Sionna Therapeutics (NasdaqGM:SION) FY Conference Transcript

Summary of Sionna Therapeutics FY Conference Call Company Overview - Company: Sionna Therapeutics (NasdaqGM:SION) - Date of Conference: December 03, 2025 - Key Speakers: Mike, Elena, Charlotte, and Corey Casimov (Senior Biotech Analyst at Evercore) Key Accomplishments in 2025 - Successful completion of Phase 1 programs for two NBD1 stabilizers: SION-719 and SION-451 with positive data outcomes [2][4] - Initiation of Phase 2 proof of concept study for SION-719 in combination with Trikafta, aimed at demonstrating improved CFTR function [2][3] - Progression of SION-451 into a Phase 1 study with healthy volunteers, testing its combination with two other modulators [3][4] - Completion of IPO in February 2025, raising over $219 million, providing cash runway into 2028 [4][5] Unmet Needs in Cystic Fibrosis (CF) - Acknowledgment of Vertex's contributions to CF treatment but recognition of ongoing unmet needs, as only about one-third of patients achieve normal CFTR function with current therapies [6][7] - Focus on improving patient outcomes by lowering sweat chloride levels and enhancing overall CFTR function [6][8] Mechanism of Action and Clinical Strategy - Emphasis on the unique mechanism of NBD1 stabilizers, which may provide additional efficacy compared to existing treatments [12][15] - Data from preclinical studies indicating that NBD1 stabilizers can improve CFTR protein half-life to wild-type levels, supporting the rationale for the NBD1 anchored pipeline [13][15] Clinical Trials and Future Directions - Phase 2a precision proof of concept trial for SION-719 aims to show significant improvement in sweat chloride levels compared to Trikafta [22][24] - The dual combination approach is preferred, with expectations of better efficacy than current standard care [25][26] - Plans to evaluate safety and pharmacokinetics in the combination studies of SION-451 with other modulators [30] Assay Confidence and Predictive Power - High confidence in the CFHBE assay used to predict clinical outcomes, validated through comparisons with Vertex's compounds [31][32] - The assay is seen as a tool to support the development of new treatment options for CF patients [34] Strategic Options and Future Pathways - Potential to pursue multiple combinations if data supports it, with a focus on capital availability to fund both add-on and dual combination approaches [35][36] - Anticipation of significant developments in 2026 as data from ongoing studies becomes available [37] This summary encapsulates the key points discussed during the conference call, highlighting Sionna Therapeutics' progress, strategic focus, and future plans in the cystic fibrosis treatment landscape.