Sionna Therapeutics, Inc. · NASDAQ:SION
Sionna Therapeutics — NACFC (North American Cystic Fibrosis Conference) 2025
16 slides from Sionna Therapeutics's conference presentation, Mar 2, 2026
Slide 1: Safety, Tolerability, and Pharmacokinetics of Novel NBD1 Stabilizers SION-719 and SION-451
Safety, Tolerability, and Pharmacokinetics of Novel NBD1 Stabilizers SION-719 and SION-451 from Two Phase 1 First-in-Human Studies Jason Maley, Heather Wolff, Jessica Hauben, Steve Altmann, Gregory Hurlbut, Kenneth Huttner, Monette Cotreau, Shane Raines, and Charlotte McKee Sionna Therapeutics, Walt
Slide 2: NACFC Presentation Disclaimer
NACFC Presentation Disclaimer Unless explicitly stated, opinions shared by presenters do not necessarily represent the views of the Cystic Fibrosis Foundation. The Foundation supports NACFC, but does not generally review presentations in advance. The information provided during this conference is in
Slide 3: Presenter Disclosures
Presenter Disclosures The following relationships exist related to this presentation: • Jason Maley, Heather Wolff, Jessica Hauben, Steve Altmann, Gregory Hurlbut, and Charlotte McKee are paid employees of Sionna Therapeutics and hold stock or stock options in Sionna Therapeutics • Kenneth Huttner,
Slide 4: Despite treatment advances, the unmet need remains high in CF
Despite treatment advances, the unmet need remains high in CF CHEC-SC Study; All Patients Pre- and Post- Modulator1* >2/3rd of Abnormal patients on ETI and VTD do not SwCl (mmol/L) sweat chloride ≥30 mmol/L have normal CFTR function1,2,3 as measured by sweat chloride <30mmol/L Normal sweat chloride
Slide 5: NBD1 stabilizers aim to address central driver of CFTR dysfunction
NBD1 stabilizers aim to address central driver of CFTR dysfunction to unlock meaningful improvements in clinical outcomes Sionna is leveraging over 15 years of research, including support by CFF, Genzyme, and Sanofi Cell Membrane F508del defect resides within the NBD1 domain and severely destabilize
Slide 6: Methods
Methods Phase 1 Healthy Volunteer Single-Agent Studies of SION-719 and SION-451 Overall Phase 1 Design SION-719 • 100 total participants dosed: • Safety, tolerability, and PK profiles of single and multiple • SAD: 20mg (fasted & fed), 40mg, 80mg, 160mg ascending doses of SION-719 and SION-451 in hea
Slide 7: Overall Study Design: Evaluating safety, tolerability and PK of SION-451 and SION-719
Overall Study Design: Evaluating safety, tolerability and PK of SION-451 and SION-719 Part A: Single Ascending Dose (SAD) N=8 ; 6 Active, 2 Placebo Part B: 10-Day Multiple Ascending Dose (MAD) N=8 ; 6 Active, 2 Placebo Cohort Cohort Part C: Food Effect & Tablet 1 1 Cohort Cohort Bioequivalence 2 2 C
Slide 8: SION-719 Phase 1 Results
SION-719 Phase 1 Results Favorable Safety and Tolerability Profile Across Single and Multiple Dosing Cohorts SION-719 MAD Safety Summary Placebo BID 20 mg BID 40 mg BID 80 mg BID 120 mg BID 160 mg BID MAD Total Study Participants (n)* (n=10) (n=6) (n=6) (n=6) (n=6) (n=6) (n=40) • SAD and MAD with ov
Slide 9: SION-719 exceeded target exposures predicted by our CFHBE assay
SION-719 exceeded target exposures predicted by our CFHBE assay High potency at lower doses supports add-on to standard-of-care modulators Steady State MAD PK: Day 10 Through 36 Hours Post-administration 20mg BID 1000.0 40 mg BID Add-on target coverage at all doses 80mg BID studied; dual combination
Slide 10: SION-719's potency at low doses has the potential to provide a superior treatment option when added to SOC
SION-719’s potency at low doses has the potential to provide a superior treatment option when added to SOC Potential of SION-719 as an add-on to SOC* 2.50 2.25 current compared to ETI at its Emax SION-719 + ELX/TEZ/IVA 2.00 Mean CFHBE CFTR-dependent Potential zone based on Wild-type levels Phase 1 P
Slide 11: SION-451 Phase 1 Results
SION-451 Phase 1 Results Favorable Safety and Tolerability Profile Across Single and Multiple Dosing Cohorts SION-451 MAD Safety Summary Placebo BID 25 mg BID 75 mg BID 150 mg BID 225 mg BID 300 mg BID MAD Total • SAD and MAD overall consistent safety Study Participants (n)* (n=9) (n=6) (n=5) (n=6)
Slide 12: SION-451 is our preferred anchor for dual combinations
SION-451 is our preferred anchor for dual combinations given exposures achieved in target concentration zones in single agent Phase 1 Steady State MAD PK: Day 10 Through 36 Hours Post-administration 10000.0 25mg BID Fed 75mg BID Dual combination target coverage at 150mg BID Mean SION-451 Concentrati
Slide 13: SION-451 in a dual combination has the potential to provide a superior treatment option
SION-451 in a dual combination has the potential to provide a superior treatment option for people living with CF Potential of SION-451 in dual combination* 2.50 2.25 current compared to ETI at its Emax SION-451 + SION-2222 2.00 Mean CFHBE CFTR-dependent SION-451 + SION-109 Wild-type levels Phase 1
Slide 14: Our vision is to develop treatments anchored by our NBD1 stabilizers
Our vision is to develop treatments anchored by our NBD1 stabilizers to deliver meaningful clinical benefit to people with CF Prioritized Development Path PreciSION CF: Add-on to SOC for POC Dual Combination Development Lower dose SION-719 + SOC SION-451 + ICL4 / TMD1 Advancing SION-719 to Ph 2a POC
Slide 15: Conclusions
Conclusions • Novel NBD1 stabilizers SION-719 and SION-451 were generally safe and well tolerated in healthy volunteers in these Phase 1 studies. • Both compounds exceeded concentrations that, based on the CFHBE assay, have the potential to deliver clinically meaningful benefit when: • SION-719 is a
Slide 16: Thank You!
Thank You!
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