United States securities and exchange commission logo





                              March 18, 2022

       Anatoly Dritschilo
       Chief Executive Officer
       Shuttle Pharmaceuticals Holdings, Inc.
       One Research Court, Suite 450
       Rockville, MD 20850

                                                        Re: Shuttle
Pharmaceuticals Holdings, Inc.
                                                            Draft Registration
Statement on Form S-1
                                                            Submitted September
16, 2019
                                                            CIK No. 0001757499

       Dear Dr. Dritschilo:

              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.

       Amendment No. 1 to Draft Registration Statement Submitted February 11,
2022

       Summary Financial Information, page 12

   1.                                                   Please revise the
financial information presented here to also include loss per share
                                                        calculations.
       Research and Development-Net of contract expense reimbursements, page 44

   2.                                                   Please revise to
disclose the costs incurred during each period presented for each of your
                                                        key research and
development products/projects. If you do not track your research and
                                                        development costs by
project, please disclose that fact and explain why you do not
                                                        maintain and evaluate
research and development costs by project. Provide other
                                                        quantitative or
qualitative disclosure that provides more transparency as to the type of
 Anatoly Dritschilo
FirstName  LastNameAnatoly   Dritschilo
Shuttle Pharmaceuticals Holdings, Inc.
Comapany
March      NameShuttle Pharmaceuticals Holdings, Inc.
       18, 2022
March2 18, 2022 Page 2
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FirstName LastName
         research and development expenses incurred (i.e., by nature or type of
expense) which
         should reconcile to total research and development expense on the
Consolidated
         Statements of Operations.
Financial Statements
Note 2- Summary of Significant Accounting Policies
Fair Value of Finanicial Statements, page F-10

3.       We note your disclosures stating, "In drawing its conclusions,
management considered
         various relevant factors, including the work of an independent
third-party valuation firm
         engaged to provide a valuation analysis as of June 30, 2019, which
indicated a valuation
         of $12.61 per common share. Management ultimately determined, and the
valuation firm
         concurred, that the Market Approach method was the most appropriate
valuation
         methodology under the circumstances." Please tell us your reliance on
a third-party and
         how you considered filing a written consent of this entity as an
exhibit to your registration
         statement. Refer to Rule 436 and Section 7 of the Securities Act and
Question 141.02 of
         the Compliance and Disclosure Interpretations on Securities Act
Sections, which can be
         found at https://www.sec.gov/corpfin/securities-actsections.
Note 8- Stockholders' Equity
Equity Incentive Plan, page F-17

4.       We note your disclosure stating that your 2018 Equity Incentive Plan
provides for equity
         incentives to be granted to your employees, executive officers, or
directors and to key
         advisers and consultants, which may be in the form of stock options,
restricted stock
         awards, other stock based awards, or any combination of the foregoing.
As it relates to
         the 773,453 shares granted under your 2018 equity Incentive Plan,
please expand your
         disclosure to include all of the information required by ASC
718-10-50-2, as applicable to
         you.
Amendment to Form S-1 filed February 11, 2022

Cover Page

5.       We note your response to comment 1 indicating that you are not
registering any shares for
         resale. However, your registration statement references 500,000 shares
being sold by your
         selling shareholders. Please revise your fee table to include the
shares being offered by
         your selling shareholders and file the fee table as an exhibit to your
registration statement.
         Please see Item 601(b)(107) of Regulation SK. Additionally, we note
your cover page
         indicates your intention to offer securities on a delayed and
continuous basis. Given that
         you are conducting a firm commitment offering, please explain why you
have indicated
         that you are relying on Rule 415.
 Anatoly Dritschilo
FirstName  LastNameAnatoly   Dritschilo
Shuttle Pharmaceuticals Holdings, Inc.
Comapany
March      NameShuttle Pharmaceuticals Holdings, Inc.
       18, 2022
March3 18, 2022 Page 3
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FirstName LastName
Prospectus Summary, page 1

6.       Please revise your summary to present a balanced view of your company
and its current
         stage of development by focusing on the most material aspects of your
company,
         eliminating the predictive assumptions and clearly stating that you
have no FDA approved
         products, disclosing that you are several years away from applying for
a new drug
         application, have never generated any product revenue and received an
audit report that
         raised substantial doubt about your ability to continue as a going
concern. For example:

                Eliminate the description of your product candidates as
"first-in-class." The
              description applies to a product that has received FDA approval;
                Remove your statement that you intend to follow the FDA's
fast-track development
              program for developing Ropidoxuridine as it is not appropriate to
assume the
              required evidence of efficacy from trials that you have not yet
conducted;
                Remove statements predicting positive results and future
partnerships, such as
              "Positive results from proof-of-concept studies will enable
collaborative partnerships
              with other pharmaceutical companies for Phase III clinical
trials";
                Ensure that you discuss the risks and obstacles you face in
developing your product
              candidates with the same level of detail as you use to discuss
the positive aspects of
              your operations.

7.       Move the detailed scientific explanations of the mechanism of action
of your candidates
         and discussions of clinical trial results to the Business section
where the disclosure can be
         placed in the proper context.
8.       We have reviewed your revisions in response to our prior comment 4 and
reissue. There
         are still multiple numerous references to the safety and efficacy
throughout your
         disclosure. Efficacy and safety are determinations that are solely
within the authority of
         the FDA. You may present clinical trial end points and objective data
resulting from trials
         without concluding efficacy, and you may state that your product
candidates are well
         tolerated, if accurate. Please revise any statements referencing
safety and efficacy
         throughout your document, including but not limited to the following:

                on page 44, "The clinical development of Ropidoxuridine has
shown drug safety,
              bioavailability and a maximum tolerated dose has been established
for use in Phase II
              clinical trials."
                on page 48, "These results support the safety and potential
efficacy in combination
              with radiation and provide the foundation for design of Phase
Ib/II clinical trials in
              brain tumors and Phase II clinical trials in sarcomas or
un-resectable pancreatic
              cancers, with all three disease sites being eligible for orphan
disease designations."
                on page 49, "suggesting that a combination of SP-1-303 with an
immune checkpoint
              blocker may enhance the therapeutic efficacy in hormone
responsive breast cancer."
 Anatoly Dritschilo
FirstName  LastNameAnatoly   Dritschilo
Shuttle Pharmaceuticals Holdings, Inc.
Comapany
March      NameShuttle Pharmaceuticals Holdings, Inc.
       18, 2022
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FirstName LastName
9.       Please provide a textual discussion explaining the graphic appearing
at the bottom of page
         2. It appears to depict two product candidates and the potential
disease indications you
         intend to develop the candidates to address but it is not clear what
the arrows are intended
         to depict. Additionally, it does not indicate provide any indication
of what remains to be
         done to develop the product candidate.
10.      Please revise your disclosure to clarify whether you have filed an IND
for your Phase I
         study of Extended Bio-availability Ropidoxurdine (IPdR/TPI) and, if
accurate clarify
         that SP-1-161 and SP-1-303 are in pre-clinical stages of development.
11.      We note your statement on page 4 indicating that you "intend to
perform clinical studies
         to support the FDA's efficacy and safety findings (IND-enabling
studies) for the -
         IPdR/TPI combination..." Please explain your reference to the FDA's
efficacy and safety
         findings. If this is a reference to the approval to conduct a Phase I
clinical trial, please
         delete the reference to the FDA's efficacy and safety findings. The
FDA continues to
         assess safety and efficacy throughout the entire development process
and it is not
         appropriate to interpret FDA approval of your Phase I trial as an FDA
finding related to
         safety and/or efficacy.
Development Strategy, page 6

12.      Please clarify the meaning of "CTEP," and "MTD" and explain the
significance of
         Temodar.
Market Opportunity, page 6

13.      Please revise your table on page 6 to explain the significance of the
asterisks and to
         explain the the headers "RT Cases Annually" and "RT Cases
(estimated)." Do the RT
         Cases estimated relate to a different time period? What is the basis
for the estimate?
Pre-IPO Bridge Financing, page 8

14.      Please explain the timing of your plan to use funds from this offering
to repay two
         accredited investors, who will use such proceeds to exercise their
warrants and sell their
         shares in this offering. It appears that the shares they are planning
to sell in this offering
         will not be outstanding at the time of your offering.
 Anatoly Dritschilo
FirstName  LastNameAnatoly   Dritschilo
Shuttle Pharmaceuticals Holdings, Inc.
Comapany
March      NameShuttle Pharmaceuticals Holdings, Inc.
       18, 2022
March5 18, 2022 Page 5
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FirstName LastName
Business
Our Pipeline, page 48

15.      We note that your table indicates you have completed Phase I in your
development of
         Ropidoxuridine. However, the description of your product candidate
indicates that your
         Phase I clinical trial results provide the foundation for the design
of Phase Ib/II clinical
         trials. Your pipeline table should depict when an entire phase of
development has been
         completed, as opposed to one of multiple trials in a phase of
development. Please tell us
         why you believe it is appropriate to indicate that you have completed
Phase I testing when
         you are planning to conduct a Phase Ib/II trial.
16.      Please revise your table to clarify which product candidates Class II
HDAC6 Selective,
         Class I - ER+ Targeting and Dual Functional Pan HDAC are and identify
the indications
         you are seeking to treat with your candidates.
17.      Please expand your business section to explain the Cell Lines and Cell
Products and
         Patient Metabolite testing kit.
18.      We note your description of Ropidoxuridine discloses the results of
fourteen of the
         eighteen participants in the study, please revise to describe the
results of the other four
         participants.
Our Product Candidates, page 60

19.      We note your disclosure indicates you have received an SBIR contract
from NIH to fund a
         Phase I trial with Brown University to determine the maximum tolerated
dose in patients
         with advanced gastrointestinal cancers. This disclosure appears to
related to the Phase I
         trial that has been completed. Please revise to update your
disclsoure.
Strategic Agreements, page 60

20.      The significance of the identified strategic agreements is unclear.
Please revise to your
         descriptions to provide additional information. For example:

                With respect to the agreement with Georgetown, we note that
Georgetown acted as a
              subcontractor for the work you conducted pursuant to two SBIR
contracts. Please
              clarify whether the intellectual property you have the option to
license is related to
              those subcontract agreements, including whether the intellectual
property was
              developed by Georgetown in the course of conducting such work or
if Georgetown
              University used it's own previously developed intellectual
property in performing the
              subcontracted work. If you develop candidates related to the
African-American
              prostate cancer health disparities project or the metabolomic
biomarker project, is
              such development dependent on intellectual property owned by
Georgetown
              University?
                With respect to the material transfer agreement with Georgetown
University, please
              clarify whether your HDAC inhibitor platform technology is
dependent on this
 Anatoly Dritschilo
FirstName  LastNameAnatoly   Dritschilo
Shuttle Pharmaceuticals Holdings, Inc.
Comapany
March      NameShuttle Pharmaceuticals Holdings, Inc.
       18, 2022
March6 18, 2022 Page 6
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FirstName LastName
              agreement. If so, please describe the material terms of this
agreement, including
              payment terms as well as your rights and obligations under the
agreement.
21.      Please describe all material provisions of your agreement with
Propagenix, including
         identifying your product candidates that are dependent on the
agreement, and quantifying
         any amounts paid, potential future milestone payments and royalty
provisions.
The SBIR Program, page 63

22.      Please clarify the material terms of each of your SBIR contracts,
including funding
         received to date, potential future funding and what you need to
accomplish to qualify for
         the future funding. Additionally, clarify the ownership of any
intellectual property
         developed during the course of the program. To the extent the NIH
receives any rights to
         the intellectual property, please clarify.
23.      Please clarify your strategy for commercializing prostate cancer cell
lines and and
         predictive biomarkers. For example, your table on page 48 references a
testing kit, but
         there is no disclosure about plans to develop a testing kit.
Collaborative Arrangements, page 64

24.      We note your response to our prior comment 12, stating that all
relevant references to
         Doranidazole have been removed from the prospectus. However, there are
still several
         references to Doranidazole throughout your disclosure. Please remove
them or advise.
Executive Compensation, page 81

25.      Please update your Summary Compensation Table.
Related Party Transactions, page 83

26.      Please revise your descriptions of the related party transactions to
also include the identify
         the related party.
Signatures, page II-3

27.      We have reviewed your response to our prior comment 24 and reissue.
Please ensure that
         the requisite signatures and dates are provided when you amend your
registration
         statement.
 Anatoly Dritschilo
Shuttle Pharmaceuticals Holdings, Inc.
March 18, 2022
Page 7

       You may contact Kevin Kuhar at 202-551-3662 or Tracie Mariner at
202-551-3744 if
you have questions regarding comments on the financial statements and related
matters. Please
contact Jordan Nimitz at 202-551-5831 or Suzanne Hayes at 202-551-3675 with any
other
questions.



                                                          Sincerely,
FirstName LastNameAnatoly Dritschilo
                                                          Division of
Corporation Finance
Comapany NameShuttle Pharmaceuticals Holdings, Inc.
                                                          Office of Life
Sciences
March 18, 2022 Page 7
cc:       Megan Penick, Esq.
FirstName LastName