EXHIBIT 10.42

 

*** INDICATES MATERIAL THAT WAS OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT WAS
REQUESTED. ALL SUCH OMITTED MATERIAL WAS FILED SEPARATELY WITH THE SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE SECURITIES
EXCHANGE ACT OF 1934, AS AMENDED.

 

EXECUTION VERSION

 

CLINICAL TRIAL COLLABORATION AGREEMENT

This Clinical Trial Collaboration Agreement (this “Agreement”) is made and
entered into effective as of November 21, 2014 (the “Effective Date”) by and
between Five Prime Therapeutics, Inc., a Delaware corporation having a place of
business at 2 Corporate Drive, South San Francisco, California 94080 (“Five
Prime”), and BriMstol-Myers Squibb Company, a Delaware corporation headquartered
at 345 Park Avenue, New York, New York 10154 (“BMS”). Five Prime and BMS may be
referred to herein individually as a “Party,” or collectively as the “Parties.”

RECITALS

WHEREAS, Five Prime and BMS desire to collaborate on one or more clinical trials
of a combination therapy using Five Prime’s humanized monoclonal antibody that
binds CSF1R known as “FPA008” and BMS’s human monoclonal antibody that binds
PD-1 known as “Nivolumab”, certain rights to which are licensed by BMS from, and
shared by BMS with, Ono Pharmaceutical Co. Ltd. (“Ono”).

NOW, THEREFORE, in consideration of the foregoing premises and the promises and
covenants contained herein, the Parties agree as follows:

Article 1

DEFINITIONS

The terms in this Agreement with initial letters capitalized, whether used in
the singular or the plural, shall have the meaning set forth below or, if not
listed below, the meaning designated in places throughout this Agreement.

1.1“Additional Tumor Type” shall mean any Tumor Type (other than the Initial
Tumor Types) that is added to the Development Plan by the JDC subsequent to the
Effective Date.

1.2“Affiliate” shall mean, with respect to a particular Entity, any other Entity
that, directly or indirectly, through one or more intermediaries, controls, is
controlled by or is under common control with such particular Entity. As used in
this section, the term “controls” (with correlative meanings for the terms
“controlled by” or “under common control with”) means (a) that an Entity owns,
directly or indirectly, more than fifty percent (50%) of the voting stock of
another Entity, or (b) that such Entity otherwise has the actual ability to
control and direct the management of the other Entity, whether by contract or
otherwise.

--------------------------------------------------------------------------------

EXECUTION VERSION

 

1.3“Aggregate Safety Information” shall mean, with respect to a Party's Single
Agent Compound, the (a) safety and toxicity information for such Single Agent
Compound that is Combined Therapy Study Data, plus (b) safety and toxicity
information from all other clinical trials of such Single Agent Compound,
whether alone or in combination with another pharmaceutical agent, in each case
including information related to serious adverse events, adverse drug reactions,
adverse events, discontinuations due to adverse events and Grade 3 and Grade 4
laboratory abnormalities.  Aggregate Safety Information shall be provided by a
Party to the other in the same format as is contained in the investigators’
brochures prepared by such Party for its Compound in each country where a
Combined Therapy Trial will be conducted.

1.4“Agreement” shall have the meaning set forth in the preamble to this
Agreement, as it may be amended by the Parties from time to time.

1.5“Applicable Law” shall mean all applicable laws, rules and regulations
(whether federal, state or local) that may be in effect from time to time and
applicable to conduct under this Agreement, including current Good Clinical
Practices (GCP), Good Laboratory Practices (GLP) and Good Manufacturing
Practices (GMP).

1.6“Arbitration Matter” shall mean any disputed matter that relates to or arises
out of the validity, interpretation or construction of, or the compliance with
or breach of, this Agreement; provided that such disputed matter has been
considered, but not resolved, by the Executive Officers as set forth in Section
13.3(a).  For clarity, no JDC Dispute, Publication Dispute, or any matter
requiring agreement of both Parties shall be an Arbitration Matter, provided
that certain JDC Disputes described in Section 2.8 shall be resolved through
baseball arbitration in accordance with Section 13.3(c).

1.7“Bioanalysis Plan” shall mean the bioanalysis plan for any Samples as may be
contemplated by the Development Plan or another subsequent written agreement
between the Parties, as described in Section 8.5.

1.8“BLA” means a Biological License Application (as defined by the FDA) or its
foreign equivalent (or any successor application having substantially the same
function).

1.9“BMS” shall have the meaning set forth in the preamble to this Agreement.

1.10“BMS Compound” shall mean BMS’s proprietary anti-PD-1 monoclonal antibody
known as Nivolumab.

1.11“BMS Indemnitees” shall have the meaning set forth in Section 11.2.

1.12“BMS Independent Patent Rights” shall mean any Patent Rights Controlled by
BMS (or its Affiliates) as of the Effective Date or during the Term through
efforts outside of this Agreement that Cover the use (whether alone or in
combination with other agents), manufacture, formulation or composition of
matter of the BMS Compound.

Page 2 of 84

 

*** INDICATES MATERIAL THAT WAS OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT WAS
REQUESTED. ALL SUCH OMITTED MATERIAL WAS FILED SEPARATELY WITH THE SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE SECURITIES
EXCHANGE ACT OF 1934, AS AMENDED.

--------------------------------------------------------------------------------

EXECUTION VERSION

 

1.13“BMS Regulatory Documentation” shall mean any Regulatory Documentation
related to the BMS Compound that exists as of the Effective Date or that is
created during the Term through efforts outside this Agreement.

1.14“BMS Study Data” shall have the meaning set forth in Section 8.2.

1.15“BMS Study Invention” shall mean any Invention that relates to: (a) the
composition of matter of the BMS Compound (and not the Five Prime Compound); (b)
method of manufacture or formulation of the BMS Compound (and not the Five Prime
Compound) as a single agent; (c) a method of use of the BMS Compound (and not
the Five Prime Compound) as a monotherapy or as used with agents, antibodies or
compounds other than an Invention comprising, whether generically or
specifically, the use of both the BMS Compound (and/or any other antibodies that
are designed to selectively bind to PD-1) and a Five Prime Compound (and/or any
other antibodies that are designed to selectively bind to CSF1R)); or (d)
arising from the development of the Dako Assay.

1.16“BMS Study Patent Rights” shall mean any Patent Rights that are Controlled
by BMS and Cover any BMS Study Invention (and not a Five Prime Study Invention
or Combined Therapy Invention) or BMS Study Data, excluding BMS Independent
Patent Rights and BMS Technology.  For avoidance of doubt, any such Patent
Rights, other than BMS Independent Patent Rights and Five Prime Independent
Patent Rights, that Cover both (x) a BMS Study Invention and (y) any other
Invention are included within the Combined Therapy Patent Rights.

1.17“BMS Technology” shall mean all Technology Controlled by BMS (or its
Affiliates) as of the Effective Date or during the Term through efforts outside
of this Agreement related to the BMS Compound or the Combined Therapy and
necessary for the performance of the Development Plan. For clarity, BMS
Technology does not include (a) Inventions, (b) Study Data, or (c) Combined
Therapy Trial Regulatory Documentation.

1.18“Business Day” shall mean a day other than Saturday, Sunday or any day on
which commercial banks located in both San Francisco, California and New York,
New York are authorized or obligated by Applicable Law to close.

1.19“Change of Control” means with respect to a Party any transaction in which
such Party: (a) sells, conveys or otherwise disposes of all or substantially all
of its assets to a Third Party; or (b)(i) merges, consolidates with, or is
acquired by any other Third Party; or (ii) effects any other transaction or
series of transactions; in each case of clause (i) or (ii), such that the
stockholders of such Party immediately prior thereto, in the aggregate, no
longer own, directly or indirectly, beneficially or legally, more than fifty
percent (50%) of the outstanding voting securities or capital stock of the
surviving Third Party following the closing of such merger, consolidation, other
transaction or series of transactions.

Page 3 of 84

 

*** INDICATES MATERIAL THAT WAS OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT WAS
REQUESTED. ALL SUCH OMITTED MATERIAL WAS FILED SEPARATELY WITH THE SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE SECURITIES
EXCHANGE ACT OF 1934, AS AMENDED.

--------------------------------------------------------------------------------

EXECUTION VERSION

 

1.20“Clinical Hold” shall mean that (i) the FDA has issued an order to a Party
pursuant to 21 CFR §312.42 to delay a proposed clinical investigation or to
suspend an ongoing clinical investigation of the Combined Therapy or such
Party’s Single Agent Compound in the United States or (ii) a Regulatory
Authority other than the FDA has issued an equivalent order to that set forth in
(i) in any other country or group of countries.

1.21“Combined Therapy” shall mean a therapy using the Five Prime Compound and
the BMS Compound in combination as individual formulations, for use in the
Field, with or without another agent.

1.22“Combined Therapy IND” shall have the meaning set forth in Section 2.1(b).

1.23“Combined Therapy Invention(s)” shall mean all Inventions that are not Five
Prime Study Inventions or BMS Study Inventions.  For clarity, Combined Therapy
Inventions include any Invention comprising, whether generically or
specifically, the use of both the BMS Compound (and/or any other antibodies that
are designed to selectively bind to PD-1) and a Five Prime Compound (and/or any
other antibodies that are designed to selectively bind to CSF1R.

1.24“Combined Therapy Patent Right(s)” shall mean any Patent Rights that are
Controlled by either Party that Cover any Combined Therapy Invention or Combined
Therapy Study Data, excluding BMS Independent Patent Rights and Five Prime
Independent Patent Rights.

1.25“Combined Therapy Study Data” shall have the meaning set forth in Section
8.2.

1.26“Combined Therapy Trial” shall have the meaning set forth in Section 2.1(a).

1.27“Combined Therapy Trial Regulatory Documentation” shall mean any Regulatory
Documentation to be submitted for the conduct of the Combined Therapy Trial, but
excluding (a) any Five Prime Regulatory Documentation and (b) any BMS Regulatory
Documentation.

1.28“Commercially Reasonable Efforts” means: (a) the carrying out of a Party’s
obligations or tasks, other than as set forth in clause (b), with a level of
effort and resources consistent with the commercially reasonable practices
normally devoted by a similarly situated company, subject to and in accordance
with the terms and conditions of this Agreement; and (b) where applied to a
Party’s efforts to conduct any Combined Therapy Trial under the Development
Plan, the level of effort and resources normally devoted by such Party to
conduct a clinical trial for a biopharmaceutical product or compound that is
owned by it or to which it has rights, which is of similar market potential,
profit potential or strategic value and at a similar stage in its development or
product life based on conditions then prevailing.

1.29“Confidential Information” shall have the meaning set forth in Section 9.1.

Page 4 of 84

 

*** INDICATES MATERIAL THAT WAS OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT WAS
REQUESTED. ALL SUCH OMITTED MATERIAL WAS FILED SEPARATELY WITH THE SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE SECURITIES
EXCHANGE ACT OF 1934, AS AMENDED.

--------------------------------------------------------------------------------

EXECUTION VERSION

 

1.30“Controlled” shall mean, with respect to particular information or
intellectual property, that the applicable Party owns or has a license to such
information or intellectual property and has the ability to grant a right,
license or sublicense to the other Party as provided for herein without
violating the terms of any agreement or other arrangement with any Third Party.

1.31“Cover” means, with respect to a Patent, that, but for rights granted to a
Person under such Patent, the practice by such Person of an invention described
in such Patent would infringe a Valid Claim included in such Patent, or in the
case of a Patent that is a patent application, would infringe a Valid Claim in
such patent application if it were to issue as a Patent.

1.32“CRO” means any Third Party contract research organization used to conduct a
Combined Therapy Trial, including laboratories and Third Parties used to
maintain the safety database from a Combined Therapy Trial, but, for clarity,
excluding clinical trial sites and any Third Parties who are individuals.

1.33“Dako” means Dako Denmark A/S.

1.34“Database Lock” means, with respect to each Combined Therapy Trial, such
actions as are taken with approval of the JDC to prevent any modification to the
database of Study Data generated in the course of such Combined Therapy Trial.

1.35“Developed Tumor Type” means any Initial Tumor Type or any Additional Tumor
Type.

1.36“Effective Date” shall have the meaning set forth in the preamble to this
Agreement.

1.37“Entity” means a partnership, limited partnership, limited liability
partnership, corporation, limited liability company, business trust, joint stock
company, trust, incorporated association, joint venture or similar entity or
organization.

1.38“Excluded Tumor Type” means a Tumor Type (other than a Developed Tumor Type)
for which a Proposing Party has made a proposal for an Additional Non-Developed
Study pursuant to Section 3.5 and where such Proposing Party has, after
following the procedures for nomination set forth in Section 3.5(a)((i)-(ii)),
initiated the conduct of a clinical trial (in a manner materially consistent
with the protocol synopsis last proposed to the Other Party thereunder) outside
the scope of this Agreement.

1.39“Executive Officers” shall mean the Senior Vice President and Chief Medical
Officer of Five Prime and the Senior Vice President, Global Development &
Medical Affairs of BMS (or their respective designees).

Page 5 of 84

 

*** INDICATES MATERIAL THAT WAS OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT WAS
REQUESTED. ALL SUCH OMITTED MATERIAL WAS FILED SEPARATELY WITH THE SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE SECURITIES
EXCHANGE ACT OF 1934, AS AMENDED.

--------------------------------------------------------------------------------

EXECUTION VERSION

 

1.40“FDA” shall mean the United States Food and Drug Administration, or any
successor agency having the same or similar authority.

1.41“Field” shall mean the treatment, palliation or cure of cancer in humans.

1.42“Five Prime” shall have the meaning set forth in the preamble to this
Agreement.

1.43“Five Prime Compound” shall mean the Five Prime proprietary anti-CSF1R
monoclonal antibody known as FPA008.

1.44“Five Prime Indemnitees” shall have the meaning set forth in Section 11.1.

1.45“Five Prime Independent Patent Rights” shall mean any Patent Rights
Controlled by Five Prime or a Five Prime Affiliate as of the Effective Date or
during the Term through efforts outside of this Agreement that Cover the use
(whether alone or in combination with other agents), manufacture,  formulation,
or composition of matter of the Five Prime Compound.

1.46“Five Prime Regulatory Documentation” shall mean any Regulatory
Documentation related to the Five Prime Compound that exists as of the Effective
Date or that is created during the Term through efforts outside this Agreement.

1.47“Five Prime Study Data” shall have the meaning set forth in Section 8.2.

1.48“Five Prime Study Invention” shall mean any Invention that relates to: (a)
the composition of matter of the Five Prime Compound (and not the BMS Compound);
(b) method of manufacture or formulation of the Five Prime Compound (and not the
BMS Compound) as a single agent; or (c) a method of use of the Five Prime
Compound (and not the BMS Compound) as a monotherapy or as used in combination
with agents, antibodies or compounds other than an Invention comprising, whether
generically or specifically, the use of both the BMS Compound (and/or any other
antibodies that are designed to selectively bind to PD-1) and a Five Prime
Compound (and/or any other antibodies that are designed to selectively bind to
CSF1R)).

1.49“Five Prime Study Patent Rights” shall mean any Patent Rights that are
Controlled by either Party and Cover any Five Prime Study Invention (and not a
BMS Study Invention or the Combined Therapy Invention) or Five Prime Study Data,
excluding Five Prime Independent Patent Rights and Five Prime Technology.  For
avoidance of doubt, any such Patent Rights, other than BMS Independent Patent
Rights and Five Prime Independent Patent Rights, that Cover both (x) a Five
Prime Study Invention and (y) any other Invention are included within the
Combined Therapy Patent Rights.

Page 6 of 84

 

*** INDICATES MATERIAL THAT WAS OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT WAS
REQUESTED. ALL SUCH OMITTED MATERIAL WAS FILED SEPARATELY WITH THE SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE SECURITIES
EXCHANGE ACT OF 1934, AS AMENDED.

--------------------------------------------------------------------------------

EXECUTION VERSION

 

1.50“Five Prime Technology” shall mean all Technology Controlled by Five Prime
or a Five Prime Affiliate as of the Effective Date or during the Term through
efforts outside of this Agreement related to the Five Prime Compound or the
Combined Therapy and necessary for the performance of the Development Plan.  For
clarity, Five Prime Technology does not include (a) Inventions, (b) Study Data,
or (c) Combined Therapy Trial Regulatory Documentation.

1.51“Global Safety Database” shall mean the database containing serious adverse
events, serious adverse drug reactions and pregnancy reports for the Combined
Therapy, and shall be the authoritative data source for regulatory reporting and
responding to regulatory queries.

1.52“Good Clinical Practices” or “GCP” shall mean, as to the United States and
the European Union, applicable good clinical practices as in effect in the
United States and the European Union, respectively, during the Term and, with
respect to any other jurisdiction, clinical practices equivalent to good
clinical practices as then in effect in the United States or the European Union.

1.53“Good Laboratory Practices” or “GLP” shall mean, as to the United States and
the European Union, applicable good laboratory practices as in effect in the
United States and the European Union, respectively, during the Term and, with
respect to any other jurisdiction, laboratory practices equivalent to good
laboratory practices as then in effect in the United States or the European
Union.

1.54“GAAP” means U.S. Generally Accepted Accounting Principles.

1.55“Good Manufacturing Practices” “GMP” shall mean, as to the United States and
the European Union, applicable good manufacturing practices as in effect in the
United States and the European Union, respectively, during the Term and, with
respect to any other jurisdiction, manufacturing practices equivalent to good
manufacturing practices as then in effect in the United States or the European
Union.

1.56“IND” shall mean (a) an Investigational New Drug Application as defined in
the United States Food, Drug and Cosmetic Act, as amended, and regulations
promulgated thereunder, or any successor application or procedure required to
initiate clinical testing of a drug in humans in the United States; (b) a
counterpart of such an Investigational New Drug Application that is required in
any other country before beginning clinical testing of a drug in humans in such
country, including, for clarity, a “Clinical Trial Application” in the European
Union; and (c) all supplements and amendments to any of the foregoing.

1.57“Initial Tumor Types” means non-small cell lung cancer, glioblastoma
multiforme, colorectal cancer, melanoma, head and neck cancer and pancreatic
cancer.

Page 7 of 84

 

*** INDICATES MATERIAL THAT WAS OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT WAS
REQUESTED. ALL SUCH OMITTED MATERIAL WAS FILED SEPARATELY WITH THE SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE SECURITIES
EXCHANGE ACT OF 1934, AS AMENDED.

--------------------------------------------------------------------------------

EXECUTION VERSION

 

1.58“Initial Results Date” shall mean the earlier of (x) the later of the date
that (A) BMS has received notice that subject screening has begun for the third
dose level cohort in the Phase 1a dose escalation portion of the first Combined
Therapy Trial; and (B) the date that BMS has received notice that data from a
dose cohort in the first Combined Therapy Trial show that, after dosing with the
Combined Therapy, ***; and (y) the date the first subject is dosed in the Phase
1b portion of the first Combined Therapy Trial (which shall be subject to mutual
agreement at the JDC).

1.59“Invention” shall mean any invention or Technology, whether or not
patentable, that is made, conceived, or first actually reduced to practice by or
on behalf of a Party, or by or on behalf of the Parties together (including by a
Third Party in the performance of the Combined Therapy Trial), in the
performance of the Development Plan, Statistical Analysis Plan or Bioanalysis
Plan, but excluding any data or Technology pertaining to the Dako Assay or any
Study Data.

1.60“Manufacture” or “Manufacturing” shall mean manufacturing, processing,
formulating, packaging, labeling, holding (including storage), and quality
control testing of a Single Agent Compound or the Combined Therapy, in each case
so as to be suitable for use in the Combined Therapy Trials under Applicable
Law.

1.61“Material Safety Issue” means a Party’s good faith belief that there is an
unacceptable risk for harm in humans based upon: (i) pre-clinical safety data,
including data from animal toxicology studies; or (ii) the observation of
serious adverse effects in humans after the Five Prime Compound or the BMS
Compound, either as a single agent or in combination with another pharmaceutical
agent (including as the Combined Therapy), has been administered to or taken by
humans, such as during the Combined Therapy Trial.

1.62“Ono” shall have the meaning set forth in the recitals of this Agreement.

1.63“Ono-BMS Agreements” means those certain Collaboration Agreements between
BMS and Ono dated as September 20, 2011 and as of July 23, 2014, as amended from
time to time, and agreements between Ono and BMS and their Affiliates relating
thereto that may be in effect from time to time.

1.64“Ono Territory” means Japan, Korea and Taiwan.

1.65“Party” or “Parties” shall have the meaning set forth in the preamble to
this Agreement.

Page 8 of 84

 

*** INDICATES MATERIAL THAT WAS OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT WAS
REQUESTED. ALL SUCH OMITTED MATERIAL WAS FILED SEPARATELY WITH THE SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE SECURITIES
EXCHANGE ACT OF 1934, AS AMENDED.

--------------------------------------------------------------------------------

EXECUTION VERSION

 

1.66“Patent Rights” shall mean any and all (a) United States or foreign patents;
(b) United States or foreign patent applications, including all provisional
applications, substitutions, continuations, continuations-in-part, divisions,
renewals, and all patents granted thereon; (c) United States or foreign
patents-of-addition, reissues, reexaminations (including ex parte
reexaminations, inter partes reviews, inter partes reexaminations, post grant
reviews and supplemental examinations) and extensions or restorations by
existing or future extension or restoration mechanisms, including supplementary
protection certificates, patent term extensions, or the equivalents thereof; and
(d) any other form of government-issued rights substantially similar to any of
the foregoing, and “Patent” shall mean any of the foregoing issued or granted
rights.

1.67“Person” shall mean an individual, unincorporated organization or
association, governmental authority or agency, Entity or other entity not
specifically listed herein.

1.68“Quarter” shall mean the respective periods of three consecutive calendar
months ending on March 31, June 30, September 30 and December 31.

1.69“Regulatory Authority” shall mean the FDA or any other governmental
authority outside the United States (whether national, federal, provincial
and/or local) that is the counterpart to the FDA, including the European
Medicines Agency for the European Union.

1.70“Regulatory Documentation” shall mean, with respect to a product containing
the BMS Compound as monotherapy or the Five Prime Compound as monotherapy, all
submissions to Regulatory Authorities in connection with the development of such
product, including all INDs and amendments thereto, BLAs and amendments thereto,
drug master files, correspondence with regulatory agencies, periodic safety
update reports, adverse event files, complaint files, inspection reports and
manufacturing records, in each case together with all supporting documents
(including documents with respect to clinical data).

1.71“Restricted Combination” means any clinical trial in humans to study the
combination of (x) either (A) an anti-PD-1 antagonist molecule (including
antibodies, peptides and chemical compounds) or (B) an anti-PD-L1 antagonist
molecule (including antibodies, peptides and chemical compounds), together with
(y) an anti-CSF1R antagonist molecule (including antibodies, peptides and
chemical compounds) in a Restricted Tumor Type.

1.72 “Restricted Tumor Type” means:

(a)each Initial Tumor Type for so long as the following criteria are
continuously satisfied during (or prior to) the applicable time period set forth
below:

Page 9 of 84

 

*** INDICATES MATERIAL THAT WAS OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT WAS
REQUESTED. ALL SUCH OMITTED MATERIAL WAS FILED SEPARATELY WITH THE SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE SECURITIES
EXCHANGE ACT OF 1934, AS AMENDED.

--------------------------------------------------------------------------------

EXECUTION VERSION

 

(i)during the period from the Effective Date until the date that is *** after
the Effective Date, (A) the Parties are using Commercially Reasonable Efforts to
develop a protocol for the first planned Combined Therapy Trial for such Tumor
Type, (B) the JDC has not removed such Initial Tumor Type from the Development
Plan and (C) the Parties plan to dose, or have dosed, patients in a Combined
Therapy Trial in such Initial Tumor Type;

(ii)during the period after the date that is *** after the Effective Date until
the date that is *** after the Effective Date, (A) the JDC has approved a
protocol for the first planned Combined Therapy Trial for such Tumor Type, (B)
the JDC has not removed such Initial Tumor Type from the Development Plan and
(C) the Parties plan to dose, or have dosed, patients in a Combined Therapy
Trial in such Initial Tumor Type; and

(iii)during the period after the date that is *** after the date of approval of
the IND for the first planned Combined Therapy Trial with respect to such
Initial Tumor Type, the Parties are conducting an ongoing (as defined below)
Phase 1b, randomized Phase 2 or Phase 3 Combined Therapy Trial in such Initial
Tumor Type;

provided in each case ((i) through (iii) above) such applicable time period
shall be tolled to the extent of any delay in the activities or achievement of
objectives set forth in (i) through (iii) above that is caused by (A) Five
Prime’s failure to use Commercially Reasonable Efforts in the performance and
fulfillment of its activities under this Agreement; or (B) any Regulatory
Authority.

 

(b)any Additional Tumor Type beginning on the date the JDC has approved the
addition of such Additional Tumor Type to the Development Plan (the “Tumor Type
Addition Date” with respect to such Tumor Type) and for so long as the following
criteria are continuously satisfied during (or prior to) the time periods set
forth below:

(i)during the period from the Tumor Type Addition Date until the date that is
*** after the Tumor Type Addition Date, (A) the Parties are using Commercially
Reasonable Efforts to develop a protocol for the first planned Combined Therapy
Trial for such Additional Tumor Type, (B) the JDC has not removed such
Additional Tumor Type from the Development Plan and (C) the Parties plan to
dose, or have dosed, patients in a Combined Therapy Trial in such Additional
Tumor Type;

(ii)during the period after the date that is *** after the Tumor Type Addition
Date for such Additional Tumor Type until the date that is *** after the Tumor
Type Addition Date for such Additional Tumor Type, (A) the JDC has approved a
protocol for the first planned Combined Therapy Trial for such Additional Tumor
Type, (B) the JDC has not removed such Additional Tumor Type from the
Development Plan and (C) the Parties plan to dose, or have dosed, patients in a
Combined Therapy Trial for such Additional Tumor Type; and

Page 10 of 84

 

*** INDICATES MATERIAL THAT WAS OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT WAS
REQUESTED. ALL SUCH OMITTED MATERIAL WAS FILED SEPARATELY WITH THE SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE SECURITIES
EXCHANGE ACT OF 1934, AS AMENDED.

--------------------------------------------------------------------------------

EXECUTION VERSION

 

(iii)during the period after the date that is *** after the date of approval of
the IND for the first planned Combined Therapy Trial with respect to such
Additional Tumor Type, the Parties are conducting an ongoing (as defined below)
Phase 1b, randomized Phase 2 or Phase 3 Combined Therapy Trial in such for such
Additional Tumor Type;

provided in each case ((i) through (iii) above) such applicable time period
shall be tolled to the extent of any delay in the activities or achievement of
objectives set forth in (i) through (iii) above that is caused by (A) Five
Prime’s failure to use Commercially Reasonable Efforts in the performance and
fulfillment of its activities under this Agreement; or (B) any Regulatory
Authority.

 

(c)all other Tumor Types, until such Tumor Type becomes an Excluded Tumor Type
pursuant to Section 1.38.

For purposes of this definition, a Combined Therapy Trial in a Tumor Type will
be deemed “ongoing” from the date patient screening begins in such Combined
Therapy Trial with respect to such Tumor Type until *** after the earlier of (w)
date of availability of *** for the Combined Therapy Trial; (x) *** after the
date *** in such Combined Therapy Trial; and (y) the date enrollment in such
Combined Therapy Trial (or the Tumor Type arm of such Combined Therapy Trial, if
such Combined Therapy Trial has more than one Tumor Type arm) is stopped for
safety, futility or other reasons.  If any Tumor Type ceases to be a Restricted
Tumor Type at any point, then it shall thereafter not qualify as a Restricted
Tumor Type.

1.73“Right of Cross-Reference” shall mean, with regard to a Party, allowing the
applicable Regulatory Authority in a country to have access to relevant
information (by cross-reference, incorporation by reference or otherwise)
contained in Regulatory Documentation (and any data contained therein) filed
with such Regulatory Authority with respect to a Party’s Single Agent Compound
(and, in the case of BMS, the Right to Cross-Reference the Combined Therapy
IND), only to the extent necessary for the conduct of a Combined Therapy Trial
in such country or as otherwise expressly permitted or required under this
Agreement to enable a Party to exercise its rights or perform its obligations
hereunder, and, except as to information contained in the Combined Therapy IND
relating to the Combined Therapy, without the disclosure of such information to
such Party.

1.74“Samples” shall mean biological specimens collected from Combined Therapy
Trial study subjects (including fresh or archived tumor samples, serum,
peripheral blood mononuclear cells, plasma, and whole blood for RNA and DNA
sample isolation).

1.75“Single Agent Compound” or “Compound” shall mean, (a) with respect to Five
Prime, the Five Prime Compound, and (b) with respect to BMS, the BMS Compound.

Page 11 of 84

 

*** INDICATES MATERIAL THAT WAS OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT WAS
REQUESTED. ALL SUCH OMITTED MATERIAL WAS FILED SEPARATELY WITH THE SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE SECURITIES
EXCHANGE ACT OF 1934, AS AMENDED.

--------------------------------------------------------------------------------

EXECUTION VERSION

 

1.76“Statistical Analysis Plan” shall mean the set of analyses of the Study Data
for each Combined Therapy Trial conducted hereunder prepared by Five Prime (in
consultation with BMS) and approved by the JDC in accordance with Section
2.4(d), which shall include safety analyses for the Combined Therapy in each
Combined Therapy Trial.

1.77“Technology” shall mean information, inventions, discoveries, trade secrets,
knowledge, technology, methods, processes, practices, formulae, instructions,
skills, techniques, procedures, experiences, ideas, technical assistance,
designs, drawings, assembly procedures, computer programs, specifications, data
and results not generally known to the public (including biological, chemical,
pharmacological, toxicological, pharmaceutical, physical and analytical,
pre-clinical, clinical, safety, manufacturing and quality control data and
know-how, including study designs and protocols), in all cases, whether or not
patentable, in written, electronic or any other form now known or hereafter
developed, materials, data and results, including Regulatory Documentation.

1.78“Third Party” shall mean any Person other than Five Prime or BMS and their
respective Affiliates.

1.79“Third Party License Payments” shall mean any payments (e.g., upfront
payments, maintenance payments, milestone payments and royalties) due to any
Third Party under license agreements or other written agreements granting rights
to intellectual property owned or controlled by such Third Party to the extent
that such rights are necessary for (i) the making, using or importing of a
Party’s Single Agent Compound for the conduct of the Combined Therapy Trial, or
(ii) the conduct of any Combined Therapy Trial.

1.80“Tumor Type” means any histologically distinct cancer with a particular
organ of origin, which histology and organ of origin shall be determined in
accordance with the Clinical Practice Guidelines in Oncology of the National
Comprehensive Cancer Network. Tumor Types will be deemed the same for purposes
of this Agreement if the subject cancers have the same organ of origin even if
they are, for example, of a different disease stage or different line of therapy
(e.g., well-differentiated and poorly differentiated gastric cancer, 1st line
NSCLC and 2nd line NSCLC), and will be deemed different if the subject cancers
have different organs of origin (e.g., gastric cancer and lung cancer) or
different histology (e.g., NSCLC and SCLC).  Among non-solid tumor cancers,
Tumor Types for leukemia, lymphoma and multiple myeloma, but not their subtypes
or lines of therapy, shall be considered different Tumor Types.

Page 12 of 84

 

*** INDICATES MATERIAL THAT WAS OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT WAS
REQUESTED. ALL SUCH OMITTED MATERIAL WAS FILED SEPARATELY WITH THE SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE SECURITIES
EXCHANGE ACT OF 1934, AS AMENDED.

--------------------------------------------------------------------------------

EXECUTION VERSION

 

1.81 “Valid Claim” means: (i) a claim in an issued Patent that has not: (a)
expired or been canceled; (b) been declared invalid by an unreversed and
unappealable or unappealed decision of a court or other appropriate body of
competent jurisdiction; (c) been admitted to be invalid or unenforceable through
reissue, disclaimer or otherwise; or (d) been abandoned in accordance with or as
permitted by the terms of this Agreement or by written agreement of the Parties;
or (ii) a claim under any application for a Patent, in any case, that has not
been canceled, withdrawn from consideration, finally determined to be
unallowable by the applicable governmental authority or court for whatever
reason (and from which no appeal is or can be taken), or abandoned.

Additional Definitions.  In addition to those terms defined above, definitions
for each of the following terms are found in the body of this Agreement as
indicated below:  

Defined Term

Section

Additional Non-Developed Study

3.5(b)

Alliance Manager

2.7

Breaching Party

12.2(a)

Co-Chair

2.3

Cure Period

12.2(a)

Dako Assay

Exhibit A

Development Plan

2.1

Dispute

13.3(a)

ICF

2.6(a)

Exclusive Collaboration Period

3.5(a)

Final Match Date

3.5(e)

Five Prime CSF1R Program

3.5(d)

Indemnify

11.1

Infringement

6.3(a)

IRBs

9.3(d)

JDC or Joint Development Committee

2.3

JDC Dispute

2.8

Joint Subsequent Study

5.4(b)

Losses

11.1

Non-Breaching Party

12.2(a)

Non-Prosecuting Party

6.1(c)

Officials

10.9

Page 13 of 84

 

*** INDICATES MATERIAL THAT WAS OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT WAS
REQUESTED. ALL SUCH OMITTED MATERIAL WAS FILED SEPARATELY WITH THE SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE SECURITIES
EXCHANGE ACT OF 1934, AS AMENDED.

--------------------------------------------------------------------------------

EXECUTION VERSION

 

Operational Matters

2.6(a)

Other Party

3.5(b); 5.4(b)

Packaging and Labeling Cost

4.2(b)

Parallel Study

3.5(b)

Payment

10.9

Permitted Clinical/Preclinical Research

3.5(a)

Pharmacovigilance Agreement

2.2

POTV

9.6

Proposing Party

3.5(b); 5.4(b)

Proposed Study

3.5(b)

Prosecuting Party

6.1(c)

Protocol

2.1(a)

Publication Dispute

9.5(c)

Quality Agreement

4.3

Results

9.5(b)

Section 4.2(b) Costs

4.2(b)

Site/CRO List

2.6

Study Data

8.1

Subsequent Study

5.4(b)

Subsequent Study Agreement

5.4(b)

Sunshine Laws

9.7

Term

12.1

Third Party Claim

11.1

Third Party Study Costs

7.1

 

Page 14 of 84

 

*** INDICATES MATERIAL THAT WAS OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT WAS
REQUESTED. ALL SUCH OMITTED MATERIAL WAS FILED SEPARATELY WITH THE SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE SECURITIES
EXCHANGE ACT OF 1934, AS AMENDED.

--------------------------------------------------------------------------------

EXECUTION VERSION

 

Article 2

COLLABORATION SCOPE; GOVERNANCE

2.1Scope of Collaboration; Governance of Agreement.

(a)The Parties shall, pursuant to this Agreement, collaborate to conduct the
activities set forth in the development plan agreed by the Parties and disclosed
on the Effective Date, as such plan may be amended by the Parties from time to
time (the “Development Plan”).  Each clinical trial of a Combined Therapy
conducted under the Development Plan (each, a “Combined Therapy Trial”) shall be
conducted in accordance with a protocol (each, a “Protocol”) to be drafted by
Five Prime (in consultation with BMS) and agreed upon by the Parties at a
meeting of the JDC.  Any amendments to the Development Plan will be subject to
agreement of the Parties at a meeting of the JDC or by written agreement
(including by email acknowledgment) of the JDC Co-Chairs without a meeting.

(b)The Combined Therapy Trials shall be conducted under a combination IND, for
which Five Prime will be the sponsor of record (the “Combined Therapy
IND”).  Each Party shall have a beneficial one-half interest in such Combined
Therapy IND; provided, however, that: (i) in no event will either Party be
required to obtain the consent of the other Party to transfer or encumber its
interest in the Combined Therapy IND; provided that the transferee or
encumbrance holder agrees to abide by the terms and conditions of this
Agreement, and provided that any transfer occurs only in connection with, and to
the same transferee of, a transfer of all of a Party’s rights in its Single
Agent Compound, (ii) Five Prime shall be the sole holder of all legal interests
in the Combined Therapy IND, and neither Party shall have any obligation to
share with the other Party any consideration received in connection with the
sale, license or use of its interest in the Combined Therapy IND where permitted
by this Agreement, and (iii) neither Party shall be permitted to grant any Third
Party any Right of Cross-Reference with respect to any portion of the Combined
Therapy IND relating to the other Party’s Single Agent Compound for use as
monotherapy or for use in combination with any other molecules (other than for
use with the BMS Compound, in the case of BMS, or the Five Prime Compound, in
the case of Five Prime, in each case as permitted by this Agreement), except as
required by a governmental authority.  Each Party shall provide a Right of
Cross-Reference to their respective INDs for their respective Single Agent
Compound as necessary to allow the Combined Therapy Trials to be conducted under
the Combined Therapy IND.  For the avoidance of doubt, each Party shall be
responsible for (i) drafting and updating as necessary the investigator’s
brochure for its respective Single Agent Compound, and (ii) filing all necessary
Regulatory Documentation to the existing IND for its respective Single Agent
Compound, including the submission to such existing IND of serious adverse event
and adverse drug reaction cases emerging from any Combined Therapy Trial.

(c)Information to be Provided by Five Prime

Page 15 of 84

 

*** INDICATES MATERIAL THAT WAS OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT WAS
REQUESTED. ALL SUCH OMITTED MATERIAL WAS FILED SEPARATELY WITH THE SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE SECURITIES
EXCHANGE ACT OF 1934, AS AMENDED.

--------------------------------------------------------------------------------

EXECUTION VERSION

 

(i)Five Prime shall provide BMS with the following relating to the Five Prime
Compound: (A) the latest investigator’s brochure (and annual updates), list of
ongoing clinical studies and clinically relevant safety information that emerges
from other clinical studies within *** (or as soon reasonably practicable) after
general distribution of final versions of such documents within Five Prime, in
each case, to the extent any applicable confidentiality obligations relating to
other combination therapy trials involving the Five Prime Compound and a Third
Party’s compound do not prevent Five Prime from sharing such documents with BMS,
(B) reasonably prompt notice of any material safety interactions with any
Regulatory Authority and the substance thereof regarding any clinical trials of
the Five Prime Compound during the Term; (C) a summary of all new clinically
relevant toxicology study data on the Five Prime Compound within *** (or as soon
as reasonably practicable) after generation within Five Prime; (D) Aggregate
Safety Information from all other clinical trials of the Five Prime Compound (if
not provided elsewhere) *** or as otherwise agreed to by the JDC; and (E) such
other safety data as set forth in the Pharmacovigilance Agreement.  BMS shall
use any such data provided pursuant to this Section 2.1(c)(1) solely to evaluate
the safety of (1) the Five Prime Compound for use in the Combined Therapy Trials
and (2) the Combined Therapy.  All such disclosures are Confidential Information
of Five Prime.

(ii)Five Prime shall provide BMS with the following relating to the Combined
Therapy: (A) safety analyses for each Combined Therapy Trial in accordance with
the applicable Statistical Analysis Plan and (B) such other safety data as set
forth in the Pharmacovigilance Agreement.  Each Party shall use any such data
provided pursuant to this Section 2.1(c)(ii) solely to evaluate the safety of
(1) its own Compound for use in the Combined Therapy Trials and the Combined
Therapy and (2) as permitted elsewhere in this Agreement.  All such disclosures
are Confidential Information of both Parties.

(iii)Five Prime shall provide BMS with the following relating to the BMS
Compound: (A) safety analyses for the BMS Compound as monotherapy from each
Combined Therapy Trial in accordance with the applicable Statistical Analysis
Plan and (B) such other safety data as set forth in the Pharmacovigilance
Agreement.  BMS may use such information for any purpose and all such
information and data shall be Confidential Information of BMS.

Page 16 of 84

 

*** INDICATES MATERIAL THAT WAS OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT WAS
REQUESTED. ALL SUCH OMITTED MATERIAL WAS FILED SEPARATELY WITH THE SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE SECURITIES
EXCHANGE ACT OF 1934, AS AMENDED.

--------------------------------------------------------------------------------

EXECUTION VERSION

 

(d)BMS shall provide Five Prime with the following relating to the BMS Compound:
(i) the latest investigator’s brochure (and annual updates), list of ongoing
clinical studies and clinically relevant safety information that emerges from
other clinical studies within *** (or as soon as reasonably practicable) after
general distribution of final versions of such documents within BMS, in each
case, to the extent any applicable confidentiality obligations relating to other
combination therapy trials involving the BMS Compound and a Third Party’s
compound do not prevent BMS from sharing such documents with Five Prime, (ii)
reasonably prompt notice of any material safety interactions with any Regulatory
Authority and the substance thereof regarding any clinical trials of the BMS
Compound during the Term; (iii) a summary of all new clinically relevant
toxicology study data on the BMS Compound within *** (or as soon as reasonably
practicable) after generation within BMS; (iv) Aggregate Safety Information from
all other clinical trials of the BMS Compound (if not provided elsewhere) *** or
as otherwise agreed to by the JDC; and (vi) such other safety data as set forth
in the Pharmacovigilance Agreement.  Five Prime shall use any such data provided
pursuant to this Section 2.1(d) solely to evaluate the safety of (1) the BMS
Compound for use in the Combined Therapy Trials and (2) the Combined
Therapy.  All such disclosures are Confidential Information of BMS.

(e)If further studies, including toxicity studies, are required or suggested by
a Regulatory Authority as a prerequisite for conducting any of the Combined
Therapy Trials, then the Parties agree to hold good faith discussions in a
timely manner to agree upon a protocol for such studies and amend the
Development Plan to include the conduct of such studies; provided that, if the
Parties are unable to agree upon a protocol for such study or if the conduct of
such study shall cause a delay deemed unsatisfactory by either Party, then any
disputed matters precluding agreement shall be referred to the Executive
Officers (or their respective designees) for resolution.  If the Executive
Officers are unable to reach resolution within *** after such referral to them
(and do not mutually agree to an extension of time to arrive at such
resolution), then this Agreement shall automatically terminate following the
conclusion of any then-active Combined Therapy Trial (unless and until the
Protocol for such required/suggested study(ies) is finalized by mutual agreement
prior to the completion of such Combined Therapy Trial) and the provisions of
Section 12.5 shall apply to any such termination.

(f)The Parties may agree to vary the timing and scope of the information to be
provided under Sections 2.1(c) and (d) above in the Pharmacovigilance Agreement.

Page 17 of 84

 

*** INDICATES MATERIAL THAT WAS OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT WAS
REQUESTED. ALL SUCH OMITTED MATERIAL WAS FILED SEPARATELY WITH THE SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE SECURITIES
EXCHANGE ACT OF 1934, AS AMENDED.

--------------------------------------------------------------------------------

EXECUTION VERSION

 

2.2Safety Data Exchange. The Parties shall use diligent efforts to define and
finalize the processes the Parties shall employ to protect patients and promote
their well-being in connection with the use of the Combined Therapy, and to
execute a written pharmacovigilance agreement (the “Pharmacovigilance
Agreement”) within *** after the Effective Date, and prior to the dosing of the
first patient in the first Combined Therapy Trial under the Development
Plan.  Such Pharmacovigilance Agreement shall (a) provide that Five Prime or its
designee shall hold and be responsible for the maintenance of the Global Safety
Database for the Combined Therapy and safety reporting for the Combined Therapy,
and shall lead all pharmacovigilance activities for the Combined Therapy, and
(b) include mutually acceptable guidelines and procedures for the receipt,
investigation, recordation, communication, and exchange (as between the Parties)
of adverse event reports, pregnancy reports, and any other information
concerning the safety of the Combined Therapy. Such guidelines and procedures
shall be in accordance with, and enable the Parties and their Affiliates to
fulfill, local and international regulatory reporting obligations to government
authorities. Furthermore, such agreed procedures shall be consistent with
relevant International Council for Harmonization (ICH) guidelines, except where
said guidelines may conflict with existing local regulatory safety reporting
requirements or Applicable Law, in which case local reporting requirements or
Applicable Law shall prevail. In the event that this Agreement is terminated,
the Parties agree to implement the necessary procedures and practices to ensure
that any outstanding pharmacovigilance reporting obligations are fulfilled.  To
the extent any provision set forth in the Pharmacovigilance Agreement conflicts
with any provision in this Agreement, the provision set forth in the
Pharmacovigilance Agreement shall control to the extent related solely to the
exchange and reporting of safety information associated with use of the products
in the performance of the Development Plan as well as product safety
surveillance, and the provisions of this Agreement shall control with respect to
any other such conflict.

Page 18 of 84

 

*** INDICATES MATERIAL THAT WAS OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT WAS
REQUESTED. ALL SUCH OMITTED MATERIAL WAS FILED SEPARATELY WITH THE SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE SECURITIES
EXCHANGE ACT OF 1934, AS AMENDED.

--------------------------------------------------------------------------------

EXECUTION VERSION

 

2.3Joint Development Committee. Promptly after the Effective Date, the Parties
shall form a Joint Development Committee (the “JDC”).  The JDC shall consist of
*** of representatives from each Party.  Each Party shall be responsible for
determining the qualifications and substitutions of its JDC members. It is
anticipated that each Party’s representatives may include experts in clinical
development, project management, patient safety and regulatory affairs and
CMC.  Each Party may invite representatives of such Party who are not JDC
members to attend JDC meetings, provided that any JDC meeting that includes
representatives of either Party who are not JDC members may, at the request of
any JDC member, include a closed session consisting of only JDC members and
Alliance Managers.  The JDC shall be co-chaired with one chairperson designated
by each Party (each, a “Co-Chair”).  The JDC shall meet at least ***, or at such
other frequency as the JDC agrees (and it may appoint subteams to meet more
frequently), provided that either Party through its Co-Chair may request a
meeting of the JDC at any time upon *** notice to the other Party, with the
understanding that the other Party will use reasonable efforts to comply with
such request but such other Party will not be in breach of this Agreement in the
event that it is unable to comply with such request but is using reasonable
efforts to conduct a JDC meeting as promptly as practicable.  Upon request by
either Party, such meetings will be held by audio or video teleconference;
provided that face-to-face meetings shall occur at least ***, the location of
which shall alternate between South San Francisco, California and Princeton, New
Jersey.  There must be a minimum of *** JDC representatives from each Party at
any meeting of the JDC.  No fewer than *** prior to each meeting, and in any
event as soon as reasonably practicable, each Party shall use good faith efforts
to disclose to the other Party any proposed agenda items together with
appropriate supporting information.  The JDC Co-Chairs shall alternate
responsibility for preparing and circulating definitive minutes of each meeting
of the JDC.  Such minutes shall provide a description, in reasonable detail, of
the discussions at the meeting, a list of material actions and decisions made by
the JDC, a list of action items made by the JDC and a list of material issues
not resolved by the JDC.  The JDC Co-Chair who drafts the minutes shall provide
the other Co-Chair and each Party’s Alliance Managers with the initial draft
meeting minutes, who shall return the draft with any proposed changes, and this
process shall be repeated until a final version of the meeting minutes is agreed
upon and signed (or acknowledged as final via email) by the two Co-Chairs.  The
Parties shall reasonably cooperate to complete and agree upon a final version of
meeting minutes within *** from the date of the relevant meeting.  The final
version of the meeting minutes shall be signed (or acknowledged as final via
email) by the two Co-Chairs, and each Party shall be provided with a copy of the
final meeting minutes for its safekeeping.  A reasonable number of additional
representatives of a Party may attend meetings of the JDC in advisory capacity
with the prior written consent of the other Party.  All representatives to the
JDC or attending JDC meetings shall be subject to confidentiality and nonuse
restrictions at least as restrictive as those set forth herein.

2.4Responsibilities of the Joint Development Committee.  Each Party shall keep
the JDC informed about activities performed by that Party hereunder. The JDC (or
in the absence of a formal JDC meeting the Co-Chairs) shall be responsible for
the following:

Page 19 of 84

 

*** INDICATES MATERIAL THAT WAS OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT WAS
REQUESTED. ALL SUCH OMITTED MATERIAL WAS FILED SEPARATELY WITH THE SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE SECURITIES
EXCHANGE ACT OF 1934, AS AMENDED.

--------------------------------------------------------------------------------

EXECUTION VERSION

 

(a)overseeing the activities of the Parties with respect to the Development
Plan, and providing a forum for the Parties to discuss, monitor and coordinate
all activities and communications under the Development Plan;

(b)approving a budget for activities under the Development Plan, including any
Combined Therapy Trial;

(c)reviewing (i) the progress of activities under the Development Plan, (ii) the
proposed plan for medical monitoring and site audits (with Five Prime to take
comments of the JDC members to such proposed plan into account) and (iii) the
results of such medical monitoring and site audits;

(d)reviewing and approving any Additional Tumor Type pursuant to Section 3.5(b)
and/or reviewing and approving any substitution of any Developed Tumor Type with
an Additional Tumor Type;

(e)reviewing and approving with respect to each Combined Therapy Trial (i) the
applicable Protocol and any proposed amendments thereto and (ii) the applicable
Statistical Analysis Plan, which the JDC shall approve before the date the
Database Lock for such Combined Therapy Trial occurs, and any proposed
amendments thereto;

(f)approving any immunogenicity analysis for each Combined Therapy Trial,
including the Protocol and the Entity selected to conduct the analysis;

(g)approving any Bioanalysis Plan (other than the Dako Assay) not set forth in
the Protocol or on Exhibit A, and any amendments thereto (except those relating
to the Dako Assay);

(h)reviewing proposed communication strategies and communications with any
Regulatory Authority regarding the conduct of the Combined Therapy Trials and
approving such proposed communications and communication strategies;

(i)approving any IND submitted for a Combined Therapy Trial, as well as
reviewing submissions to any such IND in accordance with Article 5;

(j)reviewing any Combined Therapy Trial Regulatory Documentation, or portions
thereof, that relate to the Combined Therapy, in accordance with Article 5;

(k)agreeing on the selection of study sites pursuant to Section 2.6(d),
and  agreeing on any communications to study sites or IRBs relating to patient
safety or early termination/cessation of a Combined Therapy Trial;

Page 20 of 84

 

*** INDICATES MATERIAL THAT WAS OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT WAS
REQUESTED. ALL SUCH OMITTED MATERIAL WAS FILED SEPARATELY WITH THE SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE SECURITIES
EXCHANGE ACT OF 1934, AS AMENDED.

--------------------------------------------------------------------------------

EXECUTION VERSION

 

(l)appointing working teams, including a clinical execution working team, to be
made up of representatives from each Party, that will hold telephone discussions
at an agreed-upon frequency to review clinical development, patient safety and
regulatory issues that arise in the course of the Combined Therapy Trials and
approving the template ICF, template case report form and template clinical site
study agreement to be used in a given Combined Therapy Trial;

(m)determining the quantities of Five Prime Compound and BMS Compound and any
co-medications necessary for the Combined Therapy Trials and coordinating the
supply of such quantities by the appropriate Party in accordance with Article 4;

(n)reviewing and approving, in advance, any additional analyses of, or that
include, the Combined Therapy Study Data proposed by either Party that are not
included in the Statistical Analysis Plan; provided that, for clarity, such
review and approval shall not apply to analyses by a Party of the monotherapy
data for its own Compound from a Combined Therapy Trial;

(o)reviewing and approving use of any Samples in accordance with Section 8.5
that are not described in the Development Plan and ICF, so long as the JDC
remains in force and effect;

(p)reviewing and approving (1) the selection of any CRO and any Third Party
contractor (other than individuals in a Party’s workforce who are engaged on an
independent contractor basis) that has a material role in each Combined Therapy
Trial pursuant to Section 2.6(d) and (2) the terms of the CRO contract or
pharmacovigilance contract (including costs thereof and any impact on the budget
described in clause (b) above) with a Third Party;

(q)reviewing and approving the countries in which each Combined Therapy Trial
will be conducted, as set forth in Section 2.6(d);

(r)approving the final clinical trial report (and/or final statistical analysis
in accordance with the Statistical Analysis Plan) from each Combined Therapy
Trial; and

(s)discussing any other topics or issues relating to the Combined Therapy Trials
that either Party requests that cannot be resolved at the working team level.

For clarity, the JDC shall continue to meet to discuss the matters set forth in
clauses (a)-(r) above with respect to any Parallel Study or Subsequent Study
(other than a Joint Subsequent Study); provided that a Proposing Party with
respect to a Parallel Study shall have final decision-making authority with
respect to any such Parallel Study; provided further that the Proposing Party
with respect to a Subsequent Study shall have final decision-making authority
with respect to any such Subsequent Study.

 

Page 21 of 84

 

*** INDICATES MATERIAL THAT WAS OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT WAS
REQUESTED. ALL SUCH OMITTED MATERIAL WAS FILED SEPARATELY WITH THE SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE SECURITIES
EXCHANGE ACT OF 1934, AS AMENDED.

--------------------------------------------------------------------------------

EXECUTION VERSION

 

2.5Joint Development Committee Authority.

(a)The JDC shall take action by unanimous consent, with each Party having a
single vote, irrespective of the number of its representatives actually in
attendance at a meeting. In the absence of a formal meeting, the Co-Chairs shall
have decision-making authority for the JDC, so long as any decisions are
documented as provided below.

(b)The JDC shall have the right to make only those determinations expressly
enumerated as decisions of the JDC in this Agreement; provided that such
determinations are documented in the written minutes signed (or acknowledged as
final via email) by the JDC Co-Chairs.

(c)Notwithstanding anything to the contrary in this Agreement, the JDC will have
no power to amend this Agreement, the Development Plan, the Pharmacovigilance
Agreement or Quality Agreement without such Party’s prior written consent; in
each case, except by a writing (and that is not the minutes of a meeting) signed
by both Parties.

2.6Five Prime Operational Authority Generally.

(a)Five Prime shall, subject to the oversight and determinations of the JDC as
provided in Sections 2.3 and 2.4, the terms of the applicable Combined Therapy
Protocol, the decisions and guidance of applicable Committee(s), and applicable
terms and conditions of this Agreement: (i) manage and be primarily responsible
for the conduct of the Combined Therapy Trials; (ii) be the sponsor and
regulatory lead with respect to the Combined Therapy Trials; and (iii) as
between the Parties, be the lead with respect to (1) the selection and
management of clinical study sites (including budget negotiations with vendors,
timelines and contingency planning), subject to Sections 5.1(a)(x) and
5.1(b)(vi) with respect to site selection and subject to BMS’s consent as to the
country(ies) where each Combined Therapy Trial will be conducted, (2) conducting
clinical study start-up activities, communicating with and obtaining approval
from institutional review boards and/or ethics committees, as applicable, and
drafting for both Parties’ approval the template informed consent form (“ICF”)
for each Combined Therapy Trial, (3) subject recruitment and retention
activities, (4) ongoing site monitoring and quality assurance audits, (5)
subject to the terms of the Pharmacovigilance Agreement, management of safety
reporting by contract research organizations and clinical study sites, (6)
ongoing medical monitoring, (7) management, monitoring and audits of CROs in
connection with each CRO involved in the conduct of the Combined Therapy Trial,
and (8) inquiries from clinical study subjects ((1)-(8), collectively, the
“Operational Matters”). Five Prime shall use Commercially Reasonable Efforts to
perform such Operational Matters.  The JDC shall set up a mechanism for BMS or a
working team of the JDC to be informed and updated on a timely periodic basis
regarding Operational Matters, so that if BMS has any concerns or disagreements
regarding same, the matter can be escalated to the JDC for review.

Page 22 of 84

 

*** INDICATES MATERIAL THAT WAS OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT WAS
REQUESTED. ALL SUCH OMITTED MATERIAL WAS FILED SEPARATELY WITH THE SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE SECURITIES
EXCHANGE ACT OF 1934, AS AMENDED.

--------------------------------------------------------------------------------

EXECUTION VERSION

 

(b)Each Party shall be responsible for paying the full amount of any Third Party
License Payments that it is obligated to pay pursuant to its agreement with a
Third Party on account of the conduct of any Combined Therapy Trial or pursuant
to Sections 4.1(a) or 4.2(a).

(c)Five Prime shall provide BMS with access to the Study Data in accordance with
Sections 5.1(a)(xvi) and 5.1(a)(xvii).

(d)Five Prime, after discussion with BMS, will create and provide the JDC with a
proposed list of potential clinical trial site(s), CROs and investigators that
may be used to conduct each Combined Therapy Trial, with the final list to be
subject to JDC (or Co-Chair) approval (such JDC-approved list being the
“Site/CRO List”).  The proposed Site/CRO List will be provided to the JDC prior
to Five Prime initiating site selection negotiations or visits (for
sites/investigators) or CRO negotiations (for CROs).  Five Prime shall have the
authority to select the final clinical trial sites, CROs and investigators from
the Site/CRO List. In the event that additional sites need to be added after the
initial list is approved, Five Prime will create a new CRO/Study Site List that
includes the new sites and provide such list to the JDC for approval by the JDC
(or Co-Chairs) per this Section 2.6(d).

2.7Alliance Managers.  Each of the Parties will appoint one representative to
act as its Alliance Manager (each, an “Alliance Manager”).  The role of the
Alliance Manager is to act as a primary point of contact between the Parties to
assure a successful relationship between the Parties.  The Alliance Managers
will attend all meetings of the JDC and support the JDC in the discharge of its
responsibilities.  An Alliance Manager may bring any matter concerning a Party's
performance under this Agreement to the attention of the JDC if the Alliance
Manager reasonably believes that such attention is warranted.  Each Party may
change its designated Alliance Manager from time to time upon written notice to
the other Party.  Any Alliance Manager may designate a substitute to temporarily
perform the functions of such Alliance Manager upon written notice to the other
Party’s Alliance Manager.  Each Alliance Manager will be charged with creating
and maintaining a collaborative work environment within the JDC.  Each Alliance
Manager also will:

(a)be the point of first referral in all matters of dispute resolution in
accordance with Section 13.3;

(b)provide a point of communication both internally within its respective
Party’s organizations and between the Parties regarding the Combined Therapy
Trials;

(c)assist in coordinating any collaborative efforts under this Agreement, if
any, and any external communications; and

(d)take responsibility for ensuring that JDC activities, such as the conduct of
required JDC meetings, occur as set forth in this Agreement and that relevant
action items, if any, resulting from such meetings are appropriately carried out
or otherwise addressed.

Page 23 of 84

 

*** INDICATES MATERIAL THAT WAS OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT WAS
REQUESTED. ALL SUCH OMITTED MATERIAL WAS FILED SEPARATELY WITH THE SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE SECURITIES
EXCHANGE ACT OF 1934, AS AMENDED.

--------------------------------------------------------------------------------

EXECUTION VERSION

 

2.8Dispute Resolution.  The representatives of the JDC shall attempt in good
faith to reach consensus on all matters properly brought before the JDC.  Except
as otherwise provided in this Agreement, if, after a good faith, reasonable and
open discussion at a JDC meeting among the members of the JDC, the JDC is unable
to agree on a matter within the scope of the JDC’s responsibilities as set forth
in Section 2.4, that has been properly before the JDC for a period of at least
*** and that calls for a decision, either Party may refer the dispute (a “JDC
Dispute”) to the Executive Officers for resolution.  If the Executive Officers
are unable to reach a resolution within *** of such referral, then the JDC
Dispute will be referred to the Chief Executive Officer of Five Prime or his or
her designee and the Chief Scientific Officer of BMS or his or her designee for
attempted resolution by good faith negotiations within *** after such referral
is made.  In the event such officers are unable to resolve such JDC Dispute
within such *** period, then:

(a)if such JDC Dispute regards whether or not to commence any Combined Therapy
Trial, then such Combined Therapy Trial shall not proceed absent mutual
agreement of the Parties;

(b)if such JDC Dispute occurs subsequent to the commencement of any Combined
Therapy Trial, and relates to either (1) an amendment requiring mutual agreement
proposed by either Party to an agreed-upon Protocol or protocol synopsis, CRO
Agreement, Bioanalysis Plan (not relating to the Dako Assay) or Statistical
Analysis Plan with respect to such Combined Therapy Trial, or (2) any other
matter relating to the strategy, conduct, rationale, or safety of such Combined
Therapy Trial, there shall be no decision on the matter and the then-existing
terms of the applicable Protocol, protocol synopsis, CRO Agreement, Bioanalysis
Plan or Statistical Analysis Plan shall govern; or

(c)if such JDC Dispute is not addressed by Section 2.8(a) or (b), the dispute
shall be resolved through arbitration as provided for in Section 13.3(c).  

2.9Conduct.  Each Party shall use Commercially Reasonable Efforts to perform and
fulfill its respective activities under this Agreement, and shall do so in
accordance with Applicable Law, including GCP, GLP and GMP.

 

Page 24 of 84

 

*** INDICATES MATERIAL THAT WAS OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT WAS
REQUESTED. ALL SUCH OMITTED MATERIAL WAS FILED SEPARATELY WITH THE SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE SECURITIES
EXCHANGE ACT OF 1934, AS AMENDED.

--------------------------------------------------------------------------------

EXECUTION VERSION

 

Article 3

LICENSE GRANTS

3.1Grant by BMS.  Subject to the terms of this Agreement, BMS hereby grants to
Five Prime a non-exclusive, worldwide (other than within the Ono Territory),
non-transferable, royalty-free license (with the right to sublicense solely
pursuant to the terms of and subject to the limitations of Section 3.3) under
the BMS Independent Patent Rights, BMS Technology, and BMS Regulatory
Documentation to use the BMS Compound, solely to the extent necessary to (1)
discharge Five Prime’s obligations under this Agreement with respect to the
conduct of the Development Plan and (2) conduct any Subsequent Studies.

3.2Grant by Five Prime.  Subject to the terms of this Agreement, Five Prime
hereby grants to BMS a non-exclusive, worldwide, non-transferable, royalty-free
license (with the right to sublicense solely pursuant to the terms of and
subject to the limitations of Section 3.3) under the Five Prime Independent
Patent Rights, Five Prime Technology, and Five Prime Regulatory Documentation to
use the Five Prime Compound, solely to the extent necessary to (1) discharge
BMS’s obligations under this Agreement with respect to the conduct of the
Development Plan and (2) conduct any Subsequent Studies.

3.3Sublicensing.

(a)Subject to Section 3.3(b) and Section 3.3(c), each Party shall have the right
to grant sublicenses under the licenses granted to it under Section 3.1 to
Affiliates and, if required for a Third Party to perform its duties with respect
to the conduct of the Development Plan and any Subsequent Studies (and agreed to
by the other Party, such consent not to be unreasonably withheld), to Third
Parties, solely as necessary to assist a Party in carrying out its
responsibilities with respect to the Development Plan and any Subsequent
Studies.

(b)For the avoidance of doubt, in no event shall BMS (or any of its
sublicensees) have the right to grant Ono or any of Ono’s Affiliates any
sublicense under the license granted to BMS in Section 3.2.

(c)With regard to any such sublicenses permitted and made under this Agreement,
(i) such sublicensees, except Affiliates (so long as they remain Affiliates of a
Party), shall be subject to written agreements that bind such sublicensees to
obligations that are consistent with a Party’s obligations under this Agreement
including confidentiality and non-use provisions no less restrictive than those
set forth in Sections 8.2 and 8.3 and Article 9, and provisions regarding
intellectual property that ensure that the Parties will have the rights provided
under this Agreement to any intellectual property created by such sublicensee,
(ii) each Party shall provide written notice to the other of any such sublicense
(and obtain approval for sublicenses to Third Parties); and (iii) the licensing
Party shall remain liable for all actions of its sublicensees.

Page 25 of 84

 

*** INDICATES MATERIAL THAT WAS OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT WAS
REQUESTED. ALL SUCH OMITTED MATERIAL WAS FILED SEPARATELY WITH THE SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE SECURITIES
EXCHANGE ACT OF 1934, AS AMENDED.

--------------------------------------------------------------------------------

EXECUTION VERSION

 

3.4No Implied Licenses. Except as specifically set forth in this Agreement,
neither Party shall acquire any license or other intellectual property interest,
by implication or otherwise, in any intellectual property of the other Party,
including Confidential Information disclosed to it under this Agreement or under
any Patent Rights Controlled by the other Party or its Affiliates.

3.5Exclusivity.

(a)BMS and Five Prime will be exclusive collaborators with respect to each
Restricted Combination, during the period such combination is a Restricted
Combination (such period for such Restricted Combination, the “Exclusive
Collaboration Period”).  During the Exclusive Collaboration Period for a
Restricted Combination, neither Party will (i) conduct any clinical research in
collaboration with a Third Party with respect to such Restricted Combination
(for clarity, the foregoing shall not prohibit either Party from contracting
with any clinical research organization or other Third Party engaged to
operationalize the conduct of clinical research (e.g., drug depots,
laboratories, drug product labelers, etc.)), or (ii) grant any right to a Third
Party under its IND, BLA or other Regulatory Documentation for its Compound or
under the Combined Therapy Trial IND during the Exclusive Collaboration Period
for such Restricted Combination to enable a Third Party to research or develop
such Restricted Combination, except as required by Applicable Law or as
otherwise expressly permitted by this Agreement. The foregoing shall not (1)
restrict or preclude either Party from conducting any clinical research, or
other activities with respect to such Party’s Compound, including any
combination studies, involving such Party’s Compound, other than those for a
Restricted Combination in collaboration with a Third Party during the Exclusive
Collaboration Period for such Restricted Combination, (2) restrict or preclude
the out-license or sale of a Party’s Compound (provided that the licensee or
acquirer of such Compound, as applicable, agrees to comply with the restrictions
set forth herein), (3) subject to Section 3.5(b), restrict or prohibit either
Party from conducting any Combined Therapy Trial, including in a Restricted
Tumor Type, on its own (including through one or more clinical research
organizations or other Third Parties engaged to operationalize the conduct of
clinical research (e.g., drug depots, laboratories, drug product labelers,
etc.)) or (4) restrict or preclude either Party from performing preclinical
research in a Restricted Tumor Type regarding a Restricted Combination with any
non-profit entities (including university and academic research institutions),
provided that each Party shall share with the other Party any data generated
from any such clinical research under subpart (3) and preclinical research under
subpart (4) during the Exclusive Collaboration Period and, if requested by the
other Party, hereby grants the other Party a nonexclusive license to use such
data and any Technology, inventions and intellectual property rights made by the
granting Party or such non-profit Third Party arising from such clinical
research or preclinical research during the Exclusive Collaboration Period to
the extent relating to a Restricted Combination, subject to any conditions and
restrictions that apply to such granting Party’s use of such data, Technology,
inventions, and intellectual property rights (“Permitted Clinical/Preclinical
Research”).

Page 26 of 84

 

*** INDICATES MATERIAL THAT WAS OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT WAS
REQUESTED. ALL SUCH OMITTED MATERIAL WAS FILED SEPARATELY WITH THE SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE SECURITIES
EXCHANGE ACT OF 1934, AS AMENDED.

--------------------------------------------------------------------------------

EXECUTION VERSION

 

(b)Proposed Additional Non-Developed Studies; Non-Developed Tumor Types

(i)If one Party (for purposes of this Section 3.5(b) only, the “Proposing
Party”) would like to conduct a clinical trial of a Restricted Indication in a
Tumor Type other than a Developed Tumor Type (for purposes of this Section
3.5(b) only, an “Additional Non-Developed Study”), the Proposing Party shall
present the other Party (for purposes of this Section 3.5(b) only, “Other
Party”) with a proposed protocol synopsis, substantially in the format of
Exhibit B, for such Additional Non-Developed Study as a Combined Therapy. The
Other Party shall have the right, which must be exercised (if at all) within ***
after the later of (X) the date on which the Other Party has received the
protocol synopsis and (Y) the Initial Results Date whether to participate in
such Additional Non-Developed Study as a Combined Therapy under this Agreement,
and, upon the election of the Other Party, the JDC shall amend the Development
Plan to include the conduct of such Additional Non-Developed Study as a Combined
Therapy Study, with the protocol (and any changes thereto) for the Proposed
Study to be subject to approval by the JDC, and (for clarity), such Tumor Type
shall become a Developed Tumor Type and a Restricted Tumor Type.

(ii)In the case the Other Party has declined to participate, but where material
changes are made to the protocol for an Additional Non-Developed Study (relative
to the protocol synopsis that was most recently reviewed by the Other Party)
before it is initiated, such protocol and such Additional Non-Developed Study
shall then be subject to a new review by the Other Party as a new proposal for
an Additional Non-Developed Study (with the Other Party having the right to
participate as set forth above, and otherwise review as set forth
below).  Notwithstanding the foregoing, a change to the protocol for an
Additional Non-Developed Study to substitute the Combined Therapy with a
combination of (x) either (A) an anti-PD-1 antagonist molecule (including
antibodies, peptides and chemical compounds) (other than Nivolumab) or (B) an
anti-PD-L1 antagonist molecule (including antibodies, peptides and chemical
compounds), together with (y) an anti-CSF1R antagonist molecule (including
antibodies, peptides and chemical compounds), which combination is not a
Combined Therapy, shall not be deemed a material change to the protocol for such
Additional Non-Developed Study, and any revisions to such protocol necessary
because such combination is not a Combined Therapy (e.g., changes in dosing
frequency, changes in inclusion or exclusion criteria, etc.) shall not be deemed
a material change to the protocol for such Additional Non-Developed Study.

(iii)In the event that, notwithstanding the procedure set forth above in clauses
(i) and (ii) above, the Other Party declines to participate in such Additional
Non-Developed Study, the Proposing Party may proceed with such study and, in
such event, the applicable Tumor Type shall no longer be a Restricted Tumor
Type.

Page 27 of 84

 

*** INDICATES MATERIAL THAT WAS OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT WAS
REQUESTED. ALL SUCH OMITTED MATERIAL WAS FILED SEPARATELY WITH THE SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE SECURITIES
EXCHANGE ACT OF 1934, AS AMENDED.

--------------------------------------------------------------------------------

EXECUTION VERSION

 

(c)Proposed Combined Therapy Studies; Parallel Studies

(i)If one Party (for purposes of this Section 3.5(c) only, the “Proposing
Party”) would like to conduct a clinical trial of the Combined Therapy in a
Developed Tumor Type, outside the scope of the Development Plan (for purposes of
this Section 3.5(c) only, a “Proposed Study”), the Proposing Party shall present
the other Party (for purposes of this Section 3.5(c) only, “Other Party”) with a
proposed protocol synopsis, substantially in the format of Exhibit B, for such
Proposed Study. The Other Party shall have the right, which must be exercised
(if at all) within *** after the later of (X) the date on which the Other Party
has received the protocol synopsis and (Y) the Initial Results Date whether to
participate in such Proposed Study under this Agreement, and, upon the election
of the Other Party, the JDC shall amend the Development Plan to include the
conduct of such Proposed Study as a Combined Therapy Study, with the protocol
(and any changes thereto) for the Proposed Study to be subject to approval by
the JDC.

(ii)In the case the Other Party has declined to participate, but where material
changes are made to the protocol for a Proposed Study (relative to the protocol
synopsis that was most recently reviewed by the Other Party) before it is
initiated, such protocol and Proposed Study shall then be subject to a new
review by the Other Party as a new proposal for a Proposed Study (with the Other
Party having the right to participate as set forth above, and otherwise review
as set forth below).

(iii)In the case where the Other Party does not desire to participate in the
Proposed Study under this Agreement or if the Other Party elects to participate
but both Parties otherwise do not reach agreement with respect to the Protocol
or amendment to the Development Plan with respect to the Proposed Study within
*** following the Other Party’s decision to participate in the Proposed Study
(but no later than *** from the receipt by the Other Party of the proposed
protocol synopsis (as amended pursuant to clause (ii) above, if applicable) for
the Proposed Study), the Proposing Party may proceed with the Proposed Study on
its own (a “Parallel Study”), subject to the conditions set forth below:

(1)such Parallel Study is approved by all applicable IRBs, and is otherwise
conducted in compliance with all Applicable Law;

(2)the Parallel Study shall not proceed if the Other Party has a reasonable
significant safety objection to the conduct of the Parallel Study (unless and
until such safety objection is addressed to the Other Party’s reasonable
satisfaction);

Page 28 of 84

 

*** INDICATES MATERIAL THAT WAS OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT WAS
REQUESTED. ALL SUCH OMITTED MATERIAL WAS FILED SEPARATELY WITH THE SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE SECURITIES
EXCHANGE ACT OF 1934, AS AMENDED.

--------------------------------------------------------------------------------

EXECUTION VERSION

 

(3)unless the Parties agree otherwise in writing, the dosage and dosage regimen
of the Other Party’s Compound to be used in the Parallel Study shall be within
(i) the dosage and regimen in the approved label for such Compound (if such
Compound is approved), (ii) the protocol-determined expansion dosage and regimen
for such Compound in any Phase 1b Combined Therapy Trial, (iii) the final
recommended Phase 2 dosage and regimen used for such Compound in any Phase 2
Combined Therapy Trial, (iv) the dosage and regimen then being used for such
Compound in any on-going Phase 2 or Phase 3 clinical study then being conducted
by the Other Party for its Compound or (v) such other dose and regimen that the
Parties agree on;

(4)for Parallel Studies where Five Prime is the non-participating Other Party,
the total number of subjects to be treated with Five Prime Compound in aggregate
in all such Parallel Studies shall not exceed *** (such that the total amount of
Five Prime Compound to be manufactured by Five Prime for all such Parallel
Studies where Five Prime is the Other Party shall not exceed the amount required
for the treatment of ***). BMS shall reimburse Five Prime for *** (without
profit mark-up and determined in accordance with Five Prime’s customary
practices in accordance with GAAP), ***;

(5)for Parallel Studies where BMS is the non-participating Other Party, the
total number of subjects to be treated with BMS Compound in aggregate in all of
such Parallel Studies shall not exceed *** (such that the total amount of BMS
Compound to be manufactured by BMS for all such Parallel Studies where BMS is
the Other Party shall not exceed the amount required for the treatment of ***).
BMS shall supply the amount required for such Parallel Studies ***;

(6)the Proposing Party hereby grants to the Other Party a non-exclusive,
worldwide, non-transferable, royalty-free license (with the right to sublicense
solely pursuant to the terms of Section 3.3) to use any intellectual property
generated as a result of a Parallel Study solely to the extent such intellectual
property relates to such non-participating Other Party’s Compound;

(7)the Parties will enter into a mutually acceptable written supply agreement (a
“Supply Agreement”) governing forecasting, ordering, procedures for acceptance
and rejection, and other customary provisions for the supply of the Other
Party’s Compound (giving the Parallel Study the same supply priority as the
Other Party’s other clinical studies for the Compound), as well as a mutually
acceptable quality agreement (in each case, the Parties to act in good faith and
reasonably in finalizing such Supply and Quality Agreements);

(8)Exhibit D sets forth a list of possible countries in which Parallel Studies
may be conducted, provided that a Party shall not be obligated to supply its
Compound for use in a country listed on Exhibit D or otherwise if such Party’s
Compound has not previously been made available for clinical or commercial use
in such country;

Page 29 of 84

 

*** INDICATES MATERIAL THAT WAS OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT WAS
REQUESTED. ALL SUCH OMITTED MATERIAL WAS FILED SEPARATELY WITH THE SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE SECURITIES
EXCHANGE ACT OF 1934, AS AMENDED.

--------------------------------------------------------------------------------

EXECUTION VERSION

 

(9)the Proposing Party shall indemnify, defend and hold harmless the Other Party
against all third claims and any resulting liabilities, losses, damages, cost
and expenses incurred by the Other Party arising out of such Third Party claims
based on the use of the Other Party’s Compound in such Parallel Study, except to
the extent attributable to (i) the Other Party’s Compound not meeting applicable
specifications or (ii) the negligence or willful misconduct of the Other Party
(with the indemnification procedures to follow those set forth in Section 11.3);
and

(10)the Other Party hereby grants a non-exclusive, fully-paid (with the Other
Party to be responsible for any Third Party Payments as may be owed in
connection therewith relating to the use of the Other Party’s Compound) license
under the intellectual property controlled by it and its Affiliates to enable
the Proposing Party to conduct the Parallel Study.

For clarity, the Other Party’s Compound would be used in the form supplied and
in no event would the formulation of the Other Party’s Compound be altered,
except for purposes of packaging or labeling same for clinical purposes as long
as regulatory requirements for use of same are met.

Page 30 of 84

 

*** INDICATES MATERIAL THAT WAS OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT WAS
REQUESTED. ALL SUCH OMITTED MATERIAL WAS FILED SEPARATELY WITH THE SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE SECURITIES
EXCHANGE ACT OF 1934, AS AMENDED.

--------------------------------------------------------------------------------

EXECUTION VERSION

 

(iv)Subject to the above, the Other Party would provide the Proposing Party
under the Supply Agreement with sufficient quantities of its Compound (subject
to any forecasting, minimum order quantity, and similar provisions to be set
forth in the Supply Agreement) to conduct the applicable Parallel Study and
promptly provide written authorization to the FDA and other applicable
regulatory authorities of the Proposing Party’s Right to Cross-Reference the
appropriate INDs (including any Combined Therapy Trial IND) and other Regulatory
Documentation of the Other Party for its Single Agent Compound as may be
required for the conduct of the Parallel Study (subject to Applicable
Law).  Subject to Section 3.5(b)(v), the same rights and obligations as set
forth in this Agreement would apply with respect to each Parallel Study with
respect to the use and disclosure of results, sharing of information, safety
data exchange and patent rights in connection with the applicable Parallel Study
(with such rights and obligations to be confirmed/restated in the Supply
Agreement for such Parallel Study).  Accordingly, under the Supply Agreement for
each Parallel Study (but subject to Section 3.5(b)(v)): (i) the Proposing Party
will keep the Other Party informed of the progress of the Parallel Study; (ii)
the Other Party shall be entitled to use the Combination Therapy Data from the
Parallel Study to (1) submit regulatory filings and, subject to Section
3.5(b)(v), seek approvals for its own Compound, either alone or as part of a
combination use therapy with the Proposing Party’s Compound and (2) following
the applicable approval, to promote indications based on, and to disseminate,
the Combination Therapy Data for the benefit of its own Compound, either alone
or as part of the combination therapy with the Proposing Party’s Compound, where
permitted by and in accordance with Applicable Law and (iii) in the case where a
Party submits Combination Therapy Data for regulatory approval for the use of
its Single Agent Compound in combination with the other Party’s Single Agent
Compound (including any reference to the Combination Therapy Data in its label),
then the Party seeking approval shall be granted by the other Party a  Right of
Cross-Reference to the other Party’s Regulatory Documentation (including any
INDs owned or controlled by it for any Combined Therapy Trials) solely to the
extent required for such purpose.

Page 31 of 84

 

*** INDICATES MATERIAL THAT WAS OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT WAS
REQUESTED. ALL SUCH OMITTED MATERIAL WAS FILED SEPARATELY WITH THE SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE SECURITIES
EXCHANGE ACT OF 1934, AS AMENDED.

--------------------------------------------------------------------------------

EXECUTION VERSION

 

(v)In the case where the Other Party for a Parallel Study elects to use the
Combination Therapy Data from such Parallel Study in a regulatory filing in the
FDA or European Medicines Agency (“EMA”) for its Compound for purposes of
obtaining approval of an indication for the Combination Therapy for its
Compound, and the Other Party obtains such regulatory approval for such
Combination Therapy indication (i.e., such approved Combination Therapy
indication is included in the label for its Compound allowing promotion of such
indication), then the Other Party shall thereafter be obligated to pay to the
Proposing Party an amount in aggregate equal to *** of the documented
out-of-pocket payments (other than costs of drug supply) to clinical trial
sites, CROs and other contractors reasonably incurred by the Proposing Party
directly as a result of the conduct of the applicable Parallel Studies in such
indication relied upon for the approval of the new indication (including costs
for project management, document management, monitoring and site management,
specimen management, laboratory, imaging, investigator grants, site costs,
Compound labeling and storage, EDC, IVRS, consultants, contractors for the
testing and screening of patients and lab costs) (for purposes of this Section
3.4(b)(v) only, such aggregate amount, the “Cost Sharing Payment”).  The Other
Party shall pay the Proposing Party *** of the Cost Sharing Payment each year
(without interest) (for purposes of this Section 3.4(b)(v) only, each such
payment, a “Cost Sharing Installment”), such that the Cost Sharing Payment would
be fully paid after *** Cost Sharing Installment payments, with the first
payment to be made within *** after the date Regulatory Approval is obtained by
the Other Party for such Combination Therapy indication and the next *** Cost
Sharing Installments to be made within *** after each of the next *** of such
Regulatory Approval.  For clarity, use of the Combination Therapy Data by the
Other Party in a regulatory filing for safety reporting purposes (or other
purposes that do not permit the promotion of its Compound for the Combination
Therapy indication) shall not trigger any Cost Sharing Payment.

3.6Access to Information. During the period from the Effective Date until the
date which is *** subsequent to the Initial Results Date, BMS shall have the
right to conduct due diligence on the anti-CSF1R antagonist molecules (including
antibodies, peptides and chemical compounds) Controlled by Five Prime, including
the Five Prime Compound (the “Five Prime CSF1R Program”), in order to determine
whether BMS is interested in exclusively licensing the right to develop and
commercialize the Five Prime CSF1R Program.  In furtherance of the foregoing, if
requested by BMS, Five Prime will disclose to BMS all material information and
results relating to the Five Prime CSF1R Program as promptly as practicable
after such information and results become available. Any such information and
results shall be treated as Confidential Information of Five Prime hereunder.

Page 32 of 84

 

*** INDICATES MATERIAL THAT WAS OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT WAS
REQUESTED. ALL SUCH OMITTED MATERIAL WAS FILED SEPARATELY WITH THE SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE SECURITIES
EXCHANGE ACT OF 1934, AS AMENDED.

--------------------------------------------------------------------------------

EXECUTION VERSION

 

3.7Right of First Refusal.  If at any time prior to the date which is ninety
(90) days subsequent to the Initial Results Date (such period, the “ROFR Offer
Period”) Five Prime determines that it wishes to out-license the right to
commercialize the Five Prime CSF1R Program in any territory, Five Prime will
promptly notify BMS in writing of same and the territory as to which the license
will cover, and BMS will have the exclusive right to negotiate for the right to
obtain an exclusive license to develop and commercialize the Five Prime CSF1R
Program in such territory (the “Right of First Refusal”), for a period of three
(3) months thereafter (the “ROFR Negotiation Period”); provided that the ROFR
Negotiation Period shall be extended for any period during which Five Prime has
not complied with Section 3.6 above.  For clarity, if the original notice is not
for a worldwide license, then BMS’s rights shall remain in effect during the
ROFR Offer Period with respect to the territory not covered by the original
notice if Five Prime subsequently determines to expand the territory of the
license. During the ROFR Negotiation Period, if requested by BMS, Five Prime
will disclose to BMS all material information and results relating to the Five
Prime CSF1R Program as promptly as practicable after such information and
results become available. Any such information and results shall be treated as
Confidential Information of Five Prime hereunder.   If BMS and Five Prime do not
reach an agreement for such rights within the ROFR Negotiation Period, then Five
Prime will be free to out-license any and all rights (subject to the terms of
this Agreement) to the Five Prime CSF1R Program in such territory; provided,
however, that Five Prime shall not out-license the right to commercialize the
Five Prime CSF1R Program in such territory (including any modification to such
territory than was previously considered by BMS) to a Third Party within the
ninety (90) day period after the end of the ROFR Offer Period without first
offering to BMS the same terms that such Third Party offered to Five Prime (with
such terms being memorialized in a written term sheet or proposed definitive
agreement) (such terms, “Third Party Terms”) and allowing BMS ten (10) Business
Days to accept such Third Party Terms (the end of such ten (10) Business Day
period, the “Final Match Date”).  In the event that Five Prime does not enter
into a transaction with a Third Party with respect to the rights that are the
subject of such Right of First Refusal within a period of *** subsequent to the
Final Match Date or Five Prime does not receive (or make) an offer to any such
Third Party that would give rise to the existence of any Third Party Terms and
the ROFR Offer Period has not ended, then BMS rights under this Section 3.7
shall be reinstated for the remainder of the ROFR Offer Period, such that in the
event that Five Prime determines that it wishes to out-license the right to
commercialize the Five Prime CSF1R Program in any territory prior to the end of
the ROFR Offer Period, Five Prime will again promptly notify BMS in writing of
same and the territory as to which the license will cover, and BMS’s Right of
First Refusal will once again apply on the same terms and conditions described
above.

Page 33 of 84

 

*** INDICATES MATERIAL THAT WAS OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT WAS
REQUESTED. ALL SUCH OMITTED MATERIAL WAS FILED SEPARATELY WITH THE SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE SECURITIES
EXCHANGE ACT OF 1934, AS AMENDED.

--------------------------------------------------------------------------------

EXECUTION VERSION

 

3.8Right of First Negotiation. During the Term and subsequent to the ROFR Offer
Period, if Five Prime determines that it wishes to out-license the right to
commercialize the Five Prime CSF1R Program in any territory, Five Prime will
inform BMS in writing of same and the territory as to which the license will
cover.  BMS will have an exclusive right to negotiate, for a period of three (3)
months thereafter, to obtain exclusive rights to develop and commercialize the
Five Prime CSF1R Program for such territory (the “ROFN Negotiation
Period”).  During the ROFN Negotiation Period, if requested by BMS, Five Prime
will disclose to BMS all material information and results relating to the Five
Prime CSF1R Program as promptly as practicable after such information and
results become available. Any such information and results shall be treated as
Confidential Information of Five Prime hereunder.  Notwithstanding the
foregoing, the ROFN Negotiation Period shall be extended for any period during
which Five Prime has not complied with its obligations in the preceding
sentence. If the original notice is not for a worldwide license, then BMS’s
rights shall remain in effect with respect to the territory not covered by the
original notice if Five Prime subsequently determines to expand the territory of
the license.  If BMS does not exercise its right of first negotiation for such
rights to the Five Prime CSF1R Program or if an agreement is not reached between
BMS and Five Prime for such rights within the ROFN Negotiation Period, then Five
Prime will be free to out-license any and all rights (subject to the terms of
this Agreement) to the Five Prime CSF1R Program for such territory.

 

Page 34 of 84

 

*** INDICATES MATERIAL THAT WAS OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT WAS
REQUESTED. ALL SUCH OMITTED MATERIAL WAS FILED SEPARATELY WITH THE SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE SECURITIES
EXCHANGE ACT OF 1934, AS AMENDED.

--------------------------------------------------------------------------------

EXECUTION VERSION

 

Article 4

MANUFACTURE AND SUPPLY

4.1Five Prime Compound.

(a)Manufacture and Supply.  Five Prime shall use Commercially Reasonable Efforts
to Manufacture or have Manufactured the Five Prime Compound in drug product or
drug substance form (as necessary) in reasonable quantities and at the points in
time as agreed by the JDC for each Combined Therapy Trial.  The cost of
Manufacture and supply (including shipping, insurance, taxes and duty, if
applicable) of Five Prime Compound for the performance of the Development Plan
(i) with respect to any Phase 1a Combined Therapy Trial, shall be borne solely
by Five Prime, and (ii) with respect to any Phase 1b or later Combined Therapy
Trial, fifty percent (50%) shall be borne by Five Prime and fifty percent (50%)
shall be borne by BMS, and Five Prime shall bear the risk of loss for the Five
Prime Compound.  Five Prime shall also be responsible for the payment of any
Third Party License Payments that may be due exclusively on the supply of Five
Prime Compound for the performance of the Development Plan.  The Five Prime
Compound shall be Manufactured in accordance with Applicable Law (including GMP)
and shall be of similar quality to the Five Prime Compound used by Five Prime
for its other clinical trials of the Five Prime Compound.  Five Prime shall
deliver to BMS certificates of analysis, and any other documents specified in
the Quality Agreement, including such documentation as is necessary to allow BMS
to compare the Five Prime Compound certificate of analysis to the Five Prime
Compound specifications.  The Parties shall cooperate in accordance with
Applicable Law to minimize indirect taxes (such as value added tax, sales tax,
consumption tax and other similar taxes) relating to the Five Prime Compound in
connection with this Agreement.

Page 35 of 84

 

*** INDICATES MATERIAL THAT WAS OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT WAS
REQUESTED. ALL SUCH OMITTED MATERIAL WAS FILED SEPARATELY WITH THE SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE SECURITIES
EXCHANGE ACT OF 1934, AS AMENDED.

--------------------------------------------------------------------------------

EXECUTION VERSION

 

4.2BMS Compound.

(a)Manufacture and Supply.  BMS shall use Commercially Reasonable Efforts to
Manufacture or have Manufactured the BMS Compound in drug substance and/or drug
product form (as necessary) in reasonable quantities and at the points in time
as agreed by the JDC for the performance of the Development Plan or as necessary
for Permitted Clinical/Preclinical Research conducted by Five Prime, and shall
supply such BMS Compound in unmarked vials to Five Prime or its designee for use
in the Combined Therapy Trials or such Permitted Clinical/Preclinical
Research.  Five Prime will package and label the BMS Compound for use in the
Combined Therapy Trials or such Permitted Clinical/Preclinical Research, subject
to Section 4.2(b).  The cost of Manufacture and supply (including shipping,
insurance, taxes and duty, if applicable) of the BMS Compound shall be borne
solely by BMS.  BMS shall bear the risk of loss for the BMS Compound until
delivery of the BMS Compound to Five Prime or its designee.  BMS shall also be
responsible for the payment of any Third Party License Payments that may be due
to Ono or to others exclusively on the supply of BMS Compound hereunder for the
performance of the Development Plan or Five Prime’s performance of Permitted
Clinical/Preclinical Research.  The BMS Compound shall be Manufactured in
accordance with Applicable Law (including GMP) and shall be of similar quality
to the BMS Compound used by BMS for its other clinical trials of the BMS
Compound.  BMS shall deliver certificates of analysis, and any other documents
specified in the Quality Agreement, including such documentation as is necessary
to allow Five Prime to compare the BMS Compound certificate of analysis to the
BMS Compound specifications.  The Parties shall cooperate in accordance with
Applicable Law to minimize indirect taxes (such as value added tax, sales tax,
consumption tax and other similar taxes) relating to the BMS Compound in
connection with this Agreement.  BMS will provide Five Prime with
country-specific customs valuations for the BMS Compound, which Five Prime must
use for deliveries to each country. Five Prime must request these valuations at
least *** prior to each shipment through the BMS’s clinical supply organization.

(b)Packaging Costs for BMS Compound.  Notwithstanding Section 4.2(a), ***
(“Section 4.2(b) Costs”).  For purposes of this Agreement, “Packaging and
Labeling Costs” shall be in accordance with its customary practices in
accordance with GAAP, without labor, profit or mark-up.

(c)Use of BMS Compound Supplied by BMS to Five Prime.  Five Prime shall use the
quantities of BMS Compound supplied to it under this Agreement solely as
necessary for, and in accordance with, this Agreement and the Development Plan,
and for no other purpose, including as a reagent or tool to facilitate its
internal research efforts, for any commercial purpose, or for other research
unrelated to the performance of the Development Plan.  Except as may be required
under this Agreement, the Development Plan or a Bioanalysis Plan, Five Prime
shall not perform, and shall not allow any Third Parties to perform, any
analytical testing of the quantities of BMS Compound supplied to it under this
Agreement.

Page 36 of 84

 

*** INDICATES MATERIAL THAT WAS OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT WAS
REQUESTED. ALL SUCH OMITTED MATERIAL WAS FILED SEPARATELY WITH THE SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE SECURITIES
EXCHANGE ACT OF 1934, AS AMENDED.

--------------------------------------------------------------------------------

EXECUTION VERSION

 

4.3Quality Agreement.  Within *** after the Effective Date, but in no event
later than the date on which the first shipment of bulk BMS Compound is supplied
for use in the performance of the Development Plan, the Parties shall enter into
a quality agreement (the “Quality Agreement”). The Quality Agreement shall
outline the additional roles and responsibilities relative to the quality of BMS
Compound in support of the Combined Therapy Trials. The Quality Agreement shall
include the responsibility for quality elements including, by way of example,
audits & inspections, sub-contractors and suppliers, change control, results
that are outside of specifications, deviations and investigations required to
conduct the activities set forth in the Development Plan.  In addition, the
Quality Agreement shall detail the documentation required for each shipment of
BMS Compound supplied to Five Prime or its designee for use in the performance
of the Development Plan. The Quality Agreement shall also indicate whether any
required transfer from BMS to Five Prime of analytical methods will be necessary
to support identity testing of the BMS Compound by Five Prime.

 

Page 37 of 84

 

*** INDICATES MATERIAL THAT WAS OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT WAS
REQUESTED. ALL SUCH OMITTED MATERIAL WAS FILED SEPARATELY WITH THE SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE SECURITIES
EXCHANGE ACT OF 1934, AS AMENDED.

--------------------------------------------------------------------------------

EXECUTION VERSION

 

Article 5

RESPONSIBILITIES

5.1Specific Responsibilities of the Parties.  Subject to the terms of this
Agreement, each Party shall use Commercially Reasonable Efforts to (i) supply
the quantities of its Compound as needed to conduct the activities set forth in
the Development Plan on a timely basis, and package and deliver same to study
sites, in accordance with the time frame(s) established by the JDC; (ii) to
conduct and complete each Combined Therapy Trial and any Statistical Analysis
Plans and Bioanalysis Plans relating thereto on a timely basis in accordance
with the Development Plan, Bioanalysis Plans, Statistical Analysis Plans and
Third Party agreements relating thereto, and (iii) to timely provide Rights of
Cross-Reference where required by this Agreement.

Each Party shall be responsible for activities assigned to it under the
Development Plan that such Party is not otherwise obligated to perform by this
Agreement, provided that, except as set forth in this Agreement, in no event
shall either Party be obligated to perform any such assigned activities without
its prior written consent.  As of the Effective Date, each Party shall be
responsible for the following activities:

(a)Responsibilities of Five Prime.  Subject to JDC direction and oversight as
provided in Section 2.4, Five Prime shall be responsible for the following
activities, in each case (except as expressly provided in Section 4.1(a) with
respect to the Manufacture and supply of the Five Prime Compound) in accordance
with Section 7.2:

(i)(A) manufacturing, packaging and labeling GMP-grade quantities of the Five
Prime Compound and of the Combined Therapy for use in the performance of the
Development Plan, (B) packaging and labeling the vials provided by BMS of the
BMS Compound for use in the performance of the Development Plan, and (C)
providing the JDC (or a working team designated by the JDC) on a monthly basis
with a clinical drug supply forecast for the BMS Compound and the Five Prime
Compound that includes strategy for drug supply overages, drug supply quantity
and required delivery dates;

(ii)with the cooperation of BMS, compiling, amending and filing all necessary
Combined Therapy Trial Regulatory Documentation with Regulatory Authority(ies),
maintaining and acting as the sponsor of record as provided in 21 CFR 312.50
(and applicable comparable ex-US laws) with responsibility, unless otherwise
delegated in accordance with 21 CFR 312.52 (and applicable comparable ex-US
laws), for each Combined Therapy Trial and making all required submissions to
Regulatory Authorities related thereto on a timely basis;

Page 38 of 84

 

*** INDICATES MATERIAL THAT WAS OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT WAS
REQUESTED. ALL SUCH OMITTED MATERIAL WAS FILED SEPARATELY WITH THE SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE SECURITIES
EXCHANGE ACT OF 1934, AS AMENDED.

--------------------------------------------------------------------------------

EXECUTION VERSION

 

(iii)with BMS cooperation, and subject to the provisions of Section 9.5, listing
any Combined Therapy Trial required to be listed on a public database on
www.clinicaltrials.gov or other public registry in any country in which such
Combined Therapy Trial is being conducted in accordance with Applicable Law and
in accordance with each Party’s internal policies relating to clinical trial
registration;

(iv)providing BMS with reasonable advance notice of scheduled meetings or other
material non-written communications with a Regulatory Authority and the
opportunity to participate in each such meeting or other non-written
communication, to the extent that it relates to the Combined Therapy or the BMS
Compound, and providing BMS with the opportunity to review, provide comments to
Five Prime within *** on, and, if inconsistent with the Development Plan or JDC
guidance, approve all submissions and written correspondence with a Regulatory
Authority that relates to the Combined Therapy or the BMS Compound; provided,
however, in no event shall Five Prime or any Affiliate of Five Prime communicate
with any Regulatory Authority solely with respect to the BMS Compound without
the prior written consent of BMS; and provided further that BMS shall (unless
otherwise permitted by Five Prime) step out of any portions of such meetings or
other non-written communications with a Regulatory Authority that relate solely
to the Five Prime Compound and Five Prime shall (unless otherwise permitted by
BMS) step out of any portions of such meetings or other non-written
communications with a Regulatory Authority that relate solely to the BMS
Compound;

(v)providing to BMS (1) a written summary of meetings or other non-written
communications with a Regulatory Authority within *** of such meeting or
communication, (2) copies of any official correspondence to or from a Regulatory
Authority within *** of receipt or provision, in each case to the extent that it
relates to the Combined Therapy or the BMS Compound (or to the extent the
communication would adversely impact the performance of the Development Plan or
the Five Prime Compound), and (3) copies of all Combined Therapy Trial
Regulatory Documentation that relate to the Combined Therapy or the BMS Compound
within *** of submission to Regulatory Authorities;

(vi)drafting, and, subject to Sections 2.4 and 2.6(d), providing to BMS (through
the JDC or otherwise) for its review, each Protocol and investigator’s brochure
for a Combined Therapy Trial, and the related template ICF, template clinical
site agreement, Bioanalysis Plan (other than the Dako Assay) and Statistical
Analysis Plan, and any amendments to each of the foregoing (provided that BMS
shall provide Five Prime with any comments within *** of the date on which Five
Prime provides the applicable document to BMS);

Page 39 of 84

 

*** INDICATES MATERIAL THAT WAS OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT WAS
REQUESTED. ALL SUCH OMITTED MATERIAL WAS FILED SEPARATELY WITH THE SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE SECURITIES
EXCHANGE ACT OF 1934, AS AMENDED.

--------------------------------------------------------------------------------

EXECUTION VERSION

 

(vii)coordinating with BMS and providing to the JDC (or a subcommittee
designated by the JDC for such purpose) *** in advance of submission, drafts of
(1) submissions to the Combined Therapy IND (if applicable); and (2) Combined
Therapy Trial Regulatory Documentation, or portions thereof, that relate to the
Combined Therapy or the BMS Compound, for JDC review and approval, and providing
BMS with the opportunity to review and comment on all other written
correspondence with a Regulatory Authority relating to the Combined Therapy
Trials, to the extent such correspondence relates to the Combined Therapy, and
to approve such written correspondence to the extent such correspondence relates
to the BMS Compound; provided that BMS shall provide Five Prime with written
notice of any such comments (and, where applicable, approvals or rejections)
within *** of the date on which Five Prime provides the applicable document to
BMS;

(viii)to the extent necessary for the conduct of any Combined Therapy Trial,
providing a Right of Cross-Reference to the relevant Regulatory Documentation
for the Five Prime Compound, provided that, such Right of Cross-Reference shall
terminate upon the expiration or termination of this Agreement for purposes of
conducting any new clinical studies (other than Subsequent Studies and except as
otherwise expressly provided in this Agreement), except that in the case of
termination for a Material Safety Issue pursuant to Section 12.4, such Right of
Cross-Reference shall remain in effect solely (1) to the extent necessary to
permit Five Prime to comply with any outstanding obligations required by a
Regulatory Authority and/or Applicable Law or (2) as necessary to permit Five
Prime to continue to dose subjects enrolled in each Combined Therapy Trial
through completion of the applicable Protocol if required by the applicable
Regulatory Authority(ies) and/or Applicable Laws;

(ix)managing the operations of the Combined Therapy Trials in accordance with
the Development Plan, including overseeing compliance by any CRO with the terms
of its agreement with Five Prime relating to the Combined Therapy Trial;

(x)subject to Sections 2.4 and 2.6(d), providing to BMS a list of all proposed
clinical trial sites and principal investigator(s) for each Combined Therapy
Trial;

(xi)subject to Sections 2.4 and 2.6(d), ensuring that all clinical trial service
agreements and clinical trial site agreements (A) contain intellectual property
provisions that retain each of the Parties’ respective intellectual property
rights in the Five Prime Compound, BMS Compound and Combined Therapy, and (B)
allow for BMS, as well as Five Prime, to the extent permitted by Applicable Law
and any Third Party confidentiality restrictions or obligations, to audit
Combined Therapy Trial study sites for quality assurance and to inspect and copy
all data, documentation and work products relating to the activities performed
by the site, including the medical records of any patient participating in any
clinical study.  This right to inspect and copy all data, documentation, and
work product of a study site may be exercised at any time during the Term, or
such longer period as shall be required by Applicable Law;

(xii)providing BMS with copies of each final site template ICF (if requested by
BMS);

Page 40 of 84

 

*** INDICATES MATERIAL THAT WAS OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT WAS
REQUESTED. ALL SUCH OMITTED MATERIAL WAS FILED SEPARATELY WITH THE SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE SECURITIES
EXCHANGE ACT OF 1934, AS AMENDED.

--------------------------------------------------------------------------------

EXECUTION VERSION

 

(xiii)providing BMS with minutes from any and all external drug safety
monitoring boards for the Combined Therapy Trials, if applicable, within *** (or
as soon as practicable) after receipt by Five Prime;

(xiv)providing BMS with updates on the status of the Combined Therapy Trials at
each teleconference for the clinical execution working group, or upon BMS’s
reasonable request, including information regarding the number and status of
study sites, the number of screened subjects (actual to target), the number of
randomized subjects (actual to target), the number of dosed, ongoing,
discontinued and completed subjects, and any safety updates as contemplated by
the Development Plan, Section 2.1(c), and/or routinely performed by a Party in
its normal course of trial management and reporting;

(xv)subject to the provisions of Section 2.2 and the Pharmacovigilance
Agreement, owning and being responsible for (or appointing a Third Party
reasonably acceptable to BMS to be responsible for) the maintenance of the
Global Safety Database and safety reporting for the Combined Therapy,
collecting, evaluating and reporting serious adverse events, other safety data
and any further pharmacovigilance information from the Combined Therapy Trials,
and providing BMS with the opportunity to participate in and comment on such
pharmacovigilance activities;

(xvi)providing BMS with access to all safety information (including any updates
to the investigator’s brochure for the Five Prime Compound) in the safety
databases through the provision of case safety reports and listings related to
the Combined Therapy or the BMS Compound during the Combined Therapy Trials in
accordance with Section 2.2 and the Pharmacovigilance Agreement;

(xvii)analyzing the Study Data in a timely fashion and providing BMS with access
to the Study Data from the applicable Combined Therapy Trial as follows:

(1)pursuant to an appropriate timetable determined by the JDC: (A) sharing with
BMS for review and comment drafts of interim and/ or final clinical trial
reports (and/or statistical analyses in accordance with the Statistical Analysis
Plan) from each Combined Therapy Trial and (B) providing the raw Study Data in
electronic or other agreed format;

(2)within *** after Database Lock, access to safety databases that will be used
for an interim review by an external consultant (or drug safety monitoring
board, if required) to be agreed upon by the Parties;

(3)within *** after Database Lock, access to case report forms or patient
profiles for all patients in each Combined Therapy Trial;

Page 41 of 84

 

*** INDICATES MATERIAL THAT WAS OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT WAS
REQUESTED. ALL SUCH OMITTED MATERIAL WAS FILED SEPARATELY WITH THE SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE SECURITIES
EXCHANGE ACT OF 1934, AS AMENDED.

--------------------------------------------------------------------------------

EXECUTION VERSION

 

(4)within *** of the creation of a clean database for the Combined Therapy
Trial, copies of the Form 1572s, financial disclosures and other relevant
documents required to meet regulatory requirements related to the Combined
Therapy Trials (including any data or documents that may be required to provide
Aggregate Safety Information to a Regulatory Authority with respect to the BMS
Compound);

(5)within *** of the creation of an electronic clean database for the Combined
Therapy Trial, an electronic copy of the clean database (it being understood
that the form and format of the clean database must be reasonably acceptable to
both Parties and shall be determined by the JDC); and

(6)providing BMS with any programs or SAS codes to be used for the Statistical
Analysis Plan for the Combined Therapy Trial;

(xviii)obtaining supplies of any co-medications, to the extent any such
co-medications are required for use in any Combined Therapy Trial, and providing
to BMS any information related to each Combined Therapy Trial that is provided
to the manufacturer of any co-medication pursuant to Section 9.5 within ***
after the provision of the information to the manufacturer;

(xix)providing BMS with any information regarding the pharmacokinetics, efficacy
and safety of the BMS Compound alone or in combination with the Five Prime
Compound;

(xx)providing for the release by a Qualified Person (as such term will be
defined in the Quality Agreement), or providing the necessary documentation in
support of such quality release, of the Five Prime Compound if such release is
required for any Combined Therapy Trial;

(xxi)performing either directly or through Third Parties the collection of
Samples; and

(xxii)such other responsibilities as may be agreed to by the Parties or
determined by the JDC.

(b)Responsibilities of BMS.  Subject to JDC direction as provided in Section
2.4, BMS shall be responsible for the following activities, subject in each case
(except as expressly provided in Section 4.2(a) with respect to the Manufacture
and supply of the BMS Compound and any Third Party License Payments due Ono) to
sharing by the Parties of the Third Party Study Costs related to such activities
in accordance with Section 7.2:

Page 42 of 84

 

*** INDICATES MATERIAL THAT WAS OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT WAS
REQUESTED. ALL SUCH OMITTED MATERIAL WAS FILED SEPARATELY WITH THE SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE SECURITIES
EXCHANGE ACT OF 1934, AS AMENDED.

--------------------------------------------------------------------------------

EXECUTION VERSION

 

(i)manufacturing and supplying GMP-grade quantities of unlabeled vials of the
BMS Compound, as further described in Article 4, and providing for the release
by a Qualified Person or providing the necessary documentation in support of
quality release, of the BMS Compound if such release is required for the
Combined Therapy Trial;

(ii)promptly reviewing each Protocol, the BMS and Five Prime investigator’s
brochures for each Combined Therapy Trial (as it relates to the BMS Compound and
the Combined Therapy), any template ICF, Bioanalysis Plan and Statistical
Analysis Plan, and any amendments to each of the foregoing (provided that BMS
shall provide Five Prime with written notice of any such comments within *** of
the date on which Five Prime provides the applicable document to BMS;

(iii)to the extent necessary for the conduct of any Combined Therapy Trial,
providing a Right of Cross-Reference to the relevant Regulatory Documentation
for the BMS Compound, provided that, except as provided in Section 3.2, such
Right of Cross-Reference shall terminate upon the expiration or termination of
this Agreement for purposes of conducting any new clinical studies (other than
Subsequent Studies and except as otherwise expressly provided in this
Agreement), except that in the case of termination for a Material Safety Issue
pursuant to Section 12.4, such Right of Cross-Reference shall remain in effect
solely (1) to the extent necessary to permit Five Prime to comply with any
outstanding obligations required by a Regulatory Authority and/or Applicable Law
or (2) as necessary to permit Five Prime to continue to dose subjects enrolled
in each Combined Therapy Trial through completion of the applicable Protocol if
required by the applicable Regulatory Authority(ies) and/or Applicable Laws;

(iv)jointly reviewing, providing comments to Five Prime within *** on, and (if
inconsistent with the Development Plan) approving all Combined Therapy Trial
Regulatory Documentation and providing Five Prime with copies of BMS Regulatory
Documentation, as both Parties agree is necessary or reasonably expected to be
necessary, and is requested by Five Prime, (1) to obtain and maintain the IND
for the Combined Therapy Trials and prepare and file any Combined Therapy Trial
Regulatory Documentation in accordance with this Agreement, or (2) to comply
with Applicable Law with regard to the Five Prime Compound and the Combined
Therapy Trials, which may include information regarding the pharmacokinetics,
efficacy and safety of the BMS Compound alone or in combination with the Five
Prime Compound (provided that BMS shall provide Five Prime with written notice
of any such comments (and, where applicable, approvals or rejections) within ***
of the date on which Five Prime provides the applicable document to BMS;

(v)providing comment and input on the management of each Combined Therapy Trial
pursuant to the Development Plan;

(vi)reviewing and, if applicable, suggesting alternatives to Five Prime’s
proposed list of clinical trial sites and principal investigator(s) for each
Combined Therapy Trial;

Page 43 of 84

 

*** INDICATES MATERIAL THAT WAS OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT WAS
REQUESTED. ALL SUCH OMITTED MATERIAL WAS FILED SEPARATELY WITH THE SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE SECURITIES
EXCHANGE ACT OF 1934, AS AMENDED.

--------------------------------------------------------------------------------

EXECUTION VERSION

 

(vii)providing Five Prime with access to an investigator’s brochure for the BMS
Compound as determined by BMS (and any updates thereto), as well as all relevant
safety information (including any SUSAR reports) for the BMS Compound in
accordance with the Pharmacovigilance Agreement;

(viii)managing and providing funding for the development of the Dako Assay (and,
to the extent required by the Protocol, providing Five Prime with access to the
results of the Dako Assay);

(ix)providing and making available as necessary information and/or persons with
knowledge concerning the BMS Compound to support the performance of the
Development Plan, including any interactions with a Regulatory Authority; and

(x)such other responsibilities as may be agreed to by the Parties or determined
by the JDC.

5.2Documents and Combined Therapy Trial Contracts.

(a)The Parties agree that Five Prime bears primary responsibility for conduct of
each Combined Therapy Trial and the analysis of the Study Data under the
applicable Statistical Analysis Plan.  In consultation with BMS, Five Prime
shall draft the Protocols and Statistical Analysis Plans, and any amendments to
each of the foregoing, and shall provide such documents to BMS for review and
comment pursuant to Section 5.1(a)(vi) and Sections 2.4 and 2.6(d).  BMS shall
have *** from the date on which Five Prime provides the applicable document to
BMS to provide any comments to Five Prime concerning the applicable draft
Protocol or Statistical Analysis Plan, or any amendment to each of the
foregoing.

(b)Subject to Sections 2.4 and 2.6(d), Five Prime shall be responsible for
negotiating and entering into contracts for services relating to the activities
contemplated under the Development Plan, including selecting vendors, approving
contract deliverables and managing contract performance, including site
contracts, obtaining IRB approval for site ICFs, obtaining signed informed
consents, monitoring plans, etc. Five Prime will be responsible for ensuring
that any such contracts allow Five Prime to provide BMS with access to and use
of Study Data, Samples, and other information and documents as required pursuant
to this Agreement (and in no event not less than the same access or use as is
granted Five Prime).

Page 44 of 84

 

*** INDICATES MATERIAL THAT WAS OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT WAS
REQUESTED. ALL SUCH OMITTED MATERIAL WAS FILED SEPARATELY WITH THE SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE SECURITIES
EXCHANGE ACT OF 1934, AS AMENDED.

--------------------------------------------------------------------------------

EXECUTION VERSION

 

5.3Other Clinical Trials.  Except for the Combined Therapy Trials, each clinical
trial for the BMS Compound and the Five Prime Compound, alone or in combination
with other pharmaceutical agents, is independently conducted and shall not be
subject to this Agreement (but without limiting each Party’s obligation to share
relevant safety information as provided in Section 2.1(c), Section 2.1(d) and
Section 2.2 and to comply with its obligations with respect to any Subsequent
Studies).  BMS Compound provided to Five Prime under this Agreement shall not be
used for such other clinical trials.  Except as provided in Section 3.5, nothing
in this Agreement shall preclude either Party from conducting any such other
clinical trials as it may determine in its discretion, so long as it does not
use or rely on the Confidential Information of the other Party in doing so.

5.4Additional Studies. After completion of a Combined Therapy Trial in a
Developed Tumor Type, the Parties agree to discuss in good faith additional
clinical trials (other than clinical trials contemplated by Section 2.1(a)) of
the Combined Therapy in such Developed Tumor Type for a period of up to ***
after such Developed Tumor Type ceases being a Restricted Tumor Type.  If the
Parties jointly agree to conduct any such further clinical trials of such
Combined Therapy in such Developed Tumor Type, such further clinical trials will
be conducted in accordance with a separate agreement between the Parties and a
revised Pharmacovigilance Agreement between the Parties (such revised
Pharmacovigilance Agreement to be executed *** after the execution of the
separate agreement but in any case before the initiation of any further clinical
trials).  For clarity, no Party shall be obligated to collaborate with the other
Party or agree on terms with the other Party with respect to such additional
clinical trials, except as follows:

(a)The provisions as set forth below shall only be in effect (and the Parties
will only have the rights set forth below) with respect to each Subsequent Study
in an indication that was a Developed Tumor Type for which the proposed protocol
synopsis has been submitted by the Proposing Party to the Other Party (as set
forth below) by the earlier of (i) *** after such indication ceased being a
Restricted Tumor Type and (ii) the date that the Compounds of both parties have
been approved in the U.S. and are commercially available for purchase (such
earlier date, the “Subsequent Study Request Deadline”); provided that the
proposed Subsequent Study must be commenced (first patient first visit) within
*** of such protocol synopsis being provided to the Other Party; provided
further that, in the event of termination of this Agreement, the provisions as
set forth below shall only be in effect for a Proposing Party (and the Proposing
Party will only have the rights set forth below) to the extent that Section 12.5
provides that the Proposing Party’s license to conduct Subsequent Studies under
Section 3.1 or Section 3.2 (as applicable) survives such termination of this
Agreement.

Page 45 of 84

 

*** INDICATES MATERIAL THAT WAS OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT WAS
REQUESTED. ALL SUCH OMITTED MATERIAL WAS FILED SEPARATELY WITH THE SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE SECURITIES
EXCHANGE ACT OF 1934, AS AMENDED.

--------------------------------------------------------------------------------

EXECUTION VERSION

 

(b)If one Party (for purposes of this Section 5.4 only, the “Proposing Party”)
would like to conduct one or more clinical or required non-clinical studies of
the use of the Combined Therapy in a Developed Tumor Type (each study being a
“Subsequent Study”), the Proposing Party shall provide the other Party (for
purposes of this Section 5.4 only, the “Other Party”) with a proposed protocol
synopsis for such proposed Subsequent Study and the opportunity to participate
in such Subsequent Study by the Subsequent Study Request Deadline. The Other
Party shall have the right, which must be exercised (if at all) within *** after
receipt of the protocol synopsis, to co-participate in and co-fund the proposed
Subsequent Study under the same terms and conditions as the Agreement and, upon
the election of the Other Party, the Parties shall enter into an agreement for
the conduct of such Subsequent Study having substantially the same terms and
conditions as this Agreement (the “Subsequent Study Agreement”), with the
protocol (and any changes thereto) for the Subsequent Study to be subject to
agreement of both parties and with the Proposing Party to be the sponsor of and
primarily be responsible for conducting the Subsequent Study (i.e., as Five
Prime is doing for the Combined Therapy Trials under the Development Plan).  Any
such Subsequent Study that the Parties co-participate in and co-fund is referred
to in this Agreement as a “Joint Subsequent Study.”

(c)In the case the Other Party has declined to participate, but where material
changes are made to the protocol for a proposed Subsequent Study (relative to
the protocol synopsis that was most recently reviewed by the Other Party) before
it is initiated, such protocol and Subsequent Study shall then be subject to a
new review by the Other Party as a new proposal for a Subsequent Study (with the
Other Party having the right to co-participate and co-fund set forth above, and
otherwise review as set forth below).

(d)In the case where the Other Party does not desire to co-participate and
co-fund the proposed Subsequent Study under a Subsequent Study Agreement or, if
the Other Party elected to participate but both Parties otherwise do not reach
agreement with respect to the Protocol or Subsequent Study Agreement within ***
following the Other Party’s decision to participate in the proposed Subsequent
Study (but no later than *** from the receipt by the Other Party of the proposed
protocol synopsis (as amended pursuant to clause (c) above, if applicable) for
the proposed Subsequent Study), the Proposing Party may proceed with the
Subsequent Study, subject to the following conditions:

(i)such Subsequent Study is approved by all applicable IRBs, and is otherwise
conducted in compliance with all Applicable Law;

(ii)the Subsequent Study shall not proceed if the Other Party has a reasonable
significant safety objection to the conduct of the Subsequent Study (unless and
until such safety objection is addressed to the Other Party’s reasonable
satisfaction);

Page 46 of 84

 

*** INDICATES MATERIAL THAT WAS OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT WAS
REQUESTED. ALL SUCH OMITTED MATERIAL WAS FILED SEPARATELY WITH THE SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE SECURITIES
EXCHANGE ACT OF 1934, AS AMENDED.

--------------------------------------------------------------------------------

EXECUTION VERSION

 

(iii)unless the Parties agree otherwise in writing, the dosage and dosage
regimen of the Other Party’s Compound to be used in the Subsequent Study shall
be within (A) the dosage and regimen in the approved label for such Compound (if
such Compound is approved), (B) the protocol-determined expansion dosage and
regimen for such Compound in any Phase 1b Combined Therapy Trial, (C) the final
recommended Phase 2 dosage and regimen used for such Compound in any Phase 2
Combined Therapy Trial, (D) the dosage and regimen then being used for such
Compound in any on-going Phase 2 or Phase 3 clinical study then being conducted
by the Other Party for its Compound or (E) such other dose and regimen that the
Parties agree on;

(iv)for the Subsequent Studies where Five Prime is the non-participating Other
Party, the total number of subjects to be treated with Five Prime Compound in
aggregate in all such Subsequent Studies shall not exceed *** (such that the
total amount of Five Prime Compound to be manufactured by Five Prime for all
such Subsequent Studies where Five Prime is the Other Party shall not exceed the
amount required for the treatment of ***). BMS shall reimburse Five Prime for
*** (without profit mark-up and determined in accordance with Five Prime’s
customary practices in accordance with GAAP), ***;

(v)for the Subsequent Studies where BMS is the non-participating Other Party,
the total number of subjects to be treated with BMS Compound in aggregate in all
of such Subsequent Studies shall not exceed *** (such that the total amount of
BMS Compound to be manufactured by BMS for all such Subsequent Studies where BMS
is the Other Party shall not exceed the amount required for the treatment of
***). BMS shall supply the amount required for such Subsequent Studies ***;

(vi)the Proposing Party hereby grants to the Other Party a non-exclusive,
worldwide, non-transferable, royalty-free license (with the right to sublicense
solely pursuant to the terms of Section 3.3) to use any intellectual property
generated as a result of a Subsequent Study solely to the extent such
intellectual property relates to such non-participating Other Party’s Compound;

(vii)the Parties will enter into a mutually acceptable written Supply Agreement
for the supply of the Other Party’s Compound (giving the Subsequent Study the
same supply priority as the Other Party’s other clinical studies for the
Compound), as well as a mutually acceptable quality agreement (in each case, the
Parties to act in good faith and reasonably in finalizing such Supply and
Quality Agreements);

(viii)Exhibit D sets forth a list of possible countries in which the Subsequent
Studies may be conducted, provided that a Party shall not be obligated to supply
its Compound for use in a country listed on Exhibit D or otherwise if such
Party’s Compound has not previously been made available for clinical or
commercial use in such country;

Page 47 of 84

 

*** INDICATES MATERIAL THAT WAS OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT WAS
REQUESTED. ALL SUCH OMITTED MATERIAL WAS FILED SEPARATELY WITH THE SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE SECURITIES
EXCHANGE ACT OF 1934, AS AMENDED.

--------------------------------------------------------------------------------

EXECUTION VERSION

 

(ix)the Proposing Party shall indemnify, defend and hold harmless the Other
Party against all third claims and any resulting liabilities, losses, damages,
cost and expenses incurred by the Other Party arising out of such Third Party
claims based on the use of the Other Party’s Compound in such Subsequent Study,
except to the extent attributable to (i) the Other Party’s Compound not meeting
applicable specifications or (ii) the negligence or willful misconduct of the
Other Party (with the indemnification procedures to follow those set forth in
Section 11.3); and

(x)the Other Party hereby grants a non-exclusive, fully-paid (with the Other
Party to be responsible for any Third Party Payments as may be owed in
connection therewith relating to the use of the Other Party’s Compound) license
under the intellectual property controlled by it and its Affiliates to enable
the Proposing Party to conduct the Subsequent Study.

For clarity, the Other Party’s Compound would be used in the form supplied and
in no event would the formulation of the Other Party’s Compound be altered,
except for purposes of packaging or labeling same for clinical purposes as long
as regulatory requirements for use of same are met.

Page 48 of 84

 

*** INDICATES MATERIAL THAT WAS OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT WAS
REQUESTED. ALL SUCH OMITTED MATERIAL WAS FILED SEPARATELY WITH THE SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE SECURITIES
EXCHANGE ACT OF 1934, AS AMENDED.

--------------------------------------------------------------------------------

EXECUTION VERSION

 

(e)Subject to the above, the Other Party would provide the Proposing Party under
the Supply Agreement with sufficient quantities of its Compound (subject to any
forecasting, minimum order quantity, and similar provisions to be set forth in
the Supply Agreement) to conduct the applicable Subsequent Study and promptly
provide written authorization to the FDA and other applicable regulatory
authorities of the Proposing Party’s Right to Cross-Reference the appropriate
INDs (including any Combined Therapy Trial IND) and other Regulatory
Documentation of the Other Party for its Single Agent Compound as may be
required for the conduct of the Subsequent Study (subject to Applicable
Law).  Subject to Section 5.4(f), the same rights and obligations as set forth
in the Agreement would apply with respect to each Subsequent Study with respect
to the use and disclosure of results, sharing of information, safety data
exchange and patent rights in connection with the applicable Subsequent Study
(with such rights and obligations to be confirmed/restated in the Supply
Agreement for such Subsequent Study).  Accordingly, under the Supply Agreement
for each Subsequent Study (but subject to Section 5.4(f)): (i) the Proposing
Party will keep the Other Party informed of the progress of the Subsequent
Study; (ii) the Other Party shall be entitled to use the Combination Therapy
Data from the Subsequent Study to (1) submit regulatory filings and, subject to
Section 5.4(f), seek approvals for its own Compound, either alone or as part of
a combination use therapy with the Proposing Party’s Compound and (2) following
the applicable approval, to promote indications based on, and to disseminate,
the Combination Therapy Data for the benefit of its own Compound, either alone
or as part of the combination therapy with the Proposing Party’s Compound, where
permitted by and in accordance with Applicable Law and (iii) in the case where a
Party submits Combination Therapy Data for regulatory approval for the use of
its Single Agent Compound in combination with the other Party’s Single Agent
Compound (including any reference to the Combination Therapy Data in its label),
then the Party seeking approval shall be granted by the other Party a  Right of
Cross-Reference to the Other Party’s Regulatory Documentation (including any
INDs owned or controlled by it for any Combined Therapy Trials) solely to the
extent required for such purpose.

Page 49 of 84

 

*** INDICATES MATERIAL THAT WAS OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT WAS
REQUESTED. ALL SUCH OMITTED MATERIAL WAS FILED SEPARATELY WITH THE SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE SECURITIES
EXCHANGE ACT OF 1934, AS AMENDED.

--------------------------------------------------------------------------------

EXECUTION VERSION

 

(f)In the case where the non-participating Other Party for a Subsequent Study
elects to use the Combination Therapy Data from such Subsequent Study in a
regulatory filing in the FDA or EMA for its Compound for purposes of obtaining
approval of an indication for the Combination Therapy for its Compound, and the
non-participating Other Party obtains such regulatory approval for such
Combination Therapy indication (i.e., such approved Combination Therapy
indication is included in the label for its Compound allowing promotion of such
indication), then the Other Party shall thereafter be obligated to pay to the
Proposing Party an amount in aggregate equal to *** of the documented
out-of-pocket payments (other than costs of drug supply) to clinical trial
sites, CROs and other contractors reasonably incurred by the Proposing Party
directly as a result of the conduct of the applicable Subsequent Studies in such
indication relied upon for the approval of the new indication (including costs
for project management, document management, monitoring and site management,
specimen management, laboratory, imaging, investigator grants, site costs,
Compound labeling and storage, EDC, IVRS, consultants, contractors for the
testing and screening of patients and lab costs) (for purposes of this Section
5.4(f) only, such aggregate amount, the “Cost Sharing Payment”).  The Other
Party shall pay the Proposing Party *** of the Cost Sharing Payment each year
(without interest) (for purposes of this Section 3.4(b)(v) only, each such
payment, a “Cost Sharing Installment”), such that the Cost Sharing Payment would
be fully paid after *** Cost Sharing Installment payments, with the first
payment to be made within *** after the date Regulatory Approval is obtained by
the Other Party for such Combination Therapy indication and the next *** Cost
Sharing Installments to be made within *** after each of the next *** of such
Regulatory Approval.  For clarity, use of the Combination Therapy Data by the
Other Party in a regulatory filing for safety reporting purposes (or other
purposes that do not permit the promotion of its Compound for the Combination
Therapy indication) shall not trigger any Cost Sharing Payment.

 

Page 50 of 84

 

*** INDICATES MATERIAL THAT WAS OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT WAS
REQUESTED. ALL SUCH OMITTED MATERIAL WAS FILED SEPARATELY WITH THE SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE SECURITIES
EXCHANGE ACT OF 1934, AS AMENDED.

--------------------------------------------------------------------------------

EXECUTION VERSION

 

Article 6

INTELLECTUAL PROPERTY

6.1Inventions.  All rights to Inventions shall be allocated as follows:

(a)Five Prime Ownership.  Subject to the terms of this Agreement, all Five Prime
Study Inventions shall be owned solely by Five Prime, and Five Prime will have
the full right to exploit such Five Prime Study Inventions without the consent
of, or any obligation to account to, BMS.  BMS shall assign and hereby assigns
(and shall cause its Affiliates and contractors to assign) all right, title and
interest in any Five Prime Study Inventions to Five Prime.  Any assignments
necessary to accomplish the foregoing are hereby made, and BMS shall execute
such further documents and provide other assistance as may be reasonably
requested by Five Prime to perfect Five Prime’s rights in such Five Prime Study
Inventions, all at Five Prime’s expense. Five Prime shall have the sole right
but not the obligation to prepare, file, prosecute (including any proceedings
relating to reissues, reexaminations, protests, interferences, oppositions,
post-grant reviews or similar proceedings and requests for patent extensions)
and maintain any Five Prime Study Patent Rights at its own expense.

(b)BMS Ownership.  Subject to the terms of this Agreement, all BMS Study
Inventions shall be owned solely by BMS, and BMS will have the full right to
exploit such BMS Study Inventions without the consent of, or any obligation to
account to, Five Prime.  Five Prime shall assign and hereby assigns (and shall
cause its Affiliates and contractors to assign) all right, title and interest in
any BMS Study Inventions to BMS.  Any assignments necessary to accomplish the
foregoing are hereby made, and Five Prime shall execute such further documents
and provide other assistance as may be reasonably requested by BMS to perfect
BMS’s rights in such BMS Study Inventions, all at BMS’s expense. BMS shall have
the sole right but not the obligation to prepare, file, prosecute (including any
proceedings relating to reissues, reexaminations, protests, interferences,
oppositions, post-grant reviews or similar proceedings and requests for patent
extensions) and maintain any BMS Study Patent Rights at its own expense.

Page 51 of 84

 

*** INDICATES MATERIAL THAT WAS OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT WAS
REQUESTED. ALL SUCH OMITTED MATERIAL WAS FILED SEPARATELY WITH THE SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE SECURITIES
EXCHANGE ACT OF 1934, AS AMENDED.

--------------------------------------------------------------------------------

EXECUTION VERSION

 

(i)Combined Therapy Inventions.  All Combined Therapy Inventions shall be
jointly owned by the Parties, and either Party shall have the right to freely
exploit the Combined Therapy Inventions and Combined Therapy Patent Rights, both
within and outside the scope of this Agreement, without accounting or any other
obligation to the other Party (except as expressly set forth in this Section
6.1(c) and Section 6.3(d) with regard to the filing, prosecution, maintenance
and enforcement of Combined Therapy Patent Rights) and each Party may use,
exploit and grant licenses (with the right to sublicense) to Third Parties under
its interest in such Combined Therapy Inventions and Combined Therapy Patent
Rights.  The Parties shall agree as to which Party, using outside counsel
acceptable to both Parties, shall be responsible for preparing and prosecuting
Patent applications and maintaining Patents within the Combined Therapy Patent
Rights.  The Party drafting and prosecuting any Combined Therapy Patent Right
(the “Prosecuting Party”) shall keep the other Party (the “Non-Prosecuting
Party”) advised as to material developments and all steps to be taken with
respect to any such Patents and shall furnish the Non-Prosecuting Party with
copies of applications for such Patents, amendments thereto and other related
correspondence to and from Patent offices, and permit the Non-Prosecuting Party
a reasonable opportunity to review and offer comments.  The Non-Prosecuting
Party shall reasonably assist and cooperate in obtaining, prosecuting and
maintaining the Combined Therapy Patent Rights.  Notwithstanding the foregoing,
the Prosecuting Party shall not take any position in a submission to a Patent
office that interprets the scope of a Patent or Patent application of the
Non-Prosecuting Party without the prior written consent of such Non-Prosecuting
Party.  The Prosecuting Party shall be reimbursed for any costs and expenses
incurred in prosecuting Combined Therapy Patent Rights and the subsequent
maintenance of Combined Therapy Patent Rights by the Non-Prosecuting Party such
that BMS shall be responsible for *** of such costs and Five Prime shall be
responsible for *** of such costs.  In case one of the two Parties decides not
to file or maintain a Combined Therapy Patent Right application in a given
country (and also elects not to reimburse the other Party for *** of the costs
of prosecution and maintenance of such Combined Therapy Patent Right in such
country), the other Party shall have the right to file or maintain such patent
application in such country in its own name and at its own expense upon the
prior consent of the other Party, which shall not be unreasonably withheld or
delayed.  In this case, the Party who decides not to file or maintain (and also
decides not to reimburse the other Party for its share of the costs of) a joint
application for a given country shall promptly assign its rights to the joint
invention in said country to the Party who wishes to file or maintain said
patent application. The Party who does not wish to file or maintain a patent
application in any country shall assist in the timely provision of all documents
required under national provisions to register said assignment of rights with
the corresponding national authorities at the sole expense of the Party who
wishes to file or maintain such patent application in that given country.

Page 52 of 84

 

*** INDICATES MATERIAL THAT WAS OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT WAS
REQUESTED. ALL SUCH OMITTED MATERIAL WAS FILED SEPARATELY WITH THE SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE SECURITIES
EXCHANGE ACT OF 1934, AS AMENDED.

--------------------------------------------------------------------------------

EXECUTION VERSION

 

(c)Separation of Patent Rights. In order to more efficiently enable the
prosecution and maintenance of the BMS Study Patent Rights, Five Prime Study
Patent Rights and Combined Therapy Patent Rights relating to Inventions as
described above, the Parties will use good faith efforts to separate BMS Study
Patent Rights, Five Prime Study Patent Rights, Combined Therapy Patent Rights,
BMS Independent Patent Rights and Five Prime Independent Patent Rights into
separate patent filings to the extent possible and without adversely impacting
such prosecution and maintenance.

6.2Disclosure and Assignment of Inventions.  Each Party shall disclose promptly
to the other Party in writing and on a confidential basis all Inventions, prior
to any public disclosure or filing of Patent applications and allowing
sufficient time for comment by the other Party.  In addition, each Party shall,
and does hereby, assign, and shall cause its Affiliates and contractors to so
assign, to the other Party, without additional compensation, such right, title
and interest in and to any Inventions as well as any intellectual property
rights with respect thereto, as is necessary to fully effect, as applicable, the
sole ownership provided for in Sections 6.1(a) and 6.1(b) and the joint
ownership provided for in Section 6.1(c).

6.3Infringement of Patent Rights by Third Parties.

(a)Notice.  Each Party shall promptly notify the other Party in writing of any
alleged or threatened (in writing) infringement, or misappropriation by a Third
Party, of Combined Therapy Patent Rights, of which its in-house patent counsel
becomes aware (such infringement, “Infringement”).

(b)Infringement of Five Prime Study Patent Rights.  For all Infringement of Five
Prime Study Patent Rights anywhere in the world, Five Prime shall have the
exclusive right to prosecute such Infringement as it may determine in its sole
and absolute discretion, and Five Prime shall bear all related expenses and
retain all related recoveries.  BMS shall reasonably cooperate with Five Prime
or its designee (to the extent BMS has relevant information arising out of this
Agreement), at Five Prime’s request and expense, in any such action.

(c)Infringement of BMS Study Patent Rights.  For all Infringement of BMS Study
Patent Rights anywhere in the world, BMS shall have the exclusive right to
prosecute such Infringement as it may determine in its sole and absolute
discretion, and BMS shall bear all related expenses and retain all related
recoveries.  Five Prime shall reasonably cooperate with BMS or its designee (to
the extent Five Prime has relevant information arising out of this Agreement),
at BMS’s request and expense, in any such action.

Page 53 of 84

 

*** INDICATES MATERIAL THAT WAS OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT WAS
REQUESTED. ALL SUCH OMITTED MATERIAL WAS FILED SEPARATELY WITH THE SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE SECURITIES
EXCHANGE ACT OF 1934, AS AMENDED.

--------------------------------------------------------------------------------

EXECUTION VERSION

 

(d)Infringement of Combined Therapy Patent Rights.

(i)With respect to Infringement of Combined Therapy Patent Rights, the Parties
shall agree as to whether to bring an enforcement action to seek the removal or
prevention of such Infringement and damages therefor and, if so, which Party
shall bring such action, with any costs and expenses relating thereto to be
allocated in accordance with Section 6.3(d)(ii).

(ii)Regardless of which Party brings an enforcement action pursuant to Section
6.3(d)(i), the other Party hereby agrees to cooperate reasonably in any such
action, including, if required, by bringing a legal action or furnishing a power
of attorney.  If the Parties agree to bring an enforcement action, BMS shall be
responsible for ***, and Five Prime shall be responsible for ***, of the
reasonable and verifiable costs and expenses incurred in connection with any
such action.  If either Party recovers monetary damages from any Third Party in
an action approved by the Parties and brought under this Section 6.3(d)(ii),
such recovery shall be allocated first to the reimbursement of any actual,
unreimbursed costs and expenses incurred by the Parties in such litigation
(including, for this purpose, a reasonable allocation of expenses of internal
counsel) pro rata in accordance with the aggregate amounts spent by both
Parties, and any remaining amounts shall be split *** to Five Prime and *** to
BMS, unless the Parties agree in writing to a different allocation.  In
connection with any proceeding under this Section 6.3(d), neither Party shall
enter into any settlement without the prior written consent of the other Party.

6.4Infringement of Third Party Rights.

(a)Notice.  If the activities relating to the Combined Therapy Trials become the
subject of a claim of infringement of a patent, copyright or other proprietary
right by a Third Party anywhere in the world, the Party first having notice of
the claim shall promptly notify the other Party and, without regard to which
Party is charged with said infringement and the venue of such claim, the Parties
shall promptly confer to discuss the claim.

Page 54 of 84

 

*** INDICATES MATERIAL THAT WAS OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT WAS
REQUESTED. ALL SUCH OMITTED MATERIAL WAS FILED SEPARATELY WITH THE SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE SECURITIES
EXCHANGE ACT OF 1934, AS AMENDED.

--------------------------------------------------------------------------------

EXECUTION VERSION

 

(b)Defense.  If both Parties are charged with infringement pursuant to a claim
described in Section 6.4(a), the Parties shall defend such claim jointly, unless
they agree otherwise.  If only one Party is charged with infringement, such
Party will have the first right but not the obligation to defend such claim.  If
the charged Party does not commence actions to defend such claim within ***
after being so charged, then the other Party shall have the right, but not the
obligation, to defend any such claim.  In any event, the non-defending Party
shall reasonably cooperate with the Party conducting the defense of the claim
and shall have the right to participate with separate counsel at its own
expense, and the defending Party shall consider comments by the non-defending
Party in good faith.  The Party defending the claim shall bear the cost and
expenses of the defense of any such Third Party infringement claim and shall
have sole rights to any recovery.  If the Parties jointly defend the claim, Five
Prime shall bear ***, and BMS shall bear *** of any costs and expenses of the
defense of any such Third Party infringement claim; provided, however, that,
notwithstanding the foregoing, if the claim relates solely to one Party’s
Compound, such Party will bear *** of the costs and expenses of the defense of
such claim and shall have the sole right, but not the obligation, to defend,
settle and otherwise handle the disposition of such claim.  Neither Party shall
enter into any settlement concerning activities under this Agreement or the
Combined Therapy that affects the other Party’s rights under this Agreement or
imposes any obligations on the other Party, including any admissions of
wrongdoing on behalf of the other Party, without such other Party’s prior
written consent, not to be unreasonably withheld or delayed, except that a Party
may settle any claim that solely relates to its Compound without the consent of
the other Party as long as such other Party’s rights under this Agreement are
not adversely impacted (in which case, it will obtain such other Party’s prior
written consent, not to be unreasonably withheld or delayed).

6.5Combined Therapy Trial Regulatory Documentation.  Subject to the license and
other rights granted by each Party to the other Party pursuant to this
Agreement, Five Prime and BMS shall jointly own all right, title and interest in
and to the Combined Therapy Trial Regulatory Documentation; provided, however,
that BMS shall retain sole and exclusive ownership of any BMS Regulatory
Documentation provided to Five Prime under this Agreement that is submitted with
or referenced in the Combined Therapy Trial Regulatory Documentation and that
Five Prime shall retain sole and exclusive ownership of any Five Prime
Regulatory Documentation that is submitted with or referenced in the Combined
Therapy Trial Regulatory Documentation.  This Section 6.5 is without limitation
of any other disclosure obligations under the Pharmacovigilance Agreement or
this Agreement.

 

Page 55 of 84

 

*** INDICATES MATERIAL THAT WAS OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT WAS
REQUESTED. ALL SUCH OMITTED MATERIAL WAS FILED SEPARATELY WITH THE SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE SECURITIES
EXCHANGE ACT OF 1934, AS AMENDED.

--------------------------------------------------------------------------------

EXECUTION VERSION

 

Article 7

ONE-TIME PAYMENT; COLLABORATION COSTS AND EXPENSES

7.1One-time Payment; Refund.  

(a)BMS shall pay Five Prime a one-time payment in the amount of Thirty Million
Dollars ($30,000,000) within *** after the Effective Date.  

(b)If (i) a Change of Control of Five Prime closes prior to the Initial Results
Date, (ii) immediately prior to such Change of Control, the Third Party acquirer
in such Change of Control (or any of its Affiliates) owns or controls (including
pursuant to an exclusive license or an exclusive option to acquire an exclusive
license) (A) an anti-PD-1 antagonist molecule (including antibodies, peptides
and chemical compounds) or (B) an anti-PD-L1 antagonist molecule (including
antibodies, peptides and chemical compounds), which molecule in (A) or (B) is
then in clinical development for use in treating cancer or is then being
commercialized for use in treating cancer, (iii) BMS is using Commercially
Reasonable Efforts in the performance and fulfillment of its activities under
this Agreement and the Parties are developing or pursuing the development of the
Combined Therapy Trial under this Agreement, and (iv) a Change of Control of BMS
has not occurred, then Five Prime shall, within *** after the closing of such
Change of Control, pay to BMS the lesser of (x) Thirty Million Dollars
($30,000,000) and (y) ten percent (10%) of the sum (x) of the aggregate purchase
price paid to Five Prime or the stockholders of Five Prime at the closing of
such Change of Control plus (y) the risk-adjusted, discounted value of any
contingent consideration paid to Five Prime or the stockholders of Five Prime
with respect to such Change of Control.

7.2Combined Therapy Trial Expenses.  Expenses incurred as described in Article 4
(regarding manufacturing and supply), and Article 6 (regarding intellectual
property) shall be borne or shared by the Parties as provided in such
Articles.  In addition, each Party shall bear its own Third Party License
Payments as set forth in Section 2.6(b).  For all other expenses that are
directly attributable to the conduct of activities under the Development Plan,
including any pharmacokinetic, pharmacodynamics and biomarker research, any
Combined Therapy Trials and any additional studies required under Section
2.1(d), (a) BMS will be responsible for all payments made to Third Parties for
such expenses (“Third Party Study Costs”) , and (b) each Party shall be solely
responsible for all of its own internal costs (including costs of individual
independent contractors) incurred by such Party or any of its Affiliates, to the
extent not included in the definition of Third Party Study Costs.  For avoidance
of doubt, Third Party Study Costs do not include Third Party License Payments by
Five Prime or any Third Party Claims.

Page 56 of 84

 

*** INDICATES MATERIAL THAT WAS OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT WAS
REQUESTED. ALL SUCH OMITTED MATERIAL WAS FILED SEPARATELY WITH THE SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE SECURITIES
EXCHANGE ACT OF 1934, AS AMENDED.

--------------------------------------------------------------------------------

EXECUTION VERSION

 

7.3Invoicing; Payment.

(a)Reconciliation.  Five Prime shall provide a report to BMS within *** after
the end of each Quarter which shall set forth in reasonable detail all Third
Party Study Costs and Section 4.2(b) Costs actually incurred during such Quarter
by Five Prime (a “Quarterly Report”).  If requested by BMS, Five Prime shall
provide invoices or other appropriate supporting documentation for any payments
to a Third Party exceeding ***.  The Parties shall seek to resolve any questions
related to such Quarterly Reports within *** following receipt by BMS of such
Quarterly Report.  Based on these Quarterly Reports, the Parties finance teams
will determine the amount, if any, owed by BMS for such Quarter and such payment
will be made by BMS within *** after the end of such *** reconciliation period.

(b)Budget Overruns.  Any costs that are incurred by Five Prime that are ***
greater than the JDC-approved budget shall require approval of the JDC for
payment. If the reason for the costs exceeding such JDC-approved budget by more
than *** is attributable to a Party’s negligence or breach of its obligations
under this Agreement, then the costs incurred that are more than *** greater
than the JDC-approved budget shall be the sole responsibility of such Party.

(c)Payment Method.  BMS shall pay all amounts due hereunder in United States
dollars to the bank account Five Prime designates in writing from time to time.

7.4Customs Valuation.  Five Prime will provide BMS in writing with a list of
all countries participating in a Combined Therapy Trial prior to study start
initiation of such Combined Therapy Trial.  During the conduct of such Combined
Therapy Trial, Five Prime will send in writing any changes to the list of
participating countries to BMS one month prior to the end of each Quarter. If no
changes are sent to BMS by Five Prime for a particular Quarter, the prior
Quarter’s participating country list will be used as the basis for customs
valuation for that Quarter. BMS will provide Five Prime with Nivolumab
country-specific customs valuations initially prior to study start initiation of
Combined Therapy Trial(s) and at the end of each Quarter during the conduct of
the Combined Therapy Trial. Five Prime will use the BMS provided values for the
import/export process to the listed participating countries and not make any
change to such valuations without BMS’s prior written consent.  

Page 57 of 84

 

*** INDICATES MATERIAL THAT WAS OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT WAS
REQUESTED. ALL SUCH OMITTED MATERIAL WAS FILED SEPARATELY WITH THE SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE SECURITIES
EXCHANGE ACT OF 1934, AS AMENDED.

--------------------------------------------------------------------------------

EXECUTION VERSION

 

7.5Audit. At the request (and expense) of BMS, Five Prime shall permit an
independent certified public accountant appointed by BMS and reasonably
acceptable to Five Prime, at reasonable times and upon reasonable notice, to
examine only those records as may be reasonably necessary to determine, with
respect to any calendar year ending not more than *** prior to BMS’s request,
the correctness or completeness of any invoice submitted to  BMS or other
payment made to Five Prime pursuant to this Agreement.  The foregoing right of
review may be exercised *** per year and *** with respect to each such Quarterly
Report and payment.  Results of any such examination shall be (a) made available
to both Parties and (b) subject to Article 9.  BMS shall bear the full cost of
the performance of any such audit, unless such audit discloses a variance to the
detriment of BMS of more than *** from the amount of the original payment
calculation, in which case, Five Prime shall bear the full cost of the
performance of such audit.

7.6Taxes. Each Party will pay any and all taxes levied on accounts of all
payments it receives under this Agreement. If Applicable Law requires
withholding of any taxes imposed upon Five Prime on account of any payments paid
under this Agreement, BMS shall withhold such taxes as required by such
Applicable Law from such remittable payments and timely pay such withheld taxes
to the proper tax authorities. BMS shall promptly secure official receipts of
payment of any withholding tax and send such receipts to Five Prime as evidence
of such payment.  BMS shall cooperate with Five Prime in the event Five Prime
claims exemption from such withholding or seeks deductions under any double
taxation or other similar treaty or agreement from time to time in force. In
addition, the Parties shall cooperate in accordance with Applicable Law to
minimize indirect taxes (such as value added tax, sales tax, consumption tax and
other similar taxes ) in connection with this Agreement.

 

Page 58 of 84

 

*** INDICATES MATERIAL THAT WAS OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT WAS
REQUESTED. ALL SUCH OMITTED MATERIAL WAS FILED SEPARATELY WITH THE SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE SECURITIES
EXCHANGE ACT OF 1934, AS AMENDED.

--------------------------------------------------------------------------------

EXECUTION VERSION

 

Article 8

RECORDS AND STUDY DATA

8.1Records.  Each Party shall maintain complete and accurate records of all work
conducted under the Development Plan and of all results, information, data, data
analyses, reports, records, methods, processes, practices, formulae,
instructions, skills, techniques, procedures, experiences and developments made
by or provided to either Party, or by the Parties together, in the course of
each such Party’s performance of the Development Plan (including the Statistical
Analysis Plan and any Bioanalysis Plan to be conducted pursuant to this
Agreement) (such results, information, data, data analyses, reports, case report
forms, adverse event reports, trial records, methods, processes, practices,
formulae, instructions, skills, techniques, procedures, experiences,
developments, and each Protocol referred to as the “Study Data”).  Such records
shall fully and properly reflect all work done and results achieved in the
performance of the Development Plan in sufficient detail and in good scientific
manner appropriate for patent and regulatory purposes.

8.2Ownership of Study Data.  BMS shall own the Study Data to the extent that it
relates exclusively to the BMS Compound (“BMS Study Data”), and Five Prime shall
own the Study Data to the extent that it relates exclusively to the Five Prime
Compound (“Five Prime Study Data”).  Both Parties shall jointly own any Study
Data that does not relate exclusively to the Five Prime Compound or the BMS
Compound (“Combined Therapy Study Data”).  Each Party shall, and does hereby,
assign, and shall cause its Affiliates to so assign, to the other Party, without
additional compensation, such right, title and interest in and to any Study Data
as is necessary to fully effect the foregoing, and agrees to execute all
instruments as may be reasonably necessary to effect same.

8.3Use of Study Data.

(a)Use of a Party’s Own Study Data.  Each Party may use and analyze its own
Study Data for any purpose without obligation or accounting to the other.

Page 59 of 84

 

*** INDICATES MATERIAL THAT WAS OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT WAS
REQUESTED. ALL SUCH OMITTED MATERIAL WAS FILED SEPARATELY WITH THE SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE SECURITIES
EXCHANGE ACT OF 1934, AS AMENDED.

--------------------------------------------------------------------------------

EXECUTION VERSION

 

(b)Use of Combined Therapy Study Data by BMS.  BMS and its Affiliates and
(sub)licensees shall have the right to use and analyze the Combined Therapy
Study Data (x) in connection with its independent development, commercialization
or other exploitation of the BMS Compound (alone or in combination with the Five
Prime Compound and/or other pharmaceutical agents (but not with any Third
Party’s molecule that is designed to selectively bind CSF1R)) and/or for
inclusion in the safety database for the BMS Compound, in each case without the
consent of, or any obligation to account to, Five Prime, and (y) to conduct
studies with Samples pursuant to Section 8.5.  Subject to Section 8.5, the
results of all such analyses or uses shall be owned by BMS, including any
intellectual property arising out of same, unless the Parties shall have agreed
otherwise in writing.  BMS,  its Affiliates and licensees shall also be entitled
to use the Combined Therapy Study Data during and following the Term to (1) make
regulatory filings and seek approvals for the BMS Compound, either alone or as
part of the Combined Therapy and (2) to promote indications based on, and to
disseminate, the Combined Therapy Study Data for the benefit of the BMS
Compound, either alone or as part of the Combined Therapy, where permitted by
and in accordance with Applicable Law; provided that nothing in the foregoing is
intended or shall be construed as granting BMS any right or license, expressly
or implicitly: (i) to make, have made, use, sell, offer for sale, or import the
Five Prime Compound.  Five Prime grants BMS, its Affiliates and licensees a
Right of Cross-Reference to the relevant Regulatory Documentation Controlled by
Five Prime for the Five Prime Compound or the Combined Therapy for the sole
purpose of enabling each of them to exercise its rights under clause (1) of this
Section 8.3(b) (other than for use in the Ono Territory), which right shall
survive any expiration or termination of this Agreement.

Page 60 of 84

 

*** INDICATES MATERIAL THAT WAS OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT WAS
REQUESTED. ALL SUCH OMITTED MATERIAL WAS FILED SEPARATELY WITH THE SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE SECURITIES
EXCHANGE ACT OF 1934, AS AMENDED.

--------------------------------------------------------------------------------

EXECUTION VERSION

 

(c)Use of Combined Therapy Study Data by Five Prime.  Five Prime, its Affiliates
and licensees shall have the right to use and analyze the Combined Therapy Study
Data (x) in connection with its independent development, commercialization or
other exploitation of the Five Prime Compound (alone or in combination with the
BMS Compound and/or other pharmaceutical agents (but not with any Third Party
molecule that is designed to selectively bind to PD-1)) and/or for inclusion in
the safety database for the Five Prime Compound, in each case without the
consent of, or any obligation to account to, BMS and (y) to conduct studies with
Samples pursuant to Section 8.5.  Subject to Section 8.5, the results of all
such analyses or uses shall be owned by Five Prime, including any intellectual
property arising out of same, unless the Parties shall have agreed otherwise in
writing.  Five Prime, its Affiliates and licensees shall be entitled to use the
Combined Therapy Study Data during and following the Term to (1) make regulatory
filings and seek approvals for the Five Prime Compound, either alone or as part
of the Combined Therapy and (2) to promote indications based on, and to
disseminate, the Combined Therapy Study Data for the benefit of the Five Prime
Compound, either alone or as part of the Combined Therapy, where permitted by
and in accordance with Applicable Law; provided that nothing in the foregoing is
intended or shall be construed as granting Five Prime any right or license,
expressly or implicitly, to make, have made, use, sell, offer for sale, or
import the BMS Compound.  BMS grants Five Prime, its Affiliates and licensees of
the Five Prime Compound a Right of Cross-Reference to the relevant Regulatory
Documentation Controlled by BMS for the BMS Compound for the sole purpose of
enabling each of them to exercise its rights under clause (1) of this Section
8.3(c) (for clarity, such Right of Cross-Reference shall not extend to the Ono
Territory or use of any Ono-controlled Regulatory Documentation), which right
shall survive any expiration or termination of this Agreement.

(d)Biomarker/Diagnostic Agent Development.  Each Party may use and disclose to a
Third Party the Combined Therapy Study Data and its Compound’s Study Data, under
obligations of confidentiality consistent with this Agreement, to develop and
commercialize a biomarker or diagnostic test for use with its Compound and/or
the Combined Therapy, and, unless otherwise agreed by the Parties in writing,
will own any intellectual property arising out of the work funded or conducted
by it with or through such Third Party.  The Parties will discuss in good faith
any opportunities to jointly participate in the development of any such
biomarker or diagnostic test for use with the Combined Therapy.

(e)No Other Uses.  All other uses of Study Data are limited solely to those
permitted by this Agreement, and neither Party may use Study Data for any other
purpose without the written consent of the other Party during and after the
Term.

8.4Access to Study Data.  Subject to the provisions of Sections 2.2, 5.1(a)(xvi)
and 5.1(a)(xvii) and the Pharmacovigilance Agreement, each Party shall have
access to all Study Data (including de-identified patient records) promptly
after such Study Data is available to or generated by the Party responsible for
generating or collecting such Study Data.

Page 61 of 84

 

*** INDICATES MATERIAL THAT WAS OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT WAS
REQUESTED. ALL SUCH OMITTED MATERIAL WAS FILED SEPARATELY WITH THE SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE SECURITIES
EXCHANGE ACT OF 1934, AS AMENDED.

--------------------------------------------------------------------------------

EXECUTION VERSION

 

8.5Samples.  Samples collected in the course of activities conducted under this
Agreement shall be jointly owned by the Parties (to the extent not owned by the
patient and/or the clinical trial site).  Any such Samples shall be collected in
accordance with the Development Plan and ICFs.  Neither Party shall be permitted
to use such Samples for any purpose without the prior written consent of the
other Party, which consent shall not be unreasonably withheld if such use is
directed to the Combined Therapy and with the terms of such use to be set forth
in a written agreement between the Parties setting forth the Samples to be used,
and any appropriate terms/restrictions on such use.  Any data and intellectual
property arising out of such Sample use shall be owned by the Party conducting
such study using same; provided that to the extent that any such data or
intellectual property relates solely to the Combined Therapy (or biomarkers
solely for use with the Combined Therapy), such data or intellectual property
shall be considered Combined Therapy Study Data or Combined Therapy
Inventions/Combined Therapy Patent Rights, as the case may be.  Samples for PK
and ADA serum analysis will be stored for future use in Five Prime’s sample
repository (with the expectation that BMS will store those samples that it
expects to use in studies), provided that if the Party holding the Samples
determines that it no longer has a use for the Samples and the other Party
determines that it does, then the Samples shall, subject to applicable Law and
the terms of the signed ICFs, be transferred to the other Party and may be used
solely thereafter by the other Party.   If neither Party has any further use for
the Samples, then the remaining Samples will be destroyed pursuant to the
respective Party’s standard operating procedures for sample retention and
destruction, subject to the terms of and permission(s) granted in the ICFs
signed by the subjects contributing the Samples in the Combined Therapy Trials.

Page 62 of 84

 

*** INDICATES MATERIAL THAT WAS OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT WAS
REQUESTED. ALL SUCH OMITTED MATERIAL WAS FILED SEPARATELY WITH THE SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE SECURITIES
EXCHANGE ACT OF 1934, AS AMENDED.

--------------------------------------------------------------------------------

EXECUTION VERSION

 

Article 9

CONFIDENTIALITY

9.1Nondisclosure of Confidential Information.

(a)All written, visual, oral and electronic data, information, know-how or other
confidential information or materials, both technical and non-technical,
disclosed by one Party to any other Party pursuant to this Agreement that (a) if
in tangible form, is labeled in writing as “proprietary” or “confidential” (or
similar reference); or (b) if in oral or visual form, is identified as
proprietary or confidential or for internal use only at the time of disclosure
or within *** thereafter shall be “Confidential Information” of the disclosing
Party, and all Study Data and Inventions shall be the Confidential Information
of the Party owning such Study Data or Invention (as provided in Section 8.2
with regard to Study Data and Section 6.1 with regard to Inventions).  For
purposes of this Agreement, regardless of which Party discloses such
Confidential Information to the other, (i) all Five Prime Study Inventions, Five
Prime Technology and Five Prime Regulatory Documentation shall be Confidential
Information of Five Prime and BMS shall be deemed the receiving Party, (ii) all
BMS Study Inventions, BMS Technology, and BMS Regulatory Documentation shall be
Confidential Information of BMS and Five Prime shall be deemed the receiving
Party and (iii) all Combined Therapy Inventions, Combined Therapy Study Data and
Combined Therapy Trial Regulatory Documentation shall be Confidential
Information of each Party.

(b)Except to the extent expressly authorized in this Section 9.1 and Sections
9.2, 9.3 and 9.5, or as otherwise agreed in writing by the Parties, each Party
agrees that, for the Term and for a period of *** thereafter (or for any
Confidential Information that is identified in writing at the time of disclosure
as a trade secret related to each Party’s Compound, for as long as it is not
part of the public domain), it shall (x) keep confidential and shall not publish
or otherwise disclose and shall not use for any purpose other than as expressly
provided for in this Agreement any Confidential Information owned by the other
Party, (y) treat the other Party’s Confidential Information with the same degree
of care the receiving Party uses for its own confidential information but in no
event with less than a reasonable degree of care; and (z) reproduce the
disclosing Party’s Confidential Information solely to the extent necessary to
accomplish the receiving Party’s obligations under this Agreement, with all such
reproductions being considered the disclosing Party’s Confidential Information;
provided that with respect to BMS Confidential Information that BMS received as
confidential information from Ono, the obligations of confidentiality and
non-use shall continue for the longer of the period set forth above or *** after
the termination of the Ono-BMS Agreements.

Page 63 of 84

 

*** INDICATES MATERIAL THAT WAS OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT WAS
REQUESTED. ALL SUCH OMITTED MATERIAL WAS FILED SEPARATELY WITH THE SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE SECURITIES
EXCHANGE ACT OF 1934, AS AMENDED.

--------------------------------------------------------------------------------

EXECUTION VERSION

 

(c)Notwithstanding anything to the contrary in this Section 9.1, and subject to
Section 8.3, the receiving Party may disclose the disclosing Party’s
Confidential Information to its employees, consultants, agents or permitted
sublicensees solely on a need-to-know basis for the purpose of fulfilling the
receiving Party’s obligations under this Agreement; provided, however, that (1)
any such employees, consultants, agents or permitted sublicensees are bound by
obligations of confidentiality at least as restrictive as those set forth in
this Agreement, and (2) the receiving Party remains liable for the compliance of
such employees, consultants, agents or permitted sublicensees with such
obligations.  Each receiving Party acknowledges that in connection with its and
its representatives examination of the Confidential Information of the
disclosing Party, the receiving Party and its representatives may have access to
material, non-public information, and that the receiving Party is aware, and
will advise its representatives who are informed as to the matters that are the
subject of this Agreement, that State and Federal laws, including United States
securities laws, impose restrictions on the dissemination of such information
and trading in securities when in possession of such information.  Each
receiving Party agrees that it will not, and will advise its representatives who
are informed as to the matters that are the subject of this Agreement to not,
purchase or sell any security of the disclosing Party on the basis of the
Confidential Information to the extent such Confidential Information constitutes
material non-public information about the disclosing Party or such security.

9.2Exceptions.  Information of a disclosing Party shall not be deemed
“Confidential Information” of such disclosing Party to the extent the receiving
Party can demonstrate by contemporaneous tangible records or other competent
proof that such information:

(a)was already known to the receiving Party (or its Affiliates), other than
under an obligation of confidentiality, either (a) at the time of disclosure by
the disclosing Party, or (b) if applicable, at the time that it was generated
hereunder, whichever ((a) or (b)) is earlier;

(b)was generally available to the public or otherwise part of the public domain
either (a) at the time of its disclosure to the receiving Party, or (b) if
applicable, at the time that it was generated hereunder, whichever ((a) or (b))
is earlier;

(c)became generally available to the public or otherwise part of the public
domain after its disclosure and other than through any act or omission of the
receiving Party in breach of this Agreement;

(d)was disclosed to the receiving Party (or its Affiliates), other than under an
obligation of confidentiality, by a Third Party who had no obligation to the
Party owning or Controlling the information not to disclose such information to
others; or

(e)was independently discovered or developed by the receiving Party (or its
Affiliates) without the use of or reference to the Confidential Information
belonging to the disclosing Party.

Page 64 of 84

 

*** INDICATES MATERIAL THAT WAS OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT WAS
REQUESTED. ALL SUCH OMITTED MATERIAL WAS FILED SEPARATELY WITH THE SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE SECURITIES
EXCHANGE ACT OF 1934, AS AMENDED.

--------------------------------------------------------------------------------

EXECUTION VERSION

 

9.3Authorized Disclosure.  Notwithstanding any other provision of this
Agreement, each Party may disclose Confidential Information belonging to the
other Party to the extent such disclosure is reasonably necessary in the
following instances:

(a)filing or prosecuting Patent Rights;

(b)prosecuting or defending litigation;

(c)complying with Applicable Law or the rules or regulations of any securities
exchange on which such Party’s stock is listed;

(d)disclosure, in connection with the performance of this Agreement, to
Affiliates, permitted sublicensees, contractors, ethics committees and
institutional review boards (collectively, “IRBs”), CROs, academic institutions,
consultants, agents, investigators, and employees and contractors engaged by
Study sites and investigators involved with the Combined Therapy Trials, each of
whom prior to disclosure must be bound by similar terms of confidentiality and
non-use at least equivalent in scope to those set forth in this Article 9;

(a)disclosure that is deemed necessary by either Party to be disclosed to its
respective Affiliates, agents, consultants or other Third Parties for any and
all purposes such Party or its Affiliates deem necessary or advisable in the
ordinary course of business in furtherance of the development, manufacture
and/or commercialization of such Party’s Compound and in accordance with this
Agreement, on the condition that such Third Parties agree to be bound by
confidentiality and non-use obligations that are substantially consistent with
the confidentiality and non-use provisions contained in this Agreement;
provided, however, that the term of confidentiality for such Third Parties shall
be no less than ***;

(e)disclosure of the Combined Therapy Study Data, Combined Therapy Inventions
and Combined Therapy Patent Rights to Regulatory Authorities in connection with
the development of the Combined Therapy, the Five Prime Compound or the BMS
Compound; and

(f)disclosure of relevant safety information contained within the Combined
Therapy Study Data to investigators, IRBs and/or ethics committees and
Regulatory Authorities that are involved in other clinical trials of the Five
Prime Compound with respect to Five Prime, the BMS Compound with respect to BMS,
and (in the event of a Material Safety Issue) to Third Parties that are
collaborating with Five Prime or BMS, respectively in the conduct of such other
clinical trials of the Five Prime Compound or the BMS Compound, in each case
solely to the extent necessary for the conduct of such clinical trials and/or to
comply with Applicable Law and regulatory requirements.

Page 65 of 84

 

*** INDICATES MATERIAL THAT WAS OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT WAS
REQUESTED. ALL SUCH OMITTED MATERIAL WAS FILED SEPARATELY WITH THE SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE SECURITIES
EXCHANGE ACT OF 1934, AS AMENDED.

--------------------------------------------------------------------------------

EXECUTION VERSION

 

Notwithstanding the foregoing, if a Party is required or otherwise intends to
make a disclosure of the other Party’s Confidential Information pursuant to
Section 9.3(b) and/or Section 9.3(c), it shall give advance notice to such other
Party of such impending disclosure and endeavor in good faith to secure
confidential treatment of such Confidential Information and/or reasonably assist
the Party that owns such Confidential Information in seeking a protective order
or other confidential treatment.  BMS acknowledges that Five Prime plans to (i)
file a Current Report on Form 8-K (the “Current Report”) with the Securities and
Exchange Commission (the “SEC”) within four (4) Business Days of the full
execution and delivery of this Agreement, which Current Report shall include a
description of the terms and conditions of this Agreement, and (ii) attach this
Agreement as an exhibit to either an amendment to the Current Report or the
Annual Report on Form 10-K for the fiscal year ending December 31, 2014 that
Five Prime will file with the SEC (the “Annual Report”). BMS hereby consents to
Five Prime’s filing of such Current Report and the attachment of this Agreement
to an amendment to the Current Report or the Annual Report, subject to Five
Prime’s compliance with the first sentence of this paragraph; provided that Five
Prime allow BMS at least *** to review the contents of such Current Report and a
reasonable opportunity for BMS to discuss with Five Prime any comments or
proposed revisions it may have with respect to the information disclosed in such
Current Report.

9.4Disclosure to Ono.  Notwithstanding any other provision of this Agreement,
Five Prime hereby expressly authorizes BMS to disclose to Ono (i) the existence
(but not the terms) of this Agreement and the Development Plan, and (ii) any
Five Prime Confidential Information, BMS Study Data and the Combined Therapy
Study Data solely to the extent necessary for BMS to fulfill its obligations to
Ono under the Ono-BMS Agreements; provided that Ono is under confidentiality
obligations at least as restrictive as set forth herein.

9.5Press Releases and Publications.

(a)Subject to this Section 9.5, the Parties shall jointly agree to the content
and timing of all external communications with respect to this Agreement
(including an initial press release, the content of which shall be as attached
hereto as Exhibit C, subsequent press releases, Q&As, and the content and
wording of any listing any Combined Therapy Trial required to be listed on a
public database or other public registry such as www.clinicaltrials.gov).  If
either Party terminates this Agreement pursuant to Section 12.4, the Parties
shall agree upon any external communication related to such termination, which
shall not include the rationale for such termination unless (and to the extent)
agreed by the Parties.  Notwithstanding any provision of this Agreement to the
contrary, each Party shall be permitted to publicly disclose information,
including the existence of this Agreement or any of its terms or conditions or
the results of any activity under this Agreement, that such Party determines in
good faith is necessary to be disclosed to comply with Applicable Law, including
pursuant to an order of a court or governmental entity, or to comply with the
rules or regulations of any securities exchange on which such Party’s stock may
be listed.

Page 66 of 84

 

*** INDICATES MATERIAL THAT WAS OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT WAS
REQUESTED. ALL SUCH OMITTED MATERIAL WAS FILED SEPARATELY WITH THE SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE SECURITIES
EXCHANGE ACT OF 1934, AS AMENDED.

--------------------------------------------------------------------------------

EXECUTION VERSION

 

(b)Five Prime and BMS agree to collaborate to disclose publicly, publish or
present (1) top-line results from the performance of the Development Plan,
limited if possible to avoid jeopardizing the future publication of the Study
Data at a scientific conference or in a scientific journal, solely for the
purpose of disclosing, as soon as reasonably practicable, the safety or efficacy
results and conclusions that are material to either Party under applicable
securities laws, and (2) the conclusions and outcomes (the “Results”) of each
Combined Therapy Trial at a scientific conference as soon as reasonably
practicable following the completion of such Combined Therapy Trial, subject in
the case of (2) to the following terms and conditions.  The Party proposing to
disclose, publish or present the Results shall deliver to the other Party a copy
of (i) any abstract or press release at least *** before submission to a Third
Party and (ii) any proposed slide presentation, publication, poster presentation
or any other disclosure, publication or presentation at least *** before
submission to a Third Party.  The reviewing Party shall determine whether any of
its Confidential Information that may be contained in such disclosure,
publication or presentation should be modified or deleted, whether to file a
patent application on any Five Prime Study Invention (solely with respect to
Five Prime) or BMS Study Invention (solely with respect to BMS) or Combined
Therapy Invention disclosed therein.  The disclosure, publication or
presentation shall be delayed for an additional *** (i.e., a total of *** from
the initial proposal) if the reviewing Party reasonably requests such extension
to allow time for the preparation and filing of relevant patent
applications.  If the reviewing Party reasonably requests modifications to the
disclosure, publication or presentation to prevent the disclosure of a material
trade secret or proprietary business information, the publishing Party shall
edit such publication to prevent the disclosure of such information prior to
submission of the disclosure, publication or presentation.  In the event of a
disagreement as to content, timing and/or venue or forum for any disclosure,
publication or presentation of the Results, such dispute (a “Publication
Dispute”) shall be referred to the Executive Officers (or their respective
designees); provided that, in the absence of agreement after such good faith
discussions, and upon expiration of the additional ***-period, academic
collaborators engaged by Five Prime in connection with the performance of the
Combined Therapy Trials may publish Combined Therapy Study Data obtained by such
academic collaborator solely to the extent that such ability to publish such
Combined Therapy Study Data is set forth in an agreement between Five Prime and
such academic collaborator relating to the conduct of Combined Therapy
Trials.  Authorship of any publication shall be determined based on the accepted
standards used in peer-reviewed academic journals at the time of the proposed
disclosure, publication or presentation.  The Parties agree that they shall make
reasonable efforts to prevent publication of a press release that could
jeopardize the future publication of Study Data at a scientific conference or in
a scientific journal but in no way will this or any other provision of this
Agreement supersede the requirements of any Applicable Law or the rules or
regulations of any securities exchange or listing entity on which a Party’s
stock is listed (including any such rule or regulation that may require a Party
to make public disclosures about interim results of a Combined Therapy
Trial).  Notwithstanding the foregoing, Five Prime hereby authorizes disclosure
to Ono in accordance with Section 9.4.  Notwithstanding the foregoing, nothing
herein shall prevent or restrict Ono from making any disclosures of published
Study Data disclosed to it by BMS pursuant to Section 9.4 or of the existence of
this Agreement, in each case in order for Ono to comply with requirements of

Page 67 of 84

 

*** INDICATES MATERIAL THAT WAS OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT WAS
REQUESTED. ALL SUCH OMITTED MATERIAL WAS FILED SEPARATELY WITH THE SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE SECURITIES
EXCHANGE ACT OF 1934, AS AMENDED.

--------------------------------------------------------------------------------

EXECUTION VERSION

 

Applicable Law, the rules or regulations of any securities exchange or listing
entity on which its stock may be traded or pursuant to an order of a court or
governmental entity to publicly disclose the existence of the Agreement and the
Study Data.

9.6Compliance with Sunshine Laws.

(a)For purposes of compliance with reporting obligations under Sunshine Laws,
Five Prime represents that it is not, as of the Effective Date, subject to
reporting obligations under the Sunshine Laws.  Therefore, as between the
Parties, BMS will report payments or other transfers of value (“POTV”) made by
Five Prime or the CRO related to the conduct of the Combined Therapy Trials and
any applicable associated contractor engagements as required under the Sunshine
Laws, for each Combined Therapy Trial initiated prior to such date that Five
Prime becomes responsible for reporting POTV for studies sponsored by it.  BMS
shall request delayed publication for any reported POTV for the studies
sponsored by Five Prime as permitted under the Sunshine Laws and if consistent
with BMS’s normal business practices.  In the event Five Prime becomes
responsible for reporting POTV for studies sponsored by it in a given country
during the Term, Five Prime shall provide written notification to BMS, and the
Parties will meet and confer to discuss how they wish to handle reporting
thereafter.  Interpretation of the Sunshine Laws for purposes of reporting any
POTV by a Party shall be in such Party’s sole discretion so long as the
interpretation complies with Applicable Law.

(b)Five Prime (i) will provide (to the extent in the possession of Five Prime),
or will utilize Commercially Reasonable Efforts to obligate and ensure that each
CRO and other applicable Third Party contractors for a Combined Therapy Trial
provide, BMS with any information requested by BMS as BMS may reasonably
determine is necessary for BMS to comply with its reporting obligations under
Sunshine Laws (with such amounts paid to, or at the direction of, each Recipient
to be reported to BMS within a reasonable time period specified by BMS) and (ii)
will reasonably cooperate with, and will utilize Commercially Reasonable Efforts
to obligate and ensure that each CRO and other applicable Third Party
contractors for a Combined Therapy Trial reasonably cooperate with, BMS in
connection with its compliance with such Sunshine Laws. The form in which Five
Prime provides any such information shall be mutually agreed but sufficient to
enable BMS to comply with its reporting obligations and BMS may disclose any
information that it believes is necessary to comply with Sunshine Laws.   BMS
shall have the right to allocate payments or other transfers of value in
connection with this Agreement in any required reporting under Sunshine Laws in
accordance with its normal business practices. These obligations shall survive
the expiration and termination of the agreement to the extent necessary for BMS
to comply with Sunshine Laws.

(c)For purposes of this Section 9.7, “Sunshine Laws” means Applicable Laws
requiring collection, reporting and disclosure of POTVs to certain healthcare
providers, entities and individuals.  These Applicable Laws may include relevant
provisions of the Patient Protection and Affordable Health Care Act of 2010 and
implementing regulations thereunder.  “Recipients” means healthcare providers,
teaching hospitals and/or any other Persons for whom transfers of value or
payments must be reported under Sunshine Laws.

Page 68 of 84

 

*** INDICATES MATERIAL THAT WAS OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT WAS
REQUESTED. ALL SUCH OMITTED MATERIAL WAS FILED SEPARATELY WITH THE SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE SECURITIES
EXCHANGE ACT OF 1934, AS AMENDED.

--------------------------------------------------------------------------------

EXECUTION VERSION

 

9.7Destruction of Confidential Information.  Upon expiration or termination of
the Agreement, the receiving Party shall, upon request by the other Party,
immediately destroy or return all of the other Party’s Confidential Information
relating solely to such other Party’s Compound as monotherapy (but not to the
Combined Therapy or the Combined Therapy Study Data) in its possession;
provided, however, that the receiving Party shall be entitled to retain one (1)
copy of Confidential Information solely for record-keeping purposes and shall
not be required to destroy any computer files created during automatic system
back up which are subsequently stored securely by the receiving Party

 

Page 69 of 84

 

*** INDICATES MATERIAL THAT WAS OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT WAS
REQUESTED. ALL SUCH OMITTED MATERIAL WAS FILED SEPARATELY WITH THE SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE SECURITIES
EXCHANGE ACT OF 1934, AS AMENDED.

--------------------------------------------------------------------------------

EXECUTION VERSION

 

Article 10

REPRESENTATIONS AND WARRANTIES

10.1Authority and Binding Agreement. Five Prime and BMS each represent and
warrant to the other that (a) it has the corporate power and authority and the
legal right to enter into this Agreement and perform its obligations hereunder;
(b) it has taken all necessary corporate action on its part required to
authorize the execution and delivery of the Agreement and the performance of its
obligations hereunder; and (c) the Agreement has been duly executed and
delivered on behalf of such Party and constitutes a legal, valid and binding
obligation of such Party that is enforceable against it in accordance with its
terms subject to bankruptcy, insolvency, reorganization, arrangement,
winding-up, moratorium, and similar laws of general application affecting the
enforcement of creditors’ rights generally, and subject to general equitable
principles, including the fact that the availability of equitable remedies, such
as injunctive relief or specific performance, is in the discretion of the court.

10.2No Conflicts. Five Prime and BMS each represent, warrant and covenant that,
to the best of its knowledge as of the Effective Date, it has not entered, and
shall not thereafter enter, into any agreement with any Third Party that is or
would be in conflict with the rights granted to the other Party under this
Agreement, and has not taken any action that would in any way prevent it from
granting the rights granted to the other Party under this Agreement, or that
would otherwise materially conflict with or materially adversely affect the
rights granted to the other Party under this Agreement.

10.3Litigation.  Five Prime and BMS each represent and warrant that, to the best
of its knowledge as of the Effective Date, it is not aware of any pending or
threatened litigation (and has not received any communication) that alleges that
its activities related to this Agreement have violated, or that by conducting
the activities as contemplated in this Agreement it would violate, any of the
intellectual property rights of any other Person (after giving effect to the
license grants in this Agreement).

10.4No Adverse Proceedings.  To the knowledge of each Party as of the Effective
Date, no claim, suit, action or governmental proceeding is pending or threatened
against such Party that would, if adversely determined, materially impair the
ability of such Party to perform its obligations under this Agreement or the
Development Plan.

10.5Consents.  Five Prime and BMS each represent and warrant that, to the best
of its knowledge, all necessary consents, approvals and authorizations of all
regulatory and governmental authorities and other Persons (i) required to be
obtained by such Party in connection with the execution and delivery of this
Agreement have been obtained (or will have been obtained prior to such execution
and delivery) and (ii) required to be obtained by such Party in connection with
the performance of its obligations under this Agreement or the Development Plan
have been obtained or will be obtained prior to such performance.

Page 70 of 84

 

*** INDICATES MATERIAL THAT WAS OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT WAS
REQUESTED. ALL SUCH OMITTED MATERIAL WAS FILED SEPARATELY WITH THE SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE SECURITIES
EXCHANGE ACT OF 1934, AS AMENDED.

--------------------------------------------------------------------------------

EXECUTION VERSION

 

10.6No Debarment. Each Party hereby certifies to the other that it has not used,
and will not use the services of any person disqualified, debarred, banned,
subject to debarment or convicted of a crime for which a person could be
debarred by the FDA under 21 U.S.C. 335a, as amended (or subject to a similar
sanction of any other Regulatory Authority), in any capacity in connection with
any of the services or work provided under the Development Plan and that this
certification may be relied upon in any applications to the FDA or any other
Regulatory Authority.  It is understood and agreed that this certification
imposes a continuing obligation upon each Party to notify the other promptly of
any change in the truth of this certification.  Upon request by a Party, the
other Party agrees to provide a list of persons used to perform the services or
work provided under any activities conducted for or on behalf of such Party or
any of its Affiliates pursuant to this Agreement who, within the five years
preceding the Effective Date, or subsequent to the Effective Date, were or are
convicted of one of the criminal offenses required by 21 U.S.C. 335a, as
amended, to be listed in any application for approval of an abbreviated
application for drug approval.

10.7Compliance with Applicable Law.  Each of Five Prime and BMS represents,
warrants and covenants that it shall comply with all Applicable Laws of the
country or other jurisdiction, or any court or agency thereof, applicable to the
performance of its activities hereunder and under the Development Plan or any
obligation or transaction hereunder or under the Development Plan, including
those pertaining to the production and handling of drug products, such as those
set forth by the Regulatory Agencies, as applicable, and the applicable terms of
this Agreement, in the performance of its obligations hereunder.

10.8Affiliates.  Each of Five Prime and BMS represents and warrants that, to the
extent the intellectual property, Regulatory Documentation or Technology
licensed by it hereunder are Controlled by its Affiliates or a Third Party, it
has the right to use, and has the right to grant (sub)licenses to the other
Party to use, such intellectual property, Regulatory Documentation or Technology
in accordance with the terms of this Agreement.

10.9Ethical Business Practices.  Each of Five Prime and BMS represents and
warrants that neither it nor its Affiliates will make any payment, either
directly or indirectly, of money or other assets, including the compensation
such Party derives from this Agreement (collectively a “Payment”), to government
or political party officials, officials of International Public Organizations,
candidates for public office, or representatives of other businesses or Persons
acting on behalf of any of the foregoing (collectively “Officials”) where such
Payment would constitute violation of any law, including the Foreign Corrupt
Practices Act of 1977, 15 U.S.C. §§ 78dd-1, et seq.   In addition, regardless of
legality, neither it nor its Affiliates will make any Payment either directly or
indirectly to Officials if such Payment is for the purpose of improperly
influencing decisions or actions with respect to the subject matter of this
Agreement.  All activities will be conducted in compliance with the U.S. False
Claims Act and the U.S. Anti-Kickback Statute.

Page 71 of 84

 

*** INDICATES MATERIAL THAT WAS OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT WAS
REQUESTED. ALL SUCH OMITTED MATERIAL WAS FILED SEPARATELY WITH THE SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE SECURITIES
EXCHANGE ACT OF 1934, AS AMENDED.

--------------------------------------------------------------------------------

EXECUTION VERSION

 

10.10Single Agent Compound Safety Issues. Each Party represents and warrants
that, to the best of its knowledge, it is not aware of any material safety or
toxicity issue with respect to its Single Agent Compound that are not reflected
in the investigator’s brochure for its Single Agent Compound existing as of the
Effective Date.

10.11Accounting.  Each Party represents and warrants that all transactions under
the Agreement shall be properly and accurately recorded in all material respects
on its books and records and that each document upon which entries in such books
and records are based is complete and accurate in all material respects.

10.12Compliance with Ono Agreements.  BMS shall not breach its obligations under
the Ono-BMS Agreements or voluntarily terminate or amend the Ono-BMS if such
breach, termination or amendment would adversely affect the Parties’ ability to
perform this Agreement or the Development Plan or Five Prime’s rights and
benefits under this Agreement.

10.13No Combination Patents.  As of the Effective Date, BMS represents and
warrants that it does not Control any Patent that claims or discloses, whether
generically or specifically, the use of both the BMS Compound (and/or any other
antibodies that are designed to selectively bind to PD-1) and a Five Prime
Compound (and/or any other antibodies that are designed to selectively bind to
CSF1R)).

10.14DISCLAIMER OF WARRANTY. THE EXPRESS REPRESENTATIONS AND WARRANTIES STATED
IN THIS ARTICLE 10 ARE IN LIEU OF, AND THE PARTIES DO HEREBY DISCLAIM, ALL OTHER
REPRESENTATIONS AND WARRANTIES, EXPRESS, IMPLIED OR STATUTORY, INCLUDING
WARRANTIES OF MERCHANTABILITY, FITNESS FOR A PARTICULAR PURPOSE OR USE, AND
NON-INFRINGEMENT OF THIRD PARTY INTELLECTUAL PROPERTY RIGHTS.

Page 72 of 84

 

*** INDICATES MATERIAL THAT WAS OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT WAS
REQUESTED. ALL SUCH OMITTED MATERIAL WAS FILED SEPARATELY WITH THE SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE SECURITIES
EXCHANGE ACT OF 1934, AS AMENDED.

--------------------------------------------------------------------------------

EXECUTION VERSION

 

Article 11

INDEMNIFICATION

11.1BMS Indemnification. BMS hereby agrees to defend, hold harmless and
indemnify (collectively, “Indemnify”) Five Prime, its Affiliates, and its and
their agents, directors, officers, and employees (the “Five Prime Indemnitees”)
from and against any and all liabilities, expenses and/or losses, including
reasonable legal expenses and attorneys’ fees (collectively “Losses”) resulting
from Third Party suits, claims, actions and demands (each, a “Third Party
Claim”) to the extent that they arise or result from (a) the negligence or
intentional misconduct of BMS, any BMS Indemnitee or any (sub)licensee of BMS
conducting activities on behalf of BMS under this Agreement; (b) any breach by
BMS of any provision of this Agreement; (c) any injury to a subject in a
Combined Therapy Trial or Joint Subsequent Study (but not any other Subsequent
Study) to the extent caused by the development, use or manufacture of the BMS
Compound; (d) any injury to a subject in a Combined Therapy Trial or Joint
Subsequent Study (but not any other Subsequent Study) where it ultimately cannot
be or is not determined if such injury is the direct result of the BMS Compound
on the one hand or the Five Prime Compound on the other hand, provided that, in
the case of this clause (d), BMS shall only Indemnify the Five Prime Indemnitees
for *** of any such Loss; or (e) the use by BMS, its Affiliates, contractors or
(sub)licensees of Combined Therapy Study Data, BMS Study Data, BMS Study
Inventions, BMS Study Patent Rights, Combined Therapy Inventions and Combined
Therapy Patent Rights outside the scope of this Agreement (other than with
respect to Third Party Claims that are covered under Section 6.4)), including in
the conduct of a Parallel Study or Subsequent Study (other than a Joint
Subsequent Study) by BMS; but excluding, in each case ((a) through (e)), any
such Losses to the extent Five Prime is obligated to Indemnify the BMS
Indemnitees pursuant to Section 11.2 or to the extent that the Third Party Claim
is attributable to a failure of the Five Prime Compound used by BMS in a
Parallel Study or Subsequent Study to have been manufactured  in accordance with
applicable specifications.

Page 73 of 84

 

*** INDICATES MATERIAL THAT WAS OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT WAS
REQUESTED. ALL SUCH OMITTED MATERIAL WAS FILED SEPARATELY WITH THE SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE SECURITIES
EXCHANGE ACT OF 1934, AS AMENDED.

--------------------------------------------------------------------------------

EXECUTION VERSION

 

11.2Five Prime Indemnification.  Five Prime hereby agrees to Indemnify BMS, its
Affiliates, and its and their agents, directors, officers, and employees (the
“BMS Indemnitees”) from and against any and all Losses resulting from Third
Party Claims to the extent that they arise or result from (a) the negligence or
intentional misconduct of Five Prime or any Five Prime Indemnitee or any
(sub)licensee of Five Prime conducting activities on behalf of Five Prime under
this Agreement; (b) any breach by Five Prime of any provision of this Agreement;
(c) any injury to a subject in a Combined Therapy Trial or Joint Subsequent
Study (but not any other Subsequent Study) to the extent caused by the
development, use or manufacture of the Five Prime Compound; (d) any injury to a
subject in a Combined Therapy Trial or Joint Subsequent Study (but not any other
Subsequent Study) where it ultimately cannot be or is not determined if such
injury is the direct result of the Five Prime Compound on the one hand or the
BMS Compound on the other hand; provided that, in the case of this clause
(d),  Five Prime shall only Indemnify the BMS Indemnitees for *** of any such
Loss; or (e) the use by Five Prime, its Affiliates, contractors or
(sub)licensees of Combined Therapy Study Data, Five Prime Study Data, Five Prime
Study Inventions, Five Prime Study Patent Rights, Combined Therapy Inventions
and Combined Therapy Patent Rights outside the scope of this Agreement (other
than with respect to Third Party Claims that are covered under Section 6.4)),
including in the conduct of a Parallel Study or Subsequent Study other than a
Joint Subsequent Study) by Five Prime, but excluding, in each case ((a) through
(e)), any such Losses to the extent BMS is obligated to Indemnify the Five Prime
Indemnitees pursuant to Section 11.1 or to the extent that the Third Party Claim
is attributable to a failure of the BMS Compound used by Five Prime in a
Parallel Study or Subsequent Study to have been manufactured  in accordance with
applicable specifications.

11.3Indemnification Procedure. Each Party’s agreement to Indemnify the other
Party is conditioned on the performance of the following by the Party seeking
indemnification: (a) providing written notice to the Indemnifying Party of any
Loss of the types set forth in Section 11.1 and 11.2 within *** after the Party
seeking indemnification has knowledge of such Loss; provided that any delay in
complying with the requirements of this clause (a) will only limit the
Indemnifying Party’s obligation to the extent of the prejudice caused to the
Indemnifying Party by such delay; (b) permitting the Indemnifying Party to
assume full responsibility to investigate, prepare for and defend against any
such Loss; (c) providing reasonable assistance to the Indemnifying Party, at the
Indemnifying Party’s expense, in the investigation of, preparation for and
defense of any Loss; and (d) not compromising or settling such Loss without the
Indemnifying Party’s written consent, such consent not to be unreasonably
withheld or delayed.

11.4Separate Defense of Claims. In the event that the Parties cannot agree as to
the application of Sections 11.1, 11.2 and/or 11.3 to any particular Loss, the
Parties may conduct separate defenses of such Loss. Each Party further reserves
the right to claim indemnity from the other in accordance with Sections 11.1,
11.2 and/or 11.3 upon resolution of the underlying claim, notwithstanding the
provisions of Section 11.3(b).

Page 74 of 84

 

*** INDICATES MATERIAL THAT WAS OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT WAS
REQUESTED. ALL SUCH OMITTED MATERIAL WAS FILED SEPARATELY WITH THE SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE SECURITIES
EXCHANGE ACT OF 1934, AS AMENDED.

--------------------------------------------------------------------------------

EXECUTION VERSION

 

11.5Insurance.  Each Party shall maintain commercially reasonable levels of
insurance or other adequate and commercially reasonable forms of protection or
self-insurance to satisfy its indemnification obligations under this
Agreement.  Each Party shall provide the other Party with written notice at
least *** prior to the cancellation, non-renewal or material change in such
insurance or self-insurance which would materially adversely affect the rights
of the other Party hereunder.  The maintenance of any insurance shall not
constitute any limit or restriction on damages available to a Party under this
Agreement.

11.6LIMITATION OF LIABILITY.

(a)NEITHER PARTY SHALL BE LIABLE TO THE OTHER PARTY FOR INDIRECT, INCIDENTAL,
CONSEQUENTIAL OR SPECIAL DAMAGES, INCLUDING BUT NOT LIMITED TO LOST PROFITS,
ARISING FROM OR RELATING TO THIS AGREEMENT AND/OR SUCH PARTY’S PERFORMANCE
HEREUNDER, REGARDLESS OF ANY NOTICE OF THE POSSIBILITY OF SUCH DAMAGES AND
REGARDLESS OF THE CAUSE OF ACTION (WHETHER IN CONTRACT, TORT, BREACH OF WARRANTY
OR OTHERWISE).  NOTHING IN THIS SECTION 11.6(a) IS INTENDED TO LIMIT OR RESTRICT
THE INDEMNIFICATION RIGHTS OR OBLIGATIONS OF A PARTY UNDER SECTIONS 11.1 OR
11.2, OR DAMAGES AVAILABLE FOR BREACHES OF CONFIDENTIALITY OBLIGATIONS IN
ARTICLE 9 OR FOR A PARTY’S WILLFUL MISCONDUCT.

(b)EACH PARTY’S MAXIMUM, CUMULATIVE LIABILITY ARISING OUT OF OR RELATING TO A
GIVEN COMBINED THERAPY TRIAL PERFORMED PURSUANT TO THIS AGREEMENT AND THE
DEVELOPMENT PLAN AND/OR SUCH PARTY’S PERFORMANCE RELATING THERETO, REGARDLESS OF
THE CAUSE OF ACTION (WHETHER IN CONTRACT, TORT, BREACH OF WARRANTY, INDEMNITY OR
OTHERWISE), WILL NOT EXCEED IN THE AGGREGATE FOR ALL CLAIMS RELATING TO SUCH
COMBINED THERAPY TRIAL THE GREATER OF (1) *** OR (2) *** OF ALL TOTAL TP STUDY
COSTS INCURRED  FOR SUCH COMBINED THERAPY TRIAL; PROVIDED, HOWEVER, THAT NOTHING
IN THIS SECTION 11.6(b) IS INTENDED TO LIMIT OR RESTRICT THE INDEMNIFICATION
RIGHTS OR OBLIGATIONS OF A PARTY UNDER SECTIONS 11.1 OR 11.2, OR ANY DAMAGES
AVAILABLE FOR BREACHES OF CONFIDENTIALITY OBLIGATIONS IN ARTICLE 9 OR FOR A
PARTY’S WILLFUL MISCONDUCT.

Page 75 of 84

 

*** INDICATES MATERIAL THAT WAS OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT WAS
REQUESTED. ALL SUCH OMITTED MATERIAL WAS FILED SEPARATELY WITH THE SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE SECURITIES
EXCHANGE ACT OF 1934, AS AMENDED.

--------------------------------------------------------------------------------

EXECUTION VERSION

 

Article 12

TERM AND TERMINATION

12.1Term.  This Agreement shall be effective as of the Effective Date and,
unless earlier terminated pursuant to Sections 12.2, 12.3 or 12.4 or any other
termination right expressly stated in this Agreement, shall continue in effect
until the date which is ninety (90) days subsequent to completion by all centers
or institutions participating in the Combined Therapy Trials, the delivery of
all Study Data, including all completed case report forms, all final analyses
and all final clinical study reports contemplated by the Combined Therapy
Trials, to both Parties, and the completion of the Development Plan and any
then-agreed upon Statistical Analysis and Bioanalysis Plan (the “Term”).

12.2Termination for Material Breach.

(a)Notice and Cure Period.  If a Party (the “Breaching Party”) is in material
breach, the other Party (the “Non-Breaching Party”) shall have the right to give
the Breaching Party notice specifying the nature of such material breach.  The
Breaching Party shall have a period of *** after receipt of such notice to cure
such material breach (the “Cure Period”) in a manner reasonably acceptable to
the Non-Breaching Party.  For the avoidance of doubt, this provision is not
intended to restrict in any way either Party’s right to notify the other Party
of any other breach or to demand the cure of any other breach.

(b)Termination Right.  The Non-Breaching Party shall have the right to terminate
this Agreement, upon written notice, in the event that the Breaching Party has
not cured such material breach within the Cure Period, provided, however, that
if such breach is capable of cure but cannot reasonably be cured within the Cure
Period, and the Breaching Party notifies the non-Breaching Party of its intent
to cure such material breach, commences actions to cure such material breach
within the Cure Period and thereafter diligently continues such actions, the
Breaching Party shall have an additional *** to cure such breach.  If a Party
contests such termination pursuant to the dispute resolution procedures under
Section 13.3, such termination shall not be effective until a conclusion of the
dispute resolution procedures in Section 13.3, as applicable, resulting in a
determination that there has been a material breach that was not cured within
the Cure Period (or, if earlier, abandonment of the dispute by such Party).

12.3Termination for Bankruptcy.  Either Party may terminate this Agreement if,
at any time, the other Party shall file in any court or agency pursuant to any
statute or regulation of any state, country or jurisdiction, a petition in
bankruptcy or insolvency or for reorganization or for an arrangement or for the
appointment of a receiver or trustee of such other Party or of such other
Party’s assets, or if the other Party proposes a written agreement of
composition or extension of its debts, or if the other Party shall be served
with an involuntary petition against it, filed in any insolvency proceeding, and
such petition shall not be dismissed or stayed within *** after the filing
thereof, or if the other Party will propose or be a party to any dissolution or
liquidation, or if the other Party shall make an assignment for the benefit of
its creditors.

Page 76 of 84

 

*** INDICATES MATERIAL THAT WAS OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT WAS
REQUESTED. ALL SUCH OMITTED MATERIAL WAS FILED SEPARATELY WITH THE SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE SECURITIES
EXCHANGE ACT OF 1934, AS AMENDED.

--------------------------------------------------------------------------------

EXECUTION VERSION

 

12.4Termination due to Material Safety Issue; Clinical Hold.

(a)Either Party shall have the right to terminate this Agreement immediately
upon written notice if it reasonably deems it necessary to protect the safety,
health or welfare of subjects enrolled in any Combined Therapy Trial due to the
existence of a Material Safety Issue.  In the event of a termination due to a
Material Safety Issue, prior to the terminating Party providing written notice,
each Party’s safety committee shall, to the extent practicable, meet and discuss
in good faith the safety concerns raised by the terminating Party and consider
in good faith the input, questions and advice of the non-terminating Party, but
should any dispute arise in such discussion, the dispute resolution processes
set forth in Sections 2.8 or 13.3 shall not apply to such dispute and the
terminating Party shall have the right to issue such notice and such termination
shall take effect without the Parties first following the procedures set forth
in Sections 2.8 or 13.3.

(b)If a Clinical Hold with respect to either the BMS Compound or the Five Prime
Compound should arise at any time after the Effective Date, the Parties will
meet and discuss the basis for the Clinical Hold, how long the Clinical Hold is
expected to last, and how they might address the issue that caused the clinical
hold.  If, after ninety (90) days of discussions following the Clinical Hold,
either Party reasonably concludes that the issue is not solvable or that
unacceptable and material additional costs/delays have been and/or will continue
to be incurred in the conduct of the Combined Therapy Trial, then such Party may
immediately terminate this Agreement.

Page 77 of 84

 

*** INDICATES MATERIAL THAT WAS OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT WAS
REQUESTED. ALL SUCH OMITTED MATERIAL WAS FILED SEPARATELY WITH THE SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE SECURITIES
EXCHANGE ACT OF 1934, AS AMENDED.

--------------------------------------------------------------------------------

EXECUTION VERSION

 

12.5Effect of Termination. Upon expiration or termination of this Agreement, (a)
the licenses granted to each Party to conduct the activities in the Development
Plan in Sections 3.1 and 3.2 shall terminate, but the license grants to conduct
Subsequent Studies under Sections 3.1 and 3.2 (and section 5.3(d)(ix)) shall not
terminate unless this Agreement is terminated pursuant to Sections 2.1(e), 12.2
(but termination of such license grant shall apply only to the Party who
materially breached the Agreement), 12.3 (but termination of such license grant
shall apply only to the licensee Party who is insolvent or bankrupt), 12.4(a),
12.4(b), (b) Rights of Cross-Reference to conduct a Parallel Study or Subsequent
Study shall only be permitted shall only be permitted where the licensee Party
has the right to conduct same under clause (a) of this Section 12.5, and (c) the
Parties shall use reasonable efforts to wind down activities under this
Agreement and the Development Plan in a reasonable manner and avoid incurring
any additional expenditures or non-cancellable obligations; provided that, in
the case of termination pursuant to Section 12.4, Five Prime may continue to
dose subjects enrolled in any then ongoing Combined Therapy Trial through
completion of the applicable Protocol if dosing is required by the applicable
Regulatory Authority(ies) and/or Applicable Law(s). Any such wind-down
activities will include the return to BMS, or destruction, of all BMS Compound
provided to Five Prime and not consumed in the performance of the Development
Plan.  If applicable, upon termination of this Agreement, the Parties shall
remain responsible pursuant to the terms of this Agreement for any expenses
incurred that are associated with terminating any ongoing clinical trial work
and/or result from such ongoing activities under this Agreement solely to the
extent such activities are deemed necessary by Five Prime (after discussion at a
meeting of the JDC) based on reasonable medical judgment to protect the health
of subjects participating in any Combined Therapy Trial.

12.6Survival.  The following Articles and Sections of this Agreement and all
definitions relating thereto shall survive any expiration or termination of this
Agreement for any reason: Section 2.1(b) (second sentence), Section
3.5(c)(iii)(6), Section 3.5(c)(iii)(9), Section 3.5(c)(iv), Section 3.5(c)(v),
Section 5.1(a)(viii), Section 5.1(b)(iii), Section 5.4 (“Additional Studies”)
(to the extent provided therein), Article 6 (“Intellectual Property”), Section
7.1 (“One-time Payment”), Section 7.2 (“Combined Therapy Trial Expenses”),
Section 7.3 (“Invoicing; Payment”), Section 8.1 (“Records”), Section 8.2
(“Ownership of Study Data”), Section 8.3 (“Use of Study Data”), Section 8.4
(“Access to Study Data”), Section 8.5 (“Samples”), Article 9
(“Confidentiality”); Article 10 (“Representations and Warranties”), Article 11
(“Indemnification”), Section 12.5 (“Effect of Termination”), Section 12.6
(“Survival”), Section 13.1 (“Entire Agreement”), Section 13.2 (“Governing Law”),
Section 13.3 (“Dispute Resolution”), Section 13.4 (“Injunctive Relief”), Section
13.6 (“Notices”), Section 13.7 (“No Waiver, Modifications”), Section 13.8 (“No
Strict Construction”), Section 13.9 (“Independent Contractor”), Section 13.10
(“Assignment”), Section 13.11 (“Headings”), Section 13.13 (“Severability”),
Section 13.15 (“No Benefit to Third Parties”), Section 13.16 (“Construction”).

Page 78 of 84

 

*** INDICATES MATERIAL THAT WAS OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT WAS
REQUESTED. ALL SUCH OMITTED MATERIAL WAS FILED SEPARATELY WITH THE SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE SECURITIES
EXCHANGE ACT OF 1934, AS AMENDED.

--------------------------------------------------------------------------------

EXECUTION VERSION

 

Article 13

MISCELLANEOUS

13.1Entire Agreement. The Parties acknowledge that this Agreement shall govern
all activities of the Parties with respect to the Development Plan  from the
Effective Date forward.  This Agreement, including the Exhibits hereto and
together with the Development Plan, Quality Agreement and Pharmacovigilance
Agreement, sets forth the complete, final and exclusive agreement between the
Parties concerning the subject matter hereof and supersedes all prior agreements
and understandings between the Parties with respect to such subject
matter.  There are no covenants, promises, agreements, warranties,
representations, conditions or understandings, either oral or written, between
the Parties with respect to such subject matter other than as are set forth in
this Agreement.  All Exhibits attached hereto are incorporated herein as part of
this Agreement.

13.2Governing Law.  This Agreement and all claims relating to or arising out of
this Agreement or the breach thereof shall be governed and construed in
accordance with the internal laws of the State of Delaware, USA, excluding any
choice of law rules that may direct the application of the laws of another
jurisdiction.

13.3Dispute Resolution.

(a)In the event of any dispute, controversy or claim arising out of, relating to
or in connection with any provision of this Agreement (each a “Dispute”), other
than a JDC Dispute or a Publication Dispute or a dispute as to whether a
Material Safety Issue exists, the Parties shall refer such Dispute promptly to
the Alliance Managers for resolution.  If the Alliance Managers are unable to
resolve such Dispute within *** after a matter has been presented to them, then
upon the request of either Party by written notice, the Parties shall refer such
Dispute to the Executive Officers.  This Agreement shall remain in effect during
the pendency of any such dispute.  In the event that no resolution is made by
them in good faith negotiations within *** after such referral to them, such
unresolved Dispute shall be referred to the Chief Executive Officer of Five
Prime or his or her designee and the Chief Scientific Officer of BMS or his or
her designee for attempted resolution by good faith negotiations within ***
after such referral is made.  In the event such officers are unable to resolve
such Dispute within such *** period then, if such Dispute constitutes an
Arbitration Matter, such Dispute shall be resolved through arbitration in
accordance with Section 13.3(b); provided, however, that with respect to any
such Dispute that relates to a matter described in Section 13.4, either Party
shall have the right to seek an injunction or other equitable relief without
waiting for the expiration of such *** negotiation period, and with respect to
any JDC Dispute or Publication Dispute, the specific dispute resolution
processes contained in Sections 2.8 or 9.5(b), as applicable, will apply.

Page 79 of 84

 

*** INDICATES MATERIAL THAT WAS OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT WAS
REQUESTED. ALL SUCH OMITTED MATERIAL WAS FILED SEPARATELY WITH THE SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE SECURITIES
EXCHANGE ACT OF 1934, AS AMENDED.

--------------------------------------------------------------------------------

EXECUTION VERSION

 

(b)If a Dispute that constitutes an Arbitration Matter remains unresolved after
escalation to the senior executives as described above, either Party may refer
the matter to arbitration as described herein. Any arbitration under this
Agreement shall be conducted under the auspices of the American Arbitration
Association (the “AAA”) by a panel of three (3) arbitrators pursuant to that
organization’s Commercial Arbitration Rules then in effect; provided, however,
that the Parties hereby agree that the time schedule for the appointment of
arbitrators and the time schedule for submission of the statement of defense
shall follow the American Arbitration Association Arbitration Rules.  The fees
and expenses of the arbitrators shall be borne in equal shares by the Parties.
Each Party shall bear the fees and expenses of its legal representation in the
arbitration. The arbitral tribunal shall not reallocate either the fees and
expenses of the arbitrators or of the Parties’ legal representation. The
language of the arbitration shall be English.

(c)Disputes with respect to matters specifically set forth in Section 2.8(c)
shall be resolved through baseball arbitration, in accordance with the
Commercial Arbitration Rules of the AAA then in effect.  Baseball arbitration
will be conducted by one (1) arbitrator who shall be reasonably acceptable to
the Parties and who shall be appointed in accordance with AAA rules.  If the
Parties are unable to select an arbitrator within *** of the date that the
Executive Officers decide to escalate any applicable matter to arbitration, then
the arbitrator shall be appointed in accordance with AAA rules. Any arbitrator
chosen hereunder shall have educational training and industry experience
sufficient to demonstrate a reasonable level of scientific, financial, medical
and industry knowledge relevant to the particular dispute. Within *** after the
selection of the arbitrator, each Party shall submit to the arbitrator and the
other Party a proposed resolution of the dispute that is the subject of the
arbitration, together with any relevant evidence in support thereof (the
“Proposals”).  Within *** after the delivery of the last Proposal to the
arbitrator, each Party may submit a written rebuttal of the other Party’s
Proposal and may also amend and re-submit its original Proposal.  The Parties
and the arbitrator shall meet within *** after the Parties have submitted their
final Proposals (and rebuttals, if any), at which time each Party shall have ***
to argue in support of its Proposal.  The Parties shall not have the right to
call any witnesses in support of their arguments, nor compel any production of
documents or take any discovery from the other Party in preparation for the
meeting. Within *** after such meeting, the arbitrator shall select one of the
final Proposals so submitted by one of the Parties as the resolution of the
dispute, but may not alter the terms of either final Proposal and may not
resolve the dispute in a manner other than by selection of one of the submitted
final Proposals. If a Party fails to submit a Proposal within the initial time
frame set forth in the fourth sentence of this Section 13.3(c), the arbitrator
shall select the Proposal of the other Party as the resolution of the dispute.
Any time period set forth in this Section 13.3(c) may be extended by agreement
of the Parties.

Page 80 of 84

 

*** INDICATES MATERIAL THAT WAS OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT WAS
REQUESTED. ALL SUCH OMITTED MATERIAL WAS FILED SEPARATELY WITH THE SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE SECURITIES
EXCHANGE ACT OF 1934, AS AMENDED.

--------------------------------------------------------------------------------

EXECUTION VERSION

 

13.4Injunctive Relief.  Notwithstanding anything herein to the contrary, a Party
may seek an injunction or other injunctive relief from any court of competent
jurisdiction in order to prevent immediate and irreparable injury, loss or
damage on a provisional basis.  For the avoidance of doubt, if either Party (a)
discloses Confidential Information of the other Party other than as permitted
under Article 9, (b) uses (in the case of Five Prime) the BMS Compound or BMS
Technology or (in the case of BMS) the Five Prime Compound or Five Prime
Technology in any manner other than as expressly permitted under this Agreement
or (c) otherwise is in material breach of this Agreement and such material
breach could cause immediate harm to the value of the Five Prime Compound (by
BMS) or the BMS Compound (by Five Prime), the other Party shall have the right
to seek an injunction or other equitable relief precluding the other Party from
continuing its activities related to the applicable activity without waiting for
the conclusion of the dispute resolution procedures under Section 13.3.

13.5Force Majeure. The Parties shall be excused from the performance of their
obligations under this Agreement (other than the payment of monies owed to the
other Party) to the extent that such performance is prevented by force majeure
and the non-performing Party promptly provides notice of the prevention to the
other Party.  Such excuse shall be continued so long as the condition
constituting force majeure continues and the nonperforming Party takes
reasonable efforts to remove the condition.  For purposes of this Agreement,
force majeure shall mean acts of God, strikes or other concerted acts of workers
(except for strikes or other concerted acts of a Party’s respective workers),
civil disturbances, fires, earthquakes, acts of terrorism, floods, explosions,
riots, war, rebellion, sabotage or failure or default of public utilities or
common carriers or similar conditions beyond the control of the Parties.

13.6Notices.  Any notice required or permitted to be given under this Agreement
shall be in writing, shall specifically refer to this Agreement and shall be
deemed to have been sufficiently given for all purposes if such notice is timely
and is: (a) mailed by first class certified or registered mail, postage prepaid,
return receipt requested, (b) sent by express delivery service, or (c)
personally delivered.  Unless otherwise specified in writing, the mailing
addresses of the Parties shall be as described below.

For Five Prime:

Five Prime Therapeutics, Inc.

 

2 Corporate Drive

 

South San Francisco, California 94080

 

Attention:  Chief Business Officer

 

With a copy to:

Five Prime Therapeutics, Inc.

 

2 Corporate Drive

 

South San Francisco, California 94080

 

Attention:  General Counsel

 

Page 81 of 84

 

*** INDICATES MATERIAL THAT WAS OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT WAS
REQUESTED. ALL SUCH OMITTED MATERIAL WAS FILED SEPARATELY WITH THE SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE SECURITIES
EXCHANGE ACT OF 1934, AS AMENDED.

--------------------------------------------------------------------------------

EXECUTION VERSION

 

For BMS:

Bristol-Myers Squibb Company

 

Route 206 and Province Line Road

 

Princeton, NJ 08543-4000

 

Attention: VP, Business Development

 

With a copy to:

Bristol-Myers Squibb Company

 

Route 206 and Province Line Road

 

Princeton, NJ 08543-4000

 

Attention: VP & Assistant General Counsel,
Licensing and Business Development

 

Any such communication shall be deemed to have been received when delivered.  It
is understood and agreed that this Section 13.6 is not intended to govern the
day-to-day business communications necessary between the Parties in performing
their duties, in due course, under the terms of this Agreement.

13.7No Waiver; Modifications.  It is agreed that no waiver by a Party of any
breach or default of any of the covenants or agreements herein set forth shall
be deemed a waiver as to any subsequent and/or similar breach or default.  The
failure of either Party to insist on the performance of any obligation hereunder
shall not be deemed to be a waiver of any such obligation.  No amendment,
modification, release or discharge shall be binding upon the Parties unless in
writing and duly executed by authorized representatives of both Parties.

13.8No Strict Construction.  This Agreement has been prepared jointly and shall
not be strictly construed against either Party. No presumption as to
construction of this Agreement shall apply against either Party with respect to
any ambiguity in the wording of any provision(s) of this Agreement irrespective
of which Party may be deemed to have authored the ambiguous provision(s).

13.9Independent Contractor.  The Parties are independent contractors of each
other, and the relationship between the Parties shall not constitute a
partnership, joint venture or agency. Neither Party shall be the agent of the
other or have any authority to act for, or on behalf of, the other Party in any
matter.

13.10Assignment; Licensees.

(a)Assignment.  Neither Party may assign or transfer this Agreement or any
rights or obligations hereunder without the prior written consent of the other
Party, except that a Party may make such an assignment without the other Party’s
consent (a) to an Affiliate, (b) to a Third Party that merges with, consolidates
with or acquires substantially all of the assets or voting control of the
assigning Party or (c) to a Third Party that acquires all the rights to the Five
Prime Compound, in the case of Five Prime, or the BMS Compound, in the case of
BMS. Any assignment or attempted assignment by any Party in violation of the
terms of this Section 13.10 shall be null and void and of no legal effect.

Page 82 of 84

 

*** INDICATES MATERIAL THAT WAS OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT WAS
REQUESTED. ALL SUCH OMITTED MATERIAL WAS FILED SEPARATELY WITH THE SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE SECURITIES
EXCHANGE ACT OF 1934, AS AMENDED.

--------------------------------------------------------------------------------

EXECUTION VERSION

 

(b)Licensees.  If a Party grants a Third Party a license (other than a license
solely to make a Product for a Party and other than any license rights granted
to Ono for the Ono Territory) to develop and commercialize its Single Agent
Compound on a worldwide basis or in any geographic region and/or for all
purposes or a limited field, (a “Licensee”), such Party will obtain the
Licensee’s agreement to abide by the terms of this Agreement in the same manner
as the licensor Party and to not take any action that is inconsistent with such
Party’s obligations under Section 5.4.

13.11Headings.  The captions to the several Sections and Articles hereof are not
a part of this Agreement, but are included merely for convenience of reference
only and shall not affect its meaning or interpretation.

13.12Counterparts.  This Agreement may be executed in two (2) or more
counterparts, each of which shall be deemed an original, but all of which
together shall constitute one (1) and the same instrument.  This Agreement may
be executed by facsimile or electronic (e.g., .pdf) signatures and such
signatures shall be deemed to bind each Party as if they were original
signatures.

13.13Severability. If any provision of this Agreement is held to be illegal,
invalid or unenforceable under any present or future law, and if the rights or
obligations of a Party under this Agreement will not be materially and adversely
affected thereby, (a) such provision shall be fully severable, (b) this
Agreement shall be construed and enforced as if such illegal, invalid or
unenforceable provision had never comprised a part hereof, (c) the remaining
provisions of this Agreement shall remain in full force and effect and shall not
be affected by the illegal, invalid or unenforceable provision or by its
severance herefrom and (d) in lieu of such illegal, invalid or unenforceable
provision, there shall be added automatically as a part of this Agreement a
legal, valid and enforceable provision as similar in terms to such illegal,
invalid or unenforceable provision as may be possible and reasonably acceptable
to the Parties.

13.14Further Assurance. Each Party shall duly execute and deliver, or cause to
be duly executed and delivered, such further instruments and do and cause to be
done such further acts and things, including the filing of such assignments,
agreements, documents and instruments, as may be necessary or as the other Party
may reasonably request in order to perfect any license, assignment or other
transfer or any properties or rights under, or pursuant, to this Agreement.

13.15No Benefit to Third Parties.  The representations, warranties and
agreements set forth in this Agreement are for the sole benefit of the Parties
and their successors and permitted assigns, and they shall not be construed as
conferring any rights on any other parties.

Page 83 of 84

 

*** INDICATES MATERIAL THAT WAS OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT WAS
REQUESTED. ALL SUCH OMITTED MATERIAL WAS FILED SEPARATELY WITH THE SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE SECURITIES
EXCHANGE ACT OF 1934, AS AMENDED.

--------------------------------------------------------------------------------

EXECUTION VERSION

 

13.16Construction.

(a)General.  Except as otherwise explicitly specified to the contrary, (a)
references to a Section, Article or Exhibit means a Section or Article of, or
Exhibit to, this Agreement and all subsections thereof, unless another agreement
is specified; (b) references to a particular statute or regulation include all
rules and regulations promulgated thereunder and any successor statute, rules or
regulations then in effect, in each case including the then-current amendments
thereto; (c) words in the singular or plural form include the plural and
singular form, respectively; (d) the terms “including,” “include(s),” “such as,”
and “for example” used in this Agreement mean including the generality of any
description preceding such term and will be deemed to be followed by “without
limitation”; and (e) the words “hereof,” “herein,” “hereunder,” “hereby” and
derivative or similar words refer to this Agreement.   No presumption as to
construction of this Agreement shall apply against either Party with respect to
any ambiguity in the wording of any provision(s) of this Agreement irrespective
of which Party may be deemed to have authored the ambiguous provision(s).

(b)No Response.  Where a provision of this Agreement provides for a Party to
respond within a designated period following written notice from the other Party
(e.g., Sections 5.1(a)(vi) and 5.1(b)(iv), and if such Party fails to respond,
then the failure to respond shall not be deemed to create or imply: (i) that the
non-responding Party agrees or disagrees with the proposed action to be taken by
the other Party, (ii) any amendment, change or waiver of the terms of this
Agreement, or (iii) any consent that an action proposed to be taken may be taken
if it conflicts with the terms of this Agreement and/or waiver of any rights it
may have to seek remedies at law or in equity for breach of this Agreement as a
result of the action taken.

[Signature page follows]

 

Page 84 of 84

 

*** INDICATES MATERIAL THAT WAS OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT WAS
REQUESTED. ALL SUCH OMITTED MATERIAL WAS FILED SEPARATELY WITH THE SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE SECURITIES
EXCHANGE ACT OF 1934, AS AMENDED.

--------------------------------------------------------------------------------

EXECUTION VERSION

 

IN WITNESS WHEREOF, the Parties, intending to be legally bound hereby, have
caused this Agreement to be executed by their duly authorized representatives as
of the Effective Date.

 

Five Prime Therapeutics Inc.

Bristol-Myers Squibb Company

By: /s/ Lewis T. Williams                  

Lewis T. Williams

President and Chief Executive Officer

 

 

By: /s/ Lynne M. Croucher                

Name: Lynne M. Croucher                

Title: Executive Director, BD            

Date: November 21, 2014                 

Date: November 21, 2014                 

 

 

[SIGNATURE PAGE TO CLINICAL TRIAL COLLABORATION AGREEMENT]

 

*** INDICATES MATERIAL THAT WAS OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT WAS
REQUESTED. ALL SUCH OMITTED MATERIAL WAS FILED SEPARATELY WITH THE SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE SECURITIES
EXCHANGE ACT OF 1934, AS AMENDED.

--------------------------------------------------------------------------------

EXECUTION VERSION

 

Exhibit Index

Attached:

Exhibit A:Bioanalysis Plan

Exhibit B:Protocol Synopsis Template

Exhibit C:Press Release

Exhibit D:Potential Countries for Subsequent/Parallel Studies

 

 

- i –

 

*** INDICATES MATERIAL THAT WAS OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT WAS
REQUESTED. ALL SUCH OMITTED MATERIAL WAS FILED SEPARATELY WITH THE SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE SECURITIES
EXCHANGE ACT OF 1934, AS AMENDED.

--------------------------------------------------------------------------------

EXECUTION VERSION

 

EXHIBIT A

BIOANALYSIS PLAN

***

 

 

 

Page A-1

 

*** INDICATES one page of MATERIAL THAT WAS OMITTED AND FOR WHICH CONFIDENTIAL
TREATMENT WAS REQUESTED. ALL SUCH OMITTED MATERIAL WAS FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE
SECURITIES EXCHANGE ACT OF 1934, AS AMENDED.

--------------------------------------------------------------------------------

EXECUTION VERSION

 

EXHIBIT B

PROTOCOL SYNOPSIS TEMPLATE

Clinical Protocol PROTOCOL NUMBER

 

Protocol Title:  Protocol Title

 

Investigational Product(s), Dose and Mode of Administration, Duration of
Treatment with Investigational Product(s): [Click here to enter text]

 

Study Phase:  [Click here to enter text]

 

Research Hypothesis: [Click here to enter text]

 

Objectives: [Click here to enter text]

 

Study Design:  [Click here to enter text]

[Do not insert page break. Click here to add schematic]

 

Study Population: [Click here to enter text]

Study Drug: includes both Investigational [Medicinal] Products (IP/IMP) and
Non-investigational [Medicinal] Products (Non-IP/Non-IMP) as listed:

Study Drug for XXXXXXXX

Medication

Potency

IP/Non-IP

 

 

 

 

Study Assessments: [Click here to enter text]

 

Statistical Considerations:

Sample Size: [Click here to enter text]

Endpoints: [Click here to enter text]

Analyses:  [Click here to enter text]

 

Page B-1

 

*** INDICATES MATERIAL THAT WAS OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT WAS
REQUESTED. ALL SUCH OMITTED MATERIAL WAS FILED SEPARATELY WITH THE SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE SECURITIES
EXCHANGE ACT OF 1934, AS AMENDED.

--------------------------------------------------------------------------------

EXECUTION VERSION

 

EXHIBIT C

PRESS RELEASE

 

[g201503181915284837304.jpg]

[g201503181915287487305.jpg]

 

Bristol-Myers Squibb and Five Prime Therapeutics Announce Exclusive Clinical
Collaboration to Evaluate the Combination of Investigational Immunotherapies
Opdivo (nivolumab) and FPA008 in Six Tumor Types

(NEW YORK and SOUTH SAN FRANCISCO, CA – November 24, 2014) - Bristol-Myers
Squibb Company (NYSE:BMY) and Five Prime Therapeutics, Inc. (Nasdaq:FPRX) today
announced that they have entered into an exclusive clinical collaboration
agreement to evaluate the safety, tolerability and preliminary efficacy of
combining Opdivo (nivolumab), Bristol-Myers Squibb’s investigational PD-1 immune
checkpoint inhibitor, with FPA008, Five Prime’s monoclonal antibody that
inhibits colony stimulating factor-1 receptor (CSF1R). The Phase 1a/1b study
will evaluate the combination of Opdivo and FPA008 as a potential treatment
option for patients with non-small cell lung cancer (NSCLC), melanoma, head and
neck cancer, pancreatic cancer, colorectal cancer and malignant glioma.
Bristol-Myers Squibb has proposed the name Opdivo, which, if approved by health
authorities, will serve as the trademark for nivolumab.

Opdivo and FPA008 are part of a new class of cancer treatments known as
immunotherapies that are designed to harness the body’s own immune system to
fight cancer. Opdivo is approved in Japan for the treatment of patients with
unresectable melanoma, and is being developed in multiple tumor types in more
than 50 clinical trials. FPA008, in development as a potential treatment for
rheumatoid arthritis (RA) and solid tumors, has initiated dosing for a Phase 1
clinical trial in RA. Preclinical data suggest that combining antibodies
targeting PD-1 and CSF1R may lead to an enhanced anti-tumor immune response
compared to either approach alone in treating cancer.

Page C-1

 

*** INDICATES MATERIAL THAT WAS OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT WAS
REQUESTED. ALL SUCH OMITTED MATERIAL WAS FILED SEPARATELY WITH THE SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE SECURITIES
EXCHANGE ACT OF 1934, AS AMENDED.

--------------------------------------------------------------------------------

EXECUTION VERSION

 

“This collaboration supports our strategy to expand the clinical development of
Opdivo, including novel combination regimens and across numerous tumor types,”
said Michael Giordano, senior vice president, Head of Development, Oncology,
Bristol-Myers Squibb. “We are excited to build upon our existing relationship
with Five Prime Therapeutics in immuno-oncology, and explore the full potential
of Opdivo and FPA008 in multiple tumor types.”

“We are pleased to establish a second collaboration with Bristol-Myers Squibb in
the area of immuno-oncology,” said Lewis T. “Rusty” Williams, M.D., Ph.D.,
president and chief executive officer of Five Prime. “Their vision aligns with
our commitment to advancing promising immune-modulating targets, alone or in
combination, to create next-generation immunotherapies for cancer patients. We
look forward to initiating this study and expanding the development of FPA008 as
a potential immunotherapy for these six types of cancer.”

Under the terms of this agreement, Bristol-Myers Squibb will make a one-time
payment of $30 million to Five Prime and will be responsible for study costs.
Five Prime will conduct the clinical trial, which is expected to begin in the
second half of 2015. The agreement provides for exclusivity with respect to the
development, with a collaborative partner, of combination regimens of an
anti-PD-1/PD-L1 antagonist together with an anti-CSF1R antagonist. Bristol-Myers
Squibb will have a time-limited right of first refusal subject to certain
conditions if Five Prime wishes to seek a partner for FPA008.

About Opdivo (nivolumab)

Cancer cells may exploit “regulatory” pathways, such as checkpoint pathways, to
hide from the immune system and shield the tumor from immune attack. Opdivo is
an investigational, fully-human PD-1 (programmed death-1) immune checkpoint
inhibitor that binds to the checkpoint receptor PD-1 expressed on activated
T-cells.

 

Bristol-Myers Squibb has a broad, global development program to study Opdivo in
multiple tumor types consisting of more than 50 trials – as monotherapy or in
combination with other therapies – in which more than 7,000 patients have been
enrolled worldwide. Among these are several potentially registrational trials in
non-small cell lung cancer (NSCLC), melanoma, renal cell carcinoma (RCC), head
and neck cancer, glioblastoma and NHL.

Page C-2

 

*** INDICATES MATERIAL THAT WAS OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT WAS
REQUESTED. ALL SUCH OMITTED MATERIAL WAS FILED SEPARATELY WITH THE SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE SECURITIES
EXCHANGE ACT OF 1934, AS AMENDED.

--------------------------------------------------------------------------------

EXECUTION VERSION

 

In 2013, the FDA granted Fast Track designation for Opdivo in NSCLC, melanoma
and RCC. In April 2014, the company initiated a rolling submission with the FDA
for Opdivo in third-line pre-treated squamous cell NSCLC and expects to complete
the submission by year-end. The FDA granted its first Breakthrough Therapy
Designation for Opdivo in May 2014 for the treatment of patients with Hodgkin
lymphoma after failure of autologous stem cell transplant and brentuximab. On
July 4, Ono Pharmaceutical Co. announced that Opdivo received manufacturing and
marketing approval in Japan for the treatment of patients with unresectable
melanoma, making Opdivo the first PD-1 immune checkpoint inhibitor to receive
regulatory approval anywhere in the world. On September 26, Bristol-Myers Squibb
announced that the FDA accepted for priority review the Biologics License
Application for previously treated advanced melanoma, and the Prescription Drug
User Fee Act goal date for a decision is March 30, 2015. The FDA also granted
Opdivo Breakthrough Therapy status for this indication. In the European Union,
the European Medicines Agency (EMA) has validated for review the Marketing
Authorization Application (MAA) for Opdivo in advanced melanoma. The application
has also been granted accelerated assessment by the EMA’s Committee for
Medicinal Products for Human Use. The EMA also validated for review the MAA for
Opdivo in NSCLC.

About FPA008

FPA008, an antibody that inhibits colony stimulating factor-1 receptor (CSF1R),
blocks the activation and survival of monocytes and macrophages. Inhibition of
CSF1R in inflamed RA joints blocks the production of inflammatory cytokines by
macrophages and inhibits osteoclasts, monocyte-lineage cells that can cause
bone erosions and joint destruction. Inhibition of CSF1R in many cancers reduces
the number of immunosuppressive tumor-associated macrophages (TAMs), thereby
facilitating an immune response against tumors. 

Page C-3

 

*** INDICATES MATERIAL THAT WAS OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT WAS
REQUESTED. ALL SUCH OMITTED MATERIAL WAS FILED SEPARATELY WITH THE SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE SECURITIES
EXCHANGE ACT OF 1934, AS AMENDED.

--------------------------------------------------------------------------------

EXECUTION VERSION

 

About Bristol-Myers Squibb

Bristol-Myers Squibb is a global biopharmaceutical company whose mission is to
discover, develop and deliver innovative medicines that help patients prevail
over serious diseases. For more information, please visit www.bms.com or follow
us on Twitter at http://twitter.com/bmsnews.

About Five Prime Therapeutics

Five Prime Therapeutics, Inc. discovers and develops innovative therapeutics to
improve the lives of patients with serious diseases. Five Prime's comprehensive
discovery platform, which encompasses virtually every medically relevant
extracellular protein, positions it to explore pathways in cancer, inflammation
and their intersection in cancer immunotherapy, an area of oncology with
significant therapeutic potential and a growing focus of the company's R&D
activities. Five Prime has entered into strategic collaborations with leading
global pharmaceutical companies and has promising product candidates in clinical
and late preclinical development. For more information, please visit
www.fiveprime.com.

Page C-4

 

*** INDICATES MATERIAL THAT WAS OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT WAS
REQUESTED. ALL SUCH OMITTED MATERIAL WAS FILED SEPARATELY WITH THE SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE SECURITIES
EXCHANGE ACT OF 1934, AS AMENDED.

--------------------------------------------------------------------------------

EXECUTION VERSION

 

Bristol-Myers Squibb Forward-Looking Statement

This press release contains “forward-looking statements” as that term is defined
in the Private Securities Litigation Reform Act of 1995 regarding the research,
development and commercialization of pharmaceutical products. Such
forward-looking statements are based on current expectations and involve
inherent risks and uncertainties, including factors that could delay, divert or
change any of them, and could cause actual outcomes and results to differ
materially from current expectations. No forward-looking statement can be
guaranteed. Among other risks, there can be no guarantee that nivolumab will
receive regulatory approval in the U.S. either as a single agent or in a
combination regimen, or, if approved, that it will become a commercially
successful product. Forward-looking statements in this press release should be
evaluated together with the many uncertainties that affect Bristol-Myers
Squibb's business, particularly those identified in the cautionary factors
discussion in Bristol-Myers Squibb's Annual Report on Form 10-K for the year
ended December 31, 2013 in our Quarterly Reports on Form 10-Q and our Current
Reports on Form 8-K. Bristol-Myers Squibb undertakes no obligation to publicly
update any forward-looking statement, whether as a result of new information,
future events or otherwise.

Five Prime Forward-Looking Statement

This press release contains forward-looking statements within the meaning of the
Private Securities Litigation Reform Act of 1995. Words such as "may," "will,"
"expect," "plan," "anticipate," "estimate," "intend" and similar expressions (as
well as other words or expressions referencing future events, conditions or
circumstances) are intended to identify forward-looking statements. These
forward-looking statements are based on Five Prime's expectations and
assumptions as of the date of this press release. Each of these forward-looking
statements involves risks and uncertainties. Actual results may differ
materially from these forward-looking statements. Forward-looking statements
contained in this press release include statements regarding the planned
clinical development of a combination of FPA008 and nivolumab. Factors that may
cause actual results to differ from those expressed or implied in the
forward-looking statements in this press release are discussed in Five Prime's
filings with the U.S. Securities and Exchange Commission, including the "Risk
Factors" contained therein. Except as required by law, Five Prime assumes no
obligation to update any forward-looking statements contained herein to reflect
any change in expectations, even as new information becomes available.

 

Page C-5

 

*** INDICATES MATERIAL THAT WAS OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT WAS
REQUESTED. ALL SUCH OMITTED MATERIAL WAS FILED SEPARATELY WITH THE SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE SECURITIES
EXCHANGE ACT OF 1934, AS AMENDED.

--------------------------------------------------------------------------------

EXECUTION VERSION

 

 

Contacts

 

Bristol-Myers Squibb

 

Media:

Ken Dominski, 609-252-5251, ken.dominski@bms.com

 

Investors:

Ranya Dajani, 609-252-5330, ranya.dajani@bms.com

Ryan Asay, 609-252-5020, ryan.asay@bms.com

 

Five Prime Therapeutics:

Amy Kendall, 415-365-5776, amy.kendall@fiveprime.com

 

Page C-6

 

*** INDICATES MATERIAL THAT WAS OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT WAS
REQUESTED. ALL SUCH OMITTED MATERIAL WAS FILED SEPARATELY WITH THE SECURITIES
AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE SECURITIES
EXCHANGE ACT OF 1934, AS AMENDED.

--------------------------------------------------------------------------------

EXECUTION VERSION

 

EXHIBIT D

POTENTIAL COUNTRIES FOR SUBSEQUENT/PARALLEL STUDIES

***

Page D-1

 

*** INDICATES one page of MATERIAL THAT WAS OMITTED AND FOR WHICH CONFIDENTIAL
TREATMENT WAS REQUESTED. ALL SUCH OMITTED MATERIAL WAS FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE
SECURITIES EXCHANGE ACT OF 1934, AS AMENDED.