Sionna Therapeutics has achieved a significant milestone in cystic fibrosis (CF) drug development, announcing positive Phase 1 results for its first-in-class nucleotide-binding domain 1 (NBD1) stabilizers SION-719 and SION-451. The clinical-stage biopharmaceutical company reported that both compounds were generally well tolerated and achieved desired pharmacokinetic targets that reinforce their potential to provide clinically meaningful benefit for CF patients.
Phase 1 Trial Results Demonstrate Safety and Target Achievement
The randomized, double-blind, placebo-controlled Phase 1 trials evaluated the safety, tolerability, and pharmacokinetic profiles of single ascending doses and multiple ascending doses of both NBD1 stabilizers in healthy volunteers. The SION-719 trial enrolled 100 subjects, while the SION-451 trial included 110 subjects.
Both compounds demonstrated favorable safety profiles with no serious adverse events, treatment emergent adverse events leading to drug discontinuation, or dose-limiting adverse events observed. Most treatment emergent adverse events were mild to moderate (Grade 1 or Grade 2). Notably, there were no treatment emergent adverse events related to liver function tests in SION-719 treated subjects, while SION-451 showed only one Grade 1 liver function test-related event in a subject who tested positive for influenza.
"Today's announcement brings us one step closer to our vision of developing novel NBD1-led proprietary dual combinations to transform the treatment paradigm for CF patients," said Mike Cloonan, President and Chief Executive Officer of Sionna. "The successful completion of two NBD1 Phase 1 trials and being the first company to bring NBD1 compounds into the clinic are important milestones."
Pharmacokinetic Targets Support Clinical Potential
Both SION-719 and SION-451 achieved desired target pharmacokinetic concentrations at multiple dose levels in a twice daily regimen. The stabilizers met exposure thresholds that, based on Sionna's preclinical CF human bronchial epithelial model, have the potential to provide clinically meaningful benefit if administered as an add-on to standard of care or in a proprietary dual combination with complementary modulators.
The data from Part C of each trial support the use of a tablet formulation in future studies and indicate that both compounds can be dosed in either fed or fasted states, providing dosing flexibility for future clinical development.
Differentiated Development Pathways for Each Compound
Sionna plans to advance both NBD1 stabilizers through distinct clinical development pathways. SION-719 will proceed to a Phase 2a proof-of-concept trial evaluating the compound as an add-on to standard of care in CF patients. The trial objectives will be to demonstrate improvement in CFTR function as defined by sweat chloride reduction and to show that NBD1 is mechanistically unique from, and synergistic with, the components of standard of care.
The FDA has cleared the Investigational New Drug application for SION-719, and the first subject has been dosed in a midazolam drug-drug interaction study to confirm SION-719 can be dosed in combination with standard of care according to its label. This study will be completed prior to initiation of the Phase 2a trial.
SION-451 will advance to a Phase 1 healthy volunteer dual combination trial evaluating the compound in combination with SION-2222 (galicaftor), a transmembrane domain 1-directed CFTR corrector, and with SION-109, an intracellular loop 4-directed CFTR corrector. The trial will assess the safety, tolerability, and pharmacokinetics of varying doses of the dual combinations and will inform selection of a dual combination for a Phase 2b trial in CF patients.
Addressing Unmet Medical Need in Cystic Fibrosis
The clinical advancement of these NBD1 stabilizers addresses a significant unmet medical need in CF treatment. According to Patrick Flume, M.D., Professor of Medicine and Pediatrics at the Medical University of South Carolina, "While advances in CF treatments have improved the lives of CF patients over the past decade, there still remains a large unmet need. The majority of CF patients on approved modulators do not have normal CFTR function and many patients discontinue or reduce dosages due to tolerability issues."
Strong Financial Position Supports Development Timeline
Sionna's clinical development programs are supported by a strong financial position following the completion of an upsized IPO in February 2025. The company raised approximately $219 million in gross proceeds before deducting underwriting discounts and commissions, issuing 12,176,467 shares at $18.00 per share. With the net IPO proceeds, Sionna expects its current cash position to fund operations into 2028.
Both next-stage trials are on track to initiate in the second half of 2025, with topline data anticipated in mid-2026. The company's mission focuses on revolutionizing the current treatment paradigm for CF by developing novel medicines that normalize the function of the cystic fibrosis transmembrane conductance regulator protein, with the goal of restoring CFTR function to as close to normal as possible.
