Common use of Manufacturing and Supply Clause in Contracts

Manufacturing and Supply. (a) For a period to be established by the JSC and agreed to by Ambit, such agreement not to be unreasonably withheld, which period is intended to support the orderly completion of the manufacturing technology transfer to Astellas to enable the First Commercial Sale in the Territory, Ambit shall continue to have primary operational responsibility for manufacturing and supply to Astellas of Clinical Trial supplies of the Lead Product (including manufacturing any intermediary or any Licensed Compound or other material contained therein for purpose of such supply), and all other activities in support of preparation of the Chemistry, Manufacturing and Controls sections of any Regulatory Materials or Regulatory Approval necessary to support receipt of Regulatory Approval of the Lead Product in the Joint Development Territory. At and after the end of the foregoing period, Astellas shall have sole responsibility and decision making authority on (i) all manufacturing activities and regulatory activities designed to support preparation of the Chemistry, Manufacturing and Controls sections of any Regulatory Materials or Regulatory Approval, pharmaceutical process development (provided that such process development activities shall be overseen by the JSC), and (ii) manufacturing of Clinical Trial supplies and commercial manufacturing for the Lead Product and each other Product developed or commercialized under this Agreement (including any intermediate of any Licensed Compound or other material contained therein) in the Territory. For clarity, nothing in this Section 3.6.2 or any other term or condition of this Agreement is intended to or shall be construed to limit Astellas’s right and license, as provided in Section 3.1, to make and have made any Product (including any intermediary or any Licensed Compound or other material contained therein) at any time during the Term. (b) Each Party shall have the following obligations with respect to costs and expenses incurred in connection with the manufacturing activities described in clause (a): (i) costs incurred by either Party in pharmaceutical development and the Manufacturing Costs of any quantities of Clinical Trial supplies required to carry out the Development Program shall constitute Development Costs; (ii) the Manufacturing Costs with respect to the commercialization of Co-Promoted Products to be commercialized in the U.S. shall be included in the Annual U.S. Profit/Loss calculation; and (iii) all other Manufacturing Costs with respect to Products (including any intermediate or any Licensed Compound or other material contained therein) incurred by Astellas in support of commercialization of Products for sale in the Territory by or on behalf of Astellas or its Related Parties shall be borne solely by Astellas. (c) Subject to the terms and conditions of this Agreement, until the completion of the manufacturing technology transfer and the occurrence of the date selected by the JSC, promptly upon request of Astellas, Ambit shall use Commercially Reasonable Efforts to supply to Astellas clinical supplies of the Lead Product and placebos (if applicable), in such form and in such quantities as may be required for any activities conducted by Astellas or its Related Parties pursuant to the Development Program for the Lead Product. Such supply shall be pursuant to reasonable forecasting and ordering procedures agreed to by the Parties, consistent with industry standards and intended to cover amounts sufficient for clinical purposes. For clarity, in the event that Astellas procures supplies of the Lead Product that exceed its need for clinical supplies, nothing herein shall prohibit Astellas from using supply secured under this Section 3.6.2(c) for commercial purposes, provided that Astellas complies with all Applicable Law in such use. (d) In the event that Astellas desires Ambit to supply Lead Product specifically intended for commercial use, the Parties shall negotiate in good faith and (if they reach agreement) enter into an appropriate supply agreement (which would include appropriate warranties and indemnities and other commercially reasonable terms typical for such supply agreements). (e) Within a reasonable period to be agreed following the Effective Date, Ambit and Astellas shall cooperate to execute a reasonable quality agreement in a form to be agreed, which shall govern the Parties’ respective responsibilities with respect to quality-related matters applicable to clinical supplies of the Lead Product and placebos (if applicable). (f) On a schedule to be agreed by the JSC as set forth below, Ambit shall, and shall cause its Affiliates to, disclose and make available to Astellas or any of its Related Parties or one or more Third Party manufacturers designated by Astellas all Ambit Know-How and all Ambit Program Know-How and Joint Program Know-How Controlled by Ambit or its Affiliates as of the Effective Date and during the Term that is reasonably necessary for Astellas, its Related Parties or such Third Party manufacturers (as appropriate) to manufacture the Lead Product and the Ambit Compound contained in the Lead Product. The JSC shall determine and agree a schedule to transfer such information from Ambit to Astellas in a smooth transition that minimizes any disruption or delay to the Development Program. Ambit shall provide such reasonable assistance and cooperation to Astellas or its designee(s) to permit Astellas or the designee(s), as applicable, to be qualified by all required Regulatory Authorities as a manufacturer(s) of the Lead Product and the Licensed Compound contained in the Lead Product as soon as practicable. In addition, Ambit shall perform or renew this technology transfer and qualification with respect to any Product at Astellas’s request, and from time to time to the extent that Ambit acquires or develops new data, processes, know-how, or other Information relevant to the manufacture of a Product. The reasonable costs and expenses incurred by Ambit, including without limitation any internal personnel costs, in carrying out such transfer shall be shared as a Development Costs.

Manufacturing and Supply. Prior to the payment by Pyxis for GMP Clinical Supply Product under Section 5.1(c) (a) For a period Reimbursement of CMC and Product Costs), LCB shall Manufacture or have Manufactured the Licensed Compound and Licensed Products on behalf of Pyxis according to be established the quantities and timelines set forth in the Global Development Plan; provided that Pyxis shall have full access to documentation relating to such Manufacturing, including true and complete copies of all LCB CMO agreements, the ability to manage and interact directly with LCB CMOs, and final approval and acceptance of any Licensed Product delivered by the JSC and agreed to by Ambit, such agreement not to be unreasonably withheldLCB, which period is intended shall be, in each case, provided to support Pyxis in English. Following the orderly completion payment by Pyxis for GMP Clinical Supply Product under Section 5.1(c) (Reimbursement of CMC and Production Cost), Pyxis shall have the sole right (and shall solely control, at its discretion) itself or with or through its Affiliates, sublicensees, or other Third Parties, to Manufacture or have Manufactured the Licensed Compound and Licensed Products for Development and Commercialization in the Pyxis Territory. All such Manufacturing shall be at Pyxis’s sole cost and expense. Notwithstanding the foregoing, the Parties agree that LCB shall control the Manufacture or use of the manufacturing technology conjugation methods and materials, linker and payload elements of LCB Background IP (the “LCB Elements”) and LCB Regulatory Information (other than for the Licensed Compound after the GMP Clinical Supply Product); provided that Pyxis shall have oversight over all such Manufacturing and use. Promptly following the payment for Clinical Supply, LCB shall transfer to Astellas to enable the First Commercial Sale in the Territory, Ambit shall continue to have primary operational responsibility for manufacturing and supply to Astellas of Clinical Trial supplies of the Lead Product (including manufacturing any intermediary Pyxis or any Licensed Compound or other material contained therein for purpose of such supply), and all other activities in support of preparation of the Chemistry, Manufacturing and Controls sections of any Regulatory Materials or Regulatory Approval necessary to support receipt of Regulatory Approval of the Lead Product in the Joint Development Territory. At and after the end of the foregoing period, Astellas shall have sole responsibility and decision making authority on its designated CMO (i) all manufacturing activities and regulatory activities designed to support preparation of the Chemistry, Manufacturing and Controls sections of any Regulatory Materials or Regulatory Approval, pharmaceutical process development (provided that such process development activities shall be overseen by the JSC), and (ii) manufacturing of Clinical Trial supplies and commercial manufacturing for the Lead Product and each other Product developed or commercialized under this Agreement (including any intermediate of any Licensed Compound or other material contained therein) in the Territory. For clarity, nothing in this Section 3.6.2 or any other term or condition of this Agreement is intended to or shall be construed to limit Astellas’s right and license, as provided in Section 3.1, to make and have made any Product (including any intermediary or any Licensed Compound or other material contained therein) at any time during the Term. (b) Each Party shall have the following obligations with respect to costs and expenses incurred in connection with the manufacturing activities described in clause (a): (i) costs incurred by either Party in pharmaceutical development and the Manufacturing Costs of any quantities of Clinical Trial supplies required to carry out the Development Program shall constitute Development Costs; (ii) the Manufacturing Costs with respect to the commercialization of CoLCB Product-Promoted Products to be commercialized in the U.S. shall be included in the Annual U.S. Profit/Loss calculation; and (iii) all other Manufacturing Costs with respect to Products (including any intermediate or any Licensed Compound or other material contained therein) incurred by Astellas in support of commercialization of Products for sale in the Territory by or on behalf of Astellas or its Related Parties shall be borne solely by Astellas. (c) Subject to the terms and conditions of this Agreement, until the completion of the manufacturing technology transfer and the occurrence of the date selected by the JSC, promptly upon request of Astellas, Ambit shall use Commercially Reasonable Efforts to supply to Astellas clinical supplies of the Lead Product and placebos (if applicable), in such form and in such quantities as may be required for any activities conducted by Astellas or its Related Parties pursuant to the Development Program for the Lead Product. Such supply shall be pursuant to reasonable forecasting and ordering procedures agreed to by the Parties, consistent with industry standards and intended to cover amounts sufficient for clinical purposes. For clarity, in the event that Astellas procures supplies of the Lead Product that exceed its need for clinical supplies, nothing herein shall prohibit Astellas from using supply secured under this Section 3.6.2(c) for commercial purposes, provided that Astellas complies with all Applicable Law in such use. (d) In the event that Astellas desires Ambit to supply Lead Product specifically intended for commercial use, the Parties shall negotiate in good faith and (if they reach agreement) enter into an appropriate supply agreement (which would include appropriate warranties and indemnities and other commercially reasonable terms typical for such supply agreements). (e) Within a reasonable period to be agreed following the Effective Date, Ambit and Astellas shall cooperate to execute a reasonable quality agreement in a form to be agreed, which shall govern the Parties’ respective responsibilities with respect to quality-related matters applicable to clinical supplies of the Lead Product and placebos (if applicable). (f) On a schedule to be agreed by the JSC as set forth below, Ambit shall, and shall cause its Affiliates to, disclose and make available to Astellas or any of its Related Parties or one or more Third Party manufacturers designated by Astellas all Ambit Specific Know-How and all Ambit Program Knowdata, information, assets and other materials (including starting materials and research materials, DNA, protein sequences, constructs, cell lines, reagents, antibodies and tissue samples), and GMP and shelf-How and Joint Program Know-How life information relating thereto, Controlled by Ambit LCB or its Affiliates as of (or Third Party CMOs, to the Effective Date and during extent LCB has the Term that is reasonably necessary for Astellasright to assign, transfer and/or sublicense such materials under its Related Parties or agreements with such Third Party manufacturers (as appropriate) CMOs; provided, that LCB shall use good-faith efforts to manufacture the Lead Product and the Ambit Compound contained in the Lead Product. The JSC shall determine and agree a schedule to transfer obtain such information from Ambit to Astellas in a smooth transition that minimizes any disruption or delay to the Development Program. Ambit shall provide such reasonable assistance and cooperation to Astellas or its designee(s) to permit Astellas or the designee(sright), as applicable, necessary or reasonably useful for Pyxis to be qualified by all required Regulatory Authorities as a manufacturer(s) of the Lead Product and Manufacture the Licensed Compound contained and Licensed Product, in each case as a whole, in the Lead Product Pyxis Territory, as soon as practicableits sole cost and expense. In addition, Ambit shall perform or renew this technology transfer and qualification with respect to any Product at Astellas’s request, and At the reasonable request of Pyxis from time to time time, LCB shall make its employees and consultants (including personnel of its Affiliates and Third Party CMOs) available to Pyxis and its designees to provide reasonable consultation and technical assistance in order to ensure an orderly transfer of such materials and technology to Pyxis and its designees and to assist Pyxis and its designees in the extent that Ambit acquires Manufacture of the Licensed Compound or develops new data, processes, know-how, or other Information relevant to the manufacture of a Product. The reasonable costs and expenses incurred by Ambit, including without limitation any internal personnel costsLicensed Products, in carrying out such transfer shall be shared each case as a whole. It is expressly acknowledged and agreed by the Parties that Pyxis or its Affiliates may contract directly with Third Party CMOs that Manufacture the Licensed Compounds or Licensed Products, in each case as a whole, on behalf of LCB or its Affiliates, provided however, that the Parties shall cooperate and coordinate in good faith through the JSC as to such matters and LCB shall retain decision making authority in respect of Manufacturing matters concerning the LCB Elements or involving the LCB Regulatory Information, unless such Manufacturing matters are reasonably likely to have a material adverse impact on the safety of the Licensed Products or will delay any material Development Costsactivities of Pyxis, its Affiliates or their Sublicensees, in which case the dispute resolution mechanism in the Agreement will apply.

Manufacturing and Supply. (a) For a period During the term of this Agreement, Immuno shall manufacture for and supply to Haemacure, and Haemacure shall purchase from Immuno, all of Haemacure's requirements of the Product according to Section 3 hereof and the specifications for the Product as of the date of Immuno FDA Approval (as to be established attached to this Agreement at the time of such approval as Exhibit A, the "Specifications"). The parties agree that the Specifications may be modified or revised by mutual agreement of the parties, upon request of the FDA, or upon approval by the JSC FDA of manufacturing improvements, and agreed in the event of any such modification or revision, the Specifications as so modified or revised shall be the Specifications for purposes of this Agreement. (b) The parties agree that the Product for purposes of this Agreement shall include any Volume Variations included in the Immuno PLA (as defined below). "Volume Variations" means 2 ml and 5 ml quantities of Product and such other quantities as Immuno may, in its discretion, manufacture during the Manufacturing Period. Immuno agrees to use commercially reasonable efforts commencing one year following Immuno's commencement of manufacturing hereunder (or, if the parties mutually agree that such will not impede marketing or further regulatory approval of the Product as initially licensed, during such one year period) to cause Volume Variations requested by Ambit, such agreement not Haemacure to be unreasonably withheldapproved by the FDA and. if approved, which period is intended to support be manufactured for sale by Haemacure under the orderly completion terms of this Agreement, provided that (i) Haemacure shall pay all costs and expenses incurred by Immuno in obtaining such FDA approval and in altering the manufacturing technology transfer process to Astellas to enable the First Commercial Sale accommodate such approved Volume Variations (which, for Volume Variations of Product not being sold by Immuno in the Territory, Ambit shall continue to have primary operational responsibility for manufacturing and supply to Astellas of Clinical Trial supplies of the Lead Product (including manufacturing any intermediary or any Licensed Compound or other material contained therein for purpose of such supply), and all other activities in support of preparation of the Chemistry, Manufacturing and Controls sections of any Regulatory Materials or Regulatory Approval necessary to support receipt of Regulatory Approval of the Lead Product in the Joint Development Territory. At and after the end of the foregoing period, Astellas shall have sole responsibility and decision making authority on (i) all manufacturing activities and regulatory activities designed to support preparation of the Chemistry, Manufacturing and Controls sections of any Regulatory Materials or Regulatory Approval, pharmaceutical process development (provided that such process development activities shall be overseen include lost production time caused by the JSCproduction changes), and (ii) manufacturing any Product used for purposes of Clinical Trial supplies and commercial manufacturing for the Lead obtaining such FDA approvals shall be from Haemacure's allocation of Product and each other Product developed or commercialized under this Agreement (including contemplated by Section 3(d) hereof. If Immuno subsequently sells any intermediate of any Licensed Compound or other material contained therein) such Volume Variations in the Territory. For clarity, nothing in this Section 3.6.2 or any other term or condition of this Agreement is intended to or it shall be construed to limit Astellas’s right and license, as provided in Section 3.1, to make and have made any Product (including any intermediary or any Licensed Compound or other material contained therein) at any time during reimburse Haemacure for one-half the Term. (b) Each Party shall have the following obligations with respect to costs and expenses incurred in connection with the manufacturing activities described in clause (a): (i) costs incurred by either Party in pharmaceutical development and the Manufacturing Costs of any quantities of Clinical Trial supplies required to carry out the Development Program shall constitute Development Costs; (ii) the Manufacturing Costs with respect Haemacure has paid Immuno pursuant to the commercialization of Co-Promoted Products preceding sentence. If Immuno is licensed by the FDA to be commercialized in the U.S. shall be included in the Annual U.S. Profit/Loss calculation; sell and (iii) all other Manufacturing Costs with respect to Products (including sells any intermediate or any Licensed Compound or other material contained therein) incurred by Astellas in support of commercialization of Products for sale Volume Variations in the Territory by or on behalf of Astellas or its Related Parties shall be borne solely by Astellas. (c) Subject prior to one year after Immuno FDA Approval, Immuno will also manufacture such Volume Variations for Haemacure under the terms and conditions of this Agreement, until the completion without reimbursement to Immuno for expenses of the manufacturing technology transfer and the occurrence of the date selected by the JSC, promptly upon request of Astellas, Ambit shall use Commercially Reasonable Efforts type described above. Any stability data regarding Volume Variations available to supply Immuno prior to Astellas clinical supplies of the Lead Product and placebos (if applicable), in such form and in such quantities as may be required for any activities conducted by Astellas or its Related Parties pursuant to the Development Program for the Lead Product. Such supply one year after Immuno FDA Licensure shall be pursuant to reasonable forecasting and ordering procedures agreed to by the Parties, consistent with industry standards and intended to cover amounts sufficient for clinical purposes. For clarity, in the event that Astellas procures supplies of the Lead Product that exceed its need for clinical supplies, nothing herein shall prohibit Astellas from using supply secured under this Section 3.6.2(c) for commercial purposes, provided that Astellas complies with all Applicable Law in such use. (d) In the event that Astellas desires Ambit to supply Lead Product specifically intended for commercial use, the Parties shall negotiate in good faith and (if they reach agreement) enter into an appropriate supply agreement (which would include appropriate warranties and indemnities and other commercially reasonable terms typical for such supply agreements). (e) Within a reasonable period to be agreed following the Effective Date, Ambit and Astellas shall cooperate to execute a reasonable quality agreement in a form to be agreed, which shall govern the Parties’ respective responsibilities with respect to quality-related matters applicable to clinical supplies of the Lead Product and placebos (if applicable). (f) On a schedule to be agreed by the JSC as set forth below, Ambit shall, and shall cause its Affiliates to, disclose and make made available to Astellas or any of its Related Parties or one or more Third Party manufacturers designated by Astellas all Ambit Know-How and all Ambit Program Know-How and Joint Program Know-How Controlled by Ambit or its Affiliates as of the Effective Date and during the Term that is reasonably necessary for Astellas, its Related Parties or such Third Party manufacturers (as appropriate) to manufacture the Lead Product and the Ambit Compound contained in the Lead Product. The JSC shall determine and agree a schedule to transfer such information from Ambit to Astellas in a smooth transition that minimizes any disruption or delay to the Development Program. Ambit shall provide such reasonable assistance and cooperation to Astellas or its designee(s) to permit Astellas or the designee(s), as applicable, to be qualified by all required Regulatory Authorities as a manufacturer(s) of the Lead Product and the Licensed Compound contained in the Lead Product as soon as practicable. In addition, Ambit shall perform or renew this technology transfer and qualification with respect to any Product at Astellas’s request, and from time to time to the extent that Ambit acquires or develops new data, processes, know-how, or other Information relevant to the manufacture of a Product. The reasonable costs and expenses incurred by Ambit, including without limitation any internal personnel costs, in carrying out such transfer shall be shared as a Development CostsHaemacure.

Manufacturing and Supply. (a) For a period to be established by the JSC and agreed to by Ambit, such agreement not to be unreasonably withheld, which period is intended to support the orderly completion of the manufacturing technology transfer to Astellas to enable the First Commercial Sale in the Territory, Ambit shall continue to have primary operational responsibility for manufacturing and supply to Astellas of Clinical Trial supplies of the Lead Product (including manufacturing any intermediary or any Licensed Compound or other material contained therein for purpose of such supply), and all other activities in support of preparation of the Chemistry, Manufacturing and Controls sections of any Regulatory Materials or Regulatory Approval necessary to support receipt of Regulatory Approval of the Lead Product in the Joint Development Territory. At and after the end of the foregoing period, Astellas shall have sole responsibility and decision making authority on (i) all manufacturing activities and regulatory activities designed to support preparation of the Chemistry, Manufacturing and Controls sections of any Regulatory Materials or Regulatory Approval, pharmaceutical process development (provided that such process development activities shall be overseen by the JSC), and (ii) manufacturing of Clinical Trial supplies and commercial manufacturing for the Lead Product and each other Product developed or commercialized under this Agreement (including any intermediate of any Licensed Compound or other material contained therein) in the Territory. For clarity, nothing in this Section 3.6.2 or any other term or condition of this Agreement is intended to or shall be construed to limit Astellas’s right and license, as provided in Section 3.1, to make and have made any Product (including any intermediary or any Licensed Compound or other material contained therein) at any time during the Term. (b) Each Party shall have the following obligations with respect to costs and expenses incurred in connection with the manufacturing activities described in clause (a): (i) costs incurred by either Party in pharmaceutical development and the Manufacturing Costs of any quantities of Clinical Trial supplies required to carry out the Development Program shall constitute Development Costs; (ii) the Manufacturing Costs with respect to the commercialization of Co-Promoted Products to be commercialized in the U.S. shall be included in the Annual U.S. Profit/Loss calculation; and (iii) all other Manufacturing Costs with respect to Products (including any intermediate or any Licensed Compound or other material contained therein) incurred by Astellas in support of commercialization of Products for sale in the Territory by or on behalf of Astellas or its Related Parties shall be borne solely by Astellas. (c) Subject to the terms and conditions of this Agreement, until Merck shall have the completion of exclusive right after the manufacturing technology transfer Development Transfer Date to manufacture the Licensed Products and corresponding Compound for the occurrence of the date Field itself or through one or more Third Parties selected by the JSC, promptly upon request of Astellas, Ambit shall use Commercially Reasonable Efforts to supply to Astellas clinical supplies of the Lead Product and placebos (if applicable), in such form and in such quantities as may be required for any activities conducted by Astellas or its Related Parties pursuant to the Development Program for the Lead Product. Such supply shall be pursuant to reasonable forecasting and ordering procedures agreed to by the Parties, consistent with industry standards and intended to cover amounts sufficient for clinical purposesMerck. For clarity, the foregoing shall not be construed to preclude Lpath’s (or its Affiliate’s or a Third Party licensee’s) manufacture of Ocular Products and other products outside the Field, and corresponding Compounds for such Ocular Products and other Products outside the Field. Starting from the Development Transfer Date, Lpath shall for a period of up to *** make its employees that are knowledgeable on the manufacture of the Compound (solely as such manufacture relates to Licensed Products in the event that Astellas procures supplies of and for the Lead Product that exceed its need for clinical supplies, nothing herein shall prohibit Astellas from using supply secured under this Section 3.6.2(cField) for commercial purposes, provided that Astellas complies with all Applicable Law in such use. (d) In the event that Astellas desires Ambit to supply Lead Product specifically intended for commercial use, the Parties shall negotiate in good faith and (if they reach agreement) enter into an appropriate supply agreement (which would include appropriate warranties and indemnities and other commercially reasonable terms typical for such supply agreements). (e) Within a reasonable period to be agreed following the Effective Date, Ambit and Astellas shall cooperate to execute a reasonable quality agreement in a form to be agreed, which shall govern the Parties’ respective responsibilities with respect to quality-related matters applicable to clinical supplies of the Lead Product and placebos (if applicable). (f) On a schedule to be agreed by the JSC as set forth below, Ambit shall, and shall cause its Affiliates to, disclose and make available to Astellas or any of its Related Parties or one or more Third Party manufacturers designated by Astellas all Ambit Know-How and all Ambit Program Know-How and Joint Program Know-How Controlled by Ambit or its Affiliates as of the Effective Date and during the Term that is reasonably necessary for Astellas, its Related Parties or such Third Party manufacturers (as appropriate) to manufacture the Lead Product and the Ambit Compound contained in the Lead Product. The JSC shall determine and agree a schedule to transfer such information from Ambit to Astellas in a smooth transition that minimizes any disruption or delay to the Development Program. Ambit shall provide such reasonable assistance and cooperation to Astellas or its designee(s) to permit Astellas or the designee(s), as applicable, to be qualified by all required Regulatory Authorities as a manufacturer(s) of the Lead Product and the Licensed Compound contained in the Lead Product as soon as practicable. In additionreasonably available to Merck for scientific and technical explanations, Ambit shall perform or renew this technology transfer advice and qualification with respect to any Product at Astellas’s requeston-site support, and from time to time to the extent that Ambit acquires or develops new datamay reasonably be required by Merck, processes, know-how, or other Information relevant relating to the manufacture of a Productthe Compound (solely as such Development and registration relate to Licensed Products in the and for the Field) and the Licensed Products and the Manufacturing Technology Transfer (the “Manufacturing Support”). The reasonable costs Merck shall reimburse Lpath for Lpath’s Out-of-Pocket Expenses incurred in providing the Manufacturing Support, subject to Lpath providing Merck with documented evidence of such Expenses having been incurred, and expenses incurred by Ambit, including without limitation any internal personnel costs, the limitations applicable to Development Support set forth in carrying out Section 3.10 shall likewise apply to the Manufacturing Support such transfer that the Manufacturing Support shall be shared deemed to be included in the Development Support as a Development Coststhe same is limited in Section 3.10. ***CONFIDENTIAL PORTIONS OF THIS AGREEMENT HAVE BEEN OMITTED AND FILED SEPARATELY WITH THE COMMISSION PURSUANT TO A REQUEST FOR CONFIDENTIAL TREATMENT.

Manufacturing and Supply. (a) For a period to Crinetics shall be established by responsible for manufacturing or having manufactured the JSC Licensed Product in bulk and agreed to by Ambit, such agreement not to be unreasonably withheldunpackaged form, which period is intended to support may be coated or uncoated, or packaged in bottles for use by SKK in the orderly completion of the manufacturing technology transfer to Astellas to enable the First Commercial Sale Field in the Territory, Ambit . SKK shall continue to have primary operational responsibility for manufacturing and supply to Astellas of Clinical Trial supplies of the Lead specify if Licensed Product (including manufacturing any intermediary or any Licensed Compound or other material contained therein for purpose of such supply), and all other activities in support of preparation of the Chemistry, Manufacturing and Controls sections of any Regulatory Materials or Regulatory Approval necessary to support receipt of Regulatory Approval of the Lead Product in the Joint Development Territory. At and after the end of the foregoing period, Astellas shall have sole responsibility and decision making authority on will be provided by Crinetics (i) all manufacturing activities and regulatory activities designed to support preparation of the Chemistry, Manufacturing and Controls sections of any Regulatory Materials as coated or Regulatory Approval, pharmaceutical process development (provided that such process development activities shall be overseen by the JSC), uncoated tablets and (ii) in bulk and unpackaged form or packaged in bottles. Such specification shall be provided by SKK prior to commencement of manufacturing of Clinical Trial supplies and commercial manufacturing for the Lead Product and each other Product developed or commercialized activities under this Agreement (including for supply to SKK and in any intermediate of event promptly after Crinetics’s request for instruction. SKK shall be responsible for any further manufacturing, packaging and labeling such Licensed Compound Product by itself or other material contained therein) its subcontractors for use by SKK in the Field in the Territory. For clarity, nothing in this Section 3.6.2 or any other term or condition of this Agreement is intended to or shall be construed to limit Astellas’s right and license, as provided in Section 3.1, to make and have made any Product (including any intermediary or any Licensed Compound or other material contained therein) at any time during the Term. (b) Each Party shall have the following obligations with respect to costs and expenses incurred in connection with the manufacturing activities described in clause (a): (i) costs incurred by either Party in pharmaceutical development and the Manufacturing Costs of any quantities of Clinical Trial supplies required to carry out the Development Program shall constitute Development Costs; (ii) the Manufacturing Costs with respect to the commercialization of Co-Promoted Products to be commercialized in the U.S. shall be included in the Annual U.S. Profit/Loss calculation; and (iii) all other Manufacturing Costs with respect to Products (including any intermediate or any Licensed Compound or other material contained therein) incurred by Astellas in support of commercialization of Products for sale in the Territory by or on behalf of Astellas or its Related Parties shall be borne solely by Astellas[***]. (c) [***]. (d) Subject to Section 6.1(e) and the terms of the Manufacturing and Supply Agreement and the Clinical Supply Agreement to be entered into between the Parties in accordance with Sections 6.2 and 6.3, SKK shall obtain from Crinetics and Crinetics shall use Commercially Reasonable Efforts to supply, SKK’s requirements of the Licensed Product (the form as specified in accordance with Section 6.1(a)) for SKK's Development of Licensed Product in accordance with the Development Plan and Commercialization of the Licensed Product, in each case in the Field in the Territory. Crinetics may have the Licensed Product manufactured and tested by one or more Third Parties pursuant to agreements entered into between Crinetics and such Third Party (each such Third Party, a “CMO” and each such agreement, a “CMO Supply Agreement” ). In addition, Crinetics shall provide to SKK the scope of remedy and details of the remedy, prior to agreeing on such CMO Supply Agreement. [***]. (e) If Crinetics decides to cease manufacturing or having manufactured Licensed Product for delivery to SKK pursuant to Section 6.1(d), Crinetics shall give two (2) year prior written notice thereof to SKK. Upon receiving such prior notice, SKK shall be entitled, at its sole discretion, to request that Crinetics’s CMOs manufacture and test the Licensed Product directly for SKK, or SKK may engage other Third Parties to manufacture and test the Licensed Product. (f) [***]. (g) If, pursuant to Section 6.1(e), SKK will have manufactured Licensed Product in the Territory, Crinetics shall grant SKK a non-exclusive, sublicensable license with the right to grant sublicenses solely in accordance with Section 2.2 without any requirement to pay additional royalty, under the Licensed IP, to have manufactured the Licensed Product for use in the Field in the Territory. (h) If, after SKK receives from Crinetics a notice cease manufacturing or having manufactured Licensed Product set forth in Section 6.1(e), SKK decides not to exercise its right to have manufactured the Licensed Product, Crinetics and SKK shall discuss in good faith how to ensure that the Licensed Product continues to be supplied to SKK under the terms and conditions of this Agreement, until the completion of the manufacturing technology transfer Manufacturing and Supply Agreement and the occurrence of the date selected by the JSC, promptly upon request of Astellas, Ambit shall use Commercially Reasonable Efforts to supply to Astellas clinical supplies of the Lead Product and placebos (if applicable), in such form and in such quantities as may be required for any activities conducted by Astellas or its Related Parties pursuant to the Development Program for the Lead Product. Such supply shall be pursuant to reasonable forecasting and ordering procedures agreed to by the Parties, consistent with industry standards and intended to cover amounts sufficient for clinical purposes. For clarity, in the event that Astellas procures supplies of the Lead Product that exceed its need for clinical supplies, nothing herein shall prohibit Astellas from using supply secured under this Section 3.6.2(c) for commercial purposes, provided that Astellas complies with all Applicable Law in such use. (d) In the event that Astellas desires Ambit to supply Lead Product specifically intended for commercial use, the Parties shall negotiate in good faith and (if they reach agreement) enter into an appropriate supply agreement (which would include appropriate warranties and indemnities and other commercially reasonable terms typical for such supply agreements). (e) Within a reasonable period to be agreed following the Effective Date, Ambit and Astellas shall cooperate to execute a reasonable quality agreement in a form to be agreed, which shall govern the Parties’ respective responsibilities with respect to quality-related matters applicable to clinical supplies of the Lead Product and placebos (if applicable). (f) On a schedule to be agreed by the JSC as set forth below, Ambit shall, and shall cause its Affiliates to, disclose and make available to Astellas or any of its Related Parties or one or more Third Party manufacturers designated by Astellas all Ambit Know-How and all Ambit Program Know-How and Joint Program Know-How Controlled by Ambit or its Affiliates as of the Effective Date and during the Term Clinical Supply Agreement that is reasonably necessary for Astellas, its Related Parties or such Third Party manufacturers (as appropriate) to manufacture the Lead Product and the Ambit Compound contained then in the Lead Product. The JSC shall determine and agree a schedule to transfer such information from Ambit to Astellas in a smooth transition that minimizes any disruption or delay to the Development Program. Ambit shall provide such reasonable assistance and cooperation to Astellas or its designee(s) to permit Astellas or the designee(s), as applicable, to be qualified by all required Regulatory Authorities as a manufacturer(s) of the Lead Product and the Licensed Compound contained in the Lead Product as soon as practicable. In addition, Ambit shall perform or renew this technology transfer and qualification with respect to any Product at Astellas’s request, and from time to time to the extent that Ambit acquires or develops new data, processes, know-how, or other Information relevant to the manufacture of a Product. The reasonable costs and expenses incurred by Ambit, including without limitation any internal personnel costs, in carrying out such transfer shall be shared as a Development Costseffect.

Manufacturing and Supply. (a) For a period to be established by the JSC and agreed to by Ambit, such agreement not to be unreasonably withheld, which period is intended to support the orderly completion of the manufacturing technology transfer to Astellas to enable the First Commercial Sale in the Territory, Ambit shall continue to have primary operational responsibility for manufacturing and supply to Astellas of Clinical Trial supplies of the Lead Product (including manufacturing any intermediary or any Licensed Compound or other material contained therein for purpose of such supply), and all other activities in support of preparation of the Chemistry, Manufacturing and Controls sections of any Regulatory Materials or Regulatory Approval necessary to support receipt of Regulatory Approval of the Lead Product in the Joint Development Territory. At and after the end of the foregoing period, Astellas shall have sole responsibility and decision making authority on (i) all manufacturing activities and regulatory activities designed to support preparation of the Chemistry, Manufacturing and Controls sections of any Regulatory Materials or Regulatory Approval, pharmaceutical process development (provided that such process development activities shall be overseen by the JSC), and (ii) manufacturing of Clinical Trial supplies and commercial manufacturing for the Lead Product and each other Product developed or commercialized under this Agreement (including any intermediate of any Licensed Compound or other material contained therein) in the Territory. For clarity, nothing in this Section 3.6.2 or any other term or condition of this Agreement is intended to or shall be construed to limit Astellas’s right and license, as provided in Section 3.1, to make and have made any Product (including any intermediary or any Licensed Compound or other material contained therein) at any time during the Term. (b) Each Party shall have the following obligations with respect to costs and expenses incurred in connection with the manufacturing activities described in clause (a): (i) costs incurred by either Party in pharmaceutical development and the Manufacturing Costs of any quantities of Clinical Trial supplies required to carry out the Development Program shall constitute Development Costs; (ii) the Manufacturing Costs with respect to the commercialization of Co-Promoted Products to be commercialized in the U.S. shall be included in the Annual U.S. Profit/Loss calculation; and (iii) all other Manufacturing Costs with respect to Products (including any intermediate or any Licensed Compound or other material contained therein) incurred by Astellas in support of commercialization of Products for sale in the Territory by or on behalf of Astellas or its Related Parties shall be borne solely by Astellas. (c) 3.3.1 Subject to the terms and conditions of this AgreementSection 3.3, until EPIZYME shall be responsible for the completion Manufacture and supply of Licensed Compounds and Licensed Products (including the active pharmaceutical ingredients thereof) for use for Development and Commercialization purposes by EPIZYME in the EPIZYME Territory and (unless EISAI elects to undertake such Manufacture and supply as set forth in Section 3.3.2) by EISAI in the EISAI Territory during the Term. 3.3.2 EISAI shall have the right, but not the obligation, to elect to itself Manufacture and supply or have Manufactured and supplied Licensed Compounds and Licensed Products for use for Japan-Specific Development Activities and Commercialization purposes by EISAI in the EISAI Territory during the Term upon written notice to EPIZYME of such election, provided that if such notice is provided after the date that is [**] prior to the projected date (as reasonably determined by EISAI) of the manufacturing technology transfer and first filing of an NDA for a Licensed Product in the occurrence of the date selected by the JSCEISAI Territory, promptly upon request of Astellas, Ambit shall use Commercially Reasonable Efforts to supply to Astellas clinical supplies of the Lead Product and placebos then: (if applicable), in such form and in such quantities as may be required for any activities conducted by Astellas or its Related Parties pursuant to the Development Program for the Lead Product. Such supply shall be pursuant to reasonable forecasting and ordering procedures i) unless otherwise agreed to by the Parties, consistent with industry standards EISAI shall continue to purchase from EPIZYME its requirements of Licensed Compounds and intended to cover amounts sufficient Licensed Products for clinical purposes. For clarity, in the event that Astellas procures supplies a period of the Lead Product that exceed its need for clinical supplies, nothing herein shall prohibit Astellas from using supply secured under this Section 3.6.2(c) for commercial purposes, provided that Astellas complies with all Applicable Law in [**] following such use. notice date (d) In the event that Astellas desires Ambit unless EPIZYME fails to supply Lead Product specifically intended for commercial use, such requirements of Licensed Compounds and Licensed Products as required under Section 3.3 and the Parties shall negotiate in good faith supply agreement(s) contemplated thereby); and (if they reach agreementii) enter into an appropriate supply agreement (which would include appropriate warranties and indemnities and other commercially reasonable terms typical EISAI shall reimburse EPIZYME for such supply agreements). (e) Within a reasonable period to be agreed following the Effective Date, Ambit and Astellas shall cooperate to execute a reasonable quality agreement in a form to be agreed, which shall govern the Parties’ respective responsibilities with respect to qualityall EISAI Territory-related matters applicable to clinical supplies of the Lead Product and placebos (if applicable). (f) On a schedule to be agreed by the JSC as set forth below, Ambit shall, and shall cause its Affiliates to, disclose and make available to Astellas or any of its Related Parties or one or more Third Party manufacturers designated by Astellas all Ambit Know-How and all Ambit Program Know-How and Joint Program Know-How Controlled by Ambit or its Affiliates as of the Effective Date and during the Term that is reasonably necessary for Astellas, its Related Parties or such Third Party manufacturers (as appropriate) to manufacture the Lead Product and the Ambit Compound contained in the Lead Product. The JSC shall determine and agree a schedule to transfer such information from Ambit to Astellas in a smooth transition that minimizes any disruption or delay to the Development Program. Ambit shall provide such reasonable assistance and cooperation to Astellas or its designee(s) to permit Astellas or the designee(s), as applicable, to be qualified by all required Regulatory Authorities as a manufacturer(s) of the Lead Product and the Licensed Compound contained in the Lead Product as soon as practicable. In addition, Ambit shall perform or renew this technology transfer and qualification with respect to any Product at Astellas’s request, and from time to time to the extent that Ambit acquires or develops new data, processes, know-how, or other Information relevant to the manufacture of a Product. The reasonable specific costs and expenses incurred by AmbitEPIZYME attributable to the Manufacture and supply of Licensed Compounds and Licensed Products to EISAI and not recovered through transfer pricing amounts paid by EISAI to EPIZYME prior to such transition (such as, including without limitation by way of example, costs incurred in meeting any internal personnel regulatory requirements relating to the EISAI Territory and translation costs, in carrying out such transfer shall be shared as a Development Costs).

Manufacturing and Supply. (a) For a period to be established by the JSC and agreed to by Ambit, such agreement not to be unreasonably withheld, which period is intended to support the orderly completion of the manufacturing technology transfer to Astellas to enable the First Commercial Sale in the Territory, Ambit The LICENSOR shall continue to have primary operational responsibility for manufacturing use Commercially Reasonable Efforts to conduct, at its own cost, the drug substance and supply to Astellas of Clinical Trial supplies drug product Development and Manufacturing of the Lead Existing Product (including manufacturing any intermediary or any and of the Licensed Compound or other material contained therein for purpose of such supply), and all other activities use in support of preparation of the Chemistry, Manufacturing and Controls sections of any Regulatory Materials or Regulatory Approval necessary to support receipt of Regulatory Approval of the Lead Existing Product in accordance with the Joint Technical Development Territory. At Plan and after the end of the foregoing period, Astellas shall have sole responsibility and decision making authority on (i) all manufacturing activities and regulatory activities designed to support preparation of the Chemistry, Manufacturing and Controls sections of any Regulatory Materials or Regulatory Approval, pharmaceutical process development (provided that such process development activities shall be overseen by the JSC), and (ii) manufacturing of Clinical Trial supplies and commercial manufacturing for the Lead Product and each other Product developed or commercialized under this Agreement (including any intermediate of any Licensed Compound or other material contained therein) in the Territory. For clarity, nothing in this Section 3.6.2 or any other term or condition of this Agreement is intended to or shall be construed to limit Astellas’s right and license, as provided in Section 3.1, to make and have made any Product (including any intermediary or any Licensed Compound or other material contained therein) at any time during the Termapplicable laws. (b) Each Party shall have Subject to anything stated to the following obligations with respect to costs and expenses incurred in connection with the manufacturing activities described in clause (a): (i) costs incurred by either Party in pharmaceutical development and contrary, the Manufacturing Costs and supply of any quantities of Clinical Trial supplies required to carry out the Development Program shall constitute Development Costs; (ii) the Manufacturing Costs with respect to the commercialization of Co-Promoted Licensed Compound and Licensed Products to be commercialized for Commercialization in the U.S. Licensed Territory, including partner selection, shall be included transferred to LICENSEE in due course, and, upon such transfer, it shall be the right and responsibility of LICENSEE to conduct and control Manufacturing and supplies of Licensed Compound and Licensed Products in the Annual U.S. Profit/Loss calculation; and (iii) Licensed Territory, including all other Manufacturing Costs with respect to Products (including any intermediate or any Licensed Compound or other material contained therein) incurred by Astellas in support of commercialization of Products for sale in the Territory by or on behalf of Astellas or necessary related authorizations, at its Related Parties shall be borne solely by Astellasown cost. (c) Subject The Parties shall agree, within sixty (60) days of the Effective Date, on a Manufacturing strategy encompassing, without limitation, the following matters, such discussions and agreement to be conducted and achieved in the terms JTC (the Manufacturing Strategy): (i) To assure that LICENSEE assumes control and conditions takes responsibility for Manufacturing and supply of this AgreementLicensed Compound and Licensed Products, including partner selection, for Commercialization within the Licensed Territory; (ii) To assure that the contributions of both Parties meet all quality and safety related requirements to obtain regulatory approvals and reimbursement by local health insurance schemes in the Licensed Territory; (iii) To assure that the Manufacturing of Licensed Products meet the quantity and quality requirements in accordance with LICENSEE's business plans for the exploitation of Licensed Products under the License; (iv) To assure LICENSOR's Manufacturing activities until the completion of the manufacturing technology transfer and the occurrence of the date selected Manufacturing responsibility to either LICENSEE or CMOs under LICENSEE's control; (v) To assure the transfer of LICENSOR's documented Know-How within the LICENSOR Product Technology to LICENSEE or CMOs controlled by LICENSEE in case of a transfer of Manufacturing responsibilities to such recipients; (vi) To discuss potential opportunities for the JSC, promptly upon request involvement of Astellas, Ambit shall use Commercially Reasonable Efforts to supply to Astellas clinical supplies LICENSEE or its CMOs in the Manufacturing of the Lead Licensed Product and placebos (if applicable), in such form and in such quantities as may be required for any activities conducted sales by Astellas LICENSOR or its Related Parties pursuant Affiliates or sub-licensees outside the Licensed Territory; and (vii) any other matter reasonably necessary or helpful to the Development Program for the Lead Product. Such supply shall be pursuant to reasonable forecasting permit and ordering procedures agreed to by the Partiesfacilitate best in class, consistent with industry standards professional and intended to cover amounts sufficient for clinical purposes. For clarity, cost-effective Manufacturing of Licensed Compound and Licensed Products in the event that Astellas procures supplies Licensed Territory throughout the Term, including without limitation the critical terms of a Supply Agreement to be negotiated and agreed in accordance with the Lead Product that exceed its need for clinical supplies, nothing herein shall prohibit Astellas from using supply secured under this Section 3.6.2(c) for commercial purposes, provided that Astellas complies with all Applicable Law in such useimmediately below paragraph (d). (d) In Within one hundred twenty (120) days of the event that Astellas desires Ambit to supply Lead Product specifically intended for commercial useEffective Date, the Parties shall will negotiate in good faith and (if they reach agreement) enter into an appropriate execute in line with the Manufacturing Strategy a manufacturing and supply agreement regulating the details of Manufacturing and supply of Licensed Compound and Licensed Products (which would include appropriate warranties and indemnities and other commercially reasonable terms typical for such supply agreementsthe Supply Agreement) as well as a respective quality agreement (the Quality Agreement). (e) Within a reasonable period In so far as is necessary to ensure the transfer of Manufacturing of Licensed Compound and Licensed Product, LICENSEE shall be agreed following given access to the Effective Date, Ambit and Astellas shall cooperate to execute a reasonable quality agreement in a form to be agreed, which shall govern the Parties’ respective responsibilities with respect to quality-related matters applicable to clinical supplies of the Lead LICENSOR Product and placebos (if applicable)Technology. (f) On In case LICENSOR will supply products to LICENSEE and the Parties have failed to enter into a schedule Supply Agreement, supplies will be subject to be agreed by the JSC as set forth below, Ambit shallcustomary supply agreement terms, and shall cause its Affiliates to, disclose and make available to Astellas or any of its Related Parties or one or more Third Party manufacturers designated by Astellas all Ambit Know-How and all Ambit Program Know-How and Joint Program Know-How Controlled by Ambit or its Affiliates as of the Effective Date and during the Term that is reasonably necessary for Astellas, its Related Parties or such Third Party manufacturers (as appropriate) to manufacture the Lead Product and the Ambit Compound contained in the Lead Product. The JSC shall determine and agree a schedule to transfer such information from Ambit to Astellas in a smooth transition that minimizes any disruption or delay to the Development Program. Ambit shall provide such reasonable assistance and cooperation to Astellas or its designee(s) to permit Astellas or the designee(s), as applicable, to be qualified by all required Regulatory Authorities as a manufacturer(s) of the Lead Product and the Licensed Compound contained in the Lead Product as soon as practicable. In addition, Ambit shall perform or renew this technology transfer and qualification with respect to any Product at Astellas’s request, and from time to time to the extent that Ambit acquires or develops new data, processes, know-how, or other Information relevant to the manufacture of a Product. The reasonable costs and expenses incurred by Ambit, including without limitation any internal personnel costs, in carrying out such transfer supplies shall be shared as provided at a Development Costssupply price of COGS plus [***]%.