EX-10.37 COLLABORATION AND LICENSE AGREEMENT

Exhibit 10.37

COLLABORATION AND LICENSE AGREEMENT

     THIS COLLABORATION AND LICENSE AGREEMENT (the " Agreement ") is made effective as of the 7th day of September, 2006 (the " Effective Date ") by and between GTx, Inc., a Delaware corporation having its principal place of business at 3 North Dunlap St., Memphis, Tennessee 38163 (" GTx ") each on behalf of itself and its Affiliates and Ipsen Limited, a company organized under the laws of England and Wales, with its principal place of business at 190 Bath Road, Slough SL1 3XE, United Kingdom (" Ipsen "), each on behalf of itself and its Affiliates. GTx and Ipsen are sometimes referred to herein individually as a " Party " and collectively as the " Parties ", and references to " GTx " and " Ipsen " shall include their respective Affiliates.

RECITALS

      Whereas, Ipsen is a multinational healthcare company with research, development and marketing activities, which desires to obtain additional potential drug products for the prevention of prostate cancer, the treatment of complications arising from androgen deprivation therapy for advanced prostate cancer, and other possible indications;

      Whereas, GTx is a men’s health biotech company, which is developing certain compounds to prevent prostate cancer and treat complications arising from androgen deprivation therapy, including Acapodene®;

      Whereas, GTx is conducting two clinical studies of Acapodene® for two separate indications in the United States (" US ") under special protocol assessments (" SPA ") with the US Food and Drug Administration: (a) a Phase III clinical trial of a 20 mg dose of Acapodene for the prevention of prostate cancer in men with high grade prostatic intraepithelial neoplasia (the " PIN Trial "), and (b) a Phase III clinical trial of a 80 mg dose of Acapodene for the prevention of bone fractures and serious side effects of androgen deprivation therapy in men with prostate cancer (the " ADT Trial ");

      Whereas, GTx is the exclusive licensee of the compound, Toremifene, the active ingredient of Acapodene, from Orion Corporation, a Finnish pharmaceutical company (" Orion "), and the exclusive licensee from the University of Tennessee Research Foundation (" UTRF ") of certain methods of use patents and patent applications claiming or covering Toremifene and other selective estrogen receptor modulators for the treatment of high grade prostatic intraepithelial neoplasia and the prevention of prostate cancer; and

      Whereas, GTx desires to exclusively sublicense to Ipsen, and Ipsen desires to exclusively sublicense from GTx, rights under GTx’s license agreements from Orion and UTRF

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to Acapodene for all human uses within the European Union (and certain other countries) except for the treatment and prevention of breast cancer, in accordance with the terms and provisions of this Agreement.

      Now, Therefore, in consideration of the foregoing premises and the mutual covenants contained herein and other good and valuable consideration, the receipt and sufficiency of which are hereby acknowledged, the Parties agree as follows:

ARTICLE I

DEFINITIONS

     The following terms shall have the following meanings as used in this Agreement:

      1.1 " Active Ingredient " means the material(s) in a pharmaceutical product which provide its pharmacological activity (excluding formulation components such as coatings, stabilizers or controlled release technologies).

      1.2 "ADT" means androgen deprivation therapy.

      1.3 "ADT Indication " means the treatment or prevention of the side effects of ADT in men with prostate cancer.

      1.4 " ADT Trial " shall have the meaning set forth in the Recitals.

      1.5 " Affiliate " means an entity that, directly or indirectly, through one or more intermediaries, controls, is controlled by or is under common control with GTx or Ipsen, as applicable. For the purposes of this Section 1.5, the term "control" (including, with correlative meanings, the terms "controlled by" and "under common control with") as used with respect to a Party, shall mean the possession, directly or indirectly, of the power to direct, or cause the direction of, the management or policies of such person or entity, whether through the ownership of voting securities, by contract or otherwise.

      1.6 " Agreement " shall have the meaning set forth in page one.

      1.7 " Bundled Product " means any combination of a Licensed Product and another pharmaceutical product that is not a Licensed Product where such products are not formulated together but are sold together for a single invoiced price.

      1.8 " Business Day " means a day on which banking institutions in New York (USA) and London (United Kingdom) are open for business.

      1.9 " Clinical Studies " means human studies designed to measure the Safety, efficacy, tolerability, pharmacokinetics and appropriate dosage of a Licensed Product. Clinical Studies shall include, without limitation: (a) the PIN Trial and the ADT Trial ; (b) any other clinical studies that GTx determines is necessary or useful to conduct in the GTx Territory for the Initial Products to achieve or maintain Regulatory Approvals in the ADT Indication or the

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PIN Indication, including a Phase IIIB Clinical Trial and/or Phase IV Clinical Trial, as defined herein; or (c) any clinical studies that Ipsen determines is necessary or useful to conduct in the European Territory for the Initial Products to achieve or maintain Regulatory Approvals in the ADT Indication or the PIN Indication.

      1.10 " Combination Product " means any pharmaceutical product that consists of a Licensed Product that also contains another Active Ingredient that is not Toremifene.

      1.11 " Commercialization Activities " means activities relating to the marketing and sale of a Licensed Product.

      1.12 " Competing Product " shall mean [ * ] .

      1.13 " Confidential Information " shall have the meaning set forth in Section 8.1 of this Agreement.

      1.14 " Control " or " Controlled " means the possession by a Party of the right to grant a license or sublicense to intangible property rights (including patent rights, know-how and/or trade secret information), and the right to provide access to or cross-reference to regulatory filings or other data or information, or the terms of any pre-existing agreement or other arrangement with any Third Party. "Control" expressly includes the right of ownership, in whole or in part, unless the Party having such right is restricted by contract or under law from granting such a license, access or right to reference.

      1.15 "Cost of Goods Sold" or "COGS" means the sum of (a) the Supply Price, (b) all payments made by Ipsen to Third Party contract manufacturer(s) for supply and delivery to Ipsen of fully packaged and labeled Licensed Products and/or any direct costs incurred internally by Ipsen for the packaging and labeling of the Licensed Products, (c) Royalty Payments to GTx for such Licensed Products, (d) Third Party royalty payments, and (e) any other customary and reasonable overhead costs actually incurred in, and reasonably allocable to, the procurement of Licensed Product, including: import and export duties; applicable taxes assessed on the purchase of such material; port fees and storage fees; shipping and handling; quality control; and quality assurance. The methodology for calculating Cost of Goods Sold shall be consistent with Ipsen’s accounting policies and procedures for other products and shall be consistent from year-to-year.

      1.16 " Cover " shall mean with respect to Patents that, but for a license granted to a Party under such Patents, the manufacture, use, offer for sale, sale or importation of such product would infringe a Valid Claim.

      1.17 "Data and Market Protection " means, as to a given country, for the Licensed Product and a given time period, that (a) no Third Party has the right to cross-reference the data generated for the obtaining of the Regulatory Approval of a Licensed Product in a given Indication in order to obtain a Regulatory Approval for a Generic and (b) no Third Party has the right to commercialize a Generic in a given Indication in such country.

      1.18 " Developing Party " shall have the meaning ascribed to it in Section 4.3(c)(i) of this Agreement.

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      1.19 " Dominating Patent " means an unexpired patent of a Third Party which has not been invalidated by a court or other governmental agency of competent jurisdiction and which would be infringed by the use, manufacture, sale or import of the Licensed Product under this Agreement.

      1.20 " Drug Approval Application " means an application for Regulatory Approval required before commercial sale or use of a product as a drug in a regulatory jurisdiction.

      1.21 " Effective Date " shall have the meaning set forth on page one of this Agreement.

      1.22 "Election" and "Election Fee" shall have the meaning set forth in Section 4.2(e) of this Agreement.

      1.23 " EMEA " means the European Medicines Agency or any successor thereto.

      1.24 " EU " means the European Union and shall include Austria, Belgium, Denmark, Finland, France, Germany, Greece, Ireland, Italy, Luxembourg, The Netherlands, Portugal, Spain, Sweden, United Kingdom, Cyprus, Czech Republic, Estonia, Hungary, Latvia, Lithuania, Malta, Poland, Slovakia, Slovenia, and any such other country or territory that may become part of the European Union after the Effective Date.

      1.25 " European Territory " means the EU, Switzerland, Norway, Iceland and Lichtenstein and the Commonwealth of Independent States (which for purposes hereof means Russia, Belarus, Ukraine, Moldova, Kazakhstan, Azerbaijan, Armenia, Kyrgyzstan, Uzbekistan, Tajikistan and Georgia).

      1.26 " Executive Officers " means the Chief Executive Officer of GTx (or another senior officer of GTx designated by GTx’s Chief Executive Officer) and the Chief Executive Officer of Ipsen (or another senior officer of Ipsen designated by the Chief Executive Officer of Ipsen).

      1.27 "Fareston " means the Orion drug product, containing Toremifene as the Active Ingredient, that is promoted in the US under the brand name "Fareston" by GTx, and in the rest of the world by Orion or its Affiliates, sublicensees and distributors for the treatment and prevention of advanced breast cancer.

      1.28 " FDA " means the United States Food and Drug Administration or any successor agency thereto having the administrative authority to regulate the marketing of human pharmaceutical products or biological therapeutic products, delivery systems and devices in the United States of America.

      1.29 " FDC Act " means the Federal Food, Drug and Cosmetic Act, as amended from time to time.

      1.30 " FTE " means the equivalent of the work of one (1) employee full time for one (1) calendar year (consisting of at least a total of [ * ] of work pursuant to the development activities with respect to Licensed Products. Any employee who devotes less than [ * ] shall be

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treated as an FTE on a pro-rata basis calculated by dividing the actual number of hours worked during such calendar year by [ * ] .

      1.31 " FTE Cost " means the cost to GTx of its scientific, technical, regulatory or clinical personnel directly dedicated to the execution of the development activities (excluding administrative personnel), and shall be calculated by multiplying the FTE Rate by the number of FTEs.

      1.32 " FTE Rate " means, as of the Effective Date, [ * ] per FTE. Such rate shall be adjusted annually to reflect the total percentage increase in the U.S. Consumer Price Index for the time period from the Effective Date until the time at which such index was recalculated at the time of adjustment (with the first adjustment to occur [ * ] , with subsequent adjustments on each anniversary thereof). For clarity, said rate includes charges for standard and/or existing lab supplies and equipment and customary business expenses such as insurance.

      1.33 " Generic " means any pharmaceutical product sold by a Third Party, not authorized by Ipsen, an Affiliate or sublicensee, that contains Toremifene as an Active Ingredient and which can be substituted by the prescriber or dispenser for the Licensed Product for use in the Indications.

      1.34 " GTx Initial Development " means Initial Development by GTx of the Initial Products for the ADT and PIN Indications in the GTx Territory.

      1.35 " GTx Initial Development Budget " and " GTx Initial Development Plan " shall have the meaning ascribed to it in Section 4.2 (a)(i) of this Agreement.

      1.36 " GTx Invention " means any Invention made solely by GTx as from the Effective Date including a GTx Product Improvement.

      1.37 " GTx Know-how " means Information which is within the Control of GTx and is reasonably necessary for the development, import, offer for sale, use or sale of the Licensed Products in the Indications within the European Territory. GTx Know-how shall include Information obtained by GTx under the GTx Licenses, GTx Inventions, GTx Product Improvements, and GTx’s interest in any Joint Inventions. Notwithstanding anything herein to the contrary, GTx Know-how shall exclude GTx Patents.

      1.38 " GTx Licenses " means the Orion License and the UTRF License.

      1.39 " GTx Patent " means all Patents Controlled by GTx in the European Territory which Cover the Licensed Products. A list of the GTx Patents identified as of the Effective Date is attached hereto as Exhibit A. GTx Patents include without limitation GTx’s interest in any Joint Patents and Patents relating to GTx Inventions.

      1.40 " GTx Product Improvement " means any Product Improvement Controlled by GTx as from the Effective Date.

      1.41 " GTx Territory " means the United States and all other parts of the world, except the European Territory.

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      1.42 " IND " shall mean (a) an Investigational New Drug Application as defined in the United States Food, Drug and Cosmetic Act and applicable regulations promulgated thereunder by the FDA, or (b) the equivalent application to the equivalent agency in any other country or group of countries, the filing of which is necessary to commence clinical testing of a pharmaceutical product in humans in a particular jurisdiction.

      1.43 " Indication " means any disease or condition in humans, except the treatment and prevention of breast cancer. The Parties expressly acknowledge that the use of Licensed Products for any disease or condition in animals is excluded from the scope of this Agreement.

      1.44 " Information " means techniques and data relating to Toremifene, Initial Products or Licensed Products including (but not limited to) inventions, practices, methods, knowledge, know-how, skill, experience, test data including Pre-Clinical Studies and Clinical Studies test data, analytical and quality control data, statistical analyzing plan (SAP), marketing, pricing, distribution, cost, sales data or descriptions, and compounds, compositions of matter, assays and biological materials related thereto.

      1.45 " Initial Development " means activities relating to obtaining Regulatory Approval of the Initial Products in the ADT Indication and the PIN Indication, in each of GTx’s and Ipsen’s respective territories. Initial Development includes, but is not limited to, Pre-Clinical Studies, Clinical Studies and regulatory affairs activities.

      1.46 " Initial Development Expenses " means the expenses incurred by a Party or for its account by a Third Party which are consistent with a Initial Development Plan and Initial Development Budget and are incurred in connection with Pre-Clinical and Clinical Studies (whether conducted internally or by a Third Party, individual investigators or consultants, including Phase IIIB Clinical Trials), toxicological, pharmacological, pharmacokinetic, metabolic, analytical, formulation, chemical studies, and qualification and validation batches of product, as required by the Regulatory Authorities for the purpose of obtaining Regulatory Approval of the Initial Product, and costs (and related fees) for preparing, submitting, reviewing or developing data or information for the purpose of submission to a Regulatory Agency to obtain and/or maintain Regulatory Approval of the Initial Product in the PIN and the ADT Indication.

      1.47 " Initial Development Plan " shall mean either Ipsen Initial Development Plan or GTx Initial Development Plan.

      1.48 " Initial Election Period " shall have the meaning ascribed to it in Section 4.2(e)(iii) of this Agreement.

      1.49 " Initial Products " means the Licensed Products currently being studied in the PIN Trial and the ADT Trial under the appropriate dosages.

      1.50 " Invention " means any invention relating to Toremifene or Licensed Product (whether patentable or not and including but not limited to Know-How) including without

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limitation a Product Improvement made by the Parties after the Effective Date during the course of, in furtherance of, and as a direct result of the activities of the Parties hereunder.

      1.51 " Ipsen Initial Development " means all Initial Development by Ipsen of the Initial Products for purposes of obtaining Regulatory Approval within the European Territory for the ADT Indication and the PIN Indication.

      1.52 " Ipsen Initial Development Plan " shall have the meaning ascribed to it in Section 4.2 (a)(ii) of this Agreement

      1.53 " Ipsen Invention " shall mean any Invention made solely by Ipsen as from the Effective Date including an Ipsen Product Improvement which development, manufacture, import, sale and use is Covered by a Valid Claim of GTx Patents.

      1.54 " Ipsen Know-how " means Information relating to the Licensed Product, including Ipsen Inventions, Ipsen Product Improvement and Ipsen’s interest in Joint Inventions which is within the Control of Ipsen and which is reasonably necessary for the development, import, offer for sale, use or sale of the Licensed Products in the Indications within the GTx Territory.

      1.55 " Ipsen Patents " means any Patents relating to an Ipsen Invention which Patents are owned or Controlled by Ipsen. Ipsen Patents shall include Ipsen’s interest in Joint Patents.

      1.56 " Ipsen Product Improvement " means a Product Improvement Controlled by Ipsen as from the Effective Date and which development, manufacture, import, sale and use are Covered by a Valid Claim of GTx Patents.

      1.57 " Joint ADT Initial Development Expenses " shall have the meaning set forth in Section 4.2(f)(iii) of this Agreement.

      1.58 " Joint Development Committee " or " JDC " means the committee established pursuant to Article II of this Agreement.

      1.59 " Joint Initial Development Expenses " means Initial Development Expenses incurred by GTx [ * ] relating to the Initial Development of the Initial Products in the ADT Indication and the PIN Indication; provided however , that (a) such Joint Initial Development Expenses shall only include Initial Development Expenses incurred in connection with Initial Development activities which are required for or conducted taking into consideration potential requirements for (i) the Initial Development of Initial Products in the ADT Indication and the PIN Indication (subject to Ipsen’s Election pursuant to Section 4.2(e)(i) of this Agreement) within the European Territory or (ii) the obtaining of Regulatory Approvals for the Initial Products in the ADT Indication and the PIN Indication (subject to Ipsen’s Election pursuant to Section 4.2(e)(i) of this Agreement) in the European Territory or (iii) the maintenance of Regulatory Approvals for the Initial Products in the ADT Indication and the PIN Indication (subject to Ipsen’s Election pursuant to Section 4.2(e)(i) of this Agreement) in the European Territory, and (b) such Joint Initial Development Expenses are included in the GTX Initial Development Budget. Such Joint Initial Development Expenses shall include [ * ] .

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      1.60 " Joint Invention " means any Invention made by the Parties in the course of the Initial Development pursuant to Section 4.2(g) of this Agreement and/or a Joint Subsequent Development pursuant to Section 4.3 (b)(v) of this Agreement.

      1.61 " Joint Patent " shall mean any Patent Covering a Joint Invention.

      1.62 " Joint PIN Initial Development Expenses " shall have the meaning set forth in Section 4.2(f)(iii) of this Agreement.

      1.63 " Joint Subsequent Development " shall have the meaning ascribed to it in Section 4.3(a) of this Agreement.

      1.64 "Joint Subsequent Development Budget", "Joint Subsequent Development Costs", "Joint Subsequent Development Plan" shall have the meaning ascribed to it in Section 4.3(b) of this Agreement.

      1.65 " Launch Date " means the date of the first offer for commercial sale, following Regulatory Approval of a Licensed Product within the European Territory. [ * ] .

      1.66 " Licensed Product " means a drug product containing Toremifene as an Active Ingredient for use in humans for all Indications, in a form suitable for sale to an end user, and/or for use in conducting Pre-Clinical Studies and Clinical Studies. Licensed Product shall include, without limitation, all doses of the Initial Products and any Product Improvement.

      1.67 "Licensed Trademark" means trademarks Controlled by GTx licensed hereunder to Ipsen pertaining to the Initial Products and which are listed in Appendix B.

      1.68 " List Price" shall mean Ex-manufacturer IMS-MIDAS price list on a per milligram basis.

      1.69 " Major Country " means any of the following countries: the United Kingdom, France, Germany, Spain and Italy.

      1.70 " Marketing and Sales Committee " shall have the meaning set forth in Section 6.2 of this Agreement.

      1.71 "Marketing and Sales Plan " shall have the meaning set forth in Section 6.3 of this Agreement.

      1.72 " Milestone Event " shall have the meaning set forth in Section 3.2 of this Agreement.

      1.73 " NDA " shall mean New Drug Application (as that term is used in Title 21 of the United States Code of Federal Regulations) or any foreign equivalent filed with a Regulatory Agency to market and sell any product for a particular indication.

      1.74 " Net Sales " means, consistent with, in the European Territory, Ipsen’s worldwide

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accounting policies and procedures, and in each such case as consistently applied across the Ipsen pharmaceutical product line, the gross sales invoiced by Ipsen, its Affiliates, and sub-licensees to Third Parties for Licensed Product in the European Territory, less:

           (a) credits and allowances or adjustments granted to customers on account of rejections, recalls or returns of Licensed Product previously sold;

           (b) any customary and reasonable trade and cash discounts, rebates, including government rebates, granted in connection with sale of Licensed Product to such customers;

           (c) sales, tariff duties and/or use taxes directly imposed and with reference to particular sales; and

           (d) outbound transportation prepaid or allowed, amounts allowed or credited on returns, export licenses, import duties, value added tax, and prepaid freight.

Sales of Licensed Product by and between Ipsen and its Affiliates, sublicensees are not sales to Third Parties and shall be excluded from Net Sales calculations for all purposes. Sales of Licensed Product for use in conducting clinical trials of Licensed Product candidates in a country within the European Territory in order to obtain applicable Regulatory Approval of the Licensed Product in the European Territory shall be excluded from Net Sales calculations for all purposes.

"Net Sales" of a Bundled Product. In the event Licensed Product is sold as part of a Bundled Product in a country within the European Territory, the Net Sales of the Licensed Product, for the purposes of determining payments based on Net Sales, shall be determined by multiplying the Net Sales of the Bundled Product in such country, during the applicable Net Sales reporting period, by the fraction, A/(A+B), where:

A is the average sale price of the Licensed Product by Ipsen ( i.e. Net Sales divided by units sold), its Affiliates or sublicensees when sold separately in finished form in such country and B is the average sale price by Ipsen, its Affiliates or sublicensees of the other product(s) included in the Bundled Product when sold separately in finished form in such country, in each case during the applicable Net Sales reporting period.

In the event the Licensed Product is sold as part of a Bundled Product and is sold separately in finished form in such country, but the other product(s) included in the Bundled Product are not sold separately in finished form in such country, the Net Sales of the Licensed Product, for the purposes of determining payments based on Net Sales, shall be determined by multiplying the Net Sales of the Bundled Product in such country by the fraction C/D where:

C is the average sale price, in such country, of the Licensed Product contained in such Bundled Product when sold separately and D is the average sale price, in such country, for the Bundled Product, in each case during the applicable Net Sales reporting period.

In the event that the Licensed Product is not sold separately in finished form in the country, but all of the other product(s) included in the Bundled Product in such country are sold separately, the Net Sales of the Licensed Product, for the purposes of determining payments based on Net

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Sales, shall be determined by multiplying the Net Sales of the Bundled Product in such country by the fraction (D-E)/D, where:

D is the average sale price, in such country, of the Bundled Product, and E is the average sale price of the other product(s) included in the Bundled Product in finished form in such country, in each case during the applicable Net Sales reporting period.

In the event that the Net Sales of the Licensed Product when included in a Bundled Product cannot be determined using the methods above, Net Sales for the purposes of determining payments based on Net Sales shall be calculated by multiplying the Net Sales of the Bundled Product by the fraction of F/(F+G) where:

F is the fair market value of the Licensed Product and G is the Fair Market Value of all other pharmaceutical product(s) included in the Bundled Product, as reasonably determined in good faith by the Parties. For the purposes of this Section 1.74, " Fair Market Value " shall mean the cash consideration that a willing seller would realize from an unaffiliated, unrelated and willing buyer in an arms’ length sale of an identical item sold in the same quantity and at the same time and place of the transaction.

      1.75 " Opt-in " shall have the meaning set forth in Section 4.3(c)(i) of this Agreement.

      1.76 " Opt-in Information " shall have the meaning set forth in Section 4.3(c)(ii) of this Agreement.

      1.77 "Opt-in Party", "Opt-in Payment", "Opt-in Period", "Opt-in Period 1", "Opt-in Period 2", "Opt-in Period 3", "Opt-in Period 4", "Opt-in Period 5", "Opt-in Notification" , and "Opt-in Payment" shall have the meaning set forth in Section 4.3(c)(iii) of this Agreement.

      1.78 " Opt-out Party " shall have the meaning set forth in Section 4.3(b)(iv) of this Agreement.

      1.79 " Non-Developing Party " shall have the meaning set forth in Section 4.3(c)(i) of this Agreement.

      1.80 " Orion " shall have the meaning set forth in the Recitals.

      1.81 " Orion License " means the Amended and Restated License and Supply Agreement dated January 1, 2005 by and between GTx and Orion, as the same may be amended from time to time.

      1.82 " Past Initial Development Expenses " shall have the meaning ascribed to it in Section 4.2(e)(iii) of this Agreement.

      1.83 " Patent " means (a) United States patents, re-examinations, reissues, renewals, extensions and term restorations, supplemental protection certificates, and foreign counterparts thereof, and (b) pending applications for United States patents, including, without limitation,

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provisional applications, continuations, continuations-in-part, divisional and substitute applications, including, without limitation, inventors’ certificates, and (c) foreign counterparts of any of the foregoing.

      1.84 " Patent Expenses " means the fees, expenses and disbursements of outside counsel, and payments to Third Party agents, incurred in connection with the preparation, filing, prosecution and maintenance of GTx Patents, Joint Patents or Ipsen Patents including the costs of Patent interference and opposition proceedings but excluding the costs of any other Patent enforcement proceedings.

      1.85 " Phase III Clinical Trial(s) " means that portion of the clinical development program which provides for continued trials of a Licensed Product on sufficient numbers of patients to establish the Safety and efficacy of a Licensed Product and generate pharmaco-economic data to support Regulatory Approval in the proposed therapeutic indication, as more fully defined in 21 C.F.R. § 312.21(c).

      1.86 " Phase IIIB Clinical Trial(s) " means product support clinical trials of a Licensed Product, which is not required for receipt of initial Regulatory Approval but which may be useful in providing additional drug profile data or expansion of the Licensed Product’s label claim. Phase IIIB Clinical Trials shall include GTx’s one year extension trial of an 80 mg dose of Initial Products for the ADT Indication.

      1.87 " Phase IV Clinical Trial(s) " means product support clinical trials, including but not limited to trials for new drug delivery systems, of a Licensed Product with an approved label claim that is commenced after receipt of Regulatory Approval in the country where such trial is being conducted.

      1.88 " PIN " means high grade prostatic intraepithelial neoplasia.

      1.89 " PIN Indication " means the prevention of prostate cancer in men with PIN.

      1.90 " PIN Trial " shall have the meaning set forth in the Recitals.

      1.91 " Pre-Clinical Studies " means studies of a Licensed Product in animals other than humans, including those studies conducted in whole animals and other test systems, designed to determine the pharmacology, toxicity, absorption, distribution, metabolism, excretion, and immunology of an Active Ingredient.

      1.92 " Pre Opt-in Development Costs " shall have the meaning set forth in Section 4.3(c)(ii) of this Agreement.

      1.93 "Pricing and Reimbursement Approval" means the pricing and reimbursement approval for the Licensed Product from the Relevant Agency, as required.

      1.94 " Primary Endpoint " means each of the primary efficacy endpoints within the PIN Trial and ADT Trial, respectively, as set forth in the respective SPA approved by the FDA for each such trial and the protocol for each such trial encompassed within each such SPA.

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Primary Endpoints for each of the PIN Trial and ADT Trial are set forth in Exhibit C.

      1.95 " Product Improvement " shall mean [ * ] .

      1.96 " Regulatory Agency " means any governmental authority, including without limitation the FDA or EMEA and the European Commission, with responsibility for granting any licenses or Regulatory Approvals or granting pricing and/or reimbursement approvals necessary for the marketing and sale of a Licensed Product in any country or group of countries.

      1.97 " Regulatory Approval " means any approvals by a Regulatory Agency (with the exception of conditional approvals) that are necessary for the commercial manufacture, use, storage, importation, export, transport or sale of Licensed Products in a regulatory jurisdiction.

      1.98 " Royalty Payment " shall have the meaning set forth in Section 3.4 of this Agreement.

      1.99 " Royalty Reduction " and " Royalty Reduction Cap " shall have the meaning set forth in Section 3.4 of this Agreement.

      1.100 " Royalty Term " shall have the meaning set forth in Section 3.8 of this Agreement.

      1.101 " Safety " means the absence of adverse experiences associated with the administration of a drug to a patient that are significant, serious or life threatening to the patient or demonstrate significant toxicological effect(s) of such drug on one or more body tissues that are not balanced by a countervailing benefit to the patient. The Safety of a product will be determined in view of the risk to benefit relationship of such product in the relevant patient population.

      1.102 " SERM " means selective estrogen receptor modulator other than Toremifene.

      1.103 " Sole Subsequent Development " shall have the meaning set forth in Section 4.3(a) of this Agreement.

      1.104 " SPA " shall have the meaning set for in the Recitals.

      1.105 " Subsequent Development " shall have the meaning set forth in Section 4.3(a) of this Agreement.

      1.106 " Supply Price " shall refer to the " PIN Supply Price" and the "ADT Supply Price" described in Section 3.4 of this Agreement.

      1.107 " Tax " shall have the meaning set forth in Section 3.12(c) of this Agreement.

      1.108 " Third Party " means any entity other than GTx or Ipsen, or any of their respective Affiliates.

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      1.109 " Third Party License " have the meaning set forth in Section 4.3(b)(ii) of this Agreement.

      1.110 " Toremifene " shall mean [ * ] .

      1.111 " UTRF " shall have the meaning set forth in the Recitals.

      1.112 " UTRF License " means the Amended and Restated Exclusive License Agreement dated July 24, 1998, by and between GTx and UTRF (formerly known as the University of Tennessee Research Corporation) exclusively licensing to GTx all UTRF know-how and Patents pertaining to methods of using Toremifene for the PIN Indication, as the same may be amended from time to time

      1.113 " Valid Patent Claim " means an unexpired claim (a) of any issued Patent that has not been revoked or held unenforceable or invalid by a decision of a court or governmental agency of competent jurisdiction from which no appeal can be taken, or with respect to which an appeal is not taken within the time allowed for appeal, and that has not been disclaimed or admitted to be invalid or unenforceable through reissue, disclaimer or otherwise, or (b) of any patent application that has not been cancelled, withdrawn or abandoned or been pending more than seven (7) years.

      1.114 " Withholding Royalty Payments " shall have the meaning set forth in Section 3.9 of this Agreement.

ARTICLE II

JOINT DEVELOPMENT COMMITTEE

      2.1 Formation of JDC . Promptly after the Effective Date, GTx and Ipsen shall form a Joint Development Committee (" JDC ") comprised of equal numbers of reasonably qualified representatives of each Party (not to exceed three (3) representatives of each Party) who have expertise in the clinical development, registration and commercialization of pharmaceutical products, with one such person assigned by each Party as such Party’s co-chair (each, a " Co-Chair "). Either Party may designate a substitute for a committee member to participate in the event one of that Party’s regular committee members is unable to be present at a meeting. The formation of the JDC as well as its responsibilities may be amended from time to time by mutual agreement of the Parties.

      2.2 Meetings . Meetings of each of the JDC may be called by either Party on [ * ] written notice to the other unless such notice is waived by the Parties. Such committees may be convened, polled or consulted from time to time by means of telecommunication, video communication, or correspondence. Notwithstanding the foregoing, the JDC will meet at least quarterly, with face-to-face meetings being required at least twice a year at alternating sites to be designated by GTx and Ipsen, and the other meetings being conducted face-to-face or through teleconference or video conference, as agreed upon by the JDC. With the prior consent of the

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other Party’s Co-Chair (such consent not to be unreasonably withheld or delayed), each Party may invite non-members to participate in the discussions and meetings of the JDC, provided that such participants shall have no vote and shall be subject to the confidentiality provisions set forth in Article IX.

      2.3 Agendas . Each Party will disclose to the other proposed agenda items for discussion, along with appropriate related Information, at least [ * ] in advance of each meeting of the JDC.

      2.4 Responsibilities of the JDC .

           (a) The JDC will facilitate communications between the Parties regarding each of the Parties’ development of Licensed Products in each of their respective territories (e.g., GTx’s development of Licensed Products in the GTx Territory, and Ipsen’s development of Licensed Products in the European Territory).

           (b) Ipsen shall present to the JDC within [ * ] of the Effective Date the Ipsen Initial Development Plan that relates to the Ipsen Initial Development in the European Territory through 2007 with such level of detail as is necessary and appropriate for all JDC members to fully understand such Ipsen Initial Development Plan.

           (c) For each calendar year subsequent to 2007, a revised annual Initial Development Plan and Initial Development Budget for GTx Initial Development in the GTx Territory and a revised Ipsen Initial Development Plan in the European Territory will be prepared by the appropriate Parties and submitted to the JDC before [ * ] of the calendar year proceeding the calendar year for which the revised Initial Development Plans and the revised Initial Development Budget applies.

           (d) The JDC will review, discuss and comment on the Initial Development Plans and Initial Development Budget. GTx and Ipsen will each update the JDC periodically, but at least quarterly, of all of their respective material Initial Development activities.

           (e) The JDC will review, comment on, and provide recommendations on any Subsequent Development of Product Improvements under the terms set forth in Section 4.3.

           (f) All recommendations by the JDC that relate to either GTx Initial Development or Ipsen Initial Development shall be made [ * ] , after an open and informed discussion of the matters as to which decisions are being made, including, but not limited to those matters relating to each such Initial Development Plan and Initial Development Budget. If the JDC is unable to make a [ * ] decision on such matters, the matter will be referred to the Executive Officers of GTx and Ipsen. If such officers do not reach agreement on such matter within [ * ] after it is referred to them, then the decision of [ * ] on matters pertaining to [ * ] (except those related to (i) Initial Development activities conducted by [ * ] which are supportive of the [ * ] and (ii) Joint Initial Development Expenses related thereto) and the decision of [ * ] on matters pertaining to [ * ] will be final and determinative, so long as such

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decision does not contradict or modify the terms of this Agreement. Notwithstanding the preceding sentence, (i) any decision relating to Joint Initial Development Expenses shall require the mutual consent of both Parties and (ii) both Parties agree that before they undertake any Initial Development activities that can materially affect the Initial Development activities of the other Party (including, in particular, Initial Development activities conducted by GTx which are supportive of the Initial Development activities of Ipsen for the European Territory), the Party desiring to conduct such Initial Development activities shall take into account any reasonable suggestion of the other Party. In the event the Parties (through the JDC, or, their Executive Officers) do not reach agreement on matters relating to [ * ] , Ipsen shall have the right not to fund its share of such Joint Initial Development Expenses which GTx shall have the right to undertake. In the event that Ipsen later decides that it wishes to have access to and use the data from such Initial Development activities that Ipsen refused to fund pursuant to its right above, Ipsen shall reimburse GTx [ * ] of Initial Development Expenses pertaining to such Initial Development activities.

      2.5 Subcommittees of the JDC . The JDC will have the power to form subcommittees with equal (unless otherwise agreed in writing) and appropriate representation from GTx and Ipsen.

ARTICLE III

LICENSING FEES; MILESTONE PAYMENTS; ROYALTIES; REPORTING

      3.1 License Fee, Initial Development Expenses, and Election Fee .

           (a) License Fee. As partial consideration for the rights granted by GTx pursuant to this Agreement, Ipsen shall pay to GTx a non-refundable, non-creditable license fee of [ * ] (the " License Fee ") as follows: (i) [ * ] of such License Fee shall be paid to GTx within [ * ] after the Effective Date of this Agreement; and (ii) the remaining 1.5 Million Euro amount of the License Fee shall be paid in three (3) equal installments of 500,000 Euros each on the 1st, 2nd and 3rd anniversary dates of the Effective Date of the Agreement.

           (b) Initial Products Development Expenses Reimbursement. Within [ * ] after the Effective Date, Ipsen shall pay to GTx a non-refundable, non-creditable fee of [ * ] as reimbursement for Initial Development Expenses incurred by GTx in connection with Pre- Clinical Studies and Clinical Studies for the Initial Products that were initiated, conducted, or ongoing prior to the Effective Date.

           (c) Election Fee. In the event that Ipsen exercises its Election (as defined in Section 4.2(e)(i) of this Agreement), Ipsen shall pay to GTx an additional fee of [ * ] (the " Election Fee ") within [ * ] following notice of exercise of such Election to GTx; provided, however, that such Election Fee shall not be due in the event that Ipsen exercises its Election during the Initial Election Period, as provided in Section 4.2(e)(iii).

      3.2 Milestone Payments . In addition to the payments due to GTx under Section 3.1, and in consideration for the rights granted by GTx pursuant to this Agreement, Ipsen shall make

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the following non-refundable, non-creditable (except as expressly provided for in the payments described in Milestone Events 5 and 6 below) milestone payments to GTx after the occurrence of each event that follows (each, a " Milestone Event "). The payments set forth herein shall each be due and payable by Ipsen within [ * ] following receipt from GTx of a notice and invoice regarding the achievement of each Milestone Event set forth herein.

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      3.3 Limitation on Milestone Payments . Other than the milestone payments recited in Section 3.2, Ipsen shall not be obligated to make any other milestone payments in connection with Initial Products or any other Licensed Product.

      3.4 Royalty Payments.

           (a) In consideration for the rights granted to Ipsen under this Agreement, Ipsen shall pay to GTx quarterly royalty payments on Net Sales determined as follows (the " Royalty Payment ") :

                (i)  For the first calendar year as from the first Launch Date of the Licensed Product in the European Territory (" Y1 "), Ipsen shall pay, on a country-by-country basis a Royalty Payment equal to the applicable royalty rates set forth in this Section 3.4(a)(i) (the " Base Royalty Rate "), multiplied by the Net Sales of Licensed Product for the PIN and ADT Indications (respectively the "PIN Base Royalty rate" and the "ADT Base Royalty Rate") .

                    (A) the PIN Base Royalty shall be equal to the greater of [ * ] and F, where F is the result of the following calculation:

[ * ] .

                    (B) the ADT Base Royalty shall be equal to the greater of [ * ] and G, where G is the result of the following calculation:

[ * ] .

For the purposes of calculating Expected Price for the PIN and ADT Indications for the initial calculation of the PIN and ADT Base Royalty, Ipsen shall update its forecast based upon the actual prices received from the appropriate agency upon receiving Pricing and Reimbursement Approval for products that have launched in the first quarter when the Royalty Payment is due.

                (ii)  Within [ * ] as from the end of the Y1, Ipsen shall determine the following amounts :

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                    (A) In the event B is superior to C, then:

                         (i)  [ * ] ;

                         (ii)  [ * ] .

                    (B) In the event B is inferior to C, then:

                         (i)  [ * ] .

                         (ii)  [ * ] .

                         For the following calendar years (" Y ") (notwithstanding the Offset set forth above):

                         (A)  [ * ] ;

                         (B)  [ * ] ;

                         (C)  [ * ] ;

                         (D)  [ * ] ;

                         (E)  [ * ] .

                         Examples Rates are attached hereto as Exhibit D for purposes of further clarification for the calculations described in this Section 3.4.

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           (b) Generic Competition. If a Generic is sold in any Major Country of the European Territory and for two (2) succeeding calendar quarters the sales of such Generic in that country equal or exceed [ * ] of the Net Sales of Licensed Products (calculated on a unit basis) in that country by Ipsen, its Affiliates or sublicensees, then the Royalty Payments shall be reduced to [ * ] of the amount of the Royalty Payment otherwise due to GTx on account of Net Sales of such Licensed Product for the ADT Indication or [ * ] of the amount of the Royalty Payment otherwise due to GTx on account of Net Sales of such Licensed Product for the PIN Indication in such country with such reduction to be applicable to the immediately succeeding calendar quarters only.

           (c) Dominating Patents. If (i) Ipsen would be prevented from developing, using, selling, or importing the Licensed Products in any country of the European Territory on the grounds that by doing so they would infringe one (or more) Dominating Patent held by a Third Party in said country and (ii) Ipsen licenses rights to such Dominating Patent in said country, then [ * ] of any royalties on Licensed Products sales paid by Ipsen to such Third Party in any calendar year in such country with respect to such Dominating Patent shall be deducted from any Royalty Payments payable to GTx by Ipsen in such calendar year (the " Royalty Reduction "), provided, however, that (i) such Dominating Patent relates solely to [ * ] and (ii) GTx has been informed of the Dominating Patent and has had an opportunity to provide input on any related discussion of whether to license such Dominating Patent and negotiation of royalty rates; and (iii) subject to the warranties and representations made by GTx under Section 10.1 (b) of this Agreement, the amount of the Royalty Reduction in any calendar year shall not exceed [ * ] of the Royalty Payments (the " Royalty Reduction Cap ") that would have otherwise been payable by Ipsen to GTx for such calendar year and for such country. Any amount of the Royalty Reduction which is not offset against Royalty Payments due to GTx from Ipsen (because it exceeds the Royalty Reduction Cap) shall be carried forward to and deducted in subsequent calendar years until the expiration of the Royalty Term.

      3.5 Sales by Sublicensees . In the event Ipsen, subject to the provisions of this Agreement, grants licenses or sublicenses to others to market and/or sell Licensed Product, including Initial Products, such licenses or sublicenses shall include an obligation for the licensee or the sublicensee to account for and report its Net Sales of Licensed Product on the same basis as if such sales were Net Sales by Ipsen, and Ipsen shall pay royalties to GTx as if such sales by such sublicensees were the Net Sales of Ipsen, subject to the provisions of this Article III.

      3.6 Relief From Certain Marketing Obligations. Notwithstanding anything to the contrary herein, in the event that Ipsen’s COGS of a particular Licensed Product for a particular country exceeds [ * ] of the Net Sales of such Licensed Product in such country:

           (a) Ipsen shall promptly provide notice to GTx of its belief that the COGS of a particular Licensed Product has exceeded or will exceed [ * ] of Net Sales in such country. Ipsen shall include with any such notice a calculation of such percentage and appropriate documentation and records supporting its calculation of COGS and Net Sales of such Licensed Product in such country.

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           (b) The Parties will have [ * ] following GTx’s receipt of such notice to discuss in good faith whether an adjustment of the Royalty Payments under Section 3.4 of this Agreement is appropriate so that COGS for such Licensed Product do not exceed [ * ] of Net Sales of such Licensed Product in such country or whether other circumstances exist that may warrant Ipsen continuing to sell such Licensed Product in the country in question. In the event the Parties fail to reach an agreement on any such adjustment, Ipsen shall not have to commercialize the Licensed Products in such country as long as Ipsen reasonably believes circumstances have not sufficiently changed to allow it to have COGS [ * ] .

      3.7 Payment of Royalties; Reporting . Within [ * ] after the end of each calendar quarter for which Royalty Payments are payable by Ipsen to GTx with respect to Net Sales by Ipsen, its Affiliates and their respective sublicensees, Ipsen shall pay to GTx by wire transfer the Royalty Payment due for such quarter and submit to GTx a report, on a country by country basis, providing in reasonable detail an accounting of all Net Sales (including an accounting of all unit sales of Initial Products on a per dose and per Indication basis) made during such calendar quarter, and the calculation prepared by Ipsen to determine the applicable Royalty Payment due for such quarter pursuant to this Article III. Within [ * ] after the end of each calendar year for which Royalty Payments are payable by Ipsen to GTx, Ipsen shall provide to GTx a report, on a country by country basis, reconciling the number of Initial Products sold on a per dose and a per Indication basis to the number of Initial Products consumed per Indication. In the event any payment due to GTx, including the Royalty Payments due hereunder, are late by more than [ * ] , GTx shall have the right to assess interest on the amounts which are then past due and owing to GTx at a rate of interest equal to the prime rate [ * ] .

      3.8 Royalty Term. Royalties shall be payable [ * ] (hereinafter, the " Royalty Term "). In the event that: (i) a Product Improvement is either jointly developed pursuant to Section 4.3(b) of this Agreement or developed by Ipsen and GTx has opted-in pursuant to Section 4.3(c), (ii) such Product Improvement is covered by an Ipsen Patent or a Joint Patent and (iii) such Product Improvement is commercialized in the European Territory by Ipsen, then, with regards to such Product Improvement, the Royalty Term shall [ * ] .

      3.9 [ * ] .

      3.10 Ipsen’s Rights Upon Expiration of Royalty Term. Upon expiration of the Royalty Term for a Licensed Product on a country-by-country basis as described above, Ipsen shall thereafter have a paid-up, non-exclusive license under the GTx Patents and GTx Know-how to use, sell, offer for sale, have sold and import that Licensed Product in that country.

      3.11 Tax Matters .

           (a) Ipsen Payments to GTx of Withholding Tax. If provision is made in law or regulation of any country in the European Territory for withholding of Taxes with respect to any amounts payable by Ipsen to GTx pursuant to this Agreement, Ipsen shall promptly pay such Tax on behalf of GTx to the proper governmental authority and Ipsen shall promptly furnish GTx with certificate of Taxes deducted under such withholding tax laws. Ipsen shall have the right to offset any such Tax actually paid from any payment due to GTx or shall be

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promptly reimbursed by GTx if no further payments are due. GTx and Ipsen shall cooperate with each other in obtaining any exemption from or reduced rate of Tax available under any applicable law or tax treaty.

           (b) Income and Other Taxes of the Parties. Ipsen and GTx shall pay for their own account all sales, turnover, income, revenue, value added and other taxes levied on account of payments accruing or made under this Agreement. All amounts expressed in this Agreement exclude such taxes where required by law

           (c) Tax. Solely for purposes of this Section 3.11, " Tax " or " Taxes " means any present or future taxes, levies, imposts, duties, charges, assessments or fees of any nature (including interest, penalties and additions thereto) that are imposed by a government taxing authority on GTx’s receipt of payments hereunder. Notwithstanding the foregoing, " Tax " or " Taxes " shall not include charges, value-added taxes, taxes imposed on Ipsen’s income, or assessments or fees of any nature (or any interest, penalties or additions thereto) imposed by the FDA or any Regulatory Agencies.

           (d) Protest . Ipsen shall promptly notify GTx in writing of any assessment, proposed assessment or other claim for any additional amount of Tax assessed by the US. Notwithstanding any other provision of this Section 3.11, GTx may, at its own expense, protest any assessment, proposed assessment, or other claim by any governmental authority for any additional amount of Tax or seek a refund of such amounts paid if permitted to do so by law or if the payment of such amounts are its ultimate contractual responsibility under the terms of this Agreement. Ipsen shall cooperate with GTx in any protest by providing records, giving testimony and providing such additional information or assistance as may reasonably be necessary to pursue such protest.

      3.12 Currency . Except as specified in the last sentence of this Section, all amounts specified in this Agreement which are to be paid to GTx are to be in Euros, as set forth in Section 15.16 of this Agreement. When calculating Net Sales for Royalty Payments, Ipsen shall convert the amount of invoiced sales in currencies other than Euros into Euros using the exchange rates [ * ] . All payments related to the development costs will be made in the currency of the invoicing party.

      3.13 Payments to or Reports by Affiliates . Any payment required under any provision of this Agreement to be made to GTx, or any report required to be made by Ipsen, shall be made to or by an Affiliate of such Party if such Affiliate is designated by that Party as the appropriate recipient or reporting entity.

      3.14 Payments by Wire Transfer. Any payments due to GTx hereunder shall be made by wire transfer to the following (or as provided in any alternative instructions that GTx may provide by written notice to Ipsen from time to time): [ * ]

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ARTICLE IV

DEVELOPMENT AND REGISTRATION

      4.1 Development Responsibilities . As a general principle, GTx will be solely responsible for the development of Licensed Products in the GTx Territory and for any communication with Regulatory Agencies in the GTx Territory, and Ipsen will be solely responsible for the development of Licensed Products in the European Territory and for any communication with Regulatory Agencies in the European Territory. Neither Party will undertake to conduct any development activities for Licensed Products in the territory of the other Party without first submitting the proposed development activities to the JDC and receiving the approval of the other Party which shall not be unreasonably withheld or delayed.

4.2 Initial Development.

           (a) Initial Development Plan.

                (i) GTx Initial Development. The Initial Development of the Initial Products for the ADT Indication and the PIN Indication in the GTx Territory shall be carried out by GTx pursuant to a development plan (the " GTx Initial Development Plan ") and a development budget (the " GTx Initial Development Budget "), both of which are attached as Exhibit E of this Agreement. The GTx Initial Development Budget comprises the Initial Development Expenses incurred by GTx as from [ * ] through [ * ] and the forecasted Initial Development Expenses as from [ * ] and until the obtaining of the Regulatory Approval for the Initial Products in the GTx Territory, differentiated between (i) Initial Development Expenses incurred/forecasted for the Development of the ADT Indication and the Initial Development of the PIN Indication and (ii) Joint Initial Development Expenses and other Initial Development Expenses. In the event that there are Joint Initial Development Expenses that are not clearly dedicated to the Initial Development of either ADT Indication or PIN Indication, the sum of such Joint Initial Development Expenses shall be allocated equally as the Initial Development of ADT Indication and PIN Indication. For each calendar year subsequent to 2006, a revised GTx Initial Development Plan and a revised GTx Initial Development Budget will be prepared by GTx and submitted for approval to the JDC before [ * ] of each calendar year, provided, however that any revision of the GTx Initial Development Plan and GTx Initial Development Budget shall not result in an increase of [ * ] of Joint Development Expenses per year, except as otherwise agreed by Ipsen.

                (ii) Ipsen Initial Development. The Initial Development of the Initial Products for the obtaining of the ADT Indication and the PIN Indication in the European Territory shall be carried out by Ipsen pursuant to a development plan for the remainder of 2006 and 2007 (the " Ipsen Initial Development Plan "). The Ipsen Initial Development Plan will be submitted by Ipsen to the JDC within [ * ] as from the Effective Date. For each calendar year subsequent to 2007, a revised Ipsen Initial Development Plan will be prepared by Ipsen and submitted for information to the JDC before [ * ] of each calendar year.

           (b) Content of Initial Development Plan. Each Initial Development Plan

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shall describe the proposed overall program of all the Initial Development of a Party in its respective territory, including, but not limited to, Pre-Clinical Studies, toxicology, formulation, chemical process development, Clinical Studies, regulatory plans and other elements of obtaining Regulatory Approval, and projected timelines for the Initial Development events. Each Initial Development Plan for either GTx Initial Development or Ipsen Initial Development will identify endpoints needed for initiation of the next phase of the Initial Development. Both GTx Initial Development Plan and Ipsen Initial Development Plan will be submitted for comments by GTx to Orion and GTx shall inform Ipsen of all comments made by Orion on the Initial Development Plans. Ipsen agrees to change and/or amend the Ipsen Initial Development Plan to the extent such Ipsen Initial Development Plan could reasonably be deemed to affect adversely Orion’s development, commercialization, sales or registration of Fareston by Orion.

           (c) Initial Development Efforts. In carrying out Initial Development and its Initial Development Plan in its respective territory, each Party agrees to use commercially reasonable efforts to conduct the Initial Development of the Initial Products in the ADT Indication and the PIN Indication and to conduct the activities set forth in their respective Initial Development Plan in accordance with the timelines set forth therein. A Party’s material failure to comply with such diligence obligations shall constitute a breach of this Agreement.

           (d) Drug Approval Applications . Consistent with its Initial Development Plan, GTx shall be responsible for the filing of all Drug Approval Applications and seeking Regulatory Approvals for Initial Products in the GTx Territory in the ADT Indication and the PIN Indication, and Ipsen shall be responsible for the filing of Drug Approval Applications and seeking Regulatory Approvals for Initial Products in the European Territory in the ADT Indication and the PIN Indication. If Ipsen does not exercise the Election as set forth in Section 4.2(e) of this Agreement, GTx shall have the right to seek Regulatory Approvals for Licensed Products for the PIN Indication in the European Territory, provided, however, that GTx shall seek such Regulatory Approval under a trademark which is not confusingly similar to the Licensed Trademarks to be used for the commercialization of the Initial Products in the ADT Indication in the European Territory. The Parties shall consult and cooperate in the preparation of each such Drug Approval Application and in obtaining Regulatory Approvals. GTx shall solely own all Drug Approval Applications and Regulatory Approvals for the GTx Territory and Ipsen shall solely own all Drug Approval Applications and Regulatory Approvals for the European Territory. In the event that Ipsen does not exercise its Election, GTx shall solely own all Drug Approval Applications and Regulatory Approvals for Licensed Products for the PIN Indication in the European Territory.

           (e) Ipsen’s Election to Retain License Rights to Licensed Products for the PIN Indication.

                (i)  Exercise of Election . Ipsen shall have the option, at its sole discretion, to retain its license rights under Article V in connection with Licensed Products for the PIN Indication, by notifying such election to GTx at any time after the Effective Date and until [ * ] following receipt of the first Regulatory Approval in [ * ] (the " Election ").

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               ( ii)  Failure to Exercise Election . In the event Ipsen does not make the Election within the period set forth in Section 4.2(e)(i) above or fails to make the payments required under Section 4.2(e)(iii) below, then GTx shall have the right to terminate Ipsen’s license and associated rights to Licensed Products for the PIN Indication, and thereafter GTx shall have the exclusive right to commercialize the Licensed Product in the European Territory for the PIN Indication, provided however that such commercialization shall be made under a trademark which shall not be confusingly similar to the Licensed Trademarks to be used for the commercialization of the Initial Products in the ADT Indication. Upon termination of such rights:

                     (1)  Ipsen shall grant to GTx an exclusive, royalty-free license under any Ipsen Inventions which would directly result from the conduct of the Ipsen Initial Development activities for the PIN Indication to Develop, use, sell, have sold, offer for sale, import, export, and distribute the Licensed Product for the PIN Indication in the European Territory;

                     (2)  Within [ * ] of such termination, Ipsen shall transfer to GTx all data from Preclinical Studies and Clinical Studies and other related Information as Ipsen may then Control pertaining to such Licensed Product for the treatment of the PIN Indication, including any IND or similar Regulatory Agency documents Ipsen may then Control for the purposes of conducting Clinical Studies within the European Territory for the PIN Indication;

                     (3)  Ipsen shall use commercial reasonable efforts to transfer to GTx all Regulatory Approvals relating to the Licensed Product in the PIN Indication obtained in the European Territory; and

                     (4)  Ipsen shall cease all on-going Initial Development of the Licensed Product in the PIN Indication in the European Territory and shall not be obligated to make any payment pursuant to Section 4.2(e)(iii) below.

                (iii) Election Fee and Payment of Past Initial Development Expenses. In the event Ipsen makes such Election, Joint PIN Indication Development Expenses (as defined in Section 4.2(f)(iii)(2) of this Agreement) shall be considered part of Joint Initial Development Expenses, and Ipsen will be required to make the following payments : (i) within [ * ] as from the date of Election, the Election Fee (as provided for in the chart below), (ii) within [ * ] as from the date of Election, the reimbursement of the Joint PIN Initial Development Expenses which shall have accrued from the date at which the aggregate Joint Initial Development Expenses (now inclusive of Joint PIN Initial Development Expenses) incurred by GTx exceeded [ * ] in the aggregate and until the date of Election (such costs during such period, the " Past Initial Development Expenses ") with a premium as shown in the chart below and (iii) the payment of the Joint PIN Development Expenses as provided for in Section 4.2(f)(iii)(2) of this Agreement.

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By way of example only, in the event that GTx has expended more than [ * ] in Joint Initial Development Expenses, and Ipsen exercises its Election after the expiration of the Initial Election Period but before Ipsen’s receipt of G300104 (IND [ * ] ) final data, it shall owe a payment to GTx that is the sum of [ * ] of Past Initial Development Expenses, as well as an Election Fee of [ * ] .

           (f) Initial Development Expenses.

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                (i) Initial Development Expenses Solely Borne by Ipsen. Ipsen shall be solely responsible for paying all Initial Development Expenses that are not Joint Initial Development Expenses relating to the obtaining of Regulatory Approvals in the European Territory for the Initial Products for the ADT Indication and the PIN Indication (subject to the provisions of Section 4.2(e)(ii) of this Agreement), which shall include the costs for any additional Pre-Clinical Studies and Clinical Studies required exclusively by the EMEA or other Regulatory Agencies to grant Regulatory Approvals for Initial Products within the European Territory.

                (ii) Initial Development Expenses Solely Borne by GTx. GTx shall be solely responsible for paying all Initial Development Expenses that are not Joint Initial Development Expenses relating to the obtaining of Regulatory Approvals for the Initial Products in the GTx Territory, including the Initial Products for the ADT Indication and the PIN Indication (subject to the provisions of Section 4.2(e)(ii) of this Agreement ), which shall include the costs for any additional Pre-Clinical Studies and Clinical Studies required exclusively by the FDA or other Regulatory Agencies to grant Regulatory Approvals for the Initial Products within the GTx Territory .

                (iii) Joint Initial Development Expenses. GTx shall bear the [ * ] of Joint Initial Development Expenses. Thereafter, Joint Initial Development Expenses shall be allocated between GTx and Ipsen as follows: [ * ] of Joint Initial Development Expenses shall be paid by GTx, and [ * ] of Joint Initial Development Expenses shall be paid by Ipsen as set forth below.

                     (1) Joint Initial Development Expenses for the Initial Products in the ADT Indication . At such time as Joint Initial Development Expenses incurred by GTx exceed [ * ] , GTx shall invoice Ipsen on a quarterly basis for [ * ] of the Joint Initial Development Expenses relating to the Initial Development of the Initial Products for the treatment of the ADT Indication (such Initial Development Expenses referred to as the " Joint ADT Initial Development Expenses "). Ipsen shall reimburse GTx for such costs within [ * ] of its receipt of such invoice.

                     (2) Joint Initial Development Expenses for Initial Products in the PIN Indication. Ipsen shall not be responsible for paying any Joint Initial Development Expenses incurred in relation to the Initial Development of the Initial Products for the treatment of the PIN Indication (" Joint PIN Initial Development Expenses "), unless and until such time as Ipsen exercises its Election as set forth in Section 4.2(e)(i). As from the Election and at such time as Joint Initial Development Expenses (including Joint PIN Initial Development Expenses) incurred by GTx exceed [ * ] , GTx shall invoice Ipsen on a quarterly basis for [ * ] of the on-going Joint PIN Initial Development Expenses and Ipsen shall reimburse GTx for such costs within [ * ] of its receipt of such invoice.

                     (3) Reports and Adjustment. Within [ * ] after the end of each calendar quarter, GTx shall provide Ipsen with a report detailing all GTx FTEs actually utilized by GTx during such calendar quarter (by names and major tasks) and external costs (for which invoices were received and approved for payment by GTx), as well as a comparison of

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such expenditures with the relevant provisions of the GTx Initial Development Budget. Within [ * ] of the end of 2006, and each calendar year thereafter, GTx shall provide to Ipsen an accounting report of the actual Joint Initial Development Expenses incurred during the previous calendar year including without limitation all detailed GTx FTE Costs as well as all invoiced external costs. In the event Ipsen has overpaid or underpaid any amount in excess of its [ * ] share in the Joint Initial Development Expenses as set forth in this report, GTx and Ipsen agree to reimburse one another such amounts as are appropriate within [ * ] from the date of receipt by Ipsen of this report. GTx agrees to maintain appropriate and accurate records of all Joint Initial Development Expenses incurred by it.

                     (iv) Audits. Upon the written request of Ipsen (which shall be no more than [ * ] ), GTx and Ipsen shall agree on a mutually acceptable date on which to permit an independent certified public accounting firm of an internationally recognized standing [ * ] to have access during normal business hours to such of the records of GTx as may be reasonably necessary to verify the accuracy of the reports and to audit the records as provided for in Section 4.2(f)(iii) of this Agreement. The accounting firm shall disclose to GTx and Ipsen whether the reports/records are correct or incorrect, the specific details concerning any discrepancies and such other information that should properly be contained in an accounting report required under this Section. If such accounting firm concludes that additional amounts relating to Ipsen’s share in Joint Initial Development Expenses were owed, Ipsen shall pay such additional amounts within [ * ] of the date Ipsen delivers to GTx such accounting firm’s written report so concluding. In the event such accounting firm concludes that amounts relating to Ipsen’s share in Joint Initial Development Expenses were overpaid by Ipsen, GTx shall repay Ipsen the amount of such overpayment within [ * ] of the date Ipsen delivers to GTx such accounting firm’s written report so concluding. The fees charged by such accounting firm shall be paid by Ipsen; provided , however , if the audit reveals that Ipsen has overpaid by more than [ * ] Ipsen’s share of Joint Initial Development Expenses due hereunder for the period being reviewed, then the fees and expenses of the accounting firm for the audit shall be paid by GTx. Upon the expiry of [ * ] following the end of any calendar year for which Ipsen has made payment of Joint Development Expenses with respect to such calendar year, and in the absence of gross negligence or willful misconduct of GTx or a contrary finding by an accounting firm pursuant to this Section, such calculation shall be binding and conclusive upon the Parties, and GTx shall be released from any liability or accountability with respect to any over payment by Ipsen for Joint Development Expenses for such calendar year. !

           (g) Inventions under the Initial Development and license grant.

               In the event any Party makes an Invention during the course of the conduct of the Initial Development, any such Invention shall be considered as a " Joint Invention" .

               Ipsen shall grant GTx an exclusive, royalty-free license on Ipsen’s interest in such Joint Invention to develop, use, sell, have sold, offer for sale, import, export and distribute the Initial Product in the GTx Territory.

      4.3 Subsequent Development.

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           (a) Subsequent Development Proposals.

               Each Party acknowledges that no development of a GTx Product Improvement or an Ipsen Product Improvement shall be made without first having been proposed to the other Party in accordance with the provisions of this Section 4.3.

               The Party (the " Proposing Party ") intending to conduct the development of respectively an Ipsen Product Improvement or a GTx Product Improvement (the " Subsequent Development ") shall notify the JDC of such intent and shall provide to JDC all necessary information relating to the concerned Product Improvement and the related Subsequent Development in order to enable the other Party to reasonably assess the scientific, technical and commercial implications of the proposed Subsequent Development. Within [ * ] from receipt of all such information, the other Party shall notify the Proposing Party its decision or not to participate in the Subsequent Development.

               In the event the other Party decides not to participate in the Subsequent Development, the Proposing Party shall be free to conduct the Subsequent Development at its own cost and expenses (the " Sole Subsequent Development ") subject to the other Party’s right to decide at a later stage to opt-in in such Subsequent Development in accordance to Section 4.3(c).

               In the event the other Party decides to participate to the Subsequent Development, the Parties shall jointly perform and fund such Subsequent Development (the " Joint Subsequent Development ") as set forth in Section 4.3(b) of this Agreement.

           (b) Joint Subsequent Development

                (i) Joint Subsequent Development Plan and Budget.

                    Following the other Party’s notification to join in the Subsequent Development, the Parties working through the JDC shall agree upon a plan and a budget for the conduct of the Joint Subsequent Development (respectively, the " Joint Subsequent Development Plan " and the " Joint Subsequent Development Budget ") which shall include at least the following items:

               (A) research and development activities to be performed by each Party for the purpose of obtaining Regulatory Approval for the Product Improvement in each Party’s respective territory;

               (B) specific tasks, location of work, milestones, estimated timelines, immediate objectives and long term objectives;

               (C) the global budget for the Joint Subsequent Development and the estimated budget for the development activities of each Party under the Joint Subsequent Development Plan. The costs of the development activities of the Parties (the " Joint Subsequent Development Costs ") will be determined in accordance with Section 4.3(b)(ii) of this Agreement.

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               Once agreed by the Parties within the JDC, each Party undertake to use its reasonable commercial efforts to conduct its development activities under the Joint Subsequent Development Plan. The Joint Subsequent Development Plan and the Joint Subsequent Development Budget shall be updated annually by the JDC at a time decided by the JDC and suitable for both Parties’ planning and budgeting processes, provided however that any update or amendment of the Joint Subsequent Development Plan and the Joint Subsequent Development Budget shall be approved by both Parties within the JDC.

                (ii) Determination of Subsequent Development Costs

                    All research and development activities conducted by the Parties under the Joint Subsequent Development Plan shall be valued as follows:

               (A) internal costs: [ * ] ;

               (B) external costs: [ * ] .

                    In the event the Parties reasonably agree that there is a need to enter into an agreement with a Third Party having intellectual property rights which would be infringed by the development and commercialization of the Product Improvement which is the subject matter of the Joint Subsequent Development (the " Third Party License "), the Parties shall reasonably cooperate to negotiate and enter into the Third Party License. Any payments to be made to this Third Party under the Third Party License during the Joint Subsequent Development shall be included in the Joint Subsequent Development Budget as Joint Subsequent Development Costs.

                (iii) Funding of Joint Subsequent Development

                    All activities undertaken by the Parties pursuant to the Joint Subsequent Development Plan shall be funded by the Parties in the following proportion : Ipsen shall be responsible for [ * ] of all Joint Subsequent Development Costs and GTx shall be responsible for [ * ] of all Joint Subsequent Development Costs, only to the extent the foregoing Joint Subsequent Development Costs are set forth in the Joint Subsequent Development Budget or revisions thereof. Within [ * ] of the end of each calendar quarter, each Party will notify the JDC in writing of the Joint Subsequent Development Costs incurred by such Party during such calendar quarter, and the JDC shall aggregate such Joint Subsequent Development Costs and allocate them to the Parties in accordance with the percentages set forth in the foregoing sentence. Where needed in order to reflect such allocated Joint Subsequent Development Costs, corresponding "true up" payments will be made by the Party underpaying its share of Joint Subsequent Development Costs to the Party having overpaid its share, quarterly within [ * ] following the end of each calendar quarter.

                (iv) Disagreement and Opt-out of the Joint Subsequent Development

                    In case of failure of the Parties within the JDC to agree upon the Joint Subsequent Development Plan, the Joint Subsequent Development Budget and any

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revisions thereof or the terms and conditions of a Third Party License, such disagreement shall be referred to the Executive Officers. In case the Executive Officers fail to reach an agreement within [ * ] as from the date such matter was referred to them, then each Party shall have the right to opt-out of the Joint Subsequent Development, subject to a [ * ] notice period.

                    The decision to opt-out shall be notified to the JDC. The Party exercising this opt-out right (the " Opt-Out Party ") shall continue all development activities under the Joint Subsequent Development Plan during the [ * ] notice period, fund the Joint Subsequent Development in accordance with the provisions of Section 4.3(b)(iii) of this Agreement during such period and enable the other Party to take over, if the other Party wishes to, such development activities to avoid any disruption of the Joint Subsequent Development.

                    The Opt-Out Party shall grant to the other Party an exclusive royalty-free license under the Opt-Out Party’s interest in any Joint Inventions for the sole purpose of the development of the Product Improvement in the other Party’s territory.

                    After the expiry of the [ * ] notice period, in the event the other Party decides to continue the development of the Product Improvement at its own cost and expenses, such development shall be considered as a Sole Subsequent Development and the provisions of Section 4.3(c) shall apply including the right for the Opt-Out Party to Opt-In under the terms and conditions of this Section.

                (v) Inventions under the Joint Subsequent Development

                    All Inventions made by the Parties during the course of, or in furtherance of, and as direct result of the development activities of the Parties in the Joint Subsequent Development shall be deemed Joint Inventions. For the avoidance of doubt, any Ipsen Invention and GTx Invention which does not directly result from the development activities under the Joint Subsequent Development shall be or remain owned by Ipsen or GTx, as the case may be.

                (vi) Commercialization of the Product Improvement developed under a Joint Subsequent Development

                    Each Party shall have the right to obtain Regulatory Approval and commercialize the Product Improvement in its respective Territory provided that:

                    (A) each Party shall grant to the other Party a royalty-free, exclusive license on its interest in the Joint Inventions in the other Party’s territory ;

                    (B) in the event the Parties have entered into a Third Party License, each Party shall pay to such Third Party any royalty due with respect to each Party’s respective territory. In the event any other payment would be due to this Third Party, any such payment will be allocated [ * ] GTx/Ipsen;

                    (C) in the event a Party Controls Patents which are not GTx Patent Rights or Joint Patent Rights and which would be infringed by the manufacture, use or

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commercialization of the Product Improvement in the other Party’s territory, the Parties shall negotiate in good faith the terms and conditions of a royalty-bearing license agreement relating to those Patent Rights for the other Party’s territory.

           (c) Sole Subsequent Development and Opt-in

                (i) Decision for Sole Subsequent Development. In the event that the Parties have not agreed to jointly perform or fund any Subsequent Development, either Party may pursue and fund at its own cost and expenses the Subsequent Development (the " Developing Party "), subject to the other Party’s (the " Non-Developing Party ") right to opt-in in the conduct and funding of the Subsequent Development (the " Opt-in ").

                (ii) Conduct of the Sole Subsequent Development

                  (1) Reporting. The Developing Party shall provide the JDC with quarterly reports outlining the results of each completed material pre-clinical and clinical study during the preceding calendar quarter. Notwithstanding the foregoing, the Developing Party shall not be required to continue any Sole Subsequent Development or to complete any tasks therein, prior to the time the other Party exercises its rights to Opt-in.

                  (2) Territorial Restrictions. If Ipsen is the Developing Party, it shall only carry out the development activities under the Sole Subsequent Development in the European Territory or, outside the European Territory, but only with the prior written consent of GTx which shall not be unreasonably withheld or delayed. If GTx is the Developing Party, it shall only carry out development activities under the Sole Subsequent Development in the GTx Territory or, in the European Territory, but only with the prior written consent of Ipsen which shall not be unreasonably withheld or delayed.

                  (3) Development Costs under Sole Subsequent Development. The Developing Party shall be responsible for all development costs related to such Sole Subsequent Development, subject to Opt-in by the other Party and sharing of costs pursuant to Section 4.3(c)(iii)(3) below (the " Pre Opt-in Development Costs "). The Developing Party shall record separately in its books in an auditable manner, all its Pre Opt-in Development Costs including costs of acquiring ownership or Control of Patents or Know-How in relation to the New Product.

                  (4) Provision of Information . The Developing Party shall provide to the Non-Developing Party, on a continuing basis, all relevant information relating to the Sole Subsequent Development through the JDC (the " Opt-in Information "). Such information shall include but is not limited to: [ * ] . The Non-Developing Party shall only use such Opt-in Information to decide whether to exercise an Opt-in.

                    If Non-Developing Party does not exercise an Opt-in, such Party shall not use such Opt-in Information for any other purpose, shall return the same to the Developing Party and shall maintain its confidentiality, provided that such information qualifies as Know-How of the Developing Party.

                    The Non-Developing Party may request additional information

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which would be reasonably material for it to make an Opt-in decision and the Developing Party shall supply such information to the extent it is reasonably available and necessary for the Opt-in decision.

                (5) Third Party License. In the event the Developing Party decides to enter into a Third Party License, such Developing Party shall so inform in advance the Non-Developing Party and provide the Non-Developing Party with the opportunity to make any reasonable recommendation with respect to the terms and conditions of the Third Party License, provided however, that the Developing Party shall have the sole right to negotiate and execute the Third Party License.

                (6) Inventions under the Sole Subsequent Development. Any Inventions made by the Developing Party during the course of, or in furtherance of, and as direct result of the development activities in the Sole Subsequent Development shall be owned by the Developing Party and shall be considered as an Ipsen Invention if the Developing Party is Ipsen and a GTx Invention if the Developing Party is GTx.

                (iii) Opt-in.

                  (1) Opt-In Period . With respect to each Sole Subsequent Development Plan, the Non-Developing Party (the " Opt-in Party ") shall have the right to Opt-in in the performance and the funding of such Subsequent Development at such times during the performance of the Sole Subsequent Development as are set forth below (each, an " Opt-in Period "):

                    (A)  [ * ] (" Opt-in Period 1" );

                    (B)  [ * ] (" Opt-in Period 2" );

                    (C)  [ * ] (" Opt-in Period 3 ");

                    (D)  [ * ] (" Opt-in Period 4 ");

                    (E)  [ * ] (" Opt-in Period 5 ").

                      As used above with respect to a clinical trial, "receipt of data following completion" shall mean the receipt by the Non-Developing Party of the results from the completed clinical trial at issue in the form of a final report fully compliant with applicable regulatory requirements, signed by Chief Research Officer and delivered to the Non-Developing Party.

                      In such event of Opt-in, the Non-Developing Party shall notify its exercise of its right to Opt-in in writing to the JDC (the " Opt-in Notification ").

                     (2) Extension of the Opt-in Period . In the event a Developing Party is required to supply additional information pursuant to Section 4.3(c)(ii)(4) above and there are fewer than [ * ] remaining in the relevant Opt-in Period, such Opt-in Period shall be extended to

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such date that is [ * ] after the provision of such additional information. The Non-Developing Party may, at its sole discretion, notify the Developing Party in writing before the expiration of its rights set forth herein, that it waives such rights and such Opt-in rights shall thereby terminate.

                (3) Opt-in Payment. The Opt-in Party shall reimburse to the Developing Party its share of the Pre Opt-in Development Costs determined as follows (the " Opt-in Payment").

(A) Calculation of the Opt-in Payment

        The Opt-in Payment will be equal to the relevant percentage as set forth below applied to (i) [ * ] and (ii) [ * ]

                          (A)  The relevant percentage shall be [ * ] if the Opt-in Party exercises its Opt-in during Opt-in Period 1;

                          (B)  The relevant percentage shall be [ * ] if the Opt-in Party exercises its Opt-in during Opt-in Period 2;

                         ( C ) The relevant percentage shall be [ * ] if the Opt-in Party exercises its Opt-in-during Opt-in Period 3;

                         ( D ) The Opt-in Payment shall be [ * ] if the Opt-in Party exercises its Opt-in during Opt-in Period 4;

                          (E)  The Opt-in Payment shall be [ * ] if the Opt-in Party exercises its Opt-in during Opt-in Period 5.

                          (B) Timing of Reimbursement of Pre Opt-in Development Costs . Within [ * ] as from the Opt-in Notification, the Opt-in Party shall pay to