Document:

EX-10.11

 Exhibit 10.11 

EPIZYME, INC. 
 Executive
Severance and Change in Control Plan 
 (as amended February 25, 2016) 

Section I: Establishment and Purpose of Plan 
 Epizyme,
Inc. (the “Company”) hereby establishes an unfunded Executive Severance and Change in Control Plan (the “Plan”), which is intended to be a welfare benefit plan within the meaning of Section 3(1) of the Employee Retirement
Income Security Act of 1974, as amended (“ERISA”). The Plan is in effect for those Company executives and certain other employees designated as participants (the “Participants”) under the Plan by the Company’s Board of
Directors (the “Board”) or the Compensation Committee. This document is intended to serve as the plan document and the summary plan description of the Plan. 

Section II: Definitions 
 For purposes of this Plan: 

“Participant” means: 

(a) the Chief Executive Officer of the Company; (b) all C-level executives and Executive Vice Presidents of the Company (each, a
“Senior Executive”); (c) all Senior Vice Presidents of the Company; (d) all Vice Presidents of the Company and (e) such other employees who are designated by the Board or an authorized committee thereof to be Participants
for purposes of this Plan. 
 “Cause” means any of: 

(a) a Participant’s conviction of, or plea of guilty or nolo contendere to, any crime involving dishonesty or moral turpitude or any
felony; or b) a good faith finding by the Company that the Participant has (i) engaged in dishonesty, willful misconduct or gross negligence, (ii) breached or threatened to breach the terms of any restrictive covenants or confidentiality
agreement or any similar agreement with the Company, (iii) violated Company policies or procedures, and/or (iv) failed to perform his or her assigned duties to the Company’s satisfaction, following notice of such failure by the
Company and a period of 15 days to cure. 
 “Good Reason” means the occurrence, without the Participant’s prior written
consent, of any of the following events: 
 (i) a material reduction in the Participant’s authority, duties, or responsibilities;
(ii) the relocation of the principal place at which the Participant provides services to the Company by at least 30 miles and to a location such that his or her daily commuting distance is increased; or (iii) a material reduction of the
Participant’s base salary (other than in connection with, and in an amount substantially proportionate to, reductions made by the Company to the base salaries of other similarly-situated employees). 

No resignation will be treated as a resignation for Good Reason unless (x) the Participant has given written notice to the Company of his
or her intention to terminate his or her employment for Good Reason, describing the grounds for such action, no later than 90 days after the first 

  
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occurrence of such circumstances, (y) the Participant has provided the Company with at least 30 days in which to cure the circumstances, and (z) if the Company is not successful in
curing the circumstances, the Participant ends his or her employment within 30 days following the cure period in (y). 
 “Change in
Control” means any of the following: 
 (i) the acquisition by an individual, entity or group (within the meaning of
Section 13(d)(3) or 14(d)(2) of the Securities Exchange Act of 1934 (the “Exchange Act”) (a “Person”) of beneficial ownership of any capital stock of the Company if, after such acquisition, such Person beneficially owns
(within the meaning of Rule 13d-3 under the Exchange Act) more than 50% of either (x) the then-outstanding shares of common stock of the Company (the “Outstanding Company Common Stock”) or (y) the combined voting power of the
then-outstanding securities of the Company entitled to vote generally in the election of directors (the “Outstanding Company Voting Securities”); provided, however, that for purposes of this subsection any acquisition directly from the
Company will not be a Change in Control, nor will any acquisition by any individual, entity, or group pursuant to a Business Combination (as defined below) that complies with clause (ii) of this definition; 

(ii) the consummation of a merger, consolidation, reorganization, recapitalization or share exchange involving the Company or a sale or other
disposition of all or substantially all (i.e., in excess of 85%) of the assets of the Company (a “Business Combination”), unless, immediately following such Business Combination, all or substantially all of the individuals and entities who
were the beneficial owners of the Outstanding Company Common Stock and Outstanding Company Voting Securities immediately prior to such Business Combination beneficially own, directly or indirectly, more than 50% of the then-outstanding shares of
common stock and the combined voting power of the then-outstanding securities entitled to vote generally in the election of directors, respectively, of the resulting or acquiring corporation in such Business Combination (which shall include a
corporation that as a result of such transaction owns the Company or substantially all of the Company’s assets either directly or through one or more subsidiaries) in substantially the same proportions as their ownership of the Outstanding
Company Common Stock and Outstanding Company Voting Securities, respectively, immediately prior to such Business Combination; or 
 (iii) the
liquidation or dissolution of the Company; 
 provided that, where required to avoid additional taxation under Section 409A, the event
that occurs must also be a “change in the ownership or effective control of a corporation, or a change in the ownership of a substantial portion of the assets of a corporation” as defined in Treasury Reg. § 1.409A-3(i)(5). 
 Section III: Severance Benefits 

 

	 	a.	Severance Benefits Not Contingent on a Change in Control. If, prior to or more than twelve (12) months following a Change in Control, the Company terminates the Participant’s employment without
Cause or, if the Participant is the Chief Executive Officer of the Company, the Participant terminates his or her employment for Good Reason, and provided the Participant abides by the conditions set forth in Section IV below, the Participant shall
be eligible to receive the following severance benefits: 

 (i) the Company will pay to the Participant as severance pay an
aggregate amount equivalent to (a) in the case of the Chief Executive Officer, twelve months of his or her 

  
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then current base salary, less all applicable taxes and withholdings, (b) in the case of a Senior Executive level Participant, nine months of his or her then current base salary, less all
applicable taxes and withholdings, (c) in the case of a Senior Vice President level Participant, six months of his or her then current base salary, less all applicable taxes and withholdings or (d) in the case of a Vice President level
Participant, three months of his or her then current base salary, less all applicable taxes and withholdings. The foregoing severance pay will be paid ratably in installments in accordance with the Company’s normal payroll practices, but in no
event shall payment begin earlier than the eighth day after the Participant’s execution and timely return of the “Severance Agreement” (as defined in Section IV below); and 

(ii) should the Participant timely elect and be eligible to continue receiving group medical coverage pursuant to the “COBRA” law,
and so long as the Company can provide such benefit without violating the nondiscrimination requirements of applicable law, the Company will (a) in the case of the Chief Executive Officer, for a period of twelve months following his or her
termination, (b) in the case of a Senior Executive level Participant, for a period of nine months following his or her termination, (c) in the case of a Senior Vice President level Participant, for a period of six months following his or
her termination, or (d) in the case of a Vice President level Participant, for a period of three months following his or her termination continue to pay the share of the premium for such coverage that is paid by the Company for active and
similarly-situated employees who receive the same type of coverage. The remaining balance of any premium costs shall timely be paid by the Participant on a monthly basis for as long as, and to the extent that, such Participant remains eligible for
COBRA continuation. 
  

	 	b.	Severance Benefits Contingent on a Change in Control. If, within twelve (12) months following a Change in Control, a Participant’s employment is terminated by the Company without Cause or by the
Participant for Good Reason, and provided the Participant abides by the conditions set forth in Section IV below, the Participant shall be eligible to receive the following severance benefits: 

(i) the Company will pay to the Participant as severance pay an aggregate amount equivalent to (a) in the case of the Chief Executive
Officer, eighteen months of his or her then current base salary, less all applicable taxes and withholdings, (b) in the case of a Senior Executive level Participant, twelve months of his or her then current base salary, less all applicable
taxes and withholdings, (c) in the case of a Senior Vice President level Participant, nine months of his or her then current base salary, less all applicable taxes and withholdings, or (d) in the case of a Vice President level Participant,
six months of his or her then current base salary, less all applicable taxes and withholdings. The foregoing severance pay will be paid ratably in installments in accordance with the Company’s normal payroll practices, but in no event shall
payment begin earlier than the eighth day after the Participant’s execution and timely return of the Severance Agreement; 
 (ii) the
Company will pay to the Participant as a severance bonus an amount equivalent to (a) in the case of the Chief Executive Officer, 150% of his or her target bonus for the year in which his or her employment is terminated, less all applicable
taxes and withholdings, (b) in the case of a Senior Executive level Participant, 100% of his or her target bonus for the year in which his or her employment is terminated, less all applicable taxes and withholdings, (c) in the case of a
Senior Vice President level Participant, 75% of his or her target bonus for the year in which his or her employment is terminated, less all 

  
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applicable taxes and withholdings, or (d) in the case of a Vice President level Participant, 50% of his or her target bonus for the year in which his or her employment is terminated, less
all applicable taxes and withholdings. The foregoing severance bonus will be paid in lieu of any other bonus the Participant may have been eligible to receive with respect to the year in which his or her termination occurs, and shall be paid in one
lump sum at such time as the last installment of severance pay is made; provided, however, that to the extent necessary to comply with Section 409A for a Participant who had an alternate severance arrangement in place prior to March 22,
2013, the foregoing severance bonus shall be paid to the Participant at such time as is required by the provisions of Section 409A; 

(iii) should the Participant timely elect and be eligible to continue receiving group medical coverage pursuant to the “COBRA” law,
and so long as the Company can provide such benefit without violating the nondiscrimination requirements of applicable law, the Company will (a) in the case of the Chief Executive Officer, for a period of eighteen months following his or her
termination, (b) in the case of a Senior Executive level Participant, for a period of twelve months following his or her termination, (c) in the case of a Senior Vice President level Participant, for a period of nine months following his
or her termination, or (d) in the case of a Vice President level Participant, for a period of six months following his or her termination continue to pay the share of the premium for such coverage that is paid by the Company for active and
similarly-situated employees who receive the same type of coverage. The remaining balance of any premium costs shall timely be paid by the Participant on a monthly basis for as long as, and to the extent that, such Participant remains eligible for
COBRA continuation; and 
 (iv) any unvested stock options or restricted stock unit awards (or, in the case of restricted stock awards, any
such awards that remain subject to repurchase by the Company) the Participant may have as of his or her termination date will immediately vest (or become free from repurchase) and, if applicable, become exercisable in full. 

Section IV: Severance Agreement and Release 
 As a
condition of the Participant’s receipt of the severance benefits set forth in Section III, the Participant must timely execute and return to the Company a severance and release of claims agreement provided by and satisfactory to the Company
(the “Severance Agreement”), and such Severance Agreement must become binding and enforceable within 60 calendar days after the Participant’s termination of employment (or such shorter period as the Company may direct). Severance pay
will begin, and any applicable severance bonus will be made, in the first pay period beginning after the Severance Agreement becomes binding, provided that if the foregoing 60 day period would end in a calendar year subsequent to the year in which
the Participant’s employment ends, payment will not begin or be made before the first payroll period of the subsequent year. 
 Section V:
Miscellaneous Provisions 
  

	 	1.	No Employment Rights. Nothing in this Plan shall be construed to provide any Participant with a guarantee of employment or shall supersede the Company’s policy of employment at will. 

 

	 	2.	Governing Law. The Plan and the rights of all persons under the Plan shall be construed in accordance with and under applicable provisions of ERISA, and the regulations thereunder, and the laws of the
Commonwealth of Massachusetts (without regard to conflict of laws provisions) to the extent not preempted by federal law. 

  
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	 	3.	No Limitation upon Rights of Company. The Plan shall not affect in any way the right or power of the Company to make adjustments, reclassifications or changes of its capital or business structure; to merge or
consolidate; to dissolve or liquidate; or to sell or transfer all or any part of its business or assets. 

  

	 	4.	Indemnification. To the extent permitted by law, the Plan Administrator and all employees, officers, directors, agents and representatives of the Plan Administrator will be indemnified by the Company and held
harmless against any claims and the expenses of defending against such claims, resulting from any action or conduct relating to the administration of the Plan except to the extent that such claims arise from gross negligence, willful neglect, or
willful misconduct. 

  

	 	5.	Plan Name and Type. The name of the Plan is the Epizyme, Inc. Executive Severance and Change in Control Plan. The Plan is intended to constitute an “Employee Welfare Benefits Plan” under Department of
Labor Regulation 2510.3-2(b) and other applicable regulations and statutes. Under no circumstances will any benefit under this Plan ever vest or become nonforfeitable. The Plan must be construed and interpreted in a manner consistent with the
foregoing intent. 

  

	 	6.	Funding. The Plan is unfunded and all payments under the Plan will be made from the Company’s general assets. 

  

	 	7.	Name and Address of Employer. The Plan is sponsored by: 

 Epizyme, Inc. 

400 Technology Square 
 4th Floor 
 Cambridge, MA 02139 

 

	 	8.	Employer and Plan Identification Number. The Internal Revenue Service has assigned the Company the following employer identification number: 26-1349956. The ERISA plan number assigned to this program is 502.

  

	 	9.	Agent for Service of Legal Process. Legal process with respect to claims under the Plan may be served on the Plan Administrator. 

 

	 	10.	ERISA. The provisions set forth in Appendix A are incorporated herein and made a part of this Plan. 

  

	 	11.	Fiscal Year of the Plan. The Plan and its records are kept on a calendar-year basis. The first plan year will be a short plan year beginning on March 22, 2013 and ending on December 31, 2013. Subsequent
plan years are the 12-month period beginning January 1 and ending December 31. 

  

	 	12.	Entire Agreement. This Plan supersedes any and all severance or equity acceleration plans, policies, and provisions applying to the Participants, including, without limitation, any provision in any
Participant’s offer letter, employment agreement, or equity agreement providing the Participant with any pay, benefits, or equity acceleration following a change in control of the Company and/or termination of his or her employment for any
reason (including termination due to death or disability). To the extent any such plan, policy, or provision contradicts the Plan, the terms of the Plan shall govern. 

  
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	 	13.	Successor and Assigns. The Company shall require any successor (whether direct or indirect, by purchase, merger, consolidation or otherwise) to all or substantially all of the business and/or assets of the
Company to expressly assume and agree to perform the Company’s obligations under the Plan in the same manner and to the same extent that the Company would be required to perform it if no such succession had taken place. 

 

	 	14.	Severability. In case any one or more of the provisions of this Plan (or part thereof) shall be held to be invalid, illegal or unenforceable in any respect, such invalidity, illegality or unenforceability shall
not affect the other provisions hereof, and this Plan shall be construed as if such invalid, illegal or unenforceable provisions (or part thereof) never had been contained herein. 

 

	 	15.	Non-Assignability. No right or interest of any Participant shall be assignable or transferable in whole or in part either directly or by operation of law or otherwise,
including, but not limited to, execution, levy, garnishment, attachment, pledge or bankruptcy; provided, however, that this provision shall not be applicable in the case of obligations of a Participant to the Company. 

 

	 	16.	Duration; Amendment or Termination. The Plan is effective March 22, 2013, and will continue in force until the Company terminates the Plan. The Company reserves the right to modify, amend or terminate the
Plan in whole or in part at any time. Such amendment, modification or termination shall be effected by a written instrument executed by an authorized officer of the Company. However, in no event shall such modification, amendment or termination
reduce or diminish any equity acceleration or severance benefits owing under the Plan prior to the date of such modification, amendment or termination without the consent of the Participant to whom the benefits are owed. 

 

	 	17.	Integration with Other Pay or Benefits Requirements. The severance benefits provided for in the Plan are the maximum benefits that the Company will pay to covered Participants. To the extent that the Company owes
any amounts in the nature of severance benefits under any other program, policy, or plan of the Company, or to the extent that any federal, state, or local law, including so called “plant closing” laws, requires the Company to give advance
notice or make a payment of any kind to an employee because of that employee’s involuntary termination due to a layoff, reduction in force, plant or facility closing, sale of business, or similar event, the benefits provided under this Plan or
the other arrangement will either be reduced or eliminated to avoid any duplication of payment. The Company intends for the benefits provided under this Plan to partially or fully satisfy any and all statutory obligations that may arise out of an
employee’s involuntary termination for the foregoing reasons and the Plan Administrator must so construe and implement the terms of the Plan. 

Section VI: Section 409A 
 It is expected that
payments under this Plan will be exempt from the application of Section 409A of the Internal Revenue Code of 1986, as amended, and the guidance issued thereunder (“Section 409A”) either because of the application of the short-term
deferral rule or because of the Two Times Exception (as described below). The following rules shall apply with respect to distribution of the payments to be provided under this Plan to Participants. Each installment of the payments provided under
this policy will be treated as a separate “payment” for purposes of Section 409A. Neither the Company nor any Participant will have the right to accelerate or defer the delivery of any such payments or benefits except to the extent
specifically permitted or required by Section 409A. 
 If, as of the date of the “separation from service” of the Participant from the
Company, the Participant is not a “specified employee” (each within the meaning of Section 409A), then each installment of the payments and benefits will be made on the dates and terms set forth in this Plan. If, as of the date of the

  
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separation from service of the Participant from the Company, the Participant is a specified employee, then: 

(A) Each installment of the payments and benefits due under this Plan that will be paid within the Short-Term Deferral Period (as hereinafter
defined) will be treated as a short-term deferral within the meaning of Section 409A to the maximum extent permissible under Section 409A. For purposes of this Plan, the “Short-Term Deferral Period” means the period ending on the
later of the 15th day of the third month following the end of the Participant’s tax year in which the Participant’s separation from service occurs and the 15th day of the third month following the end of the Company’s tax year in
which the Participant’s separation from service occurs; and 
 (B) Each installment of the payments and benefits due under this Plan
that is not paid within the Short-Term Deferral Period and that would, absent this subsection, be paid within the six-month period following the separation from service of the Participant will not be paid until the date that is six months and one
day after such separation from service (or, if earlier, the death of the Participant) (as applicable, the “New Payment Date”), with any such installments that are required to be delayed being accumulated during the six-month period and
paid in a lump sum in the payroll period next following the New Payment Date and any subsequent installments, if any, being paid in accordance with the dates and terms set forth herein; provided, however, that the preceding provisions
of this sentence shall not apply to any installment of payments and benefits if and to the maximum extent that that such installment is deemed to be paid under a separation pay plan that does not provide for a deferral of compensation by reason of
the application of Treasury Regulation 1.409A-1(b)(9)(iii) (relating to separation pay upon an involuntary separation from service, the “Two Times Exception”), including the dollar limit in the Two Times Exception. Any installments that
qualify for the Two Times Exception must be paid no later than the last day of the second taxable year of the Participant following the taxable year of the Participant in which the separation from service occurs. 

In any event, the Company makes no representations or warranty and will have no liability to any Participant or any other person if any provisions of or
payments under this Plan are determined to constitute deferred compensation subject to Section 409A of the Code but not to satisfy the conditions of that section. 

Section VII: Section 280G/4099 
  

	 	a.	 Anything in this document to the contrary notwithstanding, if it is determined that any payment by the Company to a Participant or for his or her
benefit (whether paid or payable or distributed or distributable pursuant to the terms of this Plan or otherwise) (the “Payments”) would be subject to the excise tax imposed by Section 4999 (or any successor provisions) of the Code,
or any interest or penalty would be incurred by the Participant with respect to such excise tax (such excise tax, together with any such interest and penalties, is hereinafter collectively referred to as the “Excise Tax”), then the
Payments shall be reduced (but not below zero) if and to the extent that such reduction would result in the Participant’s retaining a larger amount, on an after-tax basis (taking into account federal, state and local income taxes and the
imposition of the Excise Tax), than if he or she received all of the Payments. To that end, the Payments will be reduced or eliminated as follows, as determined by the Company, in the following order: (i) nonacceleration of any stock options
whose exercise price is at or above the fair market value of the stock as determined in the discretion of the Board of Directors (taking into account, as appropriate, the proceeds that would be received in connection with the event covered by
Section 4999) (“Underwater Options “), (ii) nonacceleration of any stock options other than Underwater Options, (iii) any vesting or 

  
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distribution of restricted stock or restricted stock units and (iv) the cash severance due under the Plan above. Within each category described in clauses (i), (ii), and (iii), reductions or
eliminations shall be made in reverse order beginning with vesting or distributions that are to be paid the farthest in time from the date of the event covered by Section 4999. 

 

	 	b.	All determinations required to be made under this Section, including whether and when an adjustment to any Payment is required and, if applicable, which Payments are to be so adjusted, shall be made by an independent
accounting firm or any nationally recognized financial planning and benefits consulting company (the “Accounting Firm”) selected by the Company, which shall provide detailed supporting calculations both to the Company and to the
Participant within fifteen (15) business days of the receipt of notice by the Company. All fees and expenses of the Accounting Firm shall be borne solely by the Company. Any determination by the Accounting Firm shall be binding upon the Company
and the Participant. 

  

			
	Adopted by Epizyme, Inc. on March 22, 2013
	
	Amended by Epizyme, Inc. on February 25, 2016
		
	By:	 	 /s/ Robert B. Bazemore

	Name:	 	Robert B. Bazemore
	Title:	 	President and Chief Executive Officer

  
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 APPENDIX A 

Plan Administration 
 The Company’s Head of Human
Resources and Director is the Plan Administrator. The general administration of the Plan and the responsibility for carrying out its provisions are vested in the Plan Administrator. The Plan Administrator will be the “administrator” within
the meaning of Section 3(16) of ERISA and will have all the responsibilities and duties contained therein. 
 The Plan Administrator can be contacted
at the following address: Epizyme, Inc., 400 Technology Square, 4th Floor, Cambridge, MA 02139; or through the Human Resources Department at 617-500-0854. The Plan Administrator will operate,
interpret and implement the Plan. The Plan Administrator’s decisions and determinations (including determinations of the meaning and reference of terms used in the Plan) will be conclusive upon all persons. The Plan Administrator will be the
Named Fiduciary for purposes of ERISA. 
 The Plan Administrator will have the full power and discretionary authority to administer the Plan in all its
details and such powers and discretion as are necessary to discharge its duties, including interpretation and construction of the Plan, the determination of all questions of eligibility, participation and benefits and all other related or incidental
matters, and such duties and powers of plan administration that are not assumed from time to time by any other appropriate entity, individual, or institution. The Plan Administrator will decide all such questions in accordance with the terms of the
controlling legal documents and applicable law, and its good faith decision will be binding on the Participant, the Participant’s spouse or other dependent or beneficiary and all other interested parties. 

The Plan Administrator may adopt rules and regulations of uniform applicability in its interpretation and implementation of the Plan. 

The Plan Administrator may require each Participant to submit, in such form as it considers reasonable and acceptable, proof of any information that the Plan
Administrator finds necessary or desirable for the proper administration of the Plan. 
 The Plan Administrator must maintain such records as are necessary
to carry out the provisions of the Plan. The Plan Administrator must also make all disclosures that are required by ERISA. 
 If there has been a mistake in
the amount of a Participant’s benefits paid under the Plan, the Plan Administrator may correct the mistake when the mistake is discovered. The mistake may be corrected in any reasonable manner authorized by the Plan Administrator (e.g., by
offset against payments remaining to be paid or by payments between the Participant and the Company). In appropriate circumstances (e.g., where a mistake is not timely discovered), the Plan Administrator may waive the making of any correction. 

The Company will pay all costs and expenses incurred in administering this Plan, including expenses of the Plan Administrator and its designee(s). 

  
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 Statement of ERISA Rights 

The following statement is required by federal law and regulations. ERISA provides that all Plan participants are entitled to: 

 

	 	•	 	Examine, without charge at the Plan Administrator’s office and at other specified locations, such as work sites, all Plan documents, and copies of all documents filed by the Plan with the U.S. Department of Labor,
such as detailed annual reports and Plan descriptions. 

  

	 	•	 	Obtain copies of all Plan documents and the Plan information upon written request to the Plan Administrator. The Plan Administrator may make a reasonable charge for copies. 

 

	 	•	 	Receive a copy of a summary of the Plan’s annual financial report. The Plan Administrator is required by law to furnish each participant with a copy of this Summary Annual Report. 

 

	 	•	 	Obtain a statement advising the Participant whether he or she has a right to receive benefits under the Plan and what benefits he or she may receive. This statement must be requested in writing and is not required to be
given more than once a year. The Plan Administrator must provide the statement free of charge. 

 In addition to creating rights for
Participants, ERISA imposes duties upon the people who are responsible for the operation of the employee benefit plan. The people who operate the Plan, called “fiduciaries” of the Plan, have a duty to do so prudently and in the interest of
Plan participants and beneficiaries. Employers nor any other person may fire an employee or otherwise discriminate against an employee in any way to prevent an employee from obtaining a benefit under the Plan or exercising the employee’s rights
under ERISA. 
 If an employee’s claim for a benefit is denied in whole or in part, the employee must receive a written explanation of the reason for
the denial. The employee has the right to have the Plan Administrator review and reconsider the employee’s claim. Under ERISA, there are steps an employee can take to enforce the above rights. For instance, if the employee requests materials
from the Plan Administrator and does not receive them within 30 days, the employee may file suit in a federal court. In such a case, the court may require the Plan Administrator to provide the materials and pay the employee up to $110 per day until
the employee receives the materials, unless the materials were not sent because of reasons beyond the control of the Plan Administrator. 
 If an
employee’s claim for benefits is denied or ignored, in whole or in part, the employee may file suit in a state or federal court. If the Plan fiduciaries misuse the Plan’s funds, or if an employee is discriminated against for asserting his
or her rights, the employee may seek assistance from the U.S. Department of Labor, or may file suit in a federal court. The court will decide who should pay court costs and legal fees. 

If an employee is successful, the court may order the person sued to pay costs and fees. If the employee loses, the court may order the employee to pay these
fees (for example, if the claim is frivolous). Employees should contact the Plan Administrator concerning questions about the Plan. Employees who have any questions about this statement or rights under ERISA should contact the nearest area office of
the Employee Benefits Security Administration, U.S. Department of Labor listed in the telephone directory or the Division of Technical Assistance and Inquiries, Employee Benefits Security Administration, U.S. Department of Labor, 200 Constitution
Avenue, N.W., Washington, DC 20210. 
 Claims Procedure 

Ordinarily, benefits will be provided to eligible employees without their having to file a claim or take any action other than signing a Severance Agreement
and, where applicable, not revoking such agreement during the applicable revocation period. Any Participant who believes he or she is entitled to benefits under the Plan that are not being provided may submit a written claim to the Plan
Administrator. Any 

  
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claim for benefits shall be in writing, addressed to the Plan Administrator and must be sufficient to notify the Plan Administrator of the benefit claimed. If the claim of a Participant is
denied, the Plan Administrator shall, within a reasonable period of time, provide a written notice of denial to the Participant. The notice will include the specific reasons for denial, the provisions of the Plan on which the denial is based, and
the procedure for a review of the denied claim. Where appropriate, it will also include a description of any additional material or information necessary to complete or perfect the claim and an explanation of why that material or information is
necessary. The Participant may request in writing a review of a claim denied by the Plan Administrator and may review pertinent documents and submit issues and comments in writing to the Plan Administrator. The Plan Administrator shall provide to
the Participant a written decision upon such request for review of a denied claim. The decision of the Plan Administrator upon such review shall be final. 

  
 3EX-10.22

 Exhibit 10.22 

 

Confidential Materials omitted and filed separately with the 

Securities and Exchange Commission. Double asterisks denote omissions. 

SECOND AMENDMENT 
 TO

 COMPANION DIAGNOSTICS AGREEMENT 

This Second Amendment (“Second Amendment”) shall be effective as of this 16th day of November (“Amendment Effective Date”),
by and between Epizyme, Inc., having a place of business at 400 Technology Square, 4th Floor, Cambridge, Massachusetts 02139, U.S.A. (“Epizyme”) and Eisai Co., Ltd.,
having a place of business at Koishikawa 4-6-10, Bunkyo-ku, Tokyo 112-8088, Japan (individually, “Eisai” and collectively with Epizyme, “Pharmaceutical Partners”), on the one side, and Roche Molecular Systems,
Inc., having a place of business at 4300 Hacienda Drive, Pleasanton, California 94588, U.S.A. (“RMS”), on the other side, as an amendment to the Companion Diagnostics Agreement, dated 18th December 2012 as previously amended on 31 May 2013 (“Agreement”). Capitalized terms used in this Amendment and not defined in this Amendment shall have the meanings
ascribed to them in the Agreement. 
 WHEREAS, Epizyme, Eisai and RMS are Parties to the Agreement and desire to amend the Agreement
as set forth in this Second Amendment; and 
 WHEREAS, the Parties agree to modify the Project Plan and the Payment Plan, as well as
the other provisions specifically set forth herein, in accordance with Section 4.2 of the Agreement, to reflect the revised timing of the Pivotal Registrational Trial. 

NOW, THEREFORE, in consideration of the agreements contained herein, and other good and valuable consideration, the receipt and
sufficiency of which each Party hereby acknowledges, the Parties hereby agree as follows: 
  

	 	1.	Section 15.7(b) under the Agreement is hereby replaced in its entirety with the following amended and restated Section 15.7(b): 

“(b) If Pharmaceutical Partners terminate this Agreement or a Project Plan pursuant to Section 15.4, and RMS is not in material
breach of this Agreement, then the Parties shall agree [**] and Pharmaceutical Partners shall pay to RMS [**]. If the Parties cannot agree [**], the Parties agree that such disputes shall be resolved by Senior Officers in accordance with
Section 4.3, and then, if applicable, by Arbitration in accordance with Article 16. Without limiting the foregoing, (i) in the event that such termination occurs prior to initiation of [**], Pharmaceutical Partners shall pay to RMS [**]
dollars ($[**]), and (ii) in the event that such termination occurs after initiation of [**], Pharmaceutical Partners shall pay to RMS [**] dollars ($[**]) (either the fees in (i) or (ii), the “Deferred Fee”); provided
that, for clarity, in the event that Pharmaceutical Partners are obligated to make a payment for Deferred Fee to RMS pursuant to clause (ii), they shall not also be obligated to make a payment for Deferred Fee to RMS pursuant to clause (i). Any
applicable Deferred Fee in addition to any applicable [**] that may be due as set forth above in this Section 15.7(b) shall be collectively the “Termination Fees”. In addition, Pharmaceutical Partners shall pay to RMS and any
additional costs associated with the agreed upon orderly wind down of any then-ongoing activities under the Project Plan. For clarity, (1) for purposes of calculating the Termination Fees (if any) due to RMS pursuant to this
Section 15.7(b) only, the milestone reference amounts set forth on Part I.B of Exhibit E shall apply, (2) for purposes of any milestones that have been completed prior to termination (which were not invoiced and/or paid), such milestones
shall be 

  
 Page 1 of 8 

 
deemed earned and the milestone amounts set forth in Exhibit B shall apply and be paid in accordance with Article 7; and, unless otherwise expressly agreed by the Parties in writing, in no event
shall Pharmaceutical Partners be obligated to pay RMS more than an aggregate of fifteen million dollars ($15,000,000) following the execution of the Second Amendment to this Agreement in milestones and Termination Fees under this Agreement. For
illustrative purposes only, Part II of Exhibit E provides a sample calculation for a scenario under this Section 15.7(b).” 
  

	 	2.	The current Project Plan under the Agreement is hereby replaced in its entirety with the amended and restated Project Plan set forth in Attachment 1 to this Amendment. 

 

	 	3.	The current Exhibit B of the Agreement is hereby replaced in its entirety with the amended and restated Exhibit B set forth in Attachment 2 to this Amendment. 

 

	 	4.	The current Exhibit C of the Agreement is hereby replaced in its entirety with the amended and restated Exhibit C set forth in Attachment 3 to this Amendment. 

 

	 	5.	The current Exhibit E of the Agreement is hereby replaced in its entirety with the amended and restated Exhibit E set forth in Attachment 4 to this Amendment. 

 

	 	6.	This Amendment is effective and shall become part of the Agreement as of the Amendment Effective Date. 

  

	 	7.	Except as provided herein, all other terms and conditions of the Agreement remain unchanged and are in full force and effect. 

  

	 	8.	This Amendment may be signed in any number of counterparts (facsimile and electronic transmission included), each of which shall be deemed an original, but all of which shall constitute one and the same instrument.
After facsimile or electronic transmission, the Parties agree to execute and exchange documents with original signature. 

  
 Page 2 of 8 

 The Parties have executed this Amendment, by their duly authorized representatives. 

 

							
	ROCHE MOLECULAR SYSTEMS, INC.	    	EPIZYME, INC.
				
	By:	 	 /s/ Paul Brown
	    	By:	 	 /s/ Robert Bazemore

		 	(signature)	    		 	(signature)
				
	Name:	 	 Paul Brown
	    	Name:	 	 Robert Bazemore

		 	(printed name)	    		 	(printed name)
				
	Title:	 	President & CEO	    	Title:	 	President & CEO
				
	Date:	 	8 December 2015	    	Date:	 	11-16-15
			
		 		    	EISAI CO., LTD.
				
		 		    	By:	 	 /s/ Terushige Iike

		 		    		 	(signature)
				
		 		    	Name:	 	 Terushige Iike

		 		    		 	(printed name)
				
		 		    	Title:	 	Chief Product Creation Officer
				
		 		    	Date:	 	December 15, 2015

  
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 ATTACHMENT 1 

PROJECT PLAN (updated October 2015) 

To Develop a Companion Diagnostic (CoDx) Test for EZH2 Mutation Detection to Select Patients for Treatment with E7438 (tazemetostat)

 This Project Plan describes the activities and deliverables planned for a joint collaboration between Epizyme and Eisai (collectively and applicably
the Pharmaceutical Partners) and RMS to develop a companion diagnostic (CoDx) testing kit against EZH2 change of function mutations in the catalytic domain for the selection of Non-Hodgkin Lymphoma (NHL) patients for treatment with tazemetostat.

 Background – Diagnostic Test: 

Confidential Materials omitted and filed separately with the Securities and Exchange Commission. A total of 3 pages were omitted. [**]. 

Scope of this Project Plan: 
 The Pharmaceutical
Partners and RMS would like to engage in a collaboration to develop and commercialize a companion diagnostic test (RMS Product) for the prospective selection of EZH2 mutation positive Non-Hodgkin’s Lymphoma (NHL) patients for treatment with
tazemetostat. This Project Plan describes the activities, deliverables, and estimated budget anticipated for a collaboration between the Pharmaceutical Partners and RMS for Stage 1 – Specimen access, pre-IDE development activities with minimal
set of verification studies required for IND supplement/IDE submission, Stage 2 – IVD development/core TPV studies required for Device Authorization Application submission and start of Proof of Concept (PoC) Phase 2 studies, Stage 3 –first
pivotal registrational (open-label, single-arm) clinical trials to establish clinical utility, Stage 4 – Clinical reproducibility studies required for Device Authorization Application submission, and Stage 5 – CE-IVD marking and Device
Authorization Application submission to FDA. 
 Note: This updated project plan and updated payment plan are based on the Key Assumptions (updated
October 2015) set forth in Attachment 2. Any changes to the updated Key Assumptions may lead to a change in the project plan and payment plan. 

[**]. 
 In addition, high level budget estimates of
activities that are planned in the long term for support of a [**] will be provided to the Pharmaceutical Partners. These “ball park” estimates are based on the assumptions listed below and may be modified in the future as the scope of the
project becomes more fully defined. Modification of the scope and budget of long term activities will be agreed upon by the Pharmaceutical Partners and RMS. 

Confidential Materials omitted and filed separately with the Securities and Exchange Commission. A total of 7 pages were omitted. [**]. 

  
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 ATTACHMENT #2 

EXHIBIT B 
 PAYMENT PLAN

 Milestones: Epizyme, on behalf of Epizyme and Eisai, will pay RMS the following milestone payments upon completion of activities
associated with the milestone: 
 I. Milestone payments made prior to the execution of the Second Amendment to this Agreement: 

 

			
	Milestone	  	Payment
		
	[**]	  	[**]
		
	[**]	  	[**]
		
	[**]	  	[**]
		
	[**]	  	[**]

 II. Milestone payment to be paid by Epizyme, on behalf of Epizyme and Eisai, to RMS within [**] days after the
execution of the Second Amendment to this Agreement: 
  

			
		
	[**]	  	[**]  

 III. Remaining milestone payments that may become payable after the execution of the Second Amendment to this
Agreement: 
  

					
			
	[**]	  	[**]	 	
			
	            [**]	  	[**]	 	
			
	[**]	  	[**]	 	
			
	            [**]	  	[**]	 	
			
	[**]	  	[**]	 	
			
	[**]	  	[**]	 	

  
 Page 5 of 8 

					
			
	[**]	  	[**]	 	
			
	[**]	  	[**]	 	
			
	[**]	  	[**]	 	
			
	[**]	  	[**]	 	
			
	[**]	  	[**]	 	
			
	[**]	  	[**]	 	

 In the event that RMS has completed [**] Project Plan and thereafter any excessive delay or failure of
performance by Pharmaceutical Partners prevents RMS from filing and therefore obtaining Regulatory Approval thereof in the United States, where RMS would otherwise have earned such subsequent milestone(s) but for such excessive delay or failure of
performance by Pharmaceutical Partners, then RMS may send a notice to Pharmaceutical Partners asserting that such circumstances exist. If Pharmaceutical Partners do not either send RMS a notice of termination pursuant to Article 15 or a notice
disputing the existence of such circumstances within [**] days after the notice from RMS asserting such circumstances, and if RMS is not in material breach of the Agreement, RMS shall be deemed to have earned [**] dollars ($[**]), which amount shall
be creditable against all unearned milestones and Termination Fees, if any. Any dispute as to the applicability of this paragraph shall be resolved in accordance with the terms of Article 16. For clarity, unless otherwise expressly agreed by the
Parties in writing, in no event shall Pharmaceutical Partners be obligated to pay RMS more than an aggregate of fifteen million dollars ($15,000,000) ) following the execution of the Second Amendment to this Agreement in milestones (including any
amount that may become payable pursuant to this paragraph) and Termination Fees under this Agreement. 

  
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 ATTACHMENT #3 

KEY ASSUMPTIONS (updated October 2015 ) 

As of the Amendment Effective Date, the following items shall be deemed Key Assumptions which were used to prepare the updated Project Plan (updated May 2013)
and updated Payment Plan agreed upon by the Parties: 
 Note: The updated project plan ( October 2015) and updated payment plan are based on the
assumptions stated below. Any changes to the assumptions may lead to a change in the project plan and payment plan. 
 [**]. 

In addition, high level budget estimates of activities that are planned in the long term for support of a [**] will be provided to the Pharmaceutical
Partners. These “ball park” estimates are based on the assumptions listed below and may be modified in the future as the scope of the project becomes more fully defined. Modification of the scope and budget of long term activities will be
agreed upon by the Pharmaceutical Partners and RMS. 
 Key Assumptions: 

Key Assumptions for: [**] 
 [**] 

  
 Page 7 of 8 

 ATTACHMENT #4 

EXHIBIT E 
 MILESTONES
AND EXAMPLES FOR SECTION 15.7(b) 
 Part I.A: Milestone Reference Amounts No Longer Applicable for Purposes of Section 15.7(b) After the
Execution of the Second Amendment to the Agreement 
  

			
		
	Milestone	  	Payment
		
	[**]	  	[**]
		
	[**]	  	[**]
		
	[**]	  	[**]

 Part I.B: Milestone Reference Amounts Applicable for Purposes of Section 15.7(b) After the Execution of the Second
Amendment to the Agreement 
  

			
		
	[**]	  	[**]
		
	[**]	  	[**]
		
	[**]	  	[**]
		
	[**]	  	[**]
		
	[**]	  	[**]
		
	[**]	  	[**]
		
	[**]	  	[**]
		
	[**]	  	[**]

 Part II: Sample Calculation under Section 15.7(b) (for illustrative purposes only) 

[**] 

  
 Page 8 of 8

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