AMENDED LICENSE & SUPPLY AGREEMENT

Exhibit 10.15

[ * ] = Certain confidential information contained in this document, marked by brackets, has been omitted and filed separately with the Securities and Exchange Commission pursuantis pursuant to Rule 406 of the Securities Act of 1933, as amended.

AMENDED AND RESTATED LICENSE AND SUPPLY AGREEMENT

      This Amended And Restated License And Supply Agreement (this “Agreement”) is entered into and made effective as of this ___day of October, 2001 (the “Amendment Date”) by and between Orion Corporation , a corporation organized and existing under the laws of Finland and having its principal office at Orionintie 1 FIN-02200 Espoo, Finland (“Orion”), and GTx Inc ., (fka Genotherapeutics, Inc.) a corporation organized and existing under the laws of the State of Tennessee, U.S.A. and having its principal office at 3 North Dunlap Avenue, Van Vleet Building, Third Floor, Memphis, Tennessee 38163, USA (“GTX”).

      Whereas , Orion and GTX entered into a Toremifene License and Supply Agreement effective as of March 30, 2000 (the “Effective Date”), to govern the Parties’ rights and obligations with respect to the research, development, commercialization and manufacture of Product (as defined in said agreement) (the “Original Agreement”);

      Whereas , the Parties desire with this Agreement to supercede the Original Agreement as of the Amendment Date to provide that GTX shall have the sole responsibility for researching, developing, registering and commercializing the Product (as defined below) within the Field (as defined below) worldwide, and that Orion shall have no monetary or other responsibilities for researching, developing, registering and commercializing Product, but shall remain responsible for manufacturing Orion Product (as defined below), as agreed herein;

      Now Therefore for and in consideration of the mutual covenants contained herein, the receipt and sufficiency of which are hereby acknowledged, Orion and GTX (hereinafter individually a “Party”; and collectively the “Parties”) hereto agree as follows:

1. DEFINITIONS

     For purposes of this Agreement, the following terms shall be defined as set forth below. Additional terms used in specific Sections of this Agreement shall be defined in such Sections.

      1.1 “Affiliate” shall mean any business entity controlled by a Party, or which controls a Party, or which is under common control with a Party. “Control” herein means the direct or indirect ownership of more than fifty percent (50%) of the authorized issued voting shares in such entity, or such other relationship as in fact legally results in effective control over the management, business and affairs of such entity or Party, as the case may be.

      1.2 “Annual Net Sales” shall mean Net Sales (as defined below) in any calendar year.

      1.3 “Calendar Quarter” shall mean each of the three (3) month periods beginning on January 1, April 1, July I and October 1 of each year during the Term (as defined below).

      1.4 “Competing Product” shall mean any pharmaceutical product containing an anti-estrogen and/or a SERM as a therapeutically active ingredient as well as any salt thereof, which product is licensed, sold and/or marketed for use in the Field, including, but not limited to, other dosage forms licensed, sold and/or marketed for use in the same Field as the Product. Competing Product does not include Orion Product, its Affiliate or subcontractor, but includes any generic form of the Product.

      1.5 “DMF” shall have the meaning provided in Section 7.4.

      1.6 “Field” shall mean the prevention and treatment of prostate cancer, which shall mean for purposes hereof: preventing prostate carcinogenesis; suppressing or inhibiting prostate cancer; reducing the risk of developing prostate cancer; increasing the survival rate of a subject with prostate cancer; and treating prostate cancer.

      1.7 “First Commercial Sale” means in each country, the date the Product is first sold, marketed, or publicly made available for sale for use in the Field by GTX, its Affiliate or a GTX Unaffiliated Sublicensee. Product for use in the Field, distributed or used for clinical trial purposes shall not be considered sold, marketed or made publicly available for sale and shall not constitute First Commercial Sale.

      1.8 “Generic Product” shall mean a generic pharmaceutical product for human use containing Toremifene as an active ingredient and which can be substituted by the prescriber or dispenser for a Product for use in the Field.

      1.9 “GTX Final Development and Registration Plan” shall mean the final product development and registration plan for each Product in the Field prepared by GTX, its Affiliate or a GTX Unaffiliated Sublicensee, as the same may be modified from time to time pursuant to Section 7.3.

      1.10 “GTX Know-How” shall mean such non-patented and unpublished non-clinical, pre-clinical and clinical documentation, information, and data including information and data in the US IND [ * ] relating to the use of any anti-estrogen and/or SERM in the Field, that is owned or controlled by, and disclosable by and available to, GTX and its Affiliates as of the Effective Date or at any time during the Term, including but not limited to all registration materials for the Product developed, acquired or compiled by GTX and/or its Affiliates as of the Effective Date or at any time during the Term, and all non-patented and unpublished documentation, information and data relating to the formulation, manufacture and/or quality control of the Product that is owned or controlled by GTX and/or its Affiliates as of the Effective Date or at any time during the Term.

      1.11 “GTX Patents” shall mean the patents issued from GTX Patent Applications as of the Effective Date and other patents owned or controlled by GTX and its Affiliates that are issued at any time during the Term and that relate to the manufacture, sale or use of any anti-estrogen and/or SERM for use in the Field (including any divisions, continuations, continuations-

in-part, re-examinations, reissues, additions, renewals and extensions thereof). GTX Patents in existence as of the Effective Date are set forth in Part I of Schedule A.

      1.12 “GTX Patent Applications” shall mean patent applications of GTX and/or its Affiliates pending as of the Effective Date and patent applications owned or controlled by GTX and/or its Affiliates that are filed at any time during the Term, in each case that relate to the manufacture, sale or use of any anti-estrogen and/or SERM for use in the Field (including any divisions, continuations, continuations-in-part, re-examinations, reissues, additions, renewals and extensions thereof). GTX Patent Applications in existence as of the Effective Date are set forth in Part II of Schedule A. For purposes of this Agreement, the Parties acknowledge that GTX Patent Applications shall include patent application U.S. Serial No. [ * ] which claims the use of Product in the Field, which application is in the name of and owned by The University of Tennessee Research Corporation. GTX represents and warrants that it has acquired sufficient rights and licenses from The University of Tennessee Research Corporation to said application for the purpose of performing its obligations under this Agreement.

      1.13 “GTX Patent Rights” shall mean GTX Patents and GTX Patent Applications.

      1.14 “GTX Preliminary Development and Registration Plan” shall mean the preliminary product development plan for the development of the Product in the Field prepared by GTX which has been provided to Orion prior to Effective Date, and which was attached to the Original Agreement.

      1.15 “GTX Territory” shall mean all countries or territories worldwide.

      1.16 “GTX Unaffiliated Sublicensee” shall mean any sublicensee of GTX other than a GTX Affiliate. For avoidance of doubt, Orion shall not be a GTX Unaffiliated Sublicensee.

      1.17 “Major Country” shall mean the United States of America including its fifty states, the District of Columbia, Puerto Rico, and all other USA territories and possessions (“USA”), Canada, Japan, Great Britain, France, Germany, Spain and Italy.

      1.18 “Manufacturing Patents” shall have the meaning provided in Section 7.6.

      1.19 “Net Sales” shall mean the invoiced gross sales of the Product to a Third Party which is not a GTX Unaffiliated Sublicensee, less: (A) credits and allowances or adjustments (consistent with generally accepted accounting principles), granted to such customers on account of rejections, recalls or returns of the Product previously sold; (B) any customary and reasonable trade and cash discounts, rebates, including government rebates, granted in connection with sale of 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.

      1.20 “North American Territory” shall mean (i) the USA (ii) Mexico, and (iii) Canada.

      1.21 “Orion Know-How” shall mean such non-patented and unpublished non-clinical, pre-clinical and clinical documentation, information, and data relating to the Orion Product that is owned or controlled by, and disclosable by and available to, Orion and its Affiliates as of the Effective Date or at any time during the Term which is necessary for the development by GTX of Product for use in the Field (including without limitation filing an application for Regulatory Approval for the Product for use in the Field), including information and data in U.S. NDA [ * ] relating to the Orion Product, registration materials for the Orion Product, documentation, information and data relating to the formulation and/or quality control of the Orion Product. Except as otherwise provided in Sections 7.6, 13.9, 15.1, 16.3.2, 16.4 and 20.2, Orion Know-How shall exclude information relating to Orion’s manufacture of Toremifene (as defined below) and Orion Product (as defined below).

      1.22 “Orion Patents” shall mean the patents owned or controlled by Orion that are directed to the compound Toremifene per se, and relate to the use or sale of Toremifene and all other patents issued from Orion Patent Applications during the Term (including any divisions, continuations, continuations-in-part, re-examinations, reissues, additions, renewals and extensions thereof). Orion Patents in existence as of the Effective Date are set forth in Part I of Schedule B. Schedule B shall be amended by Orion from time to time during the Term to include future Orion Patents.

      1.23 “Orion Patent Applications” shall mean patent applications owned or controlled by Orion and its Affiliates that are pending as of the Effective Date, and patent applications owned or controlled by Orion and its Affiliates that are filed at any time during the Term, in each case that are directed to the compound Toremifene per se and relate to the use or sale of Toremifene (including any divisions, continuations, continuations-in-part, re-examinations, reissues, additions, renewals and extensions thereof). Orion Patent Applications in existence as of the Amendment Date are set forth in Part II of Schedule C. Schedule C shall be amended by Orion from time to time during the Term to include future Orion Patent Applications.

      1.24 “Orion Patent Rights” shall mean Orion Patents and Orion Patent Applications.

      1.25 “Orion Product” shall mean tablets containing [ * ] of Toremifene respectively, that are manufactured by Orion and are commercially available as of the Amendment Date, and such other dosage strength or formulation of Toremifene as a therapeutically active ingredient as Orion may agree to manufacture pursuant to Section 16.4.

      1.26 “Orion Unaffiliated Sublicensee” shall mean any licensee or sublicensee under the Orion Patent Rights, other than an Orion Affiliate, GTX, a GTX Affiliate or a GTX Unaffiliated Sublicensee.

      1.27 “Premium” shall mean, with respect to an equity investment by a Third Party in GTX, an amount equal to the difference between the total consideration paid for the purchase of shares of GTX stock and the fair market value of such stock, as defined herein. Such fair market value shall be equal to either (i) if GTX has not had an initial public offering of its stock prior to the date of such investment by such Third Party, and does not conduct such a public offering concurrently with such investment, the average price per share of GTX stock offered in GTX’s two (2) most recent rounds of equity financing, multiplied by the number of shares of GTX stock

issued to such Third Party investor, also on an as-warranted basis, or (ii) if GTX has had an initial public offering of its stock prior to the date of such investment by such Third Party, or is then conducting such a public offering concurrently with such Third Party investment, the trading price of a share of GTX common stock on the date such Third Party investment is made (or, if such date is not a trading day, the price of a share of GTX common stock on the most recent trading day prior to the date of such investment, and if such Third Party investment occurs concurrent with the initial public offering, then the price per share at which stock is offered to the public), multiplied by the number of shares issued to such Third Party investor.

      1.28 “Product” shall mean any pharmaceutical product for human use within the Field containing Toremifene as a therapeutically active ingredient.

      1.29 “Regulatory Approval” shall mean all governmental approvals required to import, market, promote and sell the Product for use in the Field in any given country or territory in the GTX Territory, including but not limited to, product registrations, medical approvals and price and marketing approvals.

      1.30 “ROW Territory” shall mean the GTX Territory except the North American Territory and Japan.

      1.31 “Sales of Generic Product” shall mean the documented sale and use of a Generic Product.

      1.32 “Specifications” shall mean the current specifications (as of the Amendment Date) for the Orion Product, as such specifications are, with regard to [ * ] containing Toremifene, set forth in the Orion NDA [ * ] approved by the U.S. FDA, and with regard to [ * ] and [ * ] tablet of Orion Product set forth in Schedule C (Copies of such current specifications are set forth in Schedule C attached hereto and made a part hereof.) The Specifications shall also include any other modified or additional specifications applicable to Orion Product which may be manufactured by Orion, pursuant to Section 16.3 or 16.4. Schedule C may be amended from time to time as necessary to reflect modifications to the Specifications that may be implemented pursuant to Section 16.3 or to include Specifications for any Other Product that Orion may agree to manufacture pursuant to Section 16.4.

      1.33 “Term” shall mean the period commencing on the Amendment Date and continuing, on a country by country basis until the date of expiration or invalidation of the last to expire or be invalidated of the GTX Patent Rights, subject to earlier termination under Section 20 as provided herein.

      1.34 “Third Party” or “Third Parties” shall mean any party or parties other than GTX, Orion, an Affiliate of GTX, or an Affiliate of Orion.

      1.35 “Toremifene” shall mean [ * ] .

      1.36 “Trademarks” shall mean the trademarks GTX selects and registers for the Product in the Territory in accordance with Section 9 of this Agreement.

      1.37 “U.S. FDA” shall mean the United States Food and Drug Administration and any successor regulatory agency.

      1.38 “U.S. IND” shall mean an Investigational New Drug Application filed with the U.S. FDA.

      1.39 “U.S. NDA” shall mean a New Drug Application filed with the U.S. FDA.

      1.40 “Upfront and Milestone Income” shall have the meaning provided in Section 3.1.1(c).

      1.41 “Valid Claim” shall mean a claim of an issued patent which has not expired and which has not been held revoked, invalid or unenforceable by decision of a court or other governmental agency of competent jurisdiction, unappealable or unappealed with the time allowed for appeal having expired, and which has not been admitted to be invalid through reissue or disclaimer or otherwise.

2. GRANT AND SCOPE OF RIGHTS GRANTED

      2.1 Orion Grants to GTX

           2.1.1 License Grants. Orion hereby grants to GTX:

                (i)  an exclusive right and license, with the right to grant sublicenses as provided in Section 2.1.4, under Orion Patent Rights and Orion Know-How, to develop, use, have used, sell, have sold, import, market and distribute the Product in the North American Territory and in Japan in the Field;

                (ii)  a non-exclusive right and license, with the right to grant sublicenses as provided in Section 2.1.4, under Orion Patent Rights and Orion Know-How, to develop, use, have used, sell, have sold, import, market and distribute the Product in the ROW Territory for exclusive use in the Field;

                (iii)  a non-exclusive license, under the Orion Patents and Orion Know-How, to perform research and preclinical development activities in accordance with Section 2.5 using the Powder (as defined in Section 13.6.2) to be provided to GTX pursuant to Section 13.6.2; and

     Licenses under Sections 2.1.1 (i) and (ii) may be expanded to include the right to make and have made Products as provided in Sections 7.6, 13.9, 15.1, 16.3.2, 16.4 and 20.2.2 on such terms as are set forth in such Sections.

     For the avoidance of doubt, nothing herein shall limit or restrict or be construed to limit or restrict Orion from using, and GTX acknowledges that Orion may use Toremifene and Product as a reference compound and/or product in its R&D and business activities.

           2.1.2 Manufacturing Rights Reserved. Except as otherwise provided in Sections 7.6, 13.9, 15.1, 16.3.2, 16.4 and 20.2.2, Orion retains the exclusive right to manufacture

or have manufactured Toremifene, Orion Product and Product including, without limitation, any Toremifene and Orion Product to be supplied to GTX under this Agreement and subject to Sections 7.6, 13.9, 15.1, 16.3.2, 16.4 and 20.2.2 herein, during the Term GTX undertakes to purchase all its requirement of Product exclusively from Orion.

           2.1.3 Use of Orion Know-How. Under the licenses granted pursuant to Sections 2.1.1 (i)-(ii), GTX shall, subject to the terms and conditions of this Agreement, including without limitation Section 8, have the right to use and reference Orion Know-How in support of GTX’s clinical trials and applications for Regulatory Approval within the Field for the Product in the GTX Territory. Subject to the license rights granted hereunder, Orion retains full ownership rights to all Orion Know-How.

           2.1.4 Sublicensing. GTX shall have the right to sublicense its rights received under this Agreement in the GTX Territory to any Third Party, provided that GTX shall notify Orion within fifteen (15) days after execution of an agreement between GTX and a GTX Unaffiliated Sublicensee. GTX shall endeavor to include in its agreement with each GTX Unaffiliated Sublicensee a provision stating that, upon termination of this Agreement, such Sublicensee and Orion shall discuss, and as appropriate, negotiate the terms and conditions under which Orion and such sublicensee would be willing to collaborate with regard to the further development and/or commercialization of the Product for use in the Field in which GTX and such sublicensee were previously developing and/or commercializing Products, provided that any such further development and/ or commercialization of the Product by Orion and such sublicensee shall be subject to and conditioned by a definite written agreement, if any, accepted and signed by duly authorized representatives of Orion. GTX shall forward to Orion a complete copy of each sublicense agreement. No sublicense shall relieve GTX of any of its obligations or commitments under this Agreement and GTX shall cause its Affiliates and GTX Unaffiliated Sublicensees to comply with all of GTX obligations and commitments under this Agreement.

     GTX shall remain jointly and severally liable to Orion with its Affiliate(s) and GTX Unaffiliated Sublicensee(s) that obtain a sublicense under the licenses granted to GTX pursuant to Section 2.1.1 for performance of GTX’s obligations under this Agreement. GTX shall be responsible for complying and ensuring that such of its Affiliates and GTX Unaffiliated Sublicensees, as applicable, comply with all relevant laws, regulations and requirements relating to the importation, packaging, distribution, marketing, promotion, sale and use of Product in the GTX Territory.

     Orion shall have the right to propose to GTX one or more potential sub-licensees for the Product for use in the Field in Japan, South Korea and China (including, for the purpose of this Agreement, the People’s Republic of China and Taiwan). GTX shall consider such proposal(s) in good faith when appointing a sub-licensee for the Product for use in the Field for Japan, South Korea and China. After the Amendment Date, Orion may disclose to its current licensee for Toremifene in the breast cancer field in the USA, Japan, South Korea and China the existence of this Agreement and the fact that it pertains to the development and commercialization of Toremifene in the Field, [ * ] .

           2.1.5 GTX Rights of First Negotiation

                (a)  Orion grants GTX, on a country by country basis, the right of first negotiation to negotiate further agreements under commercially reasonable terms and conditions regarding the further development, registration, promotion, marketing, sales and distribution of a pharmaceutical product for human use within the Field containing anti-estrogens and/or SERMs, including analogs, metabolites, and/or derivatives thereof, as the active ingredient (a) which is covered by a Valid Claim within the GTX Patent Rights in such country; and (b) for which Orion has both a license or other right to develop and commercialize such products and within five (5) years after the Amendment Date, Orion has commenced Phase I clinical trials for such product anywhere in the world for a primary indication falling within the Field (a product fulfilling (a) and (b), hereinafter referred to as “Additional Product”). Within thirty (30) days after GTX’s receipt in writing of a first offer from Orion regarding commercially reasonable terms and conditions for obtaining rights in and to such Additional Product, GTX shall notify Orion in writing if it wishes to enter into negotiations with respect to such Product. Should GTX elect to exercise such right, the Parties agree to negotiate in good faith the commercially reasonable terms and conditions for a letter of intent to be completed within ninety (90) days of receipt by Orion of such notification from GTX Any deadlines may be extended by mutual written agreement. Should GTX fail to provide written notification to Orion by the end of the thirty (30) day period, or GTX notifies Orion that it does not wish to enter into negotiations; or the Parties, despite conducting good faith negotiations, are unable to finalize the commercial terms of the letter of intent within the ninety day (90) period, GTX shall have no further rights in the anti-estrogens and/or SERM including analogs, metabolites, and/or derivatives thereof, and Orion shall be free to contract with a Third Party concerning same or itself pursue the development, registration, promotion, marketing, sales and distribution of such Additional Product.

                (b)  During the term of any Orion Patent or pendency of Orion Patent Application in the relevant country, Orion grants GTX, on a country by country basis and as set forth in this Section 2.1.5 (b), a right of first negotiation to negotiate with Orion an agreement under which GTX would, on commercially reasonable terms and conditions, develop, register, promote, market, sell and distribute pharmaceutical products containing Toremifene for use outside the Field (“Other Activities”), provided, however, that such right of first negotiation described in this Section 2.1.5(b) shall not extend to breast cancer indications.

                     (i)  If after the Amendment Date, a Third Party (including without limitation an Orion Unaffiliated Sublicensee or a GTX Unaffiliated Sublicensee) approaches Orion in writing and indicates its desire to obtain a license and/or other rights from Orion to conduct Other Activities, or if an Orion Affiliate refers such a Third Party having such interest to Orion, then Orion shall advise such Third Party to approach GTX and discuss such Other Activity with GTX. Orion shall for a period of two hundred and ten (210) days from the date that Orion notifies GTX in writing that a Third Party has an interest in an Other Activity, refrain from granting such Third Party such license and/or other rights to conduct such Other Activities. If GTX desires to obtain a license and other support from Orion to conduct such Other Activities (alone or together with such Third Party) GTX shall notify Orion in writing thereof. If GTX so notifies Orion, then the Parties shall negotiate exclusively with each other the terms of a binding, commercially reasonable license agreement under which Orion would grant GTX a license to conduct such Other Activities and provide other related support to GTX, provided that GTX’s right to conduct such Other Activity shall be subject to and conditioned by, and become

effective only upon the execution by the Parties of a separate, mutually acceptable written agreement, if any, with respect thereto. Such negotiations, if any, shall continue for up to one hundred and eighty (180) days after Orion receives such notification from GTX or until the expiry of said period of two hundred and ten (210) days, which ever is earlier (hereinafter referred to as “Negotiation Period”). If the Parties, despite conducting good faith negotiations, if any, are unable to or do not finalize and execute a binding license agreement within the Negotiation Period, then GTX shall have no rights with respect to such Other Activities, and Orion and/or its Affiliate shall have the right to conduct such Other Activities alone or together with a Third Party(ies) or grant a Third Party a license and/or other rights from Orion to conduct Other Activities without any obligation to GTX.

                     (ii)  If after the Amendment Date a Third Party (including without limitation an Orion Unaffiliated Sublicensee or a GTX Unaffiliated Sublicensee) approaches GTX or a GTX Affiliate and indicates its desire to obtain a license and/or other rights to conduct Other Activities, then GTX shall Promptly notify Orion in writing. Within thirty (30) days after GTX provides any such notice to Orion, GTX shall inform Orion if GTX desires to negotiate the terms and conditions under which GTX would be willing to obtain a license from Orion to conduct the Other Activities that are the subject of such notice. If GTX so notifies Orion of its interest, then the Parties shall negotiate exclusively with each other a letter of intent providing for the material, commercially reasonable terms and conditions under which Orion would be willing to grant GTX a license to conduct such Other Activities and provide other related support to GTX. Such negotiations shall continue for up to one hundred and eighty (180) days after Orion receives such notification from GTX. If GTX fails to provide written notice to Orion of GTX’s interest in conducting such Other Activities by the end of such thirty (30) day period, or if the Parties, despite conducting good faith negotiations, are unable to finalize such a letter of intent within such one hundred and eighty (180) day period, then GTX shall have no further rights with respect to such Other Activities, and Orion shall have the right to grant to such Third Party a license and/or other rights to conduct such Other Activities without further obligation to GTX with respect to such Other Activities. If the Parties finalize a letter of intent pursuant to this subsection (ii) providing for the material terms and conditions under which GTX would obtain a license conduct Other Activities within such one hundred and eighty (180) day period, then the Parties shall promptly thereafter meet to negotiate an agreement setting forth more fully the terms and conditions contained in such letter of intent as well as other applicable terms and conditions typically contained in agreements of similar nature, provided that GTX’s right to conduct such Other Activity shall be subject to and conditioned by, and become effective only upon the execution by the Parties of a separate, mutually acceptable written agreement, with respect thereto, if any, and further provided that neither GTX nor Orion shall either itself conduct such Other Activities or grant any Third Party the right to do so unless (I) GTX has provided Orion notice that it is not interested in conducting such Other Activity, or (II) GTX has failed to provided Orion with such notice of its interest in conducting such Other Activity within such thirty (30) day period, or (III) the Parties fail to agree upon the terms of a letter of intent or execute such agreement within the applicable one hundred eighty (180) day period, which ever of items (I)-(III) occur first.

                     (iii)  If after the Amendment Date Orion or an Orion Affiliate desires to initiate the conduct of Other Activities, then Orion shall promptly so notify GTX in

writing. Within thirty (30) days after GTX receives any such notification from Orion, GTX shall inform Orion if GTX desires to negotiate the terms and conditions under which Orion would be willing to grant GTX a license and other support from Orion to conduct the Other Activities that are the subject of such notice. If GTX so notifies Orion of its interest, then the Parties shall negotiate exclusively with each other on a binding, commercially reasonable license agreement under which Orion would grant GTX a license to conduct such Other Activities and Orion would provide other related support to GTX, provided that GTX’s right to conduct such Other Activity shall be subject to and conditioned by, and become effective only upon the execution by the Parties of a separate, mutually acceptable written agreement, if any, with respect thereto. Such negotiations shall continue for up to one hundred and eighty (180) days after Orion receives such notification from GTX. If GTX fails to provide written notice to Orion of GTX’s interest in conducting such Other Activities by the end of such thirty (30) day period, or if the Parties, despite conducting good faith negotiations, are unable to finalize and execute a binding license agreement within such one hundred and eighty (180) day period, then GTX shall have no rights with respect to such Other Activities, and Orion or its Affiliate shall have the right to conduct such Other Activities alone or together with a Third Party(ies) without any obligation to GTX. Orion shall not grant a license to any Third Party to commercialize products containing Toremifene for such Other Activities unless and until (I) GTX has provided Orion notice that it is not interested in conducting such Other Activity, or (II) GTX has failed to provide Orion with such notice of its interest in conducting such Other Activity within such thirty (30) day period, or (III) the Parties fail to execute such binding license agreement within such one hundred eighty (180) day period, which ever of items (I)-(III) occur first.

                     (iv)  If GTX desires to conduct Other Activities, then GTX shall promptly notify Orion in writing of GTX’s desire to conduct such Other Activity and the terms and conditions under which GTX would be willing to obtain a license to conduct such Other Activities and other related support from Orion, provided that any such license to GTX to conduct such Other Activity shall be subject to and conditioned by, and become effective only upon the execution by the Parties of a separate, mutually acceptable written agreement, if any (“Additional Agreement”). If GTX so notifies Orion of its interest, then the Parties shall discuss, and as appropriate, negotiate exclusively with each other with regard to an Additional Agreement for up to one hundred and eighty (180) days after Orion receives such notification from GTX. If the Parties are unable to or do not finalize and execute such Additional Agreement within such one hundred and eighty (180) day period, then GTX shall have no rights with respect to such Other Activities, and Orion or its Affiliate shall have the right to itself conduct such Other Activities or to grant to such Third Party a license and/or other right to conduct such Other Activities without further obligation to GTX with respect thereto.

                     (v)  Any deadlines provided in this Section 2.1.5(b) may be extended by mutual written agreement of the Parties. GTX’s rights under this Section 2.1.5(b) shall apply on an indication by indication basis.

      2.2 No Implied Licenses. Any rights not expressly granted by either Party to the other Party in this Agreement are expressly reserved by the Party owning or controlling such rights and, accordingly, no licenses other than those specified herein shall be deemed granted by this Agreement by implication, estoppel or otherwise.

      2.3 United States Government Rights. In the event it is determined that any GTX Patent Rights were developed with the support of the United States Government or any agency thereof (the “Government”), the Government will retain rights in the GTX Patent Rights as set forth in Title 35 U.S.C. §200 et seq. All rights herein granted to GTX are subject to any such rights held by the Government and further subject to any restrictions or obligations that may be imposed by the Government pursuant to such rights, at such time that it is determined.

      2.4 Orion’s Right of First Negotiation .

           2.4.1 Whereas Orion has considerable knowledge and experience in the marketing, sales and distribution of pharmaceutical products in, inter alia, Scandinavia (which term shall for purpose of this Section 2.4 comprise the countries of Denmark, Finland, Norway and Sweden), GTX undertakes to regard Orion as its preferential partner for the marketing, sales and distribution of the Product in Scandinavia for use in the Field. Consequently, GTX grants, and shall cause its Affiliates and Unaffiliated Sublicensees who receive a sublicense under the license granted to GTX pursuant to Section 2.1.1 in Scandinavia to grant, to Orion a right of first negotiation to negotiate in good faith an agreement(s) under commercially reasonable terms and conditions regarding the marketing, sales and/or distribution by Orion of the Product in Scandinavia for use in the Field, with the express understanding that such commercially reasonable terms and conditions shall not comprise an obligation to develop and register the Product for use in the Field in any country of Scandinavia.

           2.4.2 Within thirty (30) days after Orion’s receipt of a first written offer from GTX regarding commercially reasonable terms and conditions governing such rights, Orion shall notify GTX in writing if it wishes to negotiate the terms and conditions under which Orion could obtain the rights contemplated in this Section 2.4. Should Orion so exercise such right, the Parties shall negotiate exclusively with each other and in good faith the commercially reasonable terms and conditions for a license and distribution agreement for the marketing, sales and distribution by Orion of the Product in Scandinavia for use in the Field, such negotiations to be completed within one hundred and eighty (180) days from the date of Orion’s notification to GTX. Any deadlines may be extended by mutual agreement upon reasonable request. If Orion fails to provide written notification to GTX by the end of the thirty (30) day period; Orion notifies GTX that it does not wish to enter into negotiations; or the Parties, despite conducting good faith negotiations, are unable to finalize the material commercial terms of agreement within such one hundred and eighty (180) day period (any such event, a “Termination of the Orion Right”), Orion shall have no further right under this Agreement to market, sell and distribute the Product in Scandinavia and GTX shall be free to offer to or enter into an agreement with any Third Party or any GTX Affiliate with respect to such activities after the Termination of the Orion Right occurs.

           2.4.3 In the event that GTX’s Unaffiliated Sublicensee for Product for use in the Field in the USA does not obtain the right and license to sell, have sold, import, market and distribute the Product in the Field in Europe at the time of execution of the sublicense agreement for the Product for use in the Field in the USA, then Orion shall, on the terms and conditions of Sections 2.4.1 and 2.4.2, have a right of first negotiation to negotiate in good faith an agreement(s) under commercially reasonable terms and conditions regarding the marketing, sales and/or distribution of the Product for use in the Field in Europe.

      2.5 Use of Toremifene by GTX for Research . Subject to Sections 2.1.1 (iii) and 13.6.2, GTX may use the Powder provided to it pursuant to Section 13.6.2 to perform stability studies and other activities with respect to Products for use in the Field that are necessary for supporting Regulatory Approval of Products or expanding the indications for Products within the Field. GTX shall, upon Orion’s request therefor, provide Orion with written updates of any and all activities undertaken by or on behalf of it pursuant to this Section 2.5, and with the results thereof in reasonable detail.

      2.6 Prohibited Actions. During the Term of this Agreement, Orion shall not grant any rights to any Third Party that are inconsistent with the licenses granted to GTX pursuant to Section 2.1.1.

3. PAYMENTS

      3.1 Types of Payments . For the rights, privileges and licenses granted hereunder, GTX shall pay Orion in the manner provided as follows:

           3.1.1 In the event GTX or its Affiliate receives Upfront and Milestone Income (as defined in Section 3.1.1(c)), GTX shall pay Orion as follows:

                (a)  Any Upfront and Milestone Income shall first be applied to [ * ] both prior to and after the Amendment Date, and also for the [ * ] .

                (b)  Upon full reimbursement of such [ * ] pursuant to Section 3.1.1 (a), any remaining Upfront and Milestone Income (the “Net Upfront and Milestone Income”) shall then be paid by GTX to Orion as follows:

                     (i)  GTX shall pay Orion [ * ] of the portion of Net Upfront and Milestone Income that is [ * ] ; and

                     (ii) [ * ] of the portion of the Net Upfront and Milestone Income that is [ * ] .

                (c)  For the purposes of this Agreement, “Upfront and Milestone Income” shall mean any bona fide consideration (either in cash or non-cash form) received by GTX or its Affiliate from a GTX Unaffiliated Sublicensee for sublicensing GTX’s rights in and to the Product for use in the Field in the GTX Territory excluding: (i) Royalty Income (as defined in Section 3.1.4); (ii) cost of goods payments for supply of Product manufactured by Orion and supplied at the prices set forth in Section 13 herein below, or payments to reimburse GTX’s fully burdened costs of manufacturing or having manufactured Product by or on behalf of GTX as permitted under this Agreement; (iii) in the form of a loan; or (iv) for the purchase of an equity interest in GTX (except to the extent such purchase price is a Premium over the fair market value of such stock, in which case the Premium, but not the portion of such price that is at the fair market value of such stock, shall be included in Upfront and Milestone Income). Notwithstanding the foregoing, if GTX receives Upfront and Milestone Income received in the form described in (ii) or (iii) [ * ] . For example and without limitation, if [ * ] .

           3.1.2 If` GTX is Acquired prior to the first Regulatory Approval of Product for use in the Field, then GTX shall pay to Orion an amount equal to the lesser of one million dollars ($1,000,000) or [ * ] of the fair market value of GTX at the time of such acquisition. “Acquired” means that GTX either (i) sells all or substantially all of its assets to a Third Party, or (ii) is merged with or consolidated or reorganized into a Third Party, or becomes a subsidiary of a Third Party, and, as a result of such transaction, the stockholders of GTX immediately prior to such transaction own less than fifty percent (50%) of the surviving parent entity.

           3.1.3 For commercial sales of each Product by GTX, or its Affiliates in a country of GTX Territory commencing on the First Commercial Sale of Product, GTX shall during the Term pay Orion a running royalty in the amount of [ * ] of Net Sales of Product on a country by country basis, subject to the provisions of Sections 3.1.6 and 20.2.2.

           3.1.4 Subject to the provisions of Sections 3.1.6 and 20.2.2, in the event GTX receives running royalty income from GTX Unaffiliated Sublicensees for sublicensing GTX’s rights in and to the Product for use in the Field and/or based upon sales by GTX Unaffiliated Sublicensees of Product for use in the Field in the Territory (“Royalty Income”), GTX shall during the Term pay Orion the lesser of, on a country by country basis, either (i) [ * ] of such Royalty Income; or (ii) [ * ] of such GTX Unaffiliated Sublicensees, provided, however, that in no event shall the amounts due to Orion pursuant to this Section 3.1.4 be [ * ] of Net Sales of such GTX Unaffiliated Sublicensees.

           3.1.5 As of December 31, 2000, an upfront license fee of four hundred thousand dollars ($400,000) (the “Upfront License Fee”), was paid in full by GTX to Orion. This payment shall be creditable by GTX against fees or payments due to Orion with respect to Upfront and Milestone Income pursuant to Section 3.1.1.

           3.1.6 If a Generic Product is sold in any Major Country of the GTX Territory, and, for two (2) succeeding calendar quarters the Sales of Generic Product in that country [ * ] of the sales of Product (calculated on a unit basis) in that country, then the royalty on Net Sales owed by GTX to Orion under Section 3.1.3 and the payments due to Orion on Royalty Income pursuant to Section 3.1.4, respectively, shall be reduced to [ * ] of the amount otherwise due to Orion pursuant to either Section 3.1.3 or 3.1.4, as applicable, with regard to such country with such reduction to be applicable to the immediately succeeding calendar quarter only.

      3.2 Non-Refundability . All milestone payments GTX makes to Orion pursuant to Section 3.1.1 shall be non-refundable once paid. However, if this Agreement is terminated for any reason prior to a given milestone payment becoming due or if the events specified for a given milestone payment do not occur, then GTX shall have no obligation to make such milestone payment.

      3.3 Royalty Reports and Payments . Commencing with the first Calendar Quarter in which GTX, its Affiliates or a GTX Unaffiliated Sublicensees make the First Commercial Sale of the Product, GTX shall provide Orion with a written report of Net Sales and Royalty Income on a country-by-country basis within forty-five (45) days after the last day of March, June, September and December for Royalty Income accruing on Net Sales during the three (3)

preceding calendar months. Concurrently with the submission of each such written report, GTX shall pay or cause to be paid to Orion the total amount of royalties shown to be due thereon.

      3.4 Currency . GTX shall make all Upfront and Milestone Income and royalty payments to Orion pursuant to Section 3.1 in U.S. Dollars except that GTX shall make all cost of goods payments to Orion pursuant to Section 13 in euros. Where royalty payments are made, payments earned shall be first determined by GTX in the currency of the country where the Net Sales on the sales giving rise to payments were made and then converted directly to its equivalent in U.S. dollars. The rates of exchange for converting the currencies involved to U.S. dollars shall be the Foreign Exchange Rates quoted in the Wall Street Journal rate on the last business day of the quarterly period in which the royalty payments were earned.

      3.5 No Royalties Payable Between Affiliates. No royalties shall be payable to a Party on sales between the other Party, its Affiliates or between the Party’s Affiliates.

      3.6 No Multiple Royalties. No multiple royalties shall be payable because the Product, its manufacture, use or sale is or shall be covered by multiple patents.

4. LIAISON

     Representatives of the Parties shall meet bi-annually or as otherwise agreed to review development, sales and marketing activities for the Product for use in the Field in the GTX Territory, with the exact dates and locations of such meetings to be mutually agreed upon. Such meetings shall alternate between GTX’s and Orion’s offices or be at other mutually agreed upon locations, with each Party to be responsible for the travel and living costs and expenses of its own representatives attending such meetings.

5. PAYMENT, RECORD KEEPING AND AUDIT RIGHTS

      5.1 Method of Payment . In the event of any required tax withholding, the paying Party will provide the receiving Party with any relevant certificates or documents required for national, state or local tax credit and reporting purposes. Payments hereunder shall not be creditable against any other amounts payable by a Party under this Agreement, except as otherwise expressly stated herein. All payments shall be made by bank wire transfer (e.g., “SWIFT” or other comparable electronic transfer method) to such account(s) as the receiving Party shall designate beforehand in writing to the paying Party. Payments shall be deemed paid once funds are freely available to the receiving Party at such account(s).

      5.2 Late Payments. The Party entitled to payment hereunder reserves the right to charge the paying Party interest on any amounts owing from the paying Party which are overdue by more than fourteen (14) business days at a rate of [ * ] per annum, or the maximum rate allowed by law, whichever is lower, calculated from the date any payment was due and payable.

      5.3 Record Keeping and Audit Rights. Each Party shall keep or cause to be kept accurate records relating to Net Sales, royalties, development and any other costs and expenses subject to payment, deduction or reimbursement by either Party to the other Party in sufficient detail to enable the amounts payable hereunder to be determined. Upon the written request of

either Party (but not more frequently than once in any calendar year), the requesting Party may retain an independent certified public accountant, subject to approval by the other Party (which approval shall not be unreasonably withheld), to review such records to verify the accuracy of the payments made or payable hereunder. Such accountant shall be required to execute a confidentiality agreement in a form reasonably acceptable to the audited Party and shall report to the auditing Party only the amount of any underpayment or overcharge. Within ten (10) business days after completion of such review, the Parties shall reconcile any underpayment or overcharge. The auditing Party shall pay the cost of any review of records conducted at its request under this Section. However, if the review establishes underpayment or overcharge by the audited Party of over three percent (3%) during the period of the review, the audited Party shall promptly reimburse the auditing Party for the fees and expenses of the accountant. Such audit rights may be exercised by the Parties only with respect to records for the current calendar year and the preceding two (2) calendar years.

6. GTX PRODUCT MARKETING AND SALES ACTIVITIES

      6.1 Minimum Sales Requirements for USA .

           6.1.1 Levels of MSRs. GTX shall have annual minimum sales requirements for Product for use in the Field (“MSRs”) in the second year and fourth year after Product Launch in the USA equal to [ * ] of GTX’s annual Product Sales Projections (as defined below) in the USA. To establish such projections for the purpose of the foregoing sentence, GTX shall provide to Orion annual Product Sales Projections in the USA within ninety (90) days after GTX, its Affiliate or Unaffiliated Sublicensee completes the last pivotal clinical trial as provided in the GTX Final Development and Registration Plan for Product in the USA. The Parties shall set forth in Schedule D GTX’s MSR obligations within sixty (60) days after GTX provides such projections, and such MSRs shall be made a part hereof. Beginning with the [ * ] year after Product Launch in USA for use in the Field until the end of the Term, GTX shall have an annual MSR equal to [ * ] of the average of GTX’s Actual Product Sales (as defined below) in the USA for Product in the Field for the [ * ] . “Product Sales Projections” means GTX’s good faith estimates of the target patient population in a given year for Products in the Field, multiplied by the price per tablet of Product for use in the Field that GTX plans to be able to charge during the [ * ] after Product Launch. “Actual Product Sales” means GTX’s, its Affiliate’s or a GTX Unaffiliated Sublicensee’s actual Net Sales of Product in the Field during a given year in the USA.

     For example, in year [ * ] if the target patient population is [ * ] subjects in the Field and the Product would be consumed [ * ] for the Field at a hypothetical price of [ * ] , GTX’s Product Sales Projections would [ * ] . The hypothetical price for a tablet set forth above is hypothetical and was only used for the sole purpose of explaining the mechanism for calculating the Product Sales Projections and MSRs. Nothing contained in such example shall be so construed to deny the right of GTX to freely set its resale price of the Product.

           6.1.2 Product Launch Date. “Product Launch in USA” shall be determined by the date on which the Product has received Regulatory Approval and is commercially available in the USA as follows: (i) if such date occurs during the first six (6) months of any calendar year (i.e., January 1-June 30), Product Launch in USA shall be deemed to have

occurred on January 1 of such calendar year, and (ii) if such date occurs during the last six (6) months of any calendar year (i.e., July 1-December 31), Product Launch in USA shall be deemed to have occurred on January 1 of the following calendar year.

           6.1.3 Adjustment. GTX’s annual Product Sales Projections for the Field in the USA shall be subject to adjustment by written agreement of the Parties, with a corresponding adjustment in the MSRs, in the event of government intervention in given markets (including, but not limited to, government mandated health care reforms, rebates or regulatory changes), failure to obtain (or delay in obtaining) approval for a Product indication in the Field, or other events or causes affecting the market for the Product for use in the Field beyond the control of GTX, including but not limited to lower than anticipated pricing approvals measured on an aggregate basis throughout USA; GTX Patent Rights and/or Orion Patent Rights invalidation, infringement or expiration; Product safety and/or efficacy issues and/or major therapeutic advances materially affecting the market potential for the Product for use in the Field (including but not limited to new surgical procedures or introduction of new competitive products with superior safety and/or efficacy profiles); or a Force Majeure event (as described in Section 26).

           6.1.4 Failure to Achieve MSRs. If GTX’s annual Product Sales in USA for the Field are less than the MSRs in any applicable calendar year, GTX shall, without prejudice to its payment obligations under Section 3.1, pay Orion royalties corresponding to the “shortfall” between the actual royalties paid by GTX for such year and the royalties which would have been payable pursuant to Section 3.1 had GTX achieved the MSRs during such year. GTX’s payment of such “shortfall” hereunder shall be Orion’s sole and exclusive remedy for GTX’s failure to achieve MSRs in USA for such year. However, if GTX fails to pay such “shortfall,” then Orion may, without prejudice to its right to such shortfall, also terminate this Agreement pursuant to Section 20.2.2.

      6.2 No Minimum Sales Requirements Outside of USA . GTX shall not have any MSRs with respect to sale of the Product in any countries in GTX Territory outside of the USA.

      6.3 Marketing and Sales Efforts in the Major Countries

           6.3.1 Commercially Reasonable Obligation. On a country by country basis, subject to Sections 6.3 and 6.4, during the period commencing with Regulatory Approval in a Major Country, and for the remainder of the Term, GTX, its Affiliate and/or a GTX Unaffiliated Sublicensee shall use commercially reasonable efforts to promote, market, distribute and sell the Product for use in the Field in the Major Countries. For purposes of this Section 6.3, “commercially reasonable” shall mean using, in each of the Major Countries, an equivalent degree of effort as GTX, its Affiliate or a GTX Unaffiliated Sublicensee would use to promote, market, distribute and sell a product of it own that is of comparable market potential in the respective Major Countries during the same time period (as determined by consideration of, without limitation, potential market, patent protection, and availability of competitive products), including but not limited to, engaging in the following activities (subject to any applicable U.S. FDA restrictions or other applicable legal restrictions):

                (a)  Using reasonable diligence to establish and maintain good business relationships with hospitals, health systems, doctors and other medical professionals in accordance with standard and customary practices in the Major Countries;

                (b)  Using commercially reasonable efforts to establish and maintain an adequate capacity of sales personnel consisting of reasonably qualified personnel who have been certified, as trained by GTX, its Affiliate or a GTX Unaffiliated Sublicensee, to promote and market the Product for use in the Field in the Major Countries, and to provide such sales force with adequate sales and promotional materials for the Product;

                (c)  Promoting and detailing the Product for use in the Field throughout the Major Countries, provided that GTX, its Affiliate or a GTX Unaffiliated Sublicensee may, in its discretion use relatively greater promotional and detailing efforts (i) in some Major Countries than it uses in other of such countries, and (ii) in some parts of each Major Country than in other parts thereof, consistent with its overall marketing plan; and further provided, however, that the foregoing shall in no event be deemed to limit GTX’s its Affiliate or a GTX Unaffiliated Sublicensee overall obligations under the first paragraph of this Section 6.3.1.

                (d)  Advertising the Product for use in the Field in professional journals and publications and sponsoring or attending appropriate symposia, trade exhibitions and medical education programs in a manner equivalent to that used for GTX’s, its Affiliate’s or a GTX Unaffiliated Sublicensee’s, as applicable, own products of comparable market potential in such Major Country; and

                (e)  Formulating and using reasonable efforts to implement annual sales and marketing plans for the Product for use in the Field in the Major Countries and providing copies of such plans to Orion for review and comment, provided that Orion shall not have approval rights with respect to such plans.

           6.3.2 Sales Objectives and Other Factors for the USA. GTX and Orion shall agree in writing upon annual target sales objectives for the Product for use in the Field in the USA, commencing with the fourth calendar year after First Commercial Sale of the Product for use in the Field in the USA, provided that such annual target sales objectives shall not be considered MSRs for any purposes, but instead shall be used by the Parties for informational and planning purposes and shall be one (1) factor, among others, to be considered in assessing whether GTX has complied with its commercially reasonable obligations hereunder. GTX’s level of sales and marketing expenses for the Product for use in the Field in the USA and events or causes affecting the market for the Product for use in the Field beyond the control of GTX shall also be among the factors to be considered in assessing whether GTX has complied with its commercially reasonable obligations hereunder.

      6.4 Product Launch

           6.4.1 Timing of Launch. GTX shall use commercially reasonable efforts to launch the Product for use in a given indication in the Field as soon as practical in every Major Country of the GTX Territory where GTX, its Affiliates and/or GTX Unaffiliated Sublicensees have obtained Regulatory Approval for such indication. Notwithstanding the foregoing, GTX, its

Affiliate or a GTX Unaffiliated Sublicensee may, acting in good faith in the exercise of its reasonable business judgment, determine either to delay the launch of the Product for use in a given indication in the Field or not to launch the Product for use in a given indication in the Field in any given country in the GTX Territory other than a Major Country, which decision to delay or not to launch shall not be deemed a failure to use commercially reasonable efforts. Further, GTX’s, its Affiliates’ or a GTX Unaffiliated Sublicensee’s decision to delay the launch of the Product for use in the Field in any Major Country for up to six (6) months after GTX or its Affiliates have obtained Regulatory Approval in such country, shall not be deemed a failure to use commercially reasonable efforts pursuant to Section 6.3 to the extent that GTX can demonstrate that such delay was attributable to bona fide business reasons affecting the Product.

           6.4.2 Decisions Not to Launch. GTX shall promptly notify Orion in writing if GTX, its Affiliate or a GTX Unaffiliated Sublicensee, as applicable, determines to delay the launch of the Product for use in a given indication in the Field in any Major Country after obtaining Regulatory Approval of Product therefor. If such decision is due to any reasons other than the potential for, or the existence of, adverse business effects in such Major Country, then such decision shall be deemed a material breach of this Agreement pursuant to Section 20.2.2 and GTX shall be subject to the provisions of such Section within thirty days (30) after GTX’s decision not to launch in such Major Country.

      6.5 Marketing Costs and Expenses. Except as other-wise provided herein or as otherwise mutually agreed by the Parties, GTX, its Affiliate or a GTX Unaffiliated Sublicensee shall bear all costs and expenses connected with its marketing and sales activities for the Product for use in the Field and its performance under this Agreement.

      6.6 Marketing Plans and Reports .

           6.6.1 Marketing Plans. GTX shall develop and provide to Orion by October 31 of each year during the Term marketing and sales plans for the Product for each Major Country for the following calendar year, commencing with the calendar year in which Regulatory Approval is obtained in each respective country. Such plans shall include the projected Annual Net Sales and the projected advertising and promotion budgets for such year, and shall not be applicable to the calculation of MSRs pursuant to Section 6.1, for which GTX shall separately provide information.

           6.6.2 Marketing and Sales Reports. GTX shall provide to Orion, within forty-five (45) days after the end of each calendar year, a written marketing activities and sales report for each of the Major Countries. The report shall include at least a description of sales, marketing and promotion activities and a list of scientific conferences or other events involving the Product or its therapeutic area, accompanied by a general description of the nature and extent of GTX’s participation in such conferences or events.

7. GTX PRODUCT DEVELOPMENT AND REGISTRATIONS

      7.1 GTX Development and Registration Activities .

           7.1.1 GTX Activities. In accordance with the GTX Preliminary Development and Registration Plan and the GTX Final Development and Registration Plan, GTX shall undertake development and registration activities for the Product for use in the Field in the GTX Territory, including but not limited to, conducting or sponsoring, and completing or having completed in accordance with U.S. FDA regulations and Good Clinical Practice regulations under the European Union legislation and directives requirements, all clinical studies and other activities required for Regulatory Approval under the GTX Final Development and Registration Plan. Without limiting the provisions of Section 7.6, GTX shall use its commercially reasonable efforts to pursue such development and registration activities under the GTX Final Development and Registration Plan with the objective of filing applications for Regulatory Approval in all Major Countries throughout the GTX Territory according to the anticipated filing dates set forth in the GTX Final Development and Registration Plan timetable. GTX’s Regulatory Approvals in the GTX Territory shall be owned solely by GTX.

           7.1.2 Orion Activities.

                (a)  Orion shall use its commercially reasonable efforts to assist GTX in obtaining and maintaining the U.S. FDA Regulatory Approval of Products and any other required Regulatory Approvals in the Major Countries of the GTX Territory relating to the manufacture, use, marketing or sale of Product for use in the Field (by providing to GTX relevant information, documents and data in its possession in relation to regulatory inquiries during the Regulatory Approval process for Products, necessary additional letters of cross-reference or authorization equivalent to those described in Section 7.4, assistance in obtaining free sales certificates, and other similar assistance).

                (b)  Orion shall perform any stability testing for the bulk Orion Product to be manufactured and supplied by Orion to GTX that is required by regulatory authorities in any Major Country. Such testing shall be provided at no cost to GTX, except that GTX will reimburse Orion’s direct costs of performing any such stability testing that must be conducted solely for the [ * ] tablet of the Orion Product. Orion employees shall, at Orion’s cost and expense, have the right to participate in all FDA and other regulatory agency meetings regarding the use of the Product in the Field.

                (c)  Orion shall have no obligation to research, develop, register, commercialize any Product or carry out any studies or testing in relation to Products, including without limitation with respect to any new or additional strength, dosage form, formulation or route of administration of the Orion Product or the Product, or provide any documentation, information or data relating to the foregoing, except as expressly provided in Section 7.1.2(a) or otherwise set forth in this Agreement, unless the Parties expressly mutually agree otherwise in writing after the Amendment Date. Other than as expressly agreed in this Agreement, Orion shall have no obligation to fund or pay for any of the costs and expenses of such activities. All studies, trials, tests, activities, documentation, data and information required by any regulatory or other governmental agency or which is necessary or useful for the research, development, registration or commercialization of the Product shall, unless otherwise expressly agreed to herein, be for the sole cost and responsibility of GTX.

           7.1.3 FDA File. Any regulatory filings (including without limitation any DMFs that GTX may develop if it obtains the right to manufacture Product) compiled and filed by or on behalf of GTX shall remain the property of GTX, but GTX shall, upon request therefor by Orion, negotiate with Orion the terms under which GTX would provide appropriate authorization letters to relevant regulatory bodies to enable Orion to reference such regulatory filings for purposes of applying for and supporting Orion’s applications for Regulatory Approval of products containing Toremifene outside the Field.

      7.2 Development and Registration Costs. Except as otherwise expressly provided in this Agreement or otherwise mutually agreed in writing by the Parties after the Amendment Date, GTX shall bear all costs and expenses related to Product registration and regulatory activities, including without limitation costs of filing, obtaining and maintaining all Regulatory Approvals throughout GTX Territory, as well as all costs and expenses for the research and development of the Product for use in the Field, provided that GTX shall not be responsible for any costs related to the manufacture of the Orion Product (except for payments that GTX must make to Orion pursuant to Section 7.1.2(b) or Section 13 (such costs collectively referred to herein as “Manufacturing Costs”). Except for the Manufacturing Costs or as otherwise expressly provided in this Section 7, Orion shall bear no responsibility for any costs or expenses related to Product registration, regulatory, research or development activities in relation to the Product.

           7.2.1 Development and Registration Costs prior to Amendment Date. The Parties agree that GTX shall, notwithstanding anything to the contrary in the Original Agreement or otherwise, also bear all costs and expenses related to Product research, development, registration, regulatory compliance and other activities relating to the development of Product that were incurred prior to the Amendment Date by GTX (excluding any Manufacturing Costs) (hereinafter referred to as “Incurred Costs”). Consequently, GTX shall forever release and discharge Orion of any and all claims that it purports to have at the Amendment Date or may have thereafter against Orion with respect to Incurred Costs.

      7.3 GTX Development and Registration Plan .

           7.3.1 Completion of GTX Final Development and Registration Plan. The GTX Preliminary Development and Registration Plan was attached to the Original Agreement as Schedule B. GTX will prepare a GTX Final Development and Registration Plan for each Major Country in a timely fashion upon receiving approval from the appropriate regulatory authority in each Major Country of a plan for regulatory approval in that country. Immediately upon completion of the GTX Final Development and Registration Plan for each Major Country, a copy of such Plan shall be provided to Orion.

           7.3.2 Orion’s right to comment on and object to Plan. Orion shall have the right to comment on each GTX Final Development and Registration Plan for each Major Country. Additionally, Orion shall have the right to object to each GTX Final Development and Registration Plan for each Major Country to the extent such plan could reasonably be deemed to affect adversely Orion’s development, commercialization, sales or registration of Orion’s proprietary product Fareston(R) outside the Field or Toremifene outside the Field. GTX undertakes to change and/or amend the GTX Final Development and Registration Plan for each Major Country to the extent Orion has so objected thereto as necessary to alleviate or obviate

such adverse effect. Orion shall provide GTX with such comments and/or objections within thirty (30) days from Orion’s receipt of the GTX Final Development and Registration Plan.

           7.3.3 Changes to Such Plan. GTX may modify the GTX Final Development and Registration Plan, as GTX deems necessary and consistent with Section 7.3.1, but shall notify Orion of such changes. Any changes to the GTX Final Development and Registration Plan for each Major Country shall also be subject to Section 7.3.2.

      7.4 Orion Documentation and Data

           7.4.1 GTX Access to Orion Know-How. Orion has provided and shall continue to provide GTX with copies of the Orion Know-How, documentation, information and data listed or referenced in the GTX Preliminary Development and Registration Plan, and GTX shall be authorized to use and reference the same in its applications for Regulatory Approval and regulatory compliance activities in relation to such Regulatory Approvals. Any Product Drug Master Files (“DMFs”) compiled or owned by Orion shall remain the property of Orion, but Orion shall, upon reasonable request therefor by GTX, provide appropriate authorization letters to relevant regulatory bodies in the GTX Territory within forty-five (45) days from such request to enable GTX to reference such DMFs for purposes of GTX’s applications for Regulatory Approval and regulatory compliance activities in the GTX Territory as provided for in Section 7.1. For the avoidance of doubt, neither Party is obligated to disclose the contents of its DMFs to the other Party.

           7.4.2 GTX Access to Data. During the Term, Orion shall provide GTX, within forty-five (45) days of receipt of a written request from GTX specifying in detail the documentation, information and data requested, access to Orion Know-How that GTX reasonably requires for regulatory filings for the use of Product in the Field in the GTX Territory. Upon GTX’s request, Orion shall provide GTX with copies of such Orion Know-How referenced in the preceding sentence only in such form and content as is available to Orion, provided that, upon Orion’s request, GTX shall reimburse Orion for Orion’s direct out-of-pocket cost of making such copies and providing GTX with such Orion Know-How.

     GTX shall also provide to Orion quarterly reports summarizing GTX’s progress under the GTX Preliminary Development and Registration Plan and the GTX Final Development and Registration Plan.

           7.4.3 Letter of Cross Reference. Orion agrees that the Cross Reference letter dated December 10, 1999 from Orion to GTX shall remain in effect and may not be revoked by Orion unless this Agreement is terminated. During the Term, Orion shall permit GTX, its Affiliates and the GTX Unaffiliated Sublicensees to reference, and shall provide GTX with an appropriate authorization letter to enable GTX, its Affiliates and the GTX Unaffiliated Sublicensees to reference, Orion’s existing U.S. NDA [ * ] and all other applications or filings for Regulatory Approval for Orion Products for use in the breast cancer indication and related DMFs that are identified in Schedule E hereof (hereinafter “Orion Product Approvals”) for the purpose of applying for and supporting Regulatory Approval of Products for use in the Field within the GTX Territory. Orion shall update Schedule E from time to time during the Term to set forth all Orion Product Approvals and DMFs that are owned and controlled by Orion. GTX

recognizes that Orion has obtained the Orion Product Approvals solely for the purpose of its proprietary product Fareston(R), and that nothing herein shall be construed so as to obligate Orion to maintain or cause to be maintained any Orion Product Approvals solely for allowing GTX, its Affiliates and/or GTX Unaffiliated Sublicensees referring thereto, provided that during the Term Orion shall not withdraw such Orion Product Approvals in the absence of commercially justifiable reasons in relation to Fareston(R).

           7.4.4 All requests by GTX to Orion for documentation, information or data, as agreed herein, shall be addressed only to the attention of such person(s) as is/are designated in writing or in electronic form by Orion from time to time.

      7.5 GTX Registration and Marketing Approval Applications. GTX, its Affiliates and/or GTX Unaffiliated Sublicensees shall have the responsibility and the right to submit registration applications for Regulatory Approval and marketing and price approval of the Product for use in the Field within the GTX Territory.

      7.6 Failure to File or Extend. Orion shall have the right to terminate its obligations under Section 7.1.2(a) and its obligations to manufacture and supply to GTX Orion Product upon one hundred and twenty (120) days prior written notice to GTX, if either (I) Regulatory Approval has not been granted for the Product for use in the Field in the USA by December 31, 2007, or