X0306 4 2021-12-06 0 0001571498 Epizyme, Inc. EPZM 0001746830 Agarwal Shefali C/O EPIZYME, INC., 400 TECHNOLOGY SQUARE, 4TH FLOOR CAMBRIDGE MA 02139 0 1 0 0 See Remarks Common Stock, par value $0.0001 2021-12-06 4 S 0 1780 2.93 D 163004 D Represents shares of Common Stock automatically sold by the reporting person to satisfy tax withholding obligations in connection with the vesting of restricted stock units granted under the Issuer's 2013 Stock Incentive Plan on December 6, 2021. The automatic sale of the reporting person's shares of Common Stock 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 1,277 shares of Common Stock under the Issuer's 2013 Employee Stock Purchase Plan on August 31, 2021. Executive Vice President, Chief Medical and Development Officer /s/ John Weidenbruch, attorney-in-fact 2021-12-07