Sionna Therapeutics (SION) investor relations material

Scientific and clinical program updates

• Two clinical-stage NBD1 stabilizers, SION-719 and SION-451, are in development targeting the Delta F508 mutation in CFTR, aiming for full CFTR correction in cystic fibrosis patients.

• SION-719 is in a phase IIa proof-of-concept study (PreciSION CF) as an add-on to TRIKAFTA, with a primary endpoint of sweat chloride; data expected this summer.

• SION-451 is being evaluated in healthy volunteers in dual combinations for PK, safety, and tolerability, with data also expected this summer to inform which dual to advance.

• Both programs exceeded PK targets in phase I, supporting BID dosing and advancement to next-stage studies.

• The company aims for a 10 millimole improvement in sweat chloride, which historically correlates with a meaningful FEV1 improvement.

Assay validation and differentiation

• The HBE assay, run similarly to industry leaders and validated by reproducing clinical findings of approved modulators, underpins dose predictions and confidence in clinical translation.

• Human serum is incorporated into the assay to closely mimic human biology, and collaboration with the Cystic Fibrosis Foundation further supports assay rigor.

• Assay predictions have been validated by matching outcomes of approved modulators, supporting the reliability of preclinical-to-clinical translation.

Strategic development and future plans

• The prioritized path is advancing a novel dual combination as an alternative to standard of care, with the add-on strategy also considered if efficacy targets are met.

• Phase III or pivotal studies may pursue superiority or non-inferiority versus standard of care, with flexibility to adapt based on emerging data.

• The target population is broad, focusing on the 90% of CF patients with at least one Delta F508 mutation, addressing significant unmet needs in efficacy and tolerability.

• Commercialization could be pursued independently due to the concentrated and well-identified CF patient community, but partnerships remain an option.