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EXHIBIT 10.24

 


[ * ] = 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 406 of the Securities Act of 1933, as amended.

 

COLLABORATION AND LICENSE AGREEMENT

 

This COLLABORATION AND LICENSE AGREEMENT (the “Agreement” ) is entered into on February 13, 2006 (the “Effective Date” ) between AFFYMAX, INC. , a Delaware corporation, with its principal place of business at 4001 Miranda Avenue, Palo Alto, CA  94304, U.S.A. ( “Affymax” ), and TAKEDA PHARMACEUTICAL COMPANY LIMITED, a company incorporated under the laws of Japan, with a place of business at 1-1, Doshomachi 4-chome, Chuo-ku, Osaka, 540-8645, Japan ( “Collaborator” ).  Affymax and Collaborator are sometimes referred to herein individually as a “Party” and collectively as the “Parties”.

 

RECITALS

 

WHEREAS , Affymax is developing its proprietary pegylated [ * ] drug candidate designated by Affymax as Hematide™ for the treatment of anemia in patients with chronic kidney disease and cancer;

 

WHEREAS , Collaborator possesses substantial resources and expertise in the development, marketing, and commercialization of pharmaceutical products in Japan;

 

WHEREAS , Collaborator desires to obtain exclusive rights to develop further and commercialize Hematide in Japan, and Affymax is willing to grant such rights on the terms and conditions hereof.

 

NOW THEREFORE , in consideration of the foregoing premises and the mutual promises, covenants and conditions contained in this Agreement, the Parties agree as follows:

 

1



 

TABLE OF CONTENTS

 

 

 

 

PAGE

 

 

 

 

ARTICLE 1

DEFINITIONS

2

 

1.1

“Affiliate”

2

 

1.2

“Affymax House Marks”

2

 

1.3

“Affymax Know-How”

2

 

1.4

“Affymax Patent”

3

 

1.5

“Affymax Technology”

3

 

1.6

“Affymax Territory”

3

 

1.7

“Alternative ESA”

3

 

1.8

“Backup Product”

3

 

1.9

“Bulk Hematide”

3

 

1.10

“Claims”

3

 

1.11

“CTA”

3

 

1.12

“Collaborator Know-How”

4

 

1.13

“Collaborator Patent”

4

 

1.14

“Collaborator Technology”

4

 

1.15

“Commercialization”

4

 

1.16

“Confidential Information”

4

 

1.17

“Control”

4

 

1.18

“Develop” or “Development”

5

 

1.19

“Development Plan”

5

 

1.20

“Diligent Efforts”

5

 

1.21

“[ * ]”

5

 

1.22

“Dollar”

5

 

1.23

“EMEA”

5

 

1.24

“ESA”

6

 

1.25

“FDA”

6

 

1.26

“FD&C Act”

6

 

1.27

“Field”

6

 

1.28

“Finished Manufacture”

6

 


[ * ] = 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 406 of the Securities Act of 1933, as amended.

 

i



 

TABLE OF CONTENTS

(CONTINUED)

 

 

 

 

PAGE

 

 

 

 

 

1.29

“Finished Product”

6

 

1.30

“First Commercial Sale”

6

 

1.31

“Formulation Technology”

6

 

1.32

“Good Clinical Practices” or “GCP”

6

 

1.33

“Good Laboratory Practices” or “GLP”

7

 

1.34

“Good Manufacturing Practices” or “GMP”

7

 

1.35

“Governmental Authority”

7

 

1.36

“Hematide”

7

 

1.37

“IND”

7

 

1.38

“Information”

7

 

1.39

“Initial Indications”

8

 

1.40

“Joint Committee”

8

 

1.41

“Joint Inventions”

8

 

1.42

“Joint Patent”

8

 

1.43

“Laws”

8

 

1.44

“Licensed Territory”

8

 

1.45

“Manufacturing Costs”

8

 

1.46

“Marketing Authorization Application” or “MAA”

10

 

1.47

“MHLW”

10

 

1.48

“Net Sales”

10

 

1.49

“Oncology Indications”

11

 

1.50

“Patents”

11

 

1.51

“Patent Term Extension”

12

 

1.52

“Peptide”

12

 

1.53

“Phase I Clinical Trial”

12

 

1.54

“Phase II Clinical Trial”

12

 

1.56

“Phase IIIB Clinical Trial”

12

 


[ * ] = 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 406 of the Securities Act of 1933, as amended.

 

ii



 

TABLE OF CONTENTS

(CONTINUED)

 

 

 

 

PAGE

 

 

 

 

 

1.57

“Phase IV Clinical Trial”

12

 

1.58

“Pricing Approval”

13

 

1.59

“Product”

13

 

1.60

“Product Complaint”

13

 

1.61

“Product Infringement”

13

 

1.63

“Promotional Materials”

13

 

1.64

“Reagent”

13

 

1.65

“Regulatory Approvals”

14

 

1.66

“Regulatory Authority”

14

 

1.67

“Regulatory Exclusivity”

14

 

1.68

“Regulatory Materials”

14

 

1.69

“Renal Indications”

14

 

1.70

“Required Third Party Data”

14

 

1.72

“Stock Purchase Agreement”

14

 

1.73

“Term”

15

 

1.74

“Territory”

15

 

1.75

“Third Indication”

15

 

1.76

“Third Party”

15

 

1.77

“Third Party Data”

15

 

1.78

“Third Party License Agreements”

15

 

1.79

“Third Party Partner”

15

 

1.80

“U.S.”

15

 

1.81

“Valid Claim”

15

 

1.82

“Yakka”

15

ARTICLE 2

MANAGEMENT

16

 

2.1

Joint Committee

16

 

2.2

Joint Committee Membership

17

 


[ * ] = 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 406 of the Securities Act of 1933, as amended.

 

iii



 

TABLE OF CONTENTS

(CONTINUED)

 

 

 

 

PAGE

 

 

 

 

 

2.3

Joint Committee Meetings and Agendas

18

 

2.4

Joint Committee Decisions and Actions

19

 

2.5

Project Coordinators

20

 

2.6

Collaboration Guidelines

20

ARTICLE 3

PRODUCT DEVELOPMENT

20

 

3.1

Overview

20

 

3.2

Development Plan

21

 

3.3

Principles of Product Development

22

 

3.4

Collaborator’s Performance

22

 

3.5

Records, Reports and Information

23

 

3.6

Right of First Refusal to Backup Product Developed in the Field

23

ARTICLE 4

REGULATORY MATTERS

24

 

4.1

Transfer of Data and Regulatory Materials

24

 

4.2

Regulatory Filings and Approvals

29

 

4.3

Filings for Regulatory Exclusivity

31

 

4.4

Regulatory Costs

31

 

4.5

Communications

31

 

4.6

Collaborator Regulatory Filings

32

 

4.7

No Harmful Actions

32

 

4.8

Adverse Event Reporting and Safety Data Exchange

33

 

4.9

Regulatory Authority Communications Received by a Party

34

 

4.10

Regulatory Inspection or Audit

35

 

4.11

Recalls and Voluntary Withdrawals

36

ARTICLE 5

COMMERCIALIZATION

37

 

5.1

Commercialization in the Licensed Territory

37

 

5.2

Pricing Approvals in the Licensed Territory

37

 

5.3

Pricing of the Product in the Licensed Territory

38

 


[ * ] = 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 406 of the Securities Act of 1933, as amended.

 

iv



 

TABLE OF CONTENTS

(CONTINUED)

 

 

 

 

PAGE

 

 

 

 

 

5.4

Collaborator Performance

38

 

5.5

Compliance

38

 

5.6

Product Trademark and Affymax House Marks

39

ARTICLE 6

LICENSES AND EXCLUSIVITY

40

 

6.1

Licenses to Collaborator under Affymax Technology

40

 

6.2

Limited License for Affymax House Marks

40

 

6.3

License to Affymax under Collaborator Technology

41

 

6.4

Negative Covenant

41

 

6.5

No Implied Licenses

41

 

6.6

Exclusivity

41

 

6.7

Third Party Licenses

42

ARTICLE 7

MANUFACTURE AND SUPPLY

42

 

7.1

Roles of the Parties

42

 

7.2

Preclinical and Clinical Supply of Bulk Hematide

42

 

7.3

Commercial Supply of Bulk Hematide

43

 

7.4

Finished Product

44

 

7.5

Comparator Drugs

44

 

7.6

Audit

44

 

7.7

Collaborator Audit Right of Bulk Hematide Facility

45

 

7.8

Quality Agreement

46

ARTICLE 8

COMPENSATION

46

 

8.1

License Fee

46

 

8.2

Clinical Milestone Payments

47

 

8.3

Royalties

48

 

8.4

Existing and Future Third Party Royalties

50

 

8.5

Taxes

51

 

8.6

Foreign Exchange

52

 


[ * ] = 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 406 of the Securities Act of 1933, as amended.

 

v



 

TABLE OF CONTENTS

(CONTINUED)

 

 

 

 

PAGE

 

 

 

 

 

8.7

Late Payments

52

 

8.8

Records; Audits

52

ARTICLE 9

INTELLECTUAL PROPERTY MATTERS

53

 

9.1

Ownership of Inventions

53

 

9.2

Disclosure of Inventions

53

 

9.3

Prosecution of Patents

54

 

9.4

Patent Term Extensions in the Licensed Territory

57

 

9.5

Infringement of Patents by Third Parties

58

 

9.6

Infringement of Third Party Rights in the Licensed Territory

63

 

9.7

Patent Marking

64

 

9.8

Infringement of Trademarks by Third Parties

64

 

9.9

Patent Oppositions and Other Proceedings

64

 

9.10

Parties’ Patent Rights

65

 

9.11

Orange Book Listing, Compendial Listing

66

 

9.12

Registration of Exclusive License

66

 

9.13

Certain Patent Matters

66

ARTICLE 10

REPRESENTATIONS AND WARRANTIES

66

 

10.1

Mutual Representations and Warranties

66

 

10.2

Additional Representations, Warranties and Covenants of Affymax

67

 

10.3

Disclaimer

69

 

10.4

No Other Representations or Warranties

70

ARTICLE 11

INDEMNIFICATION

70

 

11.1

Indemnification by Affymax

70

 

11.2

Indemnification by Collaborator

71

 

11.3

Indemnification Procedures

71

 

11.4

Limitation of Liability

72

 

11.5

Insurance

72

 


[ * ] = 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 406 of the Securities Act of 1933, as amended.

 

vi



 

TABLE OF CONTENTS

(CONTINUED)

 

 

 

 

PAGE

 

 

 

 

ARTICLE 12

CONFIDENTIALITY

73

 

12.1

Confidentiality

73

 

12.2

Authorized Disclosure

74

 

12.3

Publicity; Terms of Agreement

75

 

12.4

Publications

76

ARTICLE 13

TERM AND TERMINATION

77

 

13.1

Term

77

 

13.2

Early Termination

77

 

13.3

Effect of Termination of the Agreement

79

 

13.4

Other Remedies

80

 

13.5

Rights in Bankruptcy

81

 

13.6

Survival

81

ARTICLE 14

DISPUTE RESOLUTION

81

 

14.1

English Language; Governing Law

81

 

14.2

Disputes

82

 

14.3

Patent and Trademark Dispute Resolution

83

ARTICLE 15

MISCELLANEOUS

83

 

15.1

Entire Agreement; Amendment

83

 

15.2

Force Majeure

84

 

15.3

Notices

84

 

15.4

No Strict Construction; Headings

85

 

15.5

Assignment

85

 

15.6

Performance by Affiliates

86

 

15.7

Further Actions

86

 

15.8

Severability

86

 

15.9

No Waiver

86

 

15.10

Independent Contractors

87

 


[ * ] = 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 406 of the Securities Act of 1933, as amended.

 

vii



 

TABLE OF CONTENTS

(CONTINUED)

 

 

 

 

PAGE

 

 

 

 

 

15.11

Counterparts

87

 


[ * ] = 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 406 of the Securities Act of 1933, as amended.

 

viii



 

ARTICLE 1

 

DEFINITIONS

 

As used in this Agreement, the following initially capitalized terms, whether used in the singular or plural form, shall have the meanings set forth in this Article 1.  The terms in this Agreement with initial letters capitalized, whether used in the singular or the plural, shall have the meaning set forth below or, if not listed below, the meaning designated in places throughout this Agreement.

 

1.1                                “Affiliate” means, with respect to a particular Party, a person, corporation, partnership, or other entity that controls, is controlled by or is under common control with such Party.  For the purposes of this definition, the word “control” (including, with correlative meaning, the terms “controlled by” or “under the common control with”) means, for the purpose of defining the Affiliate under this Section 1.1, the actual power, either directly or indirectly through one or more intermediaries, to direct or cause the direction of the management and policies of such entity, whether by the ownership of fifty percent (50%) or more of the voting stock of such entity, or by contract or otherwise.  Notwithstanding the foregoing, (i) neither the government of Japan, nor any entity controlled by the government of Japan, shall be deemed to be an Affiliate of Collaborator, and (ii) TAP Pharmaceutical Products Inc. shall not be deemed to be an Affiliate of Collaborator.

 

1.2                                “Affymax House Marks” means the Affymax names and logo as set forth in Exhibit A.

 

1.3                                “Affymax Know-How” means all Information that is Controlled by Affymax or its Affiliates during the Term and is necessary or useful for the Development, manufacture and/or Commercialization of the Product.  For clarity, Affymax Know-How excludes the Affymax Patents.

 


[ * ] = 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 406 of the Securities Act of 1933, as amended.

 

2



 

1.4                                “Affymax Patent” means any Patent, including any Joint Patent, that (a) is Controlled by Affymax or its Affiliates at any time during the Term, and (b) claims the Peptide, [ * ] , Hematide, Product or their manufacture or use or any other invention that is otherwise necessary or useful for the Development, Finished Manufacture and/or Commercialization of the Product hereunder. The list of Affymax Patent as of the Effective Date is attached hereto as Exhibit B, and shall be from time to time amended during the Term to incorporate the then current Affymax Patents.

 

1.5                                “Affymax Technology” means the Affymax Patent and Affymax Know-How.

 

1.6                                “Affymax Territory” means worldwide except Japan, its territories and possessions.

 

1.7                                “Alternative ESA” means any peptide-based synthetic [ * ] ESA other than Hematide, including any such ESA comprised of (i) the Peptide alone, (ii) some peptide(s) other than the Peptide, (iii) the Peptide linked to a chemical moiety other than the Reagent(s) by any means, or (iv) some peptide(s) other than the Peptide linked to any chemical moiety(ies) by any means.

 

1.8                                “Backup Product” means any product(s) Controlled by Affymax or its Affiliates, the active therapeutic ingredient(s) of which are Alternative ESAs.

 

1.9                                “Bulk Hematide” means the active pharmaceutical ingredient (API) for Hematide, in bulk form.

 

1.10                         “Claims” has the meaning set forth in Section 11.1.

 

1.11                         “CTA” means an application for clinical trial authorization filed with a Regulatory Authority in the Licensed Territory to undertake clinical trials of an investigational new drug, the filing of which is necessary to commence or conduct clinical testing of a pharmaceutical product in humans in the Licensed Territory.

 


[ * ] = 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 406 of the Securities Act of 1933, as amended.

 

3



 

1.12                         “Collaborator Know-How” means all Information that is Controlled by Collaborator or its Affiliates during the Term under this Agreement and is necessary or useful for the Development, manufacture or Commercialization of the Product.  For clarity, Collaboration Know-How excludes Collaborator Patents.

 

1.13                         “Collaborator Patent” means any Patent, including any Joint Patent, that (a) is Controlled by Collaborator or its Affiliates at any time during the Term under this Agreement, and (b) claims the Peptide, [ * ] , Bulk Hematide and/or Product or any method or composition, or the manufacture or use, of the Peptide, [ * ], Bulk Hematide and/or Product.

 

1.14                         “Collaborator Technology” means the Collaborator Patents and Collaborator Know-How.

 

1.15                         “Commercialization” , with a correlative meaning for “Commercialize” , means all activities undertaken before and after obtaining Regulatory Approval relating specifically to the pre-launch, launch, promotion, marketing, sale, and distribution of  a pharmaceutical product, including: (a) strategic marketing, sales force detailing, advertising, medical education and liaison, and market and product support; and (b) any Phase IV Clinical Trials, and (c) all customer support and Product distribution, invoicing and sales activities.

 

1.16                         “Confidential Information” means, with respect to a Party, all confidential Information of such Party that is disclosed to the other Party under this Agreement, which may include specifications, know-how, trade secrets, legal information, technical information, drawings, models, business information, inventions, discoveries, methods, procedures, formulae, protocols, techniques, data, and unpublished patent applications, whether disclosed in oral, written, graphic, or electronic form.  All confidential Information disclosed by either Party pursuant to the Mutual Confidential Disclosure Agreement between the Parties dated September 30, 2005 shall be deemed to be such Party’s Confidential Information disclosed hereunder.

 

1.17                         “Control” means, with respect to any material, Information, or intellectual property right, that a Party owns or has a license to such material, Information, or intellectual property right and has the ability to grant to the other Party access, a license, or a sublicense (as

 


[ * ] = 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 406 of the Securities Act of 1933, as amended.

 

4



 

applicable) to such material, Information, or intellectual property right on the terms and conditions set forth herein without violating the terms of any agreement or other arrangement with any Third Party existing at the time such Party would be first required hereunder to grant to the other Party such access, license, or sublicense.

 

1.18                         “Develop” or “Development” means all activities relating to preparing and conducting preclinical testing, toxicology testing, human clinical studies, regulatory affairs, formulation development, process development for Finished Manufacture and associated validation, quality assurance and quality control activities.  Development shall exclude all Phase IV Clinical Trials.

 

1.19                         “Development Plan” means the plan for conducting Development of the Product to be Commercialized by Collaborator in the Licensed Territory, as set forth in Section 3.2.

 

1.20                         “Diligent Efforts” means, with respect to a Party’s obligation under this Agreement to Develop or Commercialize a Product, the level of efforts required to carry out such obligation in a sustained manner consistent with the efforts a similarly situated biopharmaceutical company (in the case of Affymax) or pharmaceutical company (in the case of Collaborator) devotes to a product of similar market potential, profit potential or strategic value  within its portfolio, based on conditions then prevailing.  Diligent Efforts requires, with respect to such an obligation, that the Party:  (a) promptly assign responsibility for such obligation to specific employee(s) who are held accountable for progress and monitor such progress on an on-going basis, (b) set and consistently seek to achieve specific, meaningful and measurable objectives for carrying out such obligation, and (c) consistently make and implement decisions and allocate resources designed to advance progress with respect to such objectives.

 

1.21                         [ * ] means Affymax’s proprietary ESA peptide [ * ] [ * ] with the chemical structure attached hereto as Exhibit C.

 

1.22                         “Dollar” means a U.S. dollar, and “$” shall be interpreted accordingly.

 

1.23                         “EMEA” means the European Agency for the Evaluation of Medicinal Products, or any successor thereto, which is responsible for coordinating the centralized system for

 


[ * ] = 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 406 of the Securities Act of 1933, as amended.

 

5



 

Regulatory Approval of pharmaceutical products in the European Union and the European Economic Area and recommending to the European Commission (the “EC” ) that the EC grant Regulatory Approval of certain pharmaceutical products in the EU and EEA under such centralized system.

 

1.24                         “ESA” means erythropoiesis stimulating agent.

 

1.25                         “FDA” means the U.S. Food and Drug Administration or its successor.

 

1.26                         “FD&C Act” means the U.S. Federal Food, Drug and Cosmetic Act, as amended.

 

1.27                         “Field” means the prevention, treatment or amelioration of anemia in humans, including the Renal Indications and the Oncology Indications.

 

1.28                         “Finished Manufacture” means the manufacture of Finished Product from Bulk Hematide.

 

1.29                         “Finished Product” means the Product containing Hematide that has been filled into vials, syringes or manufactured into other pharmaceutical presentations, finished and labeled for use in clinical trials or for commercial purposes in accordance with the applicable specifications and legal requirements.

 

1.30                         “First Commercial Sale” means the first sale to a Third Party of a Product in the Licensed Territory after Regulatory Approval has been obtained in the Licensed Territory.

 

1.31                         “Formulation Technology” means any technology useful to facilitate delivery of therapeutic compounds, or that is useful to optimize the absorption or distribution of therapeutic compounds in the body, but that is not itself a therapeutic compound; provided that Formulation Technology shall exclude any technology that comprises a chemical modification of the Peptide, [ * ] or Hematide.

 

1.32                         “Good Clinical Practices” or “GCP” means the then-current good clinical practice standards, practices and procedures promulgated or endorsed by the Regulatory

 


[ * ] = 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 406 of the Securities Act of 1933, as amended.

 

6



 

Authority in the Licensed Territory as set forth in the guidelines including related regulatory requirements imposed by such Regulatory Authority, as they may be updated from time to time.

 

1.33                         “Good Laboratory Practices” or “GLP” means the then-current good laboratory practice standards promulgated or endorsed by the Regulatory Authority in the Licensed Territory, as they may be updated from time to time.

 

1.34                         “Good Manufacturing Practices” or “GMP” means the then-current good manufacturing practices required by the Regulatory Authority in the Licensed Territory or, solely for purposes of Affymax’s obligations under Sections 1.45 and 10.2(d), by the FDA and by the guideline promulgated by the International Conference on Harmonization designated ICH Q7A, entitled “Q7A Good Manufacturing Practice Guidance for Active Pharmaceutical Ingredients” and the regulations promulgated thereunder, at least until and unless otherwise agreed by the Parties in the quality agreement entered into pursuant to Section 7.8, for the manufacture and testing of pharmaceutical materials, as they may be updated from time to time.

 

1.35                         “Governmental Authority” means any multi-national, federal, state, local, municipal or other government authority of any nature (including any governmental division, subdivision, department, agency, bureau, branch, office, commission, council, court or other tribunal).

 

1.36                         “Hematide” means Affymax’s proprietary pegylated ESA drug candidate referred to internally as [ * ] , consisting of the [ * ] attached to the Reagent.

 

1.37                         “IND” means (a) an Investigational New Drug Application as defined in the applicable regulations promulgated by the Regulatory Authority in the Licensed Territory, the filing of which is necessary to commence or conduct clinical testing of a pharmaceutical product in humans in the Licensed Territory.

 

1.38                         “Information” means any data, results, technology, business information, and information of any type whatsoever, in any tangible or intangible form, including, without limitation, know-how, trade secrets, practices, techniques, methods, processes, inventions, developments, specifications, formulations, formulae, materials or compositions of matter of any

 


[ * ] = 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 406 of the Securities Act of 1933, as amended.

 

7



 

type or kind (patentable or otherwise), software, algorithms, marketing reports, expertise, technology, test data (including pharmacological, biological, chemical, biochemical, toxicological, preclinical and clinical test data), analytical and quality control data, stability data, other study data and procedures.

 

1.39                         “Initial Indications” means the Renal Indications and/or the Oncology Indications.

 

1.40                         “Joint Committee” means the committee formed by the Parties as described in Section 2.1(a).

 

1.41                         “Joint Inventions” has the meaning set forth in Section 9.1.

 

1.42                         “Joint Patent” has the meaning set forth in Section 9.3(c).

 

1.43                         “Laws” means all relevant laws, statutes, rules, regulations, guidelines, ordinances and other pronouncements having the effect of law of any federal, national, multinational, state, provincial, county, city or other political subdivision, domestic or foreign.

 

1.44                         “Licensed Territory” means Japan, including its territories and possessions.

 

1.45                         “Manufacturing Costs” (“MC”) means:

 

(a)                                   With respect to Bulk Hematide supplied to Affymax by its Third Party contract manufacturer(s), Manufacturing Costs shall mean the sum of (i) all amounts of all payments that Affymax makes to such Third Party contract manufacturer(s) for supply and delivery to Collaborator (either directly, or first to Affymax for subsequent delivery to Collaborator) of such Bulk Hematide, plus all payments made to third party contractors for release and batch stability testing services for Bulk Hematide, and (ii) any Overhead Costs incurred in, and reasonably allocable to, the procurement of Bulk Hematide supplied to Affymax and supplied to Collaborator.  As used herein “Overhead Costs” means direct and indirect logistics, quality control, quality assurance, support and management costs incurred in support of the Third Party contract manufacturer by Affymax and shall be subject to the reasonable

 


[ * ] = 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 406 of the Securities Act of 1933, as amended.

 

8



 

approval of Collaborator.  Further, such methodology shall be consistent with U.S. Generally Accepted Accounting Principles and Affymax’s methodology for other products and shall be consistent from year-to-year ; and

 

(b)                                   With respect to Bulk Hematide manufactured by Affymax and supplied to Collaborator , if any, Manufacturing Costs shall mean Direct Expenses, Indirect Expenses and Overhead Costs incurred in, and reasonably allocable to, the manufacture of such Bulk Hematide.   As used herein:

 

(i)                                     Direct Expenses ” are those material and labor and services expenses captured in time sheets, invoices, and the like which are specifically attributable to manufacture of the Bulk Hematide supplied to Collaborator, including costs of raw materials, manufacturing supplies, solvents, containers, container components, packaging, labels and other printed materials used in production.  Direct labor expenses include salaries and fringe benefits for personnel directly involved in manufacturing Bulk Hematide in accordance with cGMP requirements such as production, quality control, quality assurance, microbiology, and other similar departments as needed who participate directly in the production of Bulk Hematide and components thereof.  Direct services expenses include reasonable out of pocket payments to Third Parties for services related to the manufacture of Bulk Hematide or components thereof.

 

(ii)                                 Indirect Expenses ” include production indirect costs such as a reasonable allocation of expenses associated with Affymax personnel supporting the direct manufacturing of Bulk Hematide in accordance with cGMP requirements.  Indirect Expenses can include labor for and indirect costs of quality control, quality assurance, raw material acquisition and acceptance, microbiology, document control, calibration/validation, and non-R&D expenses for process development and analytical methods development, and shall not include any Direct Expenses.

 

(iii)                             Overhead Costs ” are direct and indirect manufacturing costs that cannot be identified in a practical manner with specific units of production and, therefore, cannot be included in MC as Direct Expenses or Indirect Expenses. The methodology to be used in making the allocations for Overhead Costs shall be proposed by Affymax and shall be subject to

 


[ * ] = 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 406 of the Securities Act of 1933, as amended.

 

9



 

the reasonable approval of Collaborator. Further such methodology shall be consistent with U.S. Generally Accepted Accounting Principles and Affymax’s methodology for other products and shall be consistent from year-to-year.

 

For avoidance of doubt, any given cost included in Manufacturing Costs shall not be included more than once in any calculation described herein.

 

1.46                         “Marketing Authorization Application” or “MAA” means an application for Regulatory Approval (but excluding Pricing Approval) in the Licensed Territory.

 

1.47                         “MHLW” means the Ministry of Health, Labor and Welfare, otherwise referred to as “Korosho” or any successor thereto, which govern the scientific review of human pharmaceutical products in Japan.

 

1.48                         “Net Sales” means, with respect to a particular time period, the total amounts billed by Collaborator, its Affiliates and their respective sublicensees for sales of Finished Products made during such time period to unaffiliated Third Parties, less the following deductions to the extent actually allowed or incurred with respect to such sales:

 

(a)                                   discounts, including cash and quantity discounts, charge-back payments, and rebates actually granted to trade customers, managed health care organizations, federal, state, or local government and the agencies, purchasers and reimbursers of managed health organizations or federal, state or local government, including without limitation, any reasonable inventory compensation due to Yakka revision, and contribution for Drug Induced Suffering and Contribution for Measure for Drug Safety (as required by Law or applicable Regulatory Authorities), in the amount determined by the Pharmaceuticals and Medical Devices Agency (so-called “KIKO”) in Japan, with the aggregate of such discounts not to exceed [ * ] of the amounts billed; provided, however, that if such limit is not sufficient or appropriate for adequately maintaining the competitive position of Products in the Licensed Territory, the Parties shall confer in good faith regarding whether any increase in such limit is appropriate under the circumstances;

 


[ * ] = 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 406 of the Securities Act of 1933, as amended.

 

10



 

(b)                                   credits or allowances actually granted upon claims, damaged goods, rejections or returns of such Finished Products, including in connection with recalls;

 

(c)                                   freight, postage, shipping, transportation and insurance charges actually allowed or paid for delivery of Finished Products, to the extent billed; and

 

(d)                                   taxes (other than income taxes), duties, tariffs or other governmental charges levied on the sale of such Products, including, without limitation, value-added taxes, net of all reimbursements and allowances.

 

Notwithstanding the foregoing, amounts billed by Collaborator, its Affiliates, or their respective sublicensees for the sale of Finished Products among Collaborator, its Affiliates or their respective sublicensees for resale shall not be included in the computation of Net Sales hereunder.  Net Sales shall be accounted for in accordance with generally accepted accounting principles as practiced internationally, consistently applied. Net Sales shall exclude any samples of Product transferred or disposed of at no cost for promotional or educational purposes.

 

Further, the Parties agree to negotiate in good faith for an equitable determination of the Net Sales of the Product in the event Collaborator sells the Product in such a manner that gross sales of the Product are not readily identifiable (e.g., for Products to be sold as a combination product or bundling with other products.)

 

1.49                         “Oncology Indications” means use of the Product for the prevention, treatment or amelioration of anemia in patients with cancer.

 

1.50                         “Patents” means (a) pending patent applications, including provisional patents, issued patents, utility models and designs; and (b) extensions, reissues, substitutions, confirmations, registrations, validations, re-examinations, additions, continuations, continued prosecution applications, requests for continued examination, continuations-in-part, or divisions of or to any patents, patent applications, utility models or designs.

 


[ * ] = 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 406 of the Securities Act of 1933, as amended.

 

11



 

1.51                         “Patent Term Extension” means any term extensions, supplementary protection certificates and equivalents thereof offering patent protection beyond the initial term with respect to any issued patents.

 

1.52                         “Peptide” means that certain peptide ESA known as [ * ] , the chemical structure of which is attached hereto as Exhibit D.

 

1.53                         “Phase I Clinical Trial” means a small scale trial of a pharmaceutical product on subjects that generally provides for the first introduction into humans of such product with the primary purpose of determining safety, metabolism and pharmacokinetic properties and clinical pharmacology of such product.

 

1.54                         “Phase II Clinical Trial” means a small scale clinical trial of a pharmaceutical product on patients, including possibly pharmacokinetic studies, the principal purposes of which are to make a preliminary determination that such product is safe for its intended use and to obtain sufficient information about such product’s efficacy to permit the design of further clinical trials.

 

1.55                         “Phase III Clinical Trial” means one or more clinical trials on sufficient numbers of patients, which trial(s) are designed to (a) establish that a drug is safe and efficacious for its intended use; (b) define warnings, precautions and adverse reactions that are associated with the drug in the dosage range to be prescribed; and (c) support Regulatory Approval of such drug.

 

1.56                         “Phase IIIB Clinical Trial” means a Phase III Clinical Trial, possibly including pharmacokinetic studies, commenced prior to receipt of Regulatory Approval in the jurisdiction for which such trials are being conducted, but which is not required in order to obtain Regulatory Approval and which is conducted primarily for the purpose of Product support (e.g., providing additional drug profile and safety data or supporting expansion of the Product Labeling).

 

1.57                         “Phase IV Clinical Trial” means a clinical trial of a Product conducted after Regulatory Approval of such Product has been obtained from an appropriate Regulatory Authority, which trial is (a) conducted voluntarily by a Party to enhance marketing or scientific

 


[ * ] = 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 406 of the Securities Act of 1933, as amended.

 

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knowledge of the Product (e.g., for expansion of Product Labeling and dose optimization), or (b) conducted due to a request or requirement of a Regulatory Authority.

 

1.58                         “Pricing Approval” means such approval, agreement, determination or governmental decision establishing prices (i.e., Yakka) for the Product that can be charged to consumers and will be reimbursed by Governmental Authorities in the Licensed Territory.

 

1.59                         “Product” means a pharmaceutical preparation in any formulation that contains Hematide as an active ingredient.

 

1.60                         “Product Complaint” means any written, verbal or electronic expression of dissatisfaction regarding the Product, including without limitation reports of actual or suspected product tampering, contamination, mislabeling or inclusion of improper ingredients.

 

1.61                         “Product Infringement” has the meaning set forth in Section 9.5(b).

 

1.62                         “Product Labeling” means (a) the full prescribing information for the Product approved by the applicable Regulatory Authority, and (b) all labels and other written, printed or graphic information included in or placed upon any container, wrapper or package insert used with or for the Product.

 

1.63                         “Promotional Materials” means all sales representative training materials and all written, printed, graphic, electronic, audio or video presentations of information, including, without limitation, journal advertisements, sales visual aids, formulary binders, reprints, direct mail, direct-to-consumer advertising, internet postings, broadcast advertisements and sales reminder aides (for example, note pads, pens and other such items) intended for use or used by Collaborator or its Affiliates, sublicensees or licensees in connection with any promotion of a Product in the Licensed Territory (all to the extent applicable for the Commercialization in the Licensed Territory), but excluding Product Labeling.

 

1.64                         “Reagent” means the reagent described in Exhibit E.

 


[ * ] = 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 406 of the Securities Act of 1933, as amended.

 

13



 

1.65                         “Regulatory Approvals” means all approvals (including without limitation supplements, amendments, and Price Approvals), licenses, registrations or authorizations of any national, supra-national, regional, state or local regulatory agency, department, bureau, commission, council or other governmental entity, necessary for the manufacture, distribution, use or sale of a pharmaceutical product in the Licensed Territory.

 

1.66                         “Regulatory Authority” means, in a particular country or jurisdiction, any applicable Governmental Authority involved in granting Regulatory Approval in such country or jurisdiction, including without limitation, (a) in the U.S., the FDA and any other applicable Governmental Authority in the U.S. having jurisdiction over the Product, and (b) the MHLW.

 

1.67                         “Regulatory Exclusivity” means any exclusive marketing rights or data exclusivity rights conferred by any Governmental Authority with respect to the Product other than a patent right in the Licensed Territory.

 

1.68                         “Regulatory Materials” means regulatory applications, submissions, notifications, registrations, Regulatory Approvals and/or other filings made to or with a Regulatory Authority that are necessary or reasonably desirable in order to develop, manufacture, market, sell or otherwise commercialize Products in a particular country, territory or possession.  Regulatory Materials include, without limitation, INDs, CTAs, MAAs, and applications for Pricing Approvals.

 

1.69                         “Renal Indications” means the use of the Product in the prevention, treatment or amelioration of anemia in patients with chronic kidney disease, whether or not on dialysis.

 

1.70                         “Required Third Party Data” has the meaning set forth in Section 4.1(b).

 

1.71                         “Sole Inventions” has the meaning set forth in Section 9.1.

 

1.72                         “Stock Purchase Agreement” shall mean that certain Stock Purchase Agreement to be entered into by and between Collaborator and Affymax pursuant to Section 8.1(b), for the purchase by Collaborator of Preferred Stock of Affymax.

 


[ * ] = 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 406 of the Securities Act of 1933, as amended.

 

14



 

1.73                         “Term” means the term of this Agreement, as determined in accordance with Article 13.

 

1.74                         “Territory” means the Affymax Territory or the Licensed Territory, as applicable.

 

1.75                         “Third Indication” means indications other than the Initial Indications.

 

1.76                         “Third Party” means any entity other than Affymax or Collaborator or an Affiliate of either of them.

 

1.77                         “Third Party Data” has the meaning set forth in Section 4.1(a)(iv).

 

1.78                         “Third Party License Agreements” has the meaning set forth in Section 6.7.

 

1.79                         “Third Party Partner” shall have the definition ascribed thereto in Section 4.1(a)(iv).

 

1.80                         “U.S.” means the United States of America and its possessions and territories.

 

1.81                         “Valid Claim” means (a) an unexpired claim of an issued Patent that has not been disclaimed, revoked or held to be invalid or unenforceable by a court or other authority of competent jurisdiction, from which decision no appeal can be further taken; or (b) a claim of a pending Patent application.

 

1.82                         “Yakka” means the approval by the MHLW of the National Health Insurance System (NHI) reimbursable price for the Product in the Licensed Territory.

 

1.83                         “Yen” means a Japanese unit of currency, and “¥” shall be interpreted accordingly.

 


[ * ] = 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 406 of the Securities Act of 1933, as amended.

 

15



 

ARTICLE 2

 

MANAGEMENT

 

2.1                                Joint Committee .

 

(a)                                   Formation and Role.   The Parties hereby establish a Joint Committee that shall monitor and coordinate communication regarding the Parties’ performance under this Agreement to Develop and obtain Regulatory Approval for the Product in the Field and in the Licensed Territory.  Each Party shall have an equal number of representatives on the Joint Committee, who initially shall be the individuals set forth in Exhibit F.  The Joint Committee shall have the membership and authority, and shall operate by the procedures, set forth for it in this Section 2.1 and in Section 2.2.  The role of the Joint Committee shall be:

 

(i)                                     to review the overall strategy for seeking Regulatory Approval in the Licensed Territory of the Product for the Initial Indications and any other indications in the Field Collaborator seeks to develop the Product for;

 

(ii)                                 to facilitate the exchange of information between the Parties with respect to the activities hereunder for the Licensed Territory and to establish procedures for the efficient sharing of information and materials necessary for Collaborator’s Development of Products hereunder, consistent with this Agreement;

 

(iii)                             to review, approve, and, if necessary, amend the Development Plan;

 

(iv)                                to seek to resolve any issues arising under this Agreement;

 

(v)                                    to monitor the Parties’ performance against each then-current Development Plan;

 

(vi)                                to provide a forum to evaluate strategies for obtaining, maintaining and enforcing patent and trademark protection for Products in the Licensed Territory; and

 

(vii)                            to perform such other functions as appropriate to further the purposes of this Agreement, as determined by the Parties.

 


[ * ] = 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 406 of the Securities Act of 1933, as amended.

 

16



 

The Joint Committee shall perform its responsibilities under this Agreement based on the principles of prompt and diligent Development of Products in the Licensed Territory, consistent with good pharmaceutical practices and the maximization of long-term profits derived from the sale of Products in the Licensed Territory.  The Joint Committee shall have only the powers assigned expressly to it in this Article 2 and elsewhere in this Agreement, and the Joint Committee shall not have any power to amend, modify or waive compliance with this Agreement.

 

2.2                                Joint Committee Membership

 

Affymax and Collaborator shall each designate three (3) representatives to serve on the Joint Committee by written notices to the other Party.  Either Party may designate substitutes for its representatives if one (1) or more of such Party’s designated representatives are unable to be present at a meeting.  From time to time each Party may replace its representatives by written notice to the other Party specifying the prior representative(s) and their replacement(s).  Any such substitutes or replacements shall be designated consistent with the following principles:  one (1) representative shall have appropriate expertise in the clinical Development of pharmaceutical products, and one (1) representative shall have appropriate expertise in Commercialization of pharmaceutical products; provided that the Joint Committee may vary the expertise required for Joint Committee representatives of each Party as it deems appropriate as the Parties gain experience with Products, but in any event at least one (1) of such representatives on the Joint Committee shall be at the [ * ] in each of the Party’s organizations.  Collaborator shall select one (1) of its representatives as the initial chairperson of the Joint Committee.  On each anniversary of the Effective Date, the Parties shall rotate designation of the chairperson for the commencing year.  The chairperson shall be responsible for (i) calling meetings, and (ii) preparing and circulating an agenda for the upcoming meeting pursuant to Section 2.3(b), but shall have no special authority over the other members of the Joint Committee, and shall have no additional voting rights.  One of Collaborator’s Joint Committee representatives shall be responsible for preparing and issuing minutes of each such meeting within thirty (30) days thereafter.  Such minutes shall not be finalized until Affymax reviews and

 


[ * ] = 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 406 of the Securities Act of 1933, as amended.

 

17



 

confirms with Collaborator the accuracy of such minutes in writing, which review by Affymax shall be completed within thirty (30) days after the receipt of the minutes.

 

2.3                                Joint Committee Meetings and Agendas .

 

(a)                                   Meetings. The Joint Committee shall hold at least two (2) meetings per year on such dates at such times each year as it elects.  Meetings of the Joint Committee shall be effective only if at least [ * ] representatives of each Party are present or participating.  The Joint Committee may meet either (i) in person at either Party’s facilities or at such locations as the Parties may otherwise agree; or (ii) by audio or video teleconference.  With the prior consent of each Party’s representatives, other representatives of each Party or Third Parties involved with the Products may attend meetings as nonvoting participants.  Additional meetings of the Joint Committee may also be held with the consent of each Party, or as required under this Agreement, and neither Party shall unreasonably withhold or delay its consent to hold such an additional meeting.  Each Party shall be responsible for all of its own expenses incurred in connection with participating in the Joint Committee.

 

(b)                                   Meeting Agendas .  The chairperson of the Joint Committee shall prepare a draft agenda containing the topics (i.e., Development and/or manufacturing issues) for the upcoming meeting.  The chairperson shall disclose to the other members of the Joint Committee (i) the draft agenda no later than ten (10) business days in advance, and (ii) its final agenda (along with appropriate related Information) at least five (5) business days in advance, of each meeting of the Joint Committee; provided that under exigent circumstances requiring Joint Committee input, the chairperson may provide the draft and final agenda to the other members of the Joint Committee with a lesser period of time in advance of the meeting, or may propose that there not be a specific agenda for a particular meeting, so long as such other Joint Committee members consent to such temporary changes to the general process for distributing the agenda for Joint Committee meetings.

 


[ * ] = 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 406 of the Securities Act of 1933, as amended.

 

18



 

2.4                                Joint Committee Decisions and Actions .

 

(a)                                   Decision Making.   Except as expressly provided in this Section 2.4, actions to be taken by the Joint Committee shall be taken only following unanimous vote, with each Party having one (1) vote.  If the Joint Committee fails to reach unanimous agreement on a matter before it for decision for a period in excess of ten (10) business days from the discussion at the Joint Committee and unless the Parties agree to prolong such time period, the matter shall be referred to the senior executive officers of the Parties pursuant to Section 14.2, except as otherwise provided in Section 2.4(b) or 2.4(c).

 

(b)                                   Dispute.  If the members of the Joint Committee cannot reach a unanimous decision with respect to matters involving the [ * ] , [ * ] or the approval of any component of an amended or updated Development Plan (a “ Dispute ”) within the time period set forth in above subsection (a), such matter shall not be referred to the senior executive officers of the Parties; rather, the final decision on such Dispute shall be made by Collaborator, as and to the extent set forth in this subsection 2.4(b), except if such matter is an Excepted Development Matter.

 

(c)                                   Excepted Development Matters.  For the purpose of this Section 2.4, “Excepted Development Matters” means the following:

 

(i)                                     altering the [ * ] to provide for the Development of   [ * ] other than the [ * ] ; and

 

(ii)                                 [ * ] for the Product [ * ] in accordance with its protocol, as a consequence of [ * ] that are likely to affect the [ * ] the Product or [ * ] affect the [ * ] for such Product [ * ] , other than for purposes of [ * ] or pursuant to a requirement imposed by the Regulatory Authorities in the Licensed Territory or the external monitoring board for such trial;

 

(iii)                             altering the [ * ] or otherwise proposing to conduct or conducting any Development activities in a manner that would reasonably be expected to [ * ]] development or commercialization efforts for Products in the [ * ] , other than for purposes of [ * ] or pursuant to a requirement imposed by the Regulatory Authorities in the Licensed Territory or the external monitoring board for such trial.

 


[ * ] = 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 406 of the Securities Act of 1933, as amended.

 

19



 

If a matter in dispute is an Excepted Development Matter, such matter shall be referred to the senior executive officers of the Parties pursuant to Section 2.4(a), and where such senior executive officers cannot resolve any such Excepted Development Matter referred to them, then the status quo shall prevail (i.e., Collaborator shall not have the right to have such alteration or amendment implemented or a [ * ] shall not be [ * ] ), and Collaborator shall proceed with Development under the then-existing Development Plan, provided, however, in case of subsection (iii) above, Collaborator shall not have the right to so alter the [ * ] or conduct such Development activities.

 

2.5                                Project Coordinators .  Promptly following the Effective Date, each Party shall designate on Exhibit F an appropriate expert to facilitate communication and coordination of the Parties’ activities under this Agreement relating to Products and to provide support and guidance to the Joint Committee (each, a “ Project Coordinator ”).  Each Project Coordinator shall be experienced in project management and may also serve as one of the three (3) representatives of its respective Party on the Joint Committee. From time to time each Party may replace its Project Coordinator by written notice to the other Party specifying the replacement.

 

2.6                                Collaboration Guidelines .  In all matters relating to this Agreement, each Party shall seek to comply with good pharmaceutical and environmental practices consistent with the Laws and its own existing practices.  Subject to the terms of this Agreement, the activities and resources of each Party shall be managed by such Party, acting independently and in its individual capacity.  The relationship between Affymax and Collaborator is that of independent contractors and neither Party shall have the power to bind or obligate the other Party in any manner, other than as expressly set forth in this Agreement.

 

ARTICLE 3

 

PRODUCT DEVELOPMENT

 

3.1                                Overview .  Collaborator shall Develop Products in the Licensed Territory as provided in this Article 3 and in accordance with the Development Plan, which shall set forth all Development activities to be performed by Collaborator under this Agreement, including without

 


[ * ] = 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 406 of the Securities Act of 1933, as amended.

 

20



 

limitation such activities as may be required by the Regulatory Authorities in the Licensed Territory for Regulatory Approval of Products for use in the Initial Indications in the Licensed Territory, and any additional activities necessary for any Product to meet the requirements of the Japanese Pharmacopoeia or any other listings that are necessary or helpful for obtaining Price Approval for such Product in the Initial Indications in the Licensed Territory (such additional activities, “ Required Studies ”). Affymax shall complete all [ * ] regarding the Product that are listed on Exhibit G, at its own cost, risk and responsibility and shall provide Collaborator the data obtained therein as provided in Section 4.1(a).  Collaborator shall bear all of the costs and expenses incurred in connection with any of the activities performed by the Collaborator pursuant to the Development Plan.

 

3.2                                Development Plan .  An initial Development Plan has been agreed upon by the Parties and is attached hereto as Exhibit H and incorporated herein by reference.  From time to time, either Party may submit to the Joint Committee for discussion any proposed modifications to the Development Plan, and the Joint Committee shall discuss such proposed modifications at its next meeting, and any such modification may be approved by the Joint Committee as provided in Section 2.4.  The Development Plan shall, at all times, contain the following information for the Product for both of the Initial Indications in the Licensed Territory:

 

(a)                                   scope and timelines for Collaborator’s performance of all studies (including any Required Studies) designed to support Regulatory Approval of the Product in the Licensed Territory, including without limitation, clinical trial protocols, additional preclinical tests (including any and all carcinogenicity and toxicology studies), Finished Product stability studies, enrollment numbers and filing submission dates;

 

(b)                                   estimated dates of meetings with Regulatory Authorities in the Licensed Territory for such Product;

 

(c)                                   Collaborator’s forecasts of its needs for preclinical or clinical supply of such Product and/or Bulk Hematide; and

 

(d)                                   target dates for achieving milestones in Developing such Product.

 


[ * ] = 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 406 of the Securities Act of 1933, as amended.

 

21



 

3.3                                Principles of Product Development.  Collaborator’s Development of the Product in the Initial Indications in the Licensed Territory shall be conducted in a manner consistent with the following principles:

 

(a)                                   using Diligent Efforts to seek a Regulatory Approval that includes a label for such Product as broad as reasonably possible;

 

(b)                                   using Diligent Efforts to seek a product profile for such Product with maximum scope of recommended usage and minimum scope of restrictions on use, in each case to the extent reasonably possible;

 

(c)                                   using Diligent Efforts to obtain Regulatory Approval for such Product consistent with (a) and (b) in a timely manner; and

 

(d)                                   using Diligent Efforts not to unreasonably adversely impact Affymax’s or its Third Party Partner’s own Development or Commercialization efforts for Products in the Affymax Territory, including without limitation, and where reasonably practicable, using and filing in the Licensed Territory regulatory filings that are equivalent to all MAAs and related filings for Products that are provided by Affymax pursuant to Section 4.2, to ensure that all Collaborator’s filings and specifications for Products in the Licensed Territory remain consistent, as far as reasonable, with those for the relevant Products in the Affymax Territory.

 

3.4                                Collaborator’s Performance .  Collaborator shall devote Diligent Efforts to the Development of the Product in the Field and in the Licensed Territory, consistent with the then-agreed Development Plan, and in accordance with this Agreement, including without limitation by using Diligent Efforts to perform its obligations under the Development Plan and in accordance with the regulations promulgated by the MHLW for the manufacture, testing and Commercialization of pharmaceutical products in the Licensed Territory.  Collaborator shall provide financial and other support for the Development of the Product as necessary to carry out the Development Plan and to achieve the objectives of this Agreement.  Collaborator shall conduct its activities under the Development Plan in good scientific manner and in compliance in all material respects with all applicable Laws, including without limitation applicable GCP, GLP,

 


[ * ] = 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 406 of the Securities Act of 1933, as amended.

 

22



 

and GMP.  Collaborator may not conduct any material Development activities with respect to any Product that are not set forth in the Development Plan or that are inconsistent with this Agreement without Affymax’s prior written consent.

 

3.5                                Records, Reports and Information .   Collaborator shall maintain complete, current and accurate records of all work conducted by it under the Development Plan and all data and other Information resulting from such work.  Such records shall fully and properly reflect all work done and results achieved in the performance of the Development Plan in sufficient detail and in good scientific manner appropriate for patent and regulatory purposes.  Affymax shall have the right to review such records maintained by Collaborator at reasonable times, upon written request.  Collaborator shall provide written reports in English to the Joint Committee on its Development and regulatory activities with Products in the Licensed Territory, including without limitation any significant formal or informal meetings between Collaborator and the Regulatory Authority in the Licensed Territory, on a quarterly basis at the end of each calendar quarter, at a level of detail reasonably sufficient to enable Affymax to determine Collaborator’s compliance with its diligence obligation pursuant to Section 3.4.

 

3.6                                Right of First Refusal to Backup Product Developed in the Field.  If, during the ten (10) year period following the Effective Date, Affymax or its Third Party Partner develops a potential Backup Product(s) in the Field, Collaborator shall have a right of first refusal to develop and commercialize such Backup Product(s) for the Licensed Territory as provided in this Section 3.6.  Upon the initiation of the first Phase II Clinical Trial for such Backup Product(s) in the Field, and before offering to any Third Party rights to such potential Backup Product(s) in the Licensed Territory, Affymax shall notify Collaborator in writing, and shall include in such notification all material results and data with respect to such potential Backup Product(s), for Collaborator’s evaluation. Collaborator shall treat such results and data as Affymax’s Confidential Information under this Agreement, and shall respond to Affymax within thirty (30) days of receiving such notification whether it desires to exercise its right to negotiate exclusively for the rights to Develop and Commercialize such Backup Product(s) in the Field, in the Licensed Territory.  If Collaborator notifies Affymax within such thirty (30) day period of its desire to obtain such rights, then Affymax and Collaborator shall negotiate in good faith for

 


[ * ] = 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 406 of the Securities Act of 1933, as amended.

 

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ninety (90) days the terms and conditions under which Collaborator may obtain such rights.  If Collaborator and Affymax enter into an agreement under which Collaborator obtains such rights with respect to certain Backup Product, then such Backup Product(s) shall also be licensed to Collaborator under such agreed terms and conditions.  If Collaborator fails to notify Affymax of its desire to obtain such rights within such thirty (30) day period, or if the Parties, despite good faith negotiation, do not enter into an agreement governing the terms and conditions under which Collaborator may obtain such rights from Affymax within such ninety (90) day period, then, unless the Parties agree to prolong such period, Affymax shall have the right to pursue such opportunity itself or with an Affiliate or Third Party without any further obligation to Collaborator.   This Section 3.6 shall apply on a Backup Product by Backup Product basis.  For clarity, if and as far as a Backup Product is developed outside the Field by Affymax and/or its Third Party Partner, then Collaborator shall have no rights under this Section 3.6 with respect to such Backup Product.

 

ARTICLE 4

 

REGULATORY MATTERS

 

4.1                                Transfer of Data and Regulatory Materials .

 

(a)                                   Data Generated by Affymax.

 

(i)                                     Within thirty (30) days after the Effective Date, Affymax shall provide Collaborator with copies of IND and CTA filings made for the Product in the U.S. and Europe prior to the Effective Date.  With regard to all other preclinical and non-clinical data (including [ * ] above-mentioned IND and CTA filings, in the form then existing) generated as of the Effective Date and Controlled by Affymax, Affymax shall, if requested by Collaborator, provide Collaborator with copies thereof within a reasonable time after such request to the extent relevant to the Development of Product or Collaborator’s seeking Regulatory Approval for the Product in the Licensed Territory.  Thereafter, from time to time but in a timely manner compliant with the requirements of the Regulatory Authority in the Licensed Territory, Affymax shall provide Collaborator with copies of [ * ] preclinical and non-clinical data generated from

 


[ * ] = 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 406 of the Securities Act of 1933, as amended.

 

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[ * ] the Effective Date by Affymax and Controlled by Affymax.  Collaborator shall have the full right, without any additional consideration, to use any and all such data and reports supplied by Affymax under this Section 4.1(a)(i) in connection with the Development of the Product in the Licensed Territory, including the incorporation of such data or reports in any MAA.

 

(ii)                                 Within thirty (30) days after the Effective Date, Affymax shall provide Collaborator with copies of all clinical data resulting from [ * ] completed or ongoing (where available) as of the Effective Date and Controlled by Affymax.  Thereafter, following completion of any additional [ * ] ] conducted by Affymax with or without [ * ] , Affymax shall, in a timely manner compliant with the requirements of the Regulatory Authority in the Licensed Territory, provide Collaborator with copies of all resulting data, to the extent such data is Controlled by Affymax. Collaborator shall have the full right to use any and all such data and reports supplied by Affymax pursuant to this Section 4.1(a)(ii) in connection with the Development of the Product in the Licensed Territory, including the incorporation of such data or reports in any MAA.

 

(iii)                             With respect to clinical data Controlled by Affymax and resulting from [ * ] completed or ongoing as of the Effective Date, Affymax shall provide Collaborator with copies of all resulting data upon request of Collaborator after completion of such trial.  It is understood and agreed, however, that Collaborator shall have the right to use any and all such data and reports supplied by Affymax hereunder only to the extent that the Regulatory Authorities in the Licensed Territory require that such data and or reports be submitted to it to substantiate the clinical data generated by or on behalf of Collaborator in seeking Regulatory Approval for the Product in the Licensed Territory, either as part of the MAA or otherwise.  In no event shall Collaborator have the right to utilize such [ * ] data in its MAA for the Product in the Licensed Territory in lieu of additional [ * ] data generated by or on behalf of Collaborator in the Licensed Territory, without the written consent of Affymax, which consent may be withheld in its sole discretion, and which consent if given, shall require [ * ] to Affymax for such use of such data.

 


[ * ] = 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 406 of the Securities Act of 1933, as amended.

 

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(iv)                                Collaborator acknowledges and understands that Affymax intends to license the Product to one or more Third Party licensees for development and commercialization in the Affymax Territory (each, a “ Third Party Partner ”).  Pursuant to any agreements between Affymax and its Third Party Partner, Affymax and/or such Third Party Partners will generate, at the expense primarily of such Third Party Partner, additional non-clinical, preclinical and clinical data and reports (including in particular [ * ] and [ * ] with respect to the Product for use in seeking Regulatory Approval for the Product in the Affymax Territory (the “ Third Party Data ”). With respect to any Third Party Data Controlled by Affymax [ * ] , Affymax shall provide Collaborator with copies of all such Third Party Data upon request of Collaborator unless (X) Affymax [ * ] and/or (Y)  [ * ] Third Party Partner in connection therewith. For any Third Party Data to which (X) and/or (Y) applies, Collaborator shall have the rights set forth in Section 4.1(b)(ii).   It is understood and agreed, however, that Collaborator shall have the right to use any and all such Third Party Data and reports supplied by Affymax under this Section 4.1(a)(iv) only to the extent that the Regulatory Authorities in the Licensed Territory require that such data be submitted to it to substantiate the non-clinical, preclinical or clinical data generated by or on behalf of Collaborator in seeking Regulatory Approval for the Product in the Licensed Territory, either as part of the MAA or otherwise.  In no event shall Collaborator have the right to utilize such Third Party Data provided pursuant to this Section 4.1(a)(iv) in its MAA for the Product in the Licensed Territory in lieu of additional non-clinical, pre-clinical or clinical data generated by or on behalf of Collaborator in the Licensed Territory, without the written consent of Affymax, which consent may be withheld in its sole discretion, and which consent if given, shall require [ * ] for such use of such data.   For clarity, this Section 4.1(a)(iv) shall not apply to any audited data that Affymax may provide to Collaborator pursuant to Section 4.1(b)(i).

 

(v)                                    With respect to any data generated pursuant to any [ * ] that is commenced [ * ] by Affymax other than [ * ] , to the extent such data is Controlled by Affymax, Affymax shall provide Collaborator with copies of all data arising from such trial upon request of Collaborator, provided that the Parties have first agreed upon a mutually acceptable [ * ] for

 


[ * ] = 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 406 of the Securities Act of 1933, as amended.

 

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such use of such data; provided that information regarding adverse events and serious adverse events shall be provided promptly as set forth in Section 4.8.

 

(vi)                                For clarity, the foregoing shall not be deemed to limit the Parties’ obligations with respect to information to be provided pursuant to Section 4.8.  Additionally, except as expressly provided in subsections (iii) and (iv), Collaborator shall not be obligated [ * ] for the information, data and reports to be provided pursuant to this Section 4.1(a).

 

(b)                                   Audited Data Generated by Third Parties on Behalf of Affymax; Requests for Additional Data by Collaborator.

 

(i)                                     Affymax understands and acknowledges Collaborator’s need to utilize and include copies of certain [ * ] and certain summary and general information regarding the [ * ] of the Product that has been a


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