Sionna Therapeutics (SION) investor relations material

Strategic focus and pipeline development

• Targeting cystic fibrosis with a differentiated approach focused on the NBD1 domain, previously considered undruggable, aiming to transform the standard of care.

• Two main clinical strategies: SION-719 as an add-on to Trikafta and SION-451 as part of a dual combination, both with data expected in mid-2026.

• Dual combination strategy prioritized, aiming to deliver superior efficacy with two drugs versus the current triple therapy standard.

• Strong financial position with $325 million in cash, providing runway into 2028 and flexibility to pursue both clinical paths.

• Pipeline includes internally developed and in-licensed assets, notably from AbbVie, to broaden combination options.

Clinical development and trial design

• Phase 2a proof of concept for SION-719 will use sweat chloride as the primary endpoint, targeting a 10 mmol/L improvement over Trikafta.

• SION-451 dual combination is in Phase 1 healthy volunteer studies, with selection based on safety, PK, and efficacy mapping to preclinical assays.

• Both SION-719 and SION-451 showed favorable safety and PK profiles in Phase 1, with compound selection based on potency and exposure at relevant doses.

• Clinical trial design leverages established networks like the Cystic Fibrosis Foundation's TDN, facilitating patient recruitment and study execution.

• Future pivotal studies will be data-driven, with flexibility in design and strong regulatory engagement anticipated.

Market opportunity and commercial strategy

• Addressing unmet need as two-thirds of patients on current modulators do not achieve normal CFTR function; goal is to move more patients to normal function.

• Market research indicates broad enthusiasm for a dual therapy that could offer efficacy and tolerability advantages.

• Commercial opportunity in a $12–15 billion and growing CF market, with potential for premium pricing for add-on therapies and parity or premium for dual combinations.

• Pricing strategy will focus on maximizing patient access, with payer research suggesting a 25–40% premium for add-ons over base therapy.

• Global market considered, with major focus on U.S., U.K., and Europe, leveraging organized research networks and payer discussions.