Confidential Materials omitted and filed separately with the Securities and Exchange Commission. Double asterisks denote omissions.

Exhibit 10.2

Execution Copy

Amendment No. 3 to

Collaboration and License Agreement

This Amendment No. 3 (this “Amendment No. 3”) to the Collaboration and License Agreement dated as of January 8, 2011 and previously amended on July 23, 2013 and February 24, 2014 (as so amended, the “Agreement”), by and between Epizyme, Inc., a Delaware corporation having its principal place of business at 400 Technology Square, 4^th Floor, Cambridge, Massachusetts 02139 USA (“EPIZYME”) and Glaxo Group Limited, a company existing under the laws of England, having its registered office at Glaxo Wellcome House, 980 Great West Road, Brentford, Middlesex, TW8 9GS, England (“GSK”) is effective as of March 18, 2014 (the “Amendment No. 3 Effective Date”). Capitalized terms used but not defined herein shall have the meanings ascribed to such terms in the Agreement.

WHEREAS, the Parties desire to amend certain terms of the Agreement relating to the Selected Target(s) [**] and [**];

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. Amendment of Licensed Compound Definition for Compounds Directed to [**]. The “Licensed Compound” definition for Compounds directed to [**] is hereby amended and restated in its entirety to read as follows:

““Licensed Compound(s)” means any Compound that is:

(a) synthesized or identified by either Party (or by any of its respective Affiliates or any Third Party working with or on behalf of such Party or any of its respective Affiliates) in the conduct of the Collaboration;

(b) determined to have both an in vitro IC50 enzymatic potency and an RGG cellular assay EC30 potency of less than or equal to [**] with respect to [**]; and

(c) for any Compound synthesized or identified by EPIZYME, covered generically or specifically under the Patents listed in Exhibit B. For clarity, for purposes of this definition only, Compounds not covered generically or specifically under the Patents listed in Exhibit B, but covered generically or specifically under other EPIZYME patent filings shall be deemed to have been synthesized or identified by EPIZYME and not by GSK, and such Compounds shall not be considered Licensed Compounds unless otherwise agreed by EPIZYME.”

The “Licensed Compound(s)” definition shall remain as set forth in the Agreement immediately prior to the Amendment No. 3 Effective Date with respect to Compounds directed to Selected Targets other than [**].

2

If GSK either fails to notify EPIZYME in writing during the Diligence Notice Period of GSK’s election of one of the foregoing three options, or GSK notifies EPIZYME in writing during the Diligence Notice Period of GSK’s election of option iv.(a) or option iv.(b) above, but GSK fails to pay the applicable payment thereunder within the applicable payment period specified therein, then GSK shall be deemed to have elected option iv.(c).

3

4

For clarity, the [**] for which milestones are payable under Table 2 is understood and agreed by the Parties to mean [**] for which milestones are paid under Table 1. For illustrative purposes only, the [**], such as [**].

Solely for purposes of the payment of milestones set forth in Table 2, “[**].

The foregoing milestone events and milestone payments are in lieu of the milestone events and milestone payments set forth in Section 6.5.1 of the Agreement solely as they apply to Licensed Compounds and Licensed Products directed to [**]; provided that, milestones (2) and (4) in Section 6.5.1 of the Agreement shall remain unchanged; and provided further that, the milestone events and milestone payments set forth in Section 6.5.1 of the Agreement shall remain unchanged for Selected Targets other than [**] and Licensed Compounds and Licensed Products directed to Selected Targets other than [**].

The foregoing milestone events and milestone payments are in lieu of the milestone events and milestone payments set forth in Section 6.7 of the Agreement with respect to [**]; provided that, the milestone events and milestone payments set forth in Section 6.7 of the Agreement shall remain unchanged for Licensed Products directed to Selected Targets other than [**].

5

The foregoing royalties are in lieu of the royalties set forth in Section 6.8.1 of the Agreement solely with respect to Net Sales of Licensed Products directed to [**]; provided that, the royalties set forth in Section 6.8.1 of the Agreement shall remain unchanged for Net Sales of Licensed Products directed to Selected Targets other than [**].

4. Termination of January 6 Letter. This Amendment No. 3 terminates and supersedes the letter between the Parties dated January 6, 2014 (the “January 6 Letter”) regarding a proposed amendment of the Agreement with respect to [**], and the subsequent letters between the Parties dated February 27, 2014 and March 7, 2014 and March 14, 2014 extending the Interim Period (as defined in the January 6 Letter). From and after the Amendment No. 3 Effective Date, the January 6 Letter and such subsequent extension letters shall have no further force or effect and, for the avoidance of doubt, [**] will not have ceased to be a Selected Target.

5. Miscellaneous. The Parties hereby confirm and agree that, as amended herein, the Agreement remains in full force and effect. This Amendment No. 3 may be executed in counterparts, each of which shall be deemed an original, but all of which together shall constitute one and the same instrument. Facsimile signatures and signatures transmitted via PDF shall be treated as original signatures.

IN WITNESS WHEREOF, the Parties have caused this Amendment No. 3 to be executed by their duly authorized representatives.

6

Exhibit A:

Amendment to DC criteria for [**] (page 1 of 2)

[**] Amended DC Criteria

Exhibit A:

Amendment to DC criteria for [**] (page 2 of 2)

[**] Amended DC Criteria

Exhibit B

Exhibit C – Page 1 of 3

[**] Research Plan Summary

Confidential Materials omitted and filed separately with the Securities and Exchange Commission. A total of one page was omitted. [**]

EXHIBIT C – PAGE 2 of 3

[**] Timeline and 2014 Budget Summary

Confidential Materials omitted and filed separately with the Securities and Exchange Commission. A total of one page was omitted. [**]

2

EXHIBIT C – PAGE 3 of 3

[**] 2014 Budget – Detailed Summary

Confidential Materials omitted and filed separately with the Securities and Exchange Commission. A total of one page was omitted. [**]

3