WS05.01 AAV mediated gene therapy for cystic fibrosis: interim results from a phase 1/2 clinical trial

Objectives: Approximately 15% of people with cystic fibrosis (pwCF) either have a pathogenic CFTR variant that is not amenable to modulator therapy or exhibit intolerance modulators. Delivery functional copy the gene airways could provide durable benefit regardless underlying variant. 4D-710 novel aerosolized genetic medicine comprising synthetic AAV vector (A101) and human deletion in regulatory domain (CFTRΔR). Here we report interim data from first-in-human clinical trial evaluating pwCF. Methods: This U.S. multicenter, open-label, Phase 1/2 (NCT05248230) includes dose exploration phase expansion phase. Eligible participants are adults (≥18 y) CF lung disease who ineligible for did tolerate therapy. administered via breath-actuated nebulizer as single (cohort 1, 1 × 1015 vg; cohort 2, 2 vg). Study assessments performed at scheduled intervals during 12-month observation period. Bronchoscopy week 4 evaluate transfer expression endobronchial biopsy brushing samples. Results: Enrollment complete (n = 3). Initial indicated treatment was well tolerated, no 4D-710-related adverse events subsequent aerosol delivery, serious events, dose-limiting toxicities. CFTRΔR mRNA detected all evaluable samples 11). 36–47% airway cells showed transgene expression, including ciliated columnar, goblet, basal cells. Cohort currently enrolling. Two been dosed; ongoing. Conclusions: demonstrated evidence tolerability successful delivery lung. Additional will be presented.