SION-109 / Sionna Therap - LARVOL DELTA

Safety, tolerability, and pharmacokinetics of novel NBD1 stabilizers SION-719 and SION-451 from two phase 1 first-in-human studies (NACFC 2025) - "Based on in vitro CF human bronchial epithelial cell (CFHBE) assay data, the concentration targets for clinically meaningful benefit compared with SOC for both SION-451 and SION-719, as either an add-on to SOC or as part of a dual combination with one of Sionna's complementary modulators (SION-2222 or SION-109), were achieved with single and multiple doses. Novel NBD1 stabilizers SION-719 and SION-451 were generally safe and well tolerated in healthy volunteers in these Ph1 studies. Concentrations were achieved with both compounds that are predicted to deliver additional clinically meaningful benefit based on the CFHBE assay when SION-719 or SION-451 is added to SOC or as part of a novel dual combination with one of Sionna's complementary modulators."

Clinical • First-in-human • P1 data • PK/PD data

Small molecule stabilizers of CFTR NBD1 can increase the protein half-life of the apical glycoform of F508del-CFTR to that of wild-type CFTR (NACFC 2025) - " We utilized metabolic pulse-chase labeling to assess the impact of Sionna NBD1 stabilizers SION-451 and SION-719 on the protein half-life of mature and immature F508del-CFTR glycoforms in the presence and absence of TMD1-directed corrector SION-2222, and ICL4-directed corrector SION-109. Robust increases in CFTR protein half-life were seen in vitro in response to treatment with the novel clinical-stage NBD1 stabilizers SION-451 and SION-719, suggesting that NBD1 instability is a central driver of F508del-CFTR's greatly increased degradation rate. We have previously shown that either SION-451 or SION-719, in dual combination with a complementary modulator, enable full correction of F508del-CFTR and restoration of CFTR function in preclinical CF models. Here we show the effects of NBD1 stabilizers also include the correction of F508del-CFTR's protein half-life defect."

Safety, Tolerability, and Pharmacokinetics of Multiple Dose Combinations of SION-451 and Complementary Modulators SION-2222 and SION-109 in Healthy Participants. (clinicaltrials.gov) - P1 | N=144 | Recruiting | Sponsor: Sionna Therapeutics Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Cystic Fibrosis • Genetic Disorders • Immunology • Pulmonary Disease • Respiratory Diseases

Safety, Tolerability, and Pharmacokinetics of Multiple Dose Combinations of SION-451 and Complementary Modulators SION-2222 and SION-109 in Healthy Participants. (clinicaltrials.gov) - P1 | N=144 | Not yet recruiting | Sponsor: Sionna Therapeutics Inc.

New P1 trial • Cystic Fibrosis • Genetic Disorders • Immunology • Pulmonary Disease • Respiratory Diseases

Stabilizers of CFTR NBD1 synergize with galicaftor (SION-2222) or SION-109 to enable full correction of ΔF508-CFTR (ECFS 2025) - "Sionna is advancing in clinical studies a portfolio of novel NBD1 stabilizers and complementary modulators with a goal to provide pwCF with innovative options. Based on preclinical data, Sionna modulator combinations, if successfully developed and approved, have the potential to provide dramatic improvements in clinical outcomes and quality of life for pwCF."

Cystic Fibrosis • Fibrosis • Genetic Disorders • Immunology • Pulmonary Disease • Respiratory Diseases

Sionna Therapeutics Expands Pipeline with Multiple Clinical Stage Cystic Fibrosis Compounds Through a License Agreement with AbbVie (PRNewswire) - "Sionna Therapeutics...announced that it has obtained exclusive worldwide rights to develop and commercialize multiple clinical-stage compounds through a license agreement with AbbVie. Under the terms of the agreement, Sionna will assume all development responsibilities for galicaftor (ABBV-2222), a transmembrane domain 1 (TMD1)-directed cystic fibrosis transmembrane conductance regulator (CFTR) corrector, and navocaftor (ABBV-3067), a CFTR potentiator, both of which have completed Phase 2 studies, and a Phase 1 TMD1-directed corrector, ABBV-2851. Sionna will prioritize advancing one of the AbbVie compounds and SION-109 as potential dual combination options with a first nucleotide binding domain (NBD1) stabilizer. AbbVie will receive an upfront payment, an equity investment in Sionna and will be eligible to receive late-stage development and commercial milestones and royalties."

Licensing / partnership • Cystic Fibrosis

Sionna Therapeutics Announces Phase 1 Initiation for SION-109 in Cystic Fibrosis (PRNewswire) - "Sionna Therapeutics...today announced that the first healthy subject has been dosed in a Phase 1 clinical trial of SION-109 following clearance of its Investigational New Drug application (IND) by the U.S. Food and Drug Administration (FDA)."

Trial status • Cystic Fibrosis

Sionna Therapeutics Announces Presentation of Preclinical Data on NBD1 Stabilizers at 46th European Cystic Fibrosis Conference (PRNewswire) - "Sionna Therapeutics...today announced the presentation of preclinical data demonstrating the activity of the company's portfolio of compounds targeting the first nucleotide-binding domain (NBD1) of the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The results are being presented at the European Cystic Fibrosis Society (ECFS) 46th European Cystic Fibrosis Conference held June 7-10 in Vienna, Austria....Sionna is currently conducting a Phase 1 clinical trial evaluating its lead NBD1 modulator, SION-638, and has nominated two additional NBD1 modulators, SION-719 and SION-451, entering Investigational New Drug application (IND) enabling studies in the second half of 2023....The company is also advancing the development of compounds targeting complementary mechanisms including SION-109, which targets NBD1's interface with the ICL4 region, and SION-676, which targets the TMD1 of CFTR."

Pipeline update • Preclinical • Cystic Fibrosis • Genetic Disorders

Sionna Therapeutics Announces Advancement of Cystic Fibrosis Pipeline Programs and Presentation at J.P. Morgan 41st Annual Healthcare Conference (PRNewswire) - "Sionna Therapeutics...today announced advancement of the company's preclinical and clinical development programs for novel small molecules designed to target the first nucleotide-binding domain (NBD1) of the cystic fibrosis transmembrane conductance regulator (CFTR) protein and complementary mechanisms....The first subjects have been dosed in a Phase 1 study to evaluate the safety and pharmacokinetics of SION-638. Sionna expects data from this study in the second half of 2023. The company is also advancing the development of compounds targeting complementary mechanisms and plans to file an IND for SION-109, targeting NBD1's interface with the intracellular loop 4 (ICL4) region, in the first half of 2023."

IND • P1 data • Trial status • Cystic Fibrosis

Sionna Therapeutics Launches with $111 Million Series B Financing to Advance Pipeline of Novel Small Molecules with the Potential to Fully Restore CFTR Function in Cystic Fibrosis (PRNewswire) - "Sionna Therapeutics...today announced the official launch of the company and the closing of a $111 million Series B financing. The round was led by OrbiMed with participation from funds advised by T. Rowe Price Associates, Inc., Q Healthcare Holdings, LLC., a wholly owned subsidiary of QIA, the sovereign wealth fund of Qatar, and previous investors including RA Capital, TPG's The Rise Fund, Atlas Venture, and the Cystic Fibrosis Foundation. Sionna has raised approximately $150 million to date....The company plans to advance development of a franchise of small molecules targeting NBD1 and complementary modulators, including NBD1's interface with the intracellular loop 4 (ICL4) region and the transmembrane domain 1 (TMD1) of CFTR. Sionna plans to submit Investigational New Drug applications (IND) for its first NBD1 targeted program, SION-638, and for its lead ICL4 program, SION-109, within the next 12 months."

Financing • IND • Cystic Fibrosis