4DMT Announces Phase 2 PRISM Interim Results for Intravitreal 4D-150 in Wet AMD

4D Molecular Therapeutics 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 K. Maturi, MD, at the American Society of Retina Specialists (ASRS) annual meeting held in Stockholm, Sweden.

The cohort evaluated 4D-150 in wet AMD patients with broad disease activity (no minimum or maximum central subfield thickness (CST)) and prior anti-VEGF treatment (1-6 anti-VEGF injections in the prior 12 months). The trial enrolled 45 patients at two dose level arms of 4D-150: 30 at 3E10 vg/eye (planned Phase 3 dose); 15 at 1E10 vg/eye (low dose control). The dose arms enrolled in the cohort were generally well-balanced. Mean CST was 329 μm and mean number of actual injections in the prior 12 months was 4.4.

Phase 2 PRISM Population Extension Cohort Topline Interim 24-Week Landmark Results (Data cutoff: June 24, 2024)

• 4D-150 was safe and well tolerated:
  • Intraocular inflammation analysis:
    • Planned Phase 3 dose (3E10 vg/eye)
      • No anterior chamber inflammation (30 of 30 patients)
      • No significant vitreous inflammation (30 of 30 patients; trace vitreal cells noted in one patient)
      • All 30 patients completed local steroid prophylaxis on schedule and did not resume
    • Low dose (1E10 vg/eye)
      • No significant anterior chamber inflammation (15 of 15 patients; trace anterior chamber cells noted in one patient)
      • No vitreous inflammation in 14 of 15 patients, one patient with mild to moderate inflammation (1 of 45 total, ~2% overall); vitreous cells also observed in untreated fellow eye
  • No 4D-150–related serious adverse events (SAEs) 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 (3E10 vg/eye) – robust anti-VEGF treatment reduction:
    • 89% reduction in mean annualized injection rate
    • 93% received 0 or 1 injection
    • 77% injection-free; dose response evident (60% on low dose arm)
  • Visual acuity and retina anatomic outcomes:
    • Improved BCVA in 3E10 vg/eye arm patients: +4.2 Early Treatment Diabetic Retinopathy Study (ETDRS) letter improvement from baseline overall, and +4.7 letter improvement observed for injection-free patients (improvement independent of number of prior anti-VEGF doses)
    • 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 (decrease) in CST from baseline greater in supplemental injection-free patients than in overall population (-32 vs -9 μm)

PRISM Phase 1 Long-Term Follow-Up Update (Data cutoff: June 24, 2024)

• 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 (+1 letter from baseline)
• Mean CST remains stable, without fluctuations, and decreased from baseline through ~2 years (-110 microns from baseline)
• Safety results maintained in all 15 patients treated to the cutoff date (up to 2.5 years of follow-up) with no new inflammation and no change in steroid status

4D-150 Overall Safety Update Across Wet AMD and DME Patients

• 4D-150 continues to be safe and well tolerated across all patients dosed to date (n=139) in both PRISM (wet AMD, n=117) and SPECTRA (DME, n=22) 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

Planned Next Steps and Upcoming Milestones for 4D-150

• 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 2024
  • First Phase 3 clinical trial initiation expected in Q1 2025
• PRISM wet AMD Phase 2 additional landmark analyses:
  • 52-week landmark analyses for both 1) severe disease activity/high treatment burden (Dose Expansion) & 2) broad wet AMD disease activity (Population Extension) cohorts expected in February 2025
• SPECTRA DME Phase 2 initial landmark analyses:
  • Interim 24-week landmark analysis from Part 1 Dose Confirmation cohort (n=22) expected in Q4 2024

“The positive interim data presented today, coupled with previously reported data from the Dose Expansion cohort of high treatment burden patients, further reinforce our planned regulatory pathway demonstrates 4D-150’s broad potential to treat and preserve vision for the long term for all patient populations with wet AMD,” David Kirn, MD, Co-founder and CEO of 4DMT, said in a company news release. “In addition, the growing safety and efficacy database for 4D-150 continues to validate the product candidate’s potential as a pipeline-in-a-product, with multiple potential multi-billion ophthalmology market opportunities including wet AMD, DME and diabetic retinopathy (DR). We anticipate data readouts from the SPECTRA study in DME in Q4 this year, which we believe will have potential readthrough to DR.”