4DMT Reports Positive 1-Year Efficacy for AAV Cystic Fibrosis Gene Therapy

EMERYVILLE, Calif. – December 17, 2025 — 4D Molecular Therapeutics (4DMT) today released positive interim clinical data from the Phase 1 AEROW trial evaluating 4D-710, an investigational AAV (adeno-associated virus) gene therapy for cystic fibrosis (CF) lung disease. The data demonstrate that this AAV candidate achieved durable CFTR transgene expression and clinically meaningful improvements in lung function through at least one year of follow-up.

AAV-Mediated Delivery and Clinical Efficacy

The 4D-710 platform utilizes a proprietary, “evolved” next-generation aerosolized AAV vector known as A101. This AAV vector is specifically designed to bypass the thick mucus layers in CF lungs to deliver a functional CFTR gene directly to airway cells.

• Durable Expression: Biopsy results confirmed that the AAV-delivered transgene maintained expression within the target therapeutic range for over a year.

• Lung Function Gains: In the selected Phase 2 AAV dose cohort (2.5E14 vg), participants showed consistent improvements in ppFEV1 (a measure of large-airway function) and LCI2.5 (Lung Clearance Index), which detects early changes in the small airways.

• Variant-Agnostic Approach: Because the AAV vector delivers a healthy copy of the gene, the treatment is effective regardless of the patient’s specific genetic mutation, offering a “variant-agnostic” solution for those ineligible for current modulator therapies.

Safety and Phase 2 Dose Selection

The safety profile of the AAV therapy remains a highlight of the interim update. As of the December 1st data cutoff, the AAV treatment was generally well-tolerated across 16 participants.

• Long-term Follow-up: Higher-dose AAV cohorts (1E15 and 2E15 vg) have now been monitored for up to 3.5 years with no new pulmonary or serious safety events.

• Phase 2 Dose: Based on the optimal balance of safety and AAV-driven tissue expression, the 2.5E14 vg AAV dose was selected for the upcoming Phase 2 dose-expansion cohort.

• Redosability: Unlike some traditional AAV applications, 4D-710 is designed to be redosable, potentially allowing for maintained therapeutic benefit over a patient’s lifetime.

4DMT expects to complete enrollment for the Phase 2 AAV dose-expansion cohort in the first half of 2026, with a significant program update scheduled for the second half of that year.