4DMT Reports Positive Interim Data from Phase 1/2 AEROW Trial of Aerosolized 4D-710 for Modulator-Ineligible/-Intolerant Cystic Fibrosis at 47th European CF Conference

4D Molecular Therapeutics has announced encouraging interim results from its 4D-710 Phase 1/2 AEROW clinical trial, aimed at treating cystic fibrosis (CF) lung disease. The interim findings were presented by Dr. Jennifer L. Taylor-Cousar at the 47th European Cystic Fibrosis Conference in Glasgow, UK.

Dr. Taylor-Cousar, a principal investigator in the AEROW trial, expressed satisfaction with the observed widespread CFTR transgene and protein expression in airway cells across all doses. This suggests that 4D-710 could potentially benefit CF patients who do not currently respond to available therapies.

Dr. Alan H. Cohen, SVP and Therapeutic Area Head of Pulmonology at 4DMT, emphasized that the clinical data supports advancing 4D-710 to the next stage of development. The company plans to start the Phase 2 Dose Expansion stage in the latter half of 2024, focusing on participants with mild to moderate lung function impairment to confirm the clinical activity of the 1E15 vg dose.

David Kirn, Co-Founder and CEO of 4DMT, highlighted 4D-710 as the leading program in their pulmonology portfolio. The clinical results also support the continued use of their next-generation A101 pulmonary vector for other large-market lung diseases, including alpha-1 antitrypsin deficiency lung disease.

The Phase 1 Dose Exploration stage of the AEROW clinical trial enrolled 10 participants with CF lung disease who are ineligible for or intolerant of CFTR modulator therapy. The participants were divided into four dose cohorts, receiving a single aerosolized dose of 4D-710 administered via an AeroEclipse II breath-actuated nebulizer. The study included a range of baseline ppFEV1 impairment from 56% to 100%.

Interim safety data showed that the 2E15 vg high dose cohort experienced a complete resolution of a previously reported serious adverse event (SAE). Lung biopsies revealed no evidence of inflammation or toxicity, and widespread CFTR protein expression was observed. The 1E15 vg dose was selected as the highest dose for Dose Expansion, as 2E15 vg will not be further evaluated.

At lower doses (2.5E14 to 1E15 vg), 4D-710 was well tolerated with no related adverse events or dose-limiting toxicities. Biomarker analyses showed robust and widespread CFTR transgene mRNA and protein expression across all dose levels. Pre-existing AAV immunity did not impact transgene expression, biological activity, or safety.

Clinical activity data revealed that participants in the 2E15 vg and 1E15 vg cohorts had stable or improved ppFEV1 at 12 months. Two out of three participants with mild to moderate lung function impairment showed clinically meaningful improvement in ppFEV1 at 12 months.

Next steps for 4D-710 include advancing to the Phase 2 Dose Expansion stage with enrollment set to begin in H2 2024. An interim data update from the AEROW clinical trial is expected in mid-2025. Following supportive Phase 2 data, the initiation of Phase 3 is anticipated in H2 2025.

The AEROW Phase 1/2 clinical trial targets approximately 35% of people with CF initially, focusing on those whose disease is not amenable to existing CFTR modulators. 4D-710 has received Rare Pediatric Disease Designation and Orphan Drug Designation from the U.S. FDA.

4D Molecular Therapeutics is a clinical-stage genetic medicines company dedicated to developing gene therapies for large-market diseases in ophthalmology and pulmonology. Their proprietary invention platform, Therapeutic Vector Evolution, aims to create customized vectors for their product candidates, potentially offering curative therapies for millions of patients. Currently, 4DMT is advancing five clinical-stage and two preclinical product candidates.

These advancements underline 4DMT's commitment to developing innovative treatments for CF and other genetic diseases, with the goal of improving the quality of life for patients worldwide.