4DMT Secures $11 Million CF Foundation Investment to Advance Gene Therapy 4D-710 into Phase 2 for Cystic Fibrosis
核心洞察
The Cystic Fibrosis Foundation will provide up to $11 million in additional funding to 4D Molecular Therapeutics to accelerate development of 4D-710, a gene therapy for cystic fibrosis lung disease.
Phase 2 enrollment in the AEROW clinical trial is currently underway with 2.5E14 vg selected as the anticipated pivotal and commercial dose for the variant-agnostic genetic medicine.
The funding supports redosing studies and Phase 3 readiness, with interim Phase 1 data including functional durability results expected by year-end 2025.
4D Molecular Therapeutics announced that the Cystic Fibrosis Foundation will provide up to $11 million in additional funding to accelerate development of 4D-710, a gene therapy for cystic fibrosis lung disease. The investment includes an initial tranche of $7.5 million that closed in October 2025, with the second tranche contingent on specific clinical milestones. This brings the CF Foundation's total commitment to 4DMT's CF programs to nearly $32 million.
The funding supports advancement of 4D-710 through Phase 2 of the AEROW clinical trial, where enrollment is currently underway with 2.5E14 vg selected as the anticipated pivotal and commercial dose. This dose was chosen after review with the CF Foundation Safety Review Team and clinical trial leadership.
Joint Steering Committee Formed for Strategic Development
The CF Foundation and 4DMT will establish a Joint Steering Committee with senior clinical development and regulatory expertise to enhance strategic planning and coordination of 4D-710's development. The collaboration will support several key activities including Phase 1 redosing studies, Phase 2 advancement, and Phase 3 readiness preparations.
Selected participants from Phase 1 are expected to receive a second dose of 2.5E14 vg at least one year following their initial 4D-710 dosing, enabling evaluation of the therapy's redosing potential.
Enhanced Clinical Endpoints and Data Expected
The AEROW protocol has been amended to include additional clinical endpoints in lower dose cohorts. These include multiple-breath washout measuring lung clearance index (LCI2.5), which serves as a sensitive measure of small airway function that regulators have used to support pediatric CF therapy approvals. High-resolution computed tomography (HRCT) will provide detailed lung visualization to assess structural changes including mucus plugging and airway wall thickening.
Phase 1 data will focus on follow-up of nine lower dose patients over approximately 3 to 18 months, emphasizing functional respiratory endpoints including LCI2.5, ppFEV1, and CFQ-R-R. The company plans to share interim Phase 1 data and functional durability results spanning one to three years post-dosing by year-end 2025.
Addressing Significant Unmet Medical Need
According to the CF Foundation, nearly 40,000 people in the United States and more than 105,000 people worldwide live with cystic fibrosis, with approximately 1,000 new cases diagnosed annually in the US. Lung disease represents the leading cause of morbidity and mortality in CF patients, causing impaired lung function, inflammation, and bronchiectasis with persistent infections and repeated exacerbations due to inability to clear thickened mucus.
"Our next-generation A101 vector utilized in 4D-710 was invented for efficient aerosol delivery and transduction throughout the lung airways and was designed to enable repeat dosing to maintain clinical benefit over time," said David Kirn, M.D., Co-founder and Chief Executive Officer of 4DMT. "This funding and strategic support are critical as we advance 4D-710 through Phase 2, with the goal of delivering a durable, redosable, and variant-agnostic genetic medicine with the potential to become a foundational treatment for individuals with CF with remaining unmet pulmonary needs."
First-in-Class Gene Therapy Approach
4D-710 combines a targeted and evolved next-generation aerosolized AAV vector, A101, with a codon-optimized CFTR (搜索)∆R 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. 4D-710 represents the first known genetic medicine to demonstrate successful delivery and expression of the CFTR transgene throughout the airways of people with CF after aerosol delivery.
The therapy has received Rare Pediatric Disease Designation and Orphan Drug Designation from the U.S. Food and Drug Administration. The ongoing AEROW Phase 1/2 clinical trial is assessing 4D-710's impact on overall lung health, including changes to small airway function, airway structure, and quality of life.
The development program includes analysis of paired lung biopsies collected at 1-2 months and then 1-3 years post-dosing to evaluate transgene expression and functional durability data, providing critical insights into the therapy's long-term potential as a foundational treatment for CF patients regardless of their specific CFTR (搜索) variant.