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                              July 27, 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. 2 to
                                                            Draft Registration
Statement on Form S-1
                                                            Submitted July 2,
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.

       Draft Registration Statement on Form S-1

       Overview, page 1

   1.                                                   Please balance your
Summary with disclosure that doctors recommend weight loss to treat
                                                        nonalcoholic fatty
liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH)
                                                        because weight loss can
reduce fat in the liver, inflammation, and fibrosis, or scarring.
                                                        We note your Risk
Factor disclosure that the current standard of care is likely to present a
                                                        major challenge to the
market penetration of MET409 and MET642 for the treatment of
                                                        NASH, if ever
commercialized, please include this in your Summary.
   2.                                                   We note your disclosure
that you "believe FXR agonists will become first-line
 Preston Klassen, M.D.
FirstName
Metacrine, LastNamePreston Klassen, M.D.
           Inc.
Comapany
July       NameMetacrine, Inc.
     27, 2020
July 27,
Page  2 2020 Page 2
FirstName LastName
         monotherapy, as well as the backbone of combination therapy (emphasis
added), for
         patients with NASH." Please provide your basis for this statement
given that diabetes,
         obesity and metabolic syndrome appear to be the diseases with which
NASH is associated
         and it appears that the current standard of care includes antidiabetic
therapies, which
         would appear to be the principal therapy in any potential combination
with a therapy for
         NASH.
3.       Please revise here and throughout your prospectus to balance and
provide the basis
         for your disclosure that "with our program, we believe we can be the
leader [emphasis
         added] in developing best-in-class FXR agonist therapies for NASH and
other GI
         diseases." We note your disclosure that other companies are in later
stages of clinical
         trials for their FXR agonists than you and that "MET409 and MET 642
are FXR agonists,
         a class of drugs from which there are no approved therapies in the
diseases for which we
         are currently pursuing clinical trials, and our initial target
indication is NASH, for which
         there are no approved therapies." Further, please remove
"best-in-class" and "first-in-
         class" therapy references (and similar phrases) found throughout your
registration
         statement since these terms suggest that the product candidates are
effective and likely to
         be approved.
4.       We note your disclosure that "targeting FXR has demonstrated
improvements in NASH in
         large-scale clinical trials, including reversal of fibrosis, which we
believe makes this a
         well-established target (emphasis added) for the treatment of NASH
patients." Please
         revise your disclosure to provide the basis for this belief given your
disclosure that
         "MET409 and MET 642 are FXR agonists, a class of drugs from which
there are no
         approved therapies in the diseases for which we are currently pursuing
clinical trials, and
         our initial target indication is NASH, for which there are no approved
therapies." We
         further note your disclosure on page 13 that the FDA recently denied
accelerated approval
         for a competitor's product candidate based on the surrogate histologic
endpoint of
         improvement of fibrosis as shown by liver biopsy with no worsening of
NASH in lieu of
         clinical outcomes such as overall survival and time to transplant."
5.       As safety and efficacy determinations are solely within the Food and
Drug
         Administration's authority and they continue to be evaluated
throughout all phases of
         clinical trials, please remove references to these terms, along with
references to "potency,"
         and any similar references in your prospectus.
6.       We note your Summary disclosure on page 2 that you intend to pursue
development of
         your FXR agonist product candidates for the treatment of Inflammatory
Bowel Disease, or
         IBD, including Ulcerative Colitis, or UC, and Crohn   s disease.
Please provide us with
         your analysis as to why it is appropriate to include the lengthy
Summary discussion of
         these indications and emphasis on the $9 billion annual market
opportunity for IBD given
         it appears your product candidates are preclinical for such
indication. We note your
         disclosure that you plan to submit an IND for an undisclosed product
candidate in 2022.
 Preston Klassen, M.D.
FirstName
Metacrine, LastNamePreston Klassen, M.D.
           Inc.
Comapany
July       NameMetacrine, Inc.
     27, 2020
July 27,
Page  3 2020 Page 3
FirstName LastName
7.       We note your disclosure that "[i]n preclinical studies of our FXR
agonists, we have
         observed improvement in colon inflammation on a level similar to that
of biologics
         currently used for treatment. We believe an oral, once-daily therapy
with FXR agonists,
         such as those in our FXR program, could be an attractive treatment
option for IBD
         patients." Efficacy is a determination that is solely within the
authority of the FDA or
         similar foreign regulators. Additionally, comparisons to other
available treatments
         require head-to-head trials. Please delete the statements indicating
that your FXR agonists,
         which haven't been clinically tested for this indication are effective
at treating IBD and
         remove any comparisons with third party treatments, including your
perceived similarity
         to existing therapies currently used for treatment.
8.       We note that the status arrows in your pipeline chart on pages 4 and
86 end at different
         locations within the columns. Please include a narrative that
describes what the chart is
         depicting.
9.       We note that your pipeline table includes the "MET409 or MET642" for
IBD
         Monotherapy, as preclinical programs that you are exploring, but it
appears you don't plan
         to file an IND for either of these candidates for such indication
until 2022. As your
         narrative disclosure only briefly discusses these programs for any
indication within the
         class of IBD, an IND is not planned until two years from now and you
have not allocated
         any proceeds for their development in your use of proceeds section,
please explain to us
         why you believe these programs are sufficiently material to your
business to be included
         in your pipeline table. Your analysis should address specific product
candidates and
         indications within IBD.
10.      We note that your pipeline table includes "MET409 or MET642" for
"other indications"
         as preclinical programs that you are exploring. As you only discuss
these programs in
         general terms very briefly in the prospectus and you have not
allocated any proceeds for
         their development in your use of proceeds section, please provide us
your analysis
         supporting your determination to include a specific product candidate
for a specific
         indication in this category in your pipeline table.
11.      Please remove the last row of your pipeline table that generically
references
         "inflammation and fibrosis targets" and then "NASH," neither of which
are a summary of
         your research and development programs.
12.      We note your disclosure that your lead candidate, MET409, completed
Phase 1b clinical
         trial as a monotherapy in the Netherlands and that you plan to
initiate a Phase 2a
         combination trial in the first half of 2021 of MET409 with an
antidiabetic agent in patients
         with type 2 diabetes and NASH, and expect to report topline data in
the first half of 2022.
         Please revise your disclosure to indicate whether you are conducting
the Phase 2a trial in
         the United States and if so, whether you have submitted an IND to FDA.
To the extent
         that you have submitted an IND, disclose when you submitted it and
identify
         the IND sponsor(s) and the specific indications listed therein. Please
disclose whether you
         believe that clinical data generated in the Netherlands will be
accepted by the FDA and its
 Preston Klassen, M.D.
FirstName
Metacrine, LastNamePreston Klassen, M.D.
           Inc.
Comapany
July       NameMetacrine, Inc.
     27, 2020
July 27,
Page  4 2020 Page 4
FirstName LastName
         foreign equivalents and therefore enable you to commence your planned
Phase 2a trials in
         the United States, without the need to repeat your Phase 1 clinical
trial in the United
         States.
13.      Please state when you plan to submit an IND in advance of your plans
to initiate a Phase
         2a, randomized, placebo-controlled trial of MET642 in patients with
NASH in the first
         half of 2021.
14.      We note your intent to expand the development of your FXR program into
IBD. Please
         identify the product candidate and specific IBD indication referenced
and state with more
         specificity when you plan to submit an IND and when you intend to
initiate a Phase 2a
         clinical trial in IBD patients in 2022.
15.      We note your Risk Factor disclosure that "...some of our competitors
may have ongoing
         clinical trials for product candidates that would treat the same
indications as our product
         candidates, and patients who would otherwise be eligible for our
clinical trials may
         instead enroll in clinical trials of our competitors    product
candidates. This is acutely
         relevant (emphasis added) for our development of MET409 and MET642 for
the
         treatment of patients with NASH and IBD, diseases for which there are
significant
         competition (emphasis added) for clinical trial subjects." Please
consider whether this is
         material to your business and as such should be included on page 5,
Risks Associated with
         Our Business.
We are an early stage biopharmaceutical company with a very limited operating
history., page 12

16.      We note that you disclose your results for the fiscal years ended
December 31, 2018 and
         December 31, 2019, and for the six months ended June 30, 2020. Please
expand your
         disclosure here and throughout your registration statement, where
appropriate, to includes
         results for the six months ended June 30, 2019.
Risk Factors
We are very early in our development efforts and we have limited experience
conducting clinical
trials in humans., page 15

17.      We note your disclosure that "[t]o date, MET409 and MET642 have only
been evaluated
         for safety and toxicology in animals for up to 13 weeks and 16 weeks,
respectively, and
         their longer term toxicity is unknown." Please confirm that this is
current information, as
         it appears to be inconsistent with your clinical development
disclosures.
We rely, and intend to rely, on third parties to conduct our clinical trials
and perform some of our
research and preclinical studies., page 30

18.      We note that you rely, and intend to rely, on third parties to conduct
your clinical trials
         and perform certain other tasks. To the extent material, attach any
agreements covering
         such relationships.
Use of Proceeds, page 64
 Preston Klassen, M.D.
Metacrine, Inc.
July 27, 2020
Page 5

19.      Please disclose how far into development (e.g., phase of clinical
study) for each product
         candidate with a specific indication you anticipate the proceeds of
this offering will allow.
Expedited development and review programs, page 106

20.      Please expand your disclosure to explicitly state that fast track
designation does not
         guarantee an accelerated review by the Food and Drug Administration.
Amended and Restated Certificate of Incorporation and Amended and Restated
Bylaws, page
151

21.      Please provide amended bylaws that reflect your disclosures regarding
the applicability of
         your exclusive forum provision to Exchange Act and Securities claims
or revise your
         disclosure here and your risk factor to clarify that your bylaws do
not explicitly address
         the Exchange Act or Securities Act.
        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
July 27, 2020 Page 5                                           Office of Life
Sciences
FirstName LastName