Sionna Therapeutics, Inc. · NASDAQ:SION
Sionna Therapeutics — Corporate Update (September 2026)
23 slides from Sionna Therapeutics's corporate update, Sep 14, 2026
Slide 1: PreciSION CF Key Learnings and Plans to Advance Dual Combination
Sionna Therapeutics PreciSION CF Key Learnings and Plans to Advance Dual Combination September 14th, 2026
Slide 2: Disclaimers and forward-looking statements
Disclaimers and forward-looking statements This presentation contains forward-looking statements of Sionna Therapeutics, Inc. (“Sionna”, “the Company”, “we”, “us”, or “our”) that involve substantial risks and uncertainties. All statements other than historical factual information are forward-looking
Slide 3: Strong conviction in NBD1 biology and rationale to pursue the dual combination
We have strong conviction in the NBD1 biology, and believe there is compelling rationale to pursue the dual combination Post hoc observations Combination with provide evidence of Trikafta® may have Dual combination Cash preservation NBD1 target blunted NBD1 impact advancing to Ph 2a POC actions take
Slide 4: SION-719 PreciSION CF Phase 2a Trial Post Hoc Analysis
SION-719 PreciSION CF Phase 2a Trial Post Hoc Analysis
Slide 5: PreciSION CF Phase 2a trial randomized, double-blind crossover design
PreciSION CF Phase 2a trial used a randomized, double-blind crossover design to evaluate SION-719 added to background Trikafta 14 participants completed trial 28 Day 14 Day 14 Day 28 Day 14 Day 14 Day Endpoints Primary: Safety, Tolerability Secondary: Sweat Chloride, PK Phase 2a Sequence 1 n=6 SION-
Slide 6: Post hoc analysis identified three key potential confounding factors
Multiple dimensions of the PreciSION CF post hoc analysis consistently identified three key potential confounding factors 1 2 3 PK Outliers ETI Exposure CFTR Channel Biology Three participants had no or unusually low SION-719 or Trikafta ETI exposures were lower by an SION-719 + ETI showed high CFTR
Slide 7: Placebo-adjusted sweat chloride outcome was very different than expected
The placebo-adjusted sweat chloride outcome was very different than what we expected Secondary SwCl analysis - full data set (N=14) SION-719 Treatment Period Placebo Treatment Period Total Placebo-Adjusted 40 40 40 Confounded participants* Confounded participants* Confounded participants* 30 30 30 2
Slide 8: Patterns in participants consistent with dosing non-adherence
A deep dive into the data identified patterns in 3 participants consistent with dosing non-adherence that may have confounded results Observation Study Impact 1 participant with unmeasurable Trikafta and Believed to have caused direct and confounding 1 participant with unusually low levels of Trikaf
Slide 9: Removing confounded participants, data indicate NBD1 stabilization
Removing 3 confounded participants, the post hoc treatment and placebo data indicate NBD1 stabilization Secondary SwCl analysis - excluding 3 confounders (N=11) SION-719 Treatment Period Placebo Treatment Period Total Placebo-Adjusted 40 40 40 30 30 30 Mean SwCl Change (mmol/L) 20 20 20 Mean SwCl Ch
Slide 10: Post hoc analysis shows up to -8.6 mmol/L mean sweat chloride change
Post hoc analysis shows up to -8.6 mmol/L mean sweat chloride change, which we believe is evidence of NBD1 activity LS Mean Placebo-Adjusted SwCl Change (mmol/L) All participants (N = 14) Excluding confounded participants (N = 11) Study Day 1 baseline -1.0 Analysis Primary (p=0.70) Change in SwCl ca
Slide 11: Larger treatment effect expected; lower Trikafta exposures may be the cause
However, we expected a larger treatment effect – this may have been due to lower Trikafta exposures when combined with SION-719 Key observations Change in mean concentrations of Trikafta (ETI) during placebo and treatment periods Excluding 3 confounded participants (N=11) On average, decreased ETI e
Slide 12: CFTR modulators target distinct regions of CFTR
CFTR modulators target distinct regions of CFTR, and work in different ways to restore function CFTR STRUCTURE TMD1 and ICL4 Correctors help CFTR fold properly, reach the cell surface and remain more stable there by targeting regions around NBD1 Cell Membrane Potentiator NBD1 stabilizers directly ta
Slide 13: Emerging hypothesis on CFTR channel behavior when NBD1 is combined with a potentiator
PreciSION CF outcome informed an emerging hypothesis regarding CFTR channel behavior when NBD1 is combined with a potentiator Add-On Dual Combination SION-719 ETI SION-451 SION-2222 Nonclinical data: NBD1 SOC NBD1 TMD1 Protein Maturation Restored up to wild-type Restored up to wild-type Trafficking
Slide 14: CFTR channel activity in CFHBE model: normal and CF cells with ETI
CFTR channel activity in CFHBE model: normal and CF cells with ETI Normal regulation ETI modulated F508del-CFTR at Emax Wild-Type F508del CFTR 80 Strong 80 ETI response to DMSO stimulation ETI 70 70 Higher 60 60 stimulated current 50 50 Ieq (μA/cm2) Ieq (μA/cm2) 40 40 Low activity before 30 stimulat
Slide 15: CFTR channel activity in CFHBE model with SION-719 (NBD1) + ETI
CFTR channel activity in CFHBE model: normal and CF cells with SION-719 (NBD1) + ETI Normal regulation SION-719 + ETI modulated F508del-CFTR at Emax Wild-Type F508del CFTR Strong 80 response to 80 ETI DMSO stimulation SION-719+ETI ETI 70 70 Activity ETI+719 before stimulation 60 60 Increase in curre
Slide 16: CFTR channel activity in CFHBE model with SION-451 + SION-2222
CFTR channel activity in CFHBE model: normal and CF cells with SION-451 (NBD1)+ SION-2222 (TMD1) Normal regulation Dual combination modulated F508del-CFTR at Emax Wild-Type F508del CFTR 80 Strong 80 ETI response to DMSO stimulation SION-719+ETI ETI 70 70 SION-451+SION-2222 ETI+719 451+2222 60 60 Res
Slide 17: SION-451 Dual Combination Next Steps
SION-451 Dual Combination Next Steps
Slide 18: Meaningful opportunity exists for alternative CF treatment options
Meaningful opportunity exists for alternative CF treatment options beyond the standard of care High Unmet Need More Options Desired >2/3rd of patients on SOC CF is a one-player, do not have normal CFTR function, ~$13B market today6, expected to grow to as measured by sweat chloride1,2,3 ~$15B-17B by
Slide 19: Phase 1 established SION-451 + SION-2222 as preferred dual combination
Phase 1 established SION-451 + SION-2222 as our preferred dual combination Trial Design & Conduct Trial Outcome • Evaluated safety, tolerability, and PK across multiple dose • Achieved safety and tolerability objectives combinations of SION-451 + SION-2222 and SION-451 + SION-109 in healthy voluntee
Slide 20: SION-451 BID + SION-2222 QD demonstrated a favorable tolerability profile
SION-451 BID + SION-2222 QD demonstrated a favorable tolerability profile SION-451 BID + SION-451 BID + Placebo Total SION-2222 QD SION-2222 BID 3 cohorts 2 cohorts Trial Participants (n) (n=15) (n=27) (n=18) (n=60) Participants with any TEAE, n (%) 5 (33) 19 (70) 10 (56) 34 (57) SION-451 BID + SION
Slide 21: AscenSION CF proof-of-concept trial expected to initiate in 1Q27
AscenSION CF proof-of-concept trial of SION-451 + SION-2222 expected to initiate in 1Q27 PROPRIETARY Completed DUAL COMBINATION SION-451 SION-2222 Phase 1 Phase 1 Combo Phase 2a POC Phase 2b NBD1 (galicaftor) SAD/MAD in HVs in HVs AscenSION CF AscenSION CF 2 TMD1 Dual Combo Open-label Dual Combo Dos
Slide 22: Dual combination offers a differentiated two-drug approach
Dual combination offers a differentiated two-drug approach to current triple-combination therapies SION-451 SION-2222 NBD1 TMD1 Designed to target Ph 2a POC designed as an Proprietary approach meaningful CFTR benefit in ~$13B1 market seeking efficient study to evaluate anchored by novel NBD1 a two-d
Slide 23: Sionna
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