Sionna Therapeutics, Inc.

FOR THE 2025 ANNUAL MEETING OF STOCKHOLDERS

TO BE HELD ON JUNE 12, 2025

This proxy statement contains information about the 2025 Annual Meeting of Stockholders of Sionna Therapeutics, Inc. (the “Annual Meeting”), which will be held on June 12, 2025 at 10:00 a.m. Eastern Time. The board of directors of Sionna Therapeutics, Inc. is using this proxy statement to solicit proxies for use at the Annual Meeting. In this proxy statement, the terms “Sionna,” “we,” “us,” and “our” refer to Sionna Therapeutics, Inc. The mailing address of our principal executive office is Sionna Therapeutics, Inc., 21 Hickory Drive, Suite 500, Waltham, MA 02451.

All properly submitted proxies will be voted in accordance with the instructions contained in those proxies. If no instructions are specified, the proxies will be voted in accordance with the recommendation of our board of directors with respect to each of the matters set forth in the accompanying Notice of Meeting. You may revoke your proxy at any time before it is exercised at the meeting by giving our corporate secretary written notice to that effect.

We will make our proxy statement and our 2024 Annual Report to Stockholders for the fiscal year ended December 31, 2024 (the “2024 Annual Report”) available to stockholders on or about April 29, 2025.

The Annual Meeting will be held for the following purposes:

We are an “emerging growth company” under applicable federal securities laws and therefore permitted to conform with certain reduced public company reporting requirements. As an emerging growth company, we provide in this proxy statement the scaled disclosure permitted under the Jumpstart Our Business Startups Act of 2012 (the “JOBS Act”), including the compensation disclosures required of a “smaller reporting company,” as that term is defined in Rule 12b-2 promulgated under the Securities Exchange Act of 1934, as amended (the “Exchange Act”). In addition, as an emerging growth company, we are not required to conduct votes seeking approval, on an advisory basis, of the compensation of our named executive officers or the frequency with which such votes must be conducted, and we are not required to provide pay versus performance disclosure under Item 402(v) of Regulation S-K. We will remain an “emerging growth company” until the earliest of (i) the last day of the fiscal year following the fifth anniversary of our initial public offering in February 2025; (ii) the last day of the fiscal year in which our total annual gross revenue is equal to or more than $1.235 billion; (iii) the date on which we have issued more than $1 billion in nonconvertible debt during the previous three years; or (iv) the date on which we are deemed to be a large accelerated filer under the rules of the Securities and Exchange Commission (the “SEC”). Even after we are no longer an “emerging growth company,” we may remain a “smaller reporting company.”

Important Notice Regarding the Availability of Proxy Materials for

the Annual Meeting of Stockholders to be Held on June 12, 2025:

This proxy statement and our 2024 Annual Report to Stockholders are

available for viewing, printing and downloading athttps://materials.proxyvote.com/829401.

A copy of our 2024 Annual Report, as filed with the SEC, except for exhibits, will be furnished without charge to any stockholder upon written request to Sionna Therapeutics, Inc., 21 Hickory Drive, Suite 500, Waltham, MA 02451, Attention: Chief Legal Officer. This proxy statement and our 2024 Annual Report are also available on the SEC’s website at www.sec.gov.

SIONNA THERAPEUTICS, INC.

PROXY STATEMENT

FOR THE 2025 ANNUAL MEETING OF STOCKHOLDERS