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Exhibit 10.25

[ * ] = 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 June 27, 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 ( “Takeda” ). Affymax and Takeda are sometimes referred to herein individually as a “Party” and collectively as the “Parties” .

RECITALS

WHEREAS , Affymax is a pharmaceutical company focused on the development of novel, synthetic peptide-based pharmaceutical products against targets for various diseases and conditions;

WHEREAS , Takeda is a worldwide pharmaceutical company engaged in the development, manufacturing and marketing of pharmaceutical products;

WHEREAS , Affymax has been developing the Product (as hereinafter defined), which contains a proprietary pegylated [ * ] drug candidate known as Hematide™, for the treatment of anemia in patients with chronic kidney disease and cancer;

WHEREAS , Affymax and Takeda have entered into a collaboration for the development and commercialization of the Product in Japan for the treatment of anemia under the terms of the Japan Agreement (as hereinafter defined);

WHEREAS , Affymax and Takeda desire to establish a broad collaboration under this Agreement for the joint development and commercialization of the Product in the United States for the treatment of anemia in patients with chronic kidney disease and cancer and other indications as the Parties may jointly or unilaterally develop in such territory with Affymax serving as the primary responsible Party for the treatment of anemia in patients with chronic kidney disease and Takeda serving as the primary responsible Party for the treatment of anemia in patients with cancer, and to provide for the sole development by Takeda in other countries throughout the world, except for Japan (as contemplated under the Japan Agreement);

WHEREAS , the Parties desire that Affymax manufacture or have manufactured clinical and commercial supplies of the Bulk API (as hereinafter defined) and/or the Product and Takeda perform the Finished Manufacture (as hereinafter defined) for use by both Parties hereunder;

WHEREAS , Affymax and Takeda desire to co-commercialize the Product in the United States and share equally in the costs and efforts for the purpose of and in the profits resulting from marketing and sales of the Product in the United States and to provide for the payment by Takeda to Affymax of certain royalty payments on sales of the Product in the other territories of the world, except for Japan, in each case in accordance with the terms set forth below;

WHEREAS , Affymax desires to grant to Takeda exclusive rights to the Products and certain backup compounds in the United States and other countries of the world, except for Japan (which rights have separately been granted to Takeda), under this Agreement, and Takeda desires to obtain such rights in each case on the terms set forth below;

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

ARTICLE 1

DEFINITIONS

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 “Additional Indication” means any use for the Product in the Field, other than the Initial Indications.

1.2 “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 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, TAP Pharmaceutical Products Inc. shall not be deemed to be an Affiliate of Takeda.

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

1.4 “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 or Commercialization of the Product. For clarity, Affymax Know-How excludes the Affymax Patents.

1.5 “Affymax Patent” means any Patent, including Affymax’s interest in 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 or Commercialization of the Product. The list of Affymax Patents as of the Effective Date is

attached hereto as Exhibit B, and shall be from time to time amended and updated during the Term to incorporate the then-current Affymax Patents.

1.6 “Affymax Technology” means the Affymax Patents and Affymax Know-How.

1.7 “Alliance Representative” has the meaning set forth in Section 2.7.

1.8 “Anemia of Cancer” means anemia in patients with cancer (but excluding Chemotherapy-Induced Anemia).

1.9 “Backup Compound” means any synthetic peptide-based [ * ] ESA Controlled by Affymax as of the Effective Date and for ten (10) years after the Effective Date, which such ESA: (i) has [ * ], which are [ * ] Hematide; and/or (ii) has a reasonable [ * ] sufficient for the primary use of such product for the prevention, treatment or amelioration of anemia in humans. For the avoidance of doubt, Backup Compounds shall exclude any [ * ] Product subject to Section 6.6(b). The initial list of the Backup Compounds is attached hereto as Schedule 1.9 and shall be updated from time to time by Affymax and provided to Takeda promptly. The list of the Backup Compounds thus updated shall include any synthetic peptide-based [ * ] ESA which falls in the above definition which are discovered or developed by Affymax during the course of the Backup Research Agreement and thereafter.

1.10 “Backup Research Agreement” has the meaning set forth in Section 3.7.

1.11 “Bulk API” means Hematide in bulk form.

1.12 “Business Day” means any day other than (i) Saturday or Sunday or (ii) any other day on which banks in San Francisco, California, United States or Osaka, Japan are permitted or required to be closed.

1.13 “Chemotherapy-Induced Anemia” means anemia caused by chemotherapy treatments for cancer.

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

1.15 “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 Royalty Territory.

1.16 “Commercial Expenses” means those expenses incurred for the purpose of the Commercialization of the Finished Product in the U.S. which are consistent with the budget set forth in the U.S. Commercialization Plan and are specifically attributable to the Commercialization of Finished Products in the U.S., and shall consist of (i) Cost of Goods Sold, (ii) Pre-Marketing Expenses, (iii) Marketing Expenses, (iv) Distribution Expenses, (v) Clinical Phase IV and Related Expenses, (vi) Regulatory Expenses, (vii) the Launch Expense Allowance, (viii) Medical Science Liaison Expenses, and (ix) amounts paid to Third Party licensors as described in Section 8.6 (as such terms are defined in Exhibit J). Commercial Expenses shall exclude Development Expenses, even if incurred after the first commercial launch of a Finished

Product in the U.S., and shall exclude any costs that are deductible from Net Sales under the definition thereof ( e.g. , distributor fees). For avoidance of doubt, any cost deducted in the calculation of Net Sales shall not be deducted in the calculation of the Commercial Expenses.

1.17 “Commercialization” , with a correlative meaning for “Commercialize” , means all activities undertaken before and after obtaining Regulatory Approval relating specifically to the pre-marketing, 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.

1.18 “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.

1.19 “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 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.

1.20 “Cross-License Agreement” means that certain Cross-License and License Option Agreement entered into by and among Nektar, Enzon, and Inhale Therapeutic Systems, Inc. on January 7, 2002, under which Nektar obtained certain rights under the Enzon Patents and which are sublicensed to Affymax by Nektar under the Nektar Agreement.

1.21 “Detail” or “Detailing” means, with respect to the Product, the communication by a Sales Representative during a Sales Call (a) involving face-to-face contact, (b) describing in a fair and balanced manner the Regulatory Authority-approved indicated uses and other relevant characteristics of the Product, (c) using the Promotional Materials in an effort to increase the prescribing and/or hospital ordering preferences of the Product for its approved indicated uses, and (d) made at such medical professional’s office, in a hospital, at marketing meetings sponsored by a Party for the Product or other appropriate venues conducive to pharmaceutical product informational communication where the principal objective is to place an emphasis, either primary or secondary, on the Product with such medical professional.

1.22 “Develop” or “Development” means all activities relating to preparing and conducting preclinical testing, toxicology testing, human clinical studies, regulatory affairs for obtaining the Regulatory Approvals, formulation development, process development for

manufacture and associated validation, quality assurance and quality control activities (including qualification lots). Development shall exclude all Phase IV Clinical Trials.

1.23 “Development Budget” means the budget of U.S. Development Expenses set forth in the U.S. Development Plan to be incurred by the Parties in connection with the performance of the U.S. Development Plan.

1.24 “Development Expenses” means (i) the U.S. Development Expenses, (ii) Manufacturing Development Expenses incurred by either Party for relevant activities performed on or after January 1, 2007, (iii) the Third Party milestone payments identified on Exhibit N (but not other milestones payable to Third Parties on account of the Development of the Product), (iv) the costs for Phase II Clinical Trial for Oncology Indications incurred by Takeda for relevant activities conducted on or after the Effective Date until the end of December 31, 2006, (v) the price from Affymax to Takeda of Bulk API and/or the Finished Product used for the U.S. Development of the Product as well as the freight, postage, shipping, transportation, insurance, warehousing and handling charges actually allowed or paid by Takeda with regard to such Bulk API, and (vi) the cost incurred by Takeda for the Finished Manufacture of the Product used for the U.S. Development of the Product as well as the freight, postage, shipping, transportation, insurance, warehousing and handling charges actually allowed or paid by Takeda with regard to such Product; but excluding, [ * ]. For clarity, any amounts payable by Affymax for ongoing clinical, non-clinical, preclinical and other trials regarding the Product performed on or before December 31, 2006 shall not be included as Development Expenses and shall be borne by Affymax.

1.25 “Dialysis CKD Anemia” means use of the Product in the prevention, treatment or amelioration of anemia in patients with chronic kidney disease who are on dialysis.

1.26 “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 multinational pharmaceutical company (in the case of Takeda) devotes to a product of similar market potential, profit potential or strategic value within its portfolio, based on conditions then prevailing. Without limiting the foregoing, Diligent Efforts requires, with respect to such an obligation, that the Party: (a) within a reasonable time 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.

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

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

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

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.

1.30 “Enzon” means Enzon Pharmaceuticals, Inc., a Delaware corporation having its principal offices at 685 Route 202/206, Bridgewater, New Jersey 08807, USA.

1.31 “Enzon Patents” means the Patents licensed from Enzon and identified on Exhibit B.

1.32 “ESA” means erythropoiesis stimulating agent.

1.33 “European Union” or “EU” means all of the European Union member states as of the applicable time during the Term.

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

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

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

1.37 “Field” means the prevention, treatment or amelioration of any disease or condition in humans.

1.38 “Finance Subcommittee” has the meaning set forth in Section 2.6(c).

1.39 “Finished Manufacture” means the manufacture (and all reasonably necessary testing, including release and, as appropriate, stability testing) of Finished Product from Bulk API.

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

1.41 “First Commercial Sale” means, with respect to a particular country and the Product, the first sale to a Third Party of the Product in such country after Regulatory Approval has been obtained in such country.

1.42 “Fiscal Year” means the twelve (12)-month period commencing on April 1 of a given year and ending on March 31 of the following year.

1.43 “Good Clinical Practices” or “GCP” means the then-current good clinical practice standards, practices and procedures promulgated or endorsed by the FDA as set forth in the guidelines entitled “Guidance for Industry E6 Good Clinical Practice: Consolidated Guidance,” including related regulatory requirements imposed by the FDA, and comparable

regulatory standards, practices and procedures in jurisdictions outside the U.S., in each case as they may be updated from time to time.

1.44 “Good Laboratory Practices” or “GLP” means the then-current good laboratory practice standards promulgated or endorsed by the FDA as defined in 21 C.F.R. Part 58, and comparable regulatory standards in jurisdictions outside the U.S., in each case as they may be updated from time to time.

1.45 “Good Manufacturing Practices” or “GMP” means the then-current good manufacturing practices required by the FDA, as set forth in the FD&C Act and the regulations promulgated thereunder, for the manufacture and testing of pharmaceutical materials, and comparable Laws applicable to the manufacture and testing of pharmaceutical materials in jurisdictions outside the U.S., including without limitation 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, in each case as they may be updated from time to time.

1.46 “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).

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

1.48 “IND” means (a) an Investigational New Drug application as defined in the FD&C Act and applicable regulations promulgated thereunder by the FDA.

1.49 “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 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.

1.50 “Initial Indications” means the Oncology Indications and the Renal Indications.

1.51 “[ * ]” means any [ * ] agent, [ * ] , [ * ] , developed under an Affymax research or development program that is used to [ * ] , either directly or indirectly, from [ * ] due to [ * ] , or any other such [ * ] , including [ * ] ; or to treat an [ * ] , directly or indirectly, to such [ * ] with the intent of [ * ] , subject to Section 6.6(b). For clarity, an [ * ] may act as an agonist or antagonist through the EPO receptor or related receptors, or through other known or unknown receptors on the surface of the cells in question, or it may act independently of a cell surface receptor.

1.52 “Internal Expenses” means any costs for employees (to be charged at a fixed rate to be agreed by the Parties from time to time), overhead, or other internal handling incurred by a Party, which expenses are generally consistent with the U.S. Development Plan and are specifically attributable to the U.S. Development.

1.53 “Japan Agreement” means the Collaboration and License Agreement dated as of February 13, 2006 between Affymax and Takeda under which the parties have entered into a collaboration for the development and commercialization of the Product in Japan for the treatment of anemia.

1.54 “Joint Steering Committee” or “JSC” means the committee formed by the Parties as described in Section 2.3(a).

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

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

1.57 “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.

1.58 “Level 1 Market” means any of the following countries: [ * ] .

1.59 “Level 2 Market” means any of the following countries: [ * ] .

1.60 “Licensed Territory” means worldwide except Japan, its territories and possessions, as adjusted from time to time pursuant to Section 3.5.

1.61 “Major EU Market Country” means any of the following countries: [ * ].

1.62 “Manufacturing Costs” has the meaning set forth in Exhibit J.

1.63 “Manufacturing Development” means any of the following with respect to Bulk API or Finished Product: manufacturing process development and validation, process improvements, associated analytical development and validation and the manufacture and testing of clinical and stability or consistency lots (including process development, qualification, QA, and test batches).

1.64 “Manufacturing Development Expenses” means any costs incurred by a Party to a Third Party after the Effective Date for the Manufacturing Development.

1.65 “Marketing Authorization Application” or “MAA” means an application for Regulatory Approval (but excluding Pricing Approval) in any particular jurisdiction other than the U.S.

1.66 “NDA” means a New Drug Application filed with the FDA for Regulatory Approval of a product in the U.S.

1.67 “Nektar” means Nektar Therapeutics AL Corporation, an Alabama corporation having its principal place of business at 490 Discovery Drive, Huntsville, AL 35806, USA.

1.68 “Nektar Agreement” means that certain License, Manufacturing, and Supply Agreement between Affymax and Nektar Therapeutics AL, dated as of April 8, 2004, under which Affymax is granted a right, license and/or sublicense under certain of Nektar’s patents and technologies and Enzon Patents, which patents are included in the Affymax Patents.

1.69 “Net Sales” means, with respect to a particular time period, the total amounts received or invoiced by Takeda, its Affiliates and their respective sublicensees for sales of Finished Product 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 or administrative fees actually paid to trade customers, patients (including those in the form of a coupon or voucher), managed health care organizations, pharmaceutical benefit managers, group purchasing organizations, federal, state, or local government and the agencies, purchasers and reimbursers of managed health organizations, pharmaceutical benefit managers, group purchasing organizations, or federal, state or local government; provided, however, that: (i) the aggregate of such discounts, charge-back payments and rebates in each country of the Royalty Territory shall not exceed [ * ] of the amounts received or invoiced in such country; and, (ii) if such limit of [ * ] in a country of the Royalty Territory is not sufficient or appropriate due to significant amount or percentage of discounts, charge-back payments or rebates mandatorily required by Governmental Authorities in such country, and/or, if such limit is not sufficient for adequately maintaining the competitive position of the Products in such country, then the Parties shall confer in good faith regarding whether any increase in such limit is appropriate under the circumstances;

(b) credits or allowances actually granted upon prompt payment or claims, bad debts and losses actually incurred as a result of actual write-offs of uncollectible customer accounts, damaged goods, rejections or returns of such Product, including in connection with recalls;

(c) packaging, freight, postage, shipping, transportation, warehousing, handling and insurance charges, credit card processing fees and any customary payments with respect to the Products actually made to wholesalers or other distributors, in each case actually allowed or paid for distribution and delivery of Product, to the extent billed or recognized; and

(d) taxes (other than income taxes), duties, tariffs or other governmental charges levied on the sale of such Product, including, without limitation, value-added and sales taxes.

Notwithstanding the foregoing, amounts received or invoiced by Takeda, its Affiliates, or their sublicensees for the sale of Finished Product among Takeda, its Affiliates or their respective sublicensees for resale shall not be included in the computation of Net Sales hereunder. In any event, any amounts received or invoiced by Takeda, its Affiliates, or their sublicensees shall be accounted for only once. Net Sales shall be accounted for in accordance with standard Takeda

practices for operation by Takeda, its Affiliates or sublicensees, as practiced in the relevant country in the Licensed Territory, but in any event in accordance with generally accepted accounting principles, consistently applied in such country in the Licensed Territory. Net Sales shall exclude any samples of Product transferred or disposed of at no cost for promotional or educational purposes, and the cost for such samples transferred or disposed of in the U.S. shall be deemed to be included in the Commercial Expenses.

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

1.70 “Oncology Indications” means, collectively, Anemia of Cancer and Chemotherapy-Induced Anemia.

1.71 “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.

1.72 “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.

1.73 “PDE” shall mean one Primary Position Detail (as defined below), two Secondary Position Details (as defined below) or five Tertiary Position Details (as defined below).

1.74 “PEG” means poly(ethylene) glycol or a derivative thereof.

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

1.76 “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.

1.77 “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.

1.78 “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.

1.79 “Phase IV Clinical Trial” means a clinical trial of a Product, possibly including pharmacokinetic studies, which trial is (a) not required in order to obtain Regulatory Approval of the Initial Indication or the Joint Additional Indication; (b) required by the Regulatory Authority as mandatory to be conducted on or after the Regulatory Approval of the Initial Indications or the Joint Additional Indication, and (c) conducted voluntarily by a Party to enhance marketing or scientific knowledge of the Product ( e.g. , providing additional drug profile, safety data or marketing support information, or supporting expansion of Product Labeling or conducted due to a request or requirement of a Regulatory Authority.

1.80 “Pre-Dialysis CKD Anemia” means use of the Product in the prevention, treatment or amelioration of anemia in patients with chronic kidney disease who are not on dialysis.

1.81 “Pricing Approval” means such approval, agreement, determination or governmental decision establishing prices for the Product that can be charged to consumers and shall be reimbursed by Governmental Authorities in regulatory jurisdictions where the Governmental Authorities or Regulatory Authorities approve or determine pricing of pharmaceutical products for reimbursement or otherwise.

1.82 “Primary Position Detail” means a Detail during which (i) the applicable Product is discussed either itself or along with other pharmaceutical products, (ii) key product attributes of such Product are verbally promoted in the first position on such Detail, and (iii) such Product is given the majority of the emphasis during the presentation. For clarity, no more than one Detail during a Sales Call shall be considered a Primary Position Detail.

1.83 “Product” means a pharmaceutical preparation in any formulation that contains Hematide or, subject to the terms of Section 3.11, a Replacement Product Candidate as an active ingredient. In addition, an Additional Product shall become a Product pursuant to the terms of Section 3.12.

1.84 “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.

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

1.86 “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.

1.87 “Product Subcommittee” has the meaning set forth in Section 2.6(b).

1.88 “Product Trademark” means the mark “HEMATIDE” and any logos or symbols incorporating such mark and any product trademark selected pursuant to Section 5.11.

1.89 “Profit Equalization Payment” means the amount payable by one Party to the other to effect an allocation of the U.S. Product Profit between the Parties as described in Section 8.4 and the final financial statement approved by the JSC for a calendar quarter. By way of example, assuming an equal allocation of profits and losses, if Takeda has an operating profit of 40 and Affymax has an operating loss of 10, then the Profit Equalization Payment made by Takeda to Affymax shall be 25.

1.90 “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 or on behalf of Takeda 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.

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

1.92 “Regulatory Approvals” means all approvals (including without limitation supplements, amendments, and Pricing 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 a given regulatory jurisdiction.

1.93 “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, in the U.S., the FDA and any other applicable Governmental Authority in the U.S. having jurisdiction over the Product, and, in the European Union, the EMEA and any other applicable Governmental Authority having jurisdiction over the Product.

1.94 “Regulatory Materials” means regulatory applications, submissions, notifications, registrations, Regulatory Approvals or other submissions made to or with a Regulatory Authority that are necessary or reasonably desirable in order to develop, manufacture, market, sell or otherwise commercialize the Product in a particular country, territory or possession. Regulatory Materials include, without limitation, INDs, CTAs and MAAs, NDAs, and amendments and supplements for any of the foregoing, and applications for Pricing Approvals.

1.95 “Renal Indications” means, collectively, Pre-dialysis CKD Anemia and Dialysis CKD Anemia.

1.96 “Replacement Product Candidate” means any Backup Compound linked to PEG [ * ] (including [ * ] .

1.97 “Royalty Territory” means all countries in the Licensed Territory other than the U.S.

1.98 “ROW Commercialization Plan” has the meaning set forth in Section 5.2(b).

1.99 “ROW Development” means the Development of the Products specifically required only in a certain country or countries of the Royalty Territory to support Regulatory Approval of the Product for the Initial Indications and/or the Joint Additional Indications, if any, in such country or countries of the Royalty Territory, irrespective of the country wherein a study thereof is conducted. For the purpose of this definition, Manufacturing Development shall be excluded from the ROW Development.

1.100 “Sales Call” means a personal visit by a Sales Representative to one or several medical professional(s) having prescribing authority in the part of the Field for the indications in which the Product is approved, as well as to other individuals or entities that have significant impact or influence on prescribing decisions in the part of the Field in which the Product is approved during which such Sales Representative Details the Product.

1.101 “Sales Representative” means a pharmaceutical sales representative engaged or employed by either Party to conduct Detailing and other promotional efforts with respect to the Product, including contract sales organizations of such Party.

1.102 “Secondary Position Detail” shall mean a Detail during which key product attributes of a Product are verbally promoted and detailed in the second position on such Detail; provided, however, that no more than one presentation in any Detail shall be considered a Secondary Position Detail, which shall be the presentation on which the second-most time is spent during the Detail.

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

1.104 “Supply Agreement” has the meaning set forth in Section 7.3.

1.105 “Takeda Know-How” means all Information that is Controlled by Takeda 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, Takeda Know-How excludes Takeda Patents.

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

1.107 “Takeda Technology” means the Takeda Patents and Takeda Know-How.

1.108 “Tertiary Position Detail” shall mean a Detail during which key product attributes of a Product are verbally promoted and detailed in the third or lesser position on such Detail.

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

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

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

1.112 “U.S. Development” means the Development of the Products conducted hereunder for the primary purpose of supporting (whether pivotal or not) the U.S. Regulatory Approvals for the Initial Indications and/or the Joint Additional Indications, if any, irrespective of the country wherein a study thereof is conducted and irrespective whether the result of which is also used for the purpose of supporting the Regulatory Approvals in the Royalty Territory. For the purpose of this definition, Manufacturing Development shall be excluded from the U.S. Development.

1.113 “U.S. Commercialization Plan” has the meaning set forth in Section 5.2(a).

1.114 “U.S. Development Expenses” means any amounts payable by a Party for obligations to a Third Party for the U.S. Development performed on or after January 1, 2007, which expenses are generally consistent with the Development Budget.

1.115 “U.S. Development Plan” means the plan of the U.S. Development. The initial U.S. Development Plan is attached hereto as Exhibit H. Exhibit H may be from time to time added or modified by the JSC.

1.116 “U.S. Product Profit” means the profits or losses resulting from the Commercialization of the Product in the U.S. and shall be equal to Net Sales of the Product in the U.S., less Commercial Expenses.

1.117 “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.

ARTICLE 2

MANAGEMENT

2.1 Collaboration Overview . The Parties desire and intend to collaborate with respect to the Development and Commercialization of the Product in the Licensed Territory, as and to the extent set forth in this Agreement. It is understood and acknowledged by each Party that such Party shall participate in the clinical development of the Product for identified indications, including the Initial Indications, in the Licensed Territory pursuant to an agreed-upon U.S. Development Plan. The Parties shall share the development costs incurred in connection with

the performance of the U.S. Development Plan, as set forth in, and in accordance with, Article 3. Takeda shall bear the development costs incurred in connection with the performance of the ROW Development, as set forth in, and in accordance with, Article 3. Affymax shall be primarily responsible for obtaining and maintaining Regulatory Approval of the Product in the Field in the U.S. based on the then-current U.S. Development Plan, and Takeda shall be solely responsible for obtaining and be solely entitled to obtain and maintain Regulatory Approval of the Product in the Field in the Royalty Territory. In the U.S., the Parties shall co-promote the Product for the Initial Indications and share profits from the Initial Indications equally, with Affymax primarily participating in the sales and marketing efforts in the Renal Indications, subject to the payment obligations in Article 8 and the other terms of this Agreement. Takeda shall have the exclusive right to Commercialize the Product in the Royalty Territory, subject to the payment obligations in Article 8 and the other terms of this Agreement. Each Party understands and agrees that it is to the Parties’ mutual benefit to maximize the commercial potential of the Product as far as commercially reasonably possible, and accordingly, that time is of the essence in addressing the market for the Product in the Field and the Licensed Territory.

2.2 Commitment to U.S. Development Plan . Each Party agrees and acknowledges that, by entering into this Agreement, it shall fund, as and to the extent set forth in Article 3, the Development of the Product in the Initial Indications pursuant to the U.S. Development Plan, and shall use Diligent Efforts to conduct the activities assigned to such Party in the U.S. Development Plan, with the JSC overseeing the implementation of such plan. Neither Party shall be obligated to expend any funds with respect to or participate in any clinical trials in support of any Additional Indications, except as provided in Section 3.10. The conduct of clinical trials and development activities in support of any such Additional Indications and Commercialization of the Product for such indications, if any, shall be governed by Section 3.10.

2.3 Joint Steering Committee .

(a) Formation and Role. The Parties hereby establish a Joint Steering Committee that shall monitor and coordinate communication regarding the Parties’ performance under this Agreement to Develop, obtain Regulatory Approval for and Commercialize the Product in the Field. The role of the JSC shall be:

(i) to review the overall strategy for Developing and seeking Regulatory Approval for, manufacturing, and Commercializing the Product in the Licensed Territory and in the Field;

(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 each Party’s Development and Commercialization of the Product hereunder, consistent with this Agreement;

(iii) to review, approve, and, if necessary, amend the U.S. Development Plan, the Development Budget and the U.S. Commercialization Plan (including related budget);

(iv) to review the plan and the summary budget for the ROW Development to the extent customarily generated by or available to Takeda from its Affiliates or sublicensees for its internal purposes with respect to the applicable countries in the Royalty

Territory (all Level 1 Markets and Level 2 Markets wherein Takeda decides to Develop the Product, as described in further detail in Section 3.5) and the ROW Commercialization Plan and provide comments regarding the content and implementation of such plans, which comments shall not be controlling but shall be considered by Takeda in good faith;

(v) to monitor the Parties’ performance against the then-current U.S. Development Plan and Commercialization Plans;

(vi) to create subcommittees as the JSC may find necessary or desirable from time to time for implementation of the Development and Commercialization hereunder;

(vii) to oversee the activities of subcommittees created under this Agreement, and to seek to resolve any issues that such subcommittees cannot resolve;

(viii) without reducing Affymax’s obligation to obtain and maintain the Affymax Patents and/or the Product Trademark provided for herein, to provide a forum to evaluate strategies for obtaining, maintaining and enforcing patent and trademark protection for the Product in the Licensed Territory; and

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

(b) Guiding Principles. The JSC shall perform its responsibilities under this Agreement based on the principles of prompt and diligent Development and Commercialization of the Product in the Licensed Territory, consistent with good pharmaceutical practices and the maximization, to a commercially reasonable extent, of long-term profits derived from the sale of the Product in the Licensed Territory. The JSC shall have only the powers assigned expressly to it in this Article 2 and elsewhere in this Agreement, and the JSC shall not have any power to amend, modify or waive compliance with this Agreement. For clarity, with regard to the Development and the Commercialization of the Product in the Royalty Territory, Takeda shall be entitled to develop and modify the plans and budgets therefor at its discretion, subject only to Takeda’s obligations as provided in Section 3.5 and Article 4, and the JSC shall not be entitled to approve or disapprove such plans and budgets.

2.4 JSC Membership. Each Party shall have an equal number of representatives on the JSC, who initially shall be the eight (8) individuals at the [ * ] (or other equivalent individuals having senior decision-making authority over JSC matters) as set forth in Exhibit F. The JSC may change its size from time to time by mutual consent of the Parties, provided that the JSC shall at all times consist of an equal number of representatives of each of Affymax and Takeda. 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). The initial representatives and any 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, one (1) representative shall have appropriate expertise in Commercialization of pharmaceutical products, and one (1) representative shall have expertise appropriate to the then-current state of Product

Development or Commercialization; provided that the JSC may vary the expertise required for JSC representatives of each Party as it deems appropriate as the Parties gain experience with the Product, but in any event at least one (1) of such representatives on the JSC shall be at the [ * ] in each of the Party’s organizations. Affymax shall select one (1) of its representatives as the initial chairperson of the JSC. On April 1 of each year after 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, but shall have no special authority over the other members of the JSC, and shall have no additional voting rights.

2.5 JSC Meetings, Decisions and Actions .

(a) Meetings. The JSC shall hold at least three (3) meetings per year (at least two (2) of which shall be held in person) on such dates at such times each year as it elects. Meetings of the JSC shall be effective only if at least two (2) representatives of each Party are present or participating. Each Party shall bear the expense of its respective members’ participation in JSC meetings. The Chairperson of the JSC shall be responsible for preparing and issuing minutes of each such meeting within thirty (30) days thereafter. Such minutes shall not be finalized until each Party reviews and confirms the accuracy of such minutes in writing; provided that any minutes shall be deemed approved unless a member of the JSC objects to the accuracy of such minutes within thirty (30) days after the circulation of the minutes by the Chairperson. With the prior consent of both Parties’ representatives (such consent not to be unreasonably withheld or delayed), other representatives of each Party or Third Parties involved with the Products may attend meetings as nonvoting participants.

(b) Decision Making. Except as expressly provided in this Section 2.5, actions to be taken by the JSC shall be taken only following unanimous vote, with each Party having one (1) vote.

(c) Disputes. If the members of the JSC cannot reach a unanimous decision with respect to matters delegated to it under this Article 2 (including without limitation any issue involving clinical trial design, priority of clinical trials, timelines, and the like, or the approval of any component of an amended or updated U.S. Development Plan or U.S. Commercialization Plan) for a period in excess of ten (10) Business Days from the discussion at the JSC, unless the Parties agree to prolong such time period, the matter shall be referred to two appropriately qualified senior executive officers of the Parties, who shall attempt resolution by good faith negotiations for at least thirty (30) days after such referral. If the senior executive officers designated by the Parties are not able to resolve such dispute within such thirty (30) day period, then such dispute shall be finally decided by expedited arbitration in accordance with the terms described on Exhibit M , except that disputes described in Section 3.10(c) shall not be subject to such arbitration procedure.

2.6 Subcommittees.

(a) The JSC may, from time to time, form any subcommittees as it may desire. Each such subcommittees shall have those responsibilities, and operate in accordance with the procedures, established by the JSC and shall report the results of its activities to the JSC.

Each subcommittee shall provide the JSC with guidance and consultation regarding such subcommittee’s area of expertise; however, all final decision-making shall be the responsibility of the JSC, in accordance with the terms of Section 2.4.

(b) The Parties hereby establish a Product Subcommittee ( “Product Subcommittee” ) to oversee and manage the Development, Regulatory Approval, and Commercialization of the Product in accordance with the U.S. Development Plan, and to coordinate such U.S. Development with the Development activities of Takeda in the Royalty Territory. Each Party shall have an equal number of representatives on such subcommittee. The role of the Product Subcommittee shall be:

(i) to draft amendments or updates to the U.S. Development Plan and U.S. Commercialization Plan and present such amendments or updates to the JSC for review and approval;

(ii) to develop the overall strategy for Product Development and Commercialization activities in the U.S. performed hereunder;

(iii) to facilitate the flow of information between the Parties with respect to the Development, Regulatory Approval, and Commercialization of the Product hereunder; and

(iv) to perform such other functions as appropriate to further the purposes of this Agreement as determined by the JSC.

(c) The Parties hereby establish a Finance Subcommittee ( “Finance Subcommittee” ) to oversee the implementation and assist the JSC and other subcommittees with budgetary, financial and accounting issues arising out of the Development, Regulatory Approval, and Commercialization of the Product in accordance with the terms of this Agreement. Each Party shall have an equal number of representatives on such subcommittee. The role of the Finance Subcommittee shall be:

(i) to coordinate with the JSC and other subcommittees as applicable regarding the preparation and submission of budgets for the Development and Commercialization of the Product in the U.S.;

(ii) to develop specific schedules, procedures and methods to implement the financial reporting and reconciliation provisions of this Agreement; and

(iii) to perform such other functions as appropriate to further the purposes of this Agreement as determined by the JSC.

2.7 Alliance Representative . Each Party has designated on Exhibit F an appropriate employee to facilitate communication and coordination of the Parties’ activities under this Agreement relating to the Product and to provide support and guidance to the JSC (each, an “ Alliance Representative ”). From time to time each Party may replace its Alliance Representative by prior written notice to the other Party specifying the replacement.

2.8 Royalty Territory Information Sharing . Without limiting any other provisions of this Agreement, the Parties acknowledge and agree that Takeda shall provide Affymax, through the JSC, with periodic updates regarding the Development and Commercialization activities undertaken by Takeda in or for the Royalty Territory (such updates to be provided quarterly if available or, otherwise, semi-annually) including summary plan of ROW Development and ROW Commercialization Plans for such activities (which such plans shall include summary financial information in each case to the extent customarily generated by or available to Takeda from its Affiliates or sublicensees for its internal purposes, with respect to such activities in the Royalty Territory, but subject to Takeda’s right to redact or exclude detailed commercially-sensitive and proprietary information). In addition, Takeda shall provide such additional information regarding the ROW Development and Commercialization of the Product in the Royalty Territory as may be reasonably requested by Affymax and reasonably acceptable to Takeda from time to time.

ARTICLE 3

CLINICAL AND NON-CLINICAL PRODUCT DEVELOPMENT

3.1 Overview . The Parties shall Develop the Product in the Initial Indications in the Licensed Territory as provided in this Article 3 and in accordance with the then-current U.S. Development Plan. The initial U.S. Development Plan sets forth the Development activities to be performed by each Party under this Agreement in connection with the submission for Regulatory Approval of the Product in the Initial Indications for the U.S. and attached hereto as Exhibit H (assuming that the results of such activities will at least be used in EU as well). The summary plan of the ROW Development and future updates thereof shall be submitted to the JSC for review (not for approval) in accordance with Section 2.8. Without limiting the generality of the foregoing, the Parties shall have the following Development obligations for the Product:

(a) Affymax shall be responsible for all ongoing clinical, non-clinical, preclinical and other trials regarding the Product that are listed on Exhibit G and shall provide Takeda the data obtained therein as provided in Section 4.1;

(b) Affymax shall be primarily responsible for implementing the clinical trials of the Product for Regulatory Approval in the Renal Indications pursuant to the U.S. Development Plan; and

(c) Takeda shall be (i) primarily responsible for implementing the clinical trials of the Product for Regulatory Approval in the Oncology Indications pursuant to the U.S. Development Plan, and (ii) solely responsible for the ROW Development of the Product for Regulatory Approval in all Initial Indications in the Royalty Territory (other than pursuant to the U.S. Development Plan) wherein Takeda Develops and Commercializes the Product.

3.2 U.S. Development Plan . The initial U.S. Development Plan for the Initial Indications has been agreed upon by the Parties and is attached hereto as Exhibit H and incorporated herein by reference. The U.S. Development Plan shall contain the following

information for the Product for each Initial Indication in the Licensed Territory, to the extent such information is available:

(a) the proposed overall plan for Development for the Product for the Initial Indications (and each Joint Additional Indication pursued pursuant to Section 3.10) to support Regulatory Approval in the U.S. (assuming that the results of such activities will at least be used in EU as well);

(b) the Development Budget, which shall include a three (3)-year rolling budget of U.S. Development Expenses (including a detailed binding budget for the first year thereof and a non-binding forecast for subsequent two (2) years based on the then-current U.S. Development Plan);

(c) scope and target timelines for the Parties’ performance of all studies within the U.S. Development, including without limitation, clinical trial protocols, additional preclinical tests (including any and all carcinogenicity and toxicology studies), Finished Product stability studies, enrollment numbers and submission dates;

(d) estimated dates of meetings with FDA for the Product; and

(e) the Parties’ forecasts of their respective needs for preclinical or clinical supply of such Product and/or Bulk API.

In addition to the U.S. Development Plan, Takeda shall within twelve (12) months after the Effective Date, draft and provide to Affymax a proposed overall plan for the Development for the Product for the Initial Indications (and each Joint Additional Indication pursued pursuant to Section 3.10, if any at that time) to support Regulatory Approval in each country of the Level 1 Markets.

3.3 Updates to U.S. Development Plan and Development Budget. As early as necessary in each year beginning with the first full Fiscal Year after the Effective Date, the Parties shall update and prepare the U.S. Development Plan and Development Budget for the Product for the following Fiscal Year to take into account completion, commencement or cessation of U.S. Development activities not contemplated by the then-current U.S. Development Plan, and submit such proposed U.S. Development Plan to the JSC no later than November 1 of such year, as follows: (a) Affymax, in consultation with Takeda, shall update the U.S. Development Plan for Regulatory Approval of the Product in the Renal Indications; and (b) Takeda shall update the U.S. Development Plan for Regulatory Approval of the Product in the Oncology Indications in consultation with Affymax. The JSC shall have the right to approve updates to the U.S. Development Plan and Development Budget, subject to the final decision-making authority described in Section 2.5(c) above. The JSC shall endeavor to finalize its approval of each updated U.S. Development Plan by December 15 of each year.

3.4 Development Expenses .

(a) The Parties shall share any and all Development Expenses as follows: Takeda shall bear the initial fifty million Dollar ($50,000,000) of total Development Expenses;

any Development Expenses in excess of such amount shall thereafter be borne seventy percent (70%) by Takeda and thirty percent (30%) by Affymax. For clarity, the Development expenses incurred in connection with the ROW Development shall not be included in the Development Expenses; provided, that if the JSC determines that the Parties will use any results of the ROW Development to support the Regulatory Approval of the Product in the U.S., then, Affymax shall without delay reimburse Takeda for thirty percent (30%) of the external expenses incurred by Takeda on and after January 1, 2007 for the applicable ROW Development.

(i) Each Party shall calculate and maintain records of all relevant Development Expenses incurred by it for the Development of the Product, in accordance with procedures to be agreed upon between the Parties. The Parties understand and agree that Internal Expenses shall not be shared, subject to Section 3.4(a)(iv).

(ii) Within ten (10) Business Days following the end of each calendar quarter, Takeda shall submit to Affymax a written report setting forth in reasonable detail the Development Expenses it has incurred in such calendar quarter. Within ten (10) Business Days following the end of each calendar quarter, Affymax shall submit to Takeda a written report setting forth in reasonable detail the Development Expenses it has incurred in such calendar quarter.

(iii) Within twenty (20) Business Days following the end of each calendar quarter, Takeda shall submit to Affymax a written report setting forth in reasonable detail the detailed calculation of all Development Expenses for the Product, and the calculation of any net amount owed by Affymax to Takeda or by Takeda to Affymax, as the case may be, in order to ensure the appropriate sharing of Development Expenses in accordance with the provisions of Section 3.4(a). The net amount payable shall be paid by Takeda or Affymax to the other Party, as the case may be, within twenty-five (25) Business Days following the end of each calendar quarter; provided, that, in the event of a dispute, any amounts not in dispute shall be paid and the disputing Party shall provide written notice without undue delay after receipt of the written report in question to the other, specifying such dispute and explaining the basis of the dispute. Affymax and Takeda shall promptly thereafter meet and negotiate in good faith a resolution to such dispute and, promptly upon resolution of such dispute, the applicable Party shall make the agreed-upon payment. If such dispute is not resolved within forty-five (45) days after delivery of a notice of dispute with respect thereto to the other Party, the disputing Party may audit the other Party in accordance with the provisions of Section 8.11. For clarity, nothing in this Section 3.4(a)(iii) shall serve to limit a Party’s ability to seek recourse for billing errors discovered after payment is made.

(iv) The Parties acknowledge and agree that Internal Expenses shall not be reimbursed or shared except as set forth in this Section 3.4(a)(iv). In connection with the U.S. Development, either Party may refer to the Finance Subcommittee to provide certain specified Development activities using internal resources and to include such Internal Expenses as the Development Expenses to be shared hereunder. Any such referral shall include a sufficiently detailed description of the proposed Development activities, the associated Internal Expenses, and, where possible, the costs and expenses to be paid to Third Party contractors if the same Development activities were contracted out to them. If the JSC approves (which approval shall not be unreasonably withheld) the proposal of the Finance Subcommittee to include such Internal

Expenses as the Development Expenses, then the proposing Party shall obtain reimbursement as the Development Expenses for the Internal Expenses actually incurred (in an amount not to exceed any approved amount) in performing such Development activities for the Product.

(b) Takeda shall bear all costs and expenses associated with the ROW Development, subject to Section 3.4(a).

(c) Any reimbursement payments made pursuant to this Section 3.4 shall be subject to the general payment procedures set forth in Sections 8.7 through 8.11, inclusive.

3.5 Performance; Diligence .

(a) Each Party shall devote Diligent Efforts to the U.S. Development of the Product for the Initial Indications and for any Joint Additional Indication in the U.S. consistent with the then-current U.S. Development Plan and in accordance with this Agreement.

(b) Takeda shall devote Diligent Efforts to the ROW Development of the Product for the Initial Indications and for any Joint Additional Indications for all the Level 1 Markets, and such other countries of the Royalty Territory wherein Takeda at its discretion elects to Develop the Product (as described in further detail in this Section 3.5 below), in accordance with its plan of ROW Development, the overall plan and updates of which shall be submitted to the JSC for such countries pursuant to Section 3.2.

(c) Without limiting the generality of Section 3.5(b), Takeda shall (i) devote Diligent Efforts to obtaining Regulatory Approval of the Product for the Initial Indication and for any Joint Additional Indication in the Level 1 Markets, and (ii) file for Regulatory Approval of the Product with the EMEA promptly after, but in no event more than nine (9) months after, the submission for Regulatory Approval of the Product for such indication in the U.S., unless Takeda is required to conduct any additional Development activities to comply with the EMEA’s requirements. Any failure by Takeda to comply with the terms of this Section 3.5(c) shall be deemed a material breach of this Agreement by Takeda in any applicable country or countries of the Level 1 Markets, and Affymax shall have the right to terminate this Agreement with respect to the applicable country(ies) of the Level 1 Markets pursuant to the terms of Section 13.2(b)(i).

(d) Without limiting the generality of Section 3.5(b), at any time after the date of the first approval of NDA for the Product in the U.S. (for [ * ]) of the Level 2 Markets) or the date of the first Regulatory Approval from the EMEA (for the other countries of the Level 2 Markets), Affymax may request Takeda, with regard to one or more countries of the Level 2 Markets where Takeda has not yet determined or initiated efforts to Develop and Commercialize the Product, to inform Affymax of its decision on whether or not it shall devote the Diligent Efforts to Develop and Commercialize the Product for the Initial Indication and the Joint Additional Indication, if any, in such country(ies).

(i) If Takeda informs Affymax of its decision to devote the Diligent Efforts in such country(ies), then:

(1) Takeda shall thereafter be obligated to devote Diligent Efforts in such country(ies);

(2) Takeda shall develop a plan setting forth, for such country(ies) of the Level 2 Markets, a schedule of activities to be performed by Takeda for the filing of Regulatory Approval for the Product in each such country within one hundred and twenty (120) days after such Affymax’s request which period of response may be extended by Affymax’s consent;

(3) Affymax shall have a right to review and comment on the plan provided by Takeda and Takeda shall consider in good faith any reasonable comments from Affymax; and

(4) in the case of failure by Takeda to comply with such Diligent Effort obligation with respect to such country(ies), Affymax shall have the right to terminate this Agreement with respect to such country(ies) pursuant to the terms of Section 13.2(b)(i).

(ii) If Takeda informs Affymax of its decision not to use such Diligent Efforts in such country(ies) or fails to provide Affymax with such a plan with respect to such country(ies) of the Level 2 Markets within the above-mentioned one hundred and twenty (120) day period, or any extension thereof as agreed jointly by the Parties, then

(1) Affymax may prepare a plan it believes is commercially reasonable for both Parties to pursue for the Development and Commercialization of the Product in such country(ies) and provide it to Takeda within a reasonable time;

(2) if the Parties agree on a plan with respect to such country(ies) of the Level 2 Markets, then Takeda shall devote Diligent Efforts to obtaining Regulatory Approval of the Product for the Initial Indication and for any Joint Additional Indication in each such country(ies) under this Agreement; and

(3) if Affymax informs Takeda of its intention not to provide such plan as mentioned in Section 3.5(d)(ii)(1), or, both Parties cannot agree on such plan within ninety (90) days after Takeda’s receipt of such plan, then such country(ies) shall thereafter be excluded from the Licensed Territory and Affymax shall thereafter have a right, with a right to sublicense to Third Parties, to Develop and Commercialize the Product for the applicable Initial Indications or Joint Additional Indications, if any, in such country(ies) by using the Takeda Technology and the Regulatory Materials without any consideration to Takeda.

(e) With respect to any country in the Royalty Territory other than the Level 1 Markets and Level 2 Markets, Takeda shall have the discretion to decide whether and to what extent to Develop, seek Regulatory Approval for, and Commercialize the Product.

(f) Each Party shall conduct its Development activities under this Agreement in good scientific manner and in compliance in all material respects with all applicable Laws, including without limitation applicable GCP, GLP, and GMP.

3.6 Records, Reports and Information . Each Party shall maintain complete, current and accurate records of all work conducted by it under the U.S. 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 U.S. Development Plan in sufficient detail and in good scientific manner appropriate for patent and regulatory purposes. Each Party shall have the right to review such records maintained by the other Party at reasonable times, upon written request. Each Party shall provide written reports in English to the JSC on its Development and regulatory activities with the Product pursuant to the U.S. Development Plan on a quarterly basis at the end of each calendar quarter, at a level of detail reasonably sufficient to enable the other Party to determine the reporting Party’s compliance with its Diligent Efforts obligation pursuant to Section 3.5.

3.7 Backup Research Agreement . Promptly after the Effective Date, the Parties shall negotiate in good faith a research agreement setting forth the terms and conditions under which Affymax shall perform a program of research intended to [ * ] for the Initial Indications. Such research agreement (the “ Backup Research Agreement ”), if concluded, shall provide that Takeda shall bear the costs and expenses of such research program in an amount not to exceed $[ * ] per year. For the avoidance of doubt, the failure of the Parties to enter into the Backup Research Agreement shall not constitute a breach of this Agreement by either Party.

3.8 Replacement Products.

(a) In the event that Takeda discontinues its Development of the Product in its entirety within the period commencing on the Effective Date and ending five (5) years thereafter due to patient safety concerns or pursuant to a requirement imposed by Regulatory Authorities in the Licensed Territory or by the external monitoring board or upon mutual agreement of the Parties, then Takeda shall have the right to review with Affymax any and all then-existing Replacement Product Candidates and to select within ninety (90) days, jointly with Affymax, one such Replacement Product Candidate as a substitute for the then-current Product and to initiate and conduct a Development for such Replacement Product Candidate. In such event, products containing such Replacement Product Candidate shall be included in the definition of the “Product” for purposes of this Agreement (including without limitation, with respect to all relevant payment including the various milestone payments described in Section 8.2, but only to the extent that any such payment was not previously made for the discontinued Product and other obligations, and the licenses set forth in Article 6). In connection with such substitution, the U.S. Development Plan for the Product shall be amended to reflect the substitution of the replacement Product in a manner that is mutually acceptable to each Party (it being understood that the Parties shall retain the respective rights and obligations with respect to the Development and Commercialization of such Replacement Product Candidate in accordance with the terms of this Agreement).

(b) If, in the case of Section 3.8(a) above, the Parties fail to agree on the Replacement Product Candidate to take its place within above-mentioned period of ninety (90) days, then Takeda may elect to proceed with the Replacement Product Candidate of its choice pursuant to the terms of Section 3.8(a) above, except that, notwithstanding anything to the contrary in this Agreement: (i) Takeda shall bear all responsibilities and costs associated with the Development and Commercialization of such Product throughout the Licensed Territory, (ii)

Affymax shall have no co-promotion right with respect to such replaced Product in the U.S., (iii) the U.S. shall be deemed part of the Royalty Territory, except that the royalties applicable to sale of thus replaced Product in the Royalty Territory (including U.S.) shall be as set forth in Exhibit O rather than in Section 8.5(a), and (iv) Takeda shall make the various milestone payments described in Section 8.2, but only to the extent that any such payment was not previously made for the discontinued Product.

(c) Notwithstanding the foregoing, Takeda acknowledges and understands that any Replacement Product Candidate may not have been manufactured at scale, or may not have been the subject of sufficient Development or any manufacturing process development, or may not be the subject of any manufacturing agreement in place at such time between Affymax and its third party manufacturers, in each case at the time of the selection of such Replacement Product Candidate, and accordingly, that such product development, manufacturing process development and scale up activities may need to be conducted by Takeda, alone or in conjunction with Affymax, as agreed upon by Takeda and Affymax, and that such Replacement Product Candidate may be subject to Third Party patent rights which may require the acquisition of additional Third Party licenses prior to commercialization (which such licenses shall be treated in accordance with Section 6.7(b)). Subject to the terms of Section 3.9 and to the exclusivity covenant set forth in Section 6.6, after the expiration of the time period described above in Section 3.8(a), Affymax shall have the right to pursue any Replacement Product Candidate not selected by Takeda pursuant to Section 3.8(b), itself or with an Affiliate or Third Party, without any further obligation to Takeda.

3.9 Right of First Negotiation to Backup Compounds. If, within ten (10) years after the Effective Date, Affymax develops one or more potential Backup Compounds, then Takeda shall have a right of first negotiation to develop and commercialize such Backup Compound(s) for the Licensed Territory as provided in this Section 3.9. During such ten (10)-year period, Affymax shall provide Takeda on an annual basis a report stating the results of any pre-clinical and clinical studies conducted for such a Backup Compound for the prevention, treatment or amelioration of anemia in humans, as well as all other material results and data with respect to such potential Backup Compound(s), for Takeda’s evaluation. Takeda shall treat such results and data as Affymax’s Confident

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