We are a clinical-stage biopharmaceutical company on a mission to revolutionize the current treatment paradigm for cystic fibrosis (“CF”) patients by developing novel medicines that normalize the function of the cystic fibrosis transmembrane conductance regulator (“CFTR”) protein to deliver clinically meaningful benefit to CF patients. Our goal is to deliver differentiated medicines for people living with CF that can restore their CFTR function to as close to normal as possible by directly stabilizing CFTR’s nucleotide-binding domain 1 (“NBD1”). Despite having long been identified as a critical component for proper CFTR function, NBD1 has been considered “undruggable,” and none of the currently approved CF therapies directly stabilizes NBD1. Worldwide revenue for approved CFTR modulators was approximately $10 billion in 2023 and is expected to grow to $15 billion by 2029. Leveraging more than a decade of our co-founders’ research on NBD1, we are advancing a pipeline of small molecules engineered to correct the defects caused by the F508del genetic mutation, which resides in the NBD1 domain. Approximately 90% of people with CF carry at least one copy of the F508del genetic mutation. We believe stabilizing NBD1 is central to unlocking dramatic improvements in clinical outcomes and quality of life for CF patients. We have employed biophysical, cell-based and virtual screening campaigns and extensive use of structural biology to guide the optimization of novel small molecule NBD1 stabilizers. We are conducting ongoing Phase 1 trials of our two highly potent NBD1 stabilizers, SION-719 and SION-451, evaluating the safety, tolerability and pharmacokinetic (“PK”) profile of single and multiple ascending doses in healthy subjects. These trials are randomized (3:1 active:placebo), doubled-blinded, placebo-controlled and are being conducted in Australia. As of January 14, 2025, five single ascending dose (“SAD”) cohorts and three multiple ascending dose (“MAD”) cohorts of SION-719 have been completed, with over 60 healthy subjects dosed, and six SAD cohorts and three MAD cohorts of SION-451 have been completed, with over 70 healthy subjects dosed. Both SION-719 and SION-451 have been generally well tolerated based on interim Phase 1 clinical data as of the data cutoff date of January 14, 2025. We have established target exposure levels for SION-719 and SION-451 to potentially provide clinically meaningful benefit, if administered as part of a dual combination or as an add-on to the current standard of care (“SOC”), based on our preclinical cystic fibrosis human bronchial epithelial (“CFHBE”) model. In these trials, we have achieved the target concentrations for SION-719 and SION-451 with single and multiple doses. We plan to continue enrolling healthy subjects in additional MAD cohorts. We are also developing a portfolio of complementary CFTR modulators designed to work synergistically with our NBD1 stabilizers to improve CFTR function, as seen in preclinical models. In July 2024, we in-licensed three clinical-stage compounds from AbbVie Global Enterprises Ltd. (“AbbVie”) to expand our portfolio of combination product opportunities, including galicaftor (SION-2222), which targets CFTR’s transmembrane domain 1 (“TMD1”), and has completed Phase 2 clinical trials. In addition, we recently completed a Phase 1 clinical trial evaluating SION-109, which targets CFTR’s intracellular loop 4 (“ICL4”) region. We plan to evaluate multiple NBD1 stabilizer candidates and complementary modulator candidates and select the most promising candidates to advance into later-stage development. Initially, we intend to evaluate the lead NBD1 stabilizer candidate in combination with the current standard of care, Trikafta, in a proof-of-concept trial. In parallel, we will determine the proprietary dual combination that we believe is optimal to advance into a later-stage clinical trial in CF patients. We were incorporated under the laws of the State of Delaware in August 2019 under the name Sling Therapeutics, Inc., and changed our name to Sionna Therapeutics, Inc. in July 2021. Our principal executive offices are located at 21 Hickory Drive, Suite 500, Waltham, MA. We have one subsidiary, Sionna Therapeutics Securities Corporation (f/k/a Sling Therapeutics Securities Corporation), formed in 2020 under the laws of the Commonwealth of Massachusetts.
Read More
