Company: SION
Filing Date: 2025-03-20
Form Type: 10-K
Source: 0002036042-25-000005
Chunk: 1

Company: Sionna Therapeutics, Inc.
Filing Date: 2025-03-20
Form: 10-K
Item: Item 1
Chunk 1
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Figure 1. CFTR Structure

In February 2025, we disclosed interim data from two ongoing randomized, double-blinded, placebo-controlled Phase 1 clinical trials of our highly potent NBD1 stabilizers—SION-719 and SION-451—evaluating the safety, tolerability and PK of single ascending doses ("SAD") and multiple ascending doses ("MAD") of each product candidate in healthy subjects.  As of the interim data cutoff date of January 14, 2025, five SAD cohorts 

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and three MAD cohorts of SION-719 had been completed, with over 60 healthy subjects dosed, and six SAD cohorts and three MAD cohorts of SION-451 had been completed, with over 70 subjects dosed. Both SION-719 and SION-451 were generally well tolerated based on interim Phase 1 clinical data as of the interim data cutoff date. In these trials, at both single and multiple doses, SION-719 and SION-451 exposures were achieved that have the potential, based on our preclinical CFHBE model, to provide clinically meaningful benefit if SION-719 or SION-451 were administered as part of a dual combination or as an add-on to the standard of care (“SOC”). Since reporting interim data, we have completed dosing in the MAD part of the Phase 1 trial of SION-451, and the final MAD cohort of the SION-719 trial, evaluating 120 mg of SION-719, is planned.  The additional completed cohorts evaluated 225 mg and 25 mg (fed) of SION-451 and 160 mg of SION-719, dosed twice daily ("BID") over 10 days. All MAD data, including from the recently completed cohorts, remain blinded to individual subject treatment assignment. Both compounds were generally well tolerated in these additional cohorts. The Part C of each trial, in which we are evaluating the effect of food on the PK of each product candidate and the bioequivalence of a table formulation, is ongoing. Topline data from the Phase 1 trials are expected in the first half of 2025.

We are also developing a portfolio of complementary CFTR modulators designed to work synergistically with our NBD1 stabilizers to improve CFTR function, as seen in preclinical models. In July 2024, we in-licensed three clinical-stage compounds from AbbVie Global Enterprises Ltd. (“AbbVie