Positive Phase I interim results from the Phase I CORAL-1 trial for Krystal Biotech’s KB407, presented at the recent ATS 2026 International Conference, highlight the promise of this gene therapy as a mutation agnostic approach that aims to target a broad range of people with cystic fibrosis (CF). Results demonstrated dissemination of KB407 in the airway and expression of cystic fibrosis transmembrane conductance regulator (CFTR) protein and transient adverse events, and strengthen the narrative for gene therapies in cystic fibrosis independent of specific CFTR mutation, according to GlobalData, a leading intelligence and productivity platform.
KB407 is a gene therapy designed to deliver two copies of the full-length cystic fibrosis transmembrane conductance regulator (CFTR) transgene to the lung. The Phase I CORAL-1 trial was an open-label, dose-escalation, multi-center study in adult patients with CF that included three dose escalation cohorts, evaluating either one, two, or four daily administrations of 109 plaque forming units of KB407 via nebulization. Objectives of CORAL-1 included evaluation of safety and tolerability of nebulized KB407 and to assess transduction of KB407 and CFTR transgene expression in the lung.
The results presented at ATS 2026 were related to the third cohort (n=7), who received the highest dose of four daily administrations, and demonstrated broad airway distribution and transduction, with over 29% of conducting airway cells transduced in all six patients who had successful bronchoscopy yielding biopsies suitable for molecular analysis. Apical CFTR expression pattern and prolonged expression of the CFTR protein were also observed.
Vinie Varkey, Associate Director, Immunology at GlobalData, comments: “KB407’s results reflect outcomes that correlate with pulmonary functions and therapeutic efficacy. In particular, the prolonged expression that potentially supports the narrative for a repeat dosing regimen could be more convenient than that associated with the current standard of care, Vertex Pharmaceuticals’ Trikafta (elexacaftor/tezacaftor/ivacaftor), which needs to be taken twice daily. The dosing regimen of KB407 will potentially address the high pill burden and compliance issues associated with the standard of care CFTR modulators.”
KB407’s positive set of results presented at ATS 2026 follows a set of similar positive results that were announced for the first two cohorts in December 2024, highlighting a consistent safety profile observed across the three cohorts and suggesting a favorable therapeutic index at the higher doses. The results from the CORAL-1 study offer the basis for Krystal Biotech’s plan to initiate the registrational CORAL-3 study, enrollment for which is expected to take place in the second quarter of 2026.
Varkey continues: “KB407’s positive results from CORAL-1 offer an encouraging outlook for the treatment of patients with CF, especially those who are currently ineligible for approved modulator therapies or those who are currently underserved with these approved therapies. As a mutation-agnostic approach, KB407 has the potential to serve a broader CF population if superior efficacy is demonstrated, and the upcoming registrational trial will be closely watched for its efficacy and safety results.”
KB407 is one of several CFTR mutation-agnostic approaches in development for CF, with multiple mechanistic fronts being explored simultaneously, one of which was also presented at ATS 2026. Alentar Biosciences presented preclinical data for a novel gamma-secretase inhibitor capable of restoring mucociliary clearance through a CFTR-independent pathway.
Varkey concludes: “While current CFTR modulator therapies only manage symptoms and protein defects, mutation agnostic therapies potentially represent the next major frontier in cystic fibrosis care and will drive the need for universally applicable therapeutics especially for those patients who are non-responsive to current approved therapies.”
