Sionna Therapeutics (SION) investor relations material

Key strategic focus and scientific innovation

• Aims to revolutionize cystic fibrosis (CF) treatment by targeting NBD1, a previously undruggable region of the CFTR protein, with first-in-class stabilizers in novel combinations.

• NBD1 stabilization addresses the F508del mutation, present in 90% of CF patients, aiming to achieve normal CFTR function for more patients.

• Both SION-719 and SION-451 NBD1 stabilizers have shown positive phase I data and are advancing to phase IIA and dual combination studies, respectively.

• The company leverages a gold-standard CFHBE assay, predictive of clinical outcomes, to guide development and dose selection.

• The dual combination approach with NBD1 and complementary mechanisms aims to deliver wild-type CFTR function and differentiated safety profiles.

Clinical development and milestones

• SION-719 is in a phase IIA proof-of-concept study (Precision CF) as an add-on to standard of care, with data expected mid-2026.

• SION-451 anchors a dual combination strategy, being tested with TMD1 and ICL4 correctors, with healthy volunteer data also expected mid-2026.

• Both programs exceeded clinically meaningful targets in phase I, with potential to reach wild-type CFTR function.

• The Precision CF study uses a crossover design, targeting a 10 mmol sweat chloride improvement, considered clinically meaningful and expected to translate to FEV1 gains.

• Strategic decision on advancing both add-on and dual combination paths will be made after mid-2026 data readouts.

Market opportunity and commercial strategy

• The CF market is valued at $12 billion, projected to exceed $15 billion by 2030, with significant unmet need as only one-third of patients on current therapies achieve normal CFTR function.

• Target population includes all patients with at least one F508del mutation, covering both homozygous and heterozygous individuals.

• Both the add-on and dual combination approaches are seen as commercially viable, with potential for co-positioning and strong market enthusiasm for novel, more effective therapies.

• Differentiation from competitors is based on the potential for higher efficacy and improved safety profiles with fewer drugs compared to current triple or quadruple combinations.

• The company is fully funded into 2028, supporting advancement through key clinical milestones.