SecProbe.io

CORRESP
1
filename1.htm

CORRESP

 Divakar Gupta

 T:
(212) 479-6474

dgupta@cooley.com

Via EDGAR

 June 12, 2023

 U.S.
Securities and Exchange Commission

 Division of Corporation Finance

Office of Life Sciences

 100 F Street, N.E.

Washington, D.C. 20549

 Attention:    Lauren Sprague Hamill

     Joshua Gorsky

     Christine Torney

     Mary Mast

Re:
 Turnstone Biologics Corp.

Draft Registration Statement on Form S-1

Submitted on May 15, 2023

CIK No. 0001764974

 Ladies and
Gentlemen:

 On behalf of Turnstone Biologics Corp. (the “Company”), the following information is submitted in response to the
comments received from the staff (the “Staff”) of the U.S. Securities and Exchange Commission (the “Commission”) by letter dated June 9, 2023 (the “Comment Letter”)
regarding the above-referenced draft Registration Statement on Form S-1, as confidentially submitted to the Commission on May 15, 2023. Concurrently with the submission of this response letter, the
Company is filing its Registration Statement on Form S-1 (the “Registration Statement”) with the Commission. In addition to addressing the comments raised by the Staff in the Comment
Letter, the Company has included other revisions and updates to its disclosure in the Registration Statement.

 For the convenience of the Staff, the
numbering of the paragraphs below corresponds to the numbering of the respective comment in the Comment Letter, the text of which we have incorporated into this response letter for convenience in italicized type and which is followed by the
Company’s response. In the responses below, page number references are to the Registration Statement.

 Draft Registration Statement on Form S-1 submitted on May 15, 2023

 Cover Page

1.
 We note that you have applied to list your common stock on the Nasdaq Global Market. Please revise the cover
page of the prospectus as follows, and make conforming revisions where appropriate:

•

 State, if true, that no assurance can be given that your listing application will be approved.

 Cooley LLP    55 Hudson Yard    New York, NY 10001

t: +1 212 479 6000    f: +1 212 479 6275    cooley.com

 U.S. Securities and Exchange Commission

June 12, 2023

Page Two

•

 Disclose whether your offering is contingent upon final approval of your NASDAQ listing, and ensure
this disclosure is consistent with your underwriting agreement. If your offering is not contingent on listing approval, include a risk factor describing the consequences of not being listed.

Response: In response to the Staff’s comment, the Company has revised the disclosure on the cover page and pages 79, 219, and 230
of the Registration Statement.

 Prospectus Summary, page 1

2.
 We note that your auditors have issued a going concern opinion regarding your operations. Please revise your
disclosure throughout the prospectus as follows:

•

 Expand and balance your Summary disclosure by including discussion regarding your recurring net operating
losses with the exception of the year ended December 31, 2021, the expectation of continuing operating losses and negative cash flows for the foreseeable future, the termination in 2021 and 2022 of the AbbVie and Takeda Agreements
that appear to have previously been your sole sources of collaboration revenue, the need to raise additional capital to finance your future operations, and the auditor’s going concern opinion.

•

 Revise your summary risk factor on page 7 to disclose that if you cannot continue as a viable entity, your
stockholders may lose some or all of their investment in your company.

 Response: In response to the
Staff’s comment, the Company has revised the disclosure on pages 7, 8, 18 and 19 of the Registration Statement.

3.
 Please revise your prospectus summary to define or explain briefly the following scientific terms:

•

 potency and potent T cells

•

 TIL quality, function, and persistence

•

 clinically meaningful

•

 tumor heterogeneity

•

 PD-(L)1 treatments

Also, we note that you use terms such as “deep and durable response,” “progression-free survival,” “objective
response rate” and “complete response rate” throughout the prospectus when describing third party clinical trial results. Explain the meaning of these terms in relation to observed clinical trial endpoints and clarify, if true, that
they do not indicate that the patient was cured of the condition.

 Response: In response to the Staff’s comment, the
Company has revised the disclosure on pages 1, 2, 3, 4, 100, 101, 121, 123, 124, 131, 132, 133, 134, 145, and 146 of the Registration Statement and has removed references to “deep and durable response”.

Our Solution: Selected TILs, page 2

4.
 You state on page 2 and elsewhere throughout the prospectus that the company is developing next generation
TIL therapies designed to drive “curative outcomes” across multiple solid tumors. If true, please revise to clarify that no TIL therapies have received FDA approval to date and that at present, no therapies in clinical development for the
solid tumor indications that you are addressing are curative.

 Cooley
LLP    55 Hudson Yard    New York, NY 10001

 t: +1 212 479 6000    f: +1 212 479
6275    cooley.com

 U.S. Securities and Exchange Commission

June 12, 2023

 Page Three

 Response: In response to the Staff’s comment, the Company has revised the
disclosure on pages 2, 100, 122, and 130 of the Registration Statement.

5.
 You state on page 2, 113 and 120 that your selective expansion process “results in a substantially
higher absolute number and proportion of tumor-reactive T cells in the final product in comparison to the relatively infrequent tumor-reactive T cells that are routinely found in bulk TIL.” Please revise to provide the basis for this statement,
and quantify the number and proportion of tumor-reactive T cells in Selected TILs versus bulk TIL to the extent appropriate so that investors can compare against your target rate of >70% disclosed in the figure on page 3.

 Response: In response to the Staff’s comment, the Company has revised the disclosure on pages 2, 122, and
130 of the Registration Statement.

6.
 In the figure depicting advantages of Selected TILs over bulk TILs appearing on pages 3, 113, and 121,
please remove or revise the reference to tumor-reactive T cells contributing to “efficacy.” In the appropriate place(s), please provide a reference for your disclosure that the reported median of
on-target tumor-reactive T cells in bulk TIL is <3%. Additionally, on pages 2 and 113, please revise your related narrative discussion to provide context for the statement that Selected TILs hold potential
for “potent” targeted tumor killing as you have on page 121.

 Response: In response to the
Staff’s comment, the Company has revised the disclosure on pages 1, 2, 3, 121, 123, 129, 130, 133, and 136 of the Registration Statement, including to revise the figure to remove references to “efficacy”.

Supporting Clinical Evidence, page 3

7.
 You state on pages 3 and 122 that clinical studies in academic centers utilizing selection strategies to
select for tumor-reactive T cells have “demonstrated positive outcomes in challenging solid tumors, where bulk TILs have had limited to no success.” Please revise your discussion of the results of these and any other clinical trials or
preclinical studies, whether conducted by you or third parties, to remove any conclusory statements regarding the trial results or their meaning and instead focus on the specific factual details of the studies, including quantitative information
regarding the range of results observed and describe the results using objective data and/or terminology based on the trial endpoint(s).

Response: In response to the Staff’s comment, the Company has revised the disclosure on pages 3 and 124 of the Registration
Statement.

 Our Pipeline, page 4

8.
 We note that an investigator-sponsored clinical trial is ongoing with H. Lee Moffitt Cancer Center and
Research Institute, Inc., investigating TIDAL-01 as a potential therapy in both cutaneous and non-cutaneous melanoma. Please expand your disclosure in the appropriate
place(s) to clarify briefly the nature of the investigator-sponsored study, how one differs from a trial sponsored by your company, and your role/responsibility, if any, in the trial. Please also tell us your consideration of providing risk factor
disclosure concerning the clinical trial risks associated with investigator-sponsored clinical trials.

 Cooley
LLP    55 Hudson Yard    New York, NY 10001

 t: +1 212 479 6000    f: +1 212 479
6275    cooley.com

 U.S. Securities and Exchange Commission

June 12, 2023

 Page Four

 Response: In response to the Staff’s comment, the Company has revised the
disclosure on pages 1, 5, 100, 101, 121, 125, 135, and 144 of the Registration Statement. In response to the Staff’s comment, the Company also has further revised risk factor disclosure on pages 46 and 47 of the Registration Statement
concerning the clinical trial risks associated with investigator-sponsored clinical trials.

 Our History and Team, page 5

9.
 Please limit your Summary disclosure of specific investors to those identified in the Principal Shareholder
table on page 194. Additionally, indicate that prospective investors should not rely on the named investors’ investment decision, that these investors may have different investment strategies and risk tolerances. If true, disclose that the
preferred stock offering(s) in which such investors purchased shares were conducted at a significant discount to the IPO price.

Response: In response to the Staff’s comment, the Company has revised the disclosure on pages 6, 126, and 206 of the Registration
Statement. The Company respectfully acknowledges the Staff’s request to disclose if the preferred stock offerings in which investors purchased shares were conducted at a significant discount to the IPO price, however, the Company cannot at this
time ascertain whether such investors purchased shares at a significant discount to the IPO price to which the Registration Statement relates until a bona fide price range for the IPO is determined. The bona fide price range remains
subject to determination based on factors outside of the Company’s control, including market conditions at the time of determination. The Company undertakes to revise its disclosure to address the Staff’s comment
in a subsequent amendment to the Registration Statement that includes the bona fide price range.

 Our Strategy, page 5

10.
 We note your use of the term “high unmet medical need” here and elsewhere throughout the
prospectus, as well as your statement that you are pursuing a clinical development strategy designed to “support an efficient path to registration.” Such statements might imply that your products are eligible for fast track designation or
priority review granted by the FDA for products that treat certain serious unmet medical needs. If material, please expand this section to provide context for these references and briefly explain your development strategy for your TIL product
candidates in the U.S. and abroad. In this regard, we note that you state on page 55 that you intend to seek approval for your candidates in both the U.S. and in “selected foreign jurisdictions,” which should be identified to the extent
known or reasonably anticipated.

 Additionally, please revise pages 6 and 117 to explain how the design of your
analytical characterization program will “minimize regulatory hurdles” or remove this reference.

 Response: In
response to the Staff’s comment, the Company has revised the disclosure on pages 6, 7, 59, 101, 125, 126, 127, 135, 136, 137, 144, and 145 of the Registration Statement. Because the Company is very early in its clinical development efforts, it
is too preliminary at this time to discuss fast track designation or priority review that might be granted by the FDA and as a result, the Company has removed references to “high unmet medical need” and further has not added disclosure
relating to fast track designation or priority review. Furthermore, the Company acknowledges the Staff’s comment to explain the Company’s development strategy for the Company’s TIL product candidates in the U.S. and abroad, if
material, and respectfully advises the Staff that the Company did not include such disclosure because it is not material to the Company’s business at this time.

 Cooley
LLP    55 Hudson Yard     New York, NY 10001

 t: +1 212 479 6000    f: +1 212
479 6275    cooley.com

 U.S. Securities and Exchange Commission

June 12, 2023

 Page Five

11.
 We note that you have initiated two Phase 1 clinical trials for your lead product candidate, TIDAL-01, for the treatment of various cancers. On page 5, you state your belief that positive results from one or both of these clinical trials has the potential to support advancement of TIDAL-01 into registrational trials across multiple solid tumor types. Please define the term “registrational trials” and explain the basis for your belief. Your discussion
should clarify the factors that will determine whether your TIDAL-01 trials become registrational and who will make such determination.

Response: In response to the Staff’s comment, the Company has revised the disclosure on pages 6, 126, 136, 139, and 143 of the
Registration Statement, including to change references to “registrational trials” to “pivotal trials” and to define such term.

The Company acknowledges the Staff’s comment and respectfully advises the Staff that while the FDA and European Medicines Agency
(“EMA”) generally rely on well designed and executed Phase 3 randomized controlled clinical trials that demonstrate positive safety and efficacy of a product candidate to support BLA or MAA approval, both the FDA and EMA acknowledge that
there are situations where such clinical trials are not feasible operationally and ethically. Under these circumstances, evidence from early non-randomized clinical trials may be used to support approval when
an investigational product candidate is observed to demonstrate substantial benefit over currently available therapies. As indicated in the FDA guidance titled “Clinical Trial Endpoints for the Approval of Cancer Drugs and Biologics”, in
“settings where there is no available therapy and where major tumor regressions can be presumed to be attributed to the tested [product candidate], the FDA has sometimes accepted ORR and response duration observed in single-arm clinical trials as substantial evidence supporting accelerated approval[s].” A similar concept also is included in the EMA Guideline on Clinical Trials in Small Populations.

There are numerous examples in oncology where approval of new therapies has been granted based on
single-arm clinical trials. For example, four CAR-T cell therapies that have received approval have been approved based on
single-arm clinical trials. The FDA and EMA approved Kymriah for relapsed or refractory acute lymphoblastic leukemia based on a single-arm Phase 2 clinical trial with 68
treated patients and for relapsed or refractory diffuse large B-cell lymphoma based on a single-arm Phase 2 clinical trial with 106 treated patients. The FDA and EMA
also approved Yescarta for relapsed or refractory diffuse large B-cell lymphoma based on a single-arm Phase 2 clinical trial with 101 treated patients. Tecartus also was
approved by the FDA and EMA on the basis of the single arm, open label ZUMA-2 trial, evaluating 74 enrolled subjects with relapsed or refractory mantle cell lymphoma for overall response rate. Bristol-Myers
Squibb also announced on March 31, 2020 the submission of a BLA for its product candidate, bb2121, based on a single-arm Phase 2 clinical trial in patients with relapsed or refractory multiple myeloma.
The FDA also approved Bristol Myers Squibb’s Breyanzi for adults with relapsed or refractory diffuse large B-cell lymphoma, based on results of a pivotal Phase 1 clinical tri