Document:

Employment Agreement by and between Dr. Ryo Kubota, M.D. and the Registrant

 Exhibit 10.08 

April 18, 2005 
 Dr. Ryo Kubota, M.D., Ph.D. 

[Address] 
 Dear Ryo: 

This letter agreement (this “Agreement”) sets forth the terms and conditions of your employment with Acucela Inc., a Washington
corporation, (the “Company”). This Agreement has an effective date of April 18, 2005 (the “Effective Date”). 
 In
consideration of the mutual covenants and promises made in this Agreement, you and the Company agree as follows: 
 1. Position and
Responsibilities. 
 (a) As of the Effective Date, you will continue to serve as a full-time employee as the Company’s Chairman,
President and Chief Executive Officer (the “CEO”). As Chairman, President and CEO, your job duties and responsibilities will include those described under the Company’s Bylaws and such other services and duties as shall be assigned to
you from time to time by the Board of Directors. You shall make all decisions related to the day-to-day management of the Company. You will also make yourself available by e-mail, phone or, as appropriate, for in-person meetings and attendance at
negotiations and Company Board of Directors (“Board”) meetings. You shall report directly to the Board. 
 (b) While serving as
Chairman, President and CEO, you will also be nominated to serve on the Board. 
 2. Term. 

(a) Your employment with the Company is at-will and either you or the Company may terminate your employment at any time and for any reason or
for no reason, with or without cause, in each case subject to the terms and provisions of this Agreement. Either you or the Company can terminate the employment relationship by providing the other party with at least ten days advance written notice
and where such notice specifies the termination date. 
 (b) You service as a director is subject to the provisions of the Company’s
Articles of Incorporation, bylaws and applicable law. 

 Dr. Ryo Kubota, M.D., Ph.D. 

April 18, 2005 
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 3. Salary and Stock Options. 

(a) Base Salary. During your employment as Chairman, President and CEO, you will be paid an annual base salary of $225,000, adjusted
annually to reflect increases in the U.S. Consumer Price Index for All Urban Consumers (the “Base Salary”), covering all time and service hours that you render, payable in the time and manner that the Company customarily pays its
employees. During your employment as Chairman, President and CEO, your Base Salary shall at all times equal or exceed that of each other employee of the Company. 

(b) Annual Bonus. During your employment as Chairman, President and CEO, you will be eligible to receive an annual bonus equal to 50%
of your Base Salary upon achievement of objectives to be mutually agreed upon in advance by you and the Board (the “Target Bonus”). In addition, you will be eligible to receive an amount equal to two times the Target Bonus based upon
extraordinary achievement as determined by the Board. All bonus amounts earned (if any) will be paid to you within 45 days following each fiscal year-end. 

(c) Director Compensation. You shall not receive any compensation in connection with your service as a director. 

(d) Equity. 
 (i) In
connection with your employment as Chairman, President and CEO, you will be eligible to receive stock options to purchase shares of the Company’s common stock (“Options”) or may be granted restricted shares of the Company’s
common stock (“Restricted Stock”). Options and Restricted Stock shall be granted pursuant to the Company’s stock option plan (the “Plan”) and shall be subject to all the terms and conditions of the Plan. As a condition of
these Option or Restricted Stock grants, you shall also execute stock option or restricted stock agreements with the Company covering the terms and conditions of each grant. Any Option or Restricted Stock shall initially be entirely unvested.
Options shall vest pro-rata on a monthly basis over the 36 months following the date of grant subject to your continued service and shall remain exercisable for a period of 24 months following your termination of service (except if such termination
is for Cause). You shall be able to exercise Options only to the extent that such Options are vested. The Options shall have a per share exercise price equal to the fair market value of a Company common share on the date of the Option grant. Grants
of Restricted Stock shall vest pro-rata quarterly over the 36 months following the date of grant, subject to your continued service, and are eligible for share withholding to provide for the payment of withholding taxes upon vesting dates. In the
event that your employment as Chairman, President and CEO is terminated by the Company for a reason other than for “Cause” as defined below, any outstanding unvested Option or Restricted Stock grant shall receive an additional 18 months of
vesting. 

 Dr. Ryo Kubota, M.D., Ph.D. 

April 18, 2005 
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 (ii) In addition, until the Company’s initial public offering of its common stock, you
shall as often as necessary receive grants of Options or Restricted Stock so that your equity position in the Company is at least equal to 51% of the Company’s outstanding common stock on a fully-diluted, as-converted basis (“AD
Grants”). AD Grants pursuant to this subsection (ii) shall have the same terms and conditions specified in subsection (i) above. In addition, the price for AD Grants may be made by full recourse promissory notes which shall accrue
interest but shall not be due and payable until the earlier of (x) your Termination Date or (y) 36 months from the date of the grant (“AD Grant Notes”). Within 45 days following each fiscal year-end in which an AD Grant Note
remains outstanding and in which you remained an employee as of the last day of such fiscal year, the Company shall pay you a cash bonus (an “AD Grant Bonus”) in an amount equal to one-third of the principal amount of each outstanding AD
Grant Note, if any, plus accrued interest thereon plus an amount equal to the amount of additional tax incurred by you as a result of receiving such AD Grant Bonus, if any. The Company shall be permitted to retain from any AD Grant Bonus an amount
equal to one-third of the principal amount of each outstanding AD Grant Note plus accrued interest thereon pending repayment of each AD Grant Note. 

(iii) You shall be permitted to implement a Rule 10b5-1 trading plan provided such plan complies with all Company policies and such plan is
pre-approved by the Company. 
 4. Employee Benefits and Expenses. During your employment with the Company, you will be entitled to
participate in all Company employee benefit plans and programs at this time or thereafter made available to full-time employees such as yourself (the “Benefits”). The Company may amend, modify or terminate these Benefits at any time and
for any reason. You shall accrue 4 weeks of vacation annually on a pro-rata basis subject to a maximum limit of 12 weeks total accrued vacation. You will also be reimbursed for reasonable and necessary business expenses upon the properly completed
submission of requisite forms and receipts to the Company. Such reimbursements shall be in compliance with Company policy and any applicable laws and regulations. 

5. Consequences of Termination of Employment. Unless the Company requests otherwise, upon termination of your employment for any
reason, you shall be deemed to have immediately resigned from all positions as an officer or director with the Company (and its affiliates) as of your last day of employment (the “Termination Date”). Upon termination of your employment for
any reason, you shall receive payment from the Company on your Termination Date covering all of the following: (i) all unpaid salary accrued through the Termination Date, (ii) any payments/benefits to which you are entitled under the
express terms of any applicable Company employee benefit plan and (iii) any unreimbursed valid business expenses. You shall be entitled to no other compensation or consideration except as may be provided in this Agreement. If your employment is
terminated for Cause, all of your outstanding Options and Restricted Stock shall be forfeited without consideration as of the Termination Date. The unvested portion of your Options or Restricted Stock shall be forfeited upon your Termination Date
and the vested portion of your Options shall expire as provided under the Plan, this Agreement and/or your stock option agreement with the Company. 

 Dr. Ryo Kubota, M.D., Ph.D. 

April 18, 2005 
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 6. Termination without Cause (or for Good Reason). In the event that your employment
is terminated by the Company without “Cause” or by you for “Good Reason,” each as defined below, you shall receive: 

(a) An amount equal to three times your annual Base Salary paid in a single cash payment within 30 days of your Termination Date; 

(b) An amount equal to three times your annual Target Bonus plus a pro-rated amount of your Target Bonus for the fiscal year in which
termination occurs, all paid in a single cash payment within 30 days of your Termination Date; 
 (c) If you timely elect to continue your
group health insurance coverage under the Consolidated Omnibus Budget Reconciliation Act of 1985 (“COBRA”) following the Termination Date, then the Company shall continue to pay its portion of the Company’s monthly insurance premiums
until the earliest of (i) eighteen months after the Termination Date, (ii) the expiration of your continuation coverage under COBRA or (iii) the date when you commence receiving substantially equivalent health insurance coverage in
connection with new employment; and 
 (d) An additional 18 months of vesting for any Options or Restricted Stock and full vesting of any
unvested founder’s shares of common stock of the Company held by you (“Founder’s Stock”). Notwithstanding the foregoing, in the event that your employment is terminated by the Company without Cause or by you for Good Reason, in
connection with or within 18 months following a Change of Control, all of the unvested portions of any Options or Restricted Stock then held by you shall immediately become vested and exercisable. 

Notwithstanding anything to the contrary, the receipt of any of the payments and benefits provided by this Section 6 will be subject to
you signing and not revoking a separation agreement and release of claims in a form acceptable to the Company, which includes a general release in favor of the Company and its affiliates together with their respective officers, directors,
shareholders, employees, agents and successors and assigns from any and all claims you may have against them including but not limited to, arising from your employment and/or termination of employment. The aforementioned general release shall not
include a waiver of claims against the shareholders, employees or agents of the Company that do not arise out of or relate to your employment with the Company. In the event you breach the provisions of this Agreement or the separation agreement, in
addition to any other remedies of law or in equity, the Company may cease making any payments or benefits to which you otherwise may be entitled to under Section 6. No severance will be paid or benefits provided until the separation agreement
and release agreement becomes effective. 

 Dr. Ryo Kubota, M.D., Ph.D. 

April 18, 2005 
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 For the purposes of this Agreement, “Cause” means any one or more of the following:
(i) a material breach by you of the provisions of this Agreement (which shall include but not be limited to failure to perform duties as requested by the Board), or (ii) your conviction of (or plea of nolo contendere to) any felony
criminal offense or (iii) your repeated failure to follow lawful and reasonable directions of the Board. The Board shall provide you with 30 days advance written notice detailing the basis for the termination of employment for Cause. During the
30-day period after you have received such notice, you shall have an opportunity to cure (i) or (iii), and for any of the above, to present your case to the full Board before any termination for Cause is finalized by a vote of a majority of the
Board. You shall continue to receive the compensation and benefits provided by this Agreement during the 30-day period after you receive the written notice of the Company’s intention to terminate you employment for Cause. 

For the purposes of this Agreement, “Good Reason” means that any one or more of the following have occurred without your consent and
provided that the Company has received written notice from you describing the circumstances giving rise to your belief that a Good Reason event has occurred and further provided that the Company has failed to cure the circumstances within thirty
(30) days of receiving such notice: (i) a material breach of the provisions of this Agreement by the Company or any successor thereto; (ii) a reduction of your duties, authority or responsibilities (it shall be deemed to be a
reduction of your duties, authority or responsibilities if, as a result of Company action, you are no longer a member of the Board or are no longer the Company’s Chairman, President and CEO); (iii) a reduction in your Base Salary or Target
Bonus; or (iv) the relocation of the Company’s principal place of business to a location that is outside a thirty-five (35) mile radius of the Company’s principal place of business as of the Effective Date. 

7. Effect of Change of Control. 

(a) In the event of a “Change of Control” as defined below, 50% of the unvested portion of your Options and all of the unvested
portions of your Restricted Stock and Founder’s Stock held by you on the date of the Change of Control shall immediately become vested and exercisable. 

(b) In the event you terminate your employment with the Company during the 30-day period immediately following the 6-month period after a
Change of Control, such termination shall be deemed a termination for Good Reason under this Agreement and you shall be eligible for the payments and benefits provided in Section 6. 

(c) For purposes of this Agreement, “Change of Control,” means any merger or consolidation of the Company into or with another
corporation or other entity, or the sale, transfer or other disposition of all or substantially all of the assets or capital stock of the Company, or any reorganization, recapitalization or like transaction or series of related

 Dr. Ryo Kubota, M.D., Ph.D. 

April 18, 2005 
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transactions having substantially equivalent effect and purpose, at the conclusion of which such merger, consolidation, sale, transfer, disposition, reorganization, recapitalization or like
transaction the holders of the capital stock of the Company entitled to vote for the election of directors or similar governing body immediately prior to such transaction or series of related transactions own less than a majority of the capital
stock entitled to vote for the election of directors or similar governing body of the acquiring entity or entity surviving or resulting from such transaction or series of related transactions immediately thereafter; provided that a merger effected
exclusively for the purpose of changing the domicile of the Company shall not be deemed to constitute a “Change of Control.” 
 8.
Tax Effect of Payments. 
 (a) Excise Taxes. If it is determined that any payment or distribution of any type to or for your
benefit made by the Company, by any of its affiliates, by any person who acquires ownership or effective control or ownership of a substantial portion of the Company’s assets (within the meaning of Section 280G of the Internal Revenue Code
of 1986, as amended, and the regulations thereunder (the “Code”)) or by any affiliate of such person, whether paid or payable or distributed or distributable pursuant to the terms of an employment agreement or otherwise (the “Total
Payments”), would be subject to the excise tax imposed by section 4999 of the Code or any interest or penalties with respect to such excise tax (such excise tax, together with any such interest or penalties, are collectively referred to as the
“Excise Tax”), then you shall be entitled to receive an additional payment (an “Excise Tax Restoration Payment”) in an amount that shall fund the payment by you of any Excise Tax on the Total Payments, as well as all income taxes
imposed on the Excise Tax Restoration Payment, any Excise Tax imposed on the Excise Tax Restoration Payment, and any interest or penalties imposed with respect to taxes on the Excise Tax Restoration Payment or any Excise Tax. The Excise Tax
Restoration Payment shall be calculated applying the then highest marginal tax rates. Purely for illustrative purposes only, applying the current highest aggregate marginal tax rate of 45%, if you were subject to an Excise Tax of $100,000 calculated
before any Excise Tax Restoration Payment, then the aggregate Excise Tax Restoration Payment hereunder would be approximately $285,714. The Excise Tax Restoration Payment itself is subject to taxes at a marginal rate of 45% plus an Excise Tax at a
rate of 20% which in the aggregate amounts to $185,714. Thus, after payment of the $185,714 of taxes, the remaining balance of $100,000 from the Excise Tax Restoration Payment would then be used by you to pay your original Excise Tax. 

(b) Determination by Auditors. All mathematical determinations and all determinations of whether any of the Total Payments are
“parachute payments” (within the meaning of section 280G of the Code) that are required to be made under this Section 8, shall be made by the independent auditors retained by the Company most recently prior to the Change of Control
(the “Auditors”), who shall provide their determination, together with detailed supporting calculations regarding the amount of any relevant matters, both to the Company and to you within thirty (30) days of your termination date, if
applicable, or such earlier time as is requested 

 Dr. Ryo Kubota, M.D., Ph.D. 

April 18, 2005 
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by the Company or by you. The Auditors shall furnish you with a written statement that such Auditors have concluded that no Excise Tax is payable (including the reasons therefor) and that you
have substantial authority not to report any Excise Tax on your federal income tax return. Any determination by the Auditors shall be binding upon the Company and you, absent manifest error. The Company shall pay the fees and costs of the Auditors
incurred in connection with this Section 8. 
 9. Proprietary Information and Inventions Agreement. You will be required, as a
condition of your employment with the Company, to execute a proprietary information and inventions agreement. 
 10. Indemnification
Agreement. In connection with your employment as an officer of the Company and your service as a director of the Company, the Company and you will enter into the Company’s standard form of indemnification agreement. 

11. Assignability; Binding Nature. Commencing on the Effective Date, this Agreement will be binding upon you and the Company and your
respective successors, heirs, and assigns. This Agreement may not be assigned by you except that your rights to compensation and benefits hereunder, subject to the limitations of this Agreement, may be transferred by will or operation of law. 

12. Governing Law; Arbitration. This Agreement will be deemed a contract made under, and for all purposes shall be construed in
accordance with, the laws of Washington. Any controversy or claim relating to this Agreement any breach thereof, and any claims you may have against the Company or any officer, director or employee of the Company or arising from or relating to your
employment with the Company, will be settled solely and finally by arbitration in Seattle, Washington in accordance with the rules of the American Arbitration Association (“AAA”) then in effect in the State of Washington, and judgment upon
such award rendered by the arbitrator(s) may be entered in any court having jurisdiction thereof, provided that this Section 12 shall not be construed to eliminate or reduce any right the Company or you may otherwise have to obtain a temporary
restraining order or a preliminary or permanent injunction to enforce any of the covenants contained in this Agreement before the matter can be heard in arbitration. The arbitrator may provide that the cost of the arbitration (including reasonable
legal fees) incurred by you or the Company will be borne by the non-prevailing party. 
 13. Withholding. Anything to the contrary
notwithstanding, all payments made by the Company hereunder to you or your estate or beneficiaries will be subject to satisfaction of all tax withholding pursuant to any applicable laws or regulations. 

14. Entire Agreement. Except as otherwise specifically provided in this Agreement, this Agreement contains all the legally binding
understandings and agreements between you and the Company pertaining to the subject matter of this Agreement and supersedes all such agreements, whether oral or in writing, previously entered into between the parties. 

 Dr. Ryo Kubota, M.D., Ph.D. 

April 18, 2005 
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 15. Covenants. As a condition of this Agreement, you agree that you will fully and
timely comply with all of the covenants set forth in this Section 15 (which shall survive your termination of employment). 
 (a) Upon
the Termination Date, you shall execute the Company’s Proprietary Information Agreement Termination Certification (or its successor agreement); 

(b) Upon the Termination Date, you shall return to the Company all Company property including, but not limited to, computers, cell phones,
pagers, keys, laboratory notebooks, business cards, intellectual property, etc. and you shall not retain any copies, facsimiles or summaries of any Company proprietary information; 

(c) You will fully pay off any outstanding advances, loans or debts owed to the Company no later than their applicable due date or your
Termination Date (if no other due date has been previously established); 
 (d) You will submit any outstanding expense reports to the
Company prior to the Termination Date; 
 (e) You will not at any time during and subsequent to your period of employment with the Company
make any disparaging statements (oral or written) about the Company, or any of its affiliated entities, officers, directors, employees, shareholders, representatives or agents, or any of the Company’s products or work-in-progress, in any manner
that might be harmful to their businesses, business reputations or personal reputations; 
 (f) As of the Termination Date, you will no
longer represent that you are an officer, director or employee of the Company and you will immediately discontinue using your Company mailing address, telephone, facsimile machines, voice mail and e-mail; 

(g) Any and all intellectual property (including but not limited to inventions, trademarks, trade secrets, copyrights, software or literary
creations) made, developed or created by you during your employment using Company time or Company equipment, supplies, facilities, resources, or trade secret information or which reasonably relate to the business of the Company or which reasonably
relate to any business conducted by the Company (each, “Intellectual Property”), whether at the request or suggestion of the Company or otherwise, whether alone or in conjunction with others, and whether during regular working hours of
work or otherwise, shall be promptly and fully disclosed by you to the Company and shall be the Company’s exclusive property as against you, and you shall promptly deliver to the Company all papers, drawings, models, data and other material
relating to any Intellectual Property made, 

 Dr. Ryo Kubota, M.D., Ph.D. 

April 18, 2005 
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developed or created by you as aforesaid. In addition, you covenant and agree to disclose to the Company any Intellectual Property developed or created by you during the term of this Agreement,
whether or not such Intellectual Property relates to the business being conducted by the Company at the time of development or creation of such Intellectual Property; 

(h) You hereby expressly acknowledge and agree that any copyrights developed or created by you during the term of this Agreement which
reasonably relates to the business of the Company or which reasonably relates to the business conducted by the Company during your employment by the Company shall be considered “works made for hire” within the meaning of the Copyright Act
of 1976, as amended (17 U.S.C. § 101). Each such copyright as well as all copies of such copyrights in whatever medium fixed or embodied, shall be owned exclusively by the Company as of the date of creation; 

(i) You shall, upon the Company’s request and without any payment therefor, execute all documents necessary or advisable in the opinion
of the Company’s counsel to register or protect the Company’s Intellectual Property or to vest in the Company full and exclusive title to such Intellectual Property, the expense of registering or protecting the Intellectual Property to be
borne by the Company. In addition, you agree not to file any documents adverse to the Company’s ownership of such Intellectual Property; and 

(j) This Agreement does not apply to Intellectual Property that qualifies fully as a nonassignable invention. You hereby covenant and agree to
disclose promptly in writing to the Company all Intellectual Property made or conceived by you during the term of your employment and for one (1) year thereafter, whether or not you believe that such Intellectual Property is subject to this
Agreement, to permit a determination by the Company as to whether such Intellectual Property should be the property of the Company. Any such information will be received in confidence by the Company. 

16. Offset. Any payments or benefits made to you under this Agreement may be reduced, in the Company’s discretion, by any amounts
you owe to the Company. 
 17. Notice. Any notice that the Company is required to or may desire to give you as an employee of the
Company pursuant to this Agreement shall be given by personal delivery, recognized overnight courier service, email, telecopy or registered or certified mail, return receipt requested, addressed to you at your address of record with the Company, or
at such other place as you may from time to time designate in writing. Any notice that you are required or may desire to give to the Company hereunder shall be given by personal delivery, recognized overnight courier service, email, telecopy or by
registered or certified mail, return receipt requested, addressed to the Company at its principal office, or at such other office as the Company may from time to time designate in writing. The date of actual delivery of any notice under this
Section 17 shall be deemed to be the date of delivery thereof. 

 Dr. Ryo Kubota, M.D., Ph.D. 

April 18, 2005 
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 18. Waiver; Severability. No provision of this Agreement may be amended or waived
unless such amendment or waiver is agreed to by you and the Company in writing. No waiver by you or the Company of the breach of any condition or provision of this Agreement will be deemed a waiver of a similar or dissimilar provision or condition
at the same or any prior or subsequent time. Failure or delay on the part of either party hereto to enforce any right, power, or privilege hereunder will not be deemed to constitute a waiver thereof. In the event any portion of this Agreement is
determined to be invalid or unenforceable for any reason, the remaining portions shall be unaffected thereby and will remain in full force and effect to the fullest extent permitted by law. 

19. Voluntary Agreement. You acknowledge that you have been advised to review this Agreement with your own legal counsel and other
advisors of your choosing and that prior to entering into this Agreement, you have had the opportunity to review this Agreement with your attorney and other advisors and have not asked (or relied upon) the Company or its counsel to represent you or
your counsel in this matter. You further represent that you have carefully read and understand the scope and effect of the provisions of this Agreement and that you are fully aware of the legal and binding effect of this Agreement. This Agreement is
executed voluntarily by you and without any duress or undue influence on the part or behalf of the Company. 
 20. Legal Fees. The
Company shall pay up to a maximum of $5,000 for legal fees and expenses incurred by you in connection with the preparation of this Agreement. The Company shall directly make payment to your legal counsel within 45 days after the Company’s
receipt of applicable invoices. 

 Dr. Ryo Kubota, M.D., Ph.D. 

April 18, 2005 
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 Please acknowledge your acceptance and understanding of this Agreement by signing and returning it to the
undersigned. A copy of this signed Agreement will be sent to you for your records. 
  

	
	Sincerely,
	
	 /s/ Ryo Kubota

	Ryo Kubota, M.D., Ph.D.
	President and Chief Executive Officer

  

	
	ACKNOWLEDGED AND AGREED:
	
	 /s/ Ryo Kubota

	Ryo Kubota, M.D., Ph.D.
	Date: April 18, 2005

 FIRST AMENDMENT 

TO 
 EMPLOYMENT AGREEMENT

 THIS FIRST AMENDMENT TO EMPLOYMENT AGREEMENT (this “Amendment”) is dated October 1, 2006 by and between
Acucela, Inc., a Washington corporation (the “Company”), and Dr. Ryo Kubota, M.D., Ph.D. (“Employee”). 

RECITALS 
 WHEREAS, the
Company and Employee entered into the Employment Agreement dated April 18, 2005 (the “Original Agreement”), which provides in Section 3(d)(ii) that until the Company’s initial public offering of its common stock, the
Company shall as often as necessary grant options to purchase common stock or restricted shares of common stock so that Employee’s equity position in the Company is equal to at least 51% of the Company’s outstanding common stock on a
fully-diluted, as-converted basis; and 
 WHEREAS, the parties desire to amendment the provisions of Section 3(d)(ii) as set forth
below. 
 AGREEMENT 

NOW THEREFORE, IT IS HEREBY AGREED: 

1. AMENDMENT. 

A. The first sentence of Section 3(d)(ii) of the Original Agreement shall be deleted in its entirety and replaced with the following:

 “In addition, until the Company’s initial public offering of its common stock, you shall as often as necessary receive grants
of Options or Restricted Stock so that your equity position in the Company is equal to at least 51% of the Company’s issued and outstanding common stock on an as-converted basis (“AD Grants”). Outstanding options and convertible
securities shall not be included in the calculation of your equity position for purposes of the foregoing sentence; except that, if at any time outstanding options, including options under the Plan, are exercised or convertible securities are
converted into capital stock of the Company prior to the consummation of a Change of Control or the initial public offering of the Company’s common stock, you shall receive grants of Options or Restricted Stock so that when the number of such
Options or Restricted Stock are added to the shares of common stock then held by you, your equity position in the Company is equal to at least 51% of the Company’s outstanding common stock on an as-converted basis.” 

B. The second sentence of Section 3(d)(ii) of the Original Agreement provides that the AD Grants shall be granted pursuant to the
Company’s stock option plan and be subject to all the terms and conditions of such plan. Notwithstanding the foregoing, the parties agree that the Options granted and the Restricted Stock issued under Section 3(d)(ii) may be granted or
issued outside of the Plan (as such term is defined in the Original Agreement), so long as the terms governing such Options or Restricted Shares are materially consistent with the terms and conditions of the Plan and the Employment Agreement.

 2. NO OTHER CHANGES. Except as expressly amended by
this Amendment, the Original Agreement shall remain unmodified and in full force and effect. 
 3. ENTIRE
AGREEMENT. The Original Agreement, as modified by this Amendment, contains all the legally binding understandings and agreements between the Company and Employee pertaining to the subject matter hereof and supersedes all such
agreements, whether oral or in writing, previously entered into between the parties. 
 4. GOVERNING LAW. This
Amendment shall be deemed a contract made under, and for all purposes shall be construed in accordance with, the laws of Washington and subject to the arbitration provision set forth in Section 12 of the Original Agreement. 

5. AMENDMENT. No provision of this Amendment may be amended or waived unless such amendment or waiver is agreed to in writing
by the Company and Employee. No waiver of the breach of any condition or provision of this Amendment will be deemed a waiver of a similar or dissimilar provision or condition at the same or any prior or subsequent time. Failure or delay on the part
of either party hereto to enforce any right, power, or privilege hereunder will not be deemed to constitute a waiver thereof. 
 6.
SEVERABILITY. In the event any portion of this Amendment is determined to be invalid or unenforceable for any reason, the remaining portions shall be unaffected thereby and will remain in full force and effect to the fullest extent
permitted by law. 
 IN WITNESS WHEREOF, the parties hereto have executed this Amendment as of the date first written above. 

 

			
	COMPANY
	
	ACUCELA, INC.
		
	By:	 	 /s/ Ryo Kubota

		 	Ryo Kubota, M.D., Ph.D.
		 	President and Chief Executive Officer
	
	EMPLOYEE
	
	 /s/ Ryo Kubota

	Ryo Kubota, M.D., Ph.D.

 SIGNATURE PAGE TO FIRST
AMENDMENT TO EMPLOYMENT AGREEMENT 

  
 2 

 SECOND AMENDMENT 

TO 
 EMPLOYMENT AGREEMENT

 THIS SECOND AMENDMENT TO EMPLOYMENT AGREEMENT (this “Amendment”) is dated March 28, 2007 by and between
Acucela Inc., a Washington corporation (the “Company”), and Dr. Ryo Kubota, M.D., Ph.D. (“Employee”). 

RECITALS 
 WHEREAS, the
Company and Employee entered into the Employment Agreement dated April 18, 2005 (the “Original Agreement”) as amended by First Amendment to Employment Agreement dated October 1, 2006 (the “First
Amendment”). The Original Agreement as amended by the First Amendment shall be referred to herein as the “Agreement”; 

WHEREAS, the Agreement provides in Section 3(d)(ii) that until the Company’s initial public offering of its common stock, the
Company shall as often as necessary grant options to purchase common stock or restricted shares of common stock so that Employee’s equity position in the Company is equal to at least 51% of the Company’s outstanding common stock on an
as-converted basis, which equity position shall be calculated as provided in Section 3(d)(ii); 
 WHEREAS, the Agreement further
provides in Section 3(d)(ii) that the purchase price for such restricted stock or for exercise of such options may be made by full recourse promissory notes which shall not be due and payable until the earlier of (x) Employee’s
Termination Date, as defined in the Agreement, or (y) 36 months from the date of grant of such shares or options; 
 WHEREAS, the
Company wishes, among other things, to require that any loans pursuant to Section 3(d)(ii) shall be repaid prior to its filing of an S-1 in connection with any initial public offering of the Company; and 

WHEREAS, the parties desire to amend the provisions of Section 3(d)(ii) as set forth below. 

AGREEMENT 
 NOW THEREFORE,
IT IS HEREBY AGREED: 
 1. AMENDMENT. Section 3(d)(ii) of the Original Agreement, as modified by the First Amendment, shall be deleted
in its entirety and replaced with the following: 
 “In addition, until the Company’s initial public offering of its common stock,
you shall as often as necessary receive grants of Options or Restricted Stock so that your equity position in the Company is equal to at least 51% of the Company’s issued and outstanding common stock on an as-converted basis (“AD
Grants”). Outstanding options and convertible securities shall not be included in the calculation of your equity position for purposes of the foregoing sentence; except that, if at any time outstanding options, including options
under the Plan, are exercised or convertible securities are converted into capital stock of the Company prior to the consummation 

 
of a Change of Control or the initial public offering of the Company’s common stock, you shall receive grants of Options or Restricted Stock so that when the number of such Options or
Restricted Stock are added to the shares of common stock then held by you, your equity position in the Company is equal to at least 51% of the Company’s outstanding common stock on an as-converted basis. AD Grants pursuant to this sub-section
(ii) shall have the same terms and conditions specified in sub-section (i) above and the Options granted and the Restricted Stock issued under Section 3(d)(ii) may be granted or issued outside of the Plan (as such term is defined in
the Original Agreement), so long as the terms governing such Options or Restricted Shares are materially consistent with the terms and conditions of the Plan and this Agreement. In addition, the purchase price for AD Grants may be made by full
recourse promissory notes (“AD Grant Notes”) which shall accrue interest but shall not be due and payable until the earlier of (x) your Termination Date, (y) 36 months from the date of grant, or (z) the date on
which the Company files an S-1 with the Securities and Exchange Commission in connection with the initial public offering of the Company’s common stock (the “Maturity Date”). As of the Maturity Date, the AD Grant Notes
may be repaid in cash or by delivery of shares of the Company’s common stock valued at the then current fair market value, as determined in good faith by the Board of Directors of the Company. Within 45 days following each fiscal year-end in
which an AD Grant Note remains outstanding and in which you remain an employee as of the last day of such fiscal year, the Company shall pay you a cash bonus in an amount equal to one-third of the principal amount of each outstanding AD Grant Note,
plus accrued interest thereon plus an amount equal to the amount of additional tax incurred by you as a result of receiving such bonus, if any (the “AD Grant Bonus”); provided that if the Company files an S-1 with the
Securities and Exchange Commission in connection with the initial public offering of the Company’s common stock, the Company shall pay to you an amount equal to the outstanding principal amount of each AD Grant Note (for which you did not
previously receive an AD Grant Bonus), plus accrued interest thereon plus an amount equal to the amount of each additional tax incurred by you as a result of receiving such AD Grant Bonus. The Company shall be permitted to retain from any AD Grant
Bonus up to an amount equal to the principal amount of each outstanding AD Grant Note plus accrued interest thereon pending repayment of each AD Grant Note.” 

2. NO OTHER CHANGES. Except as expressly amended by this Amendment, the Agreement shall remain unmodified and in full force and effect. 

3. ENTIRE AGREEMENT. The Original Agreement, as modified by the First Amendment and this Amendment, contains all the legally binding
understandings and agreements between the Company and Employee pertaining to the subject matter hereof and supersedes all such agreements, whether oral or in writing, previously entered into between the parties. 

4. GOVERNING LAW. This Amendment shall be deemed a contract made under, and for all purposes shall be construed in accordance with, the laws
of Washington and subject to the arbitration provision set forth in Section 12 of the Original Agreement. 
 5. AMENDMENT. No provision
of this Amendment may be amended or waived unless such amendment or waiver is agreed to in writing by the Company and Employee. No waiver of the breach of any condition or provision of this Amendment will be deemed a waiver

  
 2 

 
of a similar or dissimilar provision or condition at the same or any prior or subsequent time. Failure or delay on the part of either party hereto to enforce any right, power, or privilege
hereunder will not be deemed to constitute a waiver thereof. 
 6. SEVERABILITY. In the event any portion of this Amendment is determined to
be invalid or unenforceable for any reason, the remaining portions shall be unaffected thereby and will remain in full force and effect to the fullest extent permitted by law. 

IN WITNESS WHEREOF, the parties hereto have executed this Amendment as of the date first written above. 

 

			
	COMPANY
	
	ACUCELA INC.
		
	By:	 	 /s/ Ryo Kubota

		 	Ryo Kubota, M.D., Ph.D.
		 	President and Chief Executive Officer
	
	EMPLOYEE
	
	 /s/ Ryo Kubota

	Ryo Kubota, M.D., Ph.D.

 SIGNATURE PAGE TO SECOND AMENDMENT TO EMPLOYMENT AGREEMENT 

  
 3 

 THIRD AMENDMENT 

TO 
 EMPLOYMENT AGREEMENT

 THIS THIRD AMENDMENT TO EMPLOYMENT AGREEMENT (this “Amendment”) is entered on May 1, 2007
by and between Acucela Inc., a Washington corporation (the “Company”), and Dr. Ryo Kubota, M.D., Ph.D. (“Employee”). 

RECITALS 

WHEREAS, the Company and Employee entered into the Employment Agreement dated April 18, 2005 (the “Original
Agreement”), as amended by the First Amendment to Employment Agreement dated October 1, 2006 (the “First Amendment”), and further amended by the Second Amendment to Employment Agreement dated March 28,
2007 (the “Second Amendment” and together with the Original Agreement and the First Amendment, the “Agreement”); capitalized terms used but not otherwise defined herein shall have the meaning set forth
in the Agreement. 
 WHEREAS, Section 3(d)(ii) of the Agreement provides that within 45 days following each fiscal
year-end in which an AD Grant Note remains outstanding and in which Employee remains an employee as of the last day of such fiscal year, the Company shall pay Employee a cash bonus in an amount equal to one-third of the principal amount of each
outstanding AD Grant Note, plus accrued interest thereon plus an amount equal to the amount of additional tax incurred by you as a result of receiving such bonus, if any; 

WHEREAS, the parties desire to amend Section 3(d)(ii) of the Agreement to change the payment schedule of the AD Grant Bonus as set forth
below. 
 AGREEMENT 

NOW THEREFORE, IT IS HEREBY AGREED: 

1. AMENDMENT. The sixth sentence in Section 3(d)(ii) of the Agreement (which is set forth in the Second Amendment) shall be deleted in
its entirety and replaced with the following: 
 “On the eleventh month anniversary of an AD Grant made in May, 2007, and for purposes
of any other AD Grant, on the one (1) year anniversary of an AD Grant, during the term of this Agreement and for so long as you remain an employee of the Company as of such date, the Company shall pay you a cash bonus in an amount equal to
one-third (1/3) of the principal amount of the outstanding AD Grant Note, plus accrued interest thereon plus an amount equal to the amount of additional tax incurred by you as a result of receiving such bonus, if any (the “AD Grant
Bonus”), and thereafter, the Company shall pay you a cash bonus on a monthly basis for the following twenty-four (24) months equal an amount equal to one-thirty-sixth (1/36) of the principal amount of the outstanding AD Grant
Note plus accrued interest thereon plus an amount equal to the amount of additional tax incurred by you as a result of receiving such bonus, if any; provided that if the Company files an S-1 with the Securities and Exchange Commission (or the

 
equivalent filing with the appropriate securities agency under the laws of Japan) in connection with the initial public offering of the Company’s common stock, the Company shall pay to you
an amount equal to the outstanding principal amount of each AD Grant Note (for which you did not previously receive an AD Grant Bonus), plus accrued interest thereon plus an amount equal to the amount of each additional tax incurred by you as a
result of receiving such AD Grant B onus. “ 
 2. NO OTHER CHANGES. Except as expressly amended by this Amendment, the Agreement shall
remain unmodified and in full force and effect. 
 3. ENTIRE AGREEMENT. The Original Agreement, as modified by the First Amendment, the
Second Amendment and this Amendment, contains all the legally binding understandings and agreements between the Company and Employee pertaining to the subject matter hereof and supersedes all such agreements, whether oral or in writing, previously
entered into between the parties. 
 4. GOVERNING LAW. This Amendment shall be deemed a contract made under, and for all purposes shall be
construed in accordance with, the laws of Washington and subject to the arbitration provision set forth in Section 12 of the Original Agreement. 

5. AMENDMENT. No provision of this Amendment may be amended or waived unless such amendment or waiver is agreed to in writing by the Company
and Employee. No waiver of the breach of any condition or provision of this Amendment will be deemed a waiver of a similar or dissimilar provision or condition at the same or any prior or subsequent time. Failure or delay on the part of either party
hereto to enforce any right, power, or privilege hereunder will not be deemed to constitute a waiver thereof. 
 6. SEVERABILITY. In the
event any portion of this Amendment is determined to be invalid or unenforceable for any reason, the remaining portions shall be unaffected thereby and will remain in full force and effect to the fullest extent permitted by law. 

SIGNATURE PAGE TO FOLLOW 

  
 2 

 IN WITNESS WHEREOF, the parties hereto have executed this Amendment as of the date first written
above. 
  

			
	COMPANY
	
	ACUCELA INC.
		
	By:	 	 /s/ Ryo Kubota

		 	Ryo Kubota, M.D., Ph.D.
		 	President and Chief Executive Officer
	
	EMPLOYEE
	
	 /s/ Ryo Kubota

	Ryo Kubota, M.D., Ph.D.

  
 3 

 FOURTH AMENDMENT TO EMPLOYMENT AGREEMENT 

This Fourth Amendment to the Employment Agreement (this “Amendment”) is made and entered into as of
December 30, 2008, by and between Dr. Ryo Kubota (“Executive”) and Acucela, Inc., a Washington corporation (the “Company”). 

RECITALS 

A. The Company and Executive are parties to that certain Employment Agreement between the Company and the Executive dated
April 18, 2005, as amended by the First, Second and Third Amendments thereto (collectively, the “Agreement”). All capitalized terms set forth herein shall (unless otherwise defined herein) have the meanings given to them
in the Agreement. 
 B. The Company and Executive wish to clarify the terms of the Agreement by means of this Amendment to the
Agreement. 
 AMENDMENT 
 NOW
THEREFORE, the parties hereby agree as follows: 
 1. FIRST AMENDMENT TO AGREEMENT. The sixth sentence in Section 3(d)(ii) of
the Agreement (as set forth in the Third Amendment To Employment Agreement dated May 1, 2007) is hereby amended to modify the proviso at the end thereof to read in its entirety as follows: 

“provided, that at such time the Company files an S-1 with the Securities and Exchange Commission (or the equivalent filing with the
appropriate securities agency under the laws of Japan) in connection with the initial public offering of the Company’s common stock, no further bonus shall be payable pursuant to this sentence.” 

2. SECOND AMENDMENT TO AGREEMENT. The last sentence of the paragraph following subsection (d) of Section 6 is hereby amended
to read in its entirety as follows: 
 “No severance will be paid or benefits provided unless the separation agreement and release of
claims have become effective.” 
 3. THIRD AMENDMENT TO AGREEMENT. The last paragraph of Section 6 is hereby amended to
read in its entirety as follows: 
 For purposes of this Agreement, “Good Reason” means that any one or more of the following have
occurred without your consent: (i) a material breach of the provisions of this Agreement by the 

 
Company or any successor thereto; (ii) a reduction of your duties, authority or responsibilities (it shall be deemed to be a reduction of your duties, authority or responsibilities if, as a
result of Company action, you are no longer a member of the board or are no longer the Company’s Chairman, President and CEO); (iii) a material reduction in your Base Salary or Target Bonus; or (iv) the relocation of the
Company’s principal place of business to a location that is outside a thirty-five (35) mile radius of the Company’s principal place of business as of the Effective Date. Notwithstanding anything else contained herein, you must provide
notice to the Company within ninety (90) days of the occurrence of a condition listed above and allow the Company thirty (30) day in which to cure such condition. Additionally, in the event the Company fails to cure the condition within
the cure period provided, you must terminate employment with the Company within six months of the end of the cure period. 
 4. FOURTH
AMENDMENT TO AGREEMENT. The following paragraph shall be added at the end of Section 6 following the paragraph amended by the Third Amendment to Agreement: 

Section 409A. For purposes of this Agreement, a termination of employment will be determined consistent with the rules relating to
a “separation from service” as defined in Section 409A of the Code and the regulations thereunder (“Section 409A”). Notwithstanding anything else provided herein, to the extent any payments provided under this
Agreement in connection with your termination of employment constitute deferred compensation subject to Section 409A, and you are deemed at the time of such termination of employment to be a “specified employee” under
Section 409A, then such payment shall not be made or commence until the earlier of (i) the expiration of the 6-month period measured from your separation from service from the Company or (ii) the date of your death following such a
separation from service; provided, however, that such deferral shall only be effected to the extent required to avoid adverse tax treatment to you including, without limitation, the additional tax for which you would otherwise be liable under
Section 409A(a)(1)(B) in the absence of such a deferral. The first payment thereof will include a catch-up payment covering the amount that would have otherwise been paid during the period between your termination of employment and the first
payment date but for the application of this provision, and the balance of the installments (if any) will be payable in accordance with their original schedule. To the extent that any provision of this Agreement is ambiguous as to its compliance
with Section 409A, the provision will be read in such a manner so that all payments hereunder comply with Section 409A. 

  
 2 

 
To the extent any payment under this Agreement may be classified as a “short-term deferral” within the meaning of Section 409A, such payment shall be deemed a short-term deferral,
even if it may also qualify for an exemption from Section 409A under another provision of Section 409A. Payments pursuant to this section are intended to constitute separate payments for purposes of Section 1.409A-2(b)(2) of the
Treasury Regulations. 
 5. FIFTH AMENDMENT TO AGREEMENT. Section 8(a) shall be amended by adding the following sentence at the
end thereof: 
 “Any Excise Tax Restoration Payment shall be made as soon as reasonably practicable and shall in no event be made later
than the end of the calendar year next following the calendar year in which Executive remits the related taxes.” 
 6. NO OTHER
AMENDMENTS. Except as expressly set forth above, all of the terms and conditions of the Agreement remain in full force and effect. 
 7.
COUNTERPARTS. This Amendment may be executed in any number of counterparts, each of which when so executed and delivered will be deemed an original, and all of which together shall constitute one and the same instrument. 

 

							
	COMPANY:	 		 	EXECUTIVE:
			
	 /s/ Ryo Kubota
	 		 	 /s/ Ryo Kubota

	By:	 	Ryo Kubota	 		 	(Ryo Kubota, M.D., Ph.D.)
	Its:	 	CEO	 		 	
			
	  
	 		 	  

	December 30, 2008	 		 	December 30, 2008

  
 3 

 FIFTH AMENDMENT 

TO 
 EMPLOYMENT AGREEMENT

 THIS FIFTH AMENDMENT TO EMPLOYMENT AGREEMENT (this “Amendment”) is entered into on
August 27, 2009 by and between Acucela Inc., a Washington corporation (the “Company”), and Ryo Kubota, M.D., Ph.D. (“Employee”). 

RECITALS 

WHEREAS, the Company and Employee entered into the Employment Agreement dated April 18, 2005 (the “Original
Agreement”), as amended by the First, Second, Third, and Fourth Amendments thereto (collectively, the “Agreement”). All capitalized terms used but not otherwise defined herein shall have the meaning set forth in
the Agreement. 
 WHEREAS, Section 3(d)(ii) of the Agreement provides that until the Company’s initial public
offering of its common stock, the Company shall as often as necessary grant to Employee options to purchase common stock or restricted shares of common stock so that Employee’s equity position in the Company is equal to at least 51% of the
Company’s outstanding common stock on an as-converted basis, which equity position shall be calculated as provided in Section (3)(d)(ii). 

WHEREAS, the Agreement further provides that on the eleventh month anniversary of an AD Grant made in May 2007, and, for purposes of any other
AD Grant, on the one (1) year anniversary of an AD Grant, during the term of the Agreement and for so long as Employee remains an employee of the Company as of such date, the Company shall pay Employee a cash bonus in an amount equal to
one-third (1/3) of the principal amount of an outstanding AD Grant Note, plus accrued interest thereon plus an amount equal to the amount of additional tax incurred by Employee as a result of receiving such bonus, if any, and, thereafter, the
Company shall pay Employee a cash bonus on a monthly basis for the following twenty-four (24) months in an amount equal to one-thirty-sixth (1/36) of the principal amount of the outstanding AD Grant Note plus accrued interest thereon plus
an amount equal to the amount of additional tax incurred by Employee as a result of receiving such bonus. 
 WHEREAS, the parties desire to
amend Section 3(d)(ii) of the Agreement as set forth below. 

 AGREEMENT 

NOW THEREFORE, IT IS HEREBY AGREED: 

1. AMENDMENTS. 
 (a) The first
and second sentences in Section 3(d)(ii) of the Agreement (which is set forth in the Second Amendment to Employment Agreement between the Company and Employee dated March 28, 2007) shall be deleted in their entirety and replaced with the
following: 
 “In addition, until the Company’s initial public offering of its common stock, you shall as often as necessary
receive grants of Options or Restricted Stock so that your equity position in the Company is equal to at least 51% of the Company’s issued and outstanding voting common stock on an as-converted basis (“AD Grants”).
Outstanding options and convertible securities shall not be included in the calculation of your equity position for purposes of the foregoing sentence; except that, if at any time outstanding options, including options under the Plan, are exercised
or convertible securities are converted into capital stock of the Company prior to the consummation of a Change of Control or the initial public offering of the Company’s common stock, you shall receive grants of Options or Restricted Stock so
that when the number of such Options or Restricted Stock are added to the shares of common stack then held by you, your equity position in the Company is equal to at least 51% of the Company’s outstanding voting common stock on an as-converted
basis.” 
 (b) The sixth sentence in Section 3(d)(ii) of the Agreement (which is set forth in the Third Amendment to Employment
Agreement between the Company and Employee dated May 1, 2007 and the Fourth Amendment to Employment Agreement between the Company and Employee dated December 30, 2008) shall be deleted in its entirety and replaced with the following: 

“The Company shall (a) on the eleventh month anniversary of an AD Grant made in May 2007, and for so long as you remain an employee
of the Company as of such date, pay you a cash bonus in an amount equal to one-third (1/3) of the principal amount of such outstanding AD Grant Note, plus accrued interest thereon plus an amount equal to the amount of additional tax incurred by
you as a result of receiving such bonus, if any (the “2007 AD Grant Bonus”), and thereafter, the Company shall pay you a cash bonus on a monthly basis for the following twenty-four (24) months in an amount equal to
one-thirty-sixth (1/36) of the principal amount of the outstanding AD Grant Note plus accrued interest thereon plus an amount equal to the amount of additional tax incurred by you as a result of receiving such bonus, if any, and (b) on or
before the one (1) year anniversary of any other AD Grant Note issued during the term of this Agreement and for so long as you remain an employee of the Company as of such date, pay you a cash bonus in an amount equal to the principal amount of
such outstanding AD Grant Note, plus accrued interest thereon plus an amount equal to the amount of additional tax incurred by you as a result of receiving such bonus, if any (the “Subsequent AD Grant Bonus;” the Subsequent
AD Grant Bonus and the 2007 AD Grant Bonus are each referred to herein as an “AD Grant Bonus”); provided, that at such time the Company files a Form S-1 with the Securities and Exchange Commission (or the equivalent filing
with the appropriate securities agency under the laws of Japan) in connection with the initial public offering of the Company’s common stock, no further bonus shall be payable pursuant to this sentence.” 

2. NO OTHER CHANGES. Except as expressly amended by this Amendment, the Agreement shall remain unmodified and in full force and effect. 

3. ENTIRE AGREEMENT. The Original Agreement, as modified by the First, Second, Third, Fourth and this Amendment, contains all the legally
binding understandings and agreements between the Company and Employee pertaining to the subject matter hereof and supersedes all such agreements, whether oral or in writing, previously entered into between the parties. 

  
 2 

 4. GOVERNING LAW. This Amendment shall be deemed a contract made under, and for all purposes
shall be construed in accordance with, the laws of Washington and subject to the arbitration provision set forth in Section 12 of the Original Agreement. 

5. AMENDMENT. No provision of this Amendment may be amended or waived unless such amendment or waiver is agreed to in writing by the Company
and Employee. No waiver of the breach of any condition or provision of this Amendment will be deemed a waiver of a similar or dissimilar provision or condition at the same or any prior or subsequent time. Failure or delay on the part of either party
hereto to enforce any right, power, or privilege hereunder will not be deemed to constitute a waiver thereof. 
 6. SEVERABILITY. In the
event any portion of this Amendment is determined to be invalid or unenforceable for any reason, the remaining portions shall be unaffected thereby and will remain in full force and effect to the fullest extent permitted by law. 

IN WITNESS WHEREOF, the parties hereto have executed this Amendment as of the date first written above. 

 

			
	COMPANY
	
	ACUCELA INC.
		
	By:	 	 /s/ Ryo Kubota

		 	Ryo Kubota, M.D., Ph.D.
		 	President and Chief Executive Officer
	
	EMPLOYEE
	
	 /s/ Ryo Kubota

	Ryo Kubota, M.D., Ph.D.

 SIGNATURE PAGE TO FIFTH AMENDMENT TO EMPLOYMENT AGREEMENT 

  
 3 

 SIXTH AMENDMENT 

TO 
 EMPLOYMENT AGREEMENT

 THIS SIXTH AMENDMENT TO EMPLOYMENT AGREEMENT (this “Amendment”) is entered into on December 4, 2013 by and
between Acucela Inc., a Washington corporation (the “Company”), and Ryo Kubota, M.D., Ph.D. (“Employee”). 

RECITALS 
 WHEREAS, the
Company and Employee entered into the Employment Agreement dated April 18, 2005 (the “Original Agreement”), as amended by the First, Second, Third, Fourth and Fifth Amendments thereto (collectively, the
“Agreement”). All capitalized terms used but not otherwise defined herein shall have the meaning set forth in the Agreement. 

WHEREAS, Section 3(d)(ii) of the Agreement provides that until the Company’s initial public offering of its common stock, the
Company shall as often as necessary grant to Employee options to purchase common stock or restricted shares of common stock so that Employee’s equity position in the Company is equal to at least 51% of the Company’s outstanding common
stock on an as-converted basis, which equity position shall be calculated as provided in Section (3)(d)(ii). 
 WHEREAS, the parties desire
to amend Section 3(d)(ii) of the Agreement as set forth below. 
 AGREEMENT 

NOW THEREFORE, IT IS HEREBY AGREED: 

1. AMENDMENT. The following sentence shall be added to the end of Section 3(d)(ii) of the Agreement: 

“Notwithstanding the foregoing, effective upon the filing of a registration statement related to the initial public offering of common
stock of the Company with the Securities and Exchange Commission, this Section 3(d)(ii) shall not apply until the earlier of (x) the date on which the Securities and Exchange Commission consents to the withdrawal of said registration
statement pursuant to the Company’s application therefor, or (y) May 31, 2014, if the shares of the Company’s common stock are not approved for quotation on the Tokyo Stock Exchange, Inc. by such date.” 

2. NO OTHER CHANGES. Except as expressly amended by this Amendment, the Agreement shall remain
unmodified and in full force and effect. 
 3. ENTIRE AGREEMENT. The Original Agreement, as modified by the
First, Second, Third, Fourth, Fifth and this Amendment, contains all the legally binding understandings and agreements between the Company and Employee pertaining to the subject matter hereof and supersedes all such agreements, whether oral or in
writing, previously entered into between the parties. 

 4. GOVERNING LAW. This Amendment shall be deemed a contract made
under, and for all purposes shall be construed in accordance with, the laws of Washington and subject to the arbitration provision set forth in Section 12 of the Original Agreement. 

5. AMENDMENT. No provision of this Amendment may be amended or waived unless such amendment or waiver is agreed to in writing
by the Company and Employee. No waiver of the breach of any condition or provision of this Amendment will be deemed a waiver of a similar or dissimilar provision or condition at the same or any prior or subsequent time. Failure or delay on the part
of either party hereto to enforce any right, power, or privilege hereunder will not be deemed to constitute a waiver thereof. 
 6.
SEVERABILITY. In the event any portion of this Amendment is determined to be invalid or unenforceable for any reason, the remaining portions shall be unaffected thereby and will remain in full force and effect to the fullest extent
permitted by law. 
 IN WITNESS WHEREOF, the parties hereto have executed this Amendment as of the date first written above. 

 

			
	 COMPANY
  

ACUCELA INC.

		
	By:	 	/s/ Ryo Kubota
		 	 Ryo Kubota, M.D., Ph.D.
 President and Chief
Executive Officer

  

	
	EMPLOYEE
	
	/s/ Ryo Kubota
	Ryo Kubota, M.D., Ph.D.

 SIGNATURE PAGE TO SIXTH
AMENDMENT TO EMPLOYMENT AGREEMENTDevelopment and Collaboration Agreement, Otsuka Pharmaceutical Co., Ltd.

 EXHIBIT 10.10 
 CONFIDENTIAL TREATMENT REQUESTED. CERTAIN PORTIONS OF THIS DOCUMENT HAVE BEEN OMITTED PURSUANT TO A REQUEST FOR CONFIDENTIAL TREATMENT AND, WHERE APPLICABLE, HAVE BEEN MARKED WITH AN ASTERISK TO DENOTE
WHERE OMISSIONS HAVE BEEN MADE. THE CONFIDENTIAL MATERIAL HAS BEEN FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION. 
 Execution Copy 
 DEVELOPMENT AND COLLABORATION
AGREEMENT 
 by and between 
 OTSUKA PHARMACEUTICAL CO., LTD. 
 and 

ACUCELA INC. 
 dated as of September 15, 2010 

 TABLE OF CONTENTS 

 

							
	 	 	 	  	PAGE	 
			
	 ARTICLE 1
	 	 DEFINITIONS
	  	 	1	  
			
	 1.1
	 	 “4429 Agreement”
	  	 	1	  
			
	 1.2
	 	 “Acquirer”
	  	 	1	  
			
	 1.3
	 	 “ACU-4429”
	  	 	1	  
			
	 1.4
	 	 “Affiliate”
	  	 	2	  
			
	 1.5
	 	 “Aggregate Commercialization Cost Cap”
	  	 	2	  
			
	 1.6
	 	 “Aggregate Development Cost Cap”
	  	 	2	  
			
	 1.7
	 	 “Annual Development Cost Cap”
	  	 	2	  
			
	 1.8
	 	 “Applicable Laws”
	  	 	2	  
			
	 1.9
	 	 “Calendar Quarter”
	  	 	2	  
			
	 1.10
	 	 “Change of Control”
	  	 	2	  
			
	 1.11
	 	 “Commercialization”
	  	 	3	  
			
	 1.12
	 	 “Commercialization Costs”
	  	 	3	  
			
	 1.13
	 	 “Commercialization Plan”
	  	 	3	  
			
	 1.14
	 	 “Commercially Reasonable Efforts”
	  	 	3	  
			
	 1.15
	 	 “Confidential Information”
	  	 	4	  
			
	 1.16
	 	 “Control”
	  	 	4	  
			
	 1.17
	 	 “Co-Promotion”
	  	 	4	  
			
	 1.18
	 	 “Co-Promotion Agreement”
	  	 	4	  
			
	 1.19
	 	 “Cost Overrun”
	  	 	4	  
			
	 1.20
	 	 “CRO”
	  	 	4	  
			
	 1.21
	 	 “Detail” or “Detailing”
	  	 	4	  
			
	 1.22
	 	 “Developed Know-How”
	  	 	4	  
			
	 1.23
	 	 “Developed Patent Rights”
	  	 	4	  
			
	 1.24
	 	 “Development”
	  	 	4	  
			
	 1.25
	 	 “Development Costs”
	  	 	4	  
			
	 1.26
	 	 “Development Plan”
	  	 	5	  
			
	 1.27
	 	 “Distribution” or “Distribution Activities”
	  	 	5	  
			
	 1.28
	 	 “Dr. Kubota”
	  	 	5	  
			
	 1.29
	 	 “Escalation Notice”
	  	 	5	  

  
 -i-

 TABLE OF CONTENTS 

(CONTINUED) 
  

							
	 	 	 	  	PAGE	 
			
	 1.30
	 	 “Expert”
	  	 	5	  
			
	 1.31
	 	 “Expert Matter”
	  	 	5	  
			
	 1.32
	 	 “FDA”
	  	 	6	  
			
	 1.33
	 	 “Field”
	  	 	6	  
			
	 1.34
	 	 “First Commercial Sale”
	  	 	6	  
			
	 1.35
	 	 “Force Majeure Event”
	  	 	6	  
			
	 1.36
	 	 “FTE”
	  	 	6	  
			
	 1.37
	 	 “FTE Rate”
	  	 	6	  
			
	 1.38
	 	 “General Commercialization Plan Outline”
	  	 	6	  
			
	 1.39
	 	 “General Development Plan Outline”
	  	 	6	  
			
	 1.40
	 	 “Generic Competition Commencement Date”
	  	 	6	  
			
	 1.41
	 	 “Generic Version”
	  	 	7	  
			
	 1.42
	 	 “Global Studies”
	  	 	7	  
			
	 1.43
	 	 “Good Clinical Practices” or “GCP”
	  	 	7	  
			
	 1.44
	 	 “Good Laboratory Practices” or “GLP”
	  	 	7	  
			
	 1.45
	 	 “IND”
	  	 	7	  
			
	 1.46
	 	 “Initial Commercialization Costs”
	  	 	7	  
			
	 1.47
	 	 “Initial Formulation”
	  	 	7	  
			
	 1.48
	 	 “Initial Indication”
	  	 	7	  
			
	 1.49
	 	 “Intrinsic Defect”
	  	 	8	  
			
	 1.50
	 	 “Joint Commercialization Committee” or “JCC”
	  	 	8	  
			
	 1.51
	 	 “Joint Development Committee” or “JDC”
	  	 	8	  
			
	 1.52
	 	 “Know-How”
	  	 	8	  
			
	 1.53
	 	 “Launch”
	  	 	8	  
			
	 1.54
	 	 “Launch Year”
	  	 	8	  
			
	 1.55
	 	 “Licensed Compound”
	  	 	8	  
			
	 1.56
	 	 “Licensed Know-How”
	  	 	8	  
			
	 1.57
	 	 “Licensed IP”
	  	 	8	  
			
	 1.58
	 	 “Licensed Patent Rights”
	  	 	8	  
			
	 1.59
	 	 “Licensed Product”
	  	 	9	  

  
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	 	 	 	  	PAGE	 
			
	 1.60
	 	 “Manufacture,” “Manufacturing” or “Manufacturing Activities”
	  	 	9	  
			
	 1.61
	 	 “NDA”
	  	 	9	  
			
	 1.62
	 	 “Net Sales”
	  	 	9	  
			
	 1.63
	 	 “New Compound”
	  	 	11	  
			
	 1.64
	 	 “New Compound Product”
	  	 	11	  
			
	 1.65
	 	 “New Formulation”
	  	 	11	  
			
	 1.66
	 	 “Operational Team”
	  	 	11	  
			
	 1.67
	 	 “Opt-In Right”
	  	 	11	  
			
	 1.68
	 	 “Other Indication”
	  	 	11	  
			
	 1.69
	 	 “Other Indication Product”
	  	 	11	  
			
	 1.70
	 	 “* Opt-In Right”
	  	 	12	  
			
	 1.71
	 	 “P3 Opt-In Right”
	  	 	12	  
			
	 1.72
	 	 “Participation Percentage”
	  	 	12	  
			
	 1.73
	 	 “Patent Rights”
	  	 	12	  
			
	 1.74
	 	 “PDE” or “Primary Detail Equivalent”
	  	 	12	  
			
	 1.75
	 	 “Person”
	  	 	12	  
			
	 1.76
	 	 “Phase 2 Clinical Trial”
	  	 	12	  
			
	 1.77
	 	 “Phase 2b Clinical Trial”
	  	 	12	  
			
	 1.78
	 	 “Phase 3 Clinical Trial”
	  	 	12	  
			
	 1.79
	 	 “Phase 3 Clinical Trial by Adjunctive Use”
	  	 	12	  
			
	 1.80
	 	 “Phase 3b Clinical Trial”
	  	 	12	  
			
	 1.81
	 	 “Phase 4 Clinical Trial”
	  	 	13	  
			
	 1.82
	 	 “Post-Approval Studies”
	  	 	13	  
			
	 1.83
	 	 “Post-Opt-In Cost Overrun”
	  	 	13	  
			
	 1.84
	 	 “Pre-Marketing Activities”
	  	 	13	  
			
	 1.85
	 	 “Primary Position”
	  	 	13	  
			
	 1.86
	 	 “Primary Position Detail”
	  	 	13	  
			
	 1.87
	 	 “Qualified IPO”
	  	 	13	  
			
	 1.88
	 	 “Regulatory Approval”
	  	 	13	  
			
	 1.89
	 	 “Regulatory Filings”
	  	 	13	  

  

	*	Confidential Treatment Requested. 

  
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	 	 	 	  	PAGE	 
			
	 1.90
	 	 “Responsible Party”
	  	 	13	  
			
	 1.91
	 	 “ROFN Period”
	  	 	14	  
			
	 1.92
	 	 “Secondary Position”
	  	 	14	  
			
	 1.93
	 	 “Secondary Position Detail”
	  	 	14	  
			
	 1.94
	 	 “Senior Executives”
	  	 	14	  
			
	 1.95
	 	 “Sharing Payment”
	  	 	14	  
			
	 1.96
	 	 “Territory”
	  	 	14	  
			
	 1.97
	 	 “Third Party”
	  	 	14	  
			
	 1.98
	 	 “Third Party IP”
	  	 	14	  
			
	 1.99
	 	 “Third Party IP Costs”
	  	 	14	  
			
	 1.100
	 	 “U.S.-Only Studies”
	  	 	14	  
			
	 ARTICLE 2
	 	 GOVERNANCE
	  	 	15	  
			
	 2.1
	 	 Joint Development Committee
	  	 	15	  
			
	 2.2
	 	 Joint Commercialization Committee
	  	 	18	  
			
	 ARTICLE 3
	 	 CERTAIN RIGHTS AND RESTRICTIONS
	  	 	21	  
			
	 3.1
	 	 Opt-In Right for Initial Indication in the Initial Formulation
	  	 	21	  
			
	 3.2
	 	 Other Indications
	  	 	23	  
			
	 3.3
	 	 New Formulations
	  	 	24	  
			
	 3.4
	 	 New Compound Product
	  	 	26	  
			
	 3.5
	 	 Secondment
	  	 	27	  
			
	 3.6
	 	 Exclusivity
	  	 	27	  
			
	 3.7
	 	 Activities Outside Field and Territory
	  	 	28	  
			
	 ARTICLE 4
	 	 DEVELOPMENT
	  	 	28	  
			
	 4.1
	 	 Development Plans
	  	 	28	  
			
	 4.2
	 	 Indirect FTEs
	  	 	29	  
			
	 4.3
	 	 Development Activities Prior to Exercise of Opt-In Right
	  	 	30	  
			
	 4.4
	 	 Co-Development After Exercise of Opt-In Right
	  	 	32	  
			
	 4.5
	 	 Subcontracting
	  	 	33	  
			
	 4.6
	 	 Audit Rights
	  	 	34	  
			
	 4.7
	 	 Key Member
	  	 	34	  

  
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(CONTINUED) 
  

							
	 	 	 	  	PAGE	 
			
	 ARTICLE 5
	 	 MANUFACTURE AND COMMERCIALIZATION
	  	 	35	  
			
	 5.1
	 	 Manufacture and Supply
	  	 	35	  
			
	 5.2
	 	 Sales and Distribution
	  	 	36	  
			
	 5.3
	 	 Commercialization Plans
	  	 	36	  
			
	 5.4
	 	 Co-Promotion
	  	 	38	  
			
	 5.5
	 	 Acucela Mark
	  	 	40	  
			
	 ARTICLE 6
	 	 LICENSES
	  	 	41	  
			
	 6.1
	 	 Pre-Opt-In Development License
	  	 	41	  
			
	 6.2
	 	 License for Joint Development
	  	 	41	  
			
	 6.3
	 	 License for Co-Promotion
	  	 	41	  
			
	 6.4
	 	 Sublicenses by Acucela
	  	 	42	  
			
	 6.5
	 	 Other Licenses by Otsuka
	  	 	42	  
			
	 6.6
	 	 No Implied Licenses; Retained Rights
	  	 	42	  
			
	 ARTICLE 7
	 	 FINANCIAL TERMS
	  	 	42	  
			
	 7.1
	 	 Opt-In Fee
	  	 	42	  
			
	 7.2
	 	 Development Milestone Payments
	  	 	43	  
			
	 7.3
	 	 Sales Milestone Payments
	  	 	44	  
			
	 7.4
	 	 Cost Sharing
	  	 	44	  
			
	 7.5
	 	 Sharing of Net Sales
	  	 	52	  
			
	 7.6
	 	 No Payments if Opt-In Right Not Exercised
	  	 	52	  
			
	 7.7
	 	 Other Payment Terms
	  	 	53	  
			
	 7.8
	 	 Records Retention; Audits
	  	 	53	  
			
	 ARTICLE 8
	 	 REGULATORY MATTERS
	  	 	54	  
			
	 8.1
	 	 Regulatory Filings, Labeling
	  	 	54	  
			
	 8.2
	 	 Drug Master File; Transfer by Otsuka
	  	 	55	  
			
	 8.3
	 	 Pharmacovigilance
	  	 	55	  
			
	 8.4
	 	 Product Recall or Withdrawal
	  	 	56	  
			
	 ARTICLE 9
	 	 INTELLECTUAL PROPERTY
	  	 	56	  
			
	 9.1
	 	 Development Intellectual Property
	  	 	56	  
			
	 9.2
	 	 Third Party IP
	  	 	57	  

  
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	 	 	 	  	PAGE	 
			
	 9.3
	 	 Licensed Patent Rights
	  	 	57	  
			
	 9.4
	 	 Infringement Claims Against the Parties
	  	 	58	  
			
	 9.5
	 	 Enforcement of Licensed Patent Rights in the Territory
	  	 	59	  
			
	 9.6
	 	 Costs and Recoveries
	  	 	60	  
			
	 9.7
	 	 Trademarks; Logos, Names
	  	 	61	  
			
	 9.8
	 	 Copyrights
	  	 	61	  
			
	 ARTICLE 10
	 	 REPRESENTATIONS, WARRANTIES AND COVENANTS
	  	 	61	  
			
	 10.1
	 	 Mutual Representations, Warranties and Covenants
	  	 	61	  
			
	 10.2
	 	 Additional Otsuka Representations, Warranties and Covenants
	  	 	62	  
			
	 10.3
	 	 Knowledge Definition
	  	 	63	  
			
	 10.4
	 	 Disclaimer
	  	 	63	  
			
	 ARTICLE 11
	 	 INDEMNIFICATION AND INSURANCE
	  	 	64	  
			
	 11.1
	 	 Indemnification of Otsuka
	  	 	64	  
			
	 11.2
	 	 Indemnification of Acucela
	  	 	64	  
			
	 11.3
	 	 Shared Liabilities
	  	 	64	  
			
	 11.4
	 	 Indemnification Procedures
	  	 	65	  
			
	 11.5
	 	 Insurance
	  	 	66	  
			
	 ARTICLE 12
	 	 CONFIDENTIALITY
	  	 	66	  
			
	 12.1
	 	 Confidentiality; Exceptions
	  	 	66	  
			
	 12.2
	 	 Authorized Disclosure
	  	 	67	  
			
	 12.3
	 	 Termination of Prior Confidentiality Agreement
	  	 	67	  
			
	 12.4
	 	 Disclosure of Terms
	  	 	67	  
			
	 12.5
	 	 Publications
	  	 	67	  
			
	 12.6
	 	 Conflict of Interest
	  	 	67	  
			
	 12.7
	 	 Press Releases and Announcements
	  	 	68	  
			
	 ARTICLE 13
	 	 TERM AND TERMINATION
	  	 	68	  
			
	 13.1
	 	 Term
	  	 	68	  
			
	 13.2
	 	 Termination for Material Breach
	  	 	68	  
			
	 13.3
	 	 Termination for Insolvency
	  	 	68	  
			
	 13.4
	 	 Other Termination
	  	 	69	  

  
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	 	 	 	  	PAGE	 
			
	 13.5
	 	 Other Termination by Acucela
	  	 	70	  
			
	 13.6
	 	 Automatic Termination
	  	 	70	  
			
	 13.7
	 	 Mutual Agreement
	  	 	70	  
			
	 13.8
	 	 Effects of Termination
	  	 	70	  
			
	 13.9
	 	 Accrued Obligations
	  	 	72	  
			
	 13.10
	 	 Survival
	  	 	72	  
			
	 ARTICLE 14
	 	 MISCELLANEOUS
	  	 	72	  
			
	 14.1
	 	 Governing Law
	  	 	72	  
			
	 14.2
	 	 Dispute Resolution
	  	 	72	  
			
	 14.3
	 	 Limitation of Liability
	  	 	74	  
			
	 14.4
	 	 Assignment
	  	 	74	  
			
	 14.5
	 	 Independent Contractors
	  	 	74	  
			
	 14.6
	 	 Waiver
	  	 	74	  
			
	 14.7
	 	 Force Majeure
	  	 	74	  
			
	 14.8
	 	 Severability
	  	 	75	  
			
	 14.9
	 	 Construction
	  	 	75	  
			
	 14.10
	 	 Notices
	  	 	75	  
			
	 14.11
	 	 Export Control
	  	 	76	  
			
	 14.12
	 	 Amendment
	  	 	76	  
			
	 14.13
	 	 Entire Agreement
	  	 	76	  
			
	 14.14
	 	 Execution in Counterparts; Facsimile Signatures
	  	 	76	  

  
 -vii-

 DEVELOPMENT AND COLLABORATION AGREEMENT 

THIS DEVELOPMENT AND COLLABORATION
AGREEMENT (this “Agreement”) is made and entered into as of September 15, 2010 (the “Effective Date”) by and between OTSUKA PHARMACEUTICAL
CO., LTD., a Japanese corporation having its principal place of business at Shinagawa Grand Central Tower, 2-16-4 Konan, Minato-Ku, Tokyo 108-8242, Japan (“Otsuka”), and
ACUCELA INC., a Washington corporation having its principal place of business at 1301 Second Ave, Suite 1900, Seattle, Washington 98101-3805, USA (“Acucela”). Acucela and Otsuka are sometimes
referred to herein individually as a “Party” and collectively as the “Parties.” 
 RECITALS

 A. Otsuka is an established pharmaceutical company that has expertise and capability in researching, developing, manufacturing and
marketing human pharmaceuticals. Otsuka has developed a small molecule adenosine A2a receptor agonist known as “OPA-6566” (defined below as the “Licensed Compound”) and Otsuka owns or controls certain patents, know-how and other
intellectual property relating to such compound. 
 B. Acucela is a biopharmaceutical company that has expertise and capability in
researching and developing therapies to treat human ophthalmic conditions and diseases. 
 C. Otsuka and Acucela desire to establish a
collaborative arrangement under which Otsuka will engage Acucela to develop the Licensed Compound and pharmaceutical products containing the Licensed Compound for the treatment of glaucoma and, potentially, other ophthalmologic diseases, and Acucela
will have the right to jointly develop and co-promote such compound and products for such treatment(s) in the United States, all on the terms set forth in this Agreement. 
 NOW, THEREFORE, the Parties agree as follows: 
 ARTICLE 1 

DEFINITIONS 
 Capitalized terms used in this Agreement (other than the headings of the Sections or Articles) shall have the following meanings set forth in this Article 1, or, if not listed in this Article 1, the
meaning as designated in the text of this Agreement. 
 1.1 “4429 Agreement” means the Co-Development and
Commercialization Agreement entered into by the Parties and dated as of September 4, 2008 and any amendment(s) thereto. 

1.2 “Acquirer” means another Person who controls (as defined in Section 1.4) Acucela as a result of the occurrence
of Change of Control after the Effective Date. 
 1.3 “ACU-4429” means the chemical entity defined as the
“Lead Compound” under the 4429 Agreement. 

 1.4 “Affiliate” means, with respect to a Party or an Acquirer, any person,
corporation, partnership or other entity that controls, is controlled by, or is under common control with such Party or Acquirer, as the case may be, but only for so long as such control exists. As used in this definition, the term
“control” (with correlative meanings for the terms “controlled by” and “under 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 Person, whether by the direct or indirect beneficial ownership of more than 50% of the voting stock of such Party or Acquirer or by contract or otherwise. 

1.5 “Aggregate Commercialization Cost Cap” has the meaning set forth in Section 7.4(c)(ii). 

1.6 “Aggregate Development Cost Cap” means, (a) with respect to Licensed Product for the Initial Indication in the
Initial Formulation and any New Formulation for which Acucela exercises its opt-in right under Section 3.3 and which is Developed prior to *, the amount set forth in Section 7.4(b)(i), and (b) with respect to each Other Indication
Product for Other Indications for which Acucela exercises its opt-in right under Section 3.2, the amount established by the JDC as the Aggregate Development Cost Cap for such Other Indication Product for such Other Indication. 

1.7 “Annual Development Cost Cap” has the meaning set forth in Section 7.4(b)(ii). 

1.8 “Applicable Laws” means the applicable provisions of any and all national, supranational, regional, state and local
laws, treaties, statutes, rules, regulations, administrative codes, guidance, ordinances, judgments, decrees, directives, injunctions, orders and permits (including Regulatory Approvals) of or from any court, arbitrator, or governmental agency or
authority having jurisdiction over or related to the subject activity or item, as they may be in effect from time to time. 

1.9 “Calendar Quarter” means each of the three-month periods ending on
March 31, June 30, September 30 and December 31 of any year. 
 1.10“Change of
Control” means (a) a sale, conveyance, or other disposition of all or substantially all of Acucela’s assets, (b) any merger, consolidation or other business combination transaction of Acucela with or into another Person, in
which the holders of the shares of voting capital stock of Acucela outstanding immediately prior to such transaction continue to hold (either by such shares remaining outstanding or by their being converted into shares of voting capital stock of the
surviving entity) less than a majority of the total voting power represented by the shares of voting capital stock of Acucela (or the surviving entity) outstanding immediately after such transaction, or (c) the direct or indirect acquisition
(including by way of a tender or exchange offer) by any Person, or Persons acting as a “group” within the meaning of Section 13(d) of the Securities and Exchange Act of 1934, as amended, excluding in either case any Person who was a
shareholder of Acucela as of the Effective Date, of beneficial ownership or a right to acquire beneficial ownership of shares representing a majority of the voting power of the then outstanding shares of capital stock of Acucela; provided,
however, that, in the case of clause (c) of this Section 1.10, in no event shall the acquisition of the right to acquire beneficial ownership of shares of capital stock of Acucela be deemed to be the acquisition of beneficial ownership of
such shares unless and until such right has been exercised. 

  

	*	Confidential Treatment Requested. 

  
 2 

 1.11 “Commercialization” means marketing, promoting, offering for sale,
selling, importing, distributing and other similar activities related to the commercial sale of Licensed Products in the Field in the Territory, including Licensed Product Detailing, market research, public relations, marketing (including direct
mail, telemarketing, media placement and advertising), development of visual sales aids, medical education planning and programs (including symposia, advisory boards, conferences and seminars), educational grants and sales meetings.
Commercialization includes Pre-Marketing Activities, Phase 3b Clinical Trials and Post-Approval Studies. When used as a verb, “Commercializing” means to engage in Commercialization and “Commercialize” and
“Commercialized” have corresponding meanings. 
 1.12 “Commercialization Costs” means all
(a) documented out-of-pocket costs and expenses actually incurred by a Party in accordance with a Commercialization Plan (and budget set forth therein) that are specifically attributable to Commercialization (other than Distribution or
Manufacturing), including *, (b) documented direct and indirect internal costs (calculated on an FTE basis at the FTE Rate) incurred by a Party in conducting Phase 4 Clinical Trials, if any, in accordance with a Development Plan (and budget set
forth therein), (c) documented direct and indirect internal costs (calculated on an FTE basis at the FTE Rate) incurred by a Party in conducting Phase 3b Clinical Trials and Post-Approval Studies, if any, in accordance with a Commercialization
Plan (and budget set forth therein), and (d) Third Party IP Costs. Commercialization Costs exclude the following costs and expenses, which shall be borne by the Party that incurs such costs and expenses: (i) *. 

1.13 “Commercialization Plan” means each plan setting forth the agreed Commercialization activities for each Licensed
Product in the Field in the Territory and containing the information set out in Section 5.3, as each such plan is approved and may be amended by the JCC in accordance with this Agreement. Each Commercialization Plan shall be incorporated into
this Agreement and shall form an integral part of this Agreement. 
 1.14 “Commercially Reasonable Efforts”
means: (a) where applied to carrying out specific tasks and obligations under this Agreement, deploying appropriate resources commensurate with the tasks or obligations, and carrying out such tasks or obligations in a sustained manner; and
(b) where applied to Development or Commercialization, the use of efforts and deployment of resources that a similarly situated company within the pharmaceutical industry would reasonably use were it developing or commercializing its own
pharmaceutical compounds or products that are of similar market and profit potential and of similar risk profile at a similar stage in their product life as the Licensed Compound or Licensed Product, as applicable, taking into account anticipated
product labeling, anticipated financial return, relevant medical and clinical considerations, anticipated regulatory environment and competitive market conditions, all as measured by the facts and circumstances at the time such efforts are due, but
in no event less than the type and scope of efforts that the applicable Party would devote to any of its other products of similar market and profit potential and similar risk profile at a similar stage of product life. 

  

	*	Confidential Treatment Requested. 

  
 3 

 1.15 “Confidential Information” has the meaning set forth in
Section 12.1. 
 1.16 “Control” (including any variations such as “Controlled” and
“Controlling”) means, with respect to any intellectual property right or other intangible property, the possession by license or ownership by a Party or its Affiliate of the legal authority or right to grant to the other Party
access and/or a license or sublicense or other right as provided herein without violating the terms of any agreement with any Third Party. 
 1.17 “Co-Promotion” means promotion, including Detailing and marketing, of Licensed Products by Otsuka and Acucela (and/or their respective Affiliates) under the same Regulatory Approval
and the same Licensed Product trademarks in the Field in the Territory. When used as a verb, “Co-Promote” means to engage in such activities. 
 1.18 “Co-Promotion Agreement” has the meaning given in Section 5.4(j). 
 1.19 “Cost Overrun” has the meaning set forth in Section 4.3(d). 
 1.20 “CRO” means a Third Party contract research organization. 

1.21 “Detail” or “Detailing” means, with respect to Licensed Product, a face-to-face sales call meeting in the
Territory between a Party’s sales representative and a healthcare professional (to be defined in the Co-Promotion Agreement or Commercialization Plan) in such healthcare professional’s office, hospital or at other locations (but excluding
medical convention exhibits and displays), during which the Party’s sales representative makes an oral presentation to the healthcare professional of the Licensed Product’s attributes, describing the FDA-approved indicated uses, safety,
effectiveness, contraindications, side effects, warnings and other relevant characteristics of Licensed Product in a fair and balanced manner consistent with the requirements of the Co-Promotion Agreement, applicable policies of the respective
Party, and all Applicable Laws, in a manner that is customary in the industry for the purpose of promoting a prescription pharmaceutical product. 
 1.22 “Developed Know-How” has the meaning set forth in Section 9.1(a). 
 1.23 “Developed Patent Rights” has the meaning set forth in Section 9.1(c). 
 1.24 “Development” means all human clinical trials (including bridging studies and Phase 4 Clinical Trials), regulatory affairs and other activities approved by the JDC which are
reasonably related to developing and submitting information to the FDA for purposes of seeking and obtaining Regulatory Approval; provided that “Development” does not mean or include Phase 3b Clinical Trials, Post-Approval Studies,
preclinical or CMC development activities, or Manufacturing Activities. When used as a verb, “Develop” means to engage in Development. 
 1.25 “Development Costs” means all documented direct and indirect costs and expenses, without any mark-up, actually incurred by or on behalf of a Party in accordance with a Development
Plan (and the budget set forth therein) that are specifically attributable to Development, excluding costs of conducting Phase 4 Clinical Trials (which shall be included in Commercialization Costs) *. 

  

	*	Confidential Treatment Requested. 

  
 4 

 1.26 “Development Plan” means each written plan setting forth the agreed
Development activities for the Licensed Compound and each Licensed Product in the Field in the Territory and containing the information set out in Section 4.1, as each such plan is approved and may be amended by the JDC in accordance with this
Agreement. Each Development Plan shall be incorporated into this Agreement and shall form an integral part of this Agreement. 

1.27 “Distribution” or “Distribution Activities” means all distribution activities related to the Licensed
Product in the Territory, including, without limitation, receipt and process of orders, pick, pack and ship operations, completion and provision of sales documentation, order delivery, invoicing and collection activities, inventory control, pricing,
discounting, rebating and other terms of sale, and any other distribution activities. 
 1.28 “Dr. Kubota”
means Dr. Ryo Kubota, the Chief Executive Officer of Acucela as of the Effective Date. 
 1.29 “Escalation
Notice” has the meaning set forth in Section 2.1(e)(i). 
 1.30 “Expert” means a mutually
acceptable, disinterested, conflict-of-interest-free individual with such scientific, technical, regulatory and commercial experience as is necessary to resolve an Expert Matter. The Expert shall not be or have been during the preceding five
(5) years an Affiliate, employee, consultant, officer or director of either Party or any of their respective Affiliates. 

1.31 “Expert Matter” means an issue arising under this Agreement due to a difference of business or scientific judgment,
but pertaining only to: 
 (a) Whether any (and, if so, which) Development activities or expenditures, which if conducted
(or, in the case of expenditures, if spent) would obligate Acucela to fund Development Costs in excess of the Aggregate Development Cost Cap, are necessary to be conducted (or, in the case of expenditures, are necessary to be spent) in order to
obtain Regulatory Approval; 
 (b) Whether any (and, if so, which) Commercialization activities or expenditures, which if
conducted (or, in the case of expenditures, if spent) would obligate Acucela to fund Initial Commercialization Costs in excess of the Aggregate Commercialization Cost Cap, are necessary to be conducted (or, in the case of expenditures, are necessary
to be spent) in order to improve marketing or increase sales of Licensed Product in the Field in the Territory, taking into consideration the activities conducted and expenditures incurred in connection with the commercialization of other similar
pharmaceutical products then marketed and sold in the Field in the Territory; 
 (c) Determination of the allocation of
relative fair market value of the Licensed Product and all other product(s) included in a combination product as provided in Section 1.62; 
 (d) Amounts of payments due from one Party to the other under this Agreement, including characterization of costs as Development Costs or Commercialization Costs for purposes of determining such
payments; or 
 (e) Whether to terminate this Agreement for scientific reasons pursuant to Section 13.7. 

  
 5 

 1.32 “FDA” means the United States Food and Drug Administration, or any
successor entity thereto. 
 1.33 “Field” means all human therapeutic uses for the treatment of ophthalmologic
diseases including glaucoma. 
 1.34 “First Commercial Sale” means, for any Licensed Product, the first
arm’s-length sale to a Third Party of that Licensed Product for use or consumption by an end-user in the Field in the Territory after obtaining Regulatory Approval of that Licensed Product. A First Commercial Sale shall not include a sale of
any Licensed Product for use in clinical trials, for research or for other non-commercial uses, or supply of a Licensed Product as part of a compassionate use or similar program. 

1.35 “Force Majeure Event” has the meaning set forth in Section 14.7. 

1.36 “FTE” means the equivalent of the work of one (1) employee full time for one (1) year (consisting of *
per year) in directly conducting, or indirectly supporting the conduct of, Development (including Phase 4 Clinical Trials), Phase 3b Clinical Trials and Post-Approval Studies, if any. For the avoidance of doubt, FTE does not include the work of a
Party’s employees or representatives (including any sales representatives or medical science liaisons) in conducting (directly or indirectly) any Commercialization activities other than Phase 3b Clinical Trials and Post-Approval Studies. No
additional payment shall be made with respect to any person who works more than such number of hours per year, and any person who devotes less than such number of hours per year shall be treated as an FTE on a pro-rata basis. 

1.37 “FTE Rate” means initially *, to be adjusted on September 4, 2011 and upon every anniversary thereafter by the
percentage increase, if any, in the Consumer Price Index for Urban Consumers for the West Region, All Items, as published by the U.S. Department of Labor, Bureau of Statistics, for the period since the last adjustment. 

1.38 “General Commercialization Plan Outline” has the meaning set forth in Section 5.3. 

1.39 “General Development Plan Outline” has the meaning set forth in Section 4.1. 

1.40 “Generic Competition Commencement Date” means, on a formulation-by-formulation basis, the last day of the first
Calendar Quarter in which the aggregate units of all Generic Versions (in a particular formulation) sold in the Field in the Territory equal or exceed * of the aggregate units of all Licensed Products (in that same formulation) and all Generic
Versions (in that same formulation) sold in the Territory during such Calendar Quarter. As used herein, a “unit” of Licensed Products means the equivalent of a prescription for thirty (30) day supply of Licensed Product and a
“unit” of Generic Versions shall be determined by IMS data (or an equivalent, reliable source of prescribing information as agreed by the JCC), and the aggregate units of Licensed Products and Generic Versions in any Calendar Quarter shall
be calculated based on IMS data (or an equivalent, reliable source of prescribing information as agreed by the JCC). 

  

	*	Confidential Treatment Requested. 

  
 6 

 1.41 “Generic Version” means a pharmaceutical product sold in the Territory
by a Third Party (who is not authorized by Otsuka or its Affiliates) that (a) contains the Licensed Compound as its active pharmaceutical agent, and (b) has been approved for sales introduction into interstate commerce in the Territory by
reference to the Regulatory Approval for the Licensed Product pursuant to Section 505(b)(2) or 505(j) of the United States Federal Food, Drug, and Cosmetic Act, 21 U.S.C. 301, et. seq., as it may be amended from time to time, and the rules and
regulations promulgated or issued thereunder. 
 1.42 “Global Studies” means any human clinical trials of
Licensed Product for the Initial Indication, other than bridging studies or similar studies that are conducted to show an equivalency to other clinical trials conducted in the Territory, designed to obtain information for purposes of seeking and
obtaining both (a) Regulatory Approval for Licensed Product for the Initial Indication in the Territory and (b) approval of the relevant regulatory authorities to market Licensed Product for the Initial Indication in the European Union
and/or Japan. 
 1.43 “Good Clinical Practices” or “GCP” means the then-current standards, practices
and procedures promulgated or endorsed by the FDA for designing, conducting, recording, analyzing and reporting clinical trials that involve the participation of human subjects, including as set forth in 21 C.F.R. Parts 50, 54, 56 and 312, as the
same may be amended or 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 for nonclinical laboratory studies that support or are intended to support applications to conduct research on human subjects or to obtain regulatory approval,
including as set forth in 21 C.F.R. Part 58, as the same may be amended or updated from time to time. 
 1.45
“IND” means an Investigational New Drug Application (including any amendments thereto) with respect to any Licensed Product filed with the FDA pursuant to 21 C.F.R. §312 before commencing human clinical trials of such
Licensed Product. 
 1.46 “Initial Commercialization Costs” has the meaning set forth in
Section 7.4(c)(ii). 
 1.47 “Initial Formulation” means the formulation of the Licensed Product for the
Initial Indication (a) intended to be used for the first Phase 3 Clinical Trial immediately following Acucela’s exercise of its Opt-In Right, if Acucela exercises the * Opt-In Right, or (b) intended to be used for purposes of filing
the first NDA, if Acucela exercises the P3 Opt-In Right. 
 1.48 “Initial Indication” means human therapeutic
uses for the treatment of glaucoma (including ocular hypertension), which is the indication of the first priority for which the Parties agree to Develop the Licensed Compound and Licensed Products pursuant to the Development Plan. 

  

	*	Confidential Treatment Requested. 

  
 7 

 1.49 “Intrinsic Defect” has the meaning set forth in Section 8.4.

 1.50 “Joint Commercialization Committee” or “JCC” means the committee described in
Section 2.2(a). 
 1.51 “Joint Development Committee” or “JDC” means the committee
described in Section 2.1(a). 
 1.52 “Know-How” means all information, results and data of any type, in
any tangible or intangible form, including databases, ideas, discoveries, inventions, trade secrets, practices, methods, tests, assays, techniques, specifications, processes, formulations, formulae, knowledge, know-how, skill, experience, materials,
including pharmaceutical, chemical and biological materials, products, compounds and compositions, scientific, technical or test data (including pharmacological, biological, chemical, biochemical, toxicological and clinical test data), analytical
and quality control data, stability data, studies, procedures, drawings, plans, designs, diagrams, sketches, technology, documentation or descriptions. “Know-How” does not include Patent Rights. 

1.53 “Launch” means the date of the First Commercial Sale of the Licensed Product for the Initial Indication in the
Initial Formulation. 
 1.54 “Launch Year” means each succeeding twelve (12) month period commencing with
Launch and ending on the date that is the anniversary of the Launch. 
 1.55 “Licensed Compound” means the
small molecule adenosine A2a receptor agonist developed by Otsuka prior to the Effective Date and known as “OPA-6566.” 
 1.56 “Licensed Know-How” means (i) all proprietary Know-How Controlled by Otsuka or any of its Affiliates as of the Effective Date or at any time during the term of this Agreement,
that is (a) related to the Licensed Compound or the use of the Licensed Compound (or a product containing the Licensed Compound or the use of a product containing the Licensed Compound) and (b) necessary or reasonably useful for Acucela to
exercise the rights licensed to it under this Agreement or to perform its obligations under this Agreement, and (ii) all Developed Know-How. 
 1.57 “Licensed IP” means the Licensed Know-How and the Licensed Patent Rights. 
 1.58 “Licensed Patent Rights” means those Patent Rights listed on Exhibit A, attached hereto and incorporated herein, and all other Patent Rights that are Controlled by Otsuka or
any of its Affiliates at any time during the term of this Agreement, that: (i) (a) claim the Licensed Compound or a product containing the Licensed Compound as a composition of matter, or claim a method of use of the Licensed Compound or a
product containing the Licensed Compound and (b) are necessary or reasonably useful for Acucela to exercise the rights licensed to it under this Agreement or to perform its obligations under this Agreement; or (ii) claim or disclose any
Developed Know-How. Exhibit A shall be updated from time to time as requested by either Party to reflect all Patent Rights then within the Licensed Patent Rights. 

  
 8 

 1.59 “Licensed Product” means any pharmaceutical product, in any
formulation, that contains the Licensed Compound as an active chemical entity and which is Developed for use in the Field in the Territory and/or Commercialized in the Field in the Territory. 

1.60 “Manufacture,” “Manufacturing” or “Manufacturing Activities” means the development of
manufacturing processes for, and the manufacture and supply (including formulation, filling, finishing, packaging, labeling, quality control, quality assurance testing and release, shipping, handling, storing and warehousing, as applicable) of,
active pharmaceutical ingredient, bulk drug substance, drug product or placebos to support Development or Commercialization of the Licensed Compound or Licensed Product, as the case may be, including such manufacturing activities conducted for
purposes of producing clinical supplies (or materials used in preclinical testing or research), manufacturing process development, scale-up and validation of manufacturing prior to Regulatory Approval, and manufacture and supply of commercial
quantities of Licensed Product. 
 1.61 “NDA” means a New Drug Application for Licensed Product requesting
permission to place such Licensed Product on the market in accordance with 21 C.F.R. Part 314, and all supplements or amendments thereto filed pursuant to the requirements of the FDA, including all documents, data and other information
concerning such Licensed Product which are reasonably necessary for FDA approval to market Licensed Product in the Field in the Territory. 
 1.62 “Net Sales” means the gross amounts invoiced by Otsuka, its Affiliates or sublicensees to non-sublicensee Third Parties for the sale of Licensed Products to such Third Parties in the
Field in the Territory, less the following deductions to the extent actually incurred, allowed, paid or granted with respect to such sale by the selling party: 
 (i) freight, postage and duties, and transportation charges on shipment of such Licensed Product, including handling and insurance on such shipment; 

(ii) sales (such as VAT or its equivalent) and excise taxes, other consumption taxes, customs duties and other governmental
charges imposed upon the importation, use or sale of such Licensed Product to the customer; 
 (iii) quantity, cash and
other trade discounts; 
 (iv) refunds, chargebacks, allowances and other adjustments that effectively reduce the net
selling price; 
 (v) rebates, credits, allowances, reimbursements and other adjustments paid or granted to customers,
including adjustments granted on account of price adjustments, billing errors, rejected goods, damaged or defective goods, product returns and recalls; 
 (vi) rebates and similar payments made with respect to sales paid for or reimbursed by any governmental authority (or branch thereof) or any Third Party payor, administrator or contractee
(including rebates similar to Medicare or Medicaid); 

  
 9 

 (vii) rebates, credits, chargeback and prime vendor rebates, fees (including
inventory management fees, administrative and other fees), allowances, reimbursements or similar payments or credits paid or granted to wholesalers and other distributors, buying groups, health care insurance carriers, pharmacy benefit management
companies, health maintenance organizations or other institutions or health care organizations, and price reductions/adjustments (including retroactive price reductions) required by law, regulations or contract; and 

(viii) bad debts attributable or allocable to sales of Licensed Product, up to a cap of * of gross amounts invoiced in each
calendar year; provided, however, that any amount that is uncollectible due to the bankruptcy of any of the then- five (5) largest pharmaceutical wholesalers/distributors in the Territory shall not be subject to the foregoing cap.

 Each of the above deductions shall be substantially consistent with Otsuka’s internal accounting policies as consistently applied by
Otsuka and its Affiliates in the Territory across its products at the time of sale. Any of the deductions listed in (i) through (vii) above that involves a payment by Otsuka or its Affiliate(s) or sublicensee(s) shall be taken as a
deduction in the month in which the payment is accrued by such entity. Deductions listed in (viii) above shall be taken in the month in which such bad debts are written off; provided that, for any amounts written off and deducted by
reason of bad debts which are later collected, such amounts shall be treated as a sale of Licensed Product in the month when collected. Otsuka and its Affiliates shall use Commercially Reasonable Efforts to collect and enforce such bad debts from
the debtors. 
 Sales of a Licensed Product between Otsuka and any of its Affiliates or sublicensees for resale shall be excluded from the
computation of Net Sales, but the subsequent resale of such Licensed Product to a non-sublicensee Third Party shall be included within the computation of Net Sales. Notwithstanding anything to the contrary herein, the transfer, disposal or use of
Licensed Product for de minimus or no consideration for marketing, regulatory, development or charitable purposes, such as clinical trials, compassionate use, named patient use, indigent patient programs, or commercial samples, shall not be deemed a
sale hereunder. 
 With respect to Licensed Products, if any, that are sold in the Territory with other products in the Otsuka portfolio, Otsuka
shall not, and shall cause its Affiliates not to, discount the gross invoiced sales price of such Licensed Product in an unfair or inappropriate manner that is intended to maximize the sales of other products in the Otsuka portfolio to the detriment
of revenues from the sale of Licensed Product in the Field in the Territory. 
 If a Licensed Product is sold as part of a combination product
in the Field in the Territory, the Net Sales of the Licensed Product, for the purposes of determining payments based on Net Sales, shall be determined by multiplying the *, by the fraction, A/(A+B), where: 

A is * of the Licensed Product received or set by Otsuka, its Affiliates, licensees or sublicensees when sold separately in finished form
in the Field in the Territory and B is * received or set by Otsuka, its Affiliates, licensees or sublicensees of the other active product(s) included in the combination product when sold separately in finished form in the Field in the Territory, in
each case during the applicable Net Sales reporting period or, if sales of both the Licensed Product and the other active product(s) did not occur in such period, then in the most recent Net Sales reporting period in which sales of both occurred.

  

	*	Confidential Treatment Requested. 

  
 10 

 In the event that such average sales price cannot be determined for both the Licensed Product and all other
active product(s) included in such combination product, Net Sales for the purposes of determining payments based on Net Sales shall be calculated by multiplying the Net Sales of the combination product by the fraction of C/(C+D) where C is * of the
Licensed Product and D is * of all other active product(s) included in the combination product. In such event, Otsuka shall in good faith propose to Acucela an allocation of * of the Licensed Product and all other active product(s) included in the
combination product, Acucela shall in good faith consider such proposal, and the Parties shall seek to reach agreement on such allocation. If the Parties are unable to reach such agreement within * after Otsuka provides such proposal, then such
matter shall be resolved as an Expert Matter in accordance with Section 14.2(a). 
 1.63 “New Compound”
means any adenosine A2a receptor agonist, other than Licensed Compound, which is discovered, developed or acquired by Otsuka or any of its Affiliates during the term of this Agreement. 

1.64 “New Compound Product” means any pharmaceutical product that contains a New Compound as an active chemical entity.

 1.65 “New Formulation” means the Licensed Product for the Initial Indication in any formulation other than
the Initial Formulation, and with respect to which either Otsuka or Acucela makes a proposal to the JDC to Develop as provided in Section 3.3. 
 1.66 “Operational Team” has the meaning set forth in Section 2.1(f). 
 1.67 “Opt-In Right” means either the * Opt-In Right or the P3 Opt-In Right. 
 1.68 “Other Indication” means any and all indications in any formulation within the Field, other than the Initial Indication, for which either Otsuka or Acucela makes a proposal to the
JDC for Development of the Licensed Compound or Licensed Products as provided in Section 3.2. 
 1.69 “Other
Indication Product” means Licensed Product in any formulation the Development of which for an Other Indication is either (a) proposed to the JDC by Otsuka or (b) proposed to the JDC by Acucela and agreed to by Otsuka in its
discretion. For the avoidance of doubt, in the event that the same Licensed Product is developed and/or commercialized for both the Initial Indication and any one or more Other Indications, such Licensed Product shall be construed for purposes of
this Agreement to be an Other Indication Product only with respect to those development and/or commercialization activities related to the applicable Other Indication(s), and shall remain a Licensed Product with respect to activities related to the
Initial Indication. By way of illustration and not limitation, if Acucela exercises its Opt-In Right with respect to a given Licensed Product for the Initial Indication and does not exercise its Opt-In Right with respect to a given Other Indication,
then (i) Acucela shall share Development Costs as set forth in Section 7.4(a) with respect to the Initial Indication, and not the Other Indication, and (ii) Acucela shall receive applicable Sharing Payments under Section 7.5 with
respect to Net Sales of such Licensed Product sold for the Initial Indication, but not with respect to Net Sales of such Licensed Product that are sold for the applicable Other Indication. 

  

	*	Confidential Treatment Requested. 

  
 11 

 1.70 “* Opt-In Right” has the meaning set forth in Section 3.1(a).

 1.71 “P3 Opt-In Right” has the meaning set forth in Section 3.1(b). 

1.72 “Participation Percentage” means either twenty-five percent (25%) or thirty-five percent (35%), as such
percentage is designated by Acucela in writing at the time Acucela exercises an Opt-In Right pursuant to Section 3.1. 

1.73 “Patent Rights” means all: (a) U.S. issued patents, re-examinations, reissues, renewals, extensions and term
restorations, inventors’ certificates; and (b) pending applications for U.S. patents, including provisional applications, continuations, continuations-in-part, continued prosecution, divisional and substitute applications. 

1.74 “PDE” or “Primary Detail Equivalent” means a primary Detail equivalent, where a Primary Position Detail
has a value of * and a Secondary Position Detail has a value of *. A Detail below the Secondary Position shall have *. 

1.75 “Person” means any natural person or any corporation, company, partnership, joint venture, firm, governmental
authority, or other entity, including a Party. 
 1.76 “Phase 2 Clinical Trial” means a human clinical trial of
the Licensed Product conducted in the Territory in the specific patient population with the disease or condition of interest intended to be studied in a Phase 3 Clinical Trial for the purposes of preliminary assessment of safety and efficacy, and
selection of the dose regimen(s) to be studied in a Phase 3 Clinical Trial, as described under 21 C.F.R. §312.21(b). 

1.77 “Phase 2b Clinical Trial” means any Phase 2 Clinical Trial on sufficient numbers of patients that is designed to
establish dosing parameters of the Licensed Product. 
 1.78 “Phase 3 Clinical Trial” means a human clinical
trial of the Licensed Product conducted in the Territory and intended to be a pivotal trial for obtaining Regulatory Approval and to otherwise establish safety and efficacy in patients with the disease or condition being studied for purposes of
filing an NDA for the Licensed Product with the FDA and that would satisfy the requirements under 21 C.F.R. §312.21(c). 

1.79 “Phase 3 Clinical Trial by Adjunctive Use” means any Phase 3 Clinical Trial in which the Licensed Product is used
adjunctively with other pharmaceutical product(s) that is/are approved for sale and sold in the Field in the Territory. 

1.80 “Phase 3b Clinical Trial” means a human clinical trial of the Licensed Product that (a) is voluntarily
conducted after the filing with the FDA of the NDA for the Licensed Product but prior to obtaining Regulatory Approval of such NDA and (b) is not required or requested by the FDA as a condition of or in connection with obtaining such Regulatory
Approval. For clarity, Phase 3b Clinical Trials shall be considered part of Commercialization. 

  

	*	Confidential Treatment Requested. 

  
 12 

 1.81 “Phase 4 Clinical Trial” means a human clinical trial of the Licensed
Product conducted after receipt of Regulatory Approval that is required by the FDA to be conducted after Regulatory Approval as a condition of obtaining and maintaining such Regulatory Approval. For clarity, the design and conduct of Phase 4
Clinical Trials (and review and approval of the same) shall be within the responsibilities of the JDC and included in a Development Plan but the costs of conducting Phase 4 Clinical Trials shall be included in Commercialization Costs. 

1.82 “Post-Approval Studies” means any human clinical trials or studies, including marketing studies, epidemiological
studies, modeling and pharmacoeconomic studies, investigator sponsored clinical trials and post-marketing surveillance studies, of the Licensed Product, other than Phase 4 Clinical Trials, that are conducted after receipt of Regulatory Approval and
that are not intended for use as a basis for obtaining or maintaining such Regulatory Approval. For clarity, Post-Approval Studies shall be considered part of Commercialization. 

1.83 “Post-Opt-In Cost Overrun” has the meaning set forth in Section 7.4(e). 

1.84 “Pre-Marketing Activities” means all Commercialization activities undertaken with respect to the Licensed Product
after the filing with the FDA of the NDA for the Licensed Product but prior to First Commercial Sale thereof and in preparation for the Launch. Pre-Marketing shall include advertising, education, product-related public relations, health care
economic studies, governmental affairs activities for reimbursement and formulary acceptance, trademark selection, filing, prosecution, and enforcement, and other activities included within the Commercialization Plan prior to the First Commercial
Sale of a Licensed Product in the Territory. 
 1.85 “Primary Position” means a Licensed Product presentation
in a Detail in which a Party’s sales representative promotes Licensed Product first in the Detail and emphasizes and promotes that Licensed Product more than any other product in the Detail, and where such Licensed Product receives greater than
fifty percent (50%) of the total call time in the Detail. 
 1.86 “Primary Position Detail” means a Detail
in which a Party’s sales representative promotes Licensed Product in the Primary Position. 
 1.87 “Qualified
IPO” has the meaning set forth in Section 3.1(a)(ii). 
 1.88 “Regulatory Approval” means
approval by the FDA of the NDA for the Licensed Product (including an Other Indication Product and New Formulation, if any) in the Field in the Territory. 
 1.89 “Regulatory Filings” means any document filed with the FDA, including INDs, NDAs, Drug Master Files and the like. 

1.90 “Responsible Party” means, (i) with respect to Development activities for the Territory for any Licensed
Product for the Initial Indication in the Initial Formulation and any New Formulation or for any Other Indication Product, in each case following Acucela’s exercise 

  
 13 

 
of an Opt-In Right with respect to such Licensed Product or Other Indication Product, Acucela unless otherwise mutually agreed by the Parties, and (ii) with respect to Co-Promotion by the
Parties following Acucela’s exercise of an Opt-In Right, the Party(ies) designated, in the applicable Commercialization Plan, as responsible for conducting applicable Commercialization activities under such Commercialization Plan. 

1.91 “ROFN Period” means the period commencing on the date on which Acucela exercises an Opt-In Right under
Section 3.1 and expiring on the date that is * after Launch. 
 1.92 “Secondary Position” means a Licensed
Product presentation in a Detail in which a Party’s sales representative promotes Licensed Product second in the Detail and emphasizes and promotes Licensed Product more than any other product in the Detail except for the product that is
presented in first, and where such Licensed Product receives at least * of the total call time in the Detail. 
 1.93
“Secondary Position Detail” means a Detail in which a Party’s sales representative promotes Licensed Product in the Secondary Position. 
 1.94 “Senior Executives” has the meaning set forth in Section 2.1(e)(ii). 
 1.95 “Sharing Payment” has the meaning set forth in Section 7.5. 
 1.96 “Territory” means the United States of America, including the District of Columbia and all states, territories, possessions and protectorates thereof. 

1.97 “Third Party” means any Person other than a Party or a Party’s Affiliate. 

1.98 “Third Party IP” has the meaning set forth in Section 2.1(b)(xiii). 

1.99 “Third Party IP Costs” means all upfront payments, milestone payments, license fees, royalties or other payments
paid or payable to any Third Party under any agreement to license or acquire rights to Third Party IP following a determination by the JDC or the JCC (in accordance with Section 2.1(b)(xiii) or Section 2.2(b)(viii), respectively) that it
is necessary or advisable to obtain such Third Party IP license or rights in order to use, import, offer for sale or sell Licensed Product in the Field in the Territory or in order to Manufacture Licensed Product for use, import or sale in the Field
in the Territory; provided, however, that if any agreement pursuant to which such Third Party IP license or rights are obtained also conveys rights (i) for products and/or technology that are not Licensed Products and/or (ii) for
use, import or sale outside the Territory, then only that portion of such payments that is fairly allocable to Licensed Product used, imported, offered for sale or sold or Manufactured for use, import or sale in the Territory shall be included
within Third Party IP Costs. 
 1.100 “U.S.-Only Studies” means any human clinical trials of Licensed Product
for the Initial Indication designed to obtain information for purposes of seeking and obtaining Regulatory Approval for Licensed Product for the Initial Indication in the Territory only, including bridging studies and similar studies that are
conducted to show an equivalency to other clinical trials conducted in the Territory. 

  

	*	Confidential Treatment Requested. 

  
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 ARTICLE 2 
 GOVERNANCE 
 2.1 Joint Development Committee. 

(a) Formation and Composition. Within thirty (30) days after the Effective Date, the Parties shall establish a “Joint
Development Committee,” or “JDC.” The JDC initially shall be comprised of eight (8) members, four (4) of whom shall be representatives appointed by Otsuka and four (4) of whom shall be representatives
appointed by Acucela. At least one (1) representative appointed by each Party to the JDC shall have sufficient seniority and authority to make decisions on behalf of such Party and at least two (2) representatives appointed by each Party
to the JDC shall have relevant U.S. clinical development and/or U.S. regulatory affairs expertise. Subject to Section 4.7, each Party shall appoint one (1) of its representatives as co-chairperson of the JDC. The JDC may change its size
from time to time by mutual consent of its members, provided that the JDC shall include at all times an equal number of representatives of each Party. Each Party may replace its JDC representatives at any time upon written notice to the other Party.
Any member of the JDC may designate a substitute to attend and perform the functions of that member at any meeting of the JDC. Each Party may invite non-members to participate in the discussions and meetings of the JDC, provided that such
participants shall have no voting authority at the JDC. 
 (b) Responsibilities. The JDC shall be an ongoing, operational
committee (and not merely an advisory body) responsible for the implementation of all phases of the Development Plan. The responsibilities of the JDC during Development shall be to: 

(i) review, coordinate, and discuss the overall strategy for Development, including regulatory strategies for obtaining
Regulatory Approval for each Licensed Product in the Field in the Territory; 
 (ii) prepare, review and approve each
Development Plan for Licensed Product for the Initial Indication (including in the Initial Formulation and any New Formulation), including budgets of Development Costs contained therein, and any amendments to each such Development Plan or budgets
contained therein; 
 (iii) oversee and manage the implementation of each Development Plan; 

(iv) facilitate the exchange of Know-How between the Parties with respect to the Development activities and establish procedures
for the efficient sharing of Know-How necessary or useful for Development hereunder, including sharing and discussing the clinical information and data generated by or on behalf of the Parties in the course of performing Development hereunder;

 (v) select CROs and designate Development activities to be conducted by such CROs, if any; 

  
 15 

 (vi) oversee (including through Operational Team discussions) preclinical and CMC
development activities performed by Otsuka with respect to the Licensed Product; 
 (vii) approve members of the
Development team, which must include at least one individual who has sufficient expertise and experience in ophthalmology drug development in the Initial Indication; 
 (viii) prepare, review and approve the Development Plan and any amendments thereto for any Other Indication Product, including budgets of Development Costs contained therein, and establish the
Aggregate Development Cap for such Other Indication Product; 
 (ix) review and approve the design of any Phase 4
Clinical Trials and consider and approve the use(s) and dissemination in the Territory of the data resulting from such Phase 4 Clinical Trials (notwithstanding that the costs of any such Phase 4 Clinical Trials will be Commercialization Costs);

 (x) review any information provided by a Party with respect to a Cost Overrun or Post-Opt-In Cost Overrun and approve
any appropriate steps to address such Cost Overrun or Post-Opt-In Cost Overrun; 
 (xi) consider and determine whether
the Licensed Compound or Licensed Product has failed in Development for purposes of Section 3.4(b); 
 (xii) only
if and after Acucela exercises an Opt-In Right, serve as a venue for discussing impacts, if any, of development of the Licensed Product outside the Territory or outside the Field on Development of Licensed Product in the Field in the Territory;

 (xiii) until formation of the JCC (at which time, the responsibilities described in this Section 2.1(b)(xiii)
shall be automatically transferred to the JCC), (a) determine whether it is necessary or advisable to license or otherwise acquire rights under a Third Party’s Patent Rights or Know-How in the Territory (the “Third Party
IP”) in order to use, import, offer for sale or sell Licensed Product in the Field in the Territory or in order to Manufacture Licensed Product for use, import or sale in the Field in the Territory, giving due consideration to each
Party’s information, analyses, opinions and recommendations related thereto, and (b) if such license or acquisition is determined by the JDC to be so necessary or advisable discuss and recommend appropriate financial terms and conditions
(including the scope of the license to be negotiated) for each such license or acquisition agreement; 
 (xiv) establish
Operational Teams, as set forth in Section 2.1(f) below to oversee the Parties’ activities pursuant to this Agreement, including an Operational Team to discuss the strategy and plans for filing, prosecution and maintenance of the Developed
Patent Rights; 
 (xv) review and consult with the JCC regarding the design of any Phase 3b Clinical Trials or
Post-Approval Studies and the use(s) and dissemination in the Territory of the data resulting from such Phase 3b Clinical Trials or Post-Approval Studies; 

  
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 (xvi) following submission of a proposal to Develop Licensed Product for an Other
Indication pursuant to Section 3.2 or following submission of a proposal to Develop a New Formulation pursuant to Section 3.3, discuss whether and when (if at all) to Develop an Other Indication Product or a New Formulation, as the case
may be; 
 (xvii) discuss the Parties’ scientific presentation and publication strategy relating to Licensed
Compound and Licensed Products in the Field in the Territory; and 
 (xviii) perform such other duties or functions as
are specifically assigned to the JDC by the Parties pursuant to this Agreement or in a writing executed by both Parties. 

(c) Meetings. The JDC shall hold meetings as often as the members may determine, but in any event JDC meetings shall occur not
less than once per Calendar Quarter. Each co-chairperson of the JDC shall, on a rotating basis, provide the other JDC members at least ten (10) days prior written notice of each JDC meeting. Notwithstanding the foregoing, notice of any JDC
meeting may be waived in writing at any time, either before, during or after such JDC meeting, and attendance of any member at such JDC meeting shall constitute a valid waiver of notice of any such JDC meeting, unless such member attends the JDC
meeting for the express purpose of objecting to the failure to provide valid notice. JDC meetings may be held in person or by any means of telecommunications or video conference as the members deem necessary or appropriate; provided that at
least one (1) JDC meeting per year shall be held in person and the location of such in-person JDC meeting shall alternate between a location chosen by Otsuka and a location chosen by Acucela. A quorum for JDC meetings shall be four
(4) members with at least two (2) members from each Party. Each Party shall bear its own costs to attend and participate in the JDC meetings. 
 (d) Agenda, Minutes. The co-chairpersons of the JDC shall have no independent voting power, but shall, on a rotating basis, lead each meeting of the JDC, prepare the agenda for each meeting (based
on the comments and suggestions of each Party, with each such agenda to contain all agenda items requested by a Party to be included) and prepare the minutes of each meeting for review and approval by the JDC at the next meeting. The draft minutes
shall be sent to all members of the JDC for comment promptly after each such meeting (but in no event more than thirty (30) days after each such meeting). All actions noted in the minutes shall be reviewed and approved at the next meeting of
the JDC; provided that if the Parties cannot agree as to the content of the minutes by the time the JDC next meets, such minutes shall be finalized to reflect any areas of disagreement. 

(e) Decision Making. The JDC may make decisions with respect to any subject matter that is within the purview of the JDC’s
responsibilities under Section 2.1(b). All decisions of the JDC shall be made by unanimous vote, with each Party’s members collectively having one (1) vote, which vote shall be cast by each Party’s co-chairperson of the JDC (or
his or her designee), subject to the applicable quorum requirements. The JDC shall use reasonable efforts to resolve any disputes or disagreements concerning the matters within its responsibilities. 

(i) Escalation to Senior Management. In the event the JDC cannot reach an agreement regarding a decision within the JDC’s
responsibilities within fifteen (15) days after it has met and attempted to reach such consensus, then either Party may, by written 

  
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notice to the other Party (an “Escalation Notice”), have such matter referred for resolution to a designated senior management representative who shall have authority to bind
each Party (collectively, the “Senior Executives”). The Senior Executives shall use good faith efforts to resolve any matter referred to them as soon as practicable. 

(ii) Deciding Vote. If the Senior Executives are unable to resolve any matter set forth in an Escalation Notice within thirty
(30) days after the applicable Party receives such Escalation Notice, then Otsuka shall have final decision-making authority with respect to all matters within the responsibilities of the JDC; provided that, Otsuka shall not have the
right to use such final decision-making authority to require Acucela (if and after Acucela exercises an Opt-In Right) to fund any Development Costs in excess of the applicable Aggregate Development Cost Cap. Disputes regarding matters not
within the responsibilities of the JDC (or the JCC) shall be resolved pursuant to Section 14.2(b). 
 (f) Operational
Teams. From time to time the JDC may establish and delegate duties to subcommittees or directed teams (each, an “Operational Team”), the composition of which shall be determined by the JDC. The Operational Teams may be
established on an ad hoc or “as-needed” basis; provided that, within thirty (30) days after the Effective Date, an Operational Team to discuss and provide operational input on preclinical and CMC development activities with
respect to the Licensed Product shall be established by the Parties and shall be composed of such number of members from each Party as are agreed upon by the Parties. Each Operational Team shall operate pursuant to procedures to be defined by the
JDC. Each Operational Team and its activities shall be subject to the oversight, review and approval of, and shall report to, the JDC. In no event shall the authority of any Operational Team exceed that specified for the JDC under this
Section 2.1. Any disagreement between the representatives of the Parties on an Operational Team shall be referred to the JDC for resolution in accordance with Section 2.1(e). 

(g) Scope of Governance. The JDC shall perform its responsibilities under this Agreement based on the principles of diligence,
prudence and good scientific and business judgment. Notwithstanding the creation of the JDC, each Party shall retain the rights, powers and discretion granted to it under this Agreement. The JDC shall have only the powers assigned expressly to it
under this Article 2 and elsewhere in this Agreement and shall not be delegated or vested with any rights, powers or discretion unless such delegation or vesting is expressly agreed upon by the Parties in writing. The JDC shall not have any power to
amend, modify or waive compliance under this Agreement, and no decision of the JDC shall be enforceable to the extent it is in contravention of any terms and conditions of this Agreement. Unless otherwise agreed by the Parties, the JDC shall have no
authority and no responsibility for any development of the Licensed Compound or Licensed Products outside the Territory or outside the Field. 
 2.2 Joint Commercialization Committee. 
 (a) Formation and
Composition. Within thirty (30) days after (i) if Acucela exercises the * Opt-In Right, positive top-line data have been obtained as a result of the latest Phase 3 Clinical Trial (other than any Phase 3 Clinical Trial by Adjunctive
Use), or (ii) if Acucela does not exercise the * Opt-In Right, Acucela’s exercise of the P3 Opt-In Right, the Parties shall establish a “Joint Commercialization Committee,” or “JCC.” For the avoidance

  

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of doubt, if Acucela does not exercise either the * Opt-In Right or the P3 Opt-In Right, the Parties shall not establish a Joint Commercialization Committee. If established, the JCC initially
shall be comprised of six (6) members, three (3) of whom shall be representatives appointed by Otsuka and three (3) of whom shall be representatives appointed by Acucela. At least one (1) representative appointed by each Party to
the JCC shall have sufficient seniority and authority to make decisions on behalf of such Party and at least two (2) representatives appointed by each Party to the JCC shall have relevant U.S. commercialization expertise. Each Party shall
appoint one (1) of its representatives as co-chairperson of the JCC. The JCC may change its size from time to time by mutual consent of its members, provided that the JCC shall include at all times an equal number of representatives of each
Party. Each Party may replace its JCC representatives at any time upon written notice to the other Party. Any member of the JCC may designate a substitute to attend and perform the functions of that member at any meeting of the JCC. Each Party may
invite non-members to participate in the discussions and meetings of the JCC, provided that such participants shall have no voting authority at the JCC. 
 (b) Responsibilities. The JCC shall be an ongoing, operational committee (and not merely an advisory body) responsible for the implementation of all phases of the Commercialization Plan. The
responsibilities of the JCC shall be to: 
 (i) prepare, review and approve each Commercialization Plan, including
budgets of Commercialization Costs contained therein, and any amendments to each Commercialization Plan or budgets contained therein; 
 (ii) oversee and manage the implementation of the Commercialization Plan, including Manufacturing Activities and Distribution Activities; 

(iii) coordinate regarding the creation, training, deployment and management of the Parties’ sales forces for any Licensed
Product, including regarding sales force responsibilities and adjustments in sizing, as appropriate; 
 (iv) determine
which Party will be the Responsible Party with respect to specific Commercialization activities under each Commercialization Plan, which determination will be reflected in the applicable Commercialization Plan; 

(v) communicate and coordinate regarding promotion, including Detailing, of Licensed Products; 

(vi) review, in consultation with the JDC, and approve the design of any Phase 3b Clinical Trials or Post-Approval Studies and
consider and approve the use(s) and dissemination in the Territory of the data resulting from such Phase 3b Clinical Trials or Post-Approval Studies; 
 (vii) serve as a venue for discussing impacts, if any, of commercialization of the Licensed Product outside the Territory or outside the Field on Commercialization of Licensed Product in the Field
in the Territory; 
 (viii) (a) determine whether it is necessary or advisable to license or otherwise acquire rights
under Third Party IP in order to use, import or sell Licensed Product in 

  

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the Field in the Territory or in order to Manufacture Licensed Product for use, import or sale in the Field in the Territory, giving due consideration to each Party’s information, analyses,
opinions and recommendations related thereto, and (b) if such license or acquisition is determined by the JCC to be so necessary or advisable (or was so determined by the JDC prior to formation of the JCC), discuss and recommend appropriate
financial terms and conditions (including the scope of the license to be negotiated) for each such license or acquisition agreement; 
 (ix) determine the quantities, and establish the cost, of promotional samples of Licensed Product to be provided to the Parties for use in their performance of Co-Promotion; 

(x) discuss the Parties’ publication strategy relating to commercialized Licensed Products within the Field in the
Territory; 
 (xi) review any information provided by a Party with respect to a Post-Opt-In Cost Overrun and approve any
appropriate steps to address such Post-Opt-In Cost Overrun; 
 (xii) communicate and coordinate regarding integration of
Licensed Products into the managed care system; and 
 (xiii) perform such other duties or functions as are specifically
assigned to the JCC by the Parties pursuant to this Agreement or in a writing executed by both Parties. 
 (c) Meetings.
The JCC shall hold meetings as often as the members may determine, but in any event JCC meetings shall occur not less than once per Calendar Quarter. Each co-chairperson of the JCC shall, on a rotating basis, provide the other JCC members at least
ten (10) days prior written notice of each JCC meeting. Notwithstanding the foregoing, notice of any JDC meeting may be waived in writing at any time, either before, during or after such JCC meeting, and attendance of any member at such JCC
meeting shall constitute a valid waiver of notice of any such JCC meeting, unless such member attends the JCC meeting for the express purpose of objecting to the failure to provide valid notice. JCC meetings may be held in person or by any means of
telecommunications or video conference as the members deem necessary or appropriate; provided that at least one (1) JCC meeting per year shall be held in person and the location of such in-person JCC meeting shall alternate between a location
chosen by Otsuka and a location chosen by Acucela. A quorum for JCC meetings shall be four (4) members with at least two (2) members from each Party. Each Party shall bear its own costs to attend and participate in the JCC meetings.

 (d) Agenda, Minutes. The co-chairpersons of the JCC shall have no independent voting power, but shall, on a rotating
basis, lead each meeting of the JCC, prepare the agenda for each meeting (based on the comments and suggestions of each Party, with each such agenda to contain all agenda items requested by a Party to be included) and prepare the minutes of each
meeting for review and approval by the JCC at the next meeting. The draft minutes shall be sent to all members of the JCC for comment promptly after each such meeting (but in no event more than thirty (30) days after each such meeting). All
actions noted in the 

  
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minutes shall be reviewed and approved at the next meeting of the JCC; provided that if the Parties cannot agree as to the content of the minutes by the time the JCC next meets, such
minutes shall be finalized to reflect any areas of disagreement. 
 (e) Decision Making. The JCC may make decisions with
respect to any subject matter that is within the purview of the JCC’s responsibilities under Section 2.2(b). All decisions of the JCC shall be made by unanimous vote, with each Party’s members collectively having one (1) vote,
which vote shall be cast by each Party’s co-chairperson of the JCC (or his or her designee), subject to the applicable quorum requirements. The JCC shall use reasonable efforts to resolve any disputes or disagreements concerning the matters
within its responsibilities. 
 (i) Escalation to Senior Management. In the event the JCC cannot reach an agreement
regarding a decision within the JCC’s responsibilities within fifteen (15) days after it has met and attempted to reach such consensus, then either Party may, by written Escalation Notice to the other Party, have such matter referred for
resolution to the Senior Executives. The Senior Executives shall use good faith efforts to resolve any matter referred to them as soon as practicable. 
 (ii) Deciding Vote. If the Senior Executives are unable to resolve any matter set forth in an Escalation Notice within thirty (30) days after the applicable Party receives such Escalation
Notice, then Otsuka shall have final decision-making authority with respect to all matters within the responsibilities of the JCC; provided that, Otsuka shall not have the right to use such final decision-making authority to require
Acucela to fund any Initial Commercialization Costs in excess of the Aggregate Commercialization Cost Cap. Disputes regarding matters not within the responsibilities of the JCC (or the JDC) shall be resolved pursuant to Section 14.2(b).

 (f) Scope of Governance. The JCC shall perform its responsibilities under this Agreement based on the principles of
diligence, prudence and good scientific and business judgment. Notwithstanding the creation of the JCC, each Party shall retain the rights, powers and discretion granted to it under this Agreement. The JCC shall have only the powers assigned
expressly to it under this Article 2 and elsewhere in this Agreement and shall not be delegated or vested with any rights, powers or discretion unless such delegation or vesting is expressly agreed upon by the Parties in writing. The JCC shall not
have any power to amend, modify or waive compliance under this Agreement, and no decision of the JCC shall be enforceable to the extent it is in contravention of any terms and conditions of this Agreement. Unless otherwise agreed by the Parties, the
JCC shall have no authority and no responsibility for any commercialization of the Licensed Compound or Licensed Products outside the Territory. 
 ARTICLE 3 
 CERTAIN RIGHTS AND RESTRICTIONS 

3.1 Opt-In Right for Initial Indication in the Initial Formulation. In accordance with this Section 3.1, Acucela shall have
an opt-in right to co-Develop and Co-Promote with Otsuka (and its Affiliates) the Licensed Compound and Licensed Products for the Initial Indication in the Initial Formulation in the Territory pursuant to Development Plans, Commercialization Plans
and the terms of this Agreement. 

  
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 (a) * Opt-In Right. * (such * period referred to as the “* Opt-In
Exercise Period”), Acucela shall notify Otsuka in writing of its decision as to whether it will exercise its right to co-Develop and Co-Promote the Licensed Products for the Initial Indication in the Initial Formulation in the Territory
(the “* Opt-In Right”). 
 (i) If Acucela elects to exercise the * Opt-in Right, it shall designate in
its written exercise notice the applicable Participation Percentage (25% or 35%) selected by Acucela. 
 (ii) If, within
the * Opt-In Exercise Period, Acucela notifies Otsuka of its decision not to exercise the * Opt-In Right or fails to notify Otsuka of its decision whether or not it elects to exercise the * Opt-In Right, Acucela shall have the right to exercise the
P3 Opt-In Right pursuant to Section 3.1(b) and this Agreement will remain in effect in accordance with its terms, except that, if Acucela does not exercise the * Opt-In Right within the * Opt-In Exercise Period and if an initial public
offering of Acucela’s stock on a recognized stock exchange in the Territory or in Japan with net proceeds to Acucela of at least * (a “Qualified IPO”) occurs any time prior to or during the * Opt-In Exercise Period, Acucela
shall forfeit the P3 Opt-In Right and Otsuka shall have the right to terminate this Agreement by giving written notice of termination to Acucela, provided that Otsuka shall have * after expiration of the * Opt-In Exercise Period to exercise
such termination right. 
 (b) P3 Opt-In Right. If Acucela does not exercise the * Opt-In Right during the * Opt-In
Exercise Period, and provided that Acucela has not forfeited the P3 Opt-In Right pursuant to Section 3.1(a)(ii), then, within ninety (90) days after * (such 90-day period referred to as the “P3 Opt-In Exercise Period”),
Acucela shall notify Otsuka in writing of its decision as to whether it will exercise its right to co-Develop and Co-Promote Licensed Product for the Initial Indication in the Initial Formulation in the Territory (the “P3 Opt-In
Right”). If Acucela elects to exercise the P3 Opt-in Right, it shall designate in its written exercise notice the applicable Participation Percentage (25% or 35%) selected by Acucela. 

(c) Effect of Exercise of Opt-In Right. If Acucela exercises either the * Opt-In Right or the P3 Opt-In Right within the * Opt-In
Exercise Period or the P3 Opt-In Exercise Period, respectively: (i) the licenses to Acucela pursuant to Sections 6.2 and 6.3 shall become effective; (ii) Acucela shall thereafter (A) co-Develop the Licensed Products for the Initial
Indication in the Initial Formulation in the Territory in accordance with Section 4.4, (B) Co-Promote Licensed Product for the Initial Indication in the Initial Formulation in the Territory in accordance with Section 5.4 and pursuant
to the Co-Promotion Agreement, and (C) fund a percentage of all Development Costs and a percentage of all Commercialization Costs, in each case relating to the Licensed Product for the Initial Indication in the Initial Formulation for the
Territory, in accordance with and subject to the terms of Section 7.4; (iii) subject to the terms of Section 7.4(b) and Section 7.4(c), Acucela shall obtain, without assistance from Otsuka, all funding necessary to meet and
comply with its co-Development and Co-Promotion obligations; and (iv) all other terms and conditions of this Agreement shall remain in effect. 
 (d) Failure to Exercise Opt-In Right. If Acucela does not exercise the * Opt-In Right within the * Opt-In Exercise Period and, provided that Otsuka has not terminated this Agreement pursuant to
Section 3.1(a)(ii), if Acucela subsequently notifies Otsuka of its 

  

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decision not to exercise the P3 Opt-In Right or fails to notify Otsuka of its decision whether or not it elects to exercise the P3 Opt-In Right, in either case within the P3 Opt-In Exercise
Period, this Agreement shall automatically terminate at the expiration of the P3 Opt-In Exercise Period. 
 3.2 Other
Indications. At any time during the term of this Agreement, Otsuka or Acucela may submit to the JDC a proposal for Development of Licensed Product for an Other Indication in any formulation in the Territory. Such proposal will contain data and
information supporting the proposal, including from any preclinical or other activities previously conducted by Otsuka with respect to Licensed Product for such Other Indication. If a proposal for Development of Licensed Product for an Other
Indication is submitted by Otsuka, or if a proposal for Development of Licensed Product for an Other Indication is submitted by Acucela and agreed to by Otsuka in its discretion (in which case such Licensed Product shall be deemed an “Other
Indication Product”), the JDC shall then prepare and approve a Development Plan, including a budget of Development Costs, and shall establish the Aggregate Development Cost Cap for such Other Indication Product. For the avoidance of doubt,
Otsuka may in its discretion agree upon or reject any proposal made by Acucela to Develop Licensed Product for any Other Indication. 
 (a) Development Prior to Exercise of Opt-In Right. If Otsuka makes a proposal or agrees to a proposal made by Acucela for Development of an Other Indication Product prior to Acucela’s exercise
of an Opt-In Right under Section 3.1, Acucela shall conduct Development of such Other Indication Product on behalf of Otsuka, and Otsuka shall bear all Development Costs and compensate Acucela for Development of such Other Indication Product in
accordance with the terms of Section 4.3. 
 (b) Other Indication Opt-In Right. Acucela shall have an opt-in right
to co-Develop and Co-Promote with Otsuka (and its Affiliates) any Other Indication Product in the Territory pursuant to Development Plans, Commercialization Plans and the terms of this Agreement as follows: 

(i) If Otsuka makes a proposal or agrees to a proposal made by Acucela for Development of an Other Indication Product prior to
Acucela’s exercise of an Opt-In Right under Section 3.1, then, provided that Acucela exercises an Opt-In Right under Section 3.1, Acucela shall notify Otsuka in writing of its decision as to whether it will exercise its right to
co-Develop and Co-Promote such Other Indication Product in the Territory either (A) at the same time that Acucela exercises the * Opt-In Right or the P3 Opt-In Right (as applicable) or (B) within * after the JDC has approved the
Development Plan (including budget) and Aggregate Development Cost Cap for such Other Indication Product, whichever of (A) or (B) is later. For clarity, Acucela shall have no opt-in right under this Section 3.2(b), and shall have no
right to co-Develop or Co-Promote an Other Indication Product, if Acucela does not exercise its Opt-In Right with respect to the Initial Indication in the Initial Formulation under Section 3.1. 

(ii) If Otsuka makes a proposal or agrees to a proposal made by Acucela for Development of an Other Indication Product following
Acucela’s exercise of the Opt-In Right under Section 3.1, then Acucela shall notify Otsuka in writing of its decision as to whether or not it will exercise its right to co-Develop and Co-Promote such Other Indication Product in the
Territory (in addition to co-Developing and Co-Promoting Licensed Product for the Initial Indication), within * after the JDC has approved the Development Plan (including budget) and Aggregate Development Cost Cap for such Other Indication Product.

  

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 (c) Effect of Other Indication Opt-In. If Acucela exercises the opt-in right to
co-Develop and Co-Promote an Other Indication Product within the applicable time period set forth in Section 3.2(b) above: (i) the licenses to Acucela pursuant to Sections 6.2 and 6.3 shall become effective with respect to the applicable
Other Indication Product; (ii) Acucela shall thereafter (A) co-Develop such Other Indication Product in accordance with Section 4.4, (B) Co-Promote such Other Indication Product in the Territory in accordance with
Section 5.4 and pursuant to the Co-Promotion Agreement, and (C) fund a percentage of all Development Costs and a percentage of all Commercialization Costs, in each case relating to such Other Indication Product, in accordance with the
terms of Section 7.4; (iii) subject to the terms of Section 7.4(b), Acucela shall obtain, without assistance from Otsuka, all funding necessary to meet and comply with its co-Development and Co-Promotion obligations; (iv) Acucela
shall pay the Other Indication Product opt-in fee and the Other Indication Product milestone payment as set forth in Sections 7.1(b) and 7.2(c), respectively; and (v) all other terms and conditions of this Agreement shall remain in effect and
shall apply to such Other Indication Product. 
 (d) Failure to Exercise Other Indication Opt-In Right. If Acucela does
not exercise the opt-in right to co-Develop and Co-Promote an Other Indication Product within the applicable time period set forth in Section 3.2(b) above, Otsuka shall have the right to develop and commercialize such Other Indication Product
in the Territory; provided that Acucela shall conduct Development activities for such Other Indication Product with respect to such Other Indication in the Territory on behalf of Otsuka, and Otsuka shall bear all Development Costs and
compensate Acucela for Development of such Other Indication Product in accordance with the terms of Section 4.3. For clarity, if Acucela does not exercise the opt-in right to co-Develop and Co-Promote an Other Indication Product within the
applicable time period set forth in Section 3.2(b) above, Acucela shall have no right to Co-Promote such Other Indication Product in the Territory, no Sharing Payment shall be payable to Acucela with respect to Net Sales of such Other
Indication Product and all revenue from sales of such Other Indication Product in the Territory shall be excluded from the Net Sales on which the Sharing Payment is paid to Acucela pursuant to Section 7.5. For the avoidance of doubt, if any
product is both a Licensed Product and an Other Indication Product, only Net Sales with respect to Other Indications for which Acucela did not exercise its Opt-In Right shall be so excluded in the determination of the applicable Sharing Payment.

 3.3 New Formulations. At any time during the term of this Agreement, Otsuka or Acucela may submit to the JDC a
proposal for Development of a New Formulation in the Territory. Such proposal will contain data and information supporting the proposal, including from any preclinical or other activities previously conducted by Otsuka with respect to such New
Formulation. If a proposal for Development of a New Formulation is submitted by Otsuka, or if a proposal for Development of a New Formulation is submitted by Acucela and agreed to by Otsuka in its discretion, the JDC shall then prepare and approve a
Development Plan, including a budget of Development Costs, for such New Formulation; provided, that the same Aggregate Development Cost Cap shall apply with respect to Development Costs for Licensed Product for the Initial Indication in the
Initial Formulation and in the applicable New Formulation. For the avoidance of doubt, Otsuka may in its discretion agree upon or reject any proposal made by Acucela to Develop any New Formulation. 

  
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 (a) Development Prior to Exercise of Opt-In Right. If Otsuka makes a proposal or
agrees to a proposal made by Acucela for Development of a New Formulation prior to Acucela’s exercise of an Opt-In Right under Section 3.1, Acucela shall conduct Development of such New Formulation on behalf of Otsuka, and Otsuka shall
bear all Development Costs and compensate Acucela for Development of such New Formulation in accordance with the terms of Section 4.3. 
 (b) New Formulation Opt-In Right. Acucela shall have an opt-in right to co-Develop and Co-Promote with Otsuka (and its Affiliates) any New Formulation in the Territory pursuant to Development
Plans, Commercialization Plans and the terms of this Agreement as follows: 
 (i) If Otsuka makes a proposal or agrees
to a proposal made by Acucela for Development of a New Formulation prior to Acucela’s exercise of an Opt-In Right under Section 3.1, then, provided that Acucela exercises an Opt-In Right under Section 3.1, Acucela shall notify Otsuka
in writing of its decision as to whether it will exercise its right to co-Develop and Co-Promote such New Formulation in the Territory either (A) * Acucela exercises the * Opt-In Right or the P3 Opt-In Right (as applicable) or (B) within *
days after the JDC has approved the Development Plan (including budget) for such New Formulation, whichever of (A) or (B) is later. For clarity, Acucela shall have no opt-in right under this Section 3.3(b), and shall have no right to
co-Develop or Co-Promote a New Formulation, if Acucela does not exercise its Opt-In Right with respect to the Initial Indication in the Initial Formulation under Section 3.1. 

(ii) If Otsuka makes a proposal or agrees to a proposal made by Acucela for Development of a New Formulation following
Acucela’s exercise of the Opt-In Right under Section 3.1, then Acucela shall notify Otsuka in writing of its decision as to whether it will exercise its right to co-Develop and Co-Promote such New Formulation in the Territory (in addition
to co-Developing and Co-Promoting Licensed Product for the Initial Indication in the Initial Formulation), within * after the JDC has approved the Development Plan (including budget) for such New Formulation. 

(c) Effect of New Formulation Opt-In. If Acucela exercises the opt-in right to co-Develop and Co-Promote a New Formulation within
the applicable time period set forth in Section 3.3(b) above: (i) the licenses to Acucela pursuant to Sections 6.2 and 6.3 shall become effective with respect to the applicable New Formulation; (ii) Acucela shall thereafter
(A) co-Develop such New Formulation in accordance with Section 4.4, (B) Co-Promote such New Formulation in the Territory in accordance with Section 5.4 and pursuant to the Co-Promotion Agreement, and (C) fund a percentage of
all Development Costs and a percentage of all Commercialization Costs, in each case relating to such New Formulation, in accordance with the terms of Section 7.4; (iii) subject to Section 7.4(b), Acucela shall obtain, without
assistance from Otsuka, all funding necessary to meet and comply with its co-Development and Co-Promotion obligations; (iv) Acucela shall pay the New Formulation opt-in fee as set forth in Section 7.1(c) (but, for clarity, Acucela shall
have no obligation to pay any development milestones with respect to such New Formulation); and (v) all other terms and conditions of this Agreement shall remain in effect and shall apply to such New Formulation. 

  

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 (d) Failure to Exercise New Formulation Opt-In Right. If Acucela does not exercise
the opt-in right to co-Develop and Co-Promote a New Formulation within the applicable time period set forth in Section 3.3(b) above, Otsuka shall have the right to develop and commercialize such New Formulation in the Territory; provided
that Acucela shall conduct Development activities for such New Formulation with respect to such New Formulation in the Territory on behalf of Otsuka, and Otsuka shall bear all Development Costs and compensate Acucela for Development of such New
Formulation in accordance with the terms of Section 4.3. For clarity, if Acucela does not exercise the opt-in right to co-Develop and Co-Promote a New Formulation within the applicable time period set forth in Section 3.3(b) above, Acucela
shall have no right to Co-Promote such New Formulation in the Territory, no Sharing Payment shall be payable to Acucela with respect to Net Sales of such New Formulation and all revenue from sales of such New Formulation in the Territory shall be
excluded from the Net Sales on which the Sharing Payment is paid to Acucela pursuant to Section 7.5. For the avoidance of doubt, if Licensed Product is being sold in the Territory in both the Initial Formulation and one or more New
Formulations, only Net Sales with respect to the New Formulation for which Acucela did not exercise its Opt-In Right shall be so excluded in determination of the applicable Sharing Payment. 

3.4 New Compound Product. 
 (a) Right of First Negotiation; Royalty. If, at any time during the ROFN Period, Otsuka conducts a Phase 3 clinical trial or any later stage development of any New Compound Product for treatment of
an indication in the Field in the Territory, Otsuka shall give written notice to Acucela (the “ROFN Notice”) and shall grant Acucela a right of first negotiation to obtain rights to co-develop and co-promote such New Compound
Product in the Field in the Territory (“New Compound Rights”) pursuant to a separate agreement between the Parties. Acucela shall have * after receipt of the ROFN Notice to determine and to notify Otsuka in writing whether Acucela
desires to negotiate such a separate agreement for such New Compound Rights. If Acucela fails to provide written notice to Otsuka within such * period, Acucela shall be deemed to have rejected Otsuka’s offer to negotiate for such New Compound
Rights. If, within such * period, Acucela rejects (or is deemed to have rejected) Otsuka’s offer to negotiate for such New Compound Rights, or if Acucela accepts Otsuka’s offer to negotiate for such New Compound Rights but the Parties,
after negotiating in good faith, fail to enter into a separate agreement for such New Compound Rights within * after Otsuka’s receipt of Acucela’s notification of its desire to enter into a separate agreement for such New Compound Rights,
then Otsuka shall have no further obligation to Acucela with respect to such New Compound Rights and Otsuka may develop and commercialize such New Compound Product on its own or through its Affiliate or may enter into an agreement to develop or
commercialize such New Compound Product with a Third Party; provided, however, that (i) if Otsuka proceeds on its own or through its Affiliate (not in collaboration with a Third Party) to commercialize such New Compound Product in the
Field in the Territory, then Otsuka shall pay Acucela on a Calendar Quarter basis during the remainder of the term of this Agreement * of the net sales of such New Compound Product sold in the Field in the Territory, or (ii) if Otsuka proceeds
with a Third Party to commercialize such New Compound Product in the Field in the Territory, then Otsuka will pay 

  

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Acucela on a Calendar Quarter basis during the remainder of the term of this Agreement * of the net sales of such New Compound Product sold in the Field in the Territory. For purposes of the
preceding proviso, net sales of a New Compound Product in the Field in the Territory shall be determined in the same manner as Net Sales of Licensed Product under this Agreement. 

(b) Backup Compound. If the Licensed Compound or Licensed Product fails in Development at any time after the Effective Date but
prior to Launch, and if, at the time of such failure, Otsuka is developing a New Compound that is in preclinical stage or later stage of development, then such New Compound will be deemed a backup and shall replace the failed Licensed Compound or
Licensed Product for all purposes of this Agreement. Thereafter, such New Compound shall be designated as the Licensed Compound and shall be Developed as the Licensed Product under, and subject to all of the terms of, this Agreement. The JDC shall
be responsible for considering and determining whether the Licensed Compound or Licensed Product has failed in Development for purposes of this Section 3.4(b). 
 3.5 Secondment. During the term of this Agreement, Otsuka shall have the right to send one (1) Otsuka employee to Acucela’s facilities for secondment. If the JDC approves Global Studies
that include Japan, then during the term of this Agreement, Acucela shall have the right to send one (1) Acucela employee to Otsuka’s facilities for secondment. Such seconded employees shall engage in Development, including active
participation, assistance and involvement with the Development work conducted by the Party that is hosting such seconded employee (the “Hosting Party”) and, if applicable, Commercialization activities performed under this Agreement.
Such seconded employees shall be subject to, and shall comply with, all policies and procedures of the Hosting Party that govern work and site safety and security and that are provided by the Hosting Party to such seconded employees in writing in
English and shall be under the direction of the Hosting Party; provided, however, that (a) Acucela’s seconded employee shall remain the employee of Acucela and Acucela shall be solely responsible for paying all salary or benefits
due such Acucela employee and all travel or living expenses incurred by such Acucela employee that is seconded to Otsuka’s facilities; (b) Otsuka’s seconded employee shall remain the employee of Otsuka and Otsuka shall be solely
responsible for paying all salary or benefits due such Otsuka employee and all travel or living expenses incurred by such Otsuka employee that is seconded to Acucela’s facilities; and (c) under no circumstances shall any seconded employee
be entitled to any salary or other benefits from the Hosting Party. For the avoidance of doubt, to the extent that an employee of Acucela who is seconded at Otsuka’s facilities as described herein is directly assigned to perform and is directly
performing Development, such employee’s activities with respect to Development of the Licensed Product (and/or Other Indication Product) during such secondment shall be taken into account, and included within, the number of FTEs that are
provided by Acucela under this Agreement for purposes of determining Development Costs to be paid by Otsuka or shared by the Parties, as appropriate. 
 3.6 Exclusivity. During the term of this Agreement, except in connection with Acucela’s performance of Development and Commercialization as expressly permitted under this Agreement, neither
Acucela nor any of its Affiliates shall undertake itself, collaborate with any Third Party, grant a license to a Third Party, or obtain any license or right to conduct any phase 3 clinical trials or later stage development of, or manufacture, sell,
promote, market, distribute or otherwise commercialize, any adenosine A2a receptor agonist in the Field in the 

  

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Territory. Notwithstanding the foregoing, in the case of a Change of Control, beginning on the date that is * after the effective date of the Change of Control, the restrictions set forth in this
Section 3.6 shall not apply to any product owned or controlled by the Acquirer or its Affiliates prior to the effective date of the Change of Control (a “Preexisting Product”), provided that, after the effective date of
the Change of Control, (a) such Acquirer and its Affiliates shall not use the Confidential Information of Otsuka (or its Affiliates) or Acucela pertaining to Licensed Compound or Licensed Products or their Manufacture, Distribution or use in
making, using, offering for sale, selling, importing or exporting such Preexisting Product, and (b) no person who had been an officer, director, employee, consultant, agent or representative of Acucela within * prior to the effective date of
the Change of Control shall be permitted to assist such Acquirer in making, using, offering for sale, selling, importing or exporting the Preexisting Product. 
 3.7 Activities Outside Field and Territory. Otsuka and its Affiliates shall have the exclusive right and authority, in their discretion, to exploit Licensed Compound and Licensed Products outside
the Field and outside the Territory. If and after Acucela exercises an Opt-In Right under Section 3.1, Otsuka agrees to reasonably communicate and consult with Acucela (through the JDC, with respect to development activities, and through the
JCC, with respect to commercialization activities) on material development and commercialization activities, including material clinical and regulatory matters, relating to Licensed Compound or Licensed Products outside the Field or outside the
Territory to the extent such matters or activities would be reasonably expected to adversely affect, or have a material impact on, the Development or Commercialization of Licensed Products in the Field in the Territory. Notwithstanding the foregoing
or any other provision in this Agreement, neither Acucela nor the JDC nor the JCC shall have the right or authority to manage or control or to approve, modify, impede or delay Otsuka’s or its Affiliates’ commercialization or development
plans or activities for Licensed Compound or Licensed Products outside the Field or outside the Territory. 
 ARTICLE 4

 DEVELOPMENT 
 4.1 Development Plans. As soon as practicable after formation of the JDC, the JDC shall prepare and approve the initial Development Plan for Development of the Licensed Product for the Initial
Indication in the formulation existing as of the Effective Date in the Territory. The Parties shall use Commercially Reasonable Efforts to ensure that such initial Development Plan is consistent with the general Development Plan outline set forth in
Exhibit B attached hereto and incorporated herein (the “General Development Plan Outline”). The JDC shall prepare and approve a separate Development Plan for Development of Licensed Product for the Initial Indication in the
Initial Formulation in the Territory and for Development of each Other Indication Product and New Formulation (if any) in the Territory, and shall update and amend each Development Plan not less than annually or more frequently as needed to take
into account changed circumstances or completion, commencement or cessation of Development activities not contemplated by the then-current Development Plan. Amendments and revisions to the Development Plan shall be reviewed and discussed, in
advance, by the JDC, and Otsuka agrees to consider proposals and suggestions made by Acucela regarding amendments and revisions to the Development Plan. Any amendment or revision to the Development Plan that provides for an increase or decrease in
the number of FTEs as compared to the previous version of the Development Plan, or that provides for addition or discontinuation of tasks or activities as 

  

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compared to the previous version of the Development Plan, or that moves forward the timetable for activities reflected in the Development Plan, shall provide for a reasonable ramp-up or wind-down
period, as applicable, to accommodate a smooth and orderly transition of Development activities to the amended or revised Development Plan. Each Development Plan shall identify the goals of the Development program contemplated thereunder and shall
address Development activities related to the Licensed Compound or the Licensed Product (including, if applicable, any Other Indication Product or New Formulation), including: 

(i) the budget for Development Costs (and costs of Phase 4 Clinical Trials, if any) for the forthcoming calendar year (or portion
thereof), including a reasonably detailed allocation of such costs and expenses among the activities expected to be conducted, including the number of FTEs (subject to Section 4.2) and the applicable FTE Rate and out-of-pocket expenses to be
incurred in such calendar year (or portion thereof), and a reasonable good faith projection of the budget for Development Costs (and costs of Phase 4 Clinical Trials, if any) for Development activities in the Development Plan after such calendar
year, in each case which budget shall be an amount reasonably intended to be sufficient to cover the anticipated costs associated with the activities reflected in the Development Plan; 

(ii) clinical trials (including Phase 4 Clinical Trials but excluding Phase 3b Clinical Trials or Post-Approval Studies) to
generate data for use in seeking, obtaining or maintaining Regulatory Approval and for labeling of the Licensed Product for the Initial Indication in the Initial Formulation or, if applicable, Other Indication Product or New Formulation, including
study protocol design; 
 (iii) resources required to perform each required Development activity, including the scope of
the work to be performed by internal resources of each of the Parties or by CROs or other permitted subcontractors, if applicable; 
 (iv) milestones to be met, deliverables to be provided and the timeline for completion of each Development activity; 
 (v) the members of the Development team, which must include at least one individual who has sufficient expertise and experience in ophthalmology drug development in the Initial Indication;

 (vi) design and implementation of regulatory strategy; and 

(vii) forecasts of quantities of Licensed Product to be supplied by Otsuka for use in clinical trials in the Territory.

 4.2 Indirect FTEs. The Development Costs budget to be included in the Development Plan for Development of the Licensed
Product for the Initial Indication shall include a maximum of * FTEs of Acucela who indirectly support performance of Development (“Indirect FTEs”), which maximum number is an aggregate number applicable to both Indirect FTEs and *.
Such aggregate maximum number applicable to Indirect FTEs may not be increased except upon the written agreement of Otsuka and Acucela. For the avoidance of doubt, FTEs are not limited to individuals assigned to Development activities under this
Agreement on a full-time basis, and include a pro-rata portion of the time of individuals who perform applicable Development activities under this Agreement on a less than full-time basis. 

  

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 4.3 Development Activities Prior to Exercise of Opt-In Right. Unless and until
Acucela exercises an Opt-In Right under Section 3.1, Otsuka shall have sole responsibility for Development and Development Costs, provided that until (a) Acucela exercises an Opt-In Right under Section 3.1, or (b) this
Agreement is terminated pursuant to Article 13, whichever is earlier, Otsuka hereby agrees to engage Acucela to conduct Development on behalf of Otsuka and to compensate Acucela for such Development work in accordance with this Section 4.3.
Acucela hereby accepts such engagement and shall perform all Development (i) in accordance with each Development Plan (including the applicable budget contained therein, except as otherwise provided in Section 4.3(d)) and this Agreement,
(ii) in compliance with all Applicable Laws and in accordance with GLP and GCP, as applicable, and (iii) in a professional manner, meeting the standards of diligence, care, timeliness, trust, dependability, safety, efficiency, economy and
skill customary in the field. 
 (a) Diligence. Without limiting the foregoing, Acucela shall use Commercially Reasonable
Efforts to achieve milestones, provide deliverables and meet timelines and schedules for Development, and to conduct and complete all Development within the budget, in each case as set forth in each Development Plan. Acucela shall allocate
sufficient time, effort, equipment and facilities and shall use personnel with sufficient skills and experience, in each case as are anticipated to be needed to accomplish the Development work in accordance with each Development Plan and the terms
and conditions of this Agreement. 
 (b) Information Regarding Development Activities. Acucela shall maintain, or cause
to be maintained, records of Development work in sufficient detail and in good scientific manner as appropriate for patent, regulatory and/or scientific purposes and to enable Otsuka to verify Acucela’s compliance with all of its obligations
under each Development Plan and this Agreement, which records shall fully and properly reflect all work done and results achieved by or on behalf of Acucela in the performance of Development work under the Development Plans. Acucela shall retain
such records for at least five (5) years after the term of this Agreement, or for such longer period as may be required by Applicable Laws. Acucela shall keep Otsuka appropriately informed, through the JDC or otherwise, of the status and
results of the Development work, including by providing on a monthly basis (or more frequently as reasonably requested by Otsuka) a written technical progress report describing, in sufficient detail to enable Otsuka to review and assess, on a fully
informed basis, Acucela’s progress in performing the Development Plan, the following: (i) Development activities conducted by or on behalf of Acucela, including any such activities performed by a permitted subcontractor; (ii) the
progress achieved in implementing and executing each Development Plan, including providing deliverables and achieving milestones (if any) set forth in each Development Plan; (iii) Know-How developed or created in the course of performing
Development; (iv) any difficulties and unexpected circumstances encountered, as well as variations, if any, from the schedule set forth in the Development Plan; and (v) any other relevant matters. Upon reasonable request by Otsuka, without
limiting the foregoing, Acucela shall provide Otsuka with summaries of data and results and other Know-How resulting from Development work and, if requested by Otsuka, shall provide access to all data and results and other Know-How in the possession
or under the control of Acucela or any permitted subcontractor that are generated or obtained in the course of 

  
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performance of Development work. Upon reasonable prior written notice, Otsuka shall have the right to inspect and copy any such records and notebooks reflecting the work done and results achieved
under a Development Plan by Acucela or any permitted subcontractor. 
 (c) Payment of Development Costs. Within sixty
(60) days after the end of each month during which any Development activities are performed by or on behalf of Acucela pursuant to this Section 4.3, Acucela shall provide to Otsuka a written report (each, a “Development Cost
Report”) setting forth in detail the Development Costs (together with the evidence supporting such Development Costs) actually incurred by Acucela during such month in accordance with the budget contained in the applicable Development Plan.
Each Development Cost Report will be in such form as the JDC may reasonably agree from time to time. The Development Cost Report shall accompany an appropriate invoice to Otsuka for the amount of such Development Costs owed to Acucela by Otsuka.
Within thirty (30) days of receiving such appropriate invoice, Otsuka shall reimburse Acucela the amount of Development Costs owed to Acucela; provided, however, that Otsuka shall not be responsible for Development Costs in excess of the
amount set forth in the budget in the Development Plan except as otherwise provided in Section 4.3(d). 
 (d) Cost
Overrun by Acucela. If, in the course of performing Development under this Section 4.3, Acucela determines that it is likely to overspend or has overspent the budgeted costs and expenses set forth in a Development Plan for a calendar year
(such overspend, a “Cost Overrun”), Acucela shall promptly notify the JDC of the anticipated amount and cause(s) of such Cost Overrun and the JDC shall promptly hold an ad-hoc meeting and shall discuss reasonably and in good faith
what steps to take to address the Cost Overrun, which may include amending the applicable Development Plan to modify the Development activities to reduce costs or to increase the budget contained therein so that there is no longer a Cost Overrun.
Any JDC-approved modifications to Development activities or the applicable budget in a Development Plan to address a Cost Overrun shall be included as an amendment to such Development Plan (or the budget contained therein). Any Cost Overrun that
does not exceed * of the budgeted Development Costs set forth in the applicable Development Plan (as the same may be amended) shall be a “Permitted Overrun.” If and to the extent Acucela experiences a Permitted Overrun with respect
to Development work conducted under this Section 4.3, the following shall apply: (A) Otsuka shall bear the amount of the Permitted Overrun, and (B) to the extent that any Cost Overrun is incurred that is not a Permitted Overrun (i.e.,
a Cost Overrun that exceeds * of the budgeted Development Costs set forth in the applicable Development Plan), Otsuka shall bear the full amount of such Cost Overrun unless (x) Acucela did not inform the JDC of such Cost Overrun before
incurring the costs causing the Cost Overrun or (y) Acucela informed the JDC and the JDC instructed Acucela to discontinue such activities in order to avoid such Cost Overrun, and in either of case (x) or (y), Acucela shall bear the full
amount of such Cost Overrun. For the avoidance of doubt, the provisions of Section 7.4(e), and not this Section 4.3(d), apply with respect to cost overruns (if any) incurred after Acucela’s exercise of its Opt-In Right. 

(e) The terms of Sections 7.7 and 7.8 shall apply with respect to recordkeeping, auditing and other payment terms relating to
Development Costs incurred and paid pursuant to this Section 4.3. In addition, the terms of Sections 2.1, 4.1, 4.2, 4.5, 4.6 and 4.7 shall apply at all times during Development, including prior to and, if applicable, after Acucela’s
exercise of an Opt-In Right under Section 3.1. 

  

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 4.4 Co-Development After Exercise of Opt-In Right. If Acucela exercises an Opt-In
Right under Section 3.1, the Parties shall jointly Develop the Licensed Compound and Licensed Products for the Initial Indication in the Initial Formulation in the Territory in accordance with the Development Plan. In addition, if Acucela
exercises the opt-in right to co-Develop and Co-Promote an Other Indication Product in accordance with Section 3.2(b) or a New Formulation in accordance with Section 3.3, the Parties shall jointly Develop such Other Indication Product or
New Formulation (as applicable) in the Territory in accordance with the applicable Development Plan. The provisions of Sections 4.4(a), (b) and (c) below shall apply only if and after Acucela exercises its Opt-In Right, and shall not
apply if Acucela does not exercise its Opt-In Right. 
 (a) Diligence. Each Party shall perform all Development
activities for which it is the Responsible Party under each Development Plan (i) in accordance with each Development Plan (including the applicable budget contained therein, except as otherwise provided in Section 7.4(e)) and this
Agreement, (ii) in compliance with all Applicable Laws and in accordance with GLP and GCP, as applicable, and (iii) in a professional manner, meeting the standards of diligence, care, timeliness, trust, dependability, safety, efficiency,
economy and skill customary in the field. Without limiting the foregoing, each Party shall use Commercially Reasonable Efforts to achieve milestones, provide deliverables and meet timelines and schedules for Development, and to conduct and complete
all Development within the budget, in each case with respect to Development work for which it is the Responsible Party under each Development Plan as set forth in each Development Plan. Each Party shall allocate sufficient time, effort, equipment
and facilities and shall use personnel with sufficient skills and experience, in each case as are anticipated to be needed to accomplish the Development work for which it is the Responsible Party under each Development Plan in accordance with each
Development Plan and the terms and conditions of this Agreement. 
 (b) Information Regarding Development Activities.
Each Party shall maintain, or cause to be maintained, records of Development work for which it is the Responsible Party under each Development Plan, in sufficient detail and in good scientific manner as appropriate for patent, regulatory and/or
scientific purposes, which records shall fully and properly reflect all work done and results achieved by or on behalf of such Party in the performance of Development work for which it is the Responsible Party under each Development Plan. Each Party
shall retain such records for at least * after the term of this Agreement, or for such longer period as may be required by Applicable Laws. Each Party shall keep the other Party appropriately informed, through the JDC or otherwise, of the status and
results of the Development work for which it is the Responsible Party under each Development Plan, including by providing on a monthly basis (or more frequently as reasonably requested by the other Party) a written technical progress report
describing, in sufficient detail to enable the other Party to review and assess, on a fully informed basis, the Responsible Party’s progress in performing the Development Plan activities for which it is responsible, the following:
(i) Development activities conducted by or on behalf of the Responsible Party, including any such activities performed by a permitted subcontractor; (ii) the progress achieved in implementing and executing each Development Plan, including
providing deliverables and achieving milestones (if 

  

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any) set forth in each Development Plan; (iii) Know-How developed or created in the course of performing Development; (iv) any difficulties and unexpected circumstances encountered, as
well as variations, if any, from the schedule set forth in the Development Plan; and (v) any other relevant matters. Upon reasonable request by the other Party, without limiting the foregoing, the Responsible Party shall provide the other Party
with summaries of data and results and other Know-How resulting from Development work for which it is the Responsible Party under a Development Plan and, if requested by the other Party, shall provide access to all data and results and other
Know-How in the possession or under the control of the Responsible Party that are generated or obtained by such Responsible Party or its permitted subcontractors in the course of performance of Development work. Upon reasonable prior written notice,
the other Party shall have the right to inspect and copy any such records and notebooks in the possession or under the control of the Responsible Party reflecting the work done and results achieved under a Development Plan by the Responsible Party
or any permitted subcontractor. 
 (c) Development Cost Sharing. Only if and after Acucela exercises its Opt-In Right,
the Parties shall share applicable Development Costs in accordance with the provisions of Section 7.4(a) and (b). 
 4.5
Subcontracting. Acucela shall not subcontract all or any part of the Development activities without, in each instance, obtaining the prior written approval of Otsuka; provided, however, that Development activities may be conducted by CROs
selected by the JDC as and to the extent approved by the JDC and Otsuka’s prior written approval of any other subcontractor may be evidenced in the minutes of any JDC meeting or in any Development Plan; and provided further that if
Otsuka, through the exercise of its final decision-making authority on the JDC, requires Acucela to conduct activities of a materially different nature than those that Acucela had previously agreed to perform, or that had been allocated to Acucela
pursuant to a previous Development Plan agreed to by Acucela, and if Acucela is not reasonably able to perform itself such materially different activities, then Otsuka shall not unreasonably withhold, condition or delay its approval of a
subcontractor to perform such materially different activities. Notwithstanding Otsuka’s or the JDC’s approval of a subcontractor, Acucela’s right to subcontract, including to an approved CRO, shall be subject to the following:
(a) none of Otsuka’s rights hereunder shall be diminished or otherwise adversely affected as a result of such subcontracting, (b) the subcontractor shall not have the right to further subcontract Development work unless agreed upon in
writing by Otsuka (or, in the case of approved CROs, the JDC), (c) Acucela shall be responsible and liable for the performance by any subcontractor of, or failure of any subcontractor to comply with, and Acucela guarantees the compliance by
each subcontractor with, all relevant restrictions, limitations and obligations in this Agreement, and (d) such permitted subcontracting shall not relieve Acucela of any liability or obligation under this Agreement, except to the extent
satisfactorily performed by such subcontractor. In addition, Acucela shall use Commercially Reasonable Efforts to negotiate each agreement with each such permitted subcontractor (“Development Subcontractor Agreement”) to provide
that: (i) such subcontractor shall assign to Otsuka, and all employees of such subcontractor shall be under written obligation to assign to Otsuka, in each case without any additional compensation, all inventions and intellectual property made
by such subcontractor and such subcontractor’s employees in the course of performing Development activities, (ii) such subcontractor shall be bound by obligations of confidentiality and non-use that are no less stringent than those
undertaken by the Parties pursuant to this Agreement, (iii) during the term of the Development 

  
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Subcontractor Agreement and thereafter (up to * after completion of Development) such subcontractor shall allow Otsuka or its designee to audit such subcontractor’s sites and clinical trial
sites used in Development and all data, results, records, notebooks and other information resulting from such clinical trials or other services conducted by such subcontractor (including the right to inspect and copy such records and notebooks) once
annually (or more often if any such annual audit reveals a failure by such subcontractor to comply with GLP, GCP or any other Applicable Laws or if Otsuka reasonably believes that such a failure to comply exists) in the location(s) where such data,
records and information are maintained by such subcontractor, upon reasonable notice and during such subcontractor’s regular business hours and under obligations of confidence, for the purposes of verifying such subcontractor’s compliance
with GLP, GCP and other Applicable Laws; and (iv) Otsuka is a third party beneficiary of the Development Subcontractor Agreement. Each Development Subcontractor Agreement shall be reviewed and approved by Otsuka prior to Acucela’s or the
subcontractor’s execution thereof, and Otsuka shall not be obligated to approve any Development Subcontractor Agreement that does not contain provisions consistent with clauses (i) through (iv) in the preceding sentence;
provided, however, that if Acucela has complied with its obligation to use Commercially Reasonable Efforts as set forth in the preceding sentence and Otsuka fails or declines to approve a Development Subcontractor Agreement, and Acucela is
not reasonably able to perform itself the applicable activities intended to be subcontracted pursuant to such Development Subcontractor Agreement, delays that may be attributable to the failure to approve such Development Subcontractor Agreement
shall not be construed as delays attributable to Acucela, and shall not give rise to any right of termination by Otsuka pursuant to Section 13.4(a). Acucela shall use Commercially Reasonable Efforts to monitor and enforce the terms of each
Development Subcontractor Agreement. 
 4.6 Audit Rights. Each Party shall have the right, during normal business hours,
and no more than once per year other than following a finding of material deficiency, with more frequent audits upon agreement of the Parties, to inspect and audit: (a) those portions of the facilities of the other Party, its Affiliates,
subcontractors and investigators sites used in the performance of the Development Plan, to ascertain compliance with Applicable Laws, including GLP and GCP, and the terms of the Development Plan and this Agreement, provided that the
inspecting Party shall on such occasions be accompanied by a representative of the other Party; and (b) any of the other Party’s documentation or its Affiliates’, subcontractors’ or investigators’ documentation relating to
Development, including, to the extent permitted by Applicable Laws and any applicable privacy policies, the medical records of any patient participating in any clinical study under a Development Plan. 

4.7 Key Member. Acucela shall ensure that Dr. Kubota shall be a key member of Acucela’s development team and shall
actively participate in and be primarily responsible for directing all Development work under each Development Plan. In addition, Acucela shall appoint Dr. Kubota as Acucela’s Co-Chair of the JDC. The Parties acknowledge that the
participation and contribution of Dr. Kubota at all times during Development until Otsuka receives Regulatory Approval for the Licensed Product for the Initial Indication (the “Key Milestone”) is essential to Otsuka and that
Dr. Kubota’s continued retention by and service to Acucela as the full-time Chief Executive Officer of Acucela and as on an ongoing, active member in the Acucela development team and as a Co-Chair of the JDC until the achievement of the
Key Milestone is a material inducement to Otsuka to grant rights and perform obligations 

  

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hereunder. Therefore, if (a) Dr. Kubota is removed or resigns or is otherwise no longer acting as the full-time Chief Executive Officer of Acucela, or (b) Dr. Kubota’s
employment with Acucela ends, for whatever reason, prior to the achievement of the Key Milestone, (c) Dr. Kubota ceases to act as a Co-Chair of the JDC, or (d) if, in Otsuka’s reasonable judgment, Dr. Kubota ceases to act as
an ongoing, active member of the Acucela development team primarily responsible for directing or performing Acucela’s Development work hereunder (each of the foregoing (a) through (d) a “Triggering Event”), then
Otsuka may terminate this Agreement immediately upon giving Acucela written notice of such termination, provided that Otsuka shall have ninety (90) days after the occurrence of the applicable Triggering Event to exercise such termination right.
The foregoing notwithstanding, in the case in which Otsuka, in its reasonable judgment, believes Dr. Kubota has ceased to act as an ongoing, active member of Acucela’s development team (the “Activity Cessation”), prior to
exercising its right to terminate under this Section 4.7 on account of such Activity Cessation, Otsuka shall notify Dr. Kubota in writing of its belief and shall permit Dr. Kubota a period of fifteen (15) days from receipt of
such notice from Otsuka the opportunity to resume acting as an ongoing, active member of Acucela’s development team primarily responsible for directing or performing Acucela’s Development work hereunder. If Dr. Kubota resumes acting
as such an ongoing, active member of Acucela’s development team within such fifteen (15) day period, Otsuka shall not be permitted to exercise its right to terminate under this Section 4.7 for such Activity Cessation. 

ARTICLE 5 

MANUFACTURE AND COMMERCIALIZATION 
 5.1 Manufacture and Supply. As between the Parties, Otsuka shall be responsible for, shall bear all costs associated with, and shall have all decision-making authority over, all Manufacturing
Activities (subject to discussion of CMC matters with Acucela through the JDC or applicable Operating Team as discussed below); provided, that Otsuka shall supply Licensed Product to Acucela or its permitted subcontractors for use in clinical
trials conducted in accordance with each Development Plan and, if applicable, Commercialization Plan (i.e., Phase 3b Clinical Trials or Post-Approval Studies, if any), free of charge and in such quantities as are agreed by the JDC or the JCC (as
applicable) or are otherwise required to seek or obtain Regulatory Approval. In addition, if and after Acucela exercises an Opt-In Right under Section 3.1, Otsuka shall supply promotional samples of Licensed Product to Acucela for use in its
performance of Co-Promotion, in such quantities and on such terms as are determined by the JCC. The cost of promotional samples of Licensed Product, which shall be included in Commercialization Costs, shall be established by the JCC based on
Otsuka’s per-unit cost to manufacture such promotional samples (but, for the avoidance of doubt, Otsuka shall have no obligation to disclose any information relating to its manufacturing costs), but in no event shall such promotional sample
cost exceed * per promotional sample unless mutually agreed otherwise by the Parties. Acucela’s and its permitted subcontractors’ obligations to conduct Development activities, and upon Acucela’s exercise of its Opt-in Right pursuant
to Section 3.1, to conduct Development and Commercialization activities, shall be expressly conditioned upon Otsuka fulfilling its Licensed Product supply obligations as set forth in the Development Plan or the Commercialization Plan, as
applicable. To the extent that Otsuka reasonably believes is necessary for performance of Development or Commercialization, Otsuka agrees to keep Acucela reasonably informed from time to time, through the JDC, JCC or applicable Operating Team,
regarding the general status of Manufacturing Activities related to the Licensed Product 

  

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(including Other Indication Product(s), as applicable) and from time to time shall update Acucela on any foreseeable delays and/or other material issues relating to Manufacturing the Licensed
Product (including Other Indication Product(s), as applicable). Through the JDC or applicable Operating Team, Otsuka and Acucela shall confer and discuss CMC matters, and Otsuka agrees to consider suggestions of Acucela regarding CMC matters.

 5.2 Sales and Distribution. As between the Parties, Otsuka shall be responsible for, shall bear all costs associated
with, and shall have all decision-making authority over, all Distribution Activities, including handling all returns, order processing, invoicing and collection, distribution, and inventory and receivables for the Licensed Product throughout the
Territory. Subject to the terms of the Net Sales definition, Otsuka shall have the right and sole responsibility for establishing and modifying the terms and conditions with respect to the sale of Licensed Product in the Territory, including any
terms and conditions relating to or affecting the price at which Licensed Products will be sold, discounts available to any Third Party payers (including, without limitation, managed care providers, indemnity plans, unions, self insured entities,
and government payer, insurance or contracting programs such as Medicare, Medicaid, or the U.S. Dept. of Veterans Affairs), any discount attributable to payments on receivables, distribution of the Licensed Product, and credits, price adjustments,
or other discounts and allowances to be granted or refused. All sales of Licensed Products in the Territory, whether arising from the activities of Otsuka’s (or its Affiliates’) sales forces or Acucela’s (or its Affiliates’)
sales forces (if and after Acucela exercises an Opt-In Right under Section 3.1), shall be booked in the name of Otsuka or its Affiliate(s) (as Otsuka may choose), and title to all units of Licensed Products shall remain in Otsuka or its
Affiliate until sold to customers. 
 5.3 Commercialization Plans. As soon as practicable after formation of the JCC
(following Acucela’s exercise of an Opt-In Right under Section 3.1), the JCC shall prepare and approve the initial Commercialization Plan for Commercialization of the Licensed Product for the Initial Indication in the Initial Formulation
(and, if applicable, any New Formulation or Other Indication Product) in the Territory. The Parties shall use Commercially Reasonable Efforts to ensure that such initial Commercialization Plan for Commercialization of the Licensed Product for the
Initial Indication in the Initial Formulation is consistent with the general Commercialization Plan outline set forth in Exhibit C attached hereto and incorporated herein (the “General Commercialization Plan Outline”). The
JCC shall prepare and approve a separate Commercialization Plan for Commercialization of Licensed Product for the Initial Indication in the Initial Formulation in the Territory and for Commercialization of each Other Indication Product and New
Formulation (if any) in the Territory, and shall update and amend each Commercialization Plan not less than annually or more frequently as needed to take into account changed circumstances or completion, commencement or cessation of
Commercialization activities not contemplated by the then-current Commercialization Plan. Amendments and revisions to the Commercialization Plan shall be reviewed and discussed, in advance, by the JCC, and Otsuka agrees to consider proposals and
suggestions made by Acucela regarding amendments and revisions to the Commercialization Plan. Any amendment or revision to the Commercialization Plan that provides for an increase or decrease in the number of FTEs for any Phase 3b Clinical Trials or
Post-Approval Studies as compared to the previous version of the Commercialization Plan, or that provides for addition or discontinuation of tasks or activities as compared to the previous version of the Commercialization Plan, or that moves forward
the timetable for activities reflected in the Commercialization Plan, shall provide for a 

  
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reasonable ramp-up or wind-down period, as applicable, to accommodate a smooth and orderly transition of Commercialization activities to the amended or revised Commercialization Plan. Each
Commercialization Plan shall identify the goals of Commercialization contemplated thereunder and shall address Commercialization (including Co-Promotion) activities related to the Licensed Product (including, if applicable, any Other Indication
Product), including: 
 (i) strategies for positioning and marketing of the Licensed Product in the Field in the
Territory; 
 (ii) designation of which Party will be the Responsible Party with respect to specific Commercialization
activities; 
 (iii) the personnel, Detailing and other resources to be devoted by each Party to the Co-Promotion
efforts, including the budgeted number of sales representatives, managed market representatives and medical affairs personnel, assignment of Detailing responsibilities by market segment, including the minimum number and positioning of Details
(which, with respect to Acucela shall be consistent with the Participation Percentage), the target healthcare professionals, and the type and level of other sales force activities to be performed by each Party; provided that such resources
and efforts shall be comparable to the activities actually conducted in connection with promotion of other pharmaceutical products then marketed in the Field in the Territory; 

(iv) the budget for Commercialization Costs (excluding costs of Phase 4 Clinical Trials, if any, which shall be set forth in a
Development Plan) for the forthcoming calendar year (or portion thereof), including a reasonably detailed allocation of such costs and expenses among the activities expected to be conducted in such calendar year (or portion thereof), and a
reasonable good faith projection of the budget for Commercialization Costs (excluding costs of Phase 4 Clinical Trials, if any) after such calendar year, in each case which budget shall be an amount reasonably intended to be sufficient to cover the
anticipated costs associated with the activities reflected in the Commercialization Plan; 
 (v) requirements for
programs (including medical education programs) and grants related to the Licensed Product, such as speaker programs, lunch programs, congresses, symposia, speaker and peer-to-peer activity programs, publication plans and medical information plans;

 (vi) Phase 3b Clinical Trials and Post-Approval Studies, if any; 

(vii) public relations and communications programs; 
 (viii) nature of Co-Promotion activities and call plans (including allocation of key decision makers and Co-Promotion to managed care providers); and 

(ix) marketing research plans and metrics for measuring the success of the respective Parties’ efforts in respect of
Commercialization of the Licensed Product in the Field in the Territory. 

  
 37 

 5.4 Co-Promotion. If Acucela exercises an Opt-In Right under Section 3.1, the
Parties shall Co-Promote the Licensed Product for the Initial Indication in the Initial Formulation in the Territory in accordance with the Commercialization Plan and the Co-Promotion Agreement. In addition, if Acucela exercises the opt-in right to
co-Develop and Co-Promote an Other Indication Product in accordance with Section 3.2(b) or a New Formulation in accordance with Section 3.3(b), the Parties shall Co-Promote such Other Indication Product and/or New Formulation in the
Territory in accordance with the applicable Commercialization Plan and the Co-Promotion Agreement. In such case(s), Acucela and Otsuka shall use Commercially Reasonable Efforts to carry out each of their respective responsibilities under each
Commercialization Plan and under the Co-Promotion Agreement, and the terms of this Section 5.4 shall apply. 
 (a)
Participation Percentage Participation. Acucela shall participate in Co-Promotion at a participation level that is equal to the Participation Percentage, including by performing the number of Primary Detail Equivalents equal to the Participation
Percentage of the total budgeted number of PDEs in the Field in the Territory as set forth in the Commercialization Plan. If the budgeted number of PDEs for promotion of the Licensed Product in the Field in the Territory is increased or decreased by
the JCC (as set forth in an amended Commercialization Plan), the Participation Percentage shall be applied to such increased or decreased number of PDEs; provided that, in the case of an increase, Acucela shall have a commercially reasonable
amount of time to satisfy such required increase. 
 (b) Cost Sharing; Sharing Payments. The Parties shall share
Commercialization Costs (including costs of Phase 4 Clinical Trials, if any) in accordance with the provisions of Section 7.4(c) and, in consideration of Acucela’s performance of Detailing, deployment of sales representatives and other
Co-Promotion efforts, as well as Acucela’s other commitments under this Agreement, including sharing of Development Costs pursuant to Section 7.4 and payment of amounts indicated in Sections 7.1, 7.2, and 7.3, Otsuka shall pay Sharing
Payments to Acucela in accordance with the provisions of Section 7.5. 
 (c) Sales Team Assignments. Each Party
shall deploy its sales forces in accordance with the Commercialization Plan, but each Party shall retain direct supervision of its own sales force, including the power to hire and fire. The assignment by the JCC of each Party’s sales force
within the Territory will be equitable so that the sales force of each Party is assigned valuable, productive accounts and an equitable share of responsibility for opinion leaders, large accounts, and other more desirable accounts. Acucela’s
sales representatives will be geographically dispersed in the Territory so as to have equitable representation with Otsuka’s sales representatives in the most productive areas of the Territory, based on analysis of prescriber profiles. In
geographic areas where both Parties have sales representatives, every effort will be made by the JCC to split the sales targets as equitably as possible. The Parties shall attempt to minimize sales force realignments so as not to disrupt
representative-to-representative and representative-to-physician relationships. On a monthly basis, each Party shall submit to the JCC a detailed written report describing its Detailing and promotional activities in the Territory during the
preceding month. 
 (d) Training. Otsuka shall prepare for and hold Licensed Product promotion training programs in the
Territory prior to and periodically after Launch to ensure the Parties’ 

  
 38 

 
sales forces are adequately trained to effectively promote Licensed Product, provided that, there will be a single training program which is commonly provided to both Otsuka and Acucela sales
representatives in the Territory. 
 (e) Minimum Qualifications. All sales forces who Detail Licensed Product in the
Territory (i) shall have at least a Bachelor of Arts or Bachelor of Sciences degree from a four-year college or university or the equivalent, (ii) shall have at least one (1) year of prior experience promoting and detailing
pharmaceutical products in the field of ophthalmology, and (iii) shall be subject to a reasonable proficiency examination relevant to Licensed Product. 
 (f) Effective Co-Promotion Practices. Otsuka and Acucela, and their respective Affiliates, shall cooperate to employ and implement effective Co-Promotion practices. Such cooperation shall include
the development, through the JCC, of a clear understanding of the marketing roles and responsibilities of each Party in the Territory and the establishment, through the JCC, of effective communication systems and processes to ensure that the
promotional activities of the Parties’ sales forces are efficient, coordinated and productive. 
 (g) Exchange of
Marketing Information. Otsuka and Acucela shall together develop and maintain current Detailing lists, schedules, and other appropriate information for the purpose of determining the physicians and other Persons involved in the drug purchase
decision-making process to whom Otsuka and Acucela sales forces may Detail Licensed Products in the Field in the Territory. 

(h) Advertising and Promotional Materials. Otsuka shall prepare and select, and be responsible for providing, all advertising and
promotional materials to be used for the sales and marketing of Licensed Products in the Field in the Territory, provided that there will be a single set of advertising and promotional materials used by the Otsuka sales force and the Acucela
sales forces. All advertising and promotional materials shall be in full compliance with all Applicable Laws. Otsuka shall at all times ensure that it is providing to Acucela sales representatives all promotional materials (including samples) in
order to effectively promote Licensed Product in accordance with the Commercialization Plan. 
 (i) Subcontracting.
Acucela shall not subcontract all or any part of its Co-Promotion activities without, in each instance, obtaining the prior written approval of Otsuka, which prior written approval may be evidenced in the minutes of any JCC meeting or in any
Commercialization Plan; provided, however that Otsuka shall not unreasonably withhold, condition or delay its approval of one or more subcontractors to conduct up to *, in the aggregate, of Acucela’s Co-Promotion activities.
Notwithstanding Otsuka’s approval of a subcontractor, Acucela’s right to subcontract any Co-Promotion activities shall be subject to the following: (a) none of Otsuka’s rights hereunder shall be diminished or otherwise adversely
affected as a result of such subcontracting, (b) the subcontractor shall not have the right to further subcontract Co-Promotion activities unless agreed upon in writing by Otsuka, (c) Acucela shall be responsible and liable for the
performance by any subcontractor of, or failure of any subcontractor to comply with, and Acucela guarantees the compliance by each subcontractor with, all relevant restrictions, limitations and obligations in this Agreement, (d) such permitted
subcontracting shall not relieve Acucela of any liability or obligation under this Agreement, except to the extent satisfactorily performed by such subcontractor. In addition, Acucela shall 

  

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use Commercially Reasonable Efforts to negotiate each agreement with each such permitted subcontractor (“Co-Promotion Subcontractor Agreement”) to provide that: (i) such
subcontractor shall be bound by obligations of confidentiality and non-use that are no less stringent than those undertaken by the Parties pursuant to this Agreement, (ii) during the term of the Co-Promotion Subcontractor Agreement and
thereafter (up to * after completion of Co-Promotion) such subcontractor shall allow Otsuka or its designee to audit such subcontractor’s sites and all records and other information resulting from Co-Promotion services conducted by such
subcontractor (including the right to inspect and copy such records) once annually (or more often if any such annual audit reveals a failure by such subcontractor to comply with Applicable Laws or if Otsuka reasonably believes that such a failure to
comply exists) in the location(s) where such data, records and information are maintained by such subcontractor, upon reasonable notice and during such subcontractor’s regular business hours and under obligations of confidence, for the purposes
of verifying such subcontractor’s compliance with Applicable Laws; and (iii) Otsuka is a third party beneficiary of the Co-Promotion Subcontractor Agreement. Each Co-Promotion Subcontractor Agreement shall be reviewed and approved by
Otsuka prior to Acucela’s or the subcontractor’s execution thereof, and Otsuka shall not be obligated to approve a Co-Promotion Subcontractor Agreement that does not contain provisions consistent with clauses (i) through (iii) in
the preceding sentence; provided, however, that if Acucela has complied with its obligation to use Commercially Reasonable Efforts as set forth in the preceding sentence and Otsuka fails or declines to approve such Co-Promotion Subcontractor
Agreement, and Acucela is not reasonably able to perform itself the applicable activities intended to be subcontracted under such Co-Promotion Subcontractor Agreement, delays that may be attributable to the failure to approve such Co-Promotion
Subcontractor Agreement shall not be construed as delays attributable to Acucela. Acucela shall use Commercially Reasonable Efforts to monitor and enforce the terms of each Co-Promotion Subcontractor Agreement. 

(j) Co-Promotion Agreement. The Parties shall, upon formation of the JCC, enter into good faith negotiations to conclude a
separate co-promotion agreement within * days of formation of the JCC, which shall outline in more detail the overall framework for the Co-Promotion activities of the Parties with respect thereto, including the roles and responsibilities of each
Party, and which shall be consistent with the terms and conditions described in this Section 5.4 and shall contain other, mutually agreed, customary and commercially reasonable terms, including provisions relating to ethics and compliance,
recordkeeping, reporting and auditing, and performance metrics (which in each case shall be consistent with the Commercialization Plan) and remedies, including remedies for failure to provide PDEs (the “Co-Promotion Agreement”).

 5.5 Acucela Mark. Otsuka hereby agrees, to the extent allowable under Applicable Laws, to include on all marketing
(including advertising) and promotional materials for Licensed Product(s) in the Field in the Territory the then-current Acucela corporate logo as designated by Acucela from time to time (the “Acucela Mark”). It is understood that
such inclusion of the Acucela Mark shall be consistent with industry standards and shall be of equal prominence to Otsuka’s and its Affiliates’ trademarks included on such marketing and promotional materials. In all cases the Acucela Mark
shall be legible, conspicuous and have a size of no smaller than such trademarks of Otsuka or its Affiliate, as applicable on such marketing and promotional materials. Accordingly, Acucela hereby grants to Otsuka a non-exclusive, royalty-free
license to use the Acucela Mark solely in connection with the marketing and promotion of the Licensed 

  

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Product(s) in the Field in the Territory hereunder. Otsuka’s use of the Acucela Mark on marketing and promotional materials for Licensed Product in the Field in the Territory shall be
consistent with reasonable written guidelines provided from time to time by Acucela. Notwithstanding anything herein to the contrary, upon Acucela’s written request, Otsuka and its Affiliates agree to cease (or caused to be ceased) such use of
the Acucela Mark with respect to any specified marketing or promotional materials for Licensed Product in the Field in the Territory; provided (i) that Otsuka and its Affiliates may continue to use any marketing and promotional materials in
existence as of the receipt of such notice and (ii) in such case Otsuka’s obligation to include the Acucela Mark on marketing and promotional materials for Licensed Product(s) shall terminate. 

ARTICLE 6 

LICENSES 

6.1 Pre-Opt-In Development License. Subject to the terms and conditions of this Agreement, Otsuka hereby grants Acucela a
non-exclusive, royalty-free, fully-paid license under the Licensed IP in the Field in the Territory for the sole and limited purpose of conducting Development activities pursuant to Section 4.3 in accordance with the Development Plan and the
terms of this Agreement. 
 6.2 License for Joint Development. Subject to the terms and conditions of this Agreement,
(a) effective upon Acucela’s exercise of an Opt-In Right under Section 3.1, Otsuka hereby grants Acucela a co-exclusive (with Otsuka, its Affiliates and sublicensees) license under the Licensed IP to Develop Licensed Products for the
Initial Indication in the Initial Formulation in the Territory in accordance with the Development Plan and the terms of this Agreement, and (b), if applicable, effective upon Acucela’s exercise of an opt-in right under Section 3.2 with
respect to any Other Indication Product and/or Acucela’s exercise of an opt-in right under Section 3.3 with respect to any New Formulation, Otsuka hereby grants Acucela a co-exclusive (with Otsuka, its Affiliates and sublicensees) license
under the Licensed IP to Develop such Other Indication Product(s) and/or New Formulations in the Territory in accordance with the Development Plan(s) and the terms of this Agreement. 

6.3 License for Co-Promotion. Subject to the terms and conditions of this Agreement, (a) effective upon Acucela’s
exercise of an Opt-In Right under Section 3.1, Otsuka hereby grants Acucela a co-exclusive (with Otsuka, its Affiliates and sublicensees) license under the Licensed IP to Co-Promote Licensed Products for the Initial Indication in the Initial
Formulation in the Territory in accordance with the Commercialization Plan and the terms of this Agreement, and (b) if applicable, effective upon Acucela’s exercise of an opt-in right under Section 3.2 with respect to any Other
Indication Product and/or Acucela’s exercise of an opt-in right under Section 3.3 with respect to any New Formulation, Otsuka hereby grants Acucela a co-exclusive (with Otsuka, its Affiliates and sublicensees) license under the Licensed IP
to Co-Promote such Other Indication Product(s) and/or New Formulations in the Territory in accordance with the Commercialization Plan(s) and the terms of this Agreement. For clarity, Acucela shall have no right or license to conduct
Commercialization activities other than Co-Promotion activities, and the license hereunder specifically excludes any right to sell, offer for sale, import or distribute Licensed Products in the Territory. 

  
 41 

 6.4 Sublicenses by Acucela. Acucela shall have no right to grant sublicenses of the
licenses granted Acucela under this Article 6 except (i) to subcontractors, solely in compliance with Sections 4.5 and 5.4(i), (ii) with the prior written consent of Otsuka, or (iii) to one or more of Acucela’s Affiliates;
provided that Acucela shall remain responsible for the activities of such Affiliate(s) to the same extent as if such activity were conducted by Acucela. 
 6.5 Other Licenses by Otsuka. If Otsuka grants any of its rights or delegates any of its obligations under this Agreement to any Third Party sublicensee, licensee and/or contractor, Otsuka shall be
responsible for the failure by any such sublicensee, licensee and/or contractor to comply with, and Otsuka guarantees the compliance by each sublicensee, licensee and/or contractor with, all relevant restrictions, limitations and obligations in this
Agreement. 
 6.6 No Implied Licenses; Retained Rights. No license or other right is or shall be created or granted
hereunder by implication, estoppel or otherwise. All such licenses and rights are or shall be granted only as expressly provided in this Agreement. All rights not expressly granted hereunder are reserved by Otsuka and may be used by Otsuka for any
purpose. Without limiting the foregoing, Otsuka retains any and all rights under the Licensed IP to develop, make, have made, use, sell, offer for sale, have sold or import or otherwise exploit any product for use outside of the Field or outside the
Territory. 
 ARTICLE 7 
 FINANCIAL TERMS 
 7.1 Opt-In Fee. 

(a) Licensed Product for Initial Indication in the Initial Formulation. Acucela shall pay Otsuka a non-refundable and
non-creditable one-time fee in consideration for its exercise of the Opt-In Right pursuant to Section 3.1 as follows: 

(i) if Acucela exercises the * Opt-In Right pursuant to Section 3.1(a) and if the Participation Percentage is twenty-five
percent (25%), Acucela shall pay Otsuka ten million dollars ($10,000,000) within * days of exercising the * Opt-In Right; or 

(ii) if Acucela exercises the * Opt-In Right pursuant to Section 3.1(a) and if the Participation Percentage is thirty-five
percent (35%), Acucela shall pay Otsuka * within * days of exercising the * Opt-In Right; or 
 (iii) if Acucela
exercises the P3 Opt-In Right pursuant to Section 3.1(b) and if the Participation Percentage is twenty-five percent (25%), Acucela shall pay Otsuka * within * days of exercising the P3 Opt-In Right; or 

(iv) if Acucela exercises the P3 Opt-In Right pursuant to Section 3.1(b) and if the Participation Percentage is thirty-five
percent (35%), Acucela shall pay Otsuka fifty-five million dollars ($55,000,000) within * days of exercising the P3 Opt-In Right. 
 (b) Other Indication Product. Within thirty (30) days after exercising its opt-in right with respect to any Other Indication Product pursuant to Section 3.2, Acucela shall pay Otsuka a
non-refundable and non-creditable one-time fee in consideration for its exercise of 

  

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such opt-in right, which fee shall be equal to the Participation Percentage of all clinical development costs (excluding preclinical costs) incurred by Otsuka to the extent allocable to
Development of the Other Indication Product for the applicable Other Indication prior to Acucela’s exercise of its opt-in right under Section 3.2. The foregoing payment shall be due and payable by Acucela with respect to each Other
Indication Product for which Acucela exercises its opt-in right under Section 3.2. 
 (c) New Formulation. Within *
days after exercising its opt-in right with respect to any New Formulation pursuant to Section 3.3, Acucela shall pay Otsuka a non-refundable and non-creditable one-time fee in consideration for its exercise of such opt-in right, which fee
shall be equal to the Participation Percentage of all clinical development costs (excluding preclinical costs) incurred by Otsuka with respect to such New Formulation prior to Acucela’s exercise of its opt-in right under Section 3.3. The
foregoing payment shall be due and payable by Acucela with respect to each New Formulation for which Acucela exercises its opt-in right under Section 3.3. 
 7.2 Development Milestone Payments. In addition to the other fees payable under this Agreement, Acucela shall make the following non-refundable, non-creditable, one-time milestone payments to
Otsuka: 
 (a) Filing of NDA for Licensed Product for the Initial Indication in the Initial Formulation. 

(i) if Acucela exercises the * Opt-In Right pursuant to Section 3.1(a) and if the Participation Percentage is twenty-five
percent (25%), Acucela shall pay Otsuka * within * days of *; or 
 (ii) if Acucela exercises the * Opt-In Right
pursuant to Section 3.1(a) and if the Participation Percentage is thirty-five percent (35%), Acucela shall pay Otsuka * within * days of *. 
 (b) Approval of NDA for Licensed Product for the Initial Indication in the Initial Formulation. 
 (i) if Acucela exercises the * Opt-In Right pursuant to Section 3.1(a) and if the Participation Percentage is twenty-five percent (25%), Acucela shall pay Otsuka * within * days of *; or

 (ii) if Acucela exercises the * Opt-In Right pursuant to Section 3.1(a) and if the Participation Percentage is
thirty-five percent (35%), Acucela shall pay Otsuka * within * days of *; or 
 (iii) if Acucela exercises the P3 Opt-In
Right pursuant to Section 3.1(b) and if the Participation Percentage is twenty-five percent (25%), Acucela shall pay Otsuka * within * days of *; or 
 (iv) if Acucela exercises the P3 Opt-In Right pursuant to Section 3.1(b) and if the Participation Percentage is thirty-five percent (35%), Acucela shall pay Otsuka * within * days of *.

 (c) Approval of NDA for Other Indication Product. If Acucela exercises its opt-in right with respect to an Other
Indication Product pursuant to Section 3.2, Acucela shall pay Otsuka * within * days of Regulatory Approval of the NDA for such Other Indication Product. The foregoing payment shall be due and payable by Acucela with respect to each Other
Indication Product for which Acucela exercises its opt-in right under Section 3.2. 

  

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 7.3 Sales Milestone Payments. In addition to the other fees payable by Acucela under
this Agreement, after achievement of each of the following sales milestone events, Acucela shall make each of the non-refundable, non-creditable corresponding sales milestone payments to Otsuka as set forth in the table below: 

 

					
	 Sales Milestone Event
	  	Sales Milestone Payment	 
	 Aggregate Net Sales of all Licensed Products in the Field in the Territory equal or exceed $* in *
	  	$	10,000,000	  
	 Aggregate Net Sales of all Licensed Products in the Field in the Territory equal or exceed $* in *
	  	$	15,000,000	  
	 Aggregate Net Sales of all Licensed Products in the Field in the Territory equal or exceed $* in *
	  	$	20,000,000	  
	 Aggregate Net Sales of all Licensed Products in the Field in the Territory equal or exceed $* in *
	  	$	30,000,000	  

 Acucela shall pay Otsuka each applicable sales milestone payment above within * days after Otsuka provides written
notice to Acucela that each corresponding sales milestone event has been achieved (together with supporting evidence); provided that if more than one sales milestone payment would otherwise be paid in the same calendar year (as a result of
more than one sales milestone event being achieved in the same calendar year), Acucela shall pay the first such sales milestone payment within such * period and Acucela shall pay the second, third and/or fourth such milestone payment(s) (as
applicable) on the date that is * months, * months and * months, respectively (as applicable), after the date of such first milestone payment. 
 7.4 Cost Sharing. 
 (a) Sharing of Development Costs. From and after
the time that Acucela exercises an Opt-In Right under Section 3.1, the Parties shall jointly fund all Development Costs incurred after the effective date of such opt-in by or on behalf of the Parties in connection with Development of Licensed
Product as follows: 
 (i) With respect to Development of the Licensed Product for the Initial Indication in the Initial
Formulation, Acucela shall fund its share of all Development 

  

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Costs incurred after the effective date of such opt-in by or on behalf of the Parties in accordance with the percentages set forth in clause (A) or clause (B), as applicable, and clause
(C) below (in all cases subject to the terms of Section 7.4(b)) and Otsuka shall fund the remaining share of all Development Costs incurred by or on behalf of the Parties with respect to Development of Licensed Product for the Initial
Indication in the Initial Formulation: 
 (A) if Acucela exercises the * Opt-In Right under
Section 3.1(a), Acucela’s share of the costs incurred after the effective date of such opt-in for conducting Phase 3 Clinical Trials of Licensed Product for the Initial Indication in the Initial Formulation (excluding P3b Clinical Trials
and not including, for the avoidance of doubt, Phase 4 Clinical Trials and Post-Approval Studies) shall be: (A) if such Phase 3 Clinical Trials are Global Studies that include Japan, Acucela shall fund * of all costs of conducting such Global
Studies, including all of Acucela’s direct and indirect costs and expenses (including internal costs, subject to Section 7.4(f), and payments to approved CROs and any other permitted subcontractors) related to the conduct of such Global
Studies, plus costs paid by Otsuka or its Affiliates to CROs and any other Third Party subcontractors for conduct of such Global Studies in Japan, or (B) if such Phase 3 Clinical Trials are Global Studies that do not include Japan, Acucela
shall fund * of all costs of conducting such Global Studies, including all of Acucela’s direct and indirect costs and expenses (including internal costs, subject to Section 7.4(f), and payments to approved CROs and any other permitted
subcontractors) related to the conduct of such Global Studies; or 
 (B) if Acucela exercises the P3
Opt-In Right under Section 3.1(b), Acucela shall not be obligated to fund any costs of conducting Phase 3 Clinical Trials of Licensed Product for the Initial Indication in the Initial Formulation (excluding P3b Clinical Trials and not
including, for the avoidance of doubt, Phase 4 Clinical Trials and Post-Approval Studies); and 
 (C) If
Acucela exercises its Opt-In Right (either the * Opt-In Right under Section 3.1(a) or the P3 Opt-In Right under Section 3.1(b)), Acucela shall fund 50% of all other (non-Phase 3 Clinical Trials) Development Costs incurred with respect to
the Licensed Product for the Initial Indication in the Initial Formulation after the effective date of such opt-in, including costs related to regulatory affairs in the Territory, subject to Section 7.4(f) where applicable. 

(ii) With respect to Development of any New Formulation for which Acucela has exercised an opt-in right pursuant to
Section 3.3, Acucela shall fund its share of all Development Costs incurred after the effective date of such opt-in by or on behalf of the Parties in accordance with the percentages set forth in clause (A) and/or clause (B), as applicable,
and clause (C) below (in all cases subject to the terms of Section 7.4(b)) and Otsuka shall fund the remaining share of all Development Costs incurred by or on behalf of the Parties with respect to Development of such New Formulation:

 (A) if Development of such New Formulation will include Global Studies of such New Formulation,
Acucela’s share of the costs incurred after the 

  

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effective date of such opt-in of conducting such Global Studies (excluding P3b Clinical Trials, Phase 4 Clinical Trials and Post-Approval Studies) shall be: (1) if such Global Studies
include Japan, Acucela shall fund * of all costs of conducting such Global Studies, including all of Acucela’s direct and indirect costs and expenses (including internal costs, subject to Section 7.4(f), and payments to approved CROs and
any other permitted subcontractors) related to the conduct of such Global Studies, plus costs paid by Otsuka or its Affiliates to CROs and any other Third Party subcontractors for conduct of such Global Studies in Japan, or (2) if such Global
Studies do not include Japan, Acucela shall fund * of all costs of conducting such Global Studies, including all of Acucela’s direct and indirect costs and expenses (including internal costs, subject to Section 7.4(f), and payments to
approved CROs and any other permitted subcontractors) related to the conduct of such Global Studies; and/or 

(B) if Development of such New Formulation will include U.S.-Only Studies of such New Formulation, Acucela shall
fund 50% of all costs of conducting such U.S.-Only Studies (excluding P3b Clinical Trials, Phase 4 Clinical Trials and Post-Approval Studies), including all of Acucela’s direct and indirect costs and expenses (including internal costs, subject
to Section 7.4(f), and payments to approved CROs and any other permitted subcontractors) related to the conduct of such U.S.-Only Studies; and 
 (C) Acucela shall fund 50% of all other (non-Global Studies or non-U.S.-Only Studies) Development Costs incurred with respect to such New Formulation after the effective date of such opt-in,
including costs related to regulatory affairs in the Territory, if any, subject to Section 7.4(f) where applicable. 

(iii) With respect to Development of any Other Indication Product for which Acucela has exercised an opt-in right pursuant to
Section 3.2, Acucela shall fund the Participation Percentage of all Development Costs incurred after the effective date of such opt-in by or on behalf of the Parties, subject to the terms of Section 7.4(b)(iii), and Otsuka shall fund the
remaining share of all Development Costs incurred by or on behalf of the Parties with respect to Development of such Other Indication Product. 
 (b) Aggregate Development Cost Cap. 
 (i) Notwithstanding
Section 7.4(a) but subject to Section 7.4(f) where applicable, Acucela’s share of the Development Costs of Licensed Product for the Initial Indication in the Initial Formulation and, if applicable, Acucela’s share of costs of
conducting Development, through *, of any New Formulation for which Acucela exercises an opt-in right under Section 3.3, shall not exceed, collectively, the Aggregate Development Cost Cap of twenty-three million dollars ($23,000,000) and
Acucela shall have no obligation to fund its share of such Development Costs for the Initial Indication in the Initial Formulation and, if applicable, its share of such Development Costs for such New Formulation through *, that collectively exceed
such Aggregate Development Cost Cap (the “Excess Development Share”) unless Acucela agrees to bear the Excess Development Share or an Expert determines (pursuant to 

  

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Section 14.2(a)) that activities or expenditures, which if conducted (or, in the case of expenditures, if spent) would obligate Acucela to fund Development Costs in excess of the Aggregate
Development Cost Cap, are necessary to be conducted (or, in the case of expenditures, are necessary to be spent) in order to obtain Regulatory Approval. If Acucela so agrees or an Expert so determines, then Acucela’s obligation to fund the
Excess Development Share shall be fulfilled as follows: Otsuka shall bear, on behalf of Acucela, the Excess Development Share at the time such costs are incurred and, on a monthly basis commencing the first month of *, Otsuka shall withhold from
each Sharing Payment due to be paid to Acucela pursuant to Section 7.5 * of the total Sharing Payment due for such month until the Excess Development Share borne by Otsuka is recouped in full by Otsuka. For clarity, if any New Formulation for
which Acucela has exercised an opt-in right under Section 3.3 is being Developed after *, Acucela (and not Otsuka) shall fund its share (in accordance with Section 7.4(a)(ii)) of all Development Costs incurred in connection with
Development of such New Formulation on a current basis as such Development Costs are incurred, and the Excess Development Share to be borne and recouped by Otsuka shall not include any amount of Acucela’s share of Development Costs incurred in
connection with Development of such New Formulation during or after *. 
 (ii) At the time that Acucela exercises the *
Opt-In Right under Section 3.1(a), the JDC will discuss and attempt to agree upon a yearly cap of costs of conducting Development of Licensed Product for the Initial Indication in the Initial Formulation (and, if applicable any New Formulation
for which Acucela has exercised an opt-in right pursuant to Section 3.3) (the “Annual Development Cost Cap”), provided that if the JDC cannot agree (with neither Party having a tie-breaking vote), then the Aggregate
Development Cost Cap will be pro-rated on a calendar year (or portion thereof) basis to arrive at the Annual Development Cost Cap for the Initial Indication in the Initial Formulation (and, if applicable, a New Formulation), and, provided
further that any Development Costs paid by Acucela for Development of Licensed Product for the Initial Indication in the Initial Formulation (and, if applicable, a New Formulation) in a calendar year that exceed the Annual Development Cost Cap
for such year will be carried over to the following year (and if such excess amount that is carried forward plus any such Development Costs incurred in such following year exceed the applicable Annual Development Cost Cap for such year, such excess
shall likewise be carried forward to the following year, and so on) until the Aggregate Development Cost Cap is reached (and Acucela shall not be obligated to share Development Costs for Licensed Product for the Initial Indication in the Initial
Formulation, and, if applicable, a New Formulation, in excess of the Aggregate Development Cost Cap except as provided in clause (i) above). If applicable, at the time that Acucela exercises an opt-in right under Section 3.3 with respect
to a New Formulation, the JDC will discuss and attempt to agree on an adjustment to the Annual Development Cost Cap to account for the Development Costs associated with Development of such New Formulation. 

(iii) The Aggregate Development Cost Cap set forth in Section 7.4(b)(i) shall apply only to the costs of conducting
Development of Licensed Product for the Initial Indication in the Initial Formulation and, if applicable, to the costs of conducting Development, through *, of any New Formulation for which Acucela exercises an opt-in right under Section 3.3
and, although the procedure in clauses (i) and (ii) above shall apply mutatis mutandis with respect to each Other Indication Product, a separate Aggregate Development Cost Cap, as

  

	*	Confidential Treatment Requested. 

  
 47 

 
established by the JDC, shall apply to Development Costs incurred for Development of each Other Indication Product. In other words, until the end of *, if Acucela’s share (the Participation
Percentage) of Development Costs incurred in connection with Development of an Other Indication Product for which Acucela has exercised an opt-in right under Section 3.2 exceeds the separate Aggregate Development Cost Cap established by the JDC
for such Other Indication Product, such excess amount shall be borne and recouped by Otsuka in accordance with the procedures set forth in clause (i) above, and if any Other Indication Product for which Acucela has exercised an opt-in right
under Section 3.2 is being Developed after *, Acucela (and not Otsuka) shall fund its share (the Participation Percentage) of all Development Costs incurred in connection with Development of such Other Indication on a current basis as such
Development Costs are incurred during and after *. 
 (c) Sharing of Commercialization Costs. 

(i) From and after the time that Acucela exercises an Opt-In Right under Section 3.1, Acucela shall fund its share of all
Commercialization Costs incurred after the effective date of such opt-in by or on behalf of the Parties (including in connection with Commercialization of the Licensed Product in the Initial Indication in the Initial Formulation, and
Commercialization of any Other Indication Product and/or any New Formulation for which Acucela has exercised an opt-in right pursuant to Section 3.2 and/or Section 3.3, respectively) in an amount equal to the Participation Percentage
(i.e., 25% or 35%, as applicable) of all Commercialization Costs, and Otsuka shall fund the remaining share of all Commercialization Costs, in each case subject to Section 7.4(f), where applicable. 

(ii) Notwithstanding the foregoing, during the first * Launch Years, Acucela’s share of Commercialization Costs for
Commercialization of Licensed Product (including Licensed Product for the Initial Indication in the Initial Formulation, and any New Formulation and Other Indication Product for which Acucela has exercised an opt-in right) (“Initial
Commercialization Costs”) shall not exceed an aggregate cap of either (A) fifty-five million dollars ($55,000,000), if the Participation Percentage is 25%, or (B) seventy-eight million dollars ($78,000,000) if the Participation
percentage is 35% (either (A) or (B), the “Aggregate Commercialization Cost Cap”), which is calculated based on the General Commercialization Plan Outline, and Acucela shall have no obligation to fund its share of such Initial
Commercialization Costs that exceed such Aggregate Commercialization Cost Cap (the “Excess Commercialization Share”) unless Acucela agrees to bear the Excess Commercialization Share or an Expert determines (pursuant to
Section 14.2(a)) that activities or expenditures, which if conducted (or, in the case of expenditures, if spent) would obligate Acucela to fund Initial Commercialization Costs in excess of the Aggregate Commercialization Cost Cap, are necessary
to be conducted (or, in the case of expenditures, are necessary to be spent) in order to improve marketing or increase sales of Licensed Product in the Field in the Territory, taking into consideration the activities conducted and expenditures
incurred in connection with the commercialization of other pharmaceutical products then marketed and sold in the Field in the Territory. If Acucela so agrees or an Expert so determines, then Acucela’s obligation to fund the Excess
Commercialization Share shall be fulfilled as follows: Otsuka shall bear, on behalf of Acucela, the Excess Commercialization Share at the time such costs are incurred and, on a monthly basis commencing on the later of the first month of * or the
month after Otsuka has fully recouped the entire Excess Development Share pursuant to Section 7.4(b)(i), 

  

	*	Confidential Treatment Requested. 

  
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Otsuka shall withhold from each Sharing Payment due to be paid to Acucela pursuant to Section 7.5 * of the total Sharing Payment due for such month until the Excess Commercialization Share
borne by Otsuka is recouped in full by Otsuka. 
 (iii) A yearly cap of Initial Commercialization Costs (the
“Annual Commercialization Cost Cap”) is set forth in the General Commercialization Plan Outline. Any Initial Commercialization Costs paid by Acucela in a calendar year that exceed the Annual Commercialization Cost Cap for such year
will be carried over to the following year (and if such excess amount that is carried forward plus any Initial Commercialization Costs incurred in such following year exceed the applicable Annual Commercialization Cost Cap for such year, such excess
shall likewise be carried forward to the following year, and so on) until the Aggregate Commercialization Cost Cap is reached (and Acucela shall not be obligated to share Initial Commercialization Costs in excess of the Aggregate Commercialization
Cost Cap except as provided in clause (ii) above). 
 (d) Reconciliation Payments. The following shall apply with
respect to payment of Development Costs and Commercialization Costs incurred after Acucela exercises an Opt-In Right pursuant to Section 3.1. Within thirty (30) days after the end of each month during which Development Costs or
Commercialization Costs are incurred, each Party shall provide a written report (each, a “Monthly Report”) to the other Party setting forth in detail the Development Costs or Commercialization Costs (together with the evidence
supporting such Development Costs or Commercialization Costs) incurred by such Party during such month in conducting Development work or Commercialization activities for which it is the Responsible Party under each Development Plan or
Commercialization Plan, as the case may be, in accordance with the budget contained in the applicable Development Plan or Commercialization Plan. Each Monthly Report will be in such form as the JDC or JCC, as applicable, may reasonably agree from
time to time. Within thirty (30) days after each Party has provided the other Party its Monthly Report for a particular month, the Parties shall confer and agree on a written payment report based upon the Monthly Report for such month (each, a
“Payment Report”) setting forth the amount payable by Otsuka to Acucela or the amount payable by Acucela to Otsuka (as the case may be), so that each of the Parties has borne its share of all the Development Costs or
Commercialization Costs (as set forth in Section 7.4(a) and (b) or Section 7.4(c), as applicable) incurred by the Parties in such month. The applicable Party shall pay the amount shown to be due to the other Party as set forth in the
Payment Report within thirty (30) days after the Parties agree on such Payment Report. 
 (e) Cost Overruns. The
following shall apply with respect to cost overruns that occur after Acucela exercises an Opt-In Right pursuant to Section 3.1. If, following Acucela’s exercise of an Opt-In Right under Section 3.1, either Party (as the Responsible
Party) determines that it is likely to overspend or has overspent the budgeted costs and expenses set forth in a Development Plan or a Commercialization Plan, as the case may be, for a calendar year (such overspend, a “Post-Opt-In Cost
Overrun”), such Responsible Party shall promptly notify the JDC or the JCC, as applicable, of the anticipated amount and cause(s) of such Post-Opt-In Cost Overrun and the JDC or JCC, as applicable, shall promptly hold an ad-hoc meeting and
shall discuss reasonably and in good faith what steps to take to address the Post-Opt-In Cost Overrun, which may include amending the applicable Development Plan or Commercialization Plan to modify the activities to reduce costs or to increase the
budget contained therein so that 

  

	*	Confidential Treatment Requested. 

  
 49 

 
there is no longer a Post-Opt-In Cost Overrun. Any modifications to Development or Commercialization activities or the applicable budget in a Development Plan or Commercialization Plan approved
by the JDC or the JCC, respectively, to address a Post-Opt-In Cost Overrun shall be included as an amendment to such Development Plan or Commercialization Plan (or the budget contained therein). If and to the extent a Party experiences a Post-Opt-In
Cost Overrun with respect to Development work or Commercialization activities for which it is the Responsible Party, each Party shall bear such Post-Opt-In Cost Overrun in accordance with its percentage share payable for Development Costs or
Commercialization Costs (as set forth in Section 7.4(a) or Section 7.4(c)(i), as applicable), subject to the terms of Section 7.4(b) and Section 7.4(c)(ii) and (iii). 

(f) Certain Terms with respect to FTEs. With respect to any internal FTEs of Acucela that are included in Development Costs or
Commercialization Costs to be shared by the Parties pursuant to this Section 7.4 (the “Shared Internal FTEs”), the following shall apply: 
 (i) Initial Formulation (if Acucela exercises * Opt-In Right). If Acucela exercises the * Opt-In Right, the Shared Internal FTEs with respect to the Licensed Product for the Initial
Indication in the Initial Formulation shall be shared as follows: 
 (A) the Shared Internal FTEs during
the period from the first day of the calendar month in which Acucela exercises the * Opt-In Right until the first day of the calendar month in which an NDA is filed for the Licensed Product for the Initial Indication in the Initial Formulation shall
be shared at the sharing percentages set forth in Section 7.4(a)(i)(A); 
 (B) the Shared Internal
FTEs during the period from the first day of the calendar month in which an NDA is filed for the Licensed Product for the Initial Indication in the Initial Formulation until the first day of the calendar month in which Regulatory Approval is
obtained for the Licensed Product for the Initial Indication in the Initial Formulation shall be shared at the sharing percentages set forth in Section 7.4 (a)(i)(C); and 

(C) the Shared Internal FTEs during the period from and after the first day of the calendar month in which
Regulatory Approval is obtained for the Licensed Product for the Initial Indication in the Initial Formulation shall be shared at the sharing percentages set forth in Section 7.4(c). 

(ii) Initial Formulation (if Acucela exercises P3 Opt-In Right). If Acucela exercises the P3 Opt-In Right, the Shared Internal
FTEs with respect to the Licensed Product for the Initial Indication in the Initial Formulation shall be shared as follows: 
 (A) the Shared Internal FTEs during the period from the first day of the calendar month in which Acucela exercises the P3 Opt-In Right until the first day of the calendar month in which Regulatory
Approval is obtained for the Licensed Product for the Initial Indication in the Initial Formulation shall be shared at the sharing percentages set forth in Section 7.4 (a)(i)(C); and 

(B) the Shared Internal FTEs during the period from and after the first day of the calendar month in which
Regulatory Approval is obtained for the Licensed Product for the Initial Indication in the Initial Formulation shall be shared at the sharing percentages set forth in Section 7.4(c). 

  

	*	Confidential Treatment Requested. 

  
 50 

 (iii) New Formulation (if Development includes Global Studies). If Acucela exercises
an opt-in right pursuant to Section 3.3 with respect to a New Formulation the Development of which includes Global Studies, the Shared Internal FTEs with respect to such New Formulation shall be shared on a formulation-by-formulation basis as
follows: 
 (A) the Shared Internal FTEs during the period from the first day of the calendar month in
which Acucela exercises its opt-in right with respect to the applicable New Formulation until the first day of the calendar month in which an NDA is filed for the applicable New Formulation shall be shared at the sharing percentages set forth in
Section 7.4(a)(ii)(A); 
 (B) the Shared Internal FTEs during the period from the first day of the
calendar month in which an NDA is filed for the applicable New Formulation until the first day of the calendar month in which Regulatory Approval is obtained for the applicable New Formulation shall be shared at the sharing percentages set forth in
Section 7.4 (a)(ii)(C); and 
 (C) the Shared Internal FTEs during the period from and after the
first day of the calendar month in which Regulatory Approval is obtained for the applicable New Formulation shall be shared at the sharing percentages set forth in Section 7.4(c). 

(iv) New Formulation (if Development does not include Global Studies). If Acucela exercises an opt-in right pursuant to
Section 3.3 with respect to a New Formulation the Development of which does not include Global Studies, the Shared Internal FTEs with such New Formulation shall be shared on a formulation-by-formulation basis as follows: 

(A) the Shared Internal FTEs during the period from the first day of the calendar month in which Acucela exercises its opt-in right
with respect to the applicable New Formulation until the first day of the calendar month in which Regulatory Approval is obtained for the applicable New Formulation shall be shared at the sharing percentages set forth in Section 7.4
(a)(ii)(B)and(C); and 
 (B) the Shared Internal FTEs during the period from and after the first day of the calendar month
in which Regulatory Approval is obtained for the applicable New Formulation shall be shared at the sharing percentages set forth in Section 7.4(c). 
 (v) Other Indication Product. The Shared Internal FTEs with respect to an Other Indication Product shall be shared in accordance with the applicable Participation Percentage. 

  
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 7.5 Sharing of Net Sales. If Acucela exercises an Opt-In Right under
Section 3.1, then, following commencement of Co-Promotion activities by Acucela, Otsuka shall pay Acucela a share of Net Sales (“Sharing Payment”) equal to the Participation Percentage (i.e., 25% or 35%, as applicable) of Net
Sales for each month during which Acucela conducts Co-Promotion activities. The Sharing Payment for each month shall be paid based on Net Sales of Licensed Product for the Initial Indication in the Initial Formulation, any New Formulation for which
Acucela has exercised its opt-in right under Section 3.3 and any Other Indication Product for which Acucela has exercised its opt-in right under Section 3.2 and, for clarity, any revenue from sales of New Formulation for which Acucela did
not exercise its opt-in right under Section 3.3 and/or any revenue from sales of Other Indication Product(s) for which Acucela did not exercise its opt-in right under Section 3.2 shall be excluded from the Net Sales on which the Sharing
Payment is paid. The determination and tracking of the Net Sales on which the Sharing Payment is paid and the net sales of New Formulations and/or Other Indication Product(s) which are excluded from the calculation of the Sharing Payment shall be
based on sales data from IMS or an equivalent, reliable source of sales data as agreed upon by the Parties. Otsuka shall pay the Sharing Payment within forty-five (45) days after the end of each month during which Acucela conducts Co-Promotion
activities in the Territory pursuant to this Agreement and the Co-Promotion Agreement. At the time that Otsuka pays the Sharing Payment, Otsuka shall transmit to Acucela a statement reporting the Sharing Payment due with respect to Net Sales for the
applicable month, which statement shall contain reasonable detail regarding the calculation of the Sharing Payment and the underlying sales data. Notwithstanding the foregoing, within sixty (60) days after the end of each calendar year during
which Acucela conducts Co-Promotion activities, Otsuka shall prepare a reconciliation report showing (i) the actual aggregate annual Net Sales for the immediately preceding calendar year (including Net Sales of Licensed Product for the Initial
Indication in the Initial Formulation and of any New Formulation for which Acucela exercised its opt-in right under Section 3.3 and any Other Indication Product for which Acucela exercised its opt-in right under Section 3.2), (ii) the
total Sharing Payment that should have been paid in such calendar year based on such actual aggregate annual Net Sales, (iii) the actual Sharing Payment paid to Acucela for such calendar year (i.e., the sum of the monthly Sharing Payments made
by Otsuka for the immediately preceding calendar year), and (iv) any underpayment or overpayment of the Sharing Payment in such immediately preceding calendar year (i.e., the difference between the amounts shown under clause (ii) and
clause (iii)). To the extent a reconciliation report reflects an underpayment of the Sharing Payment for a calendar year, Otsuka shall pay such difference to Acucela within thirty (30) days after Otsuka transmits the reconciliation report. To
the extent a reconciliation report reflects an overpayment of the Sharing Payment for a calendar year, such difference shall be set-off against, and deducted by Otsuka from, the Sharing Payment payable by Otsuka to Acucela in the next-succeeding
month (or months, as agreed by the Parties). 
 7.6 No Payments if Opt-In Right Not Exercised. For the avoidance of
doubt, Acucela shall not be obligated to make any of the payments (or incur any of the costs) described in Sections 7.1, 7.2, 7.3 or 7.4, and Otsuka shall not be obligated to make any Sharing Payments as described in Section 7.5, unless
and until such time as Acucela exercises its Opt-In Right under this Agreement. For clarity, disputes about such matters are not subject to a deciding vote at the JDC or the JCC. 

  
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 7.7 Other Payment Terms. 

(a) Payment Currency, Method. All dollar amounts in this Agreement are stated in, and all payments under this Agreement shall be
made in, United States Dollars. All payments between the Parties under this Agreement shall be made by bank wire transfer in immediately available funds to an account designated by the Party to which such payments are due. All payments due under
this Agreement which are not timely paid shall bear interest to the extent permitted by Applicable Laws at a rate equal to the U.S. Prime Lending Rate, as quoted in The Wall Street Journal (U.S. Eastern Edition), effective for the date on
which the payment was due. 
 (b) Taxes. Any withholding or other taxes that either Party is required by Applicable Laws
to withhold or pay on behalf of the other Party, with respect to any payments to such other Party hereunder, shall be deducted from such payments and paid to the appropriate tax authority contemporaneously with the remittance to the other Party,
provided, however, that the withholding Party shall furnish the other Party with proper evidence of the taxes so paid. Each Party shall cooperate with the other and furnish the other Party with appropriate documents to secure application of
the most favorable rate of withholding tax under Applicable Laws (or exemption from such withholding tax payments, as applicable). Notwithstanding the foregoing, the Parties understand that, as of the Effective Date, no withholding taxes are
applicable with respect to any of their payment obligations under this Agreement. 
 (c) Payment Disputes. Any dispute
between the Parties regarding amounts of payments due from one Party to the other under this Agreement, including any dispute regarding characterization of costs as Development Costs or Commercialization Costs for purposes of determining such
payments, shall be resolved as an Expert Matter in accordance with Section 14.2(a). 
 7.8 Records Retention; Audits.

 (a) Records Retention. Each Party will maintain complete and accurate books, records and accounts used for the
determination of Development Costs and Commercialization Costs incurred in connection with the performance of this Agreement or otherwise relevant for the calculation of Net Sales and the Sharing Payment, in sufficient detail to confirm the accuracy
of any payments required under this Agreement, which books, records and accounts will be retained by such Party for five (5) years after the end of the period to which such books, records and accounts pertain, or longer as is required by
Applicable Laws. 
 (b) Audit Request. Upon the written request of a Party (the “Auditing Party”) and
not more than once each calendar year, the other Party (the “Responding Party”) shall permit the Auditing Party, accompanied by an independent certified public accounting firm of internationally recognized standing, selected by the
Auditing Party and reasonably acceptable to the Responding Party, at the Auditing Party’s expense, to have access during normal business hours to the records of the Responding Party as may be reasonably necessary to verify the accuracy of the
financial reports and calculations made under Article 4 and this Article 7 for any Calendar Quarter ending not more than five (5) years prior to the date of such request. Any such audit shall be conducted at the location where the records
are normally kept, unless otherwise reasonably requested by the Responding Party. 
 (c) Discrepancies. If, as a result
of such audit, it is established that additional amounts were owed by the Responding Party for the audited period, such Party shall pay such additional amounts within thirty (30) days after the date such discrepancy is established. In the event
of a dispute as to whether there is a discrepancy, the matter shall be resolved by the JDC (with respect to Development Costs) or the JCC (with respect to Commercialization Costs or the Sharing Payment). The fees charged by such accounting firm
shall be paid by the Auditing Party; provided, however, that if the audit establishes that the aggregate amounts payable by the Responding Party for such period are more than one hundred five percent (105%) of the aggregate amounts
actually paid for such period, then the Responding Party shall pay the reasonable fees and expenses charged by such accounting firm. The Auditing Party shall treat all financial information subject to review under this Section 7.8 as
confidential, and shall cause its accounting firm to retain all such financial information in confidence. 

  
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 ARTICLE 8 
 REGULATORY MATTERS 
 8.1 Regulatory Filings, Labeling. As between
the Parties and subject to Otsuka designating Acucela as Otsuka’s agent to be the primary contact with the FDA as set forth in this Section 8.1, Otsuka shall have all ultimate decision-making authority over, and shall be responsible for
the costs of (or shall share applicable costs with Acucela as provided in Section 7.4), all of the following (including, as applicable, Acucela’s activities related to the following): (i) filing, obtaining and maintaining, in
Otsuka’s name or in the name of its Affiliate, all Regulatory Filings for Licensed Products in the Territory, including all associated submissions (e.g., safety alerts, protocol submissions, etc.); (ii) all interactions and communications
with the FDA, including responding to inquiries and correspondence from the FDA; (iii) the establishment of the Licensed Product safety database for the Territory; (iv) the monitoring of all clinical experiences and submission of all
required reports throughout Development and Commercialization of any Licensed Product in the Territory; and (v) the contents of Licensed Product labels, as submitted to the FDA, and the ensuing negotiations towards the finalization thereof as
approved by the FDA, in each case in compliance with all Applicable Laws. For the avoidance of doubt, all costs and expenses incurred in preparing and filing Regulatory Filings shall be Development Costs. Through the JDC, the Parties shall discuss
and collaborate with respect to all material aspects of Regulatory Filings and Licensed Product labels and either Party shall, at the request of the other Party, review, comment on and provide reasonable assistance regarding filings, submissions,
and responses to the FDA related to the Licensed Compound or Licensed Products in the Territory. Otsuka shall own all INDs, NDAs and other Regulatory Filings and all Regulatory Approvals with respect to the Licensed Compound and Licensed Product (in
all formulations and indications); provided, however that, Otsuka shall transmit all necessary and appropriate letters to the FDA advising the FDA that Acucela shall be the primary contact for the FDA with respect to Development matters
(including conduct of the pre-IND meeting) for the Licensed Product in the Territory. For clarity, it is understood that in acting as Otsuka’s primary contact with the FDA with respect to Development matters for the Licensed Product in the
Territory, Acucela will be subject to Applicable Laws and ethical obligations with which it must comply and, therefore, if any 

  
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instructions from Otsuka or any of its Affiliates, in Acucela’s reasonable judgment, conflict with such Applicable Laws and ethical obligations, (A) Acucela shall notify Otsuka in
writing, (B) Acucela shall not be obligated to take such action, and (C) if Otsuka or any of its Affiliates disagrees with Acucela’s judgment, Otsuka or its Affiliate may directly communicate with FDA and may be the primary contact
with FDA with respect to the relevant matter that is the subject of such disagreement. 
 8.2 Drug Master File; Transfer by
Otsuka. Notwithstanding the foregoing, Otsuka shall have the responsibility and authority to prepare and provide all Manufacturing-related data, information and other related Manufacturing documentation as is necessary to prepare Regulatory
Filings and receive Regulatory Approval. Otsuka shall provide such Manufacturing-related data, information and other documentation in the form of a Drug Master File (“DMF”) under seal directly to the FDA, Acucela shall be entitled
to reference such DMF in the IND and NDA for the Licensed Product, and Otsuka shall be entitled to respond directly to the FDA regarding Licensed Product Manufacturing. Otsuka shall provide Acucela a Letter of Authorization to reference such DMF in
the IND and NDA for the Licensed Product in the Field in the Territory. In addition, within thirty (30) days after the Effective Date, Otsuka shall transfer to Acucela all data and information (including certain CMC information requested by
Acucela prior to the Effective Date but excluding the DMF and any data and information to be contained in the DMF which are not publicly available) reasonably necessary or useful for Acucela to submit to FDA the IND (including such data and
information necessary or useful for Acucela to conduct the pre-IND meeting) for the Licensed Product for the Initial Indication in the formulation existing as of the Effective Date in the Territory. From time to time thereafter at the request of
Acucela, Otsuka shall transfer to Acucela data and information (excluding the DMF and any data and information contained in the DMF which are not publicly available) reasonably necessary or useful for Acucela’s filings, submissions and
responses to FDA related to Licensed Product in the Field in the Territory. 
 8.3 Pharmacovigilance. Although Acucela
shall be Otsuka’s primary contact with the FDA with respect to Development matters for the Licensed Product in the Territory, the Parties acknowledge that, as the owner of all Regulatory Filings and Regulatory Approvals, Otsuka is responsible
for complying with all pharmacovigilance requirements under Applicable Laws. Therefore, as soon as reasonably practicable after the Effective Date, Acucela and Otsuka shall enter into a separate agreement setting forth the pharmacovigilance
responsibilities and procedures for safety information exchange to be carried out by the Parties during the course of conducting Development and, if Acucela exercises an Opt-In Right under Section 3.1, the Parties shall enter into, as soon as
reasonably practicable after formation of the JCC, a separate agreement setting forth the pharmacovigilance responsibilities and procedures for safety information exchange to be carried out by the Parties during the course of conducting
Commercialization (each a “Pharmacovigilance Agreement”). Each Pharmacovigilance Agreement shall contain such terms as are reasonable and customary for arrangements of this type, including mutually acceptable guidelines and
procedures for the receipt, investigation, recordation, communication, and exchange of adverse event reports and other information concerning the safety of Licensed Product, and shall in all events include such terms as are necessary to ensure that
both Parties comply with Applicable Laws pertaining to adverse events and safety reporting. Subject, in each case, to compliance with Applicable Laws, each Party hereby agrees to comply with its respective obligations under each Pharmacovigilance
Agreement. 

  
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 8.4 Product Recall or Withdrawal. The terms of this Section 8.4 shall apply only
if and after Acucela exercises an Opt-In Right under Section 3.1. For clarity, if Acucela has not exercised its Opt-in Right, Otsuka shall be solely responsible for all costs associated with any recall or withdrawal of Licensed Product in the
Territory. If either Otsuka or Acucela discovers or becomes aware of any fact, condition, circumstance or event (whether actual or potential) that may reasonably require a recall or withdrawal of the Licensed Product in the Territory, such Party
shall communicate such fact, condition, circumstance or event promptly to the other Party. To the extent that it is necessary or appropriate to communicate with any Person, including to the FDA or any other regulatory authority, the media or any
customer, concerning any such fact, condition, circumstance or event, Otsuka shall be the primary contact, and shall have all decision-making authority, concerning such communication. Otsuka shall be responsible and shall have final decision-making
authority for the management and implementation of any recall or withdrawal of Licensed Product in the Territory. All costs associated with any recall or withdrawal of Licensed Product in the Territory shall be borne by Otsuka. Notwithstanding the
foregoing, if a recall or withdrawal of Licensed Product in the Territory becomes necessary due to no fault of either Party but due to an intrinsic problem or defect in the efficacy or safety of the Licensed Product (an “Intrinsic
Defect”) all costs associated with such recall or withdrawal shall be shared by the Parties as follows: Acucela shall bear the Participation Percentage of all such costs and Otsuka shall bear the remaining share of all such costs.

 ARTICLE 9 
 INTELLECTUAL PROPERTY 
 9.1 Development Intellectual Property.

 (a) Ownership. Otsuka shall own the entire right, title and interest in and to any and all (i) Know-How
discovered, developed, identified, made, conceived or reduced to practice by or on behalf of Otsuka or Acucela, solely or jointly, or its or their Affiliates or their respective employees, agents or contractors in the course of conducting
Development under this Agreement (collectively, “Developed Know-How”), and (ii) intellectual property rights in any of the Developed Know-How, including Licensed Patent Rights that claim or disclose any of the Developed
Know-How. 
 (b) Disclosure, Assignment. Acucela shall promptly disclose to Otsuka in writing the development, making,
conception or reduction to practice of any Developed Know-How, and Acucela does hereby expressly and irrevocably assign and convey, and shall cause its Affiliates and contractors (in accordance with Section 4.5) to so assign and convey, to
Otsuka, without compensation, all right, title and interest in and to any such Developed Know-How. The assignment and transfer of all such Developed Know-How to Otsuka shall occur instantly and automatically upon the development, making, conception
or reduction to practice, as the case may be, of such Developed Know-How and shall not require any further deeds or documents to be exchanged between the Parties; provided, however, that upon the request of Otsuka, Acucela shall execute and
deliver (and have executed and delivered by its contractors, employees and agents) any and all declarations, applications, assignments and other documents, and provide all 

  
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other assistance, that Otsuka reasonably determines may be necessary or desirable to apply for, obtain or perfect Otsuka’s ownership of all right, title and interest in Developed Know-How.
Acucela shall enter an appropriate agreement with each of its employees who is involved in Development, pursuant to which such employee shall agree to (i) assign to Acucela ownership of all Developed Know-How and (ii) not use (other than
in connection with conducting Development) or disclose to any Third Party any Developed Know-How. 
 (c) License to
Acucela. To the extent that Otsuka Controls after the Effective Date any Patent Rights that claim any Developed Know-How that is developed, made conceived or reduced to practice solely by Acucela or any of its Affiliate’s employees and/or
contractors or jointly by both Acucela or any of its Affiliate’s employees and/or contractors and Otsuka or any of its Affiliate’s employees and/or contractors (“Developed Patent Rights”), Otsuka hereby grants to Acucela,
subject to the terms and conditions of this Agreement, including Acucela’s exclusivity covenant set forth in Section 3.6, a worldwide, non-exclusive, perpetual, irrevocable, fully paid up, royalty-free, sub-licensable license under such
Developed Patent Rights to make, have made, use, sell, offer to sell and import any pharmaceutical product. 
 9.2 Third
Party IP. Otsuka (and not Acucela) shall have responsibility and authority for, and shall bear all costs associated with, negotiating and executing any Third Party IP license or other acquisition agreement that the JDC, prior to Acucela’s
exercise of an Opt-In Right under Section 3.1, or the JCC, after Acucela’s exercise of an Opt-In Right under Section 3.1, determines is necessary or advisable in order to use, import or sell Licensed Product in the Field in the
Territory or in order to Manufacture Licensed Product for use, import or sale in the Field in the Territory; provided that Otsuka shall keep Acucela reasonably informed with respect to the negotiations and deal terms relating to such Third
Party IP license or acquisition agreement and shall consider any comments, recommendations or analysis of Acucela in good faith, taking into consideration Acucela’s interests relating to Commercialization. For the avoidance of doubt, although
Otsuka shall bear all costs associated with negotiating any Third Party IP license or other acquisition agreement, all Third Party IP Costs shall be Commercialization Costs and shall be shared by the Parties in accordance with Section 7.4(c)
(if and after Acucela exercises an Opt-In Right under Section 3.1). 
 9.3 Licensed Patent Rights. 

(a) Prosecution and Maintenance. Otsuka shall have the exclusive right and responsibility, at its sole discretion and cost, for
the prosecution and maintenance of all Licensed Patent Rights, including all Developed Patent Rights, subject to the following: 
 (i) With respect to Developed Patent Rights, Otsuka shall copy Acucela, or have Acucela copied, on all substantive (non-procedural) documents pertaining to the Developed Patent Rights, which are
received from or to be filed with the U.S. Patent and Trademark Office (“USPTO”), promptly following receipt from the patent office and within a reasonable time prior to filing with USPTO, as applicable, including copies of each
patent application, office action, substantive correspondence with USPTO officials, response to office action, declarations, information disclosure statements, requests for terminal disclaimer, requests for patent term extension and request for
reexamination relating to Developed Patent Rights. Consistent with the foregoing, Acucela shall have the right, at its sole expense, to comment on 

  
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the prosecution of Developed Patent Rights in the Territory and provide such comments to Otsuka’s patent counsel, and Otsuka shall consider all such comments in good faith. If Acucela fails
to provide its comments with respect to such prosecution by Otsuka of such patent application or patent within the Developed Patent Rights reasonably in advance of the deadline for filing or otherwise responding to the relevant matter in the USPTO,
Otsuka shall be free to act without consideration of Acucela’s comments. 
 (ii) With respect to all Licensed
Patent Rights other than Developed Patent Rights, Otsuka shall from time to time and, in any event, at least once per year, provide Acucela with updates of the filing, prosecution and maintenance status of such Licensed Patent Rights (other than
Developed Patent Rights) in the Territory and Otsuka shall also notify Acucela of any material event occurring in relation to the same as soon as practicable following the occurrence of such material event. 

(b) Abandonment. The terms of this Section 9.3(b) shall apply only if and after Acucela exercises an Opt-In Right under
Section 3.1. Otsuka will notify Acucela in the event it desires to abandon prosecution and/or maintenance of any Patent Right within the Licensed Patent Rights in the Territory after Acucela’s exercise of an Opt-In Right under
Section 3.1. Notification will be given within a reasonable period (i.e., with sufficient time for Acucela to take whatever action may be necessary) prior to the date on which such Licensed Patent Right will lapse, go abandoned (other than to
file a continuation application for the same subject matter) or otherwise diminish. Acucela will then have the right, exercisable upon written notice to Otsuka, to continue prosecution or maintenance of such Licensed Patent Right in the Territory,
at its own expense. If Acucela elects to continue prosecution or maintenance of any such Licensed Patent Right in the Territory, then at Acucela’s request, Otsuka shall execute such documents (or shall cause its Affiliates, as applicable, to
execute such documents) as are required to assign to Acucela, and enable Acucela to prosecute and maintain, such Licensed Patent Rights in the Territory; provided that, effective upon such assignment, Acucela hereby grants to Otsuka a
worldwide, non-exclusive, perpetual, irrevocable, fully paid up, royalty-free, sub-licensable license under such assigned Licensed Patent Rights for any purpose, including to research, develop, make, have made, use, sell, offer for sale, have sold
and import any service, composition, product or process. 
 (c) Definitions. For the purposes of this Section 9.3,
“prosecution and maintenance” (and the correlative terms “prosecute and maintain’ and “prosecuting and maintaining” shall mean, with respect to a Patent Right, the preparing, filing, prosecuting and
maintenance of such Patent Right, as well as re-examinations, reissues and requests for patent term extensions and the like with respect to such Patent Right, together with the conduct of interferences, the defense of oppositions and other similar
proceedings with respect to a Patent Right. 
 9.4 Infringement Claims Against the Parties. Prior to Acucela’s
exercise of an Opt-In Right under Section 3.1, Otsuka shall have the exclusive right and responsibility, at its sole discretion and sole expense, to defend claims of or allegations by any Third Party that any Development or Commercialization
infringes or may infringe such Third Party’s intellectual property rights; provided, however, that, promptly after becoming aware of any Third Party claim or allegation that any Development or Commercialization infringes or may infringe
such 

  
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Third Party’s intellectual property rights, the Party who first learns of such infringement shall notify the other Party in writing of such claim or allegation. The following terms of this
Section 9.4 shall apply only if and after Acucela exercises an Opt-In Right under Section 3.1. 
 (a)
Notification. Each Party shall promptly notify the other Party in writing of any allegation by a Third Party in the Territory that any Development or Commercialization activities conducted by the Parties in the Field in the Territory pursuant to
and in accordance with this Agreement infringe or may infringe the intellectual property rights of such Third Party (a “Third Party Infringement Claim”). 
 (b) Right to Defend. The Parties shall discuss which Party shall defend the Third Party Infringement Claim, and absent an agreement otherwise, Otsuka shall have the first right to control any
defense of such Third Party Infringement Claim by counsel of its own choice (and Acucela shall have the right, at its own expense, to be represented in such Third Party Infringement Claim by counsel of its own choice). If Otsuka does not undertake
in good faith the defense of any such Third Party Infringement Claim by the date ten (10) days before the time limit, if any, set forth in Applicable Laws for the filing of the initial response or defense to any such Third Party
Infringement Claim, or if Otsuka (having commenced such defense) subsequently does not continue to pursue and conduct such defense diligently, Acucela shall have the right, but not the obligation, to bring and control such defense by counsel of its
own choice. 
 (c) Settlement. The defending Party may enter into a settlement or compromise of any Third Party
Infringement Claim, provided that, if such settlement or compromise would admit liability on the part of the non-defending Party or any of its Affiliates or would reasonably be expected to materially adversely affect the non-defending Party
or its Affiliates, the defending Party shall not enter into such settlement or compromise without the prior written consent of the non-defending Party. 
 (d) Counterclaim. Notwithstanding the foregoing, Otsuka shall have the sole right to determine whether to assert any counterclaim under any Licensed Patent Rights and to control any such
counterclaim, and to control the defense of any matters involving the validity or enforceability of any Licensed Patent Rights, including the right to solely make all substantive and procedural decisions relating to any such counterclaim or defense.
Otsuka may settle, compromise or dispose of any such counterclaim or defense in its discretion. 
 9.5 Enforcement of
Licensed Patent Rights in the Territory. Prior to Acucela’s exercise of an Opt-In Right under Section 3.1, Otsuka shall have the exclusive right and responsibility, at its sole discretion and cost, to enforce the Licensed Patent Rights
against infringement or suspected infringement by a Third Party; provided, however, that, promptly after becoming aware of any infringement or suspected infringement of any Licensed Patent Rights by any Third Party, the Party who first becomes aware
of such infringement or suspected infringement shall notify the other Party in writing of such known or suspected infringement. The following terms of this Section 9.5 shall apply only if and after Acucela exercises an Opt-In Right under
Section 3.1. 

  
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 (a) Notice. To the extent either Party becomes aware or suspects that any Licensed
Patent Rights are being infringed by a Third Party, and such suspected infringement does or is reasonably likely to materially adversely affect the Development or Commercialization of a Licensed Product in the Field in the Territory (the
“Possible Infringement”), the Party first having knowledge of such Possible Infringement shall promptly notify the other Party in writing. The notice shall set forth the facts of such Possible Infringement in reasonable detail. The
Parties shall thereafter consult and cooperate fully to determine a course of action, including the commencement of legal action by either or both Parties, to terminate any such Possible Infringement in accordance with the terms set forth below.

 (b) Right to Enforce. Otsuka shall have the first right, but not the obligation, to enforce the Licensed Patent Rights
against such Possible Infringement, including instituting, prosecuting and controlling any action or proceeding (including any related declaratory action) or taking other action that it believes is reasonably required to protect (i.e., prevent or
terminate the Possible Infringement) or otherwise enforce the Licensed Patent Rights in the Field in the Territory. If Otsuka does not institute an action or proceeding or take other action to prevent or terminate the Possible Infringement within
ninety (90) days following receipt of notice of the Possible Infringement pursuant to Section 9.5(a), and if Otsuka does not provide Acucela reason(s) why such action has not been taken within such 90-day period (consistent with
Otsuka’s patent strategy), then Acucela shall have the right to institute an action or proceeding or take other appropriate action that it believes is reasonably required to prevent or terminate the Possible Infringement. Notwithstanding the
foregoing, if during the course of any infringement action prosecuted under this Section 9.5, the Third Party by defense, counterclaim or counter-suit attacks the validity or enforceability of any of the Licensed Patent Rights, Otsuka shall
have the sole right to control all substantive and procedural activities and decisions relating to opposing such attack. 

(c) Conduct of Certain Actions. At the request of the Party initiating an enforcement action under this Section 9.5, the
non-initiating Party agrees to be joined as a party to the suit if necessary for the initiating Party to bring or maintain the enforcement action hereunder, and to provide reasonable assistance in any such action. Neither Party may (without
obtaining the prior written consent of the other Party) settle any action or proceeding brought under this Section 9.5 in a manner that would reasonably be expected to materially adversely affect the other Party’s interest in the Licensed
Patent Rights, and, if Acucela is the Party initiating an enforcement action under this Section 9.5, Acucela shall not (without obtaining Otsuka’s prior written consent) take any action or agree to any settlement that would impose any
financial burden on Otsuka or admit invalidity or unenforceability of any Licensed Patent Rights. 
 9.6 Costs and
Recoveries. The terms of this Section 9.6 shall apply only if and after Acucela exercises an Opt-In Right under Section 3.1. Each Party shall bear its own internal costs and expenses of any action under Sections 9.4 and 9.5. All
out-of-pocket external costs and expenses incurred in defending or bringing any action under Sections 9.4 and 9.5 (including outside counsel fees), all amounts payable by either Party as a judgment based on a Third Party Infringement Claim or in
settlement of such Third Party Infringement Claim under Section 9.4, and any recovery under any enforcement action initiated under Section 9.5 shall be shared by the Parties as follows: Acucela shall bear or share the Participation
Percentage of all such costs, payments or recoveries, and Otsuka shall bear or share the remainder of all such costs, payments or recoveries. 

  
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 9.7 Trademarks; Logos, Names. Otsuka (or its Affiliates or sublicensees) will be
responsible for, and shall have sole discretion in, selecting trademarks for use on or in connection with the Licensed Products and Otsuka (or its Affiliates or other sublicensees) will be responsible for registration of such trademarks. All right,
title and interest in trademarks used on or in connection with the Licensed Products, and the goodwill related thereto, shall be solely owned by Otsuka. Subject to Section 5.5, unless otherwise agreed by the JCC, the Otsuka trade names and
logos shall be displayed on all product packaging, labeling and other promotional materials relating to Licensed Products in the Field in the Territory. All right, title, and interest to a Party’s trade name, trademark and logo shall be owned
by such Party and use thereof shall be consistent with the quality control standards and reasonable trademark usage practices as such Party applies to its own marks. Neither Party shall permit any other person or entity to use the other Party’s
trade name, trademark or logo, without the other Party’s prior written consent except as expressly provided in this Agreement. 
 9.8 Copyrights. Otsuka shall have exclusive ownership in and to the copyrights in all Licensed Product labeling and all promotional materials pertaining to Licensed Products (the “Copyrighted
Works”), and Acucela agrees to execute documentation necessary to effect such ownership. To the extent such labeling materials include or incorporate original works of authorship created or Controlled by Acucela or its Affiliate prior to the
Effective Date or otherwise not in connection with a Licensed Product, Acucela grants to Otsuka a license to use, reproduce, modify and distribute the pre-existing works only in connection with Licensed Products in the Field. Otsuka shall have the
sole right, but not the obligation, to enforce and defend, including but not limited to registering with the United States Copyright Office, its interest in the Copyrighted Works. Effective only if and after Acucela exercises an Opt-In Right under
Section 3.1, Otsuka grants to Acucela a license to use, reproduce and distribute in the Field in the Territory the Copyrighted Works and any original works of authorship created or Controlled by Otsuka or its Affiliates incorporated or included
in the Copyrighted Works but only to the extent permitted by the Co-Promotion Agreement. 
 ARTICLE 10 

REPRESENTATIONS, WARRANTIES AND COVENANTS 
 10.1 Mutual Representations, Warranties and Covenants. 
 (a) Mutual
Authority. Each Party each represents and warrants to the other Party as of the Effective Date that: (a) it has the authority and right to enter into and perform this Agreement; (b) this Agreement is a legal and valid obligation
binding upon it and is enforceable in accordance with its terms, subject to applicable limitations on such enforcement based on bankruptcy laws and other debtors’ rights; and (c) its execution, delivery and performance of this Agreement
will not conflict in any material fashion with the terms of any other agreement or instrument to which it is or becomes a party or by which it is or becomes bound, nor violate any law or regulation of any court, governmental body or administrative
or other agency having authority over it. 

  
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 (b) Debarment. Each Party represents and warrants to the other Party as of the
Effective Date that such Party has not been debarred and is not subject to debarment and neither it nor any of its Affiliates have used or will use in any capacity, in connection with the Development, Manufacturing or Commercialization of Licensed
Products, any person or entity who has been debarred pursuant to Section 306 of the United States Federal Food, Drug and Cosmetic Act, or who is subject of a conviction described in such Section 306. Further, such Party shall inform the
other Party in writing immediately if it or any person or entity who is performing services hereunder is debarred or is the subject of a conviction described in such Section 306, or if any action, suit, claim, investigation or legal
administrative proceeding is pending or, to such Party’s knowledge, is threatened, relating to the debarment of such Party, its Affiliates or any person or entity used in any capacity by such Party or its Affiliates in connection with the
Development, Manufacturing or Commercialization of Licensed Products. 
 (c) Third Party Rights. Each Party represents
and warrants to the other Party that, to its Knowledge as of the Effective Date, the performance of its obligations under this Agreement will not in itself constitute a violation of a contractual or fiduciary obligation owed to any Third Party
(including, misappropriation of trade secrets). 
 (d) Notice of Infringement or Misappropriation. Each Party represents
and warrants to the other Party that, as of the Effective Date, neither it nor any of its Affiliates has received notice of infringement or misappropriation of any alleged rights asserted by any Third Party in relation to any technology to be used
in connection with performance of this Agreement. 
 (e) No Actions. Each Party represents and warrants to the other
Party that, as of the Effective Date, there are no existing actions, suits or proceedings against it or its Affiliates, and neither it nor its Affiliate has received any written claim or demand from a Third Party, that individually or together with
any other, does or could have a material adverse effect on its ability to perform its obligations under this Agreement, or, with respect to Otsuka, challenges Otsuka’s or its Affiliate’s rights with respect to the Licensed IP or the
Licensed Compound or Licensed Product as they exist as of the Effective Date (including any invitation to license or other notice of Patent Rights relevant to the Licensed Compound). 

(f) Compliance with Laws. Each Party shall conduct, and shall cause its Affiliates, licensees, contractors and consultants to
conduct, all of its activities contemplated under this Agreement in accordance with all Applicable Laws in the Territory. 

10.2 Additional Otsuka Representations, Warranties and Covenants. Otsuka represents, warrants and covenants to Acucela that as of
the Effective Date: 
 (a) Neither Otsuka nor any Affiliate is developing, alone or with any Third Party, any adenosine
A2a receptor agonist in pre-clinical or later than preclinical stage development, other than the Licensed Compound. 
 (b)
Otsuka Controls all right, title and interest in and to the Licensed IP existing as of the Effective Date, and Otsuka has the right to grant to Acucela all of the licenses and other rights with respect to the Licensed IP granted to Acucela under
this Agreement; Neither Otsuka nor any of its Affiliates has, or will, enter into any agreement or grant any Third 

  
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Party any rights with respect to a Licensed Product or the Licensed IP that are inconsistent with the rights granted to Acucela under this Agreement or which would limit or encumber Otsuka’s
ability to perform all of the obligations undertaken by Otsuka hereunder or limit or encumber Acucela’s ability to exercise the rights and licenses granted to Acucela under this Agreement; 

(c) To the Knowledge of Otsuka, there are no Patent Rights Controlled by Otsuka not within the Licensed IP that claim the Licensed
Compound or a product containing the Licensed Compound as a composition of matter, or claim a method of use of the Licensed Compound or a product containing the Licensed Compound in the Field. To Otsuka’s Knowledge, none of the Licensed Patent
Rights existing as of the Effective Date are invalid or unenforceable, all fees required to be paid to applicable governmental patent offices in the Territory as of the Effective Date in order to prosecute or maintain such Licensed Patent Rights
have been paid on or before the due date for payment, and all such Licensed Patent Rights have been prosecuted and maintained in a manner consistent with standard practice in the Territory; 

(d) Exhibit A contains a full and complete list of Patent Rights that are Controlled by Otsuka or its Affiliates as of the
Effective Date that: (a) claim the Licensed Compound or a product containing the Licensed Compound as a composition of matter, or claim a method of use of the Licensed Compound or a product containing the Licensed Compound and, (b) to the
Knowledge of Otsuka, are necessary or reasonably useful for Acucela to exercise the rights licensed to it under this Agreement or to perform its obligations under this Agreement; and 

(e) To the Knowledge of Otsuka, the research, development, manufacture, sale, offer for sale, import or export of the Licensed
Compound, or any product incorporating the Licensed Compound, as these exist as of the Effective Date, do not infringe or misappropriate a claim of the Patent Rights or any other intellectual property rights of any Third Party in the Field in the
Territory. 
 10.3 Knowledge Definition. For purposes of this Article 10, the term “Knowledge” means,
with respect to a particular fact or other matter, the actual knowledge of (a) Otsuka’s Director of Intellectual Property Department (when used in the context of Otsuka’s Knowledge) or (b) Dr. Kubota (when used in the
context of Acucela’s Knowledge) in either case as of the Effective Date, or if any of such individuals could be expected to discover or otherwise become aware of such fact or other matter, after reasonable investigation in the ordinary course
of such individual’s employment. 
 10.4 Disclaimer. EXCEPT AS SET FORTH IN THIS ARTICLE 10, ACUCELA AND OTSUKA
EXPRESSLY DISCLAIM ANY OTHER WARRANTIES OR CONDITIONS, EXPRESS, IMPLIED, STATUTORY OR OTHERWISE, WITH RESPECT TO THE PATENT RIGHTS OR KNOW-HOW OR THE SUBJECT MATTER OF THIS AGREEMENT (INCLUDING WITH RESPECT TO THE LICENSED COMPOUND AND LICENSED
PRODUCTS AND ANY RESEARCH AND DEVELOPMENT ACTIVITIES RELATING THERETO), INCLUDING ANY IMPLIED WARRANTIES OF MERCHANTABILITY, NON-INFRINGEMENT OR FITNESS FOR A PARTICULAR PURPOSE. 

  
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 ARTICLE 11 
 INDEMNIFICATION AND INSURANCE  
 11.1 Indemnification of Otsuka.
Acucela shall indemnify and hold harmless each of Otsuka, its Affiliates and its and their directors, officers and employees (the “Otsuka Indemnitees”) from and against any and all liabilities, damages, penalties, fines, costs
and expenses (including reasonable attorneys’ fees and other expenses of litigation) (collectively, “Liabilities”) incurred or suffered by any Otsuka Indemnitee as result of Third Party claims, actions, suits or proceedings
(including claims, actions, suits or proceedings resulting from personal injury or death caused by administration of a Licensed Product to such Third Party or property or other damages caused by a Licensed Product) (each, a “Third Party
Claim”) arising from or occurring as a result of (a) any negligence or willful misconduct of Acucela, its Affiliates or their respective directors, officers, employees, contractors, consultants, agents, representatives or sublicensees
in the exercise of any rights or performance of any obligations under this Agreement, or (b) any breach by Acucela of any representations, warranties, obligations or covenants set forth in this Agreement, except to the extent such Third Party
Claims fall within the scope of Otsuka’s indemnification obligations set forth in Section 11.2. 
 11.2
Indemnification of Acucela. Otsuka shall indemnify and hold harmless each of Acucela, its Affiliates and its and their directors, officers and employees (the “Acucela Indemnitees”) from and against any and all Liabilities
incurred by any Acucela Indemnitee as a result of any Third Party Claims, arising from or occurring as a result of (a) if and to the extent that Acucela has not exercised its Opt-In Right under Section 3.1 or an opt-in right under
Section 3.2 or Section 3.3 with respect to (respectively) (i) Licensed Product for the Initial Indication in the Initial Formulation, or (ii) a particular Other Indication Product, or (iii) a particular New Formulation,
(each of (i), (ii) and (iii), a “Non-Opt-in Product”), the Development, Manufacture or Commercialization of such Non-Opt-in Product, (b) any negligence or willful misconduct of Otsuka, its Affiliates or their respective
directors, officers, employees, contractors, consultants, agents, representatives or licensees in the exercise of any rights or performance of any obligations under this Agreement, (c) any breach by Otsuka of any representations, warranties,
obligations or covenants set forth in this Agreement, or (d) any decision of the JDC or the JCC made through the exercise by Otsuka of its final decision-making authority over the objection of Acucela, except to the extent such Third Party
Claims fall within the scope of Acucela’s indemnification obligations set forth in Section 11.1. 
 11.3 Shared
Liabilities. The following shall apply if and after Acucela exercises its Opt-In Right under Section 3.1 (with respect to a Licensed Product for the Initial Indication in the Initial Formulation), or an opt-in right under Section 3.2
or Section 3.3 (with respect to an Other Indication Product or a New Formulation, respectively): to the extent a Third Party Claim arises from (a) any decision of the JDC or the JCC and such Third Party Claim is not otherwise subject to
indemnity under Section 11.1 or Section 11.2, or (b) any Intrinsic Defect, then, in either case (a) or (b), all Liabilities with respect to the Territory with respect to the Licensed Product for the Initial Indication in the
Initial Formulation for which Acucela has exercised its Opt-In Right under Section 3.1 and/or with respect to an Other Indication Product or New Formulation for which Acucela has exercised its opt-in right under Section 3.2 or
Section 3.3 (in each case, an “Opt-in Product”) that are incurred by the Parties as a result of such Third Party Claim shall be shared by the Parties as follows: Acucela shall bear the Participation Percentage

  
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of all such Liabilities, and Otsuka shall bear the remaining share of all such Liabilities. In the event that one or more Third Party Claims involves both (i) claims subject to this
Section 11.3 with respect to an Opt-in Product and (ii) claims that relate to a Non-Opt-in Product and/or claims that are otherwise not subject to this Section 11.3, then this Section 11.3 shall apply with respect to that portion
of the applicable Third Party Claim(s) or those Liabilities that are allocable to the Opt-in Product and shall not apply with respect to that portion of the applicable Third Party Claim(s) or those Liabilities that are allocable to the Non-Opt-in
Product. By way of illustration and not limitation, if Acucela exercises its Opt-In Right with respect to Licensed Product for the Initial Indication but does not exercise its right to opt-in with respect to Licensed Product for any Other
Indications, then a Third Party Claim alleging Intrinsic Defects of Licensed Product both with respect to the Initial Indication and with respect to Other Indications that distinguishes between the Initial Indication and Other Indications or that
otherwise differentiates and allocates Liabilities between the Initial Indication and Other Indications would be subject to this Section 11.3 to the extent such third Party Claim or Liabilities are attributable to the Licensed Product for the
Initial Indication (and would not be subject to this Section 11.3 to the extent such Third Party Claim or Liabilities are attributable to the Licensed Product for Other Indications). By way of further illustration and not limitation, if
(1) a Third Party Claim relates to both (x) one or more Opt-in Products and (y) one or more Non-Opt-in Products, (2) such Third Party Claim does not differentiate between claims related to the Opt-in Products and claims related
to the Non-Opt-in Products (such as, for example, a class action suit brought on behalf of a class of individuals who used the License Product, which class includes individuals who used the Licensed Product for the Initial Indication and also
individuals who used the Licensed Product for an Other Indication for which Acucela has not exercised its Opt-In Right), and (3) some or all the Liabilities with respect to such Third Party Claim are determined in a manner that does not
differentiate and allocate Liabilities between Opt-in Products and Non-Opt-in Products, then as between the Parties those Liabilities that are determined in a manner that does not differentiate and allocate Liabilities between Opt-in Products and
Non-Opt-in Products will be allocated between applicable Opt-in Products and Non-Opt-in Products based on the pro rata Net Sales of such Opt-in Products and Non-Opt-in Products, and the portion of such Liabilities that is allocated in this manner to
Opt-in Products (i.e., the percentage obtained by dividing Net Sales of Opt-in Products by the sum of Net Sales of Opt-in Products plus Net Sales of Non-Opt-in Products and multiplying such quotient by 100) would be subject to this
Section 11.3, and the portion of such Liabilities that is allocated in this manner to Non-Opt-in Products would not be subject to this Section 11.3. Unless the Parties mutually agree otherwise at the time, Otsuka shall have the right to
assume and conduct the defense of such Third Party Claim and, for purposes of Section 11.4, Otsuka shall be deemed the “Indemnifying Party” and Acucela shall be deemed the “Indemnified Party” with respect to such Third Party
Claim. 
 11.4 Indemnification Procedures. The Party claiming indemnity under this Article 11 (the “Indemnified
Party”) shall give written notice to the Party from whom indemnity is being sought (the “Indemnifying Party”) promptly after learning of a Third Party Claim. The Indemnified Party shall provide the Indemnifying Party with
reasonable assistance, at the Indemnifying Party’s expense, in connection with the defense of the Third Party Claim for which indemnity is being sought. The Indemnified Party may participate in and monitor such defense with counsel of its own
choosing at its sole expense; provided, however, the Indemnifying Party shall have the right to assume and conduct the defense of the Third Party Claim with counsel of its choice. The Indemnifying Party shall not settle any Third Party Claim
without the prior 

  
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written consent of the Indemnified Party, not to be unreasonably withheld, conditioned or delayed, unless the settlement involves only the payment of money by the Indemnifying Party. So long as
the Indemnifying Party is defending the Third Party Claim, the Indemnified Party shall not settle any such Third Party Claim without the prior written consent of the Indemnifying Party. If the Indemnifying Party does not assume and conduct the
defense of the Third Party Claim as provided above, (a) the Indemnified Party may defend against, and consent to the entry of any judgment or enter into any settlement with respect to the Claim in any manner the Indemnified Party may deem
reasonably appropriate (provided the Indemnified Party shall give written notice to the Indemnifying Party of any settlement thereof and shall not settle without the consent of the Indemnifying Party, not to be unreasonably withheld, conditioned or
delayed), and (b) the Indemnifying Party will remain responsible to indemnify the Indemnified Party as provided in this Article 11. 
 11.5 Insurance. Each Party shall procure and maintain insurance, including product liability insurance and clinical trials insurance, adequate to cover its obligations and performance of its
activities hereunder and consistent with normal business practices of prudent companies similarly situated, at all times during which any Licensed Product is being clinically tested in human subjects or commercially distributed or sold under this
Agreement; provided that Otsuka has the right to self-insure in part or in whole for any such coverage. It is understood that such insurance shall not be construed to create a limit of either Party’s liability with respect to its
indemnification obligations under this Article 11. Each Party shall provide the other with written evidence of such insurance upon request. Each Party shall provide the other with written notice at least thirty (30) days prior to the
cancellation, non renewal or material change in such insurance or self-insurance which materially adversely affects the rights of the other Party hereunder. 
 ARTICLE 12 
 CONFIDENTIALITY 

12.1 Confidentiality; Exceptions. Except to the extent expressly authorized by this Agreement or otherwise agreed in writing, the
receiving Party shall keep confidential and shall not publish or otherwise disclose or use for any purpose other than as provided for in this Agreement any information or other confidential or proprietary materials furnished to it by the other Party
pursuant to this Agreement (collectively, “Confidential Information”), except to the extent that it can be established by the receiving Party that such information or material: 

(i) was in the lawful knowledge and possession of the receiving Party prior to the time it was disclosed to, or learned by, the
receiving Party, or was otherwise developed independently by the receiving Party, as evidenced by written records kept in the ordinary course of business, or other documentary proof of actual use by the receiving Party; 

(ii) was generally available to the public or otherwise part of the public domain at the time of its disclosure to the receiving
Party; 
 (iii) became generally available to the public or otherwise part of the public domain after its disclosure to
the receiving Party other than through any act or omission of the receiving Party in breach of this Agreement; or 
 (iv)
was disclosed to the receiving Party, other than under an obligation of confidentiality, by a Third Party who had no obligation to the disclosing Party not to disclose such information to others. 

  
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 For the avoidance of doubt, all data, information and other documentation of Otsuka and its Affiliates
relating to Manufacture of Licensed Compound or Licensed Product, including any Drug Master File and CMC documentation, shall be deemed the Confidential Information of Otsuka. 
 12.2 Authorized Disclosure. Except as otherwise expressly provided in this Agreement, each Party may use and disclose Confidential Information of the other Party as follows: (a) under
appropriate confidentiality provisions substantially equivalent to those in this Agreement, in connection with the performance of its obligations or exercise of rights granted or reserved in this Agreement (including the right to grant sublicenses
permitted hereunder), (b) to the extent such disclosure is reasonably necessary in filing or prosecuting patent, copyright and trademark applications or registrations, complying with the terms of licenses from Third Parties, prosecuting or
defending litigation in connection with this Agreement, complying with applicable governmental regulations, obtaining Regulatory Approvals, conducting preclinical or clinical trials or marketing Licensed Products, or otherwise required by Applicable
Laws (including securities laws), provided, however, that if a Party is required by Applicable Laws to make any such disclosure of the other Party’s Confidential Information it will, except where impracticable for necessary disclosures
(for example, in the event of medical emergency), give reasonable advance notice to the other Party of such disclosure requirement and, except to the extent inappropriate in the case of patent applications, use its reasonable efforts to secure, or
cooperate with the other Party in seeking to secure, confidential treatment of such Confidential Information required to be disclosed, (c) in communication with investors, consultants, advisors or others on a need to know basis, in each case
under appropriate confidentiality provisions substantially equivalent to those of this Agreement, or (d) to the extent mutually agreed to by the Parties in writing. 
 12.3 Termination of Prior Confidentiality Agreement. This Agreement supersedes the Confidentiality Agreement between the Parties dated December 4, 2009, including all modifications thereto.
All information exchanged between the Parties under such Confidentiality Agreement shall be deemed Confidential Information under this Agreement and shall be subject to the terms of this Article 12. 

12.4 Disclosure of Terms. Each Party agrees not to disclose to any Third Party the terms of this Agreement without the prior
written consent of the other Party, except as permitted for disclosures of Confidential Information pursuant to Section 12.2. 
 12.5 Publications. Except as required by Applicable Laws, Acucela shall not publish or present or otherwise disclose any information about Development, including the status, progress or results of
Development work conducted by Acucela or any permitted subcontractor, without the prior written approval, following discussion, of the JDC or the JCC. 
 12.6 Conflict of Interest. The Parties recognize that any pharmaceutical or biotechnology company other than Otsuka may, by virtue of its equity investment in Acucela or

  
 67 

 
its financial or other contribution to Acucela, have the right to appoint one or more directors or officers of Acucela in the future. In such event, if one or more directors or officers of
Acucela are appointed by any such pharmaceutical or biotechnology company, then Acucela shall strictly prevent any such appointed directors or officers from accessing any Confidential Information of Otsuka or any data, information or materials
related to Licensed Compound, Licensed Product, New Compound, New Compound Product or the subject matter of this Agreement (subject to Section 12.4). 
 12.7 Press Releases and Announcements. Upon the execution of this Agreement, the Parties shall issue a joint press release announcing the execution of this Agreement in the form of Exhibit
D. No other public statement or disclosure concerning the existence or terms of this Agreement shall be made, either directly or indirectly, by either Party, without first obtaining the written approval of the other Party. Once any public
statement or disclosure has been approved in accordance with this Section 12.7, then either Party may appropriately communicate information contained in such permitted statement or disclosure. 

ARTICLE 13 

TERM AND TERMINATION 
 13.1 Term. The term of this Agreement shall begin on the Effective Date and shall continue, on a formulation-by-formulation basis, with respect to each formulation of Licensed Product, until the
Generic Competition Commencement Date for the applicable formulation, unless and until earlier terminated as permitted under this Agreement. 
 13.2 Termination for Material Breach. In the event of a material breach of this Agreement, the non-breaching Party shall have the right to give written notice (the “Breach Notice”)
to the breaching Party, specifying the breach in reasonable detail. The allegedly breaching Party shall have ninety (90) days (or thirty (30) days, to the extent the breach relates to nonpayment) after receipt of the Breach Notice to cure
any such breach. If, at the end of such ninety (90) day (or thirty (30) day, to the extent the breach relates to nonpayment) period, the breach remains uncured, then the non-breaching Party shall have the right to terminate this Agreement
in its entirety, upon written notice to the breaching Party. The foregoing notwithstanding, solely after the exercise by Acucela of its Opt-In Right pursuant to Section 3.1, if the allegedly breaching Party disagrees that it is in material
breach, the Parties shall initiate dispute resolution pursuant to Section 14.2(b), whereupon the cure period shall be tolled until the dispute about whether the allegedly breaching Party is, in fact, in breach is resolved in accordance with
Section 14.2(b). 
 13.3 Termination for Insolvency. Either Party may terminate this Agreement in its entirety at
any time during the term of this Agreement by giving written notice to the other Party (i) if the other Party files in any court or agency pursuant to any statute or regulation of any state or country a petition in bankruptcy or insolvency or
for reorganization or for an arrangement or for the appointment of a receiver or trustee for the other Party or its assets, or (ii) if the other Party is served with an involuntary petition against it, filed in any insolvency proceeding and
such petition shall not be dismissed within ninety (90) days after the filing thereof, or (iii) if the other Party makes a general assignment for the benefit of creditors. 

  
 68 

 13.4 Other Termination. In addition to its termination rights pursuant to Sections
13.2 and 13.3, Otsuka (or, in the case of Section 13.4(b) and Section 13.4(f), Acucela) may terminate this Agreement in its entirety, without compensation or payment to the other Party of whatever nature as follows: 

(a) prior to Acucela’s exercise of an Opt-In Right under Section 3.1, Otsuka may terminate this Agreement if any
Development of the Licensed Product is significantly delayed by Acucela beyond the timeline for Development set forth in the Development Plan, provided that, Otsuka shall have ninety (90) days after such “significantly delayed”
Development (as defined in the next sentence) to exercise such termination right. For purposes of the foregoing, “significantly delayed by Acucela” means any Development work, task, deliverable or other action item is delayed by more than
* beyond the scheduled time for performance set forth in the Development Plan as a result of any act or omission of Acucela, including failure of Acucela to adequately supervise any CRO or other subcontractor engaged by Acucela to perform
Development work or failure of Acucela to use Commercially Reasonable Efforts to conduct any Development, but excluding Force Majeure Events, any delay caused in whole or in part by acts or omissions of Otsuka or any Affiliate, contractor or other
Third Party licensee or sublicensee of Otsuka, or other circumstances beyond the reasonable control of Acucela (including FDA actions or delays); 
 (b) prior to Acucela’s exercise of an Opt-In Right under Section 3.1, either Party may terminate this Agreement if there is a failure in development of ACU-4429, provided that, the
terminating Party shall have * after such failure in development of ACU-4429 (as defined in the next sentence) to exercise such termination right. For purposes of the foregoing, “failure in development of ACU-4429” means that the joint
development committee established under the 4429 Agreement has determined that development of ACU-4429 has failed, including for scientific or regulatory reasons; provided, that even if such joint development committee has not determined that
development of ACU-4429 has failed, “failure in development of ACU-4429” for purposes of this Section 13.4(b) shall be deemed to occur upon termination by Otsuka (prior to expiration) of the 4429 Agreement for any reason; 

(c) Otsuka may terminate this Agreement pursuant to Section 3.1(a)(ii) (Failure of Acucela to exercise * Opt-In Right after
Qualified IPO); 
 (d) Otsuka may terminate this Agreement pursuant to Section 4.7 (Loss of Key Member); 

(e) Otsuka may terminate this Agreement after a Change of Control has occurred, provided that, Otsuka shall have * after
Acucela has provided Otsuka with written notice of the Change of Control to exercise such termination right; and 
 (f)
Prior to Acucela’s exercise of an Opt-In Right under Section 3.1, either Party may terminate this Agreement if, for a period of *, there has been no Development activity and no payments made by Otsuka for Development under this
Agreement, provided that the terminating Party shall have * after the expiration of such * period to exercise such termination right. 

  

	*	Confidential Treatment Requested. 

  
 69 

 13.5 Other Termination by Acucela. At any time after Acucela exercises an Opt-In
Right under Section 3.1, Acucela may opt-out of its co-Development and Co-Promotion obligations for reasonable business reasons. To exercise such opt-out right, Acucela shall notify Otsuka in writing (providing a summary of the reasonable
business reasons) at least * days before the beginning of the next calendar year. In case of such opt-out by Acucela, this Agreement shall terminate in its entirety as of the beginning of such next calendar year. 

13.6 Automatic Termination. This Agreement shall automatically terminate in its entirety pursuant to Section 3.1(d) (Failure
of Acucela to exercise either Opt-In Right). 
 13.7 Mutual Agreement. The Parties may mutually agree in writing to
terminate this Agreement in its entirety for any reason; provided that if one Party proposes to mutually terminate this Agreement for scientific reasons and the other Party, after good faith discussions for a reasonable period of time, does
not agree to so mutually terminate this Agreement, the disagreement over whether to terminate this Agreement for scientific reasons shall be resolved as an Expert Matter in accordance with Section 14.2(a). 

13.8 Effects of Termination. 
 (a) Termination During Development. 
 (i) If this Agreement is
terminated during Development by Otsuka pursuant to Section 13.4(c), Otsuka shall have the option to negotiate to engage Acucela to continue Development pursuant to a separate services agreement. If Otsuka elects such option, the Parties shall
negotiate in good faith such a separate services agreement, pursuant to which, if entered into by the Parties, Acucela shall continue to conduct Development and Otsuka shall compensate Acucela for its costs incurred in conducting such Development,
plus a mark-up as mutually agreed by the Parties in such separate services agreement. 
 (ii) If this Agreement is
terminated during Development by Otsuka pursuant to Section 13.4(c) and Otsuka does not elect to engage Acucela to continue to conduct Development pursuant to a separate services agreement or if the Parties fail to enter into such a separate
services agreement after good faith negotiations, or if this Agreement is terminated during Development for any other reason under this Article 13, Acucela shall cooperate with reasonable requests by Otsuka to achieve, as promptly as
reasonably practicable after notice of termination and for a period of * thereafter, (the “Wind-Down Period”), a smooth and orderly transition to Otsuka or its designee of the Development in the Field in the Territory, including by
making its personnel and other resources reasonably available to Otsuka during the Wind-Down Period; provided, however, that if at the time of any notice of termination of this Agreement there is any ongoing clinical trial of Licensed
Product, then such termination shall become effective only after completion of such clinical trial and submission to Otsuka of the final study report for such clinical trial. If Acucela has entered into agreements with Third Parties (including CROs)
or vendors that are necessary or useful for Otsuka or its designee to take over responsibility for Development in the Field in the Territory, then Acucela shall, to the extent reasonably possible and as requested in writing by Otsuka, assign all
such Third Party agreements to Otsuka or its designee, or otherwise cooperate to make such arrangements available to Otsuka or its designee for purposes of Development. Without limiting the foregoing,

  

	*	Confidential Treatment Requested. 

  
 70 

 
during the Wind-Down Period, (i) the licenses to Acucela under Article 6 shall, to the extent they were in effect prior to notice of termination, continue in effect except that such licenses
shall be non-exclusive, and (ii) Development Costs, if any, that are incurred by either Party shall continue to be funded by Otsuka in accordance with the terms of this Agreement. 

(b) Other Effects of Termination. Upon termination or expiration of this Agreement for any reason: 

(i) Except as set forth in Section 13.8(a)(ii), all licenses granted by Otsuka to Acucela under Article 6 shall expire (or
never become effective, as the case may be). Any sublicense agreement entered into by Acucela with any permitted sublicensee shall, at the request and in the discretion of Otsuka, be assigned to Otsuka to the extent permitted. In the event that such
assignment is not requested by Otsuka or is not permitted or not approved by such permitted sublicensee, then unless Otsuka and such sublicensee enter into a direct relationship, the rights of such sublicensee with respect to Licensed Products shall
terminate upon termination of Acucela’s underlying license. 
 (ii) If Acucela has entered into contracts with
Third Parties (including contract sales organizations) or vendors that are necessary or useful for Otsuka or its designee to take over responsibility with respect to Licensed Products in the Territory, then Acucela shall, to the extent permitted by
such Third Party agreements and requested in writing by Otsuka, assign all of the relevant Third Party agreements to Otsuka or its designee, or otherwise cooperate to make such arrangements available to Otsuka or its designee for purposes of taking
over responsibility with respect to the Licensed Products in the Territory. 
 (iii) Acucela shall disclose to Otsuka
(to the extent Acucela has not already disclosed to Otsuka) all Developed Know-How (including all clinical data) in Acucela’s or its Affiliates’ possession or Control. Such disclosure shall be in electronic form to the extent available
and, if reasonably necessary in connection with Otsuka’s further Development, Manufacture or Commercialization of the Licensed Compound or Licensed Products, shall include original hardcopies or duplicate copies thereof to the extent available.

 (iv) Each Party shall use reasonable efforts promptly to return (or destroy and provide written certification
thereof) to the other Party all Confidential Information received from the other Party, including any copies thereof (except copies retained solely for legal archival purposes). 

(v) Acucela shall have no obligation to share Development Costs and/or Commercialization Costs that are incurred with respect to
any Licensed Product or Other Indication Product after the effective date of such termination or expiration. 
 (vi) If,
after Acucela exercises an Opt-In Right under Section 3.1, this Agreement is terminated (1) by Otsuka pursuant to Section 13.4(d) due to the death or disability of Dr. Kubota or (2) by Acucela pursuant to Section 13.2
(following a determination pursuant to Section 14.2(b) of Otsuka’s material breach and failure to cure, if disputed by Otsuka), then, within * of the effective date of such termination, Otsuka shall pay a termination fee to Acucela equal
to the sum of (A) the amount of the Opt-In Fee actually paid by Acucela pursuant to 

  

	*	Confidential Treatment Requested. 

  
 71 

 
Section 7.1 prior to the date of termination, (B) the amount of all Development Milestone Payments (if any) actually paid by Acucela pursuant to Section 7.2 prior to the date of
termination, and (C) the amount of all documented out-of-pocket Development Costs (if any) actually incurred by Acucela in the conduct of Development prior to the date of termination. 

(vii) Except as set forth in this Section 13.8 and in Section 13.9 and Section 13.10, neither Party shall have any
further rights or obligations under this Agreement. 
 13.9 Accrued Obligations. Expiration or termination of this
Agreement for any reason (i) shall not release either Party from any obligation or liability which, at the time of such expiration or termination, has already accrued to the other Party or which is attributable to a period prior to such
expiration or termination, and (ii) shall not preclude either Party from pursuing all rights and remedies it may have hereunder or at law or in equity with respect to any breach of this Agreement nor prejudice either Party’s right to
obtain performance of any obligation. 
 13.10 Survival. The following Sections and Articles of this Agreement shall
survive expiration or termination of this Agreement for any reason: Section 4.6(b) (for a period of 5 years after preparation of the applicable Development documentation); Section 7.8; Section 9.1; Section 9.3(b) (solely with
respect to the license set forth therein, if applicable); Section 9.8; Section 13.8; Section 13.9; Section 13.10; Section 14.1; Section 14.2; Section 14.3; Section 14.9, 14.10; Article 11; Article 12; and
Article 1 (to the extent defined terms are contained within the foregoing Sections and Articles). Except as otherwise provided in this Article 13, all rights and obligations of the Parties under this Agreement shall terminate upon expiration or
termination of this Agreement for any reason. 
 ARTICLE 14 

MISCELLANEOUS 
 14.1 Governing Law. This Agreement shall be governed by and interpreted under the laws of the State of New York, excluding its conflicts of laws principles. 

14.2 Dispute Resolution. 
 (a) Expert Matters; Expedited Arbitration. Any Expert Matter shall be first referred to the Parties’ Senior Executives prior to proceeding under the following provisions of this
Section 14.2(a). Such Senior Executives shall attempt to resolve such Expert Matter through good faith discussions. In the event that such Expert Matter is not resolved by such Senior Executives within thirty (30) days after referral to
such Senior Executives, such Expert Matter shall be resolved by expedited arbitration by a single Expert as follows: 
 (i)
Upon written request by either Party to the other Party, the Parties shall promptly negotiate in good faith to appoint an appropriate Expert. If the Parties are not able to agree upon an Expert within ten (10) days after the receipt by a
Party of the written request in the immediately preceding sentence, each Party shall select one (1) Expert within five (5) Business Days thereafter, and those two (2) Experts shall select a third Expert within ten (10) days
thereafter and such third Expert (selected by the first two Experts) shall be the designated Expert for resolution of the Expert Matter. The fees and costs of the Expert shall be borne equally (50-50) by Otsuka and Acucela. 

  
 72 

 (ii) Within fifteen (15) days after the designation of the Expert, the Parties
shall each simultaneously submit to the Expert and to one another a written statement of their respective positions on the Expert Matter in dispute and their respective proposed resolution thereof. Each Party shall have five (5) Business Days
from receipt of the other Party’s submission to submit a written response thereto, which shall include any scientific and technical information in support thereof. The Expert shall have the right to meet with the Parties, either alone or
together, as necessary to make a determination. 
 (iii) No later than forty-five (45) days after the designation
of the Expert, the Expert shall make a determination by selecting the resolution proposed by one of the Parties that as a whole is the most fair and reasonable to the Parties in light of the totality of the circumstances and the Expert shall provide
the Parties with a written statement setting forth the basis of the determination in connection therewith. The Expert shall not have authority to render any substantive decision other than to select the resolution proposed by Otsuka or Acucela. The
decision of the Expert shall be final and conclusive. 
 (b) Other Disputes. Except as otherwise expressly provided
herein (including under Sections 2.1(e), 2.2(e) and 14.2(a)), in the event of any controversy, claim or other dispute arising out of or relating to any provision of this Agreement or the interpretation, enforceability, performance, breach,
termination or validity hereof (a “Dispute”), such Dispute shall be first referred to the Parties’ Senior Executives prior to proceeding under the following provisions of this Section 14.2(b). A Dispute shall be referred
to such Senior Executives upon any Party providing the other Party with written notice that such Dispute exists, and such Senior Executives shall attempt to resolve such Dispute through good faith discussions. In the event that such Dispute is not
resolved within thirty (30) days of such other Party’s receipt of such written notice, such Dispute shall be finally and exclusively settled by binding arbitration administered by the American Arbitration Association in accordance with its
Commercial Rules. Arbitration proceedings shall be held in New York, New York, USA, unless the Parties mutually agree in writing upon a different location. Arbitration proceedings shall be conducted by a single, neutral arbitrator who shall be
experienced in the field of the dispute and shall have no ongoing business relationship with either Party. Such arbitrator shall be selected by mutual agreement of the Parties or, in the absence of such agreement, by the director of the New York
office of the American Arbitration Association. The arbitrator shall apply the governing law set forth in this Agreement. The arbitrator may grant legal, equitable and monetary relief consistent with the terms of this Agreement. The Parties shall
share equally (50-50) the administrative charges, arbitrators’ fees and related expenses of arbitration, but each Party shall pay its own attorney’s fees incurred in connection with such arbitration; provided however, if the
arbitrator specifically determines that one Party prevailed clearly and substantially over the other Party, then the arbitrator may require that the non-prevailing Party shall also pay the prevailing Party’s reasonable attorney’s fees and
expert witness costs and arbitration costs. The Parties shall instruct the arbitrator to: (i) conclude the arbitration as soon as practicable (and in any event within nine (9) months after the arbitration is first requested), and
(ii) deliver a written, reasoned opinion stating the arbitrator’s decision within thirty (30) days after the arbitration is completed. Judgment upon the award rendered by the arbitrator shall be binding, final and non-appealable

  
 73 

 
(absent manifest error) and may be entered and enforced in any court having jurisdiction thereof. Notwithstanding the above, to the fullest extent provided by law, either Party may bring an
action in any court of competent jurisdiction for injunctive relief (or any other provisional remedy) to protect a Party’s rights or enforce a Party’s obligations under this Agreement pending final resolution of any claims related thereto
in an arbitration proceeding as provided above. 
 14.3 Limitation of Liability. EXCEPT FOR AMOUNTS PAYABLE TO THIRD
PARTIES BY A PARTY FOR WHICH IT SEEKS REIMBURSEMENT OR INDEMNIFICATION FROM THE OTHER PARTY PURSUANT TO ARTICLE 11, AND EXCEPT FOR BREACH OF ARTICLE 12 HEREOF (CONFIDENTIALITY) OR SECTION 3.6 (EXCLUSIVITY), IN NO EVENT SHALL EITHER PARTY, ITS
DIRECTORS, OFFICERS, EMPLOYEES, AFFILIATES, SUBLICENSEES, SUBCONTRACTORS OR CONSULTANTS BE LIABLE TO THE OTHER PARTY FOR ANY INDIRECT, INCIDENTAL, SPECIAL, PUNITIVE, EXEMPLARY OR CONSEQUENTIAL DAMAGES, WHETHER BASED UPON A CLAIM OR ACTION OF
CONTRACT, WARRANTY, NEGLIGENCE, STRICT LIABILITY OR OTHER TORT, OR OTHERWISE, ARISING OUT OF THIS AGREEMENT, UNLESS SUCH DAMAGES ARE DUE TO THE GROSS NEGLIGENCE OR WILLFUL MISCONDUCT OF THE LIABLE PARTY. 

14.4 Assignment. This Agreement shall not be assignable by either Party to any Third Party hereto without the written consent of
the other Party hereto, except that (a) either Party may assign this Agreement without the other Party’s consent to an entity that acquires all or substantially all of the business or assets of the assigning Party relating to this
Agreement, whether by merger, asset sale or otherwise, provided that the acquirer assumes this Agreement in writing or by operation of law; and (b) either Party may assign this Agreement to an Affiliate upon written notice to the non-assigning
Party; provided that in the case of (b), (i) the assigning Party guarantees the performance of this Agreement by such Affiliate and (ii) if the non-assigning Party reasonably believes that assignment to such Affiliate would result in
adverse tax consequences to the non-assigning Party, such assignment shall not be made without the non-assigning Party’s prior written consent. Subject to the foregoing, this Agreement shall inure to the benefit of each Party, its successors
and permitted assigns. Any assignment of this Agreement in contravention of this Section 14.4 shall be null and void. 

14.5 Independent Contractors. The Parties are and shall at all times be independent contractors. In performing under this
Agreement, neither Party is an agent, employee, employer, joint venturer or partner of the other. Neither Party shall incur or hold itself out to Third Parties as having the authority to incur any expenses, liabilities or obligations on behalf of
the other Party. This Agreement is not a partnership agreement and nothing in this Agreement shall be construed to establish a relationship of co-partners or joint venturers between the Parties. 

14.6 Waiver. No waiver by a Party in any one or more instances shall be deemed to be a continuing waiver, a further waiver, a
waiver of any other provision of this Agreement or a waiver of this Agreement as a whole. No waiver of any right under this Agreement shall be effective unless it is documented in a writing signed by the Party providing the waiver. 

14.7 Force Majeure. A failure by a Party to perform any obligation under this Agreement that is prevented by an occurrence beyond
the reasonable control of the non-performing 

  
 74 

 
Party (and which did not occur as a result of its financial condition, negligence or fault), including acts of God, embargoes, fires, floods, explosions, riots, wars, civil disorders, terrorist
acts, rebellion or acts of sabotage (a “Force Majeure Event”), shall not constitute a breach of this Agreement so long as that Party notifies the other Party as soon as practicable and uses Commercially Reasonable Efforts to resume
performance as soon as possible. Neither Party shall be entitled to rely on a Force Majeure Event to relieve it from an obligation to pay money (including any interest for delayed payment) which would otherwise be due and payable under this
Agreement. 
 14.8 Severability. If any term of this Agreement is held invalid, illegal or unenforceable in any
jurisdiction, then, to the fullest extent permitted by Applicable Laws: (a) all other terms shall remain in full force and effect in such jurisdiction, (b) such invalidity, illegality or unenforceability shall not affect the validity,
legality or enforceability of such provision in any other jurisdiction and (c) the Parties shall negotiate in good faith such terms as may be necessary in order to correct any imbalance of rights and obligations that results from such
invalidity, illegality or unenforceability in the relevant jurisdiction. 
 14.9 Construction. Unless the context of this
Agreement clearly requires otherwise, (a) references to any gender include all genders, (b) “including” has the inclusive meaning frequently identified with the phrase “including but not limited to” or “including
without limitation,” (c) references to “hereunder” or “herein” relate to this Agreement and (d) the singular shall include the plural. Unless used in combination with the word “either,” the word
“or” is used throughout this Agreement in the inclusive sense (and/or). The section and other headings contained in this Agreement are for reference purposes only and shall not control or affect the construction of this Agreement or the
interpretation thereof in any respect. Section, subsection, and Exhibit references are to this Agreement unless otherwise specified. When used in this Agreement “Business Day” means a day other than a Saturday, Sunday or a day
that is a statutory holiday in Japan or a federal holiday in the United States. 
 14.10 Notices.
All notices that are required or permitted hereunder shall be in writing and shall be sufficient if personally delivered or sent by Federal Express or other international business delivery service. Any notices shall be deemed given upon the earlier
of the date when received at, or the third (3rd) day
after the date when sent by Federal Express or other international business delivery service to, the address set forth below, unless such address is changed by notice to the other Party: 
 If to Otsuka: 
 Otsuka Pharmaceutical Co., Ltd. 

Shinagawa Grand Central Tower 
 2-16-4 Konan, Monato-ku 
 Tokyo 108-8242, Japan 

Attention: General Manager, Division of Dermatologicals & Opthalmologicals, and 

Director, Legal Affairs Department 
 If to Acucela: 
 Acucela Inc 

1301, Second Ave 

Suite 1900 

Seattle, WA 98101-3805 
 Attention: Ryo Kubota, M.D., Ph.D. 

  
 75 

 14.11 Export Control. This Agreement is made subject to any restrictions concerning
the export of products or technical information from the United States of America or other countries which may be imposed upon or related to Acucela or Otsuka from time to time. Each Party agrees that it will not export, directly or indirectly, any
technical information acquired from the other Party under this Agreement or any products using such technical information to a location or in a manner that at the time of export requires an export license or other governmental approval, without
first obtaining the written consent to do so from the appropriate agency or other governmental entity. 
 14.12
Amendment. This Agreement may be amended or modified only by a writing signed by each of the Parties. 
 14.13 Entire
Agreement. This Agreement constitutes the entire understanding between the Parties as of the Effective Date with respect to the subject matter hereof and supersedes all related prior or contemporaneous oral communications, agreements or
discussions with respect to the subject matter hereof. 
 14.14 Execution in Counterparts; Facsimile Signatures. This
Agreement may be executed in two counterparts, each of which counterparts, when so executed and delivered, shall be deemed to be an original, and both of which counterparts, taken together, shall constitute one and the same instrument even if both
Parties have not executed the same counterpart. Signatures provided by facsimile or similar electronic transmission shall be deemed to be original signatures. 
 Signature Page Follows 

  
 76 

 Execution Copy 

In Witness Whereof, Acucela and Otsuka have executed this Development and Collaboration Agreement by their respective duly
authorized representatives as of the Effective Date. 
  

									
	Acucela Inc	 		 	Otsuka Pharmaceutical Co., Ltd.
					
	By:	 	  
	 		 	By:	 	  

					
	Name:	 	  
	 		 	Name:	 	  

					
	Title:	 	  
	 		 	Title:	 	  

 Execution Copy 
 Exhibit A 
 LICENSED PATENT RIGHTS 

Title: * 
  

											
	 Difference
	  	 Country
	  	 App. No.
	  	 App. Date
	  	 Registered No.
	  	 Status

	*	  	U.S.A.	  	*	  	*	  	*	  	*
	*	  	U.S.A.	  	*	  	*	  	*	  	*

  

	*	Confidential Treatment Requested. 

 Exhibit B 
 GENERAL DEVELOPMENT PLAN OUTLINE 
  

											
	  	  	 * Clinical Trial
	  	 * Clinical Trial
	  	 * Clinical Trial
(Pivotal 1)
	  	 * Clinical Trial
(Pivotal 2)
	  	 * Clinical Trial by
Adjunctive Use

	Region	  	US	  	US/Japan	  	US/EU/Japan	  	US/EU/Japan	  	US/EU/Japan
	Purpose	  	Safety, Efficacy, PK	  	Dose-Response	  	Safety, Efficacy	  	Safety, Efficacy	  	 Safety, Efficacy
 (adj. to
*)

	Design	  	*	  	*	  	*	  	*	  	*
	Comparator	  	*	  	*	  	*	  	*	  	*
	Treatment Duration	  	*	  	*	  	*	  	*	  	*
	 No. of Enrollment
 (No. of pts.
on OPA6566)
	  	*	  	*	  	*	  	*	  	*
	Total External Costs of Each Trial	  	*	  	*	  	*	  	*	  	*
	Total Annual FTEs to be provided by Acucela	  	*	  	*	  	*	  		  	

  

	*	Confidential Treatment Requested. 

 * 

  

	*	Confidential Treatment Requested. 

 Exhibit C 
 GENERAL COMMERCIALIZATION PLAN OUTLINE 
 * Clinical Trial and Post-Approval Studies Costs

  

											
	  	  	 * Clinical Trial 1
	  	 * Clinical Trial 2
	  	 Post-Approval

Study 1
	  	 Post-Approval

Study 2
	  	 Post-Approval

Study 3

	Total External Costs of Each Trial	  	*	  	*	  	*	  	*	  	*
	Total Annual FTEs to be provided by Acucela	  	*

 Promotional Activities 
  

																	
		  	*	  	*	  	*	  	*	  	*	  	*	  	*	  	*
	 Promotional Expenses

(Out-of-Pocket)
	  	*	  	*	  	*	  	*	  	*	  	*	  	*	  	*
	Annual Number of PDEs	  	*	  	*	  	*	  	*	  	*	  	*	  	*	  	*

  

	*	The costs of promotional samples are to be included in Promotional Expenses. 

	**	

	**	

	*	1 Primary Position Detail is calculated to be *. 1 Secondary Position Detail is calculated to be *. 

  

	*	Confidential Treatment Requested. 

 Exhibit D 
 PRESS RELEASE 

 AMENDMENT AGREEMENT 
 This AMENDMENT AGREEMENT (the “Amendment Agreement”) is made and entered into as of December 12, 2012 (the “Effective
Date”) by and between OTSUKA PHARMACEUTICAL CO., LTD., a Japanese corporation having its principal place of business at 2-16-4 Konan, Minato-ku, Tokyo 108-8241, Japan
(“Otsuka”) and ACUCELA INC., a Washington corporation having its principal place of business at 1301 Second Ave, Suite 1900, Seattle, Washington 98101-3805, USA (“Acucela”).
Otsuka and Acucela are individually referred to as a “Party” and collectively referred to as the “Parties”. 
 RECITALS 
 A. The Parties have entered into that certain CO-DEVELOPMENT AGREEMENT dated
September 4, 2008 relating to Rebamipide (“Co-Development Agreement”), that certain CO-DEVELOPMENT AND COMMERCIALIZATION AGREEMENT dated September 4, 2008 relating to ACU-4429 (“4429 Agreement”) and that
certain DEVELOPMENT AND COLLABORATION AGREEMENT dated September 15, 2010 relating to OPA-6566 (“6566 Agreement”). The Co-Development Agreement, the 4429 Agreement and the 6566 Agreement are collectively referred to as the
“Acucela Collaboration Agreements and individually referred to as “Acucela Collaboration Agreement.” 
 B. The
Parties desire to clarify development costs to be borne by the Parties under the Acucela Collaboration Agreements. 
 NOW, THEREFORE, the
Parties agree as follows: 
 1. Definitions. 
 (a) For the purposes of this Amendment Agreement, 
 “Direct FTE”
means FTEs of Acucela who directly conduct one or more Ongoing Collaborations; 
 “Indirect FTE” means FTEs of
Acucela who indirectly support performance of one or more Ongoing Collaborations; and 
 “Ongoing
Collaborations” means the ongoing three collaborations pursuant to the Acucela Collaboration Agreements, i.e., development of Rebamipide pursuant to the Co Development Agreement, development of ACU-4429 pursuant to the 4429 Agreement and
development of OPA-6566 pursuant to the 6566 Agreement. 
 (b) Capitalized terms used in this Amendment Agreement and not
otherwise defined herein shall have the meanings as set forth in each Acucela Collaboration Agreement. 

  
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 2. Indirect FTE. 
 (a) The rate for Indirect FTEs which shall commonly apply to each Acucela Collaboration Agreement (the “Indirect FTE Rate”) shall be (i) *, which amount shall be adjusted on * and upon
every anniversary thereafter by the percentage increase, if any, in the Consumer Price Index for Urban Consumers for the West Region, All Items, as published by the U.S. Department of Labor, Bureau of Statistics, for the period since the last
adjustment., plus (ii) a markup of * unless otherwise agreed by the Parties. The Parties agree to meet annually to review the markup percentage for appropriateness. 
 (b) The aggregate number of Indirect FTEs for all Ongoing Collaborations shall not exceed * per year. If any Ongoing Collaboration is completed, terminated or a new collaboration agreement is executed,
the Parties shall meet with a view to discussing any necessary adjustment of the foregoing cap. 
 (c) In calculating Indirect
FTEs, any person who indirectly supports performance of one or more Ongoing Collaborations shall be treated as one FTE. Acucela shall not be required to submit to Otsuka information regarding the number of hours spent by any person categorized into
Indirect FTEs. 
 (d) The Indirect FTEs shall not be calculated an Ongoing Collaboration-by-Ongoing Collaboration basis but
shall be calculated on an accumulated basis of all Ongoing Collaborations. 
 (e) The Indirect FTEs shall cover the costs
associated with the work of Acucela personnel who indirectly support performance of Ongoing Collaborations. Accordingly, Otsuka shall not be required to pay Acucela any additional costs for such personnel, unless otherwise agreed by the Parties.

 (f) Allocation of Indirect FTEs among the Ongoing Collaborations shall be determined in proportion to the number of Direct
FTEs actually spent for each Ongoing Collaboration. 
 3. Direct FTE and Indirect FTE. The Parties shall categorize each cost item into
Direct FTE or Indirect FTE through mutual consultation in good faith, which consultation shall take place when they discuss and agree upon the annual budget of development costs for the following year. If Acucela incurs any additional cost item
which is not included in the agreed-upon annual budget, the Parties shall meet with a view to discussing how to treat such additional cost item. For the avoidance of doubt, Direct FTEs shall be calculated in accordance with applicable
“FTE” and “FTE Rate” as such terms are defined in each Acucela Collaboration Agreement. 
 4. Confidentiality. The
existence or terms of this Amendment Agreement shall be deemed Confidential Information of the Parties under the Acucela Collaboration Agreements. 

  

	*	Confidential Treatment Requested. 

  
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 5. Representations and Warranties. Each Party hereby represents and warrants to the other that it has
the corporate power and authority to enter into this Amendment Agreement and this Amendment Agreement constitutes a legal, valid and binding obligation, enforceable against such party in accordance with its terms. 

6. No Other Change. Except as expressly set forth in this Amendment Agreement, all other terms of the Acucela Collaboration Agreements shall
remain in full force and effect and once this Amendment Agreement is executed by the Parties, all references in each Acucela Collaboration Agreement to “the Agreement” or “this Agreement,” as applicable, shall refer to the
Acucela Collaboration Agreement, as modified by this Amendment Agreement. 
 7. Effective Date. Except for Sections 1, 2 and 3 which
shall become effective on January 1, 2013, this Amendment Agreement shall become effective on the Effective Date. 
 8. Governing
Law. This Amendment Agreement shall be governed by and interpreted under the laws of the State of New York, excluding its conflicts of laws principles. 
 9. Successors and Assigns. This Amendment Agreement will apply to, be binding in all respects upon, and inure to the benefit of the successors and permitted assigns of the Parties. 

10. Counterparts. This Amendment Agreement may be executed in two counterparts, each of which counterparts, when so executed and delivered, shall
be deemed to be an original, and both of which counterparts, taken together, shall constitute one and the same instrument even if both Parties have not executed the same counterpart. Signatures provided by facsimile or similar electronic
transmission shall be deemed to be original signatures. 
 [Signature page follows] 

  
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 IN WITNESS WHEREOF, the Parties have caused this Amendment Agreement to be executed and delivered by
their respective duly authorized officers as of the Effective Date. 
  

									
	OTSUKA PHARMACEUTICAL CO., LTD.	 		 	ACUCELA INC.
					
	By:	 	 /s/ Yoshiko Wakana
	 		 	By:	 	 /s/ David L. Lowrance

					
	Name:	 	 Yoshiko Wakana
	 		 	Name:	 	 David L. Lowrance

					
	Title:	 	 Operating Officer
	 		 	Title:	 	 CFO

  
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