Navocaftor

Sionna Therapeutics has secured 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. "Our strategy is to build a CF franchise anchored on our novel correctors that stabilize the NBD1 of the CFTR protein," said Mike Cloonan, President and Chief Executive Officer of Sionna. "Combining NBD1 stabilizers with just one complementary CFTR modulator gives us the potential to deliver superior efficacy over the current standard of care. With this agreement, we are significantly expanding and accelerating our pipeline of complementary modulators to combine with NBD1 and creating multiple options for potentially transformational combinations to fully normalize CFTR function. We are well-positioned to execute our differentiated dual combination development path to provide more efficacious options for people with CF," Cloonan added. In clinical studies conducted by AbbVie, ABBV-2222 and ABBV-3067 have been generally safe and well-tolerated. In Phase 2 studies, ABBV-2222 in combination with ABBV-3067 demonstrated clinical efficacy, including increased percent predicted forced expiratory volume in 1 second (ppFEV1) and reduced sweat chloride (SwCl) levels, comparable to approved dual modulator combinations. In pre-clinical assays, including the Cystic Fibrosis Human Bronchial Epithelial (CFHBE) assay, performed by Sionna, dual combinations of a Sionna NBD1 stabilizer and a licensed complementary AbbVie modulator demonstrated the potential for superior efficacy over the current standard of care and some combinations have the potential to fully correct ΔF508 CFTR and achieve wild type levels of CFTR function. "With the CF therapies available today approximately two-thirds of people still do not achieve normal CFTR function," said Patrick Flume, MD, Professor of Medicine and Pediatrics at the Medical University of South Carolina and clinical advisor to Sionna. "It is exciting to see new potential modulator combinations being developed based on the novel ability to stabilize NBD1 and encouraging to see that NBD1 modulators combined with the three licensed programs from AbbVie have the potential for superior efficacy compared to standard of care. There is more we can do for people with ΔF508 CF, and I look forward to seeing these novel double combinations advanced in clinical development," Flume added. As previously announced, Sionna expects to complete a Phase 1 study of its complementary modulator SION-109, targeting the interface between the intracellular loop 4 (ICL4) region and the NBD1 domain of the CFTR protein, in the second half of 2024. The company also plans to initiate Phase 1 studies of two NBD1 stabilizers, SION-451 and SION-719, this year.