RARE Daily

4DMT Reports Positive Interim Data from Phase 1/2 Cystic Fibrosis Trial

June 8, 2023

Rare Daily Staff

4D Molecular Therapeutics reported positive interim clinical data from the 4D-710 phase 1/2 AEROW clinical trial for the treatment of the rare lung disease cystic fibrosis.

Cystic fibrosis is a major inherited disease caused by mutations in the CFTR gene. It causes impaired lung function, inflammation and bronchiectasis and is commonly associated with persistent lung infections and repeated exacerbations due to the inability to clear thickened mucus from the lungs. Patients with cystic fibrosis require lifelong treatment with multiple daily medications. The complications of the disease result in progressive loss of lung function and hospitalizations, and ultimately lead to end-stage respiratory failure.

4D-710 is comprised of 4DMT’s targeted and evolved vector, A101, and a codon-optimized CFTR∆R transgene. 4D-710 has the potential to treat a broad range of patients with cystic fibrosis, independent of the specific CFTR mutation, and is designed for aerosol delivery to achieve CFTR expression within lung airway epithelial cells.

The experimental therapy is being initially developed for the approximately 15 percent of patients whose disease is not amenable to existing CFTR modulator medicines targeting the CFTR protein. In patients with CFTR mutations whose disease is amenable to modulator medicines, the improvement in lung function is incomplete and is variable. The company expects to potentially develop 4D-710 in this broader patient population in combination with CFTR modulator small molecule medicines.

Interim data from the study was presented at the European Cystic Fibrosis Society 46th Annual Meeting held in Vienna, Austria. The data from cohort 1 included three participants with nine to 12 months of follow up. Quality of life outcomes measured by Cystic Fibrosis Questionnaire-Revised respiratory symptom score showed meaningfully improved for all three participants.

The percent predicted forced expiratory volume (ppFEV1) in one second showed meaningfully improved in a participant with moderate ppFEV1 impairment at baseline. PpFEV1 maintained stable in participants with normal or mild impairment at baseline.

Bronchoscopy sample results demonstrated widespread and consistent expression of the cystic fibrosis transmembrane conductance regulator (CFTR) transgene protein in 92-99 percent of lung airway cells at levels significantly above normal control lung tissues.

Dose selection and initiation of the phase 2 dose expansion stage is expected in the second half of 2023.

“The widespread CFTR transgene expression demonstrated in all lung samples from participants in cohort one is a critical first step for the development of 4D-710, especially given the signals of clinical activity in this CF population with the highest unmet medical need,” said David Kirn, co-founder and CEO of 4DMT. “We believe that 4D-710 represents a potentially transformative new treatment for people with CF. These interim results also demonstrate the potential of our proprietary aerosolized A101 vector for other lung diseases such as alpha-1 antitrypsin deficiency lung disease and other highly prevalent lung diseases.”

Photo: David Kirn, co-founder and CEO of 4DMT

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