AMENDED AND RESTATED RESEARCH AND LICENSE AGREEMENT between FOVEA PHARMACEUTICALS SA and COMBINATORX, INCORPORATED Dated June 12, 2007

10508642_1

AMENDED AND RESTATED RESEARCH AND LICENSE AGREEMENT

      This Amended and Restated Research and License Agreement (the “Agreement”) is dated as of June 12, 2007 (the “Effective Date”) and is between Fovea Pharmaceuticals SA, a company organized and existing under the laws of, France, with an office at 12, rue Jean-antione de Baif 75013 Paris, France (“Fovea”), and CombinatoRx, Incorporated, a company organized and existing under the laws of Delaware, with an office at 245 First Street, Cambridge, MA 02142 (“CombinatoRx”) and amends and restates in its entirety the Research and License Agreement between Fovea and CombinatoRx (the "Original Agreement") dated as of January 30, 2006 (the "Original Agreement Effective Date"). Each of Fovea and CombinatoRx are sometimes referred to herein as a “Party” and together as the “Parties.”

(A)CombinatoRx has expertise in discovery and development of combination drugs, and has drug combinations in discovery, preclinical and clinical stages of development.

(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.

      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:

Unless otherwise specifically provided herein, the following terms, when used with a capital letter at the beginning, shall have the following meanings:

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 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 Parties.

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 Original Agreement 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 Original Agreement 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, another calcineurin inhibitor or a corticosteroid.

      1.11 “ CM Combination IP ” means, with respect to a CM compound delivered by CombinatoRx to Fovea pursuant Section 3.5 hereof, all Intellectual Property conceived by either Party or jointly by both Parties prior to the termination of the Evaluation Period for such CM compound arising out of or related to Fovea's use of such CM compound, including any such Intellectual Property existing on the Original Agreement Effective Date. Specifically excluded from CM Combination IP is Intellectual Property pertaining to Formulation Technology, as defined in Section 3.2.1.

      1.12 “ CM Product ” means a pharmaceutical preparation suitable for administration to a human, containing a CM combination as an Active Ingredient.

      1.13 “ Collaboration Combination ” means (i) the SSA drug combinations in the Chalice Database identified in writing by Fovea prior to the Effective Date, (ii) the ECI drug combinations in the Chalice Database identified in writing by Fovea prior to the Effective Date and (iii) the CM drug combinations in the Chalice Database identified in writing by Fovea prior to the Effective Date, as such lists may be modified pursuant to Section 2.6 hereof.

      1.14 “ Collaboration Combination Field ” means use of a Collaboration Combination by Local Administration to treat the diseases indicated below:

For clarification, each Collaboration Combination type is licensed solely for the treatment of the corresponding disease indicated above.

      1.15 “ 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 Original Agreement 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 Collaboration Product in

the Collaboration Combination Field. Specifically excluded from Collaboration Combination IP is Intellectual Property pertaining to Formulation Technology, as defined in Section 3.2.1.

      1.16 “ Collaboration Product ” means a pharmaceutical preparation suitable for administration to a human, containing a Collaboration Combination as an Active Ingredient.

      1.17 “ Combination ” refers either to Collaboration Combination or Licensed Combination.

      1.18 “ 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.

      1.19 “ 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 Original Agreement 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, products, cultures, biological materials, drugs, drug-device combinations and other materials and compositions, Controlled by CombinatoRx or its Affiliates as of the Original Agreement 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.

      1.20 “ 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.

      1.21 “ CombinatoRx Generated Data ” means data generated and Controlled by CombinatoRx relating to a Combination.

      1.22 “ 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 Licensed Product. All CombinatoRx Licensed Combination IP shall be solely owned by CombinatoRx.

1.23 “ CombinatoRx Territory ” means North America, Singapore and South Korea.

      1.24 “ Commence ” means, with respect to a clinical trial, that the first patient in such clinical trial has been dosed with the study drug.

      1.25 “ Commercially Reasonable Efforts” means with respect to research, development, Manufacture or commercialization activities in connection with Collaboration Products and 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.

clinical trial has been first dosed with the study drug.

      1.28 “ Condition ” shall mean any malady, disease, syndrome, trauma, injury or condition.

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.

      1.31 " Development Steps " means those activities to be undertaken by Fovea for each Collaboration Combination or Licensed Combination, as applicable. Fovea must follow these Development Steps:

      (a) The Collaboration Combination or Licensed Combination shall enter formulation development;

      (b) If the Collaboration Combination or Licensed Combination can be formulated for ophthalmic use, it shall be advanced to animal ocular tolerability experiments;

      (c) If the Collaboration Combination or Licensed Combination has acceptable ocular tolerability properties, it shall be advanced to animal proof-of-concept efficacy models;

      (d) If the Collaboration Combination or Licensed Combination is efficacious in animal models it shall be advanced to ocular toxicity and pharmacokinetic studies; and

      (e) If the Collaboration Combination or Licensed Combination is tolerable, non-toxic, efficacious, and can be formulated for ophthalmic use, it shall be advanced to a Phase I human safety/pharmacokinetic study.

two or more active pharmaceutical ingredients where one of the pharmaceutical ingredients is tacrolimus, cyclosporine, ISAtx24, Rapamycin (Sirolimus), Pimecrolimus, Everolimus or another calcineurin inhibitor.

      1.36 “ EMEA ” means the European Agency for Evaluation of Medical Products or any successor thereto.

      1.37 “ Evaluation Period ” means, with respect to each Collaboration Combination, the period from the Original Agreement Effective Date to the date that Fovea selected such drug combination to be a Collaboration Combination pursuant to this Agreement or the Original Agreement, as applicable.

      1.38 “ Exploit ,” “ Exploiting ” or “ Exploitation ” means to make, use, offer for sale, sell and import, including, without limitation, to research, develop, formulate, modify, 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.

      1.39 “ FDA ” means the United States Food and Drug Administration and any successor agency thereto.

      1.40 “ First Commercial Sale ” means the first sale for monetary value for use or consumption by a member of the general public of a 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.

      1.41 “ 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 Parties pursuant to this Agreement, Pan Uveitis, and all other similar diseases as agreed to by the Parties.

      1.42 “ Fovea Background Technology ” means (a) Fovea’s proprietary in vitro and in vivo models of ophthalmic diseases as of the Original Agreement 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.

      1.43 “ Fovea CM Combination IP ” means CM Combination IP that is conceived by Fovea or Third Parties acting on behalf of Fovea.

      1.44 “ Fovea Collaboration Combination IP ” means Collaboration Combination IP that is conceived by Fovea or Third Parties acting on behalf of Fovea.

      1.45 “ Fovea Generated Data ” means data generated by Fovea relating to a Combination.

      1.46 “ Fovea Licensed Combination IP ” means any Intellectual Property conceived by Fovea and relating to a Licensed Combination or the Manufacture or use thereof.

      1.47 “ Fovea Territory ” means all countries in the world, but excluding countries in the CombinatoRx Territory and the Shared Territory.

      1.48 “ Heads ” means the Chief Executive Officer of CombinatoRx and the Chief Executive Officer of Fovea.

      1.49 “ Improvements ” means patentable or material non-patentable improvements, variations, updates, adaptations, modifications or upgrades or enhancements.

      1.50 “ 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.

      1.53 “ Indemnifying Party ” means a Party from whom recovery of a Loss is sought under Section 10.1 or 10.2.

      1.56 “ 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.

      1.57 “ Intellectual Property ” means any and all ideas, inventions, discoveries, knowhow, 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 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.

      1.58 “Availability of Key Statistical Data” means the date on which the statistical analysis of the primary endpoint and safety data of a clinical trail is available in written form for evalution.

      1.59 “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.

      1.60 “ Licensed Combination ” means the SSA drug combinations in the Chalice Database identified in writing by Fovea prior to the Effective Date, as such list may be modified pursuant to Section 4.3 hereof.

      1.61 “ Licensed Combination Field ” means use of Licensed Combinations for treating FOE Diseases by Local Administration.

1.62 “ Licensed Information ” means Information which is Controlled by

CombinatoRx as of the Original Agreement 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 Collaboration Products and/or Licensed Products, but excluding any Information to the extent covered by a Valid Claim within the Licensed Patents.

      1.63 “ 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), Collaboration Products, and/or 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 Original Agreement Effective Date and through the Term of this Agreement.

      1.64 “ Licensed Product ” means a pharmaceutical preparation suitable for administration to a human, containing a Licensed Combination as an Active Ingredient.

      1.65 “ Local Administration ” means local ophthalmic delivery to the surface or interior of the eye.

      1.66 “ 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.

      1.67 “ 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.

1.68 “ Net Sales ” means the gross invoiced amount on sales of the Licensed

Combinations or 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:

In the case of any other sale or other disposal for value, such as barter or counter-trade, of any Licensed Combinations or 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 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.

      1.69 “ North America ” means the United States, its possessions and territories, Canada and Mexico.

      1.70 “ 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.

      1.71 “ Patent Coverage ” means, for a particular 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 Licensed Product in such country.

      1.72 “ 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.

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.

      1.75 “ Phase I Study ” shall mean a study of a Collaboration Product or 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 which there are no primary endpoints (as recognized by FDA or other Regulatory Authorities) in the protocol relating to efficacy.

      1.76 “Phase II(a) Study” shall mean a preliminary efficacy and safety study of a Collaboration Product or Licensed Product in the target patient population designed to be statistically significant in comparison of the combination to its constituent parts and to demonstrate clinical proof of concept.

      1.77 “ Phase II(b) Study ” shall mean a statistically significant study of a Collaboration Product or Licensed Product to evaluate further any preliminary efficacy observed for, and the safety of, the Collaboration Product or Licensed Product in the target patient population and/or to provide data that may be useful in the design of subsequent studies of the Collaboration Product or Licensed Product such as Phase III Studies or Pivotal Trials, including, but not limited to dose level, dose ratio, and dose regimen.

      1.78 “ Phase III Study ” shall mean a controlled study to confirm with statistical significance the efficacy and safety of a Collaboration Product or Licensed Product performed to obtain marketing and/or manufacturing approval for the product in any country.

      1.79 “ 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 Collaboration Product or Licensed Product.

      1.80 "Pre-Clinical Steps" means those activities to be undertaken by Fovea for a CM Collaboration Combination in accordance with Section 3.3.3(i) as follows:

all approvals, licenses, registrations or authorizations of any Regulatory Authority necessary to commercially Manufacture, distribute, sell or market a Collaboration Product or 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.

      1.83 “ 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, Licensed Products and/or 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.

      1.84 “ 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 obtaining Regulatory Approval, Regulatory Approvals, regulatory drug lists, advertising and promotion documents, adverse event files and complaint files.

      1.85 “ Shared Territory ” means Japan and Taiwan. The Parties shall have equal rights in the Shared Territory in accordance with the terms of this Agreement.

      1.86 “ SSA ” a Selective Steroid Amplifier as a therapeutic drug containing two or more active pharmaceutical ingredients where one of the agents is a corticosteroid.

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 Collaboration Product, and (iii) conceived after the termination of the Evaluation Period.

      1.89 “ 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 Collaboration Product, and (iii) conceived after the termination of the Evaluation Period.

      1.90 “ Target Dossier ” shall mean, with respect to a particular Collaboration Combination, all data, information and materials generated by or on behalf of Fovea 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.

      1.93 “ Third Party Agreement ” means all license, research and/or other agreements entered into by CombinatoRx prior to or following the Effective Date.

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, Collaboration Products, Licensed Combinations or Licensed Products.

      1.96 “ Treatment ” or “ Treat ” means diagnosis, palliation, monitoring, cure, mitigation, treatment or prevention.

      1.97 “ United States ” or “ U.S. ” means the United States of America, including its territories, possessions and Puerto Rico.

      1.98 “ 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.

      (a) 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 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.

      (b) Collaboration Combination Exploitation License . Subject to the terms and conditions of this Agreement and delivery of each Target Dossier in accordance with Section 3.3.6, 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 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 Collaboration Combination in the Collaboration Combination Field anywhere in the world and (ii) to Exploit such Collaboration Combination and all Collaboration Products in the Collaboration Combination Field in the Fovea Territory.

      (c) Right of Reference to Data . Subject to the terms and conditions of this Agreement and delivery of a Target Dossier in accordance with Section 3.3.6, CombinatoRx hereby grants to Fovea an exclusive, royalty free right of reference to (i) Fovea Generated Data generated prior to selection of any Collaboration Combination, (ii) CombinatoRx Generated Data generated prior to selection of any Collaboration Combination, and (iii) clinical data Controlled by CombinatoRx and existing on the Original Agreement Effective Date for any Collaboration Combination for which CombinatoRx commenced clinical studies prior to the Original Agreement Effective Date, in each case for Fovea to Exploit 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 3.2.1(a) and 3.2.1(b), Fovea hereby grants to CombinatoRx:

CONFIDENTIAL

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.

      (a) Subject to the terms and conditions of this Agreement and delivery of a Target Dossier in accordance with Section 3.3.6, 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 2.1.4(c), under Collaboration Combination IP and Subsequent CombinatoRx Collaboration Combination IP to Exploit Collaboration Combinations and 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 2.1.4(c), under Subsequent Fovea Collaboration

Combination IP to Exploit Collaboration Combinations and Collaboration Products in the Collaboration Combination Field in the Shared Territory.

      (c) Neither Party may grant sublicenses of rights obtained under Section 2.1.4 unless both Parties agree to grant sublicenses of their rights under Section 2.1.4 to any particular sublicensee.

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 Licensed Products.

      (b) 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 Licensed Products in the Licensed Combination Field.

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.

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 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.

      3.1 Combination Assessment Data. Fovea acknowledges that CombinatoRx has provided to Fovea all Combination Assessment Data for each ECI, SSA and CM.

obtaining from Third Parties at its election all technology necessary to develop commercial formulations of the 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 Original Agreement Effective Date or develops any Formulation Technology at any time after the Original Agreement 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 Collaboration Products in the Collaboration Combination Field.

      (b) Fovea In-Licensed Technology . In the event that Fovea has in-licensed any Formulation Technology from a Third Party prior to the Original Agreement Effective Date or in-licenses any Formulation Technology at any time after the Original Agreement 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 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 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 Collaboration Products utilizing such Formulation Technology in the Shared Territory.

      3.2.2 Costs . Fovea shall be responsible for any and all costs necessary for developing, acquiring or licensing the Formulation Technology.

      3.2.3 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 Collaboration Product, at the same price paid by Fovea to a Third Party manufacturer. CombinatoRx shall have the right to obtain formulated Collaboration Combinations from the Third Party manufacturer Fovea uses to manufacture the formulated Collaboration Combinations; and to use a Third Party manufacturer to manufacture the formulated Collaboration Combinations if Fovea’s manufacturer cannot provide a sufficient supply to meet CombinatoRx’s requirements, and Fovea shall license to such Third Party manufacturer any necessary and useful intellectual property to manufacture formulated Collaboration Combinations.

      3.3 Diligence Obligations . Fovea (itself or through its Affiliates or a Sublicensee) shall meet the following obligations:

      (i) Complete the Development Steps of an SSA Collaboration Combination on or prior to June 30, 2008;

      (ii) Commence a Phase II(a) Study of a SSA Collaboration Combination on or prior to December 31, 2008;

      (iii) Complete the first Phase II(a) Study of an SSA Collaboration Combination on or prior to December 31, 2009;

      (iv) use Commercially Reasonable Efforts to Commence a Phase II(b) Study within 270 days after Key Statistical Analysis Availability of a Phase II(a) trial for an SSA Collaboration Combination; and

      (v) thereafter, use Commercially Reasonable Efforts to seek Regulatory Approval for an SSA Collaboration Combination in at least one indication.

      (i) Complete the Development Steps of an ECI Collaboration Combination on or prior to June 30, 2009;

      (ii) if an ECI Collaboration Combination is non-toxic and has acceptable pharmacokinetic properties in humans, Commence a Phase II(a) Study on or prior to December 31, 2009;

      (iii) Complete the first Phase II(a) Study of an ECI Collaboration Combination on or prior to September 30, 2010;

      (iv) use Commercially Reasonable Efforts to Commence a Phase II(b) Study within 270 days after Key Statistical Analysis Availability of a Phase II(a) trial for an ECI Collaboration Combination; and

      (v) thereafter, use Commercially Reasonable Efforts to seek Regulatory Approval for an ECI Collaboration Combination in at least one indication.

(ii) Complete the Development Steps for a CM Collaboration

Combination and Commence a first Phase II(a) Study of a CM Collaboration Combination on or prior to December 31, 2009;

      (iii) use Commercially Reasonable Efforts to Commence a Phase II(b) Study within 270 days Key Statistical Analysis Availability of a Phase II(a) trial for a CM Collaboration Combination; and

      (iv) thereafter, use Commercially Reasonable Efforts to seek Regulatory Approval for a CM Collaboration Combination in at least one indication.

      3.3.4 Written Report . Within thirty (30) days after the end of each Calendar Quarter following the date hereof, Fovea shall provide to CombinatoRx a written report summarizing development results and activities with respect to Collaboration Combinations from the preceding Calendar Quarter.

      3.3.5 Commercialization Diligence . In addition to the requirements of this Section to develop Collaboration Combinations pursuant to Sections 3.3.1, 3.3.2 and 3.3.3, Fovea shall use Commercially Reasonable Efforts to commercialize Collaboration Products in each jurisdiction for which Regulatory Approval has been obtained.

      (a) Notification and Meeting . If at any time CombinatoRx has a reasonable basis to believe that Fovea is in breach of its obligations under Sections 3.3.1, 3.3.2, 3.3.3 or 3.3.5, then CombinatoRx shall notify Fovea in writing, specifying the basis for its belief, and the Parties shall meet within fifteen (15) days after such written notice to discuss in good faith for a period of not more than fifteen (15) days CombinatoRx's concerns and Fovea's development activities with respect to the Collaboration Combinations.

      (b) Right of Termination for Certain Breaches. If, CombinatoRx has notified Fovea pursuant to Section 3.3.5(a) of a breach of Sections 3.3.1(i), 3.3.1(ii), 3.3.1(iii), 3.3.2(i), 3.3.2(ii), 3.3.2(iii), 3.3.3(i) or 3.3.3(ii) and, after such good faith discussions described in Section 3.3.6(a), CombinatoRx continues to believe that Fovea is in breach of its obligations under Sections 3.3.1(i), 3.3.1(ii), 3.3.2(iii), 3.3.2(i), 3.3.2(ii), 3.3.2(iii), 3.3.3(i) or 3.3.3(ii), CombinatoRx may, immediately exercise its right of termination provided under Section 11.3.

      (c) Right of Termination for Certain Breaches . Except as specified in Section 3.3.5(b), if CombinatoRx has notified Fovea pursuant to Section 3.3.5(a) of a breach of Section 3.3.1, 3.3.2, 3.3.3 or 3.3.5 and if, after such good faith discussions described in Section 3.3.6(a), (i) CombinatoRx continues to believe that Fovea is in breach of its obligations under Sections 3.3.1(iv), 3.3.1(v), 3.3.2(iv), 3.3.2(v), 3.3.3(iii), 3.3.3(iv) or 3.3.5 and (ii) Fovea has not rectified such breach within sixty (60) days of meeting with CombinatoRx pursuant to Section 3.3.6(a) (or, if such failure cannot be rectified within such sixty (60) day period, if Fovea does not commence reasonable actions to rectify such breach within such period and thereafter does not diligently pursue such actions), CombinatoRx may, subject to the provisions of Section 12, exercise its right of termination provided under Section 11.3.

      (d) Notwithstanding anything else contained in this Agreement, Fovea shall not be deemed to be in breach of its obligations under this Section 3.3 if it fails to achieve a required action under this Section 3.3 within the required timeframe due to the failure of a Collaboration Compound to meet necessary scientific or regulatory endpoints for any such required action to be undertaken.

      3.3.7 Target Dossier . Within thirty (30) days following the earlier of (i) Key Statistical Analysis Availability for a Phase II(b) Study of a Collaboration Combination or (ii) termination of this Agreement with respect to a particular Collaboration Product pursuant to Section 3.3.5(b) or 3.3.5(c), Fovea shall submit to CombinatoRx a Target Dossier for the relevant Collaboration Combination which Target Dossier may be used by CombinatoRx to initiate Phase III Studies in the CombinatoRx Territory.

      3.3.8 Non Delivery of Target Dossier . In the event that Fovea does not deliver a Target Dossier to CombinatoRx for a particular Collaboration Combination within the time period described in Section 3.3.7, such failure will be deemed a material breach of this Agreement.

      3.3.9 Termination of Collaboration Combinations by Fovea . In the event that Fovea decides to not continue development of a class of Collaboration Combinations (e.g. SSA, ECI or CM), Fovea shall have the ability to terminate development of an entire class of

Collaboration Combinations for any reason approved by CombinatoRx in writing, by providing written notice of such action to CombinatoRx, with such notice accompanied by the Target Dossier for such class of Collaboration Combinations. In such event, all grants of Intellectual Property relating to such class of Collaboration Combinations shall terminate, Fovea shall assign to CombinatoRx its rights in the Fovea Collaboration Combination IP, Fovea Generated Data and Regulatory Documentation, with respect to such class of Collaboration Combinations and CombinatoRx shall have the right to pursue development of such class of Collaboration Combinations for any indication. Such termination shall relive Fovea from the applicable obligations under this Sections 3.3.1 through 3.3.6 and shall not be deemed to be a breach pursuant to Section 11.3.

      3.4 Shared Territory. The Parties shall have co-exclusive rights in the Shared Territory to Exploit Collaboration Combinations, including development, commercialization and licensing. All decisions regarding Exploitation of Collaboration Combinations or 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.

      3.5 Election of Lead Combinations. Prior to the commencement of a Phase II(b) study with a SSA Collaboration Combination or an ECI Collaboration Combination, Fovea shall reduce the number of SSA Collaboration Combinations and ECI Collaboration Combinations from those listed on the lists of Collaboration Combinations provided prior to the Effective Date, to no more than three (3) each. After the completion of the Pre-clinical Steps with the CM Collaboration Combinations, Fovea shall reduce the number of CM Collaboration Combinations from those listed on the list of CM Collaboration Combinations provided prior to the Effective Date to no more than three (3). The reductions required by this Section shall be made by written notice to CombinatoRx specifying the SSA Collaboration Combinations, ECI Collaboration Combinations or CM Collaboration Combinations, as applicable, that Fovea has determined to remove from the applicable list of Collaboration Combinations. Collaboration Combinations that are removed from a list of Collaboration Combinations pursuant to this Section shall thereafter cease to be Collaboration Combinations under this Agreement.

      4.1 Diligence Obligations . Fovea (itself or through its Affiliates or a Sublicensee) shall meet the following obligations:

      (i) complete the Development Steps of a Licensed Combination on or prior to June 30, 2008;

      (ii) if a Licensed Combination is non-toxic and has acceptable pharmacokinetic properties in humans, commence a Phase II(a) Study on or prior to December 31, 2008;

      (iii) complete the first Phase II(a) Study of a Licensed Combination on or prior to June 30, 2009;

      (iv) use Commercially Reasonable Efforts to commence a Phase II(b) Study within 6 months after successful completion of Phase II(a) for a Licensed Combination; and

      (v) thereafter, use Commercially Reasonable Efforts to seek Regulatory Approval for a Licensed Combination in at least one indication.

Fovea may not develop a Licensed Combination for keratoconjunctivitis sicca as the first indication for which Licensed Combinations are developed. Notwithstanding the foregoing, no Licensed Combination may be developed for Pan Uveitis unless the Parties consent to such development in light of the actual and anticipated development activities for Collaboration Combinations.

      4.1.2 Written Report . Within thirty (30) days after the end of each Calendar Quarter following the date hereof, Fovea shall provide to CombinatoRx a written report summarizing development results and activities with respect to Licensed Combinations from the preceding Calendar Quarter.

      4.1.3 Commercialization Diligence . In addition to the requirements of this Section to develop Licensed Combinations pursuant to Section 4.1.1, Fovea shall use Commercially Reasonable Efforts to commercialize Licensed Products in each jurisdiction for which Regulatory Approval