Amendment No. 5 to

Collaboration and License Agreement

This Amendment (this “Amendment”) to the Collaboration and License Agreement dated as of January 8, 2011, as amended from time to time (the “Agreement”), by and between EPIZYME and GSK is effective as of the 1^st day of October, 2014 (the “Amendment Effective Date”). Capitalized terms used but not defined herein shall have the meanings ascribed to such terms in the Agreement.

WHEREAS, pursuant to the Agreement, the Parties have conducted certain activities with respect to the Selected Targets [**] and [**] under separate Research Plans;

WHEREAS, GSK has an exclusive worldwide license to Develop and Commercialize Licensed Compounds directed to [**] and has paid to EPIZYME a milestone for achievement of Development Candidate Selection Criteria for one such Licensed Compound; and

WHEREAS, the Parties desire to amend the technology transfer and data reporting requirements applicable to the ongoing work conducted under the Research Plans for the [**] and [**] programs, and to allow provision of additional data relating to the work conducted by or on behalf of EPIZYME under the Research Plan for [**].

NOW, THEREFORE, in consideration of the mutual covenants contained herein, and for other good and valuable consideration, the Parties, intending to be legally bound, hereby agree as follows:

2.5.1 Until the end of the Research Term, each Party shall provide written progress reports on the status of its activities under Research Plans during the Collaboration, on a Selected Target-by-Selected Target basis, including detailed summaries of data associated with such activities, at least [**] Business Days in advance of each JPT meeting. Without limiting the foregoing, EPIZYME shall deliver to GSK all data, reports and other results, and analyses thereof, specifically set forth in Appendix A, related to the “Lead Compounds” defined as those Lead Candidate Compounds that are under consideration for designation as Development Candidates generated in the course of performing the Research Plans for the Selected Targets known as [**] and [**] (the “Development Candidate Data”). EPIZYME will transfer the Development Candidate Data for each of [**] and [**] on the timelines set forth in Appendix A, and will complete transfer of all Development Candidate Data for both [**] and [**] within [**] weeks following EPIZYME’s completion of experiments that generate Development Candidate Data for such Selected Target. Epizyme shall notify GSK in writing (which may be provided via email between Alliance Managers) when transfer of all Development Candidate Data is complete for each Selected Target (each date referred to as a “Transfer Date”).

Execution Version

2.5.2 GSK will review Development Candidate Data as soon as reasonably practicable after receipt from EPIZYME, and in any event will commence such review prior to the applicable Transfer Date. The JPT shall discuss the Development Candidate Criteria as needed during GSK’s review thereof. Within [**] weeks after the Transfer Date for each Selected Target, the JPT shall meet to decide whether to recommend at least one (1) Lead Compound for each Selected Target to the JSC as a Development Candidate. If the JPT decides to recommend at least one (1) Lead Compound to the JSC, then the JSC shall meet promptly thereafter to determine whether the applicable Development Candidate Selection Criteria have been achieved with respect to such Lead Compound. Notwithstanding Sections 4.3 and 4.1.2 of the Agreement, the JPT and JSC shall not disband and shall continue to function beyond the end of the Research Term for so long as is necessary to fulfill the obligations set forth in this Amendment No. 5.

Execution Version

IN WITNESS WHEREOF, the Parties have caused this Amendment to be executed by their duly authorized representatives.

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Execution Version

APPENDIX A

DEVELOPMENT CANDIDATE DATA

Execution Version

Execution Version

Exhibit 1 – Raw Data Description for Biology and DMPK