential treatment request.
31
the Parties shall request any discovery that it believes is critical to a fair
resolution of the issues in dispute.
ii. Within twenty (20) days after Commencement, the arbitrator shall (1)
grant such discovery as deemed appropriate and require that it be completed
within no more than **; (2) identify the issues that will be subject to a
hearing; and (3) set a date for a hearing as to the pending termination dispute
no more than ten (10) days after the completion of all allowed discovery or
twenty (20) days after the issues are identified in the event no discovery is
allowed. In no event shall the hearing begin any later than two (2) months after
the Commencement.
iii. The arbitrator shall provide a hearing of sufficient length for each
Party to present its case but in no event longer than five (5) days total
duration. At the completion of said hearing the arbitrator may allow
post-hearing briefs to be filed within no more than ten (10) days after the
hearing.
iv. Within ten (10) days after completion of hearing, or within ten (10)
days after the submission of post-hearing briefs, if allowed, the arbitrator
shall render a decision on the termination dispute affirming or reversing the
Co-promotion termination. There shall not be a reasoned decision. In no event
shall the decision be issued any later than three (3) months after Commencement.
8. LEGAL COMPLIANCE
Section 17.2 of the Collaboration Agreement is hereby amended by adding
the following sentence at the end of Section 17.2:
--------------
** This portion has been redacted pursuant to a confidential treatment request.
32
"The Parties shall each reasonably cooperate with the other by providing
information reasonably necessary in order to enable the other Party to meet its
reporting obligations, under applicable law or regulation, to which it may be
subject as a result of its responsibilities under this Agreement."
9. COLLABORATION AGREEMENT.
Except as expressly amended herein, all provisions of the Collaboration
Agreement remain in full force and effect.
10. GOVERNING LAW.
This Amendment shall be governed by, and construed in accordance with, the
laws of the State of New York.
11. COUNTERPARTS.
This Amendment may be executed in two or more counterparts, each of which
shall be deemed an original, but all of which together shall constitute one and
the same instrument.
33
IN WITNESS WHEREOF the Parties have executed this Amendment as of the
Amendment Effective Date by their duly authorized representatives.
OSI PHARMACEUTICALS, INC. GENENTECH, INC.
By: /s/ Xxxxxx X. Xxx Xxxxxxxx By: /s/ Xxxxx X. Xxxxxxxx
-------------------------- ---------------------
Name: Xxxxxx X. Van Nostand Name: Xxxxx X. Xxxxxxxx
Title: Vice President and Chief Title: President, Product
Financial Officer Developement
34
APPENDIX A
**
--------
** This portion has been redacted pursuant to a confidential treatment request.
