SCHEDULE 13D/A 0001415889-25-004419 0001346824 XXXXXXXX LIVE 1 Common Stock, $0.001 par value per share 11/05/2025 false 0002036042 829401108 SIONNA THERAPEUTICS, INC.

21 Hickory Drive, Suite 500 Waltham MA 02451

Peter Kolchinsky 617.778.2500 RA Capital Management, L.P. 200 Berkeley Street, 18th Floor Boston MA 02116 0001346824 N RA Capital Management, L.P. AF N DE 0.00 10071712.00 0.00 10071712.00 10071712.00 N 22.6 IA PN 0001384859 N Peter Kolchinsky AF N X1 0.00 10071712.00 0.00 10071712.00 10071712.00 N 22.6 HC IN 0001619841 N Rajeev Shah AF N X1 0.00 10071712.00 0.00 10071712.00 10071712.00 N 22.6 HC IN 0001315082 N RA Capital Healthcare Fund, L.P. WC N DE 0.00 6905625.00 0.00 6905625.00 6905625.00 N 15.5 PN 0001883840 N RA Capital Nexus Fund III, L.P. WC N DE 0.00 2240708.00 0.00 2240708.00 2240708.00 N 5.0 PN Common Stock, $0.001 par value per share SIONNA THERAPEUTICS, INC. 21 Hickory Drive, Suite 500 Waltham MA 02451 This Amendment No. 1 (this "Amendment No. 1" or this "Schedule 13D/A") amends and supplements the statement on Schedule 13D originally filed with the Securities and Exchange Commission (the "SEC") on February 18, 2025 (the "Statement") by the Reporting Persons. This Amendment No. 1 is being filed to report the dilution of the Reporting Persons' beneficial ownership in the Issuer's Common Stock and not as a result of any acquisition or disposition of securities by the Reporting Persons. Unless otherwise defined herein, capitalized terms used in this Amendment No. 1 shall have the meanings ascribed to them in the Statement. Unless amended or supplemented below, the information in the Statement remains unchanged. 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 Securities Exchange Act of 1934, as amended, (the "Act") is attached hereto as Exhibit 99.1. The Reporting Persons' ownership of the Issuer's securities includes (i) 6,905,625 shares of Common Stock held directly by the Fund; (ii) 715,988 shares of Common Stock held directly by RA Capital Nexus Fund, L.P. (the "Nexus Fund"); (iii) 2,240,708 shares of Common Stock held directly by the Nexus Fund III and (iv) 209,391 shares of Common Stock directly held by a separately managed account (the "Account"). 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 convicted in a criminal proceeding (excluding traffic violations or similar misdemeanors). 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 percentages 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 44,628,788 shares of Common Stock outstanding as of October 31, 2025, as reported in the Issuer's Quarterly Report on Form 10-Q filed with the SEC on October 31, 2025. 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 Reporting No. Average Transaction Person Date Shares Price ($) Open Market Sale Fund 10/24/25 14,116 39.50 Open Market Sale Nexus 10/24/25 122,271 39.50 Open Market Sale Nexus III 10/24/25 66,672 39.50 Open Market Sale Account 10/24/25 107,941 39.50 Open Market Sale Fund 10/28/25 3,624 39.58 (1) Open Market Sale Nexus 10/28/25 31,392 39.58 (1) Open Market Sale Nexus III 10/28/25 17,118 39.58 (1) Open Market Sale Account 10/28/25 10,476 39.58 (1) (1) The price reported is a weighted average price. These shares were sold in multiple transactions at prices ranging from $39.50 to $39.81 inclusive. 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 in this footnote. 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. Not applicable. Exhibit 99.1 Joint Filing Agreement (incorporated by reference to Exhibit 99.1 to the Reporting Persons' Schedule 13D filed with the SEC on February 18, 2025). RA Capital Management, L.P. /s/ Peter Kolchinsky 11/07/2025 Peter Kolchinsky /s/ Peter Kolchinsky 11/07/2025 Rajeev Shah /s/ Rajeev Shah 11/07/2025 RA Capital Healthcare Fund, L.P. /s/ Peter Kolchinsky 11/07/2025 RA Capital Nexus Fund III, L.P. /s/ Peter Kolchinsky 11/07/2025