X0306 4 2021-01-25 0 0001571498 Epizyme, Inc. EPZM 0001620152 Bazemore Robert B C/O EPIZYME, INC. 400 TECHNOLOGY SQUARE CAMBRIDGE MA 02139 1 1 0 0 President & CEO Common Stock, par value $0.0001 2021-01-25 4 S 0 6069 11.41 D 248367 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, (ii) 1,120 shares of Common Stock under the 2013 ESPP on February 28, 2019, (iii) 971 shares of Common Stock under the 2013 ESPP on August 31, 2019, and (iv) 996 shares of Common Stock under the 2013 ESPP on February 29, 2020 that were not previously reported on Form 4. The reporting person acquired 543 shares of Common Stock under the 2013 ESPP on August 31, 2020. /s/ John Weidenbruch, attorney-in-fact 2021-01-27