4D Molecular Therapeutics, a clinical-stage biotherapeutics company harnessing the power of directed evolution for targeted genetic medicines, announced additional positive interim clinical data from the Phase 1 Dose Exploration stage (N=15) of the 4D-150 Phase 1/2 PRISM clinical trial for patients with wet age-related macular degeneration (wet AMD). The data were presented at the 2023 American Society of Retinal Specialists (ASRS) Annual Meeting in Seattle, Washington on Saturday, July 29 by Christine N. Kay, M.D., a vitreoretinal surgeon and the Director of Electrophysiology, Retinal Genetics, and Clinical Trials at Vitreoretinal Associates in Gainesville, Florida.
4D-150 is a potentially transformative genetic medicine that utilizes 4DMT’s evolved and customized retinotropic R100 vector, while targeting four VEGF family members. 4D-150 is being developed as a single dose, routine outpatient intravitreal therapy with the goal of reducing treatment burden and maintaining efficacy in patients with wet AMD and diabetic macular edema (DME).
“We are pleased to see continued evidence of a favorable safety profile and clinical activity, including clinically meaningful reductions in anti-VEGF treatment burden at all dose levels of intravitreal 4D-150 in these high anti-VEGF need patients,” said Robert Kim, M.D., Chief Medical Officer of 4DMT. “In addition, 3 of 4 evaluable patients in the 3E10 vg/eye cohort are now anti-VEGF injection-free at one year and beyond, with up to 80 weeks of follow-up, demonstrating encouraging initial evidence of long-term durability. We look forward to continuing to follow these patients and presenting initial interim Phase 2 Dose Expansion data in H1 2024.”
“The results announced today continue to support 4D-150’s favorable overall clinical profile as a potentially transformative durable intravitreal therapeutic in VEGF-driven large market ophthalmologic diseases,” said David Kirn, M.D., Co-founder and Chief Executive Officer of 4DMT. “We look forward to continuing to build upon 4D-150’s strong profile to date in the randomized Phase 2 stage of the PRISM trial in patients with wet AMD and the Phase 2 SPECTRA trial in patients with DME. In addition, we intend to continue to rapidly advance our preclinical large market ophthalmology pipeline, including 4D-175 for geographic atrophy, leveraging the same clinically validated retinotropic R100 vector.”
4D-150 Phase 1 Dose Exploration Interim Data Summary:
- 15 patients received a single intravitreal dose of 4D-150 across three dose cohorts (3E10, 1E10, and 6E9 vg/eye; n=5 each)
- Enrolled participants had a high need for anti-VEGF therapy, with mean annualized injection rates ranging from 8 to 11 across cohorts prior to 4D-150 treatment
- As of the data cutoff date of July 3, 2023, all patients had completed follow-up through at least 36 weeks
- 4D-150 was well tolerated, with no reported Grade ≥1 inflammatory cells and no hypotony, dose-limiting toxicities, or treatment-related serious adverse events
Initial durability demonstrated in 3E10 vg/eye dose cohort, with 3 of 4 evaluable patients injection-free beyond 1 year- First patient in 3E10 vg/kg cohort remains supplemental anti-VEGF injection-free at 80 weeks follow-up (longest on study) (data cutoff July 3, 2023)
- A single patient (1 of 4 evaluable patients in the 3E10 vg/eye cohort) met supplemental injection criterion beyond 36 weeks at a single timepoint. Patient was well controlled on the basis of both BCVA and CST prior to developing a retinal hemorrhage, which has resolved with no significant change from baseline in BCVA (reported as “not related” to the test article)
- 4D-150 was well tolerated, with no reported Grade ≥1 inflammatory cells and no hypotony, dose-limiting toxicities, or treatment-related serious adverse events
- Future Milestones for 4D-150 & Large Market Ophthalmology Portfolio with the Proprietary R100 Intravitreal Vector
- Initial interim efficacy data from Phase 2 Dose Expansion expected to be presented at a medical conference in H1 2024
- Expect to provide update regarding Phase 3 pivotal trial plans in Q1 2024 after initial discussion with FDA, which is anticipated in Q4 2023
- Expect to enroll first patient in Phase 2 SPECTRA clinical trial for DME in Q3 2023
- Program update for 4D-175 in geographic atrophy expected in Q4 2023
SOURCE: GlobeNewswire