Company: SION
Filing Date: 2025-02-07
Form Type: 424B4
Source: 0001193125-25-022709
Chunk: 156

Company: Sionna Therapeutics, Inc.
Filing Date: 2025-02-07
Form: 424B4
Chunk 156
---
 been evaluated in Phase 2 trials, in which it demonstrated potential as a 
 combination therapy.                                                                                                 |

114

Figure 3 below captures the targeted binding locations within the CFTR structure for our pipeline of
NBD1 stabilizers and complementary modulators.

Figure 3. Our Multi-Prong Approach to Potentially Improving CFTR Function

Our current portfolio of programs is summarized in Figure 4 below:

Figure 4. 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.

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.

115

Our Strategy Our mission is to revolutionize the current treatment paradigm for CF patients by developing novel medicines that normalize the function of the CFTR protein to deliver clinically meaningful benefit to CF patients. The key pillars of our strategy are:

| • |     | Advance our novel NBD1 stabilizers. We are evaluating SION-719 and SION-451 in ongoing Phase 1 clinical trials to                                                                                                                                  
 assess their PK profile, safety and tolerability. In preclinical studies using the CFHBE model, the combination of SION-719 or SION-451 with one of our complementary modulators or ETI showed                                                     
 increased chloride transport, which indicates improvement in in vitro CFTR activity. Given the clinically predictive nature of the CFHBE model, we believe these data indicate the potential for an NBD1-anchored dual combination to improve CFTR 
 activity, which we believe will deliver clinically meaningful benefit to CF patients. Following completion of our ongoing Phase 1 clinical trials of SION-719 and                                                                                  
 SION-451, expected in the first half of 2025, we plan to select a lead NBD1 stabilizer and conduct a drug-drug interaction trial before initiating a Phase 2a proof-of-concept trial in CF patients.                                               |

| • |     | Develop and advance our pipeline of complementary modulators for proprietary combination product development. We are                                                                                                                                     
 developing a proprietary pipeline of complementary CFTR modulators designed to work synergistically with our NBD1 stabilizers to improve CFTR function, as seen in our CFHBE model. We have several CFTR modulators in development, including galicaftor 
 (SION-2222