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Exhibit 10.42
CONFIDENTIAL
EXECUTION COPY
RESEARCH AND LICENSE AGREEMENT
BETWEEN
FOVEA PHARMACEUTICALS SA
AND
COMBINATORX, INCORPORATED
DATED JANUARY 30, 2006
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TABLE OF CONTENTS
<Table>
<S>
<C>
ARTICLE 1 DEFINITIONS
....................................................1
ARTICLE 2 GRANT OF RIGHTS
...............................................14
ARTICLE 3 COLLABORATION COMBINATIONS
....................................18
ARTICLE 4 LICENSED COMBINATIONS
.........................................26
ARTICLE 5 CONSIDERATION
.................................................27
ARTICLE 6 INTELLECTUAL PROPERTY
.........................................32
ARTICLE 7 ENFORCEMENT AND DEFENSE OF PATENTS
............................37
ARTICLE 8 CONFIDENTIALITY AND NON-DISCLOSURE
............................39
ARTICLE 9 REPRESENTATIONS, WARRANTIES AND COVENANTS
.....................43
ARTICLE 10 INDEMNITY
....................................................45
ARTICLE 11 TERM AND TERMINATION
.........................................49
ARTICLE 12 DISPUTE RESOLUTION
...........................................52
ARTICLE 13 MISCELLANEOUS
................................................53
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RESEARCH AND LICENSE AGREEMENT
This Research and License Agreement (the "Agreement") is dated as
of
January 30, 2006 (the "Effective Date") and is between Fovea
Pharmaceuticals SA,
a company organized and existing under the laws of, France, with an
office at
3-5 Impasse Reille, 75014 Paris, France ("Fovea"), and
CombinatoRx,
Incorporated, a company organized and existing under the laws of
Delaware, with
an office at 650 Albany Street, Boston, MA 02118 ("CombinatoRx").
Each of Fovea
and CombinatoRx are sometimes referred to herein as a "Party" and
together as
the "Parties."
RECITALS
(A)
CombinatoRx has expertise in discovery and development of
combination
drugs, and has drug combinations in discovery, preclinical and
clinical
stages of development.
(B)
Fovea has certain proprietary IN VITRO and IN VIVO models of
ophthalmic
diseases, and clinical expertise in developing ophthalmic
therapeutics.
(C)
The Parties wish to collaborate on certain Collaboration
Combinations
(defined herein) wherein Fovea would test certain of CombinatoRx's
drug
combinations in the ophthalmic disease models to identify
candidates
for commercialization by the Parties in certain territories.
(D)
Fovea also desires to obtain an exclusive, royalty-bearing license,
and
CombinatoRx desires to grant such license, under certain
intellectual
property relating to Licensed Combinations (defined herein) for
commercialization by Fovea.
AGREEMENT
NOW, THEREFORE, in consideration of the mutual covenants contained
in
this Agreement, and other good and valuable consideration, the
receipt and
sufficiency of which are hereby acknowledged, the Parties,
intending to be
legally bound, hereby agree as follows:
ARTICLE 1
DEFINITIONS
Unless otherwise specifically provided herein, the following terms,
when used
with a capital letter at the beginning, shall have the following
meanings:
1.1
"AAA" has the meaning set forth in Section 12.3.
1.2
"ACTIVE INGREDIENT" means any component of a drug product
intended to furnish pharmacological activity or other direct effect
in the
Treatment of disease, or to affect the structure or any function of
the body of
humans or other animals.
1.3
"AFFILIATE" means, with respect to a Person, any other Person
that controls, is controlled by or is under common control with,
such first
Person. For purposes of this definition only, "control" means (a)
to possess,
directly or indirectly, the power to direct the
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management or policies of a Person, whether through ownership of
voting
securities, by contract relating to voting rights or corporate
governance or
otherwise, or (b) to own, directly or indirectly, more than fifty
percent (50%)
of the outstanding voting securities or other voting ownership
interest of such
Person or such lesser maximum ownership percentage permitted in
those
jurisdictions restricting foreign ownership.
1.4
"APPLICABLE LAW" means the laws, rules and regulations,
including any rules, regulations, guidelines or other requirements
of Regulatory
Authorities, in effect from time to time within a country or
territory, as
applicable.
1.5
"BOE DISEASE" means the following diseases: Wet Age-related
Macular Degeneration; Dry Age-related Macular Degeneration;
Posterior uveitis
(chorioentinitis); Retinitis Pigmentosa; Retinal Vein Occlusion;
Retinal
detachment; Retinal Artery Occlusion; Proliferative diabetic
retinopathy;
Post-operative inflammation; Persistant Macular Edema; Neovascular
diseases
involving the retina or uveal tract such as neovascular
glaucoma,
neovascularization following a combined vitrectomy and
lensectomy,
neovascularization of the optic nerve, and neovascularization due
to penetration
of the eye or contusive ocular injury; Inflammation due to ocular
trauma;
Open-angle glaucoma; Closed-angle glaucoma; Exudative macular
edema; Diabetic
Retinopathy; Diabetic Macular Edema; Cystoid macular edema; Chronic
posterior
uveitis; Allograft rejection; Behcet's syndrome; Chorioiditis;
Crystalline
retinopathy; Optic neurtitis; Proliferative sickle cell
retinopathy;
Proliferative vitreoretinopathy; Retinopathy of prematurity;
Vitreitis; Temporal
arteritis; Fuchs' Dystrophy; Dacryocystitis; Giant cell arteritis;
Sympathetic
ophthalmia; Pars planitis; Pan Uveitis; and all other similar
diseases as agreed
to by the Joint Steering Committee.
1.6
"BREACHING PARTY" has the meaning set forth in Section 11.2.
1.7
"CALENDAR QUARTER" means each successive period of three (3)
calendar months commencing on January 1, April 1, July 1 and
October 1.
1.8
"CALENDAR YEAR" means each successive period of twelve (12)
calendar months commencing on January 1.
1.9
"CHALICE DATABASE" means CombinatoRx's proprietary database
containing data related to Combinations screened by or on behalf of
CombinatoRx,
including the results of such screens, as such database exists on
the Effective
Date, excluding any Information in such database resulting from any
Third Party
Agreement. The Chalice Database includes all drug combinations that
CombinatoRx
has in clinical studies as of the Effective Date.
1.10 "CM"
means a Cytokine Modulator as a therapeutic drug
containing a single active pharmaceutical ingredient or two or more
active
pharmaceutical ingredients where no component of the CM is
tacrolimus,
cyclosporine, ISAtx24, Rapamycin (Sirolimus), Pimecrolimus,
Everolimus or a
corticosteroid.
1.11
"COLLABORATION COMBINATION" means any drug combination in the
Chalice Database that consists of one of the following types of
combinations:
SSAs, ECIs or CMs.
1.12
"COLLABORATION COMBINATION FIELD" means use of a Collaboration
Combination by Local Administration to treat the diseases indicated
below:
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<Table>
<Caption>
Type of
Collaboration
Combination
Disease
-----------
-------
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SSA
BOE Disease
ECI
FOE Disease
CM
FOE Disease and/or
BOE Disease
</Table>
For clarification, each Collaboration Combination type is
licensed
solely for the treatment of the corresponding disease indicated
above.
1.13
"COLLABORATION COMBINATION PAIR" has the meaning set forth in
Section 3.3.2.
1.14
"COLLABORATION COMBINATION IP" means, with respect to a
particular Collaboration Combination, any Intellectual Property (i)
conceived by
either Party prior to the termination of the Evaluation Period for
such
Collaboration Combination, including any such Intellectual Property
existing on
the Effective Date, and (ii) relating to or covering the
composition,
manufacture, use or sale of a Collaboration Combination, and which
may be
necessary or useful in developing, making, using, or selling a
Selected
Collaboration Product in the Collaboration Combination Field.
Specifically
excluded from Collaboration Combination IP is Intellectual Property
pertaining
to Formulation Technology, as defined in Section 3.8.1.
1.15
"COLLABORATION SELECTION PERIOD" has the meaning set forth in
Section 3.3.2.
1.16
"COMBINATION" refers either to Collaboration Combination or
Licensed Combination.
1.17
"COMBINATION ASSESSMENT DATA" means the following: (i) the
identity of the Collaboration Combinations and Licensed
Combinations; (ii) the
identity of each component of the Collaboration Combinations and
Licensed
Combinations; (iii) Patents Controlled by CombinatoRx covering the
Collaboration
Combinations and Licensed Combinations, to the extent necessary to
Exploit
Collaboration Combinations and Licensed Combinations in the
Collaboration
Combination Field and Licensed Combination Field; and (iv) summary
of all
material CombinatoRx scientific data on the Collaboration
Combinations and
Licensed Combinations, including research, preclinical information,
and if
available, a copy of the Investigator's Brochure, to the extent
necessary or
useful to Exploit Collaboration Combinations and Licensed
Combinations in the
Collaboration Combination Field and Licensed Combination Field.
1.18
"COMBINATORX BACKGROUND TECHNOLOGY" means (a) CombinatoRx's
drug discovery technology (including CombinatoRx's combination high
throughput
screening platform) and any Information related thereto Controlled
by
CombinatoRx or its Affiliates as of the Effective Date or
thereafter; (b)
Improvements made to CombinatoRx's drug discovery technology by or
on behalf of
CombinatoRx and its Affiliates and/or by or on behalf of Fovea and
its
Affiliates; (c) the Chalice Database and any other discovery,
invention, assay,
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products, cultures, biological materials, drugs, drug-device
combinations and
other materials and compositions, Controlled by CombinatoRx or its
Affiliates as
of the Effective Date or thereafter, (d) any Information related to
a
Combination that is conceived or developed by or on behalf of
CombinatoRx and
its Affiliates outside of this Agreement; and (e) Intellectual
Property
pertaining to any of the foregoing.
1.19
"COMBINATORX COLLABORATION COMBINATION IP" means Collaboration
Combination IP that is conceived by CombinatoRx or Third Parties
acting on
behalf of CombinatoRx or jointly by CombinatoRx and Fovea or Third
Parties
acting on behalf of the Parties.
1.20
"COMBINATORX GENERATED DATA" means data generated and
Controlled by CombinatoRx relating to a Combination.
1.21
"COMBINATORX LICENSED COMBINATION IP" means any Intellectual
Property (i) conceived by CombinatoRx and (ii) relating to or
covering a
Licensed Combination, and which is necessary in developing, using,
selling or
registering a Selected Licensed Product. All CombinatoRx Licensed
Combination IP
shall be solely owned by CombinatoRx.
1.22
"COMBINATORX TERRITORY" means North America, Singapore and
South Korea.
1.23
"COMMERCIALLY REASONABLE EFFORTS" means, with respect to the
research, development, Manufacture or commercialization of a
Selected
Collaboration Products and Selected Licensed Products licensed
herein, as the
case may be, efforts and resources commonly used in the
research-based
pharmaceutical industry for products with similar commercial and
scientific
potential at a similar stage in their lifecycle, taking into
consideration their
safety and efficacy, their cost to develop, the competitiveness of
alternative
products, the anticipated or actual nature and extent of their
market
exclusivity (including Patent coverage and regulatory exclusivity),
the
likelihood of regulatory approval, and their estimated
profitability, including
the amounts of marketing and promotional expenditures and all other
relevant
factors.
1.24
"COMPLAINING PARTY" has the meaning set forth in Section 11.2.
1.25
"CONDITION" shall mean any malady, disease, syndrome, trauma,
injury or condition.
1.26
"CONFIDENTIAL INFORMATION" has the meaning set forth in
Section 8.1.1.
1.27
"CONTROL" means, with respect to any item, Combination,
Information, Patent or Intellectual Property Protection Right,
possession of the
right, whether directly or indirectly, and whether by ownership,
license or
otherwise, to assign, or grant a license, sublicense or other right
to or under,
such item, Combination, Information, or Intellectual Property and
has the right
to disclose such item, Combination, Information, Patent or
Intellectual Property
as provided for herein without violating the terms of any agreement
with a Third
Party, except to the extent that any of the foregoing rights arise
by virtue of
the grant of rights under this Agreement.
1.28
"DETAILED DEVELOPMENT PLAN" means the development plan to be
established with respect to each Selected Collaboration Combination
pursuant to
Section 3.1 hereof and
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containing the activities to be undertaken by Fovea to enable Fovea
to deliver a
Target Dossier in accordance with the terms of this Agreement.
Without limiting
the foregoing, the Detailed Development shall provide for the
following
development steps for each Selected Collaboration Combination, as
applicable:
(a)
The Selected Collaboration Combination shall enter
formulation development;
(b)
If the Selected Collaboration Combination can be
formulated for ophthalmic use, it shall be
advanced to ocular tolerability experiments;
(c)
If the Selected Collaboration Combination has
acceptable ocular tolerability properties, it
shall be advanced to animal proof-of-concept
efficacy models;
(d)
If the Selected Collaboration Combination is
efficacious in animal models it shall be advanced
to ocular toxicity and pharmacokinetic studies;
(e)
If the Selected Collaboration Combination is
tolerable, non-toxic, efficacious, and can be
formulated for ophthalmic use, it shall be
advanced to a Phase I human
toxicity/pharmacokinetic study; and
(f)
If the Selected Collaboration Combination is
non-toxic and has acceptable pharmacokinetic
properties in humans, all shall be advanced to a
human proof-of-concept study (e.g. Phase IIa).
(g)
If the Selected Collaboration Combination is
efficacious in human proof-of-concept studies,
then at least one such Selected Collaboration
Combination shall be advanced to Phase IIb studies
as determined by the Joint Steering Committee
pursuant to Section 3.9.1.
1.29
"DISCLOSING PARTY" has the meaning set forth in Section
10.1.1.
1.30
"DISTRIBUTOR" has the meaning set forth in Section 2.4.
1.31
"DOLLARS" means the lawful currency of the United States of
America.
1.32 "ECI"
means an Enhanced Calcineurin Inhibitor as a therapeutic
drug containing two or more active pharmaceutical ingredients where
one of the
pharmaceutical ingredients is tacrolimus, cyclosporine, ISAtx24,
Rapamycin
(Sirolimus), Pimecrolimus and Everolimus.
1.33
"EMEA" means the European Agency for Evaluation of Medical
Products or any successor thereto.
1.34
"EVALUATION PERIOD" means the period described in Section 3.4.
1.35
"EXPLOIT," "EXPLOITING" or "EXPLOITATION" means to make, use,
offer for sale, sell and import, including, without limitation, to
research,
develop, formulate, modify,
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enhance, improve, optimize, Manufacture, hold/keep for inventory,
lease, rent,
distribute, promote, market, export, or otherwise dispose of or
make available
or deal in respect of, a product or process, or have an Affiliate
or Third Party
do any of the foregoing on behalf of a Party.
1.36 "FDA"
means the United States Food and Drug Administration and
any successor agency thereto.
1.37
"FIRST COMMERCIAL SALE" means the first sale for monetary
value for use or consumption by a member of the general public of a
Selected
Licensed Product in any country in the world after receipt of all
Regulatory
Approvals for the sale of such product has been obtained in such
country. For
the avoidance of doubt, sales prior to receipt of all Regulatory
Approvals, such
as so-called "treatment IND sales," "named patient sales" and
"compassionate use
sales," shall not be construed as a First Commercial Sale.
1.38 "FOE
DISEASE" means the following diseases:
Keratoconjunctivitis Sicca, also known as Dry Eye;
Keratoconjunctivitis Sicca
due to Sjogren's Syndrome; Post-Surgical Inflammation; Vernal
keratoconjunctivitis; Anterior Uveitis (iridocyclitis); Ophthalmic
infections of
the eye resulting in inflammation of the conjunctiva
(conjunctivitis) by
staphylococci, streptococci, enterococci, euterococci,
bacillus,
corynebacterium, chlamydia, and neisseria and inflammation of the
cornea
(keratitis) caused by the same organisms; ophthalmic infections of
the eye
resulting in inflammation (e.g., corneal herpes, bacterial
keratitis, bacterial
conjunctivitis, mycotic keratitis, acanthamebic keratitis,
infectious
endophthalmitis, infectious corneal ulcer and the like);
Inflammation due to
ocular trauma; Inflammation after cataract surgery; Giant
Papillary
Conjunctivitis; Corneal ulcer (e.g., Mooren's ulcer, corneal ulcer
subsequent to
chronic rheumatoid arthritis or collagen disease, Terrien's
margine
degeneration, catarrhal corneal ulcer, infectious corneal ulcer);
Corneal
Trauma; Corneal Graft Rejection; Contact lens-induced
Keratoconjunctivitis;
Conjunctivitis; Chronic anterior uveitis; Atopic
keratoconjunctivitis; Allograft
Rejection; Allergic Conjunctivitis; Alkaline erosive
keratoconjunctivitis;
Allergic keratitis; Behcet's syndrome; Diabetic keratophathy;
Episcleritis;
Iritis; Keratoconus; Keratoconjunctival inflammatory disease;
Necrotic
keratitis; Neuroparalytic keratitis; Scleritis; Ocular rosacea;
Ocular herpes;
Rubeosis iritis; Sympathetic ophthalmia; Stevens-Johnson syndrome
(erythema
multiforme major); Phacoanaphylaxis; Corneal neovascularization
(inflammatory,
transplantation, developmental hypoplasia of the iris); Vitamin
A
insufficiency-induced keratomalacia; Papillitis; Ophthalmic
pemphigoid;
Map-dot-fingerprint dystrophy; Lattice dystrophy; Iridocorneal
endothelial
syndrome; Herpes zoster (shingles); Blepharitis; and, to the extent
approved by
the Joint Steering Committee pursuant to this Agreement, Pan
Uveitis, and all
other similar diseases as agreed to by the Joint Steering
Committee.
1.39
"FOVEA BACKGROUND TECHNOLOGY" means (a) Fovea's proprietary IN
VITRO and IN VIVO models of ophthalmic diseases as of the Effective
Date or
during the Evaluation Period; (b) Improvements made by Fovea to the
foregoing;
and (c) Intellectual Property pertaining to any of the
foregoing.
1.40
"FOVEA COLLABORATION COMBINATION IP" means Collaboration
Combination IP that is conceived by Fovea or Third Parties acting
on behalf of
Fovea.
1.41
"FOVEA GENERATED DATA" means data generated by Fovea relating
to a Combination.
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1.42
"FOVEA LICENSED COMBINATION IP" means any Intellectual
Property conceived by Fovea and relating to a Licensed Combination
or the
Manufacture or use thereof.
1.43
"FOVEA TERRITORY" means all countries in the world, but
excluding countries in the CombinatoRx Territory and the Shared
Territory.
1.44
"HEADS" means the Chief Executive Officer of CombinatoRx and
the Chief Executive Officer of Fovea.
1.45
"IMPROVEMENTS" means patentable or material non-patentable
improvements, variations, updates, adaptations, modifications or
upgrades or
enhancements.
1.46 "IND"
means an application submitted to a Regulatory Authority
to initiate human clinical studies, including (a) an
Investigational New Drug
application or any successor application or procedure filed with
the FDA, (b)
any foreign equivalent of a U.S. Investigational New Drug
application, and (c)
all supplements and amendments that may be filed with respect to
the foregoing.
1.47
"INDEMNIFICATION CLAIM NOTICE" has the meaning set forth in
Section 10.3.
1.48
"INDEMNIFIED PARTY" means a Party seeking to recover a Loss
under Section 10.1 or 10.2.
1.49
"INDEMNIFYING PARTY" means a Party from whom recovery of a
Loss is sought under Section 10.1 or 10.2.
1.50
"INDEMNITEE" has the meaning set forth in Section 10.3.
1.51
"INDIRECT TAXES" means value added taxes, sales taxes,
consumption taxes and other similar taxes.
1.52
"INFORMATION" means all technical, scientific and other
know-how and information, trade secrets, knowledge, technology,
means, methods,
processes, principles, practices, formulae, instructions,
documentation, skills,
techniques, procedures, experiences, ideas, inventions,
discoveries, technical
assistance, designs, drawings, reports, procedures, computer
programs,
apparatuses, specifications, data, results and other information
and material,
including without limitation: the process and results of
high-throughput
screening and any other drug discovery and development technology;
biological,
chemical, pharmacological, toxicological, pharmaceutical, physical
and
analytical, pre-clinical, clinical, safety, manufacturing and
quality control
data and information, including study designs and protocols; assays
and
biological methodology; Manufacturing and quality control
procedures and data,
including test procedures; and synthesis, purification and
isolation techniques,
(whether or not confidential, proprietary, patented or patentable)
in written,
electronic or any other form now known or hereafter developed.
1.53
"INTELLECTUAL PROPERTY" means any and all ideas, inventions,
discoveries, know-how, data, databases, documentation, reports,
materials,
writings, designs, computer software, processes, principles,
methods, techniques
and other information, including, without limitation, Patents,
trademarks,
service marks, trade names, registered designs, design rights,
copyrights
(including rights in computer software and database rights) and
any
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rights similar to any of the foregoing in any part of the world,
whether
registered or not, together with the right to apply for the
registration of any
such property.
1.54
"KNOWLEDGE" means a Party's and its Affiliates' understanding
in good faith of the relevant facts and information resulting from
the
reasonable conduct of its business affairs, but without the
requirement of
performing an investigation with respect to any such facts and
information.
1.55
"LICENSED COMBINATION" means any drug combination in the
Chalice Database that consists of an SSA.
1.56
"LICENSED COMBINATION FIELD" means use of Licensed
Combinations for treating FOE Diseases by Local Administration.
1.57
"LICENSED INFORMATION" means Information which is Controlled
by CombinatoRx as of the Effective Date or thereafter through the
Term of this
Agreement and which is necessary for the evaluation of
Collaboration
Combinations or Licensed Combinations or Exploitation of the
Collaboration
Combinations or Licensed Combinations or Selected Collaboration
Products and/or
Selected Licensed Products, but excluding any Information to the
extent covered
by a Valid Claim within the Licensed Patents.
1.58
"LICENSED
PATENTS" means all Patents anywhere in the world
covering or directed to the composition, Manufacture, or use of
Collaboration
Combinations or Licensed Combinations, (alone or in combination
with other
compounds or substances and/or in combination with therapeutic
devices),
Selected Collaboration Products, and/or Selected Licensed Products,
having any
application within the Collaboration Combination Field or Licensed
Combination
Field, in all such cases Controlled by CombinatoRx and/or its
Affiliates as of
or after the Effective Date and through the Term of this
Agreement.
1.59
"LICENSED SELECTED COLLABORATION PRODUCTS" means all Selected
Collaboration Products containing a particular Selected
Collaboration
Combination with respect to which a Target Dossier has been
delivered to
CombinatoRx under this Agreement and for which Regulatory Approval
may be
obtained without the need to conduct additional Phase I and/or
Phase II clinical
studies for such Selected Collaboration Product in addition to
those described
in such Target Dossier. By way of example, a Selected Collaboration
Product for
which a Target Dossier is delivered to CombinatoRx and for which
Regulatory
Approval is obtained for a particular indication shall be
considered a single
Licensed Selected Collaboration Product together with all other
indications for
which Regulatory Approval may be obtained for such Selected
Collaboration
Product based on post-marketing Phase IV studies, however if
additional Phase I
or Phase II clinical studies are required to obtain Regulatory
Approval, then
such Selected Collaboration Product shall be considered a separate
Licensed
Selected Collaboration Product requiring the delivery of a new
Target Dossier to
obtain a license to Exploit such Selected Collaboration Product for
the
indication obtained with such Regulatory Approval.
1.60
"LICENSED SELECTION PERIOD" shall have the meaning set forth
in Section 4.2.
1.61
"LOCAL ADMINISTRATION" means local ophthalmic delivery to the
surface or interior of the eye.
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1.62
"LOSSES" means any and all direct liability, damage, loss or
expense, including interest, penalties and reasonable lawyers' fees
and
disbursements. In calculating Losses, the duty to mitigate on the
part of the
Party suffering the Loss shall be taken into account.
1.63
"MANUFACTURE" and "MANUFACTURING" means, with respect to a
product or compound, the synthesis, manufacturing, processing,
formulating,
compounding, filling, finishing, packaging, labeling, holding and
quality
control testing of such product or compound.
1.64 "NET
SALES" means the gross invoiced amount on sales of the
Selected Licensed Combinations or Selected Licensed Products by
Fovea, its
Sublicensees and its Affiliates to Third Parties (including
Distributors, but
excluding Sublicensees) less the total of following deductions to
the extent
actually incurred:
(a)
normal and customary trade, quantity and prompt
settlement discounts (including chargebacks and
allowances) actually allowed and not otherwise
deducted from the amount invoiced;
(b)
amounts repaid or credited by reason of rejection,
returns or recalls of goods, rebates, bona fide price
reductions and amounts written off by reason of
uncollectible debt, in all cases as determined by
Fovea or its Affiliates in good faith;
(c)
rebates and similar payments made with respect to
sales paid for by any governmental or Regulatory
Authority such as, by way of illustration and not in
limitation of the Parties' rights hereunder, federal
or state Medicaid, Medicare or similar state program
in the United States or equivalent governmental
program in any other country;
(d)
excise taxes, Indirect Taxes, customs duties, customs
levies and import fees imposed on the sale,
importation, use and/or distribution of the Licensed
Combinations or Selected Licensed Products actually
invoiced;
(e)
reasonable and customary transportation costs,
distribution expenses, special packaging and related
insurance charges actually invoiced, excluding
commissions and fees paid to Third Party distributors;
and
(f)
any other similar deductions that are actually
credited to the customer and are consistent with
generally accepted accounting principles, or in the
case of non-United States sales, other applicable
accounting
standards.
In the case of any other sale or other disposal for value, such
as
barter or counter-trade, of any Licensed Combinations or
Selected
Licensed Products, or part thereof, Net Sales shall be
calculated
as above on the fair market value of the consideration given.
In
the case of any sale which is not invoiced or is delivered
before
invoice, Net Sales shall be calculated as of time of shipment.
Net
Sales shall be calculated using Fovea's internal systems used
to
report such sales, which
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reporting is done in accordance with GAAP consistently applied,
as
adjusted for any of items (a) to (f) above not taken into
account
in such systems.
1.65
"NORTH AMERICA" means the United States, its possessions and
territories, Canada and Mexico.
1.66
"OPHTHALMIC COMBINATION" means drug combination that consists
of two drugs, each of which is approved by a Regulatory Authority
for any
indication of the eye.
1.67
"PATENT COVERAGE" means, for a particular Selected Licensed
Product in a given country, there exists a Valid Claim within the
CombinatoRx
Licensed Combination IP or Fovea Licensed Combination IP, in such
country
(assuming, with respect to patent applications, that the Valid
Claims included
in such application are issued as set forth in such patent
applications) that,
but for the license granted to Fovea under this Agreement, would
have been
infringed by the Manufacture, use or sale of such Selected Licensed
Product in
such country.
1.68
"PATENTS" means (a) all national, regional and international
patents and patent applications, including provisional patent
applications, (b)
all patent applications filed either from such patents, patent
applications or
provisional applications or from an application claiming priority
from either of
these, including divisionals, continuations,
continuations-in-part,
provisionals, converted provisionals, and continued prosecution
applications,
(c) any and all patents that have issued or in the future issue
from the
foregoing patent applications ((a) and (b)), including utility
models, petty
patents and design patents and certificates of invention, (d) any
and all
extensions or restorations by existing or future extension or
restoration
mechanisms, including revalidations, reissues, re-examinations and
extensions
(including any supplementary protection certificates and the like)
of the
foregoing patents or patent applications ((a), (b) and (c)), and
(e) any similar
rights, including so-called pipeline protection, or any
importation,
revalidation, confirmation or introduction patent or registration
patent or
patent of additions to any such foregoing patent applications and
patents.
1.69
"PAYMENTS" has the meaning set forth in Section 5.13.1.
1.70
"PERMITTED DELAY" means any one of the following: (i) delay
relating to development resulting from safety or efficacy concerns
or caused by
a need to pursue development for a new indication, if such delays
have been
approved by the Joint Steering Committee; (ii) delay resulting from
the need to
obtain Third Party patent rights for development and/or
commercialization; (iii)
delay that is imposed by a Regulatory Authority or (iv) any other
unexpected
event approved by the Joint Steering Committee.
1.71
"PERSON" means an individual, sole proprietorship,
partnership, limited partnership, limited liability partnership,
corporation,
limited liability company, business trust, joint stock company,
trust,
unincorporated association, joint venture or other similar entity
or
organization, including a government or political subdivision,
department or
agency of a government.
1.72
"PHASE I STUDY" shall mean a study of a Selected Combination
Product or Selected Licensed Product in human volunteers or
patients the purpose
of which is preliminary determination of safety and tolerability of
one or more
dosing regimens and for
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which there are no primary endpoints (as recognized by FDA or other
Regulatory
Authorities) in the protocol relating to efficacy.
1.73
"PHASE II(a) STUDY" shall mean a statistically significant
preliminary efficacy and safety study of a Selected Combination
Product or
Selected Licensed Product in the target patient population designed
to
demonstrate clinical proof-of-concept.
1.74
"PHASE II(b) STUDY" shall mean a statistically significant
study of a Selected Combination Product or Selected Licensed
Product to evaluate
further any preliminary efficacy observed for, and the safety of,
the Selected
Combination Product or Selected Licensed Product in the target
patient
population and/or to provide data that may be useful in the design
of subsequent
studies of the Selected Combination Product or Selected Licensed
Product such as
Phase III Studies or Pivotal Trials, including, but not limited to
dose level,
dose ratio, and dose regimen.
1.75
"PHASE III STUDY" shall mean a controlled study to confirm
with statistical significance the efficacy and safety of a Selected
Combination
Product or Selected Licensed Product performed to obtain marketing
and/or
manufacturing approval for the product in any country.
1.76
"PIVOTAL TRIAL" means a clinical study conducted among the
intended patient population, of a size and rigor sufficient to
support the
filing of an application for Regulatory Approval of a Selected
Collaboration
Product or Selected Licensed Product.
1.77
"RECEIVING PARTY" has the meaning set forth in Section 8.1.1.
1.78
"REGULATORY APPROVAL" means, with respect to a country in a
territory, any and all approvals, licenses, registrations or
authorizations of
any Regulatory Authority necessary to commercially Manufacture,
distribute, sell
or market a Selected Collaboration Product or Selected Licensed
Product in such
country, including, where reasonably required to engage in such
activities, (a)
pricing or reimbursement approval in such country, (b) pre-
approval marketing
authorizations (including any prerequisite Manufacturing approval
or
authorization related thereto), and (c) labeling approval.
1.79
"REGULATORY AUTHORITY" means any applicable supra-national,
federal, national, regional, state, provincial or local regulatory
agency,
department, bureau, commission, council or other government entity
regulating or
otherwise exercising authority with respect to the Exploitation of
the
Combinations, Selected Licensed Products and/or Selected
Collaboration Products
in a country or territory. The term "Regulatory Authority"
includes, but is not
limited to, the FDA, the European Agency for the Evaluation of
Medicinal
Products, European Member State Competent Authorities and the
Ministry of
Health, Labour and Welfare.
1.80
"REGULATORY DOCUMENTATION" means all applications,
registrations, licenses, authorizations and approvals (including
all Regulatory
Approvals), all correspondence submitted to or received from
Regulatory
Authorities (including minutes and official contact reports
relating to any
communications with any Regulatory Authority) and all supporting
documents and
all clinical studies and tests, relating to any licensed
combination or licensed
products, and all data contained in any of the foregoing, including
all
applications related to
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obtaining Regulatory Approval, Regulatory Approvals, regulatory
drug lists,
advertising and promotion documents, adverse event files and
complaint files.
1.81
"SELECTED COLLABORATION COMBINATION" means a Collaboration
Combination which Fovea has selected for development pursuant to
Section 3.3.2.
1.82
"SELECTED COLLABORATION PRODUCT" means a pharmaceutical
preparation suitable for administration to a human, containing a
Selected
Collaboration Combination as an Active Ingredient.
1.83
"SELECTED LICENSED COMBINATION" means a Licensed Combination
which Fovea has selected for development pursuant to Section
4.2.
1.84
"SELECTED COLLABORATION COMBINATION QUARTERLY REPORT" shall
have the mean set forth in Section 3.4.1.
1.85
"SELECTED LICENSED PRODUCT" means a pharmaceutical preparation
suitable for administration to a human, containing a Selected
Licensed
Combination as an Active Ingredient.
1.86
"SHARED TERRITORY" means Japan and Taiwan. The Parties shall
have equal rights in the Shared Territory in accordance with the
terms of this
Agreement.
1.87 "SSA"
a Selective Steroid Amplifier as a therapeutic drug
containing two or more active pharmaceutical ingredients where one
of the agents
is a corticosteroid.
1.88
"SUBLICENSEE" has the meaning set forth in Section 2.3.1.
1.89
"SUBSEQUENT COMBINATORX COLLABORATION COMBINATION IP" means
any Intellectual Property (i) Controlled by CombinatoRx, (ii)
relating to or
covering a Collaboration Combination, which may be necessary or
useful in
developing, using, selling or registering a Selected Collaboration
Product, and
(iii) conceived after the termination of the Evaluation Period.
1.90
"SUBSEQUENT FOVEA COLLABORATION COMBINATION IP" means any
Intellectual Property (i) Controlled by Fovea, (ii) relating to or
covering a
Collaboration Combination, and which may be necessary or useful in
developing,
using, selling or registering a Selected Collaboration Product, and
(iii)
conceived after the termination of the Evaluation Period.
1.91
"TARGET DOSSIER" shall mean all data, information and
materials generated from the conduct of all formulation studies,
including
commercial formulation, pre-clinical studies and clinical
development studies,
including, to the extent necessary, toxicology, Phase I, Phase II,
and
pharmacokinetic studies necessary to initiate a Phase III study for
a drug
combination in the United States and in Europe. The Target Dossier
will meet the
guidelines set forth below. The Target Dossier and the development
plan required
to produce the Target Dossier will be finalized based on the
outcome of a
pre-IND meeting with the FDA.
A GUIDELINE FOR A TARGET DOSSIER WITH A STANDARD (NON PIVOTAL)
PHASE IIB
CLINICAL STUDY FOLLOWS:
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-
Safety and
pharmacokinetic data in patients sufficient to support
initiation of a Phase III study in the United States
-
Clinical
data in patients demonstrating statistical superiority of
combination versus parts
- Clinical and/or
preclinical safety and efficacy data sufficient to
select dose and ratio for a Phase III study
-
Final
commercial formulation for initiation of a Phase III study (no
additional work needed prior to first-patient-first-dose)
- Fixed
ratio co-formulation
-
Sufficient quantities of commercial formulation to complete
a Phase III study
- Data
from any bridging studies (e.g., safety, PK,
bioequivalence) necessary for initiation of Phase III study
- All
other chemistry, manufacturing and control (CMC)
information required to support Phase III studies and NDA
filing
-
IND-ready
pre-clinical efficacy and toxicology data
-
Additional
non clinical chronic toxicity data required for initiation
of Phase III study , if necessary
-
Regulatory
documents from FDA and/or EMEA
- Minutes from pre-IND meeting
approving experimental study
designs and clinical development plan through Phase IIb
- Minutes
from post-Phase IIb meeting
- Annual
reports to FDA and/or EMEA and other regulatory
authorities
A GUIDELINE FOR A TARGET DOSSIER WITH A PIVOTAL PHASE IIB CLINICAL
STUDY
FOLLOWS:
-
Safety and
pharmacokinetic data in patients sufficient to support
initiation of a Phase III study in the United States
-
Data
demonstrating clinical benefit in the target patient population
(i.e., data from a pivotal, randomized, controlled,
multi-center
study)
-
Clinical
data in patients demonstrating statistical superiority of
combination versus parts
-
Clinical
and/or preclinical safety and efficacy data sufficient to
select dose and ratio for a Phase III study
-
Final
commercial formulation for initiation of a Phase III study (no
additional work needed
prior to first-patient-first-dose)
- Fixed
ratio co-formulation
-
Sufficient quantities of commercial formulation to complete
a Phase III study
- Data
from any bridging studies (e.g., safety, PK,
bioequivalence) necessary for initiation of Phase III study
- All
other chemistry, manufacturing and control (CMC)
information required to support Phase III studies and NDA
filing
-
IND-ready
pre-clinical efficacy and toxicology data
-
Additional
non clinical chronic toxicity data required for initiation
of Phase III study , if necessary
-
Regulatory
documents from FDA and/or EMEA
- Minutes
from pre-IND meeting approving experimental study
designs and clinical development plan through Phase IIb
- Minutes
from post-Phase IIb meeting
- Annual
reports to FDA and/orEMEA and other regulatory
authorities
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1.92
"TARGET DOSSIER DEADLINE" has the meaning set forth in Section
3.9.2.
1.93
"TERM" has the meaning set forth in Section 11.1.
1.94
"THIRD PARTY" means any Person not including the Parties or
the Parties' respective Affiliates.
1.95
"THIRD PARTY AGREEMENT" means all license, research and/or
other agreements entered into by CombinatoRx prior to or following
the Effective
Date.
1.96
"THIRD PARTY CLAIM" has the meaning set forth in Section 10.1.
1.97
"TRADEMARK" means any word, name, symbol, color, designation
or device or any combination thereof, including any trademark,
trade dress,
brand mark, trade name, brand name, logo or business symbol used by
the Parties
in connection with the licensed Collaboration Combinations,
Selected Combination
Products, Licensed Combinations or Selected Licensed Products.
1.98
"TREATMENT" or "TREAT" means diagnosis, palliation,
monitoring, cure, mitigation, treatment or prevention.
1.99
"UNITED STATES" or "U.S." means the United States of America,
including its territories, possessions and Puerto Rico.
1.100 "VALID
CLAIM" means a claim in a pending patent application or
an issued and unexpired patent that (a) has not been finally
cancelled,
withdrawn, abandoned or rejected by any administrative agency or
other body of
competent jurisdiction not subject to further appeal, (b) has not
been revoked,
held invalid, or declared unpatentable or unenforceable in a
decision of a court
or other body of competent jurisdiction that is unappealable or
unappealed
within the time allowed for appeal, (c) has not been rendered
unenforceable
through disclaimer, abandonment, withdrawal or otherwise, and (d)
with respect
to a claim in a pending patent application, such claim is being
actively
prosecuted in good faith and is believed in good faith to meet the
requirements
of patentability in the relevant jurisdiction.
ARTICLE 2
GRANT OF RIGHTS
2.1
COLLABORATION COMBINATIONS.
2.1.1 LICENSE
GRANTS TO FOVEA.
(a)
SELECTED COLLABORATION COMBINATION RESEARCH
LICENSE. Subject to the terms and conditions of this Agreement,
CombinatoRx
hereby grants to Fovea a royalty-free, co-exclusive (with
CombinatoRx for its
internal activities), worldwide right and license, without the
right to
sublicense, under the CombinatoRx Collaboration Combination IP and
CombinatoRx's
interest in the Fovea Collaboration Combination IP to use Selected
Collaboration
Combinations in the Collaboration Combination Field solely for the
purpose of
conducting research, preclinical studies and clinical Phase I and
Phase II
studies of such Collaboration Combinations.
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(b)
SELECTED COLLABORATION COMBINATION
EXPLOITATION LICENSE. Subject to the terms and conditions of this
Agreement and
delivery of each Target Dossier in accordance with Section 3.9.2,
CombinatoRx
hereby grants to Fovea a royalty-free, exclusive (which shall be
co-exclusive
with CombinatoRx for the purpose of conducting clinical studies but
not for
otherwise Exploiting Selected Collaboration Combinations under this
Section)
right and license, with the right to grant sublicenses, under the
CombinatoRx
Collaboration Combination IP, CombinatoRx's interest in the Fovea
Collaboration
Combination IP, with respect to jointly owned Fovea Collaboration
Combination IP
pursuant to Section 6.1.1, and Subsequent CombinatoRx Collaboration
Combination
IP (i) to conduct Phase III Studies of the Selected Collaboration
Combination
described in the Target Dossier in the Collaboration Combination
Field anywhere
in the world and (ii) to Exploit such Selected Collaboration
Combination and all
Licensed Selected Collaboration Products in the Collaboration
Combination Field
in the Fovea Territory.
(c)
RIGHT OF REFERENCE TO DATA DURING EVALUATION
PERIOD. Subject to the terms and conditions of this Agreement,
CombinatoRx
hereby grants to Fovea an exclusive, royalty free right of
reference to all data
Controlled by CombinatoRx and existing on the Effective Date for
any
Collaboration Combination for which CombinatoRx has commenced
clinical studies
and CombinatoRx Generated Data generated during the Evaluation
Period for Fovea
to conduct Phase I and Phase II clinical studies for Selected
Collaboration
Combinations in the Collaboration Combination Field anywhere in the
world during
the Evaluation Period. For the avoidance of doubt, CombinatoRx
shall not be
restricted from granting additional rights of reference to the data
described in
this Section to Third Parties for uses other than those
specifically described
in this Section.
(d)
RIGHT OF REFERENCE TO DATA AFTER EVALUATION
PERIOD. Subject to the terms and conditions of this Agreement and
delivery of a
Target Dossier in accordance with Section 3.9.2, CombinatoRx hereby
grants to
Fovea an exclusive, royalty free right of reference to (i) Fovea
Generated Data
generated during the Evaluation Period, (ii) CombinatoRx Generated
Data
generated during the Evaluation Period, and (iii) clinical data
Controlled by
CombinatoRx and existing on the Effective Date for any
Collaboration Combination
for which CombinatoRx commenced clinical studies prior to the
Effective Date, in
each case for Fovea to Exploit Licensed Selected Collaboration
Products in the
Collaboration Combination Field in the Fovea Territory. For the
avoidance of
doubt, CombinatoRx shall not be restricted from granting additional
rights of
reference to the data described in this Section to Third Parties
for uses other
than those specifically described in this Section.
2.1.2 LICENSE
GRANT TO COMBINATORX. Subject to the terms and
conditions of this Agreement and in addition to the grants of
rights in Sections
3.8.1(a) and 3.8.1(b), Fovea hereby grants to CombinatoRx:
(a)
a royalty-free, exclusive (which shall be
co-exclusive with Fovea) right and license, with
the right to grant sublicenses, under Fovea's
interest in all Fovea Collaboration Combination IP
that is jointly owned by the Parties to conduct
clinical studies for Selected Collaboration
Products in the Collaboration Combination Field
anywhere in the world and a royalty-free,
exclusive (which shall be exclusive even as to
Fovea) right and license, with the right to grant
sublicenses, under Fovea's interest in all Fovea
Collaboration
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Combination IP that is jointly owned by the
Parties pursuant to Section 6.1.1 to otherwise
Exploit Selected Collaboration Products in the
Collaboration Combination Field in the CombinatoRx
Territory;
(b)
a royalty-free, non-exclusive right and license,
with the right to grant sublicenses, under Fovea's
interest in all Fovea Collaboration Combination IP
that is solely owned by Fovea pursuant to Section
6.1.1 to Exploit Collaboration Combinations,
Selected Collaboration Products and other products
other than Selected Collaboration Products for any
purpose anywhere in the world;
(c)
a royalty-free, exclusive right and license, with
the right to grant sublicenses, under Fovea's
interest in all Fovea Collaboration Combination IP
that is jointly owned by the Parties pursuant to
Section 6.1.1 to Exploit products other than
Selected Collaboration Products for any purpose
anywhere in the world; and
(d)
a royalty-free, exclusive (which shall be
co-exclusive with Fovea for the purpose of
conducting clinical studies but not for otherwise
Exploiting Selected Collaboration Combinations
under this Section) right and license, with the
right to grant sublicenses, under Subsequent Fovea
Collaboration Combination IP to conduct Phase III
Studies (or their equivalent) of such Selected
Collaboration Combinations in the Collaboration
Combination Field anywhere in the world and to
Exploit Selected Collaboration Combinations and
Selected Collaboration Products in the
Collaboration Combination Field in the CombinatoRx
Territory.
2.1.3 RIGHT OF
REFERENCE TO DATA AFTER EVALUATION PERIOD.
Subject to the terms and conditions of this Agreement, Fovea hereby
grants to
CombinatoRx an exclusive, royalty free right of reference to Fovea
Generated
Data for CombinatoRx to Exploit Collaboration Combinations in the
Collaboration
Combination Field in the CombinatoRx Territory. For the avoidance
of doubt,
Fovea shall not be restricted from granting additional rights of
reference to
the data described in this Section to Third Parties for uses other
than those
specifically described in this Section.
2.1.4
CO-EXCLUSIVE LICENSES.
(a)
Subject to the terms and conditions of this
Agreement and delivery of a Target Dossier in accordance with
Section 3.9.2,
CombinatoRx hereby grants to Fovea a royalty-free, co-exclusive
right and
license, with the right to grant sublicenses as set forth below in
Section
2.1.3(c), under Collaboration Combination IP and Subsequent
CombinatoRx
Collaboration Combination IP to Exploit Selected Collaboration
Combinations and
Selected Collaboration Products in the Collaboration Combination
Field in the
Shared Territory.
(b)
Subject to the terms and conditions of this
Agreement, Fovea hereby grants to CombinatoRx a royalty-free,
co-exclusive right
and license, with the right to grant sublicenses as set forth below
in Section
2.1.3(c), under Subsequent Fovea
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Collaboration Combination IP to Exploit Selected Collaboration
Combinations and
Selected Collaboration Products in the Collaboration Combination
Field in the
Shared Territory.
(c)
Neither Party may grant sublicenses of rights
obtained under Section 2.1.3 unless both Parties agree to grant
sublicenses of
their rights under Section 2.1.3 to any particular sublicensee.
2.2
LICENSED COMBINATIONS
2.2.1 LICENSE
GRANTS TO FOVEA
(a)
LICENSED COMBINATION RESEARCH LICENSE. Subject
to the terms and conditions of this Agreement, CombinatoRx hereby
grants to
Fovea a royalty-free, exclusive (even as to CombinatoRx), worldwide
right and
license, with the right to grant sublicenses, under the CombinatoRx
Licensed
Combination IP with respect to all Licensed Combinations prior to
the expiration
of the Licensed Selection Period and only with respect to Selected
Licensed
Combinations following the expiration of the Licensed Selection
Period, to use
Licensed Combinations in the Licensed Combination Field solely for
research and
development of such Licensed Combinations.
(b)
SELECTED LICENSED COMBINATION LICENSE. Subject
to the terms and conditions of this Agreement, CombinatoRx hereby
grants to
Fovea a royalty-bearing, exclusive (even as to CombinatoRx)
worldwide right and
license, with the right to grant sublicenses, under the CombinatoRx
Licensed
Combination IP and CombinatoRx's interest in the Fovea Licensed
Combination IP
to use Licensed Combinations in the Licensed Combination Field to
Exploit
Selected Licensed Products.
(c)
RIGHT OF REFERENCE TO DATA. Subject to the
terms and conditions of this Agreement, CombinatoRx shall grant to
Fovea a right
of reference to CombinatoRx Generated Data for Fovea to Exploit
Selected
Licensed Products in the Licensed Combination Field.
2.2.2 LICENSE
GRANTS TO COMBINATORX
(a)
Fovea hereby grants a royalty-free, exclusive
(even as to Fovea), worldwide right and license to CombinatoRx,
with the right
to grant sublicenses, under Fovea's interest in the Fovea Licensed
Combination
IP, to Exploit products outside the Licensed Combination Field.
(b)
RIGHT OF REFERENCE TO DATA. Fovea hereby
grants to CombinatoRx a right of reference to the Fovea Generated
Data relating
to Licensed Combinations, for CombinatoRx to Exploit products
outside the
Licensed Combination Field.
2.3
SUBLICENSES.
2.3.1 BY FOVEA.
Fovea has the right to grant sublicenses,
through multiple tiers of sublicensees, to the extent permitted
under the
licenses granted in Section 2.1.1 and Section 2.2.1, to its
Affiliates and to
any other Persons to the extent of the license to which any such
sublicense
relates. An agreement by Fovea not to assert any rights granted to
it under
Section 2.1 or Section 2.2 shall be considered a sublicense of such
right for
the purposes of this Agreement. Where Fovea grants a sublicense to
a Person that
is not an
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Affiliate of Fovea, and such Person is not a Distributor, such
Person shall be a
"SUBLICENSEE" for purposes of this Agreement. Fovea shall ensure
that all
Persons to which it grants sublicenses will comply with all terms
and conditions
of this Agreement and be bound by indemnification obligations to
CombinatoRx of
a scope not less than the indemnification obligations of Fovea
contained herein,
and Fovea shall remain liable for any breach of this Agreement by a
Sublicensee.
Fovea shall provide notice of the granting of any sublicense
hereunder promptly
following the making of such grant. Such notice shall identify the
Sublicensee
and the territory of the sublicense.
2.3.2 BY
COMBINATORX. CombinatoRx has the right to grant
sublicenses, through multiple tiers of sublicensees to the extent
permitted
under the licenses granted in Section 2.1.2 and Section 2.2.2, to
its Affiliates
and to any other Persons to the extent of the license to which any
such
sublicense relates. An agreement by CombinatoRx not to assert any
rights granted
to it under Section 2.1 or Section 2.2 shall be considered a
sublicense of such
right for the purposes of this Agreement. CombinatoRx shall ensure
that all
Persons to which it grants sublicenses will comply with all terms
and conditions
of this Agreement and be bound by indemnification obligations to
Fovea of a
scope not less than the indemnification obligations of CombinatoRx
contained
herein, and CombinatoRx shall remain liable for any breach of this
Agreement by
a sublicensee. CombinatoRx shall provide notice of the granting of
any
sublicense hereunder promptly following the making of such grant.
Such notice
shall identify the sublicensee and the territory of the
sublicense.
2.3.3 BY
COMBINATORX AND FOVEA. The Parties shall have the
joint right to grant sublicenses, through multiple tiers of
sublicensees, under
the licenses granted in Section 2.1.3, to its Affiliates and to any
other
Persons in the Shared Territory
2.4
DISTRIBUTORSHIPS. The Parties have the right, in their sole
discretion, to appoint their Affiliates, who shall have the right,
in their
sole, respective discretion, to appoint any other Persons, in its
territory or
in any country of its territory, to distribute, market and sell
those products
for which Exploitation rights have been granted hereunder. Where a
Party or its
Affiliates appoints such a Person that is not an Affiliate of such
Party, that
Person shall be a "DISTRIBUTOR" for purposes of this Agreement.
ARTICLE 3
COLLABORATION COMBINATIONS
3.1
DETAILED DEVELOPMENT PLAN. Fovea shall develop each Selected
Collaboration Combination for each disease indication selected in
accordance
with a Detailed Development Plan to be developed in accordance with
the terms of
this Agreement. Within thirty (30) days of the selection of a
Selected
Collaboration Combination, Fovea shall prepare a Detailed
Development Plan for
such Selected Collaboration Combination. Within such 30-day period,
the Detailed
Development Plan shall then be submitted to the Joint Steering
Committee for
approval, as specified in Section 3.2.2. A Detailed Development
Plan approved by
the Joint Steering Committee for a Selected Collaboration
Combination shall be
the Detailed Development Plan for such Collaboration
Combination.
3.2
MANAGEMENT OF
DEVELOPMENT OF COLLABORATION COMPOUNDS AND
SELECTED COLLABORATION PRODUCTS - JOINT STEERING COMMITTEE
3.2.1 FORMATION.
Within thirty (30) days after the Effective
Date, the Parties shall form a Joint Steering Committee (the "JOINT
STEERING
COMMITTEE"). The Joint Steering
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Committee shall consist of equal numbers appointed by each
respective Party,
which shall include the CombinatoRx Senior Vice President of
Commercial
Operations (or a similar CombinatoRx officer) and the Fovea Chief
Operating
Officer (or a similar Fovea officer) acting as Co-Chairs. Each
Party shall have
the right to replace its respective Joint Steering Committee
representatives
upon written notice to the other Party. Each Party shall be
entitled to bring
for an agenda item at a meeting of the Joint Steering Committee
such minimum
numbers of nonvoting advisors, consultants and other visitors which
such Party
considers in good faith necessary or useful to such Party to
protect its
interest regarding the business to be dealt with under such agenda
item. If such
visitors are not employees of a Party, their attendance at the
Joint Steering
Committee meeting shall be further conditioned upon agreement with
the inviting
Party over confidentiality and non-use obligations no less
burdensome than those
set forth herein.
3.2.2
RESPONSIBILITIES OF THE JOINT STEERING COMMITTEE.
(a)
The Joint Steering Committee shall monitor the
activities of each Detailed Development Plan. In
particular, the responsibilities of the Joint
Steering Committee shall include: (a) determining
whether or not the criteria for continued
development under a particular Detailed
Development Plan have been met; (b) defining the
Target Dossier in accordance with Section 1.91;
(c) approving the Detailed Development Plan for
each Selected Collaboration Combination and
Selected Licensed Combination; (d) planning,
reviewing and approving preclinical and clinical
study designs; (e) planning, reviewing and
approving the timelines to complete such studies,
including any amendments to the timeline
necessitated by Permitted Delays; (f) ensuring
that clinical Phase I and Phase II studies, in
accordance with the Target Dossier, are designed
such that results from such studies can be used to
initiate Phase III Studies in the United States
and Europe; (g) approving formulation technologies
and license terms, as appropriate, for developing
commercial formulations to be used to conduct the
Phase III Studies for treating FOE Disease and/or
BOE Disease; (h) ensuring proper communication
between the Parties; and (i) recommending to the
CEOs of each Party adjustments to any deadlines
described in the Development Plans, in the event
such adjustments are needed.
(b)
The Joint Steering Committee shall also coordinate
preclinical and clinical studies of Selected
Collaboration Combinations that are being
developed in the Collaboration Combination Field
by both Parties and the publication of data from
these studies, which studies will be conducted in
a manner consistent with CombinatoRx's global
development activities of the Selected
Collaboration Combinations. All of Fovea's
preclinical and clinical plans, protocols,
investigators and regulatory submissions related
to the Selected Collaboration Combination shall
each be subject to prior approval by the Joint
Steering Committee. CombinatoRx shall disclose to
the Joint
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Steering Committee all CombinatoRx Generated Data
related to Selected Collaboration Combinations.
Adverse experiences shall be promptly communicated
by each Party to the other, along with all
supporting documentation in a manner consistent
with applicable regulatory authority reporting
requirements.
3.2.3 DISPUTES.
The Joint Steering Committee shall endeavor
to reach consensus on all matters brought before it with each Party
having a
single vote, irrespective of the number of representatives actually
in
attendance at a meeting; provided, however, that in the event the
Joint Steering
Committee is unable to resolve a material dispute before it within
thirty (30)
days of the time that it first considers such matter, such matter
shall be
resolved in accordance with Article 12.
3.2.4 MEETINGS.
The Joint Steering Committee shall meet once
each Calendar Quarter following the Effective Date. Regular
quarterly meetings
shall be scheduled on a recurring schedule to be established by the
Joint
Steering Committee (e.g. the first Tuesday of January, April, July
and October
at the place of meeting, if held in person), or at such other times
mutually
agreed to no less than three (3) months in advance, except for the
initial
meeting of the Joint Steering Committee, which shall be at a
mutually agreeable
time and place and shall take place no later than thirty (30) days
after the
Effective Date. In person meetings of the Joint Steering Committee
will be held
at alternating locations of the respective Co-Chair's choosing, or
by
teleconference or videoconference at the respective Co-Chair's
discretion.
Subject to Section 3.2.1, a quorum of the Joint Steering Committee
exists
whenever there is present at a meeting each of the Co-Chairs or
their respective
designees. In addition, the Joint Steering Committee may act
without a formal
meeting by a written memorandum signed by the Co-Chairs of the
Joint Steering
Committee. Whenever any action by the Joint Steering Committee is
required
hereunder during a time period in which the Joint Steering
Committee is not
scheduled to meet, either Co-Chair shall have the right, in
accordance with
Section 3.2.5, to call a special meeting or the Co-Chairs may cause
the Joint
Steering Committee to take the action without a meeting in the
applicable time
period. Any such additional meetings shall be held at places and on
dates
selected by mutual agreement of the Co-Chairs.
3.2.5 SPECIAL
MEETING. Notwithstanding Section 3.2.4, either
Co-Chair may call for a meeting to be held on a business day by
notifying the
other Party no later than fifteen (15) days in advance of a meeting
of the Joint
Steering Committee of the exact date, time and location for the
meeting;
provided, that (a) if such notice has been timely issued and the
meeting is held
on the date, time and place so indicated, or (b) if the other Party
confirms
that it has been properly notified about the meeting, then a quorum
shall be
considered constituted at that meeting unless all members of one
Party fail to
attend the meeting because of illness, where no substitution could
be reasonably
arranged, general breakdown in the instrumentalities of
communication, travel
difficulties beyond the reasonable control of such Party, or any
other
reasonable reason. For the purpose of agreeing that a Party has
been properly
notified of the meeting in the case under (b), attendance to a
meeting without
express objection thereto shall be sufficient.
3.2.6 EXPENSES.
CombinatoRx and Fovea each shall bear all
expenses of its Joint Steering Committee members related to such
members'
participation on the Joint Steering Committee and attendance at
Joint Steering
Committee meetings
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3.2.7 MINUTES.
The Joint Steering Committee shall keep
accurate minutes of its deliberations, which minutes shall record
all proposed
decisions and all actions recommended or taken. Furthermore, all
Collaboration
Combinations disclosed to Fovea shall be recorded in the minutes of
the Joint
Steering Committee. Drafts of minutes shall be delivered to the
Co-Chairs of the
Joint Steering Committee within twenty (20) days after the
respective meeting.
The Parties, on an alternating basis, shall prepare and circulate
the draft
minutes. Draft minutes shall be edited by the Co-Chairs and shall
be issued in
final form only with the approval and agreement of the Co-Chairs.
All
communications and minutes regarding the Joint Steering Committee
shall be in
English.
3.3
SELECTION PERIOD FOR COLLABORATION COMBINATIONS.
3.3.1
COMBINATION ASSESSMENT DATA. Promptly following the
Effective Date, CombinatoRx shall provide to Fovea all Combination
Assessment
Data for each Collaboration Combination.
3.3.2 SELECTION
PERIOD AND SELECTION. Fovea shall have
ninety (90) days after receiving all Combination Assessment Data
from
CombinatoRx (the "Collaboration Selection Period") to select the
Selected
Collaboration Combinations. Fovea shall select at least five (5)
but not more
than ten (10) each of ECI Collaboration Combinations, CM
Collaboration
Combinations and SSA Collaboration Combinations during the
Collaboration
Selection Period; provided that, (x) for each Ophthalmic
Combination that Fovea
selects, Fovea must select a Collaboration Combination that is not
an Ophthalmic
Combination and shall so designate which non-Ophthalmic Combination
is selected
with respect to each such Ophthalmic Combination (each such pair
of
Collaboration Combinations, a "Collaboration Combination Pair");
(y) Fovea may
only select a Selected Collaboration Combination (i) that uses a
different
proposed delivery method from a Selected Licensed Combination or
(ii) for which
one of the components of the combination is different from the
components of a
Selected Licensed Combination, in either case for the purpose of
avoiding the
use of a SSA Combination approved for FOE Disease in an off-label
manner for BOE
Disease. Fovea shall provide notice of the Selected Collaboration
Combinations
selected during the Collaboration Selection Period by written
notice specifying
the particular Collaboration Combinations being selected.
3.4
EVALUATION PERIOD
3.4.1 EVALUATION
PERIOD. For each Selected Collaboration
Combination, the Evaluation Period shall extend from the date of
selection until
the delivery of the Target Dossier to CombinatoRx for such
Selected
Collaboration Combination in accordance with Section 3.9.2. During
the
Evaluation Period for a particular Selected Collaboration
Combination, Fovea
shall provide to CombinatoRx a written report (the "Selected
Collaboration
Combination Quarterly Report") summarizing development results and
activities
from the preceding Calendar Quarter relating to such Selected
Collaboration
Combination. The Selected Collaboration Combination Quarterly
Report shall be
delivered to CombinatoRx within fifteen (15) days after the end of
the preceding
Calendar Quarter.
3.4.2 NON
DELIVERY OF TARGET DOSSIER. In the event that
Fovea does not deliver a Target Dossier to CombinatoRx for a
particular Selected
Collaboration Combination prior to the Target Dossier Deadline (as
defined in
Section 3.9.2) or is otherwise not meeting its obligations under
Section 3.9
hereof, then:
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(a) Fovea shall return to CombinatoRx any samples of such
Collaboration Combination previously provided by
CombinatoRx that are still in Fovea's possession;
(b) Fovea shall return to CombinatoRx all Combination
Assessment Data, Regulatory Documentation and all Fovea
Generated Data associated with such Collaboration
Combination; and
(c) CombinatoRx shall have the right to pursue development of
such Collaboration Combination as follows:
a. If Fovea
has failed to deliver a Target
Dossier by the latest applicable Target
Dossier Deadline (or Fovea has otherwise
notified CombinatoRx in writing that Fovea has
ceased development) for at least one Selected
Collaboration Combination within each type
(i.e. CM, ECI, SSA) of Collaboration
Combination (or has failed to select any
Collaboration Combination within a particular
type of Collaboration Combination), then
CombinatoRx may Exploit a Collaboration
Combination of such type of Collaboration
Combination for any indication without
restriction;
b. For
Collaboration Combinations that are not
described in clause a. above, CombinatoRx may
Exploit such Collaboration Combination for any
indication provided that such Collaboration
Combination is not being developed for an
indication that directly competes with a
Collaboration Combination being developed by
Fovea at the time that CombinatoRx commences
development of such Collaboration Combination
outside of the Collaboration Combination
Field.
3.4.3 EXTENSION
OF EVALUATION PERIOD. The Evaluation Period
and the Target Dossier Deadline shall be extended by a period to be
mutually
agreed by the Parties with respect to a particular Selected
Collaboration
Combination if a new Phase II Study is necessary to commercialize
such Selected
Collaboration Combination for an indication which differs from the
indication
originally being evaluated.
3.5
INDICATIONS. The initial disease indications for a Selected
Collaboration Combination shall be provided in the Detailed
Development Plan.
Fovea shall seek the consent of the Joint Steering Committee to
develop any
follow-on indications not provided in the Detailed Development Plan
for a
Selected Collaboration Combination.
3.6
PHASE III STUDIES.
3.6.1 GENERAL.
Not later than ninety (90) days prior to the
anticipated expiration of the Evaluation Period for a Selected
Collaboration
Combination, the Parties shall agree in writing whether (a) the
Parties will
jointly pursue Phase III Trials, (b) the Parties will each
separately pursue
Phase III Trials, or (c) only a Pursuing Party (as defined below)
will pursue
the Phase III Trials; provided that, no Party that desired to
pursue Phase III
Trials shall be precluded from doing so under this Section.
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3.6.2 PURSUIT OF
PHASE III STUDIES.
(a)
JOINT PURSUIT. The Parties may decide that
they shall jointly pursue Regulatory Approval for a particular
Selected
Collaboration Combination, in which event, the Joint Steering
Committee shall
oversee such development activities and the Parties will negotiate
in good faith
the terms of any such joint pursuit.
(b)
SEPARATE PURSUIT. If the Parties do not decide
to jointly pursue Regulatory Approval of a Selected Collaboration
Combination,
each Party may separately pursue Regulatory Approval of such
Selected
Collaboration Combination in its territory. Each Party shall be
responsible for
conducting its own Phase III Trials, as well as any additional
studies necessary
to obtain Regulatory Approval in its territory. Upon request by
either Party,
the Parties shall negotiate in good faith whether the requesting
Party may
reference the other Party's Regulatory Documentation.
(c)
SINGLE PARTY PURSUIT. If a Party (the
"Non-Pursuing Party") indicates to the other Party in writing its
decision not
to pursue Regulatory Approval of a particular Selected
Collaboration
Combination, the other Party (the "Pursuing Party") shall have a
right of first
negotiation to obtain exclusive rights to Exploit such Selected
Collaboration
Combination in the Non-Pursuing Party's territory. If the Pursuing
Party desires
to obtain rights to Exploit such Selected Collaboration Combination
in the
Non-Pursuing Party's territory, the Pursuing Party shall so notify
the
Non-Pursuing Party and the Parties shall thereafter negotiate the
terms of such
rights for a period of not less than 90 days. If the Parties are
unable to reach
agreement on such terms within such 90-day period, then the
Non-Pursuing Party
shall be permitted to grant its rights in its territory to a third
party without
restriction.
3.7
SHARED TERRITORY. The Parties shall have co-exclusive rights
in the Shared Territory to Exploit Selected Collaboration
Combinations,
including development, commercialization and licensing. All
decisions regarding
Exploitation of Selected Collaboration Combinations or Selected
Collaboration
Products in the Shared Territory shall be made by mutual agreement
of the
Parties; provided that, such decisions shall not be subject to
Section 12.3 if
the Parties are unable to reach agreement regarding such
Exploitation.
3.8
FORMULATIONS OF COLLABORATION COMBINATIONS.
3.8.1
FORMULATION TECHNOLOGY. Fovea shall be responsible for
developing or obtaining from Third Parties at its election all
technology
necessary to develop commercial formulations of the Selected
Collaboration
Combinations (as so developed or obtained by Fovea, the
"Formulation
Technology"). All Formulation Technology and Intellectual Property
pertaining
thereto shall be owned by Fovea.
(a)
FOVEA DEVELOPED TECHNOLOGY. In the event that
Fovea has developed any Formulation Technology prior to the
Effective Date or
develops any Formulation Technology at any time after the Effective
Date, Fovea
shall, and does hereby, grant to CombinatoRx a royalty-free, fully
paid up,
right and license, with the right to grant sublicenses, in the
CombinatoRx
Territory and the Shared Territory to use such Formulation
Technology solely for
the Exploitation of Selected Collaboration Products in the
Collaboration
Combination Field.
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(b)
FOVEA IN-LICENSED TECHNOLOGY. In the event
that Fovea has in-licensed any Formulation Technology from a Third
Party prior
to the Effective Date or in-licenses any Formulation Technology at
any time
after the Effective Date, then (i) Fovea shall, and does hereby,
grant to
CombinatoRx a sublicense, with the right to grant further
sublicenses, in the
CombinatoRx Territory and the Shared Territory to use such
Formulation
Technology solely for the Exploitation of Selected Collaboration
Products in the
Collaboration Combination Field, (ii) CombinatoRx shall pay
royalties that may
be owed to the Third Party licensing such Formulation Technology to
Fovea on
sales of Selected Collaboration Products utilizing such Formulation
Technology
in the CombinatoRx Territory, and (iii) the Parties shall each pay
50% of the
royalties that may be owed to the Third Party licensing such
Formulation
Technology to Fovea on sales of Selected Collaboration Products
utilizing such
Formulation Technology in the Shared Territory.
3.8.2 COSTS.
Fovea shall be responsible for any and all
costs necessary for developing, acquiring or licensing the
Formulation
Technology.
3.8.3
FORMULATIONS SOLD TO COMBINATORX. If requested by
CombinatoRx, Fovea shall supply formulated Collaboration
Combinations for the
purpose of CombinatoRx conducting Phase III Studies and for
commercializing a
Selected Collaboration Product, at the same price paid by Fovea to
a Third Party
manufacturer. CombinatoRx shall have the right to obtain
formulated
Collaboration Combinati
