4DMT Reports Positive Phase 1 Data for Gene Therapy 4D-710 in Cystic Fibrosis
核心洞察
4D Molecular Therapeutics announced positive interim Phase 1 data for 4D-710, showing clinically meaningful lung function improvements measured by ppFEV1 and LCI2.5 with follow-up through one year.
The gene therapy demonstrated durable CFTR (搜索) transgene expression within target therapeutic range and was well-tolerated, with the 2.5E14 vg dose selected for Phase 2 development.
4D-710 represents the first genetic medicine to successfully deliver and express the CFTR (搜索) transgene throughout airways of cystic fibrosis patients after aerosol delivery.
4D Molecular Therapeutics announced positive interim clinical data from its Phase 1 AEROW trial evaluating 4D-710, an investigational gene therapy for cystic fibrosis lung disease. The data demonstrate clinically meaningful lung function activity and durable CFTR (搜索) transgene expression, supporting the therapy's potential as a disease-modifying treatment for patients with high unmet medical need.
The AEROW Phase 1 trial enrolled 16 participants with CF lung disease who were ineligible for or intolerant of CFTR (搜索) modulator therapy across four dose cohorts (2E15, 1E15, 5E14 and 2.5E14 vg). As of the December 1, 2025 data cutoff, participants had 4 months to 3.5 years of follow-up.
Safety Profile and Tolerability
The trial demonstrated a favorable safety profile across all dose cohorts. No new pulmonary or other safety events occurred in higher-dose cohorts (1E15 and 2E15 vg) with up to 3.5 years of follow-up. In lower-dose cohorts with 4 to 24 months of follow-up, 4D-710-related adverse events were generally mild, transient and resolved by 2 months, with no 4D-710-related severe adverse events reported.
Efficacy and Biomarker Results
Airway biopsy and brushing results demonstrated consistent and dose-dependent CFTR (搜索) transgene RNA levels at or above physiologically relevant levels compared to non-CF control samples. In the 2.5E14 vg dose cohort, results met the target expression profile.
The 2.5E14 vg dose cohort showed consistent evidence of clinically meaningful activity across all endpoints, including ppFEV1, LCI2.5 and quality of life measures (CFQ-R-R) through one year of follow-up. Based on evaluation of safety, tissue expression and efficacy data, the 2.5E14 vg dose was selected for Phase 2 development.
Clinical Significance of Lung Function Measures
"Lung clearance index, or LCI2.5, was developed to measure lung disease progression earlier and with lower variability than ppFEV1, making it a complementary measure to ppFEV1 for assessing clinical activity in trials like AEROW," said Felix Ratjen, M.D., Ph.D., Professor of Paediatrics at the University of Toronto and Co-Head of the Cystic Fibrosis Center at SickKids. "LCI2.5 can detect changes in the small airways, where CF lung disease initially progresses, even before FEV1 declines, providing a more complete view of lung health."
Therapeutic Approach and Mechanism
4D-710 combines a targeted and evolved next-generation aerosolized AAV vector, A101, with a codon-optimized CFTRΔR transgene. The therapy is designed to be durable, redosable, and variant-agnostic, addressing the underlying cause of CF to improve airway function throughout the lungs.
"The emerging data from the AEROW trial are highly encouraging, demonstrating the selected Phase 2 dose of 4D-710 was well tolerated and achieved physiologically relevant levels of CFTR (搜索) expression, with evidence of clinical benefit across multiple lung function and pulmonary symptom measures," said Jennifer L. Taylor-Cousar, M.D., MSCS, lead Principal Investigator in the AEROW clinical trial and Professor at National Jewish Health.
Disease Context and Unmet Need
According to the CF Foundation, nearly 40,000 people in the United States and more than 105,000 people worldwide are living with CF, with approximately 1,000 new cases diagnosed in the United States each year. Lung disease is the leading cause of morbidity and mortality in people with CF, causing impaired lung function, inflammation, and bronchiectasis commonly associated with persistent lung infections and repeated exacerbations.
Development Timeline
4DMT plans to complete enrollment of the AEROW Phase 2 Dose-Expansion cohort (target n=6) in the first half of 2026, with a program update expected in the second half of 2026. The therapy has received Rare Pediatric Disease Designation and Orphan Drug Designation from the U.S. Food and Drug Administration.
"Based on the data shared today, we continue to believe in 4D-710's potential as a durable, redosable and variant-agnostic genetic medicine that could become a foundational therapy for many people living with CF," said David Kirn, M.D., Co-founder and Chief Executive Officer of 4DMT.