Sionna Therapeutics, Inc.

Emerging growth company ☒ If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐

Item 2.05 Costs Associated with Exit or Disposal Activities.

The estimate of costs that the Company expects to incur and the timing thereof are subject to a number of assumptions, and actual results may differ. As the Restructuring is implemented, the Company’s management will reevaluate the estimated costs and expenses set forth above and may revise the estimated restructuring charge as appropriate, consistent with generally accepted accounting principles. The Company may also incur other non-cash charges or cash expenditures not currently contemplated due to events that may occur as a result of, or associated with, the Restructuring.

Item 5.02 Departure of Directors or Certain Officers; Election of Directors; Appointment of Certain Officers; Compensatory Arrangements of Certain Officers.

The Board approved the Option Repricing after careful consideration of various alternatives, and based in part on the recommendation of the Compensation Committee. The Option Repricing is not subject to approval of the Company’s stockholders.

Item 8.01 Other Events.

The full text of the press release is filed as Exhibit 99.1 to this Current Report on Form 8-K and is incorporated herein by reference.

Forward-Looking Statements This Current Report on Form 8-K contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, implied and express statements about the Company’s beliefs and expectations regarding: its ability to preserve cash and continue the clinical development of the Company’s product candidates; the expected timing, scope, costs and benefits of its workforce reduction and other cost-saving measures; its planned option repricing; its interpretation of the results of the PreciSION CF trial and the impact of confounding factors on the interpretation of those results; the potential for NBD1 stabilization to improve CFTR function and produce clinical benefit, including beliefs about biological activity of SION-719 in PreciSION CF and the translatability of preclinical and in vitro assay data to clinical outcomes; the objectives, design, timing, initiation and conduct of a planned Phase 2 proof-of-concept trial of SION-451 and SION-2222; the therapeutic potential, clinical benefits and safety of SION-451 and SION-2222; the Company’s ability to retain the capabilities and personnel needed to advance SION-451 and SION-2222 and operate as a public company; the Company’s expected cash runway; and other statements that are not historical facts. In some cases, forward-looking statements can be identified by terms such as “may,” “will,” “should,” “would,” “expect,” “plan,” “anticipate,” “could,” “intend,” “target,” “project,” “believe,” “estimate,” “predict,” “potential” or “continue” or the negative of these terms or other similar expressions. Any forward-looking statements in this Current Report on Form 8-K are based on management’s current expectations and beliefs and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by the forward-looking statements contained in this Current Report on Form 8-K. Factors that could cause actual results to differ include, but are not limited to, the risk that the restructuring costs and charges may be greater than anticipated or incurred in different periods than anticipated; the risk that the Company’s restructuring efforts may not generate their intended benefits, including runway extension, to the extent or as quickly as anticipated, may negatively impact the Company’s business operations and reputation and may adversely affect the Company’s internal programs and the Company’s ability to retain key personnel; uncertainties inherent in developing product candidates; interpreting the PreciSION CF results and potential confounding factors; the inherent limitations of post hoc analyses, which are exploratory and may not reliably predict future outcomes; the risk that in vitro and preclinical data may not translate to clinical benefit; the risk that results observed with one compound may not be predictive of results with a different compound or combination; risks associated with the Company’s ability to continue the clinical development of its SION-451 and SION-2222 dual combination program, including designing and conducting the planned Phase 2a trial; the Company’s ability to demonstrate that its candidates are safe and effective and obtain regulatory feedback or approvals; and general economic, industry and market conditions. These risks and uncertainties are described in the section entitled “ Risk Factors ” in the Company’s most recent Quarterly Report on Form 10-Q as well as any subsequent filings with the Securities and Exchange Commission. The events and circumstances reflected in the forward-looking statements may not be achieved or occur. In addition, any forward-looking statements represent the Company’s views only as of today and should not be relied upon as representing its views as of any subsequent date. The Company explicitly disclaims any obligation to update any forward-looking statements except as required by law. No representations or warranties (expressed or implied) are made about the accuracy of any such forward-looking statements.

Sionna believes these analyses suggest that SION-719 was biologically active in the trial, but that PK outliers and complex interactions between SION-719 and Trikafta may have affected the observed outcome and blunted a potential treatment signal.

SION-451 + SION-2222 Dual Combination Phase 2 Development Plan Sionna plans to advance SION-451 + SION-2222 into the AscenSION CF Phase 2a POC trial. The Company continues to believe that directly stabilizing NBD1 in combination with a complementary CFTR modulator has the potential to meaningfully improve CFTR function.

The decision to advance SION-451 + SION-2222 is supported by results from the Phase 1 healthy volunteer trial of SION-451-based dual combinations, for which the Company announced topline results on August 10, 2026. The trial achieved its safety, tolerability, and PK objectives. SION-451 + SION-2222 was identified as the preferred dual combination based on target exposure coverage, and the go-forward SION-451 twice daily (BID) + SION-2222 once daily (QD) regimen demonstrated a favorable tolerability profile. Phase 1 exposures of the planned doses were within the range associated with meaningful improvement in CFTR function in Sionna’s CFHBE assay.

Corporate Update Following the completion of a comprehensive review of its operations, Sionna’s Board of Directors has approved a workforce reduction of approximately 46% and the Company has implemented other cost-saving measures to focus its resources on advancing SION-451 + SION-2222 and extend its operating runway. Sionna expects to retain the core clinical, scientific, regulatory, technical, and corporate capabilities required to advance the dual combination program. The Company currently estimates it will incur aggregate restructuring and related charges of approximately $6.4 million.

Webcast Details Sionna Therapeutics’ live webcast will begin at 4:30 p.m. ET today, September 14th, 2026, and can be accessed via this link. Participants who prefer to listen via telephone, or ask a question, may register on Sionna’s Investor Relations website or by clicking here. A replay will be available on the “Events” page in the “Investors” section of Sionna’s website at https://investors.sionnatx.com/news-events/events.

About Sionna Therapeutics Sionna Therapeutics is a clinical-stage biopharmaceutical company on a mission to revolutionize the current treatment paradigm for cystic fibrosis (CF) by developing novel medicines that normalize the function of the cystic fibrosis transmembrane conductance regulator (CFTR) protein. Sionna’s goal is to deliver differentiated medicines for people living with CF that can restore their CFTR function to as close to normal as possible by directly stabilizing CFTR’s nucleotide binding domain 1 (NBD1), which Sionna believes is central to potentially unlocking meaningful improvements in clinical outcomes and quality of life for people with CF. For more information about Sionna, visit www.sionnatx.com.