WHEREAS, GTx has sought from Ipsen an Additional Milestone Payment in consideration of additionalrights granted hereunder, including but not limited to expanding Ipsen’s territory and co-promotingthe Licensed Product in the ADT Indication in the US; and Ipsen desires to effect payment inrespect thereof.WHEREAS, the Parties considered the necessity of amending their rights and obligations under theLicense Agreement subject to the terms and conditions of this First Amendment.WHEREAS, the License Agreement and this First Amendment shall be considered as the Parties’ wholeagreement (the “**Agreement**”) as of the Signature Date of this First Amendment.**NOW THEREFORE IN CONSIDERATION OF THE PREMISES SET FORTH ABOVE AND INTENDING TO BE LEGALLY BOUND,THE PARTIES HAVE AGREED AS FOLLOWS:****SECTION 1****:****DEFINITION**1. The following term used in this First Amendment have the meaning indicated below : 1.1 “**Additional Milestone Payment**” shall have the meaning ascribed to it in Section2 of this First Amendment. 1.2 “**Additional Phase III Study**” shall have the meaning ascribed to it in thePreamble of this First Amendment. 1.3 “**Calendar Year**” shall begin on January 1st of the calendar year ofthe Signature Date and “**Calendar Quarter**” shall mean each of the three consecutivecalendar month periods ending March 31, June 30, September 30 and December 31 of suchyear. 1.4 “**€**” shall mean European Euro currency. 1.5 “**Field”**shall have the meaning ascribed to it in Article 5.8(a) of the LicenseAgreement. For the sake of clarity, the side effects of ADT in men with prostatecancer include among others bone fractures. 1.6 “**GTx Patent**” shall have the meaning prescribed to it in Section 4.1 of thisFirst Amendment. For the avoidance of doubt, “**GTx Patent**”, as defined herein, shallsupersede the definition of GTx Patent defined in the License Agreement. A list of theGTx Patent identified as of the Signature Date is attached hereto as Appendix A to thisFirst Amendment. 1.7 “**GTx Territory**” shall mean the US and all other parts of the world,except the Ipsen Territory.   [ * ] = Certain confidential information contained in this document, marked by brackets, has beenomitted and filed separately with the Securities and Exchange Commission pursuant to Rule 24b-2 ofthe Securities Exchange Act of 1934, as amended.
 
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 1.8 “**Ipsen Territory**” shall mean the European Territory, Algeria, Tunisia, Morocco,Lebanon, Iran, Saudi Arabia, Egypt, Jordan, Kuwait, UAE, Australia, China, Vietnam,Korea, Taiwan, Thailand, the Philippines and Indonesia. For the avoidance of doubt,“**Ipsen Territory**”, as defined herein, shall supersede the territory granted underlicense from GTx to Ipsen as defined as the “**European Territory**” under the LicenseAgreement.  1.9 “**Signature Date**” shall mean the last signature date of this First Amendment. 1.10 **“US Net Sales”**shall have the meaning ascribed to it in Section 4.7(ii) of thisFirst Amendment. 1.10 **“US Royalty Payment”**shall have the meaning ascribed to it in Section 4.7(i) of thisFirst Amendment.**SECTION 2****:****ADDITIONAL MILESTONE PAYMENT**2.1. In consideration of the additional and amended license rights granted to Ipsen by GTx underthis First Amendment, Ipsen agrees to pay to GTx an Additional Milestone Payment in the totalamount which shall not exceed €42 million (VAT excluded).2.2. Such Additional Milestone Payment shall be paid in six installments upon written notificationby GTx that the milestone event has occurred, as follows: (i) Ipsen shall pay GTx €[ * ] within [ * ] calendar days followingnotification to Ipsen by GTx of [ * ]; (ii) Ipsen shall pay GTx €[ * ] within [ * ] calendar days followingnotification to Ipsen by GTx of [ * ]; (iii) Ipsen shall pay GTx €[ * ] within [ * ] calendar days followingnotification to Ipsen by GTx of [ * ]; (iv) Ipsen shall pay GTx €[ * ] within [ * ] calendar days followingnotification to Ipsen by GTx of [ * ]; (v) Ipsen shall pay GTx €[ * ] within [ * ] calendar days following [ * ]and (vi) Ipsen shall pay GTx €[ * ] within [ * ] calendar days following [ * ],subject to the following payment adjustment mechanisms: (a) In the event the total and final externalthird party costs for the Additional Phase III Study are known toGTx at the time [ * ], and (a) if such amount (€ X) is [ * ] but [ *], then [ * ] (i.e., [ * ]); (b) if such amount (€ X) is [ * ] andalso [ * ], then [ * ] and [ * ] (i.e., [ * ]**)**.   [ * ] = Certain confidential information contained in this document, marked by brackets, has beenomitted and filed separately with the Securities and Exchange Commission pursuant to Rule 24b-2 ofthe Securities Exchange Act of 1934, as amended.
 
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 (b) In the event the total actual amount ofthe external third party costs for the Additional Phase III Study isunknown to GTx at the time [ * ], GTx shall furnish to Ipsen thefinal actual external third party costs for the Additional Phase IIIStudy within [ * ] days of the FSR, and [ * ] if the actual totalexternal costs for the Additional Phase III Study are [ * ]. (c) For the purposes of calculating the totalamount of external third party costs that GTx has paid in US dollarsfor the Additional Phase III Study and whether [ * ] or whether [ *], all as set forth above in Section 2.2(vi)(a) and (b), the Partiesagree that at the end of each Calendar Quarter as the AdditionalPhase III Study proceeds, GTx shall aggregate that quarter’s actualexternal third party costs in US dollars and convert such costs intoeuros € using the middle market spot exchange rate on the lastbusiness day of the relevant quarter as published in the New Yorkedition of the Wall Street Journal. GTx shall inform Ipsen of suchUS dollar and euro equivalent costs within [ * ] days of the end ofeach quarter. The cumulative total of such quarterly euro amountspaid in respect of the Additional Phase III Study shall be includedin the quarterly reports from GTx. At the time that [ * ], as setforth above, GTx will determine the aggregate euro equivalent costsof the Additional Phase III Study [ * ]. This calculation shall beused to determine if [ * ] or whether [ * ] as provided in thisSection 2.2 (vi)(a) and (b) above. If [ * ] or if [ * ], the amountof the [ * ] or [ * ], will be the euro [ * ] or [ * ] and will besettled between Ipsen and GTx in euros.**SECTION 3**: **GTX’S OBLIGATION**3.1. Additional Phase III Protocol:GTx commits to conduct the Additional Phase III Study in accordance with the protocolapproved by GTx and Ipsen (the “**Additional Phase III Protocol**”) to ensure that theAdditional Phase III Protocol would meet the requirements of the FDA and the EMEA (and otherRegulatory Agencies within the Ipsen Territory), unless major safety concerns develop duringthe Additional Phase III Study or the FDA or other equivalent Regulatory Agency requiresthat the Study be stopped. GTx acknowledges and agrees that such Additional Phase IIIProtocol and any and all amendments thereto must be approved by the CMO of Ipsen or anymedical appointee designated by the CMO prior to its submission to the FDA for FDA input,which approval by Ipsen shall not be unreasonably delayed or withheld. Upon Ipsen and GTxagreeing on the Additional Phase III Protocol, GTx shall get input from the FDA on suchAdditional Phase III Protocol to determine FDA’s concurrence that the Additional Phase IIIStudy should be sufficient to support GTx’s NDA for Regulatory Approval in the US.Sufficiency for the purpose of allowing GTx and Ipsen to seek Regulatory Approvals from theFDA and the EMEA (and other Regulatory Agencies within the Ipsen Territory) respectively forthe ADT Indication assumes the study achieves the agreed upon efficacy endpoints and theproduct candidate is found to be safe.   [ * ] = Certain confidential information contained in this document, marked by brackets, has beenomitted and filed separately with the Securities and Exchange Commission pursuant to Rule 24b-2 ofthe Securities Exchange Act of 1934, as amended.
 
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   3.2. Study Budget: (i) GTx acknowledges and agrees that upon receiving FDA’s comments on theAdditional Phase III Protocol, it shall then finalize the Protocol and theassociated clinical study budget for all third party external costs for theAdditional Phase III Clinical Study (the “**Study Budget**”) and submit it to the CMOof Ipsen or any medical appointee designated by the CMO for review and approval,which Ipsen agrees to accomplish within [ * ] of its receipt of the Study Budget.The total amount set forth in the Study Budget shall be deemed to be the actualtotal third party external costs for the Additional Phase III Clinical Study. (ii) GTx acknowledges and agrees that upon finalizing the Study Budget withIpsen, it shall then have the obligation and responsibility to carry out theAdditional Phase III Clinical Study of the 80mg toremifene Initial Product to allowGTX and Ipsen to obtain Regulatory Approvals of the product candidate for the ADTIndication from the FDA and the EMEA (and other Regulatory Agencies in the Ipsenterritory) respectively. (iii) In the event the total third party external costs in the Study Budgetapproved by GTx and Ipsen exceed the amount of €42 million (VAT excluded) by anamount up to, but not exceeding, [ * ]% of Ipsen’s €42 million Additional MilestonePayment, GTx agrees that it will pay such excess costs. In the event the totalthird party external costs of the Study Budget approved by GTx and Ipsen areexpected to exceed the [ * ]% threshold, GTx shall promptly notify Ipsen of suchexcess amount accompanied with all relevant supporting documents, copies of allcorrespondence and responses received by GTx from the relevant Regulatory Agencywithin sufficient time to allow Ipsen to review and consider the same. The Partiesshall then agree to discuss as to whether to initiate the Additional Phase IIIStudy and/or to renegotiate the terms of this First Amendment. (iv) For the sake of clarity, once the Study Budget is finalized andapproved by GTx and Ipsen and the Additional Phase III Study is initiated, andshould the total actual third party external costs exceed the finalized StudyBudget, any such excess amount shall be borne by GTx’s only and shall be upon GTx’ssole responsibility unless the Parties shall otherwise agree in writing.   [ * ] = Certain confidential information contained in this document, marked by brackets, has beenomitted and filed separately with the Securities and Exchange Commission pursuant to Rule 24b-2 ofthe Securities Exchange Act of 1934, as amended.
 
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   3.3. CRO selection & auditGTx acknowledges and agrees that the execution of the contract with a global clinicalresearch organization (CRO) to conduct the data management for the Additional Phase IIIStudy [ * ] shall only occur once the Study Budget is finalized with Ipsen. Any CROs toconduct the data management for the Additional Phase III Study and the monitoring ofinvestigations shall be selected by GTx among CROs identified by GTx and acceptable to Ipsenas of the Signature Date. A list of CROs acceptable to both Parties as of the SignatureDate is attached hereto at Appendix D and incorporated herein by reference. The Partiesagree that such list may be amended by GTx after the Signature Date upon Ipsen’sconsultation and approval, which approval shall not be unreasonably withheld of delayed.Upon Ipsen’s request filed [ * ] days in advance (which shall be not more than once annuallyand at Ipsen’s own and sole costs), GTx shall permit an independent expert selected by Ipsenand reasonably acceptable to GTx to grant access to, and audit and inspect, during normalbusiness hours any of the CROs conducting the data management and/or the monitoring ofinvestigation to assess compliance with GCP standards and applicable regulatoryrequirements.   3.4. Statistical Analytical Plan and the Final Study Report:GTx acknowledges and agrees that the Statistical Analytical Plan (SAP) and any and allamendments thereto must be approved in advance of the submission to the FDA by the CMO ofIpsen or any medical appointee designated by such CMO, each review and each approval processof which shall be concluded within [ * ] days of the receipt thereof. GTx furtheracknowledges and agrees that the Final Study Report (FSR) shall be provided to the CMO ofIpsen or any medical appointee designated by the CMO for his/her review and approval priorto GTx’s submission of such documents to FDA as a part of its NDA. Ipsen agrees that eachreview and each approval of the FSR shall be concluded within [ * ] days of its receiptthereof.   3.5. Integrated Summary of Safety and Integrated Summary of Efficacy:Additionally, the NDA Integrated Summary of Safety (ISS) and Integrated Summary of Efficacy(ISE) will be both submitted to the CMO of Ipsen or any medical appointee designated by suchCMO for his/her comments. GTx shall make its best efforts to include Ipsen’s comments inthe final ISS and ISE. Ipsen agrees that its comments on the ISS and ISE shall beconcluded, within [ * ] days of their receipt thereof.3.6. All notices and communication under Sections 3.1, 3.2, 3.3, 3.4 and 3.5 shall be made inwriting and delivered by hand, facsimile, registered mail or email (with the sending partykeeping the mechanical print-out registering the sending) as follows:Ipsen Pharma SAS65, Quai George Gorse92100 Boulogne BillancourtFranceTel: +33.(0)1.58.33.50.00Fax: +33.(0)1.58.33.50.15Attn: Corporate Legal Affairs, General Counsel   [ * ] = Certain confidential information contained in this document, marked by brackets, has beenomitted and filed separately with the Securities and Exchange Commission pursuant to Rule 24b-2 ofthe Securities Exchange Act of 1934, as amended.
 
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   3.7. Records and Audit Right:During the term of the Additional Phase III Study and until the completion of the Phase IIIFinal Study Report, GTx shall be responsible for maintaining a complete, accurate anddetailed account of all third party external costs expended for the Additional Phase IIIStudy. For the sake of clarity, the costs expended for such Additional Phase III Studyshall [ * ] and shall [ * ]. GTx shall furnish to Ipsen a detailed written report of suchexpended external costs within [ * ] days of the end of each Calendar Quarter period. UponIpsen’s request, which shall be sent with at least [ * ] day prior written notice, Ipsenwill have the right not more than once per calendar year to have an inspection duringordinary business hours conducted at Ipsen’s sole cost and expense by an independentcertified accounting firm of an internationally recognized standing selected by Ipsen andto which GTx has no reasonable objection, of such GTx’s records, books and accounts as maybe necessary to verify the accuracy of information submitted in respect of the costsincurred by GTx in connection with the Additional Phase III Study [ * ]. In case anydiscrepancy is found by the independent accountant in the total actual external Third Partycosts incurred by GTx for the Additional Phase III Study, which findings shall be made inwriting and communicated to the Parties as a final and binding investigation report, theParties agree to [ * ] so that [ * ]. The amount of [ * ] as determined by the independentaccountant shall be [ * ] within [ * ] calendar days after [ * ] the final investigationreport of the independent accountant.**SECTION 4****:****IPSEN’S RIGHTS**   4.1. Ipsen Territory:The Parties agree that Ipsen’s rights granted by GTx pursuant to the License Agreement andthis First Amendment shall be extended to the Ipsen Territory. For the sake of clarity,Ipsen shall have, and GTx agrees to grant, pursuant to Article 5 of the License Agreement:(i) a non-exclusive royalty-free license to develop the Licensed Product for any Indicationunder the GTx Know-how and GTx Patent as well as (ii) an exclusive, royalty-bearing licenseto conduct Commercialization Activities, including the right to sublicense, within the IpsenTerritory for any Indication under the GTx Patent, GTx Know-how and the Licensed Trademark.In accordance with the Parties’ agreement to extend the licensed territory, the Partiesagree that Exhibit A to the License Agreement related to all Patents and Patent ApplicationsControlled by GTx in the European Territory which Cover the Licensed Products shall beamended in the form as attached hereto at Appendix A as a new Exhibit A and incorporatedherein by reference, to include all Patents and Patent Applications Controlled by GTx in theIpsen Territory (the “**GTx Patent**”).   [ * ] = Certain confidential information contained in this document, marked by brackets, has beenomitted and filed separately with the Securities and Exchange Commission pursuant to Rule 24b-2 ofthe Securities Exchange Act of 1934, as amended.
 
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   4.2. Ipsen’s Release of ADT Milestone Payments:GTx acknowledges and agrees that Ipsen shall be irrevocably, perpetually and fully releasedfrom the milestone payment obligations set forth in Article 3.2(4) and (6) of the LicenseAgreement related to the ADT Indication that are pending as of the Signature Date:       **Released** **Released Milestone Payment** **Payment** 4. Filing with the EMEA or with the relevant Regulatory Agency [* ] for Regulatory Approval of [ * ] €[ * ]6. Obtaining a Regulatory Approval by the EMEA/EuropeanCommission or by the Regulatory Agency [ * ] of [ * ] €[ * ]For the sake of clarity, the above-listed milestone payments shall no longer be due by Ipsenand owed to GTx under Article 3.2 of the License Agreement for the ADT Indication.   4.3. Ipsen’s Release of Pricing Milestone Payments:GTx acknowledges and agrees that Ipsen shall be irrevocably, perpetually and fully releasedfrom its milestone payment obligation as set forth in Article 3.2(7) of the LicenseAgreement related to the pricing of toremifene in the ADT Indication or in the PINIndication that is pending as of the Signature Date:       **Released** **Released Milestone Payment** **Payment** 7. On a [ * ] basis, the determination by the relevant Regulatory Agency of a List Price for [ * ] €[ * ]   4.4. Reduction of Royalty Payment:From and after the date hereof, GTx and Ipsen acknowledge and agree that Ipsen’s obligationto make quarterly Royalty Payments on Net Sales of the Licensed Product in the IpsenTerritory in the ADT Indication (i.e., including the prevention of bone fractures in menwith prostate cancer on ADT), will be reduced to a fixed Base Royalty Rate of 12%. Inaccordance with the agreements contained herein, the Parties hereto agree that Article 3.4of the License Agreement shall be amended by deleting the article in its entirety andsubstituting in lieu thereof a new Article 3.4 set forth in Appendix B attached hereto andmade a part hereof.   4.5. Use of Additional Phase III Data:GTx acknowledges and agrees that Ipsen shall be authorized and have the right to use,without payment of any additional costs, all data generated during the Additional Phase IIIStudy in the Ipsen Territory for purposes of, but not limited to, obtaining and maintainingRegulatory Approvals in the ADT Indication and PIN Indication within the Ipsen Territory.   [ * ] = Certain confidential information contained in this document, marked by brackets, has beenomitted and filed separately with the Securities and Exchange Commission pursuant to Rule 24b-2 ofthe Securities Exchange Act of 1934, as amended.
 
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   4.6. Co-promotion Rights: (i) GTx agrees to grant to Ipsen an exclusive right, unless otherwise agreed by theParties, to co-promote with GTx the Licensed Product in the US in the ADT Indication,which co-promotion right shall be [ * ] in accordance with the terms and conditions ofa co-promotion agreement that shall be negotiated in good faith between the Parties.The Parties agree that the negotiation to enter into a definitive co-promotionagreement shall not be initiated prior to the earlier to occur of either of thefollowing two events: (i) [ * ] or [ * ] of [ * ] of the [ * ] for the [ * ],or (ii) [ * ] days following [ * ] of the [ * ] the [ * ] for the [ * ]. TheParties shall, among others, agree that in the framework of the co-promotion agreementbetween the Parties in the US, Ipsen shall [ * ] in the [ * ] for the [ * ].Additionally, the Parties shall, among others, agree that Ipsen may [ * ] through [ * ]but [ * ] for [ * ] or [ * ] of [ * ] with a [ * ], which [ * ] or [ * ]. (ii) In the event the Parties are unable to enter into a final and bindingco-promotion agreement upon mutually acceptable terms, or should Ipsen decide toopt-out of its right to co-promote with GTx the Licensed Product in the US in the ADTIndication, which right to opt-out shall be exercised (a) within [ * ] days followingthe [ * ] or [ * ] of [ * ] of the [ * ] for the [ * ], or (b) within [ * ]days following the [ * ] of the [ * ] the [ * ] as [ * ] for the [ * ] for the [ * ] inthe event the [ * ] shall [ * ] or [ * ] of [ * ] of the [ * ] for the [ * ] (the“**Opt-Out Election**”), GTx shall pay to Ipsen running royalty payments on Net Sales inthe US (the “**US Net Sales**”) for Licensed Product in the ADT Indication in accordancewith Sections 4.7 and 4.8(ii)(e) hereof.   4.7. GTx’s Payment of Running Royalties to Ipsen on US Net Sales: (i) In the event the Parties fail to enter into a final and binding co-promotionagreement upon mutually acceptable terms, or should Ipsen exercise its Opt-OutElection, GTx acknowledges and agrees that GTx shall pay to Ipsen running royaltypayments in US dollars on US Net Sales of the Licensed Product for the ADT Indication(“**US Royalty Payment**”), until the later to occur of, but in no event earlier than [ *]: (a) the last to expire of a Valid Patent Claim in the US or (b) marketingexclusivity for the ADT Indication in the US as follows:     **Annual US Net Sales** **Royalty** < $ [ * ]  [ * ]%Between $[ * ] and $[ * ]  [ * ]%Between $[ * ] and $[ * ]  [ * ]%Between $[ * ] and $[ * ]  [ * ]%> $[ * ]  [ * ]%The US Royalty Payment due to Ipsen on account of US Net Sales shall be payable byGTx within [ * ] days of the end of each Calendar Quarter for which royalty paymentsare owed, accompanied by a quarterly report providing in reasonable detail inquantity and value an accounting of the US Net Sales made during such CalendarQuarter. Furthermore, Article 11.4 of the License Agreement (i.e., records andaudit rights) shall apply *mutatis mutandis*to Ipsen’s right to verify the accuracyof GTx’s reports for the calculation of US Net Sales of the Licensed Product for theADT Indication.   [ * ] = Certain confidential information contained in this document, marked by brackets, has beenomitted and filed separately with the Securities and Exchange Commission pursuant to Rule 24b-2 ofthe Securities Exchange Act of 1934, as amended.
 
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 (ii) US Net Sales means, consistently applied across the GTx pharmaceutical productline, the gross sales received by GTx, its Affiliates, sub-licensees (including GTx’sco-promotion and/or co-marketing partners) to Third Parties for the Licensed Product inthe ADT Indication in the US, less: **(a)** credits and allowances oradjustments granted to customers on account of rejections,recalls or returns of Licensed Product in the ADT Indicationpreviously sold; **(b)** any customary and reasonabletrade and cash discounts, any customary service fees paid toThird Party wholesalers (which are not Affiliates of GTx), andany credits, rebates and charge backs paid to managed care andgovernment agencies, granted in connection with thedistribution or sale of Licensed Product in the ADTIndication; **(c)** sales, tariff duties and/oruse taxes directly imposed and with reference to particularsales; and **(d)** outbound transportationprepaid or allowed, amounts allowed or credited on returns,export licenses, import duties, value added tax, and prepaidfreight.For the sake of clarity, Sales of Licensed Product in the ADT Indication by andbetween GTx and its Affiliates, sublicensees are not sales to Third Parties andshall be excluded from the US Net Sales calculations for all purposes. Sales ofLicensed Product in the ADT Indication for use in conducting clinical trials ofLicensed Product candidates in order to obtain applicable Regulatory Approval of theLicensed Product shall be excluded from the US Net Sales calculations for allpurposes.   4.8. Ipsen’s Release of PIN Milestone Payments: (i) Within the time-period of Article 4.2(e)(i) of the License Agreement, Ipsen shallretain the right to elect license rights to the Licensed Products for the PIN Indicationagainst payment of the Election Fee and Past Initial Development Expenses set forth inArticle 4.2(e)(iii) of the License Agreement and against payment of Milestone Paymentsprovided in Article 3.2 of the License Agreement that are applicable to the PINIndication.   [ * ] = Certain confidential information contained in this document, marked by brackets, has beenomitted and filed separately with the Securities and Exchange Commission pursuant to Rule 24b-2 ofthe Securities Exchange Act of 1934, as amended.
 
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 (ii) In the event Ipsen intends to exercise its PIN Election, it shall notify GTx of itsintent to do so within the time period prescribed in the License Agreement. If Ipsenshall exercise its Opt-Out Election or the Parties shall then fail to enter into a finaland binding co-promotion agreement upon mutually acceptable terms, then Ipsen shall haveright to elect either (i) to make the payments to GTx on account of the PIN Electioncalculated in accordance with Article 4.2(e)(iii) of the License Agreement (the “PINElection Payments”) or (ii) to have the terms and provisions of Article 4.2(e)(iii) ofthe License Agreement amended in the following particulars (the “**PIN Amendment Right**”),as follows: (a) Ipsen shall be fully, irrevocably and perpetually released by GTxfrom paying the Election Fee set forth in Article 4.2(e)(iii) of theLicense Agreement, (b) Ipsen shall be fully, irrevocably and perpetually released by GTxfrom paying the Past Initial Development Expenses set forth inArticle 4.2(e)(iii) of the License Agreement, (c) Ipsen shall be fully, irrevocably and perpetually released by GTxfrom paying the Joint Initial Development Expenses set forth inArticle 4.2(f)(iii)(2) of the License Agreement, (d) Ipsen shall be fully, irrevocably and perpetually released by GTxfrom all milestone payments set forth in Article 3.2(2), (3), (5) and(8) of the License Agreement related to the PIN Indication that arepending as of the Signature Date:     **Released Milestone Payment** **Released Payment** 2. Achievement of [ * ] €[ * ]3. Filing with the EMEA or with the relevant RegulatoryAgency [ * ] for Regulatory Approval of [ * ] €[ * ]5. Obtaining a Regulatory Approval by the EMEA/EuropeanCommission or by the Regulatory Agency [ * ] of [ * ] €[ * ]8. Obtaining a Regulatory Approval [ * ] for a diagnostictest for [ * ] €[ * ]For the sake of clarity, the pricing milestone payment related to thepricing of toremifene in the PIN Indication listed as payment #7 inArticle 3.2 of the License Agreement shall no longer be due by Ipsenand owed to GTx pursuant to Section 4.3 above.   [ * ] = Certain confidential information contained in this document, marked by brackets, has beenomitted and filed separately with the Securities and Exchange Commission pursuant to Rule 24b-2 ofthe Securities Exchange Act of 1934, as amended.
 
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 (e) If Ipsen shall exercise the PIN Election and Ipsen shall haveexercised its Opt-Out Election as set forth in Section 4.6 above orthe Parties shall have failed to enter into a final and bindingco-promotion agreement upon mutually acceptable terms, and Ipsenshall have elected the PIN Amendment Right described in Section4.8(ii) above, the US Royalty Payment by GTx to Ipsen on US NetSales, as set forth in Section 4.7 above for the ADT Indication,shall be reduced as follows:     **Annual US Net Sales** **Royalty** < $[ * ]  [ * ]%Between $[ * ] and $[ * ]  [ * ]%Between $[ * ] and $[ * ]  [ * ]%Between $[ * ] and $[ * ]  [ * ]%> $[ * ]  [ * ]% (f) For the sake of clarity, at the time of the PIN Election, in lieuof paying the PIN Election Payments to GTx, Ipsen can elect to havethe US Royalty Payment reduced as set forth in subsection (e) above.If the Parties shall also enter into a final and binding co-promotionagreement, Ipsen agrees that it shall then not be entitled to receiveany of the US Royalty Payment set forth in Section 4.7 hereof fromGTx. If Ipsen shall not exercise the PIN Election, the Parties shalldetermine [ * ] the amount of the [ * ] US Royalty Payment that wouldbe appropriate to support a co-promotion agreement that the Partiesmay then negotiate.   4.9. Ipsen’s Right of First Negotiation to GTx-758: (i) GTx shall have the sole responsibility to develop GTx-758, a ER alphaagonist. GTx aims at developing GTx-758 as an alternative treatment to LHRH-a(*e.g.*, leuprolide, triptoreline) in the treatment of prostate cancer with a bettersafety profile. The Parties acknowledge and agree that GTx shall consider Ipsen asits preferential partner for the development, marketing, sale and distribution ofGTx-758 in the Ipsen Territory, and in this regard, GTx hereby grants to Ipsen aright of first negotiation to enter into good faith negotiations with GTx for theperiod hereinafter stated for an exclusive royalty-bearing license to conductCommercialization Activities for GTx-758 in the Ipsen Territory upon such terms andconditions as the Parties may reasonably agree in a definitive agreement. (ii) GTx shall not, either by itself or by or through any of its directors,officers, subsidiary, representative, agent, or otherwise, directly or indirectly,engage in negotiations with any third party relating to the development, marketing,sale and distribution of GTx-758 in the Ipsen Territory until Ipsen shall havefailed to meet any of the time periods set forth in this Section 4.9(iv), includingthe Parties failing to enter into a definitive and binding agreement for anexclusive royalty-bearing license to conduct Commercialization Activities forGTx-758 in the Ipsen Territory or Ipsen shall have waived its right to pursue itsfirst right of negotiation. Notwithstanding the foregoing, nothing herein shallprevent GTx from entering into discussions with a Third Party interested in atransaction for GTx-758 in the GTx Territory.   [ * ] = Certain confidential information contained in this document, marked by brackets, has beenomitted and filed separately with the Securities and Exchange Commission pursuant to Rule 24b-2 ofthe Securities Exchange Act of 1934, as amended.
 
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 (iii) GTx acknowledges that it is its intent to complete a Phase IIbclinical study for GTx-758 assessing efficacy (including [ * ]) and treatmentsafety profile (including [ * ]), with a current estimated completion date for theclinical study in [ * ]. Upon completion of such Phase IIb clinical study, GTxshall furnish to Ipsen the TFL, the draft study report and such additionalinformation and data as Ipsen shall reasonably request at the time of its receiptof the TFL and draft study report for Ipsen to assess GTx-758 and make a decisionto exercise its right of first negotiation. Such additional information and dataavailable to GTx shall include all information developed at that time, includingCMC, preclinical pharmacology, toxicology, IND, clinical data, regulatory agencycorrespondence and market research information, if available. (iv) Within [ * ] days of receipt by Ipsen of the last of the informationand data described in Section 4.9(ii) above, Ipsen shall notify GTx in writing ofits desire to negotiate a definitive agreement for an exclusive royalty-bearinglicense to conduct Commercialization Activities for GTx-758 in the Ipsen Territoryand it will also then furnish GTx with a non binding term sheet setting forth thematerial financial terms of its proposal. If Ipsen so notifies GTx, the Partiesagree to enter into good faith negotiations with the aim to finalize and execute adefinitive agreement for the exclusive royalty-bearing license rights to GTx -758within an additional period that shall in no event exceed [ * ] days from GTx’sreceipt of such notice unless the time-period is extended by mutual agreement ofthe Parties. [ * ], if either [ * ] shall [ * ] to [ * ] of [ * ] to [ * ] for a [* ] within the [ * ] and [ * ] the [ * ] for [ * ] or if [ * ] shall [ * ] to [ * ]and [ * ] a [ * ] within the [ * ], [ * ] shall [ * ] or [ * ] to [ * ] hereunder. (v) [ * ], in the event of a [ * ] of [ * ] prior to [ * ], [ * ]acknowledges and agrees that [ * ], as set forth in [ * ], shall [ * ] if [ * ] orthe [ * ] a [ * ] in [ * ] in [ * ] within [ * ] days of the [ * ] of the [ * ]event that [ * ] to [ * ] described in [ * ] in the [ * ] of the [ * ]: (a) in the [ * ] (as [ * ] defined inthe License Agreement), if the [ * ] and [ * ] that [ * ] that [* ] in [ * ]; (b) in [ * ], if the [ * ] and [ * ]that [ * ] that [ * ] in [ * ]; (c) in [ * ], if the [ * ] and [ * ]that [ * ] that [ * ] in [ * ]. (d) In the event the [ * ] and [ * ]that [ * ] that [ * ] in [ * ] of the [ * ] in [ * ], then [ * ]described in [ * ] shall [ * ] in the [ * ]. For the sake ofclarity, [ * ] under this Section 4.9(v) shall mean [ * ] of the[ * ] in [ * ] listed in [ * ] which [ * ] or [ * ] the [ * ].   [ * ] = Certain confidential information contained in this document, marked by brackets, has beenomitted and filed separately with the Securities and Exchange Commission pursuant to Rule 24b-2 ofthe Securities Exchange Act of 1934, as amended.
 
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**SECTION 5**: **BANKRUPTCY**5.1 In the event of occurrence during the Additional Phase III Study of GTx’s bankruptcy or apetition against GTx under any bankruptcy, insolvency or similar laws not being dismissedwithin the applicable period of time, Ipsen shall have the right to elect to conduct orcontinue the development of the Additional Phase III Study for purposes of, but not limitedto, obtaining and maintaining Regulatory Approvals in the ADT Indication within the IpsenTerritory.5.2 In the event Ipsen exercises its right to terminate the Agreement pursuant to Article 12.4 ofthe License Agreement due to GTx’s bankruptcy or due to a petition against GTx under anybankruptcy, insolvency or similar laws not being dismissed within the applicable period oftime, whether during the Pre-Clinical, Clinical Study, or Post-Marketing Phases, Ipsen will [* ], to the extent permitted under relevant applicable law: (a) [ * ] and [ * ] (whether or not [ * ]); and (b) [ * ] and [ * ].Such [ * ] shall [ * ] as of the effective termination date, or if [ * ], from the [ * ] ona country by country basis or on an Indication by Indication basis. **SECTION 6****:****MISCELLANEOUS**6.1 GTx expressly represents and warrants that no consent is required to be obtained from UTRFand Orion under the GTx Licenses relating to the execution of this First Amendment, includingthe extension of the Territory to be granted to Ipsen. After execution of this FirstAgreement, GTx agrees to assist Ipsen in entering into negotiations with Orion to finalize andexecute an amendment to the Partial Assignment of Amended and Restated License & SupplyAgreement that shall be executed among GTx, Ipsen and Orion pertaining to the manufacture andthe supply of Licensed Product for the extended licensed territory.6.2 Except as modified herein, the terms and conditions of the License Agreement shall remain infull force and effect. In the event of conflict between the terms of the First Amendment andthe License Agreement, the terms of the First Amendment shall govern.6.3 In the event of termination of this First Amendment, the terms of the License Agreement shallbe enforceable as originally executed unless otherwise agreed to by the Parties in writing.6.4 Unless earlier terminated, this First Amendment shall expire or terminate upon the expirationor termination date of the License Agreement.   [ * ] = Certain confidential information contained in this document, marked by brackets, has beenomitted and filed separately with the Securities and Exchange Commission pursuant to Rule 24b-2 ofthe Securities Exchange Act of 1934, as amended.
 
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This First Amendment may be executed in one or more counterparts, each of which is an original butall of which together constitute one and same instrument.     Ipsen Biopharm Ltd. GTx, Inc.       /s/ Christian de la Tour Christian de la Tour /s/ Mitchell S. Steiner, M.D. Name: Mitchell S. Steiner, M.D.  Chairman Title: CEO  Date: 22 March 2010 Date: 03/22/2010     [ * ] = Certain confidential information contained in this document, marked by brackets, has beenomitted and filed separately with the Securities and Exchange Commission pursuant to Rule 24b-2 ofthe Securities Exchange Act of 1934, as amended.
 
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**APPENDIX A****AMENDED EXHIBIT A****Patents & Patent Applications Controlled by GTx, Inc.**