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.
Statement on Form S-3
                                                            Filed September 21,
                                                            File No. 333-259680

       Dear Mr. Bogle:

              This is to advise you that we have not reviewed and will not
review your registration

               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.


                          Division of Corporation Finance

                          Office of Life Sciences
       cc:                                              Molly W. Fox, Esq.