4DMT releases positive interim 1.5- to 3.5-year data from phase 1/2 PRISM trial

4D Molecular Therapeutics (4DMT) released positive interim 1.5- to 3.5-year data from the phase 1/2 PRISM clinical trial evaluating 4D-150 in patients with wet age-related macular degeneration (wet AMD).¹

4D-150 is an investigational agent designed to provide multi-year sustained delivery of anti-VEGF (aflibercept and anti-VEGF-C) from the retina with a single, safe, intravitreal injection. It utilizes the company’s customized and evolved intravitreal vector, R100.

The trial consists of 3 cohorts:

• Phase 2b (n=30):
  • Broad disease activity
• Phase 2b subgroup: Recently diagnosed (n=15):
  • Broad disease activity diagnosed within 6 months of trial entry
  • Most comparable to the cohort in the phase 3 4FRONT clinical trials, according to the company
• Phase 1/2a (n=24):
  • Severe, recalcitrant disease activity

According to the company, visual acuity and sustained control of retinal anatomy were observed in all cohorts up to 2 years, as measured by best corrected visual acuity and optical coherence tomography (OCT), respectively. Additionally, patients maintained a consistent and clinically meaningful reduction in supplemental injections following 4D-150 both in year 1 and in follow-up through year 1.5 (phase 2b cohort) and year 2 (phase 1/2a cohort).¹

The company also noted a consistent dose response on treatment burden reduction across all cohorts and that it favors the phase 3 dose (3e10 vg/eye, n=71) compared to the lower dose (1e10 vg/eye). The company noted that 4D-150 continues to be well tolerated, with 2.8% (2 of 71) of patients having 4D-150-related 1+ (mild) intraocular inflammation (IOI) (SUN/NEI scales), which was “transient 1+ vitreous cells noted at a single timepoint.”¹

David Kirn, M.D., co-founder and CEO of 4DMT, commented on the interim results, saying, “The interim data from PRISM demonstrate the meaningful treatment burden reduction, vision maintenance, and excellent tolerability we’ve observed from 4D-150, highlighting its remarkable consistency, durability, and potential to redefine clinical practice as a backbone therapy for wet AMD and other retinal vascular diseases. With the robust PRISM dataset and our APAC region strategic partnership with Otsuka announced last week, we are well positioned for global success in our Phase 3 4FRONT clinical trials, which continue to enroll ahead of initial projections.”

The APAC partnership mentioned by Kirn is the recently announced strategic partnership with Otsuka Pharmaceutical to develop and commercialize 4D-150 for the treatment of wet age-related macular degeneration (wet AMD) and diabetic macular edema (DME) in the greater Asia-Pacific (APAC) region, including Japan.²

Earlier in the year, the company also announced positive results from the SPECTRA clinical trial evaluating 4D-150 in patients with DME.³

The study enrolled 22 patients across 3 dose levels, including the phase 3 dose of 3E10 vg/eye (n=9) and supplemental doses of 1E10 vg/eye (n=12) and 5E9 vg/eye (n=1). It was noted that 2 patients dosed in the 1E10 vg/eye missed over 50% of study visits and were considered not evaluable for injection burden or other efficacy parameters.

According to the data, 4D-150 is well-tolerated with no intraocular inflammation at any timepoint over 60 weeks. Additionally, no patients required any modification to the topical corticosteroid regimen.

References

1. 4DMT announces positive long-term data from phase 1/2 PRISM clinical trial in wet AMD supporting 4d-150’s potential as a backbone therapy with consistent and durable benefit over multiple years. Published November 6, 2025. Accessed November 6, 2025. https://ir.4dmoleculartherapeutics.com/news-releases/news-release-details/4dmt-announces-positive-long-term-data-phase-12-prism-clinical

2. Harp MD. 4DMT and Otsuka Pharmaceutical partner on 4D-150 in the greater Asia-Pacific region. Published November 4, 2025. Accessed November 6, 2025. https://www.ophthalmologytimes.com/view/4dmt-and-otsuka-pharmaceutical-partner-on-4d-150-in-the-greater-asia-pacific-apac-region

3. 4DMT announces positive results from SPECTRA trial evaluating 4D-150 in patients with DME. Published August 4, 2025. Accessed November 3, 2025. https://www.ophthalmologytimes.com/view/4dmt-announces-positive-results-from-spectra-trial-evaluating-4d-150-in-patients-with-dme