Company: SION
Filing Date: 2025-02-03
Form Type: S-1/A
Source: 0001193125-25-018825
Chunk: 26

Company: Sionna Therapeutics, Inc.
Filing Date: 2025-02-03
Form: S-1/A
Chunk 26
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, the impact of such changes on our business and results of operations is difficult to predict and may have an adverse effect on us. 20

Risks Related to the Discovery and Development of Our Product Candidates We are substantially dependent on the success of our NBD1 stabilizers. If we are unable to advance a lead NBD1 stabilizer product candidate into later-stage clinical development or unable to obtain regulatory approval and commercialize an NBD1 stabilizer-anchoredtherapy for the treatment of cystic fibrosis, or experience significant delays in doing so, our business will be materially harmed. To date, as an organization, we have not completed the development of any product candidates. We are substantially dependent on the success of at least one of our NBD1 stabilizer product candidates, including SION-719and SION-451,which are currently in Phase 1 clinical trials in healthy volunteers and in development for the treatment of cystic fibrosis (“CF”). Our NBD1 stabilizers are being developed for use either in combination with one of our complementary modulator candidates or the standard of care. We intend to select a lead complementary modulator candidate from our two most advanced modulator candidates, galicaftor (SION-2222), which has been evaluated in Phase 2 clinical trials conducted by AbbVie, and SION-109,which has been evaluated in a Phase 1 clinical trial. The success of SION-719, SION-451and our other product candidates will depend on several factors, including the following:

| • |     | successful and timely initiation and enrollment of clinical trials and completion of clinical trials with favorable 
 results;                                                                                                            |

| • |     | the safety, tolerability and pharmacokinetic profile of our product candidates observed in clinical trials, potentially 
 including in combination with the current standard of care;                                                             |

| • |     | acceptance of regulatory submissions by the U.S. Food and Drug Administration (“FDA”) and/or comparable foreign                                                                                                                                 
 regulatory authorities for the conduct of clinical trials of our product candidates, including acceptance by the FDA of an investigational new drug application (“IND”) for our lead NBD1 stabilizer product candidate prior to commencement of 
 our planned Phase 2 trials and our proposed design of such planned clinical trials;                                                                                                                                                             |

| • |     | the frequency and severity of adverse safety findings in nonclinical studies and adverse events (“AEs”) in 
 clinical trials;                                                                                           |

| • |     | timely and successful completion of preclinical studies