<PAGE>
EXECUTION COPY
Exhibit 10.1
Confidential Materials omitted and filed separately with the
Securities and Exchange Commission. Asterisks denote omissions.
RESEARCH COLLABORATION AND OPTION AGREEMENT
by and between
HYBRIDON, INC.
and
NOVARTIS INTERNATIONAL PHARMACEUTICAL LTD.
<PAGE>
RESEARCH COLLABORATION AND OPTION AGREEMENT
This
Research Collaboration and Option Agreement (this "Agreement")
is
made this 31st day of May, 2005 (the
"Effective Date") by and between Hybridon,
Inc., a Delaware corporation with principal
offices at 345 Vassar Street,
Cambridge, Massachusetts 02139 ("Hybridon")
and Novartis International
Pharmaceutical Ltd., a Bermuda corporation
with principal offices at Hurst Holme
12, Trott Road, Hamilton, HM11 Bermuda
("Novartis"). Hybridon and Novartis are
sometimes referred to herein individually
as a "Party" or collectively as the
"Parties."
Capitalized terms used but not defined in this Agreement shall have
the
meanings provided in the License,
Development and Commercialization Agreement by
and between Hybridon and Novartis of even
date herewith (the "License
Agreement").
INTRODUCTION
WHEREAS,
Hybridon possesses expertise in discovering and developing
novel
therapeutics based on IMO (as defined
below) compounds;
WHEREAS,
Novartis and its Affiliates (as defined below) possess
expertise
in discovering, developing, manufacturing,
marketing and selling pharmaceuticals
worldwide;
WHEREAS,
the Parties desire to enter into a collaboration with the
objective of identifying IMO Candidates and
generating IMO Leads (each of "IMO
Candidates" and "IMO Leads" as defined
below) for use in the Research Field of
Use (the "Collaboration"); and
WHEREAS,
the Parties are entering into the License Agreement, pursuant
to
which Novartis and its Affiliates shall
have an exclusive license to
commercialize Products based on certain of
the IMO Candidates in the Commercial
Field of Use upon the terms set forth in
the License Agreement if Novartis
exercises its Commercialization Option
hereunder (each of "Affiliates,"
"Commercial Field of Use,"
"Commercialization Option," "License Agreement,"
"Products," and "Research Field of Use" as
defined below);
NOW
THEREFORE, in consideration of the mutual covenants set forth in
this
Agreement, and other good and valuable
consideration, the Parties agree as
follows:
<PAGE>
ARTICLE I
DEFINITIONS
1.1.
"ACCEPTANCE CRITERIA" shall mean the specifications for IMO
Candidates for acceptance into the CSP
Phase set forth in the Research Plan.
1.2.
"ACQUISITION INTELLECTUAL PROPERTY" shall mean (a) Patents or
Know-How held or otherwise controlled by an
Acquisition Affiliate immediately
prior to the Acquisition Event between
Hybridon and such Acquisition Affiliate
(as defined in Section 1.3 below), other
than Patents that do not specifically
relate to drug delivery or formulation
technology held or otherwise controlled
by any such Acquisition Affiliate that
would, but for a license granted
hereunder, be infringed by the development
or commercialization of IMO
Candidates or IMO Leads and (b) Patents or
Know-How developed or acquired and
controlled by an Acquisition Affiliate
after the Acquisition Event between
Hybridon and such Acquisition Affiliate
that specifically relate to drug
delivery or formulation technology, which
Patents or Know-How are not developed
or acquired through the use of, or as an
improvement to, any Hybridon
Intellectual Property or Hybridon
Background Intellectual Property Controlled
(other than through an Acquisition
Affiliate) by Hybridon.
1.3.
"ACQUISITION EVENT" shall mean any merger or other acquisition
between Hybridon and a Third Party
occurring after the Effective Date and
pursuant to which such Third Party becomes
an Affiliate of Hybridon, so long as
following such merger or acquisition
Hybridon does not control and is not merged
with or into such Affiliate (an
"Acquisition Affiliate").
1.4.
"ADDITIONAL INDICATION" shall have the meaning set forth in
Section
4.1 of the License Agreement.
1.5.
"AFFILIATE" means any Person who directly or indirectly controls
or
is controlled by or is under common control
with a Party. For purposes of this
definition, "control" or "controlled" means
ownership directly or through one or
more Affiliates, of fifty percent (50%) or
more of the shares of stock entitled
to vote for the election of directors, in
the case of a corporation, or fifty
percent (50%) or more of the equity
interest in the case of any other type of
legal entity, status as a general partner
in any partnership, or any other
arrangement whereby a
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Party controls or has the right to control
the Board of Directors or equivalent
governing body of a corporation or other
entity, or the ability to cause the
direction of the management or policies of
a corporation or other entity. The
Parties acknowledge that in the case of
certain entities organized under the
laws of certain countries outside of the
United States, the maximum percentage
ownership permitted by law for a foreign
investor may be less than fifty percent
(50%), and that in such case such lower
percentage shall be substituted in the
preceding sentence, provided, that such
foreign investor has the power to direct
the management and policies of such entity.
For the purposes of this Agreement,
Novartis Institute for Functional Genomics,
Inc. and Friedrich Miescher
Institute for Biomedical Research shall be
deemed to be Affiliates of Novartis.
1.6.
"CHEMICALLY MODIFY" OR "CHEMICAL MODIFICATION" shall mean the
modification of an IMO that [**].
1.7.
"COLLABORATION" shall have the meaning set forth in the preamble
to
this Agreement.
1.8.
"COMMERCIAL FIELD OF USE" shall mean the prophylaxis,
palliation,
diagnosis and treatment of the Initial
Indications and Additional Indications by
Products via any route of
administration.
1.9.
"COMMERCIALIZATION EXERCISE NOTICE" shall have the meaning set
forth
in Section 4.2.2 hereof.
1.10.
"COMMERCIALIZATION OPTION" shall have the meaning set forth in
Section 4.2.1 hereof.
1.11.
"CONFIDENTIAL INFORMATION" shall have the meaning set forth in
Section 5.1 hereof.
1.12.
"CONSUMER PRICE INDEX" shall mean the Consumer Price Index -
Urban
Wage Earners and Clerical Workers, U.S.
City Average, All Items, 1982-84 = 100,
published by the United States Department
of Labor, Bureau of Labor Statistics
(or its successor equivalent index).
1.13.
"CONTROLLED" shall mean, with respect to intellectual property,
the
legal authority of a Party (either directly
or through an Affiliate) to grant
the licenses or sublicenses of
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intellectual property rights as and to the
extent provided herein, or to
otherwise disclose proprietary or trade
secret information as and to the extent
provided herein, without breaching the
terms of any agreement with a Third
Party, knowingly infringing upon the
intellectual property rights of a Third
Party, or misappropriating the proprietary
or trade secret information of a
Third Party.
1.14.
"CRITICAL ISSUE" shall have the meaning set forth in Section
2.5.2
hereof.
1.15. "CSP
PHASE RESEARCH" shall have the meaning set forth in Section
2.3.2 hereof.
1.16.
"EFFECTIVE DATE" shall mean the effective date of this Agreement
as
set forth on the first page hereof.
1.17.
"EPIGENESIS" shall mean EpiGenesis Pharmaceuticals, Inc.
1.18.
"EPIGENESIS AGREEMENT" shall mean that certain Development and
License Agreement, dated as of August 9,
2000, between Hybridon and EpiGenesis.
1.19.
"EXCLUDED ANTISENSE IP" shall mean oligonucleotides or
oligonucleotide analogs or mimics thereof
that (a) are targeted to a specific
sequence of RNA and (b) the primary
mechanism of action of which is to hybridize
to such sequence of RNA and through such
hybridization to modulate the
production of the targeted gene product,
provided, that such oligonucleotides or
oligonucleotide analogs or mimics thereof
[**] proprietary to Hybridon[**].
1.20.
"EXTENDED RENEWAL PERIOD" shall have the meaning set forth in
Section 2.1.3 hereof.
1.21.
"FDA" shall mean the United States Food and Drug Administration,
and
any successor agency serving the same
function.
1.22.
"FPFV" shall mean the first visit of the first patient or first
healthy human volunteer participating in a
clinical trial with respect to an IMO
Lead.
1.23.
"FTE" shall mean the equivalent of the work of one (1) Hybridon
scientist or other Hybridon project
managerial professional, full time for one
year, which equates to a total of [**]
weeks or [**] hours per year on or
directly related to the Research Program
and shall exclude (a) managerial
activities (other than project and research
management activities as
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described below) and (b) assistance with
the manufacturing and supply activities
described in Sections 2.3.2(b) and 2.3.3(b)
hereof. Work on or directly related
to the Research Program may include, but is
not limited to, experimental
laboratory work, work related to Proof of
Concept studies, project and research
management, activities directed toward
evaluation of the commercial potential of
an IMO Candidate, recording and writing up
results, reviewing literature and
references, holding scientific discussions,
and carrying out JRC duties.
1.24. "FTE
RATE" shall mean a rate of [**] U.S. Dollars (U.S. $[**]) per
FTE, to be prorated on a daily basis if
necessary (per annum amount to be
divided by [**] to produce the rate per
whole day consisting of [**]). For the
avoidance of doubt, such rate shall include
all travel expenses, which shall not
be invoiced separately. For each calendar
year commencing with the 2007 calendar
year, the FTE Rate shall be subject to cost
of living increases on an annual
basis, based on the increase in the
Consumer Price Index as of the then most
recent December 31 over the Consumer Price
Index on December 31, 2004, it being
understood that the FTE Rate to be used as
the basis for each such increase, if
any, shall be $[**], and not the most
recent FTE Rate then in effect.
1.25.
"HYBRIDON BACKGROUND INTELLECTUAL PROPERTY" shall mean all
Patents
and Know-How Controlled by Hybridon as of
the Effective Date or at any time
during the Term that are necessary or
useful for the Parties or their Affiliates
or sublicensees to exploit the licenses
contemplated or to carry out the
activities contemplated hereunder and that
are not otherwise Hybridon
Intellectual Property or Joint Intellectual
Property. Notwithstanding the
foregoing, "Hybridon Background
Intellectual Property" shall exclude any
Acquisition Intellectual Property.
1.26.
"HYBRIDON INTELLECTUAL PROPERTY" shall mean all Hybridon Patents
and
Hybridon Know-How, but explicitly excluding
Joint Intellectual Property and any
Acquisition Intellectual Property.
1.27.
"HYBRIDON KNOW-HOW" shall mean all Know-How Controlled by
Hybridon
relating to the IMO Candidates and IMO
Leads but explicitly excluding Joint
Know-How and any Know-How included in the
Acquisition Intellectual Property, as
of the Effective Date or at any time during
the Term.
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1.28.
"HYBRIDON PATENTS" shall mean any Patents Controlled by
Hybridon
that would, but for a license granted
hereunder, be infringed by making, having
made, using, having used, researching,
having researched, developing, having
developed, commercializing, having
commercialized, manufacturing, having
manufactured, promoting, having promoted,
selling, having sold, distributing,
having distributed, marketing, having
marketed, importing, having imported,
exporting or having exported IMO Candidates
or IMO Leads, but explicitly
excluding Joint Patents and any Patents
included in the Acquisition Intellectual
Property, as in effect on the Effective
Date or at any time during the Term. The
Hybridon Patents are set forth on Schedule
1.28 hereto, as amended from time to
time.
1.29.
"IMO" shall mean an immunomodulatory oligonucleotide containing
a
motif proprietary to Hybridon and designed
to agonize toll-like receptor 9
(directly or indirectly) for the primary
purpose of inducing or modulating an
immune response.
1.30. "IMO
CANDIDATE" shall mean an IMO supplied by Hybridon in accordance
with Section 2.3.1(a) and that is
designated by Novartis, in its sole
discretion, as meeting the Acceptance
Criteria and for inclusion in the CSP
Phase Research.
1.31. "IMO
LEAD" shall have the meaning set forth in Section 2.3.2 hereof
and shall include any Improvements thereto.
IMO Leads shall continue to be IMO
Candidates for purposes hereof.
1.32.
"IMPROVEMENTS" shall mean any enhancements to the formulation,
ingredients, preparations, presentation,
means of delivery, dosage, packaging,
or manufacturing process of an IMO Lead,
IMO Candidate or Product, but excluding
as to all of the foregoing any Chemical
Modification to an IMO Lead, IMO
Candidate or the IMO Lead or IMO Candidate
component of a Product. For the
avoidance of doubt, any salt form of an IMO
Lead, IMO Candidate or IMO included
in a Product shall be deemed an Improvement
for purposes hereof.
1.33.
"INDEMNIFIED PERSON" shall have the meaning set forth in Section
7.3
hereof.
1.34.
"INDEMNIFYING PARTY" shall have the meaning set forth in Section
7.3
hereof.
1.35.
"INITIAL INDICATIONS" shall mean all human allergic and/or
respiratory diseases, but specifically
excluding oncology and infectious
diseases (other than cystic fibrosis,
asthma
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and chronic obstructive pulmonary disease
pathologies, in each case resulting
from infectious diseases) and systemic
autoimmune diseases.
1.36.
"INITIAL RESEARCH TERM" shall have the meaning set forth in
Section
2.1.1 hereof.
1.37.
"INVOICE" shall mean an invoice in the form attached hereto as
Schedule 1.37.
1.38.
"JOINT INTELLECTUAL PROPERTY" shall mean Joint Know How and
Joint
Patents.
1.39.
"JOINT KNOW-HOW" shall mean all Know-How developed, produced,
or
identified jointly by Hybridon and Novartis
or their respective Affiliates
pursuant to the Research Program and/or
under the Research Plan including, but
not limited to, such Know-How related to
joint Improvements or to the
identification, generation, modification
and/or characterization of IMO
Candidates and IMO Leads made jointly by
the Parties.
1.40.
"JOINT PATENTS" shall mean all Patents for inventions conceived
jointly by Hybridon and Novartis or their
respective Affiliates that arise out
of the activities performed under the
Research Program including, but not
limited to, inventions relating to joint
Improvements or to the identification,
generation, modification and/or
characterization of IMO Candidates and IMO Leads
made jointly by the Parties. After the
filing of the first Joint Patent, if any,
a list of Joint Patents shall be appended
hereto as Schedule 1.40, which will be
updated periodically to reflect additional
Joint Patents thereafter.
1.41.
"JRC" shall have the meaning set forth in Section 2.4 hereof.
1.42.
"KNOW-HOW" shall mean all data, technical information,
material,
experience, know-how, inventions (whether
or not patented), trade secrets,
processes and methods in any form
discovered, developed or applied (with the
consent of its owner) and Controlled by
either Party or its Affiliates,
excluding Patents.
1.43.
"LICENSE AGREEMENT" shall have the meaning set forth in the
preamble
to this Agreement.
1.44.
"LOSS" shall have the meaning set forth in Section 7.1 hereof.
1.45.
"NOVARTIS INTELLECTUAL PROPERTY" shall mean all Novartis Patents
and
Novartis Know-How, but explicitly excluding
Joint Intellectual Property.
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1.46.
"NOVARTIS KNOW-HOW" shall mean all Know-How relating to
immunomodulatory oligonucleotides
Controlled by Novartis on the Effective Date
or at any time during the Term, but
explicitly excluding Joint Know-How,
Hybridon Intellectual Property and Hybridon
Background Intellectual Property.
1.47.
"NOVARTIS PATENTS" shall mean any Patents relating to
immunomodulatory oligonucleotides
Controlled by Novartis on the Effective Date
or at any time during the Term, but
explicitly excluding Joint Patents, Hybridon
Intellectual Property and Hybridon
Background Intellectual Property.
1.48.
"NOVARTIS RESEARCH LICENSE" shall have the meaning set forth in
Section 4.1.2 hereof.
1.49.
"OPTION TERM" shall mean the Research Term and a period of [**]
thereafter, provided that in no event shall
the Option Term extend beyond the
date that is [**] after the Effective Date
without the consent of Hybridon,
which consent shall not be unreasonably
withheld.
1.50.
"PATENTS" shall mean all existing patents and patent
applications
and all patent applications hereafter
filed, including any continuation,
continuation-in-part, divisional,
provisional or any substitute applications,
any patent issued with respect to any such
patent applications, any reissue,
reexamination, renewal or extension
(including any supplementary protection
certificate) of any such patent, and any
confirmation patent or registration
patent or patent of addition based on any
such patent, and all foreign
counterparts of any of the foregoing.
1.51.
"PERSON" shall mean any individual, corporation, partnership,
association, joint-stock company, trust,
unincorporated organization or
government or political subdivision
thereof.
1.52.
"PROOF OF CONCEPT" shall mean the scientific study of the
mechanism
of action of an IMO Lead conducted in man,
which supports Novartis'
decision-making about the value of the IMO
Lead as a development candidate.
1.53. "POC
PHASE RESEARCH" shall mean research related to the technical
development of IMO Leads leading to human
clinical trials, as well as all human
clinical trials through the end of Proof of
Concept clinical trials.
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1.54.
"PRODUCT" shall mean a pharmaceutical product including,
conjugated
to, or comprised of an IMO Lead with or
without other active ingredients in
finished dosage form, ready for
administration to the ultimate consumer, and any
Improvements thereto.
1.55.
"PROVIDING PARTY" shall have the meaning set forth in Section
5.1
hereof.
1.56.
"RECEIVING PARTY" shall have the meaning set forth in Section
5.1
hereof.
1.57.
"RENEWAL NOTICE" shall have the meaning set forth in Section
2.1.2
hereof.
1.58.
"RENEWAL PERIOD" shall have the meaning set forth in Section
2.1.2
hereof.
1.59.
"RESEARCH COSTS" shall mean all research costs (internal or
external, including manufacturing costs)
incurred by a Party in performing such
Party's obligations under the Research
Program in accordance with the Research
Plan, and, in the case of Hybridon, any
such costs not contemplated by the
Research Plan for which Hybridon has
obtained prior written approval from
Novartis which are evidenced by a written
invoice, contract or other document
provided by a Third Party.
1.60.
"RESEARCH FIELD OF USE" shall mean the prophylaxis, palliation,
diagnosis and treatment of human diseases
by pharmaceutical products via any
route of administration.
1.61.
"RESEARCH PLAN" shall have the meaning set forth in Section
2.2.1
hereof.
1.62.
"RESEARCH PROGRAM" shall mean all research activities
undertaken
under this Agreement associated with the
identification, generation,
modification and/or characterization of IMO
Candidates and IMO Leads, including,
without limitation, all CSP Phase Research
activities, which shall be performed
in connection with the Research Plan.
1.63.
"RESEARCH TERM" shall have the meaning set forth in Section
2.1.1
hereof.
1.64.
"SUBSTITUTE IMO LEAD" shall mean any IMO Candidate chosen by
Novartis as a substitute for an abandoned
IMO Lead. Substitute IMO Leads, if
any, shall be considered IMO Leads for all
purposes hereof, and all references
to the term "IMO Lead" shall be deemed to
include any and all Substitute IMO
Leads. Abandoned IMO Leads shall, upon
abandonment, cease to be IMO Leads but
shall remain IMO Candidates.
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1.65.
"TERM" shall have the meaning set forth in Section 9.1 hereof.
1.66.
"TERRITORY" shall mean the entire world.
1.67.
"TEST SAMPLE" shall have the meaning set forth in Section 2.3.1
hereof, but shall exclude the following
immunomodulatory oligonucleotides: [**].
1.68.
"THIRD PARTY" shall mean any Person that is not a Party or an
Affiliate of either Party.
ARTICLE II
RESEARCH PROGRAM
2.1.
RESEARCH TERM.
2.1.1. Initial Research Term. The initial term of the Research
Program will commence on the Effective Date
and continue for a period of two (2)
years, unless earlier terminated in
accordance with the provisions hereof (the
"Initial Research Term"). The Initial
Research Term, together with any and all
extensions under Section 2.1.2, 2.1.3, or
2.1.4, shall be referred to as the
"Research Term."
2.1.2. Extension of Research Term. Unless earlier terminated
in accordance with the provisions hereof,
the Research Term may be extended
beyond the Initial Research Term for [**]
(the "Renewal Period"), in the sole
discretion of Novartis, upon the provision
of written notice to Hybridon not
later than [**] prior to the end of the
Initial Research Term ("Renewal
Notice").
2.1.3. Extension in Event of PoC Phase Research Clinical Trial
or Volunteer Study Clinical Trial. In the
event that Novartis extends the
Research Term in accordance with Section
2.1.2 and an active clinical trial that
is part of PoC Phase Research is ongoing at
the end of the Renewal Period, the
term of the Research Program will
automatically extend until completion of (a)
such clinical trial that is part of such
PoC Phase Research, if such clinical
trial is designed to establish Proof of
Concept, or (b) in the case of such
clinical trial that is part of PoC Phase
Research but that is not designed to
establish Proof of Concept, the related
clinical trial that is part of PoC Phase
Research and that is designed to establish
Proof of Concept (the
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"Extended Renewal Period"); provided that
in no event shall the Extended Renewal
Period or the Option Term extend beyond the
date that is [**] after the
Effective Date without the consent of
Hybridon, which consent shall not be
unreasonably withheld.
2.1.4. Continuation of Research Program Upon Option Exercise.
In the event that Novartis exercises the
Commercialization Option, this
Agreement shall, subject to the following
sentence or as otherwise specified
herein, continue in accordance with its
terms (including, without limitation,
the provisions of Section 2.3.3(b) hereof)
and shall remain in effect until the
date that is [**] after the Effective Date
or such longer period to which
Hybridon consents (which consent shall not
be unreasonably withheld), unless
earlier terminated in accordance with the
provisions hereof. Beginning upon the
Effective Date of the License Agreement,
the PoC Phase Research to be performed
pursuant to Section 2.3.3(a) hereof shall
be performed under, and governed by
the terms of, the License Agreement.
2.2.
RESEARCH PLAN.
2.2.1. Research Plan. Attached as Schedule 2.2.1 hereto is an
initial work plan identifying: (a) the
Acceptance Criteria; (b) the
responsibilities of each Party with respect
to research to be conducted prior to
the CSP Phase Research; and (c) the
appropriate resources of each Party to be
committed with respect to research to be
conducted prior to the CSP Phase
Research. No later than [**] after the
Effective Date, Novartis, in consultation
with Hybridon, will prepare an overall
research plan for the CSP Phase Research
to be conducted pursuant to the Research
Program identifying: (i) the Acceptance
Criteria; (ii) the responsibilities of each
Party with respect to the CSP Phase
Research to be conducted; (iii) the
appropriate resources of each Party to be
committed with respect to the CSP Phase
Research; and (iv) the research
activities, studies, developmental
milestones, performance criteria, and
timeframes for work to be completed by each
Party with respect to the CSP Phase
Research), which the Parties will submit to
the JRC for final approval at the
first meeting of the JRC (such research
plan, as approved by the JRC and as
amended from time-to-time, the "Research
Plan," except that any changes to the
Acceptance Criteria must be made upon the
mutual written consent of the Parties,
such consent not to be unreasonably
withheld). The Research Plan and any
amendments thereto shall be included on
Schedule 2.2.1 hereto.
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2.2.2. Plan Review. The Research Plan will be reviewed and
approved by the JRC shortly after the
Effective Date. The JRC may modify the
Research Plan as appropriate; provided,
that no modified Research Plan shall
impose substantial resource and/or
financial obligations on Hybridon in addition
to those obligations set forth in the
initial Research Plan without Hybridon's
consent. Any disagreements between the
Parties with respect to modification of
the Research Plan will, subject to the
proviso in the immediately preceding
sentence, be resolved in accordance with
Section 2.5 of this Agreement.
2.3.
RESEARCH PROGRAM.
2.3.1. Commencement.
(a) Within [**]
of the Effective Date, Hybridon, at its own cost,
shall generate and supply to Novartis a sufficient number and
quantity of IMOs (each a "Test Sample"), to allow evaluation
of such Test Samples by the Parties in various in vitro or in
vivo assays. In order to facilitate the goals and purposes of
the Research Program, Hybridon shall use commercially
reasonable efforts to supply Novartis with Test Samples of
those IMOs which, in Hybridon's judgment, have the greatest
chance (as compared to other IMOs) of meeting the Acceptance
Criteria. Each such Test Sample shall be accompanied by all
data generated by Hybridon with respect thereto and shall not
be required to be materially in excess of the quantity
necessary to complete such assays (currently estimated to be
up to approximately five (5) grams of each IMO). Based on the
results of its evaluation, Novartis, in its discretion, which
is reasonably exercised, shall determine whether the Test
Samples meet the Acceptance Criteria. From those Test Samples
meeting the Acceptance Criteria, Novartis shall, in its sole
discretion, identify up to [**] IMO Candidates to be included
within the CSP Phase Research. Hybridon's obligation to
provide IMOs pursuant to this Section 2.3.1(a) shall be
satisfied once Hybridon supplies, in accordance with this
Section 2.3.1, Test Samples for IMOs, [**] of which Novartis
has determined, in its discretion, which is reasonably
exercised, meet the Acceptance Criteria; provided that, if,
during the Research Term Novartis
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requests that Hybridon generate or supply modified or
additional IMOs in response to scientific results that
Novartis generates during the Research Program, Hybridon shall
use commercially reasonable efforts to provide up to [**]
additional IMOs, including Test Samples thereof, at Hybridon's
expense.
(b) The JRC
shall direct the conduct of activities under the
Research Plan, and Hybridon and Novartis shall collaborate in
the conduct of activities under the Research Plan with the
Parties having the roles and responsibilities specified in the
Research Plan, all as may be deemed appropriate by the JRC.
The JRC shall review and coordinate the efforts of the Parties
with respect to the Research Plan.
2.3.2. CSP Phase Research.
(a) During the
phase of the Research Program culminating in the
candidate selection point (the "CSP Phase Research"), the
Parties shall evaluate up to [**] IMO Candidates in various in
vitro screens and in vivo models such as those described on
Schedule 2.3.2 hereof and shall identify IMO Candidates to be
included in the PoC Phase Research to be performed under this
Agreement (each an "IMO Lead"). Novartis may designate one or
more of the IMO Candidates as IMO Leads, but shall not be
obligated to include any such IMO Leads in PoC Phase Research
to be performed under this Agreement. Notwithstanding the
foregoing, in the event Novartis abandons development of an
IMO Lead, Novartis may designate a Substitute IMO Lead and
advance the Substitute IMO Lead in place of the abandoned IMO
Lead.
(b) Hybridon
shall cooperate with Novartis and any Third Party
supplier retained by Novartis, in Novartis' sole discretion,
to enable Novartis and/or such Third Party supplier to
manufacture and supply IMO Candidates meeting Novartis'
specifications for use in the CSP Phase Research. Hybridon
shall provide to Novartis and any Third Party supplier all
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technical information and Hybridon Know-How necessary or
useful to allow Novartis and/or such Third Party supplier to
manufacture the IMO Candidates. Hybridon will make available
to Novartis those persons that are subject to Hybridon's
control with technical information or necessary or useful
expertise to assist Novartis and/or the Third Party supplier
with the manufacturing process. Hybridon will not charge
Novartis for any costs associated with the performance of its
obligations under this Section 2.3.2(b), including, without
limitation, the time spent by Hybridon personnel in providing
assistance to Novartis and/or any Third Party supplier. Other
than as set forth in this Section 2.3.2(b), Novartis shall be
responsible for the costs of such supply and all other
contractual obligations to such Third Party supplier.
(c) Novartis
management will determine, in its reasonable
discretion, whether an IMO meets the Acceptance Criteria. In
addition, Novartis management will determine, in its sole
discretion, whether to terminate the CSP Phase Research with
respect to any particular IMO Candidate, whether the CSP Phase
Research has been successfully completed and which, if any, of
the IMO Candidates to designate as IMO Leads.
2.3.3. PoC Phase Research.
(a) In the event
that Novartis designates one or more IMO Lead(s),
Novartis will conduct PoC Phase Research on such IMO Lead(s),
including, without limitation, studies regarding [**], with at
least the primary clinical endpoints for such PoC Phase
Research to be determined by the JRC. Novartis will make all
regulatory filings in Europe, the U.S. and/or any other
jurisdictions necessary to conduct the PoC Phase Research
under this Agreement. Novartis shall, for informational
purposes only, periodically share information with the members
of the JRC regarding the status of the PoC Phase Research
performed under this Agreement and summaries of the results
thereof. Novartis management will determine, in its sole
discretion, whether to continue or cease the PoC Phase
Research being conducted
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under this Agreement with respect to any IMO Lead and whether
to put forward a Substitute IMO Lead in lieu thereof, in which
case Novartis shall notify Hybridon of the same in writing.
(b) Hybridon
shall cooperate with Novartis and any Third Party
supplier retained by Novartis, in Novartis' sole discretion,
to enable Novartis and/or such Third Party supplier to
manufacture and supply IMO Candidates meeting Novartis'
specifications for use in the PoC Phase Research. Hybridon
shall provide to Novartis and any Third Party supplier all
technical information and Hybridon Know-How necessary or
useful to allow Novartis and/or such Third Party supplier to
manufacture the IMO Candidates. Hybridon will make available
to Novartis those persons that are subject to Hybridon's
control with technical information or necessary or useful
expertise to assist Novartis and/or the Third Party supplier
with the manufacturing process. Hybridon will not charge
Novartis for any costs associated with the performance of its
obligations under this Section 2.3.3(b), including, without
limitation, the time spent by Hybridon personnel in providing
assistance to Novartis and/or any Third Party supplier. Other
than as set forth in this Section 2.3.3(b), Novartis shall be
responsible for the costs of such supply and all other
contractual obligations to such Third Party supplier.
2.3.4. Research Diligence. Hybridon shall use commercially
reasonable efforts to fulfill its
obligations under the Research Program and
Research Plan. Novartis shall use
commercially reasonable efforts, similar to
those used by Novartis or its Affiliates in
the research and development of
other products of Novartis or its
Affiliates that are of similar commercial
potential and at a similar stage of
research or development, to fulfill its
obligations under the Research Plan and the
Research Program.
2.3.5. Submission of Reports. Upon achieving, or failing to
achieve, each scientific or technical
milestone specified in the Research Plan,
Hybridon and Novartis will complete and
present to the JRC a report containing
detailed summaries of the data related to
such milestone. For purposes thereof,
each Party shall provide (or request its
Affiliates to
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provide) to the other Party any necessary
information (including, without
limitation, Confidential Information) as
may be reasonably required to perform
its obligations under this Agreement.
2.4. JOINT
RESEARCH COMMITTEE. Upon execution of this Agreement, Hybridon
and Novartis will establish a joint
research committee ("JRC"), which shall
consist of an equal number of executives or
scientists as may be designated by
each Party from time to time. The JRC shall
initially have six (6) members, with
each Party having the right to appoint
three (3) members. Novartis shall have
the right to appoint one of its members as
the JRC Committee Chair. The JRC
shall hold its first meeting within [**] of
the Effective Date. Thereafter, the
JRC shall meet quarterly, or with such
other frequency as may be established by
the JRC (but in no event less often than
three (3) times per year), and at such
time and location as may be established by
the JRC. The JRC shall have the
following responsibilities:
(a) Provide
general oversight of, direct the conduct of, and
review and coordinate the efforts of the Parties with respect
to, the Research Plan, and monitor the progress of the
activities carried out pursuant to the Research Plan;
(b) Periodically
review the overall goals and strategy of the
activities to be conducted under the Research Plan;
(c) Subject to
Section 2.2.2, identify the number of FTEs required
for activities to be conducted under the Research Plan and
prioritize the allocation of resources dedicated to the
Research Plan (including FTEs);
(d) Subject to
Section 2.2.2, approve and revise, as appropriate,
the Research Plan;
(e) Revise, as
appropriate, performance milestones (other than
milestones the achievement of which are the basis for payments
to Hybridon under this Agreement or the License Agreement);
(f) Review and
edit proposed publications related to the Research
Plan and/or the Collaboration;
(g) Subject to
Sections 2.2.1, 2.2.2 and 2.5.2, revise, as
appropriate, the
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Acceptance Criteria;
(h) Resolve any
disagreement between the Parties, and discuss and
resolve any other relevant issues submitted to it, in
accordance with the dispute resolution procedure set forth in
Section 2.5 below.
The JRC shall have the authority to create teams for individual
projects, each of which will meet (via
telephone or video conference or in
person) no less frequently than monthly,
and which will report to the JRC on its
progress on activities performed with
respect to such project. In addition, the
JRC shall also have the authority to create
subcommittees as needed.
Notwithstanding the foregoing, the Parties
acknowledge that the JRC shall not
have the authority to amend or modify the
terms or conditions of this Agreement.
The JRC shall survive until expiration or
termination of this Agreement.
2.5.
DECISIONS OF THE JRC; RESOLUTION OF DISPUTES.
2.5.1. Decisions of the JRC. Each of Hybridon and Novartis
shall
have one vote on the JRC. The JRC shall
make decisions unanimously where
possible. In the event of a deadlock,
Novartis shall have the deciding vote on
all matters except Critical Issues.
2.5.2. Dispute Resolution. In the event that the JRC is
deadlocked as to any material increase in
financial or other resources required
to be expended by Hybridon in connection
with the Research Program (a "Critical
Issue"), then the Parties shall attempt to
have the issue resolved in accordance
with the dispute resolution mechanism set
forth in Section 11.3 hereof.
2.6.
EXCHANGE OF INFORMATION.
2.6.1. Reports to JRC. Hybridon and Novartis will share
information (including, without limitation,
Confidential Information) regarding
the Collaboration and/or activities
conducted under the Research Plan with the
members of the JRC no less frequently than
quarterly in order to allow such
members to monitor the progress of the
Collaboration.
2.6.2. Restrictions on Use of Know-How. Know-How disclosed by
one
Party to the other Party shall be deemed
Confidential Information of the
Providing Party subject to the provisions
of Article V.
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2.6.3. Delivery of Know-How. During, and upon conclusion of,
the
Research Program, and subject to the
provisions of this Section 2.6 and Article
V hereof, Hybridon shall (a) disclose to
Novartis all technical information
known to it which constitutes Hybridon
Know-How (to the extent licensed under
this Agreement) and Joint Know-How and (b)
transfer to Novartis all data and
materials specified in the related Research
Plan. Hybridon shall provide all
data both in hard copy form and, if
commercially and technically reasonable, in
an electronic form compatible with
Novartis' systems; provided that Novartis
shall only reimburse Hybridon's costs of
providing data in a form compatible
with its systems so long as Hybridon has
provided Novartis with a reasonably
detailed description of such costs and
obtained Novartis' prior written approval
to incur such costs. Novartis shall
reimburse such pre-approved costs actually
incurred by Hybridon within [**] after
receipt by Novartis of Hybridon's Invoice
for the same.
2.6.4. Background Intellectual Property; Non-Interference.
(a) Neither
Party shall be entitled to information from the other
Party concerning Hybridon Intellectual Property or Novartis
Intellectual Property, as applicable, discovered or developed
by that Party outside the Research Program; except that
Hybridon must disclose to the JRC in a timely manner any and
all Hybridon Background Intellectual Property that it uses
and/or is relevant to the Research Program, and each Party
must disclose to the JRC all Joint Intellectual Property it
conceives, discovers or develops under the Research Program.
(b) Hybridon
will not assert its rights in any Acquisition
Intellectual Property, Hybridon Intellectual Property,
Hybridon Background Intellectual Property or Joint
Intellectual Property, as applicable, and will use best
efforts to prevent its licensees, if any, from asserting
similar rights licensed by Hybridon to such licensees to block
or impede Novartis or
its Affiliates or their assignees,
licensees or sublicensees from exercising the rights licensed
to Novartis herein or in the License Agreement.
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2.7.
PRIMARY DATA ACCESS.
2.7.1. Recordkeeping. Hybridon and Novartis shall each maintain
records in sufficient detail, and will
document in a manner appropriate for
purposes of supporting the filing of
potential patent applications, all work
done and results achieved in the
performance of the Research Program and the
Research Plan (including, without
limitation, all data necessary in the form
required under any applicable governmental
regulations).
2.7.2. Technical Reports. Subject to Article V hereof: (a)
Hybridon shall grant to Novartis access, at
reasonable intervals and upon
reasonable notice, to all data (including,
without limitation, all primary data
and data contained in laboratory notebooks)
generated in the course of
performing its obligations under the
Research Program; (b) Novartis shall have
the right, at reasona
