4D Molecular Therapeutics Outlines Pivotal Development Plans For Cystic Fibrosis, Rare Inherited Disease

4D Molecular Therapeutics Inc FDMT announced an update on its 4D-710, an aerosolized genetic medicine for cystic fibrosis (CF) lung disease.

CF is a genetic (inherited) disease that causes sticky, thick mucus to build up in organs, including the lungs and pancreas.

Given high-level cystic fibrosis transmembrane conductance regulator (CFTR) transgene expression in all lung airway biopsies disclosed to date (significantly above normal lung CFTR levels), dose exploration continues with the evaluation of lower doses in the 4D-710 Phase 1/2 AEROW clinical trial at 5E14 vg dose (Cohort 3; n=1) and 2.5E14 vg (Cohort 4; n=1).

Phase 2 Expansion Cohort dose selection is expected in Q2 2024 based on all clinical and lung biopsy data; the company anticipates enrolling six to nine patients in the Phase 2 Expansion Cohort. 

The company submitted an AEROW trial amendment to the Cystic Fibrosis Therapeutics Development Network: 

• To enroll patients with lower baseline percent predicted forced expiratory volume in 1 second (ppFEV1) (50-90%) to assess ppFEV1 response to 4D-710
• To add a second lung biopsy procedure at a longer-term timepoint (12 months or later) to study long term durability of 4D-710 CFTR transgene expression and optimal timing for redosing. 

In addition, the company recently had discussions with the FDA and European Medicines Agency regarding the registrational path for 4D-710 for CF lung disease in patients who are ineligible for or cannot tolerate approved CF modulator therapies. 

Regarding full product approval in this patient population, the company anticipates a Phase 3 randomized, controlled pivotal study enrolling approximately 60-80 patients with low baseline ppFEV1 (planned to be approximately 40-80%). 

Phase 3 clinical endpoints include changes after 4D-710 treatment in ppFEV1, quality of life, and frequency of pulmonary exacerbations. 4DMT is preparing to initiate a Phase 3 clinical trial in H2 2025.

Additionally, the company completed the in-house process development of a suspension manufacturing process for 4D-710 at a 500-liter scale for the pivotal study and potential commercialization. 

This process, in combination with investigating lower doses, enables lower cost of goods. The company anticipates initiating technology transfer to a commercial contract development and manufacturing organization in H1 2025.

Price Action: FDMT shares are down 12.20% at $31.50 on the last check Thursday.

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