Sionna Therapeutics, Inc. · NASDAQ:SION
Sionna Therapeutics — Technical Presentation (2025)
10 slides from Sionna Therapeutics's technical presentation, Jun 6, 2025
Slide 1: Clinical Stage CFTR NBD1 Stabilizers Synergize to Enable Full Correction of ΔF508-CFTR
Clinical Stage CFTR NBD1 Stabilizers SION-719 and SION-451 Synergize with Galicaftor (SION-2222) or SION-109 to Enable Full Correction of ΔF508-CFTR Greg Hurlbut, PhD* Sionna Therapeutics Co-authors: S. Altmann1*, S. Bercury1*, J. Foley1*, O. Hurlbut-Lesk1, Z. Gao1*, A. Hunnicutt1*, J. Liao1*, M. Mu
Slide 2: NBD1 Instability and Defective Domain Assembly are Central Drivers of ΔF508-CFTR Dysfunction
NBD1 Instability and Defective CFTR Domain-Domain Assembly are Central Drivers of ΔF508-CFTR Dysfunction ΔF508-CFTR’s TMD1 TMD1 TMD2 Domain-domain Mature CFTR NBD1 domain critical NBD1 folding/stability assembly instability and TMD1 domain assembly F508 ΔF508 = ΔF508 = Failed TMD2 ICL4 errors must b
Slide 3: Developing Novel Drugs that Address Key Drivers of Dysfunction
With the Goal of Fully Normalizing ΔF508-CFTR, Sionna is Developing Novel Drugs that Address Key Drivers of Dysfunction • Leveraging over a decade of investment by Sionna, CFF, Genzyme and Sanofi, we’ve had unique success in directly targeting NBD1, a mechanism previously deemed undruggable† • >10 s
Slide 4: SION-719 and SION-451 Bind to and Stabilize the NBD1 Domain of CFTR
Sionna NBD1 Stabilizers SION-719 and SION-451 Bind to and Stabilize the NBD1 Domain of CFTR Surface Plasmon Resonance Differential Static Light Scattering 20 20 SION-719 SION-451 NBD1 Affinity 15 15 ΔTagg °C ΔTagg °C Compound ΔF508-NBD1 KD (µM) 10 10 SION-719 0.0043 5 5 SION-451 0.0024 0 0 ELX No bi
Slide 5: SION-719 Corrects ΔF508-CFTR Maturation to WT Levels in Combination
NBD1 Stabilizer SION-719 Corrects ΔF508-CFTR Maturation to WT Levels when Combined with SION-2222 or SION-109 Western blot WT and ΔF508-CFTR in CFSMEo- NBD1 SION-719 S’719 S’719 S’719 DMSO ETI S’2222 S’109 S’719 +S’2222 +S’109 +ETI DMSO CFTR C-band B-band Na+/K+ ATPase ΔF508 WT ELX (10µM) – approved
Slide 6: SION-451 Corrects ΔF508-CFTR Maturation to WT Levels in Combination
NBD1 Stabilizer SION-451 Corrects ΔF508-CFTR Maturation to WT Levels when Combined with SION-2222 or SION-109 Western blot WT and ΔF508-CFTR in CFSMEo- NBD1 SION-451 S’451 S’451 S’451 DMSO ETI S’2222 S’109 S’451 +S’2222 +S’109 +ETI DMSO CFTR C-band B-band Na+/K+ ATPase ΔF508 WT ELX (10µM) – approved
Slide 7: Dual Combos Can Correct ΔF508-CFTR Function to WT Levels in CFHBEs at Emax
NBD1 Dual Combos with SION-109 or SION-2222 can Correct ΔF508-CFTR Function to WT Levels in CFHBEs at Emax CFHBE VALI (Emax Concentrations) CFHBE VALI (Emax Concentrations) 110 110 FSK-induced CFTR current in Amps FSK-induced CFTR current in Amps 100 100 WT levels of WT levels of 90 90 CFTR functi
Slide 8: SION-719 Dual Combos Show Potential for Clinically Meaningful Benefit Below Emax
SION-719 Dual Combos Show Potential for Clinically Meaningful Benefit at Concentrations Below Emax Dose Response in ΔF508/ΔF508 CFHBE + Human Serum (20% v/v) Translation Model S1_719_Curve: Nonlin fit of Transform X of Data 1 S1-719_Transform X of S011666 2.25 2.50 2.00 SION-719 SION-719 ++SION-2222
Slide 9: SION-451 Dual Combos Show Potential for Clinically Meaningful Benefit Below Emax
SION-451 Dual Combos Show Potential for Clinically Meaningful Benefit at Concentrations Below Emax Dose Response in ΔF508/ΔF508 CFHBE + Human Serum (20% v/v) Translation Model S1_451_Curve: Nonlin fit of Transform X of Data 1 2.25 2.00 SION-451 SION-451 + SION-451 SION-109 2.00 SION-451 ++ SION-2222
Slide 10: Anchored by NBD1, Sionna's Goal is to Deliver Differentiated and Highly Effective New Medicines
Anchored by NBD1, Sionna’s Goal is to Deliver Differentiated and Highly Effective New Medicines for pwCF Sionna is advancing a portfolio of NBD1 stabilizers and complementary CFTR correctors with a goal to enable more patients to achieve normal CFTR function 10