Sionna Therapeutics, Inc. · NASDAQ:SION

Sionna Therapeutics — 49th European Cystic Fibrosis Conference 2026

11 slides from Sionna Therapeutics's conference presentation, June 2026

  1. Slide 1: Clinical-stage NBD1 stabilizers can increase F508del-CFTR protein half-life to wild-type levels

    Clinical-stage NBD1 stabilizers can increase F508del-CFTR protein half-life to wild-type levels when used alone or in combination with other CFTR modulators S. Bercury, A. Madanjian, S. Altmann, J. Foley, A. Hunnicutt, J. Liao, Z. Gao, G. Topalov, M. Munson, G. Hurlbut Sionna Therapeutics, Waltham M

  2. Slide 2: NBD1 Instability and Defective CFTR Domain-Domain Assembly are Central Drivers of F508del-CFTR Dysfunction

    NBD1 Instability and Defective CFTR Domain-Domain Assembly are Central Drivers of F508del-CFTR Dysfunction F508del-CFTR’s TMD1 TMD1 TMD2 Mature CFTR NBD1 domain Domain-domain critical NBD1 folding/stability assembly instability and TMD1 domain assembly F508 F508del = F508del = Failed TMD2 ICL4 error

  3. Slide 3: NBD1 Instability and Defective CFTR Domain-Domain Assembly are Central Drivers of F508del-CFTR Dysfunction

    NBD1 Instability and Defective CFTR Domain-Domain Assembly are Central Drivers of F508del-CFTR Dysfunction F508del-CFTR’s TMD1 TMD1 TMD2 Mature CFTR NBD1 domain Domain-domain critical NBD1 folding/stability assembly instability and TMD1 domain assembly F508 F508del = F508del = Failed TMD2 ICL4 error

  4. Slide 4: Sionna is Developing NBD1 Stabilizers and Complementary Modulators that Correct Domain Assembly

    Sionna is Developing NBD1 Stabilizers and Complementary Modulators that Correct Domain Assembly • Marketed modulators have significantly improved outcomes for people with CF, but do not fully restore normal CFTR function in at least two-thirds of patients1,2 • Leveraging over 15 years of investment

  5. Slide 5: Sionna Clinical-stage NBD1 Stabilizers Correct the Thermal Stability Defect of F508del-NBD1

    Sionna Clinical-stage NBD1 Stabilizers Correct the Thermal Stability Defect of F508del-NBD1 SION-451 and SION-719 are high affinity NBD1 ligands that can stabilize F508del-NBD1 to levels exceeding WT NBD1 Differential Static Light Scattering 100 15 WT NBD1 SION-451 75 F508del-NBD1 SION-719 ΔTagg = 1

  6. Slide 6: NBD1 Stabilizers Increase Steady-State Levels of Mature F508del-CFTR Alone and in Combination

    NBD1 Stabilizers Increase Steady-State Levels of Mature F508del-CFTR both Alone and in Combination with Complementary Modulators F508del-CFTR C-band similar to WT levels at steady state SION-451 + SION-719 + DMSO DMSO S’2222 S’109 DMSO DMSO ETI DMSO ETI DMSO CFTR CFTR C-band C-band B-band B-band Na+

  7. Slide 7: NBD1 Stabilizers Improve F508del-CFTR Protein Maturation and Function, Increase Half-life to WT Levels

    NBD1 Stabilizers Improve F508del-CFTR Protein Maturation and Function, And Pulse Chase Analysis Demonstrates They Increase F508del-CFTR Half-life to WT-CFTR Levels WT-CFTR F508del-CFTR + DMSO + DMSO + ETI Chase (h) 2 4 8 12 24 36 48 Chase (h) 2 4 6 8 2 4 8 12 24 36 48 C-band C-band B-band B-band F50

  8. Slide 8: Metabolic Pulse Chase Analysis Demonstrates NBD1 Stabilizers Improve the Half-life of F508del-CFTR

    Metabolic Pulse Chase Analysis Demonstrates NBD1 Stabilizers Improve the Half-life of F508del-CFTR to WT-CFTR Levels 125 WT CFTR ΔF508 CFTR NBD1 Stabilizers ΔF508 CFTR + ETI 100 ΔF508 CFTR + S'451 ΔF508 CFTR + S'451 + S'2222 75 ΔF508 CFTR + S'451 + S'109 ΔF508 CFTR + S'719 ΔF508 CFTR + S'719 + ETI 5

  9. Slide 9: Alone and in Combination, NBD1 Stabilizers Improve F508del-CFTR Function in the CFHBE Translation Model

    Alone and in Combination, NBD1 Stabilizers Improve F508del- CFTR Function in the CFHBE Translation Model Combinations of SION-451 with SION-2222 or SION-109, and SION-719 with ETI were Highly Active in the F508del/F508del CFHBE* (VALI) Model at Emax WT levels WT levels of CFTR of CFTR function funct

  10. Slide 10: To Fully Normalize F508del-CFTR, Sionna is Developing Novel Modulators to Address Key Drivers of Dysfunction

    To Fully Normalize F508del-CFTR, Sionna is Developing Novel Modulators to Address Key Drivers of Dysfunction • NBD1 stabilizers SION-451 and SION-719, in combination with complementary modulator(s), enable full restoration of WT-like CFTR function in preclinical CF models • Here, we demonstrate that

  11. Slide 11: Thank You

    49th EUROPEAN CYSTIC FIBROSIS CONFERENCE edds 3-6 JUNE 2026 | LISBON, PORTUGAL Thank You

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