April 26, 2019

Steven Paul, M.D.
Chief Executive Officer, President and Chairman
Karuna Therapeutics, Inc.
33 Arch Street, Suite 3110
Boston, MA 02110

       Re: Karuna Therapeutics, Inc.
           Draft Registration Statement on Form S-1
           Submitted March 29, 2019
           CIK No. 0001771917

Dear Dr. Paul:

       We have reviewed your 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 submitted March 29, 2019

Pipeline Overview, page 2

1.     We note your inclusion of "Muscarinic-Targeted Drug Candidate" in your
pipeline table
       on pages 2 and 103. Please expand your disclosure on page 115 to
describe your
       discovery and preclinical development of these programs including,
whether preclinical
       trials have been conducted, and if so, provide a summary of the studies
performed and
       identify any known potential indications. Please note, product
candidates should only be
       included in the table if they are material. If you have not conducted
studies relating to
       these additional product candidates, please remove them from the table
or explain the
       basis for your belief that they are material product candidates. .
Third-Party Clinical Trials Support Xanomelines Development, page 3
 Steven Paul, M.D.
FirstName LastNameSteven Paul, M.D.
Karuna Therapeutics, Inc.
Comapany NameKaruna Therapeutics, Inc.
April 26, 2019
April 2 2019 Page 2
Page 26,
FirstName LastName

2.       Please delete your statements indicating xanomeline's efficacy here
and in the business
         section, such as "xanomeline was associated with meaningful
dose-dependent
         improvements;" "trospium was associated with meaningfully fewer
cholergic adverse
         events;" "KarXT has strong clinical and commercial potential;"
"Xanomeline has
         exhibited promising antipsychotic and precognitive effects;" "data
suggest xanomeline
         may improve cognition in patients with AD:" and "Xanomeline has
exhibited
         antipsychotic and precognitive benefits." Safety and efficacy
determinations are the
         exclusive authority of the FDA or alternative foreign regulators. You
may provide a
         summary of the data that you used to draw these conclusions, but not
the conclusions or
         predictions that the product candidates are safe or effective.
3.       We note that Xanomeline's side effects resulted in a high rate of
discontinuation in the
         mid- and high-dose cohorts, leading to a substantial reduction of
statistical power. Please
         expand the discussion to quantify the approximate percentage of
subjects in the clinical
         trial that discontinued treatment.
4.       We note your statement that cognitive symptoms of patients with AD
treated with
         xanomeline showed improvements compared to placebo as measured by both
the ADAS-
         Cog and the CIBIC+, suggesting that xanomeline can also improve
         cognition. Please revise to present the data you used to draw this
conclusion. In addition,
         please disclose the sample size in the mid-dose cohort. Please make
corresponding
         revisions to the disclosure in your Business section on page 107.
Our Clinical Trials, page 4

5.       Please revise the discussion of your Phase 1 clinical trial to replace
the statement relating
         to "meaningfully fewer cholinergic adverse events" to present the data
you used to draw
         this conclusion. Please make corresponding revisions to the disclosure
in your Business
         section on page 110.
Use of Proceeds, page 76

6.       Please revise the discussion to clarify whether you expect to complete
each development
         phase referenced. For example, the first bullet point indicates you
expect to fund the
         completion of your ongoing Phase 2 clinical trial and a planned Phase
3 trial for the
         treatment of psychosis. Please clarify whether you expect to complete
both the Phase 2
         and 3 trials or if you expect to complete the Phase 2 trial and begin
the Phase 3 trial.
Management's Discussion and Analysis of Financial Condition and Results of
Operations
Critical Accounting Policies and Estimates
Determination of the Fair Value of Common Stock, page 97

7.       Once you have an estimated offering price or range, please explain to
us the reasons for
         any differences between the recent valuations of your common shares
leading up to the
 Steven Paul, M.D.
Karuna Therapeutics, Inc.
April 26, 2019
Page 3
         initial public offer and the estimated offering price. This
information will help facilitate
         our review of your accounting for equity issuances including stock
compensation.
Xanomeline for the Treatment of Psychotic Symptoms and Agitation in AD, page
106

8.       Please clearly disclosure the number of patients out of the 343 that
participated in the 225
         mg xanomeline arm compared to placebo.
Exclusive Jurisdiction for Certain Actions, page 171

9.       We note your restated certificate of incorporations provides that the
Court of Chancery of
         the State of Delaware will be the sole and exclusive forum for any
derivative action or
         proceeding brought on your behalf. Please revise this section, and the
risk factor on page
         72, to include a discussion regarding whether your exclusive forum
provision applies to
         actions arising under the federal securities laws. In this regard, we
note that Section 27 of
         the Exchange Act creates exclusive federal jurisdiction over all suits
brought to enforce
         any duty or liability created by the Exchange Act or the rules and
regulations thereunder.
Exhibits

10.      We note your reference to the Wellcome Funding Agreements. Please file
these
         agreements or provide further analysis as to why you are not required
to file these
         agreements as exhibits pursuant to Item 601(b)(10) of Regulation S-K.
General

11.      Please supplementally provide us with copies of all written
communications, as defined in
         Rule 405 under the Securities Act, that you, or anyone authorized to
do so on your behalf,
         present to potential investors in reliance on Section 5(d) of the
Securities Act, whether or
         not they retain copies of the communications.
12.      Please provide us proofs of all graphics, visual, or photographic
information you will
         provide in the printed prospectus prior to its use, for example in a
preliminary prospectus.
         Please note that we may have comments regarding this material.
       You may contact Bonnie Baynes at 202-551-4924 or Angela Connell at
202-551-3426 if
you have questions regarding comments on the financial statements and related
matters. Please
contact Jeffrey Gabor at 202-551-2544 or Suzanne Hayes at 202-551-3675 with any
other
questions.



FirstName LastNameSteven Paul, M.D.                             Sincerely,
Comapany NameKaruna Therapeutics, Inc.
                                                                Division of
Corporation Finance
April 26, 2019 Page 3                                           Office of
Healthcare & Insurance
FirstName LastName