4D Molecular Therapeutics (FDMT) Development Day 2024 summary

Key clinical results and efficacy

• 4D-150 demonstrated robust and durable clinical activity across all wet AMD populations, with up to 98% reduction in annualized injections for recently diagnosed patients and 83% reduction in severe cases at 52 weeks.

• 70% of the broad population and 87% of recently diagnosed patients were injection-free at 52 weeks; 44% of severe cases remained injection-free.

• Visual acuity and anatomic outcomes (CST) remained stable or improved, with fewer fluctuations compared to standard anti-VEGF therapy.

• Efficacy correlates with disease severity and duration, with better outcomes in less advanced cases.

• Longest-term patients remain injection-free for up to three years, with stable intraocular aflibercept levels.

Safety profile and tolerability

• Safety and tolerability are outstanding, with intraocular inflammation rates similar to approved anti-VEGF agents and no 4D-150-related serious adverse events.

• 2.8% of patients experienced mild, transient inflammation, with no vision-threatening complications.

• 99% of patients completed steroid taper on time, and 97% did not need to resume steroids.

• No cases of hypotony, endophthalmitis, vasculitis, choroidal effusions, or retinal artery occlusion related to 4D-150.

• Well-tolerated across all doses and cohorts, including long-term follow-up up to 2.5 years.

Phase III development and strategy

• Phase III (4FRONT-1) is a non-inferiority trial enrolling 500 treatment-naive wet AMD patients, comparing a single dose of 4D-150 to aflibercept every 8 weeks, with global expansion planned.

• Primary endpoint is mean change in BCVA at 52 weeks; design includes a run-in with aflibercept to select responders and 3 monthly loading doses.

• Central reading centers will standardize supplemental injection criteria, reducing investigator discretion.

• Study design is aligned with FDA and EMA feedback, aiming for regulatory and commercial success, with enrollment starting Q1 2025.

• Advisory board and internal team have extensive experience in retina drug development and commercialization.