Common Stock, $0.001 par value per share

SIONNA THERAPEUTICS, INC.

21 Hickory Drive, Suite 500, Waltham, MA, 02451

This Schedule 13D/A is being filed on behalf of RA Capital Management, L.P. ("RA Capital"), Peter Kolchinsky, Rajeev Shah, RA Capital Healthcare Fund, L.P. (the "Fund") and RA Capital Nexus Fund III, L.P. (the "Nexus Fund III"). RA Capital, Dr. Kolchinsky, Mr. Shah, the Fund and the Nexus Fund III are collectively referred to herein as the "Reporting Persons." The agreement among the Reporting Persons to file this Schedule 13D/A jointly in accordance with Rule 13d-1(k) of the Act is filed as Exhibit 99.1. The Reporting Persons' ownership of the Issuer's securities includes (i) 3,448,812 shares of common stock held directly by the Fund; (ii) 650,307 shares of common stock held directly by RA Capital Nexus Fund, L.P. (the "Nexus Fund"); (iii) 2,198,082 shares of common stock held directly by the Nexus Fund III; (iv) 159,033 shares of common stock directly held by a separately managed account (the "Account"); and (v) a total of 19,959 vested stock options (right to buy) held by Dr. Joshua Resnick for the benefit of RA Capital. RA Capital Healthcare Fund GP, LLC is the general partner of the Fund, RA Capital Nexus Fund GP, LLC is the general partner of the Nexus Fund and RA Capital Nexus Fund III GP, LLC is the general partner of the Nexus Fund III. The general partner of RA Capital is RA Capital Management GP, LLC, of which Dr. Kolchinsky and Mr. Shah are the controlling persons. RA Capital serves as investment adviser for each of the Fund, the Nexus Fund, the Nexus Fund III and the Account and may be deemed a beneficial owner, for purposes of Section 13(d) of the Act, of any securities of the Issuer held by the Fund, the Nexus Fund, the Nexus Fund III or the Account. Each of the Fund, the Nexus Fund and the Nexus Fund III has delegated to RA Capital the sole power to vote and the sole power to dispose of all securities held in its portfolio, including the shares of the Issuer's common Stock reported herein. Because each of the Fund, the Nexus Fund and the Nexus Fund III has divested itself of voting and investment power over the reported securities it holds and may not revoke that delegation on less than 61 days' notice, each of the Fund, the Nexus Fund and the Nexus Fund III disclaims beneficial ownership of the securities it holds for purposes of Section 13(d) of the Act and therefore disclaims any obligation to report ownership of the reported securities under Section 13(d) of the Act. As managers of RA Capital, Dr. Kolchinsky and Mr. Shah may be deemed beneficial owners, for purposes of Section 13(d) of the Act, of any securities of the Issuer beneficially owned by RA Capital. RA Capital, Dr. Kolchinsky, and Mr. Shah disclaim beneficial ownership of the securities reported in this Schedule 13D/A other than for the purpose of determining their obligations under Section 13(d) of the Act, and the filing of this Schedule 13D/A shall not be deemed an admission that either RA Capital, Dr. Kolchinsky, or Mr. Shah is the beneficial owner of such securities for any other purpose.

The address of the principal business office of each of the Reporting Persons is 200 Berkeley Street, 18th Floor, Boston, MA 02116.

Each of the Fund and the Nexus Fund III is a private investment vehicle. RA Capital provides investment management services to the Fund, the Nexus Fund, the Nexus Fund III and the Account. The principal occupation of each of Dr. Kolchinsky and Mr. Shah is investment management.

During the last five years, none of the Reporting Persons has been a party to a civil proceeding of a judicial or administrative body of competent jurisdiction and as a result of such proceeding was or is subject to a judgment, decree of final order enjoining future violations of, or prohibiting or mandating activities subject to, federal or state securities laws or finding any violation with respect to such laws.

See Item 6 of the cover pages.

Rows 11 and 13 of each Reporting Person's cover page to this Schedule 13D/A set forth the aggregate number of shares of common stock and percentage of the shares of common stock beneficially owned by such Reporting Person and are incorporated by reference. The percentage set forth in each row 13 is based upon 45,212,399 shares of common stock outstanding as of July 31, 2026, as reported in the Issuer's Quarterly Report on Form 10-Q filed with the SEC on August 6, 2026, and giving effect to stock options, to the extent exercisable within 60 days hereof, as referenced herein.

Rows 7 through 10 of each Reporting Person's cover page to this Schedule 13D/A set forth the number of shares of common stock as to which such Reporting Person has the sole or shared power to vote or direct the vote and sole or shared power to dispose or to direct the disposition and are incorporated by reference.

Except as set forth below, none of the Reporting Persons has effected any transactions with respect to the securities of the Issuer during the past sixty days. Weighted Low High Reporting Transaction No. of Average Price Price Transaction Person Date Shares Price ($) ($) ($) Block Sale Fund 09/17/2026 3,415,011 6.32 n/a n/a Open Market Sale Fund 09/17/2026 33,800 7.46 7.30 7.68 The Reporting Persons undertake to provide to the Issuer, any security holder of the Issuer, or the staff of the SEC, upon request, full information regarding the number of shares sold at each separate price within the range set forth above.

No person (other than the Reporting Persons) is known to have the right to receive or the power to direct the receipt of dividends from, or the proceeds from the sale of, the shares of common stock subject to this 13D/A.

The Nexus Fund III ceased to be the beneficial owner of greater than 5.0% of the outstanding common stock on November 17, 2025.