X0306 4 2021-01-25 0 0001571498 Epizyme, Inc. EPZM 0001673802 Ros Matthew C/O EPIZYME, INC., 400 TECHNOLOGY SQUARE CAMBRIDGE MA 02139 0 1 0 0 See Remarks Common Stock, par value $0.0001 2021-01-25 4 S 0 2872 11.41 D 55957 D Represents shares automatically sold by the reporting person to satisfy tax withholding obligations in connection with the vesting of the restricted stock units granted under the issuer's 2013 Stock Incentive Plan on January 24, 2019. The automatic sale of the reporting person's shares is provided for in a restricted stock unit agreement constituting a "binding contract" consistent with the affirmative defense to liability under Rule 10b5-1 and the sale does not represent a discretionary trade by the reporting person. The reporting person acquired (i) 708 shares of Common Stock under the Issuer's 2013 Employee Stock Purchase Plan (the "2013 ESPP") on August 31, 2018 and (ii) 614 shares of Common Stock under the 2013 ESPP on February 28, 2019 that were not previously reported on Form 4. Executive Vice President, Chief Strategy & Business Officer /s/ John Weidenbruch, attorney-in-fact 2021-01-27