4D Molecular Therapeutics (FDMT) Study Update summary

Study design and patient population

• PRISM Phase II enrolled 45 wet AMD patients with broad disease activity, randomized to 3E10 vg/eye (n=30) or 1E10 vg/eye (n=15), with 1-6 prior anti-VEGF injections in the past year.

• Baseline mean age was ~77 years, mean CST was 329 microns, and mean BCVA was 72 letters.

• All patients received aflibercept pre-treatment, a week 4 dose, and local corticosteroid prophylaxis (topical Durezol); no systemic steroids were used.

• The cohort included a broad range of disease severities, representative of the planned phase III population.

• Key endpoints included safety, annualized anti-VEGF injection rate, BCVA, and CST changes.

Safety and tolerability

• 4D-150 was safe and well-tolerated, with no drug-related serious adverse events or significant inflammation at the high dose.

• 98% of patients had no significant intraocular inflammation; one low-dose patient had mild, transient inflammation.

• No cases of hypotony, endophthalmitis, vasculitis, choroidal effusions, or retinal artery occlusions were observed.

• All patients completed steroid prophylaxis on schedule without resuming treatment.

• Safety profile was consistent across wet AMD and DME populations (N=139), with no new inflammation or steroid changes in long-term follow-up.

Efficacy and clinical activity

• High-dose (3E10 vg/eye) arm showed an 89% reduction in annualized anti-VEGF injection frequency; 93% had 0-1 injection, and 77% were injection-free at 24 weeks.

• Mean BCVA improved by 4.2 letters at 24 weeks in the high-dose arm, 5.7 letters higher than low-dose.

• Sustained and greater anatomic control observed, with mean CST reduction and minimal fluctuations, especially in injection-free patients.

• Durable improvements in visual acuity and CST maintained in supplemental injection-free participants.

• Robust efficacy observed across both severe and broad patient populations, regardless of prior treatment burden.