Company: SION
Filing Date: 2025-02-07
Form Type: 424B4
Source: 0001193125-25-022709
Chunk: 6

Company: Sionna Therapeutics, Inc.
Filing Date: 2025-02-07
Form: 424B4
Chunk 6
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 Phase 1 trial. The target exposure for SION-109 as part of a dual combination with SION-451 or 
 SION-719 was achieved with single and multiple doses.                                                                                                                                                                                             |

| • |     | Navocaftor (SION-3067), a potentiator, has been evaluated in Phase 2 trials, in which it demonstrated potential as a 
 combination therapy.                                                                                                 |

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Figure 2 below captures the targeted binding locations within the CFTR structure for our pipeline of
NBD1 stabilizers and complementary modulators.

Figure 2. Our Multi-Prong Approach to Potentially Improving CFTR Function

Our current portfolio of programs is summarized in Figure 3 below:

Figure 3. Our Proprietary Pipeline of Product Candidates for the Treatment of CF

Clinical trials for galicaftor, SION-2851, and navocaftor were conducted by AbbVie or Galapagos NV (“Galapagos”). MAD: Multiple Ascending Dose.

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We have not obtained regulatory approval for any product candidate, and it is possible that we may
never obtain regulatory approval for any product candidates we may seek to develop in the future.

Our Approach and Leveraging the CFHBE Model

Central to our development strategy is our use of the industry standard, clinically predictive CFHBE model to measure CFTR protein function in vitro. Activity in this model has been shown to be correlated to chloride transport activity, which in turn, has been shown to be correlated to improved lung function in clinical trials designed to evaluate product candidates in CF patients. We
have used, and plan to continue to use, insights from the CFHBE model to inform pipeline prioritization and development decisions. For example, we selected SION-719 and SION-451 to advance based on their preclinical profiles, including potency in
the CFHBE model. We assessed SION-719 and SION-451 in our CFHBE model in direct, head-to-head comparison to elexacaftor/tezacaftor/ivacaftor (“ETI”), the components of Trikafta, which we synthesized using methods described in publicly
available sources. When evaluated in our CFHBE model at their respective highest effective dose (“E”) concentrations, both SION-719 and SION-451, in dual combination with one of
our complementary modulators, improved in vitro CFTR protein activity to wild-type, or normal, levels. This was