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April 24, 2024
Troy Ignelzi
Chief Financial Officer
Rapport Therapeutics, Inc.
1325 Boylston Street, Suite 401
Boston, MA 02215
Re:Rapport Therapeutics, Inc.
Draft Registration Statement on Form S-1
Submitted March 27, 2024
CIK No. 0002012593
Dear Troy Ignelzi:
            We have reviewed your registration statement and have the following comments.
            Please respond to this letter by amending your registration statement and providing the
requested information. If you do not believe a comment applies 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 this letter, we may have additional comments.
Draft Registration Statement on Form S-1 submitted March 27, 2024
Introduction to RAP-219, page 4
1.We refer to your disclosures on pages 5 and 114 stating that RAP-219 binds to TARPy8
and that RAP-219 actions are restricted to specific regions of the central nervous system.
With reference to your disclosure on page 128, it is not clear that you have clinical data to
support such definitive claims.  Please revise or advise.
Our Pipeline, page 4
2.Please revise the text below the table to clarify that the Phase 1 trials were administered to
healthy adults. In this regard, the existing disclosure suggests that the Phase 1 trials were
conducted on patients who exhibited the indications identified in the table.
The successful development of pharmaceutical products..., page 19
3.We note your disclosure concerning RAP-482. With a view to disclosure, please tell us

 FirstName LastNameTroy Ignelzi
 Comapany NameRapport Therapeutics, Inc.
 April 24, 2024 Page 2
 FirstName LastName
Troy Ignelzi
Rapport Therapeutics, Inc.
April 24, 2024
Page 2
whether RAP-482 was your lead product candidate prior to the clinical hold and whether
you had devoted material resources to its development. Also, revise to discuss, as
applicable, where in the development process you were (e.g., Phase 1) when FDA
instituted the clinical hold.
Management's Discussion and Analysis of Financial Condition and Results of Operations, page
90
Results of Operations, page 97
4.We note from page 98 that most of your direct external program expenses are attributed to
RAP-219. Considering the three indications for which RAP-219 is being developed from
the pipeline on page 4, please tell us what consideration you have given to disclosing
RAP-219 research and development costs by indication or therapeutic area.
Critical Accounting Policies and Estimates, page 104
Stock-Based Compensation, page 105
5.We note the determination of fair value information provided on page 108. Noting from
page F-38 the option grants made in January-March 2024, once you have an estimated
offering price or range, please explain to us how you determined the fair value of the
common stock underlying your equity issuances and the reasons for any differences
between the recent valuations of your common stock leading up to the initial public
offering and the estimated offering price.
Introduction to RAP-219, page 114
6.We note your disclosure on page 114 referencing your “targeted therapeutic exposures.”
Please disclose these targets here or elsewhere in the Business section, or advise.
RAP-219 Preclinical Studies, page 121
7.We note that your disclosure on page 121 presents a pre-clinical trial involving a drug that
is identified as “a RAP-219 analog.” Please disclose your basis for identifying this drug as
an analog. Please provide similar disclosures on pages 122 and 126 where you present
trials involving other RAP-219 analogs.
Clinical Development Plan of RAP-219 in Focal Epilepsy, page 128
8.Please revise to clarify whether you have established the LE endpoint or whether this
remains pending. With reference to your disclosure concerning spike rate and spectral
power, please indicate whether any secondary endpoints have been established.
9.With reference to your risk factor disclosure on page 29, please revise to indicate whether
you have sought or will seek input from FDA staff regarding the RNS proof-of-concept
protocol and the establishment of your endpoint(s).

 FirstName LastNameTroy Ignelzi
 Comapany NameRapport Therapeutics, Inc.
 April 24, 2024 Page 3
 FirstName LastName
Troy Ignelzi
Rapport Therapeutics, Inc.
April 24, 2024
Page 3
Executive Compensation, page 171
Outstanding Equty Awards at 2023 Fiscal Year End , page 174
10.We note the option exercise prices listed as $0.21 per share had vesting commencement
dates of August 7, 2023 and November 1, 2023. Please explain why this table
apparently does not include the options granted on December 6, 2023 shown from the
table on page 107, if the exercise price of those options was also $0.21 per share.
Conversely, please explain why the table on page 107 does not appear to include the
options as listed in the table hereunder.
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.
            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.
            Please contact Jenn Do at 202-551-3743 or Daniel Gordon at 202-551-3486 if you have
questions regarding comments on the financial statements and related matters. Please contact
Tamika Sheppard at 202-551-8346 or Joe McCann at 202-551-6262 with any other questions.
Sincerely,
Division of Corporation Finance
Office of Life Sciences
cc:       Kingsley Taft