United States securities and exchange commission logo September 27, 2021 Grant Bogle President and Chief Executive Officer Epizyme, Inc. 400 Technology Square, 4th Floor Cambridge, Massachusetts 02139 Re: Epizyme, Inc. Registration Statement on Form S-3 Filed September 21, 2021 File No. 333-259680 Dear Mr. Bogle: This is to advise you that we have not reviewed and will not review your registration statement. Please refer to Rules 460 and 461 regarding requests for acceleration. We remind you that the company and its management are responsible for the accuracy and adequacy of their disclosures, notwithstanding any review, comments, action or absence of action by the staff. Please contact Chris Edwards at 202-551-6761 with any questions. Sincerely, Division of Corporation Finance Office of Life Sciences cc: Molly W. Fox, Esq.