4D Molecular announces interim data from PRISM trial

4D Molecular announced initial interim 24-week landmark data from the population extension cohort of the PRISM Phase 2 clinical trial, which evaluated intravitreal 4D-150 in a broad wet AMD patient population. The data were presented by Raj Maturi in an oral presentation titled, “Phase 2 Population Extension Cohort in the PRISM Trial Evaluating 4D-150 in Adults with Neovascular Age-related Macular Degeneration,” at the American Society of Retina Specialists, or ASRS, annual scientific meeting held in Stockholm, Sweden. The 4D-150 Phase 2 PRISM Population Extension Cohort evaluated 4D-150 in wet AMD patients with broad disease activity. The trial enrolled 45 patients at two dose level arms of 4D-150: 30 at 3E10 vg/eye and 15 at 1E10 vg/eye. The dose arms enrolled in the cohort were generally well-balanced. Mean CST was 329 microm and mean number of actual injections in the prior 12 months was 4.4. 4D-150 was safe and well tolerated: Intraocular inflammation analysis: planned phase 3 dose; mo anterior chamber inflammation; no significant vitreous inflammation; all 30 patients completed local steroid prophylaxis on schedule and did not resume; low dose; no significant anterior chamber inflammation; no vitreous inflammation in 14 of 15 patients, one patient with mild to moderate inflammation; vitreous cells also observed in untreated fellow eye; no 4D-150-related serious adverse events or study eye SAEs; no hypotony, retinal vasculitis, choroidal effusions, retinal artery occlusions; 24-week landmark analysis for key efficacy endpoints: planned Phase 3 dose- robust anti-VEGF treatment reduction: 89% reduction in mean annualized injection rate. 93% received 0 or 1 injection, 77% injection-free; dose response evident. Visual acuity and retina anatomic outcomes: improved BCVA in 3E10 vg/eye arm patients: +4.2 Early Treatment Diabetic Retinopathy Study letter improvement from baseline overall, and +4.7 letter improvement observed for injection-free patients. BCVA dose response demonstrated in favor of 3E10 vg/eye dose: +5.7 letter improvement in BCVA for patients in planned Phase 3 dose arm vs low dose arm. CST: sustained and greater anatomic control without fluctuations for the 3E10 vg/eye dose arm; improvement in CST from baseline greater in supplemental injection-free patients than in overall population. All three Phase 1 patients treated with 3E10 vg/eye previously reported as injection-free beyond 52 weeks remain injection-free through ~2 to 2.5 years of follow-up. Mean BCVA remains unchanged from baseline through ~2 years. Mean CST remains stable, without fluctuations, and decreased from baseline through ~2 years. Safety results maintained in all 15 patients treated to the cutoff date with no new inflammation and no change in steroid status. 4D-150 continues to be safe and well tolerated across all patients dosed to date in both PRISM and SPECTRA clinical trials. 51 patients treated in the PRISM and SPECTRA studies at 3E10 vg/eye dose and topical corticosteroid prophylactic regimen had no significant inflammation, hypotony, retinal vasculitis, choroidal effusions or retinal artery occlusions with up to 2.5 years of follow-up; no recurrent inflammation post steroid taper. 22 DME patients treated in the SPECTRA study had no inflammation, hypotony, retinal vasculitis, choroidal effusions or retinal artery occlusions with up to 36-weeks of follow-up; completed topical corticosteroid prophylactic regimen on schedule and did not resume. Phase 3 planning: phase 3 clinical trial alignment ongoing with FDA and EMA under RMAT and PRIME designations. Update on final Phase 3 clinical trial design expected in September. First Phase 3 clinical trial initiation expected in Q1 2025. PRISM wet AMD Phase 2 additional landmark analyses: 52-week landmark analyses for both severe disease activity/high treatment burden and broad wet AMD disease activity cohorts expected in February 2025. SPECTRA DME Phase 2 initial landmark analyses: interim 24-week landmark analysis from Part 1 Dose Confirmation cohort expected in Q4.