Company: SION
Filing Date: 2025-03-20
Form Type: 10-K
Source: 0002036042-25-000005
Chunk: 16

Company: Sionna Therapeutics, Inc.
Filing Date: 2025-03-20
Form: 10-K
Item: Item 1
Chunk 16
---
 candidate and NBD1 dual combination into Phase 2 clinical trials in CF patients based on initial human data on safety, tolerability and PK in healthy volunteers.

NBD1 Stabilizer Program

NBD1 is recognized as a key target in treating CF patients with the F508del mutation, as the mutation drives NBD1 instability and defects in its interface assembly. However, NBD1 has presented significant challenges as a drug target due to the attributes of the region’s binding sites. Our NBD1 program builds on more than a decade of our cofounders’ research, which has combined biophysical, cell-based and virtual screening campaigns, along with extensive use of structural biology. We believe the technical challenge associated with NBD1-targeted drug discovery, along with our intellectual property rights, represent a substantial competitive barrier.

We selected SION-719 and SION-451 for clinical evaluation based on their potency, PK profiles and safety as observed in preclinical studies. We assessed SION-719 and SION-451 in our CFHBE model in direct, head-to-head comparison to ETI, the components of Trikafta. When evaluated in our CFHBE model at their respective Emax concentrations, both SION-719 and SION-451, in dual combination with one of our complementary modulators, improved in vitro CFTR protein activity of F508del-CFTR to wild-type, or normal, levels. This was a more than 1.5-fold improvement in CFTR protein activity compared to the improvement in such activity observed with ETI at Emax in the same experiment. Based on predicted exposure levels in the CFHBE model, we believe co-administering SION-719 or SION-451 with a complementary modulator has the potential to achieve clinically meaningful benefit in CF patients.

In addition, we have nominated two NBD1 stabilizers with differentiated profiles as development candidates.

SION-719 and SION-451

Phase 1 Clinical Development

We initiated Phase 1 SAD and MAD clinical trials of SION-719 and SION-451 in healthy subjects in July 2024 and August 2024, respectively. These trials are randomized, double-blinded, placebo-controlled trials designed to evaluate safety, tolerability and PK of each product candidate. Both trials are being conducted in Australia, and we intend to enroll up to 120 healthy subjects in each trial. 

In February 2025, we disclosed interim data from both trials, which is summarized below.