On May 20, at the American Thoracic Society (ATS) international conference, during a poster session, Krystal Biotech presented positive interim results from its Phase I CORAL-1 (NCT05504837) trial for its cystic fibrosis (CF) pipeline asset KB407, a gene therapy designed to deliver two copies of the full-length cystic fibrosis transmembrane conductance regulator (CFTR) transgene to the lung. Results demonstrated dissemination of KB407 in the airway and expression of CFTR protein and transient adverse events, highlighting the promise of this therapy as a mutation-agnostic approach that aims to target a broad range of people with CF independent of specific CFTR mutation.
The Phase I CORAL-1 trial was an open-label, dose-escalation, multi-centre 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 nebulisation. Objectives of CORAL-1 included evaluation of safety and tolerability of nebulised 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. Out of the seven patients, four were ineligible for modulator therapy and six patients had successful bronchoscopy yielding biopsies suitable for molecular analysis. To assess the expression of the CFTR protein or viral markers of KB407, immunofluorescence (IF) on endobronchial biopsies was performed.
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Results demonstrated broad airway distribution and transduction, with over 29% of conducting airway cells transduced in all six patients, and all biopsies were positive for CFTR and/or viral markers of KB407. Apical CFTR expression pattern was observed, highlighting an important outcome that correlates with pulmonary function and is related to therapeutic efficacy. Prolonged expression of the CFTR protein for at least 96 hours was also observed and potentially supports the narrative for a repeat dosing regimen that 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. Adverse events were observed to be transient, and there was no evidence of a significant neutralising antibody response following administration of KB407.
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 favourable 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.
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, signaling that the competitive landscape for highly effective modulator therapy (HEMT)-ineligible patients is set to intensify beyond gene therapy alone.
