Company: SION
Filing Date: 2025-01-17
Form Type: S-1
Source: 0001193125-25-008474
Chunk: 153

Company: Sionna Therapeutics, Inc.
Filing Date: 2025-01-17
Form: S-1
Chunk 153
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’s nucleotide-binding domain 1 (“NBD1”). Despite having long been identified as a critical
component for proper CFTR function, NBD1 has been considered “undruggable,” and none of the currently approved CF therapies directly stabilizes NBD1. Worldwide revenue for approved CFTR modulators was approximately $10 billion in 2023
and is expected to grow to $15 billion by 2029. Leveraging more than a decade of our co-founders’ research on NBD1, we are advancing a pipeline of small molecules engineered to correct the defects
caused by the F508del genetic mutation, which resides in the NBD1 domain. Approximately 90% of people with CF carry at least one copy of the F508del genetic mutation.

We believe stabilizing NBD1 is central to unlocking dramatic improvements in clinical outcomes and quality of life for CF patients. The NBD1 domain of
the CFTR protein, as illustrated in Figure 1, plays a key role in the folding, stability and trafficking of CFTR to a cell’s surface, where it normally functions to conduct chloride and other ions and regulate the flow of water. Within the NBD1
domain, F508del severely destabilizes CFTR, preventing normal folding and trafficking of CFTR to a cell’s surface and impairing chloride channel function. We have employed biophysical, cell-based and virtual screening campaigns and extensive
use of structural biology to guide the optimization of novel small molecule NBD1 stabilizers.

Figure 1. CFTR Structure

We are conducting ongoing Phase 1 trials of our two highly potent NBD1 stabilizers—SION-719 and
SION-451—evaluating the safety, tolerability and PK of single and multiple ascending doses of

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each product candidate in healthy subjects. These trials are randomized (3:1 active:placebo), doubled-blinded, placebo-controlled and are being conducted in Australia. As of January 14, 2025,
five SAD cohorts and three MAD cohorts of SION-719 have been completed, with over 60 healthy subjects dosed, and six SAD cohorts and three MAD cohorts of SION-451 have been completed, with over 70 subjects dosed. Both SION-719 and SION-451 have been
generally well tolerated based on interim Phase 1 clinical data as of the cutoff date of January 14, 2025. In these trials, at both single and multiple doses, SION-