X0306 4 2021-02-01 0 0001571498 Epizyme, Inc. EPZM 0001707648 TOMBESI PAOLO C/O EPIZYME, INC., 400 TECHNOLOGY SQUARE CAMBRIDGE MA 02139 0 1 0 0 Chief Financial Officer Common Stock 2021-02-01 4 A 0 26041 0.00 A 54486 D Stock Option (Right to Buy) 11.02 2021-02-01 4 A 0 124239 0.00 A 2031-01-31 Common Stock 124239 124239 D Plan. Each RSU represents the right to receive one share of Common Stock upon vesting. These RSUs are scheduled to vest in four equal annual installments over four years from the grant date, with the first installment vesting on February 1, 2022. The reporting person acquired 996 shares of Common Stock under the Issuer's 2013 Employee Stock Purchase Plan (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. This option was granted on February 1, 2021 pursuant to the Company's 2013 Stock Incentive Plan with respect to 124,239 shares of Common Stock, with 25% vesting on February 1, 2022 and the remaining 75% vesting in 36 substantially equal monthly installments thereafter. /s/ John Weidenbruch, attorney-in-fact 2021-02-02