Exhibit 10.39 [..**..] = Certain Confidential Information Contained
in this Document, Marked by Brackets, Has Been
Omitted and Filed Separately with the Securities
and Exchange Commission Pursuant to rule 24b-2
of the Securities Exchange Act of 1934, as Amended. AMENDED AND RESTATED
COLLABORATION AND OPTION AGREEMENT by and between Myogen, Inc. and Novartis Institutes for BioMedical Research, Inc. [..**..] Confidential Treatment Requested
AMENDED AND RESTATED
COLLABORATION AND OPTION AGREEMENT This Amended and Restated Collaboration and Option Agreement (this " Agreement" ) is made this 7 th day of July, 2006 (the " Restatement Date" ) by and between Myogen, Inc. (" Myogen" ), a Delaware corporation with principal offices at 7575 W. 103 rd Avenue, Westminster, Colorado 80021, and Novartis Institutes for BioMedical Research, Inc. (" NIBRI" ), a Delaware corporation with principal offices at 400 Technology Square, Cambridge,
Massachusetts 02139. Introduction WHEREAS, Myogen and NIBRI are parties to that certain Collaboration and Option Agreement (the " Original Agreement" ) dated October 8, 2003 (the " Effective Date" ) pursuant to which the parties have agreed to collaborate on projects to identify and validate compounds which act on Myogen Targets (as defined below), and thereafter for NIBRI and its Affiliates to have the option to develop, market and sell certain of those compounds as drugs upon the terms set forth in the Original Agreement and in the form of License Agreement (as defined therein); WHEREAS, the parties amended the Original Agreement pursuant to that certain Amendment to Collaboration and Option Agreement (the " Amendment" and together with the Original Agreement, the " Amended Agreement" ) dated May 23, 2005 (the " Amendment Date" ) pursuant to which the parties have agreed to add Myogen' s intellectual property on histone deacetylase protein (" HDAC" ) inhibitors for heart muscle disease to the existing collaboration and to accommodate conducting a collaborative project relating to the use of HDAC inhibitors in the treatment of heart muscle disease; and WHEREAS, NIBRI wishes to exercise its unilateral option to extend the collaboration for an additional two (2) year period and the parties wish to further amend and restate the Amended Agreement, effective as of the Effective Date, and accept the rights and covenants herein in lieu of their rights and covenants under the Amended Agreement to provide for, among other things, certain clarifications regarding the limitation of certain payments and rights to the Field (as defined herein); [..**..] Confidential Treatment Requested
NOW THEREFORE, in consideration of the mutual covenants set forth in this Agreement, and other good and valuable consideration, the parties agree as follows: ARTICLE I
Definitions 1.1. " Active Compound" shall mean any chemical compound that has (i) a specific, desired therapeutic action on, (ii) a specific, desired interaction on, or (iii) a specific, desired modulation of a Myogen Target or a Collaboration Target, and any and all compounds having the same Active Moiety as such Active Compound, whether a small molecule, protein or antibody. 1.2. " Active Moiety" shall have the meaning assigned to that term under 21 CFR 314.108(a), as such regulation is in effect on the Effective Date; namely: " the molecule or ion excluding those appended portions of the molecule that cause the drug to be an ester, salt (including a salt with hydrogen or coordination bonds), or other noncovalent derivative (such as a complex, a chelate or clathrate) of the molecule, responsible for the physiological or pharmacological action of the drug substance." 1.3. " Affiliate" shall mean, with respect to any Person, any other Person that, directly or indirectly, by itself or through one or more intermediaries, controls, or is controlled by, or is under common control with, such Person. The term " control" means the possession, direct or indirect, of the power to direct or cause the direction of the management and policies of a Person, whether through the ownership of voting securities, by contract or otherwise. Control will be presumed if one Person owns, either of record or beneficially, at least 50% of the voting stock of any other Person. Such other relationship as in fact results in actual control over the management, business, and affairs of a Person shall also be deemed to constitute control; provided , however , that no Person shall be deemed to exercise control over another Person solely because the latter relies on the former for a majority of its business. A Person will be deemed an Affiliate only so long as such ownership or control relationship continues. In the case of NIBRI, " Affiliates" shall also expressly be deemed to include the Novartis Institute for Functional [..**..] Confidential Treatment Requested
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Genomics, Inc., and the Friedrich Miescher Institute for BioMedical Research and their respective Affiliates. 1.4. " Collaboration Compound" shall mean any chemical compound utilized by either party in the course of the Research Program, including Collaboration HDAC Inhibitor Compounds, but explicitly excluding all NIBRI Compounds, NIBRI HDAC Inhibitor Compounds and Myogen Compounds. 1.5. " Collaboration HDAC Inhibitor Compound" shall mean any HDAC Inhibitor Compound other than a NIBRI HDAC Inhibitor Compound or a Myogen Compound which is an HDAC Inhibitor Compound, including, without limitation, all derivatives and analogs of Collaboration HDAC Inhibitor Compounds and all derivatives and analogs of NIBRI HDAC Inhibitor Compounds that do not fall within the definition of NIBRI HDAC Inhibitor Compounds set forth herein. In no event, however, shall any In-Licensed NIBRI HDAC Inhibitor Compound be a Collaboration HDAC Inhibitor Compound. 1.6. " Collaboration Target" shall mean any Target identified for the first time in the course of the Research Program or a Development Program. 1.7. " Collaboration Technology" shall mean any Technology that relates to Collaboration Targets and/or Collaboration Compounds. 1.8. " Compound" shall mean any Myogen Compound, NIBRI Compound, or Collaboration Compound and other compounds having the same Active Moiety as a Myogen Compound, NIBRI Compound, or Collaboration Compound. 1.9. " Controlled" shall mean, with respect to a Target or Technology, the legal authority or right of a party hereto to grant a license or sublicense of intellectual property rights to another party hereto, or to otherwise disclose proprietary or trade secret information to such other party, without breaching the terms of any agreement with a Third Party, infringing upon the intellectual property rights of a Third Party, or misappropriating the proprietary or trade secret information of a Third Party. A party shall be deemed to " Control" a Compound, including determining the relative rights of the parties to intellectual property under Section 8.1, if (i) that party contributed or otherwise made available to the collaboration such Compound or [..**..] Confidential Treatment Requested
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(ii) such Compound is an analog, derivative, enantiomer, racemate, isomer, diastereomer, active metabolite or pharmaceutically acceptable salt or complex of a Compound contributed by such party. 1.10. " Critical Issues" shall have the meaning set forth in Section 2.8.2 hereof. 1.11. " Development Candidate" shall mean a NIBRI Compound, Myogen Compound or Collaboration Compound, and derivatives thereof, together with the Myogen Target or Collaboration Target on which it has therapeutic action, as to which NIBRI exercises its Option pursuant to Section 4.4 of this Agreement. 1.12. " Development Program" shall mean activities associated with development of a Development Candidate as specified in the License Agreement. 1.13. " Effective Date" shall mean the effective date of the Original Agreement as set forth in the Introduction hereto. 1.14. " Field" shall mean the research, treatment, prognosis, diagnosis, prophylaxis, and monitoring of heart muscle disease. 1.15. " FTE" shall mean the equivalent of the work of one Myogen scientist or other project managerial professional, full time for one year, which equates to a total of [..**..] hours per year of work, on or directly related to the Research Program, including attendance at relevant scientific seminars and symposia. FTEs shall include equivalent scientific work in the Research Program delegated to and carried out by contractors (including Myogen' s academic collaborators) under the general direction of Myogen scientists. The annual rate per FTE shall be [..**..] . 1.16. " GCP" shall mean the current Good Clinical Practice standards for clinical trials for pharmaceuticals, as set forth in the Food, Drug and Cosmetic Act and applicable regulations promulgated thereunder, as amended from time to time, and such standards of good clinical practice as are required by the regulatory authorities of the organizations and governmental agencies in countries in which Drug Products (as defined in the License Agreement) are intended to be sold. [..**..] Confidential Treatment Requested
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1.17. " GLP" shall mean the current Good Laboratory Practices regulations promulgated by the Food and Drug Administration, published at 21 CFR Part 58, as such regulations may be from time to time amended, and such equivalent regulations or standards of countries outside the United States as may be applicable to activities conducted hereunder. 1.18. " HDAC" shall mean any histone deacetylase protein. 1.19. " HDAC Inhibitor Compound" shall mean any Active Compound that has a specific, desired therapeutic action through its ability to bind directly to an HDAC and inhibit HDAC activity. 1.20. " HDAC Inhibitor Research Program" shall mean the Research Program undertaken jointly by the parties as of the Amendment Date associated with the identification, design and development of HDAC Inhibitor Compounds. 1.21. " HDAC License Agreement" shall mean the License, Development and Commercialization Agreement, identical in substance to Exhibit A-2 to this Agreement, to be executed by Myogen and NIBRI with respect to each Development Candidate that is an HDAC Inhibitor Compound. 1.22. " IC 50" shall mean the concentration of a compound that reduces activity of an enzyme by 50% in a standard, validated assay. 1.23. " IND" shall mean an application to the Food and Drug Administration, the filing of which is necessary to commence clinical testing of Compounds in humans, or the equivalent application to the equivalent agency in any other country or group of countries. 1.24. " In Vivo Validation" means, with respect to a Myogen Compound, Collaboration Compound or NIBRI Compound, the achievement of physiologically significant activity in an appropriate in vivo model or models, where the level of physiological significance and the in vivo model(s) to be used will be specified by the JSC with respect to High Priority Targets and Low Priority Targets and by Myogen with respect to Extra-Collaboration Targets. 1.25. " Joint Steering Committee" or " JSC" shall have the meaning set forth in Section 2.5 hereof. [..**..] Confidential Treatment Requested
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1.26. " Know-How" means all Technology other than inventions that are the subject of Patents. 1.27. " License Agreement" shall mean a License, Development and Commercialization Agreement, identical in substance to Exhibit A-1 hereto (with respect to any Development Candidate that is not an HDAC Inhibitor Compound) or identical in substance to Exhibit A-2 hereto (with respect to any Development Candidate that is an HDAC Inhibitor Compound), to be executed by Myogen and NIBRI with respect to a particular Development Candidate. 1.28. " Myogen Compound" shall mean any compound (i) Controlled by Myogen, its Affiliates, and/or its external academic collaborators (or, if applicable, by the licensor or assignor to Myogen or its Affiliates if the rights to such compound were licensed to or acquired by Myogen or its Affiliates) and all enantiomers, racemate(s), isomers, diastereomers, active metabolites and pharmaceutically acceptable salt or complex thereof and any Active Moiety, analog or derivative of such Myogen Compound or the foregoing, and (ii) with respect to which NIBRI' s Head of CV Chemistry or his designee consented to the contribution of such compound to the collaboration. If such consent is not given, such compounds shall remain outside of the collaboration. For the avoidance of doubt, the parties acknowledge that NIBRI or one or more of its employees, agents or Affiliates previously contented to the contribution of certain dihydrotheino pyridine compounds to the collaboration and that such compounds and all derivatives and analogs thereof are Myogen Compounds. 1.29. " Myogen Know-How" shall mean all Know-How of Myogen or its Affiliates relating to a Myogen Compound, a Collaboration Compound, a Collaboration Target, or a Myogen Target or relating to or used in connection with the Research Program. 1.30. " Myogen Patents" shall mean any Patents Controlled by Myogen or any of its Affiliates relating to the Myogen Targets, Myogen Compounds, Collaboration Targets, Collaboration Compounds, and methods or reagents used in identifying, using, developing or manufacturing such Myogen Targets, Myogen Compounds, Collaboration Targets, and Collaboration Compounds, as applicable. A list of Myogen Patents is appended hereto as [..**..] Confidential Treatment Requested
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Schedule 1.30 and will be updated periodically to reflect additions thereto during the course of this Agreement. 1.31. " Myogen Target" shall mean any Target Controlled by Myogen or identified and/or synthesized by Myogen, its Affiliates, and/or its external academic collaborators in the Field, including , as of the Amendment Date, any Targets within the HDAC Inhibitor Research Program. A list of High Priority Myogen Targets as of the date hereof is set forth on Schedule 1.31 appended hereto. Such Schedule 1.31 may be updated periodically to reflect additions thereto during the course of this Agreement. 1.32. " Myogen Technology" shall mean all Myogen Patents and Myogen Know-How. 1.33. " NIBRI Competitor" means a Person with annual pharmaceutical sales of [..**..] or more. 1.34. " NIBRI Compound" shall mean any compound (i) Controlled by NIBRI and/or its Affiliates and all enantiomers, racemate(s), isomers, diastereomers, active metabolites and pharmaceutically acceptable salt or complex thereof and any Active Moiety, analog or derivative of such NIBRI Compound or the foregoing, and (ii) with respect to which Myogen' s Head of Chemistry or his designee consented to the contribution of such compound to the collaboration. If such consent is not given, such compounds shall remain outside of the collaboration. For the avoidance of doubt, the parties acknowledge that Myogen or one or more of its employees, agents or Affiliates previously consented to the contribution of certain compounds on Schedule 1.34 to the collaboration and that such compounds and all derivatives and analogs thereof are NIBRI Compounds. For the avoidance of doubt, an HDAC Inhibitor fulfilling criteria (i) and (ii) above shall be a NIBRI Compound (regardless of whether such HDAC Inhibitor is a NIBRI HDAC Inhibitor Compound or Collaboration HDAC Inhibitor Compound as used herein and in a License Agreement for, among other things, determination of applicable milestone and royalty payment obligations). 1.35. " NIBRI HDAC Inhibitor Compound" shall mean any of the following: (a) Except as otherwise provided in Section 3.6 of the License Agreement relating to any Active Compound that is deemed to be a Development Candidate, a HDAC [..**..] Confidential Treatment Requested
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Inhibitor Compound first synthesized by NIBRI or its Affiliates outside of the collaboration contemplated by this Agreement and for which NIBRI or its Affiliates have received or have applied for or could reasonably expect to apply for and receive U.S. composition of matter patent coverage and that: (i) is shown to have an IC 50 of less than or equal to 1 b5M (micromolar) in any standard NIBRI in vitro assay for the inhibition of HDAC activity; and (ii) has been designated a " Lead Series" candidate for follow-up under the designation " Research Phase D3" in accordance with the standard drug development terminology used by NIBRI; and (b) Except as otherwise provided in Section 3.6 of the License Agreement relating to any Active Compound that is deemed to be a Development Candidate, a HDAC Inhibitor Compound licensed to, purchased or otherwise acquired by NIBRI or its Affiliates from a third party for which (i) NIBRI or its Affiliates do not have any material future license, royalty or similar payment obligations (as determined in good faith by the JSC), and (ii) the third party licensor or assignor or NIBRI or its Affiliates have received or have applied for or could reasonably expect to apply for and receive U.S. composition of matter patent coverage and that (i) is shown to have an IC 50 of less than or equal to 1 b5M (micromolar) in any standard NIBRI in vitro assay for the inhibition of HDAC activity; and (ii) has been designated a " Lead Series" candidate for follow-up under the designation " Research Phase D3" in accordance with the standard drug development terminology used by NIBRI; and (c) Except as otherwise provided in Section 3.6 of the License Agreement relating to any Active Compound that is deemed to be a Development Candidate, all derivatives and analogs of the compounds described in subsections (a) and (b) above that are shown to have an IC 50 of less than or equal to 100 nM (nanomolar) as determined by at least one standard in vitro assay for the inhibition of HDAC activity; and (d) A HDAC Inhibitor Compound licensed to, purchased or otherwise acquired by NIBRI or its Affiliates from a third party for which NIBRI or its Affiliates have any material future license, royalty or similar payment obligation (as determined in good faith by the JSC) and all derivatives and analogs of the compounds described in this subsection (d) for which NIBRI or its Affiliates have any material future license, royalty or similar payment obligation (as [..**..] Confidential Treatment Requested
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determined in good faith by the JSC) (collectively, " In-Licensed NIBRI HDAC Inhibitor Compounds" ). 1.36. " NIBRI Know-How" shall mean all Know-How of NIBRI or its Affiliates relating to a NIBRI Compound, a Collaboration Compound, a Collaboration Target, or a Myogen Target. 1.37. " NIBRI Patents" shall mean any Patents Controlled by NIBRI or any of its Affiliates relating to NIBRI Compounds, Collaboration Compounds, Myogen Targets, Collaboration Targets, and methods or reagents used in identifying, developing, or manufacturing such NIBRI Compounds, Collaboration Targets, and Collaboration Compounds, as applicable, as in effect on the Effective Date and at any time during the term of this Agreement. 1.38. " NIBRI Technology" shall mean all NIBRI Patents and NIBRI Know-How. 1.39. " Patents" means all existing patents and patent applications and all patent applications hereafter filed, including any continuation, continuation-in-part, division, provisional or any substitute applications, any patent issued with respect to any such patent applications, any reissue, reexamination, renewal or extension (including any supplementary protection certificate) of any such patent, and any confirmation patent or registration patent or patent of addition based on any such patent, and all foreign counterparts of any of the foregoing. 1.40. " Person" means any individual, corporation, partnership, association, joint-stock company, trust, unincorporated organization or government or political subdivision thereof. 1.41. " Research Plan" shall have the meaning set forth in Section 2.3.1 hereof. 1.42. " Research Program" shall mean research activities and development activities undertaken under this Agreement, associated with the identification, design and development of Targets, Compounds and Development Candidates as provided herein, including but not limited to: identification and initial testing of Targets and Compounds; selection of Development Candidates from Targets and Compounds and preparation for preclinical assessment of those Development Candidates; formulation and manufacture of Development Candidates for use in [..**..] Confidential Treatment Requested
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preclinical and clinical studies performed in accordance with GCP; preclinical animal studies performed in accordance with GLP (or the applicable equivalent); planning, implementation, administration and evaluation of human clinical trials performed in accordance with GCP and included in proof of concept studies; and manufacturing process development and scale-up as appropriate at the stage of development encompassed within the proof of concept studies. 1.43. " Research Program Costs" shall mean extraordinary external expenses and capital costs that are approved in advance by the JSC and incurred by or on behalf of a party in connection with the conduct of the Research Program. 1.44. " Research Year" means a twelve (12) month period during the term of a Research Program commencing on October 1 of a given year, and ending on September 30 of the following year. The first Research Year hereunder shall be deemed to have commenced on October 1, 2003. 1.45. " Target" shall mean any biological entity identified as being potentially involved in one or more disease states. 1.46. " Technology" shall mean all data, technical information, know-how, experience, inventions (whether or not patented), trade secrets, processes and methods discovered, developed or applied (with the consent of its owner) and Controlled by either party or its Affiliates, in connection with performance by either party under the Research Program, or in connection with the conduct of a Development Program under a License Agreement, that relate to the research, development, utilization, manufacture or use of Compounds, Targets, or Development Candidates, as applicable. 1.47. " Territory" shall mean worldwide. 1.48. " Third Party" shall mean any Person that is not a party or an Affiliate of any party to this Agreement. 1.49. " Wind-Down Period" shall have the meaning set forth in Section 9.4 hereof. 1.50. " Work Plan" shall have the meaning set forth in Section 2.3.2 hereof. [..**..] Confidential Treatment Requested
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Capitalized terms used but not otherwise defined herein that are defined in the License Agreement shall have the meaning ascribed to them therein. ARTICLE II
Research Program 2.1. Commencement. The Research Program shall commence as soon as practicable after the Effective Date. The Joint Steering Committee shall direct the conduct of the Research Program and Myogen and NIBRI shall collaborate in the conduct of the Research Program, with the parties having the roles and responsibilities specified in the Research Plan and/or applicable Work Plans, all as may be deemed appropriate by the Joint Steering Committee. The Joint Steering Committee shall review and coordinate the efforts of the parties with respect to the Research Program. 2.2. Term. The Research Program will conclude five (5) years from the Effective Date, for all Projects other than the HDAC Inhibitor Research Program, and three (3) years from the Amendment Date for the HDAC Inhibitor Research Program, unless earlier terminated in accordance with the provisions hereof. Unless earlier terminated in accordance with the provisions hereof, the Research Program may be extended for additional one (1) year periods upon the mutual written agreement of Myogen and NIBRI prior to the end of the then current Research Year. [..**..] Confidential Treatment Requested
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2.3. Research Plan; Work Plans. 2.3.1. Research Plan, Generally . NIBRI, in consultation with Myogen, will prepare an overall research plan (the " Research Plan" ) for the Research Program. The initial outline of the Research Plan was attached to the Original Agreement. A final version of the Research Plan was submitted to the Joint Steering Committee for approval at the first meeting of the Joint Steering Committee. The Research Plan will be revised, updated and submitted to the Joint Steering Committee at least semi-annually for its review and comment. 2.3.2. Work Plans . Within thirty (30) days of the Effective Date, the parties will agree upon an initial work plan (a " Work Plan" ) identifying: (a) priorities with respect to programs, Targets, and Compounds (" Projects" ) to be pursued; (b) the responsibilities of each party with respect to the same; (c) the appropriate resources of each party to be committed to the Projects; and (d) developmental milestones, performance criteria, and timeframes with respect to such Projects. The Work Plan shall be submitted for approval at the first meeting of the JSC. It is anticipated that the number of Projects selected for the Work Plan will be no less than three (3) at any time during the collaboration, unless otherwise agreed to by the parties. 2.3.3. Plan Review . The Research Plan and all Work Plans will be reviewed as necessary at each meeting of the Joint Steering Committee, and at any other time upon the request of either party, and shall be modified as appropriate to reflect material scientific or commercial developments. Any disagreements between the parties with respect to modification of the Research Plan or a Work Plan will be resolved in accordance with Section 2.8 of this Agreement. 2.3.4. Research Diligence . Each of Myogen and NIBRI shall work diligently and shall use commercially reasonable efforts to fulfill its respective obligations under the Research Plan and any Work Plan. In connection therewith and subject to the intellectual property ownership provisions contained in this Agreement, NIBRI shall make available such NIBRI Compounds as may be reasonably necessary to carry out the purposes hereof and Myogen shall make available such Myogen Compounds as may be reasonably necessary to carry out the purposes hereof. Each of NIBRI and Myogen shall further make available all data and information regarding such Compounds that are reasonably necessary for the parties to carry out [..**..] Confidential Treatment Requested
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the purposes of the collaboration and as reasonably required for achievement of collaboration milestones, including, without limitation, chemical structure, testing data, pharmacokinetic data, selectivity data, SAR data, toxicological data and potency data (including potency data versus target, target isoforms and other related targets) relating to such Compounds. In addition, during the term of this Agreement and pursuant to the Research Plan, NIBRI shall provide medicinal chemistry and other drug discovery services relating to lead compound characterization such as determination of physicochemical properties, cytotoxicity measurements, hERG channel activity, and determination of biopharmaceutical properties as is reasonably necessary for the parties to carry out the purposes of the collaboration and as reasonably required for achievement of collaboration milestones. Consistent with the terms of this Agreement, each party shall use commercially reasonable efforts to obtain intellectual property protection, including U.S. and worldwide patent protection, for inventions within the Field of this Agreement. 2.3.5. Submission of Reports . Upon achieving the developmental milestones specified in a Work Plan with respect to a particular Project, Myogen and NIBRI will complete and present to the JSC a report containing detailed summaries of the data for the Project specified in the Work Plan. 2.4. Addition of HDAC Inhibitor Research Program. Within thirty (30) days of the Amendment Date the parties agreed upon a Work Plan that conforms to the requirements of Section 2.3.1 and specified the pertinent details of the HDAC Inhibitor Research Program. The Work Plan was approved at the first meeting of the JSC after the Amendment Date. The parties will make any revisions to the Research Plan necessary to implement the HDAC Inhibitor Research Program. Furthermore, the parties hereby agree that initially any Targets within the HDAC Inhibitor Research Program will be deemed to be High Priority Targets within the meaning of Section 4.3.1. [..**..] Confidential Treatment Requested
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2.5. Joint Steering Committee. Upon execution of this Agreement, Myogen and NIBRI established a Joint Steering Committee (" JSC" ), which consists of an equal number of executives or scientists as may be designated by each party from time to time. The JSC shall have six (6) members or such other number as mutually agreed by the Parties. If the JSC chooses to designate a Committee Chair, the Chair will be appointed from among the members ...