SecProbe.io

October 10, 2024
Michael Cloonan
President and Chief Executive Officer
Sionna Therapeutics, Inc.
21 Hickory Drive, Suite 500
Waltham, MA 02451
Re:Sionna Therapeutics, Inc.
Draft Registration Statement on Form S-1
Submitted September 12, 2024
CIK No. 0002036042
Dear Michael Cloonan:
            We have reviewed your draft registration statement and have the following comments.
            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 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 the information you provide in response to this letter and your
amended draft registration statement or filed registration statement, we may have additional
comments.
Draft Registration Statement on Form S-1 submitted September 12, 2024
Prospectus Summary
Overview, page 1
Please balance the Summary to prominently state that you have not obtained
regulatory approval for any product candidates to date, and it is possible that you may
never obtain regulatory approval for any product candidates you may seek to develop
in the future. Please also include a discussion of the competitive landscape, noting, as
you have elsewhere, that there are four currently approved and marketed CFTR
modulators for the treatment of CF, including Trikafta, all marketed by Vertex
Pharmaceuticals, Inc., which also announced in July 2024 that the FDA accepted its
NDA for a second-generation, triple combination modulator,
vanzacaftor/tezacaftor/deutivacaftor (“VTD”), for the treatment of the same CF 1.

October 10, 2024
Page 2
patient population as Trikafta.
2.Please remove any references to your NBD1 stabilizers  as being potentially "first-in-
class", as this is speculative in light of your current stage of development.
3.Please clarify in the Summary that Trikafta is marketed by Vertex Pharmaceuticals,
Inc., rather than the company, where Trikafta is first noted as the standard of care for
the treatment of cystic fibrosis.
4.Please define “CFF” where first used on page 2.
5.We note your statements throughout the prospectus that your NBD1 stabilizers have
multiple potential pathways to “deliver superior clinical outcomes”. We also note your
statements throughout the prospectus that certain of your product candidates showed
“significant improvement” in  in vitro CFTR protein activity compared to the
components of Trikafta alone, which you believe “demonstrates the potential for
superior clinical outcomes for CF patients” and your statements regarding
“demonstrated improvements”. Please revise these and similar statements throughout
the prospectus to remove the implication of efficacy, as determinations of efficacy are
within the sole purview of the FDA and similar foreign regulators. You may present
clinical trial end points and objective data resulting from trials without concluding
efficacy.
Our Pipeline, page 2
6.Please revise your disclosure both here and in the Business section, where appropriate,
to disclose any p-values associated with the clinical trials conducted to date for each
of the company’s product candidates, to the extent applicable. In addition, please
disclose all endpoints for the discussed clinical trials, to the extent not already
disclosed, and whether each endpoint was achieved for those trials that have
concluded.
7.Please revise your pipeline table to indicate, by footnote or otherwise, which clinical
trials have been or are being conducted by the company and which trials have been or
are being conducted by third parties. Please also indicate the jurisdiction of each trial.
Our Approach and Leveraging the CFHBE Model, page 4
8.We note Figure 4 on page 5 depicts a “predicted clinical translation” of your NBD1
anchored dual combinations based on the CFHBE model, noted as a “potential
efficacy range” shown through a dotted line which represents “theoretical max FEV1
improvements assuming continued linearity” as compared to competitor products.
Given the stage of development of the company’s product candidates, the information
appears highly speculative and premature. This information also implies efficacy,
which is not yet known. As such, please remove Figure 4 from page 5 and Figure 10
from page 115.
9.Please remove all statements throughout the prospectus indicating that product
candidates that are not FDA approved are as effective or superior to approved
products. You may present objective results of clinical trials but such results should
not be compared to alternative products unless head-to-head studies were conducted.

October 10, 2024
Page 3
Our Strategy, page 5
10.Please remove your statement, both here and on page 108, that your mission is to
“rapidly” advance your NBD1 stabilizers, as the timing of clinical trials is uncertain
and not exclusively within the company’s control.
Our Company's History and Our Team, page 6
11.We note your disclosure that you have raised approximately $330 million from
investors including RA Capital, TPG’s the Rise Fund, Atlas Venture, OrbiMed and
Enavate Sciences. Please provide balancing disclosure that prospective investors
should not rely on such investors’ investment decisions, that these investors may have
different risk tolerances and that the shares purchased in the referenced financings
may have been conducted at a significant discount to the IPO price, if true.
Summary of Material Risks Associated With Our Business, page 6
12.Please revise your summary risk factors to quantify the company’s accumulated
deficit and operating losses.
Risk Factors
We contract with third parties for the manufacture of our product candidates for clinical drug
supply..., page 36
13.We note your disclosure regarding the proposed BIOSECURE Act (the Act) on page
37 and that you have “in the past relied on foreign CDMOs in China for
manufacturing of your clinical trial materials”. Please clarify whether you currently
contract with any of the Chinese biotechnology companies of concern named in
the Act.
We might not be able to utilize a significant portion of our net operating loss carryforwards.,
page 77
14.Please revise your disclosure to quantify the company’s net operating loss
carryforwards.
Use of Proceeds, page 82
15.Please revise your use of proceeds discussion to provide more granular disclosure
regarding the approximate amount intended to be used to advance your NBD1
stabilizer product candidates, including an indication of which product(s) you will
allocate offering funds towards. Please also indicate how far in the clinical trial
process you expect the funds to take the identified product candidates. Refer to Item
504 of Regulation S-K.
Critical Accounting Estimates, page 101
Stock-Based Compensation Expense, page 102
16.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.

October 10, 2024
Page 4
Business
Our CF Programs, page 118
17.For each of the clinical trials discussed, please disclose the date(s) of the trials, the
location, the number of patients enrolled, the duration of treatment, dosage
information, and the data evidencing proof of concept. To the extent that any
participants experienced serious adverse events, please describe them and quantify the
number of each type of event, to the extent not already disclosed.
Intellectual Property, page 128
18.Please disclose the jurisdictions for each of the discussed patent families.
General
19.Please provide us with supplemental 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, have presented or expect to present to potential investors in reliance on Section
5(d) of the Securities Act, whether or not you retained, or intend to retain, copies of
those communications.
            Please contact Jenn Do at 202-551-3743 or Angela Connell at 202-551-3426 if you
have questions regarding comments on the financial statements and related matters. Please
contact Tamika Sheppard at 202-551-8346 or Laura Crotty at 202-551-7614 with any other
questions.
Sincerely,
Division of Corporation Finance
Office of Life Sciences
cc:Gabriela Morales-Rivera