4D Molecular Therapeutics announced positive interim clinical results from its Phase 1 AEROW trial evaluating 4D-710, an investigational gene therapy for cystic fibrosis (CF) lung disease in patients ineligible for or intolerant of CFTR modulator therapies. The results—based on data cutoff Dec. 1, 2025—support advancement of the programme into Phase 2 development.
The AEROW trial enrolled 16 participants across four dose cohorts (2E15, 1E15, 5E14 and 2.5E14 vector genomes [vg]) with follow-up ranging from four months to more than three years. Across the dataset, the therapy was well-tolerated, with no new pulmonary or other safety events in higher-dose cohorts through up to 3.5 years of follow-up. Lower-dose cohorts experienced generally mild and transient adverse events that resolved within about two months.
Biological markers showed durable expression of the CFTR transgene at or above physiologically relevant levels in airway tissue, indicating successful delivery and sustained gene activity. In the 2.5E14 vg cohort—selected as the dose for Phase 2—evidence of clinically meaningful activity was observed across key endpoints, including improvements in percent predicted forced expiratory volume in one second (ppFEV₁), lung clearance index (LCI₂.₅) and patient-reported respiratory quality of life (CFQ-R) through one year.
Based on safety, tissue expression and efficacy signals, the 2.5E14 vg dose was chosen for the upcoming Phase 2 dose-expansion cohort, which aims to enrol six additional participants in H1 2026. A broader programme update is expected in the second half of 2026.
According to 4DMT, these interim data highlight 4D-710’s potential as a durable, “variant-agnostic” disease-modifying treatment for people with CF lung disease and high unmet need, supporting continued clinical evaluation.
