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                              August 10, 2020

       Preston Klassen, M.D.
       President and Chief Executive Officer
       Metacrine, Inc.
       3985 Sorrento Valley Blvd., Suite C
       San Diego, CA 92121

                                                        Re: Metacrine, Inc.
                                                            Amendment No. 3 to
                                                            Draft Registration
Statement on Form S-1
                                                            Submitted July 31,
2020
                                                            CIK No. 0001634379

       Dear Mr. Klassen:

             We have reviewed your amended draft registration statement and
have the following
       comments. In some of our comments, we may ask you to provide us with
information so we
       may better understand your disclosure.

              Please respond to this letter by providing the requested
information and either submitting
       an amended draft registration statement or publicly filing your
registration statement on
       EDGAR. If you do not believe our comments apply to your facts and
circumstances or do not
       believe an amendment is appropriate, please tell us why in your
response.

             After reviewing the information you provide in response to these
comments and your
       amended draft registration statement or filed registration statement, we
may have additional
       comments.

       Amendment No. 3 to Draft Registration Statement on Form S-1

       Overview, page 1

   1.                                                   We note your response
to our prior comment 2. Please revise your disclosure to provide
                                                        the basis for the
belief that FXR agonists can be the backbone of a combination therapy in
                                                        NASH. It remains
unclear how you determined that FXR agonists can be the chief
                                                        support in such
therapy.
   2.                                                   We note your response
to our prior comment 3 and your revisions. Given the early stage
                                                        of development of your
product candidates and the very speculative nature of assessing
                                                        your position in the
industry, we continue to object to using terms such as "best-in-class."
 Preston Klassen, M.D.
Metacrine, Inc.
August 10, 2020
Page 2
         Please remove this language and any similar language throughout your
registration
         statement.
3.       We have considered your response to our prior comment 5 and your
revisions, including
         the additional disclosure you provided. Please remove references to
the potential
         "potency" of your product candidates throughout your registration
statement.
4.       We note your response to our prior comment 7. We also note that your
disclosure appears
         to continue to make comparisons that are not head-to-head, we reissue
our comment. We
         note the following disclosure in particular: "In preclinical studies
of our FXR agonists, we
         have observed improvement in colon inflammation on a level similar to
that of injectable
         biologics currently used for treatment." Please remove any comparisons
with third party
         treatments, including your perceived similarity to existing therapies
currently used for
         treatment.
        You may contact Tracie Mariner at (202) 551-3744 or Kevin Vaughn at
(202) 551-3494
if you have questions regarding comments on the financial statements and
related
matters. Please contact Courtney Lindsay at (202) 551-7237 or Celeste Murphy at
(202) 551-
3257 with any other questions.



FirstName LastNamePreston Klassen, M.D.                        Sincerely,
Comapany NameMetacrine, Inc.
                                                               Division of
Corporation Finance
August 10, 2020 Page 2                                         Office of Life
Sciences
FirstName LastName