4DMT Announces Update On Regulatory Interactions And Development Path For 4D-710 For Treatment Of Cystic Fibrosis

Author: Benzinga Newsdesk | March 28, 2024 08:10am

• Conducted initial pivotal study interactions with the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA); Company has clear registration path for 4D-710 for treatment of cystic fibrosis (CF) lung disease in people with CF (pwCF) who are ineligible for or cannot tolerate approved CF modulator therapies
• AEROW clinical trial Phase 2 Expansion Cohort dose selection and initiation expected in Q2 2024, with pivotal trial initiation anticipated in H2 2025
• Initial GMP-ready suspension manufacturing process completed in-house at 500 liter scale; technology transfer initiation to commercial CDMO anticipated H1 2025
• Phase 1/2 AEROW clinical trial interim clinical data expected at the European Cystic Fibrosis Conference June 5-8, 2024, including safety, lung biomarker and clinical activity data on all nine patients dosed across four dose level cohorts

EMERYVILLE, Calif., March 28, 2024 (GLOBE NEWSWIRE) -- 4D Molecular Therapeutics (NASDAQ:FDMT, 4DMT or the Company))))), a leading clinical-stage genetic medicines company focused on unlocking the full potential of genetic medicines to treat large market diseases, today announced an update on its regulatory interactions and development path for 4D-710, an aerosolized genetic medicine for the treatment of CF lung disease.

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 in pwCF dosed at 5E14 vg (Cohort 3; n=1) and 2.5E14 vg (Cohort 4; n=1); nine pwCF total have been dosed to date (dose range 2.5E14 to 2E15 vg). Phase 2 Expansion Cohort dose selection is expected in Q2 2024 based on all clinical and lung biopsy data; the Company anticipates enrolling a total of six to nine pwCF in the Phase 2 Expansion Cohort. The Company submitted an AEROW trial amendment to the Cystic Fibrosis Therapeutics Development Network (TDN) as follows: 1) to enroll pwCF with lower baseline percent predicted forced expiratory volume in 1 second (ppFEV1) (50-90%) to assess ppFEV1 response to 4D-710, and 2) 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. The Company plans to share the following at the 47th European Cystic Fibrosis Conference (ECFS) held on June 5-8, 2024 in Glasgow, United Kingdom: 1) interim AEROW clinical and lung biomarker data on all nine pwCF dosed to date, 2) update on AEROW trial amendment status, and 3) development plan update for pwCF who are on modulators.

In addition, the Company recently had discussions with the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA), regarding the registrational path for 4D-710 for treatment of CF lung disease in pwCF who are ineligible for or cannot tolerate approved CF modulator therapies. With regards to a full product approval in this patient population, the Company anticipates a Phase 3 randomized, controlled pivotal study enrolling approximately 60-80 pwCF 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 (Cystic Fibrosis Questionnaire Revised Respiratory Domain, CFQ-R-RD) and frequency of pulmonary exacerbations. 4DMT is preparing for initiation of a Phase 3 clinical trial in H2 2025.

Given the high unmet need in this CF population, an accelerated approval path may be feasible. The Company intends to have discussions with the FDA and EMA on an accelerated approval pathway, in parallel with Phase 3 planning, following additional AEROW clinical and lung biomarker data in pwCF with low baseline ppFEV1. 4D-710 is the first genetic medicine product candidate to demonstrate widespread and high-level CFTR expression (both RNA and protein) in the airways of pwCF; the Company will continue to evaluate the correlation between clinical endpoints and biomarker endpoints in participants with low baseline ppFEV1 in anticipation of further interactions on an accelerated approval pathway.

In addition, the Company has completed in-house process development of a suspension GMP-ready manufacturing process for 4D-710 at 500 liter scale for the pivotal study and potential commercialization. This process, in combination with investigating lower doses, enables potentially lower cost of goods. The Company anticipates initiation of technology transfer to a commercial contract development and manufacturing organization (CDMO) in H1 2025.

"We are encouraged by our productive interactions with the FDA and EMA on pivotal development plans for 4D-710, which we believe has the potential to be a transformative therapy for people with the highest unmet medical need for CF lung disease," said David Kirn, M.D., Co-founder and Chief Executive Officer of 4DMT. "We are committed to advancing 4D-710 into pivotal trial development efficiently, while maintaining our current focus on initiation and completion of two Phase 3 wet AMD studies with 4D-150. Our goal is to initiate Phase 3 development in H2 2025 with 4D-710 suspension GMP process clinical trial material. We look forward to sharing interim clinical data from the AEROW Phase 1/2 clinical trial at the ECFS conference in June 2024."

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