United States securities and exchange commission logo





                               March 3, 2021

       Mark C. McKenna
       President and Chief Executive Officer
       Prometheus Biosciences, Inc.
       9410 Carroll Park Drive
       San Diego, California 92121

                                                        Re: Prometheus
Biosciences, Inc.
                                                            Registration
Statement on Form S-1
                                                            Filed February 19,
2021
                                                            File No. 333-253323

       Dear Mr. McKenna:

              We have reviewed your 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 amending your registration
statement and providing the
       requested information. 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 any amendment to your registration statement and
the information you
       provide in response to these comments, we may have additional comments.

       Registration Statement on Form S-1, Filed February 19, 2021

       Prospectus Summary
       Our Portfolio, page 2

   1.                                                   We note that both
product candidates added to the pipeline table, PR1800 and PR2100,
                                                        are early in the
discovery stage and that there is very little discussion of these programs in
                                                        your filing. Please
tell us why you believe these product candidates are material enough to
                                                        be included in the
pipeline table.
       Use of Proceeds, page 74

   2.                                                   We note your revisions
in response to prior comment 2 that with offering proceeds, you
                                                        will complete
IND-enabling preclinical studies and commence clinical development for
                                                        the PR600 program.
Please clarify how far in clinical development of PR600 you will
 Mark C. McKenna
Prometheus Biosciences, Inc.
March 3, 2021
Page 2
      reach with the offering proceeds. If you will not complete Phase 1,
please revise to so
      state.
Business, page 97

3.    We note your response to our prior comment number 3. Please revise your
Business
      section to include p-values for studies that were powered for statistical
significance and
      explain the meaning of p-values and how they relate to the FDA   s
standards of efficacy.
        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.

       Refer to Rules 460 and 461 regarding requests for acceleration. Please
allow adequate
time for us to review any amendment prior to the requested effective date of
the registration
statement.

       You may contact Ameen Hamady at 202-551-3891 or Daniel Gordon at
202-551-3486 if
you have questions regarding comments on the financial statements and related
matters. Please
contact Margaret Schwartz at 202-551-7153 or Mary Beth Breslin at 202-551-3625
with any
other questions.



                                                            Sincerely,
FirstName LastNameMark C. McKenna
                                                            Division of
Corporation Finance
Comapany NamePrometheus Biosciences, Inc.
                                                            Office of Life
Sciences
March 3, 2021 Page 2
cc:       Matthew T. Bush
FirstName LastName