4D Molecular announces data from PRISM, 4FRONT trials

4D Molecular Therapeutics announced data showing continued clinical activity, based on longest interim follow-up data from the Phase 1/2 PRISM clinical trial, and 4FRONT Phase 3 study design, which will be presented at its 4D-150 Wet AMD Development Day. Treatment burden reduction observed in all PRISM populations studied with the planned Phase 3 dose of 3E10 vg/eye of 4D-150. Phase 1/2a Severe: 83% overall reduction in annualized injections; 52% received 0 or 1 injection; 44% injection-free. Phase 2b Broad: 89% overall reduction in annualized injections; 80% received 0 or 1 injection; 70% injection-free. Phase 2b Recently Diagnosed: 98% overall reduction in annualized injection; 100% received 0 or 1 injection; 87% injection-free. Central Subfield Thickness: sustained anatomic control with fewer fluctuations. Mean best corrected visual acuity: stable or sustained improved. 4D-150 continues to be well tolerated with favorable safety profile. Rate of 4D-150 IOI numerically similar to that reported for approved anti-VEGF agents. Wet AMD: 2.8% had 4D-150-related IOI at any timepoint; 2 patients had transient 1+ vitreous cells; 99% completed steroid prophylaxis taper on schedule; 97% remained off steroids completely. Diabetic Macular Edema: No patients treated at any dose have experienced IOI events at any timepoint. No 4D-150-related hypotony, endophthalmitis, vasculitis, choroidal effusions or retinal artery occlusions observed to date across both the wet AMD and the DME programs. Company planning for global 4FRONT Phase 3 development program comparing a single dose of 4D-150 3E10 vg/eye to on-label aflibercept 2mg Q8 weeks: initiation of 4FRONT-1 clinical trial (N=500) expected in Q1 2025. Eligibility criteria: Patients must be both recently diagnosed and treatment naive wet AMD patients and randomization requires on study demonstration of aflibercept responsiveness. Program expected to include two double-masked, randomized, controlled noninferiority trials: Primary endpoint: noninferiority in BCVA. Sham controlled to support masking. All patients randomized to receive 3 total loading doses per aflibercept label. Supplemental aflibercept injection criteria for 4D-150 arm optimized to protect primary BCVA endpoint and to maximize reduction of supplemental treatment burden; no supplemental injections allowed in control arm Study design has been aligned with feedback from FDA under RMAT designation. Alignment ongoing with European Medicines Agency under PRIME designation.