Sec Form 4 Filing - Agarwal Shefali @ Epizyme, Inc. - 2021-08-16

FORM 4 Check this box if no longer subject to Section 16. Form 4 or Form 5 obligations may continue. See Instruction 1(b).

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 STATEMENT OF CHANGES IN BENEFICIAL OWNERSHIP Filed pursuant to Section 16(a) of the Securities Exchange Act of 1934, Section 17(a) of the Public Utility Holding Company Act of 1935 or Section 30(h) of the Investment Company Act of 1940

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1. Name and Address of Reporting Person Agarwal Shefali 2. Issuer Name and Ticker or Trading Symbol Epizyme, Inc. [ EPZM] 5. Relationship of Reporting Person(s) to Issuer (Check all applicable) _____ Director _____ 10% Owner X __ Officer (give title below) _____ Other (specify below) See Remarks (Last) (First) (Middle) C/O EPIZYME, INC., 400 TECHNOLOGY, SQUARE, 4TH FLOOR 3. Date of Earliest Transaction (MM/DD/YY) 08/16/2021 (Street) CAMBRIDGE, MA02139 4. If Amendment, Date Original Filed (MM/DD/YY) 6. Individual or Joint/Group Filing (Check Applicable Line) __ X __ Form filed by One Reporting Person _____ Form filed by More than One Reporting Person (City) (State) (Zip)

Table I - Non-Derivative Securities Acquired, Disposed of, or Beneficially Owned 1.Title of Security (Instr. 3) 2. Transaction Date (MM/DD/YY) 2A. Deemed Execution Date, if any (MM/DD/YY) 3. Transaction Code (Instr. 8) 4. Securities Acquired (A) or Disposed of (D) (Instr. 3, 4 and 5) 5. Amount of Securities Beneficially Owned Following Reported Transaction(s) (Instr. 3 and 4) 6. Ownership Form: Direct (D) or Indirect (I) (Instr. 4) 7. Nature of Indirect Beneficial Ownership (Instr. 4) Code V Amount (A) or (D) Price Common Stock, par value $0.0001 08/16/2021 A 59,166 ( 1 ) A $ 0 163,507 D

Table II - Derivative Securities Acquired, Disposed of, or Beneficially Owned ( e.g. , puts, calls, warrants, options, convertible securities) 1. Title of Derivative Security (Instr. 3) 2. Conversion or Exercise Price of Derivative Security 3. Transaction Date (MM/DD/YY) 3A. Deemed Execution Date, if any (MM/DD/YY) 4. Transaction Code (Instr. 8) 5. Number of Derivative Securities Acquired (A) or Disposed of (D) (Instr. 3, 4, and 5) 6. Date Exercisable and Expiration Date (MM/DD/YY) 7. Title and Amount of Underlying Securities (Instr. 3 and 4) 8. Price of Derivative Security (Instr. 5) 9. Number of Derivative Securities Beneficially Owned Following Reported Transaction(s) (Instr. 4) 10. Ownership Form of Derivative Security: Direct (D) or Indirect (I) (Instr. 4) 11. Nature of Indirect Beneficial Ownership (Instr. 4) Code V (A) (D) Date Exercisable Expiration Date Title Amount or Number of Shares Stock Option (Right to Buy) $ 5.31 08/16/2021 A 282,270 ( 2 ) 08/15/2031 Common Stock 282,270 $ 0 282,270 D

Reporting Owners Reporting Owner Name / Address Relationships Director 10% Owner Officer Other Agarwal Shefali C/O EPIZYME, INC., 400 TECHNOLOGY SQUARE, 4TH FLOOR CAMBRIDGE, MA02139 See Remarks Signatures /s/ John Weidenbruch, attorney-in-fact 08/18/2021 Signature of Reporting Person Date

Explanation of Responses:

( 1 )Consists of shares of Common Stock issuable under 59,166 restricted stock units ("RSUs") granted pursuant to the Company's 2013 Stock Incentive Plan. Each RSU represents the right to receive one share of Common Stock upon vesting. These RSUs are scheduled to vest in three equal annual installments over three years from the grant date, with the first installment vesting on August 16, 2022. ( 2 )This option was granted on August 16, 2021 pursuant to the Company's 2013 Stock Incentive Plan with respect to 282,270 shares of Common Stock, with 33.33% vesting on August 16, 2022 and the remaining 66.67% vesting in 24 substantially equal monthly installments thereafter.

Remarks: Executive Vice President, Chief Medical and Development Officer

Reminder: Report on a separate line for each class of securities beneficially owned directly or indirectly.

* If the form is filed by more than one reporting person, see Instruction 4(b)(v).

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