4D Molecular Therapeutics (FDMT) H.C. Wainwright 4th Annual Ophthalmology Virtual Conference summary

Platform and Pipeline Overview

• Utilizes directed evolution to create proprietary AAV vectors for targeted gene delivery to retina, lung, and heart.

• R100 capsid enables low-dose, safe intravitreal injection with high transduction and minimal inflammation.

• Pipeline includes 4D-150 for wet AMD and DME, 4D-175 for geographic atrophy, and programs in CF and Fabry disease.

• All three main vectors validated in clinic for best-in-class delivery at lower doses, improving safety and cost.

• $578M cash on hand as of June 30, 2024, with runway through the first half of 2027.

4D-150 Design and Clinical Rationale

• 4D-150 delivers Aflibercept and VEGF-C RNAi, targeting four VEGF family members in one product.

• Proprietary promoter system enhances Aflibercept expression for greater efficacy.

• Designed to reduce injection frequency and maintain steady anti-VEGF levels, potentially preventing long-term retinal damage.

• Aims to functionally cure a subset of patients and significantly reduce treatment burden for others.

Clinical Data and Safety Profile

• 4D-150 demonstrated robust and consistent reduction in treatment burden across all wet AMD populations at the 3E10 vg/eye dose.

• 89% reduction in annualized anti-VEGF injection rate and 77% of patients injection-free in the broad population.

• Three severe patients remained injection-free for up to 2.5 years with strong disease control.

• No significant inflammation observed at the planned Phase 3 dose; safety profile similar to Eylea.

• 4D-150 continues to show safety and tolerability in 139 patients with wet AMD and DME.