United States securities and exchange commission logo

                             March 15, 2022

       Keith Gottesdiener, M.D.
       President and Chief Executive Officer
       Prime Medicine, Inc.
       21 Erie Street
       Cambridge, MA 02139

                                                        Re: Prime Medicine,
                                                            Amendment No. 3 to
Draft Registration Statement on Form S-1
                                                            Submitted March 7,
                                                            CIK No. 0001894562

       Dear Dr. Gottesdiener:

             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

             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

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

       Our Prime Editing Platform, page 1

   1.                                                   We note your response
to comment 1. We understand your position that the 18 Prime
                                                        Editing programs that
are currently in development are not subject to the risks associated
                                                        with the Broad
Institute License, but we do not agree with your position that the requested
                                                        balancing disclosure
would not be appropriate disclosure for investors. While the Prime
                                                        Editing technology may
have the theoretical potential to repair approximately 90 percent
                                                        of known disease
causing mutations across many organisms, organs and cell types, there
                                                        are material
limitations to your future use of the Prime Editing technology pursuant to
                                                        your licensing
arrangement with Broad Institute. Please add balancing disclosure that that
                                                        your rights to the
Prime Editing technology may be limited by the terms of the Broad
 Keith Gottesdiener, M.D.
Prime Medicine, Inc.
March 15, 2022
Page 2
         Institute license, which are subject to an inclusive innovation model,
are subject to march-
         in-licenses, and that the Broad Institute may terminate your license
with respect to gene
         targets under the terms of the Broad License Agreement.
Our rights to develop and commercialize our Prime Editing platform technology
and product
candidates are subject to the terms. . ., page 45

2.       We note your revised disclosure on page 45 that "once we initiate a
program for a gene
         target, Broad Institute loses the right to use its march-in license
for such gene target." Per
         your agreement with the Broad Institute, please define "gene program"
and clarify how
         you determine when a gene program has been initiated. Additionally, if
true, please
         clarify in the filing that none of the Company   s current gene target
programs are subject to
         Broad Institute   s march-in license because they have been initiated.
Research Collaboration, Option and License Agreement with Myeloid, page 183

3.       We note your response to comment 16. Please tell us whether Dr. Thomas
         whom you disclose is the "founding investor and director" of Myeloid
Therapeutics on
         page 209, was a party to this contract. If so, please file your
Research Collaboration,
         Option and License Agreement with Myeloid as an exhibit.
11. License and Collaboration Agreements
Related Party Beam Collaboration Agreement, page F-40

4.     We note your response to comment 18 in which you state that for both
protected and non-
       optioned products, you are eligible to receive development and
sales-based milestones as
       well as tiered royalties with the only difference in economics being the
protected product
       option fee of either $5.0 million or $10.0 million. You further state
that you are also
       eligible to receive such milestones and royalties for collaboration
products outside of the
       United States. It therefore remains unclear to us how you determined
that the arrangement
       does not include any variable consideration at contract inception,
recognizing that such
       variable consideration may be fully constrained. In this regard, it does
not appear that
       upon exercise of either the protected product or collaboration option
that you are required
       to provide any additional goods or services under the arrangement, and
therefore any
       additional consideration would relate to the combined performance
obligation determined
       at contract inception. Please advise or revise your disclosure to
clarify that you are
FirstName LastNameKeith Gottesdiener, M.D.
       eligible for certain milestones and royalties regardless of whether any
options are
Comapany    NamePrime
       exercised  and thatMedicine,  Inc.
                           such consideration  is considered variable
consideration that may be
       fully constrained
March 15, 2022 Page 2     at contract inception.
FirstName LastName
 Keith Gottesdiener, M.D.
FirstName  LastNameKeith Gottesdiener, M.D.
Prime Medicine,  Inc.
March      NamePrime Medicine, Inc.
       15, 2022
March3 15, 2022 Page 3
FirstName LastName
       You may contact Tracey Houser at 202-551-3736 or Angela Connell at
202-551-3426 if
you have questions regarding comments on the financial statements and related
matters. Please
contact Dillon Hagius at 202-551-7967 or Tim Buchmiller at 202-551-3635 with
any other


                                                          Division of
Corporation Finance
                                                          Office of Life
cc:      Marishka DeToy, Esq.