Core Insights - The company, Sionna, is focused on developing treatments for cystic fibrosis (CF) by targeting a differentiated and previously considered undruggable target known as NBD1 [3] Company Overview - Sionna aims to transform the standard of care in cystic fibrosis, with NBD1 as the central element of its strategy [3] - The company has recently initiated a Phase IIa proof-of-concept study for its NBD1 stabilizer, SION-719, which will be tested in conjunction with TRIKAFTA, the current standard of care [4]

Sionna Therapeutics (NasdaqGM:SION) FY 2025 Conference December 04, 2025 09:45 AM ET Company ParticipantsElena Ridloff - CFOMike Cloonan - CEOCharlotte McKee - CMOConference Call ParticipantsGeoff Meacham - Senior Biopharma AnalystGeoff MeachamWelcome to the third day of the Citi Global Healthcare Conference. So my name is Jeff Beach. I'm the Senior Biopharma Analyst here. And we have Sionna with us on stage. So we have Mike, CEO, just popping up here. Elena, CFO.Mike CloonanCharlotte McKee.Geoff MeachamCha ...

Summary of Sionna Therapeutics FY Conference Call Company Overview - **Company**: Sionna Therapeutics (NasdaqGM:SION) - **Focus**: Development of treatments for Cystic Fibrosis (CF) targeting the NBD1 protein domain Industry Context - **Market Size**: The CF treatment market is currently valued at approximately $11 billion, predominantly controlled by Vertex Pharmaceuticals [3][39] - **Unmet Need**: About two-thirds of CF patients on standard care do not achieve normal CFTR function, indicating a significant opportunity for new treatments [1][3] Core Scientific Insights - **NBD1 Target**: NBD1 has historically been considered "undruggable" due to challenging chemistry and shallow binding pockets [6][7] - **F508 del Mutation**: This mutation affects approximately 90% of CF patients and causes instability in the NBD1 protein, leading to impaired functionality [7][8] - **Efficacy of NBD1 Stabilizers**: Preclinical data suggests that stabilizing NBD1 can achieve efficacy levels comparable to the current triple combination therapy, Trikafta [8][9] Clinical Development - **Current Studies**: - Phase 2A proof of concept study for NBD1 stabilizer 719 and a dual combination study with stabilizer 451 [4][5] - Both studies are expected to yield results in mid-2026 [5][36] - **Study Design**: The precision study will involve a two-way crossover design to assess the efficacy of 719 added to Trikafta, focusing on sweat chloride levels as a primary endpoint [19][21] Financial Health - **Cash Position**: As of Q3, the company reported $325 million in cash, providing a runway into 2028, which supports ongoing clinical trials and development milestones [39] Strategic Insights - **Dual Combination Strategy**: The company aims to combine NBD1 stabilizers with either an ICL4 corrector or a TMD1 corrector to enhance efficacy beyond current treatments [9][36] - **Selection of Compounds**: The decision to use 719 as an add-on and 451 for dual combination is based on their unique profiles and potency at different doses [16][18] Key Milestones - **Upcoming Data**: Results from both ongoing studies are anticipated in mid-2026, which will be critical for determining future strategies [5][36] Additional Considerations - **Assay Confidence**: The CFHBE assay used for testing has shown high predictive validity for clinical outcomes, enhancing confidence in the results [10][12] - **Market Research**: The threshold for clinically meaningful improvement has been set at a 10 millimole per liter change in sweat chloride, based on historical data and expert consensus [25][33] This summary encapsulates the key points discussed during the conference call, highlighting Sionna Therapeutics' strategic focus, clinical development plans, and financial health within the context of the CF treatment landscape.

Core Insights - Sionna Therapeutics has initiated the PreciSION CF Phase 2a proof-of-concept trial for SION-719, a first-in-class NBD1 stabilizer, in combination with the current standard of care, Trikafta, for cystic fibrosis treatment [2][3] - The trial aims to evaluate the safety, tolerability, pharmacokinetics, and efficacy of SION-719, with topline data expected in mid-2026 [3][4] Company Overview - Sionna Therapeutics is a clinical-stage biopharmaceutical company focused on developing novel medicines to normalize CFTR protein function, specifically targeting the NBD1 domain [6] - The company aims to restore CFTR function to near-normal levels for cystic fibrosis patients, leveraging over a decade of research on NBD1 [6] Clinical Trial Details - The PreciSION CF Phase 2a trial is a randomized, double-blind, placebo-controlled study enrolling adult CF patients homozygous for F508del on a stable dose of Trikafta [3] - The trial will measure changes in CFTR function through sweat chloride levels, a key indicator of CFTR activity [3] Previous Trial Results - In a Phase 1 trial, SION-719 was well tolerated and exceeded pharmacokinetic concentration targets, indicating potential for clinically meaningful improvement over the standard of care [4] - A successful drug-drug interaction study confirmed that SION-719 can be safely administered with Trikafta [4]