4DMT's 2-year PRISM data show durable treatment burden reduction with 4D-150 in wet AMD

Two-year follow-up from the Phase 2b PRISM clinical trial continues to support 4D-150, 4D Molecular Therapeutics' (4DMT) investigational gene therapy for wet age-related macular degeneration (AMD), as a potential single-injection alternative to chronic anti-VEGF dosing.¹ The data, with a cutoff of May 18, 2026, were presented in an oral session titled "2-Year Follow Up: PRISM Phase 2b Clinical Trial Evaluating Investigational 4D-150, an Intravitreal Gene Therapy, in a Broad Neovascular AMD Population" by Carl Awh, MD, FASRS, of Tennessee Retina, at the 44th Annual Scientific Meeting of the American Society of Retina Specialists (ASRS) in Montréal.^1,2

Sustained vision and anatomic outcomes, sharply reduced injection burden

PRISM Phase 2b enrolled 45 patients across two dose levels of a single intravitreal injection of 4D-150—3E10 vg/eye (n=30) and 1E10 vg/eye (n=15)—with 3E10 vg/eye subsequently selected as the dose carried forward into the 4FRONT Phase 3 program.^1,3 A recently diagnosed subgroup (diagnosed within 6 months, n=15 at 3E10 vg/eye) was included specifically because it most closely mirrors the treatment-naïve population enrolled in 4FRONT-1 and 4FRONT-2.¹

Through 2 years, the company reported consistent maintenance of best-corrected visual acuity (BCVA) and consistent control of central subfield thickness (CST) on optical coherence tomography, with the dose response favoring the Phase 3 dose holding throughout follow-up. The treatment-burden findings were the headline result: the overall cohort saw a 78% reduction in supplemental injections, averaging 2.7 injections per patient versus a projected 12.0 injections under on-label aflibercept 2 mg every 8 weeks. In the recently diagnosed subgroup, that reduction reached 87%, with a mean of 1.6 supplemental injections per patient.¹ The finding builds on interim results from the same cohort reported at 52 weeks last year and on longer-interval follow-up from the Phase 1/2a portion of PRISM, both of which pointed in the same direction.^4,5

On safety, the company said 4D-150 continues to be well tolerated. As previously reported, 2 of 71 patients (2.8%) treated at the Phase 3 dose across the pooled Phase 1/2a and 2b population had 4D-150-related mild (1+) intraocular inflammation within roughly the first 6 months after dosing, described as transient vitreous cells noted at a single timepoint. No new inflammation cases have emerged since, across follow-up now ranging from 2 to more than 4 years. The company also reported no cases of 4D-150-related hypotony, endophthalmitis, or occlusive or non-occlusive retinal vasculitis to date.¹

Voices from the field

"Two-year PRISM data continue to strengthen our conviction in 4D-150's potential to become a foundational backbone therapy for wet AMD," said David Kirn, MD, co-founder, president, and CEO of 4DMT, in a company release. "The continued consistency in visual acuity and anatomic control with meaningful reduction in treatment burden and long-term tolerability reinforces our confidence in delivering a transformative treatment option for retina specialists and their patients."¹

Awh, who presented the data at ASRS, framed the results in terms of the day-to-day burden that intensive anti-VEGF regimens place on both patients and practices. "For retina specialists and our patients, maintaining the intensive injection schedule necessary to preserve vision is a tremendous challenge," he said. "The two-year PRISM results demonstrate the potential of a single intravitreal administration of 4D-150 to provide long-term anti-VEGF and sustained disease control. Reducing treatment burden will undoubtedly improve our ability to preserve vision over the long term for our patients."¹

Program context

4D-150 uses R100, a customized intravitreal AAV vector developed through 4DMT's proprietary Therapeutic Vector Evolution platform, to deliver sustained intraretinal expression of aflibercept and anti-VEGF-C from a single injection. The company positions the candidate as a potential "backbone" therapy across retinal vascular diseases, with wet AMD as the lead indication and diabetic macular edema (DME) as a second program, the latter supported by positive data from the SPECTRA trial.^1,6

The two-year PRISM data arrive as 4DMT's Phase 3 wet AMD program moves toward readout. The company completed enrollment in 4FRONT-1, its North American trial in treatment-naïve patients, earlier this year, with topline 52-week data expected in the first half of 2027. 4FRONT-2, the global trial enrolling both treatment-naïve and recently diagnosed treatment-experienced patients, over-enrolled and completed ahead of schedule, with topline data anticipated in the second half of 2027.^3,7 Both trials compare a single dose of 4D-150 against aflibercept 2 mg Q8W, with non-inferiority in BCVA change from baseline at 52 weeks as the primary endpoint and injection-count reduction as a key secondary endpoint.³

Wet AMD, in which abnormal blood vessels proliferate into the macula and leak fluid and blood under VEGF-driven stimulation, is projected to affect more than 4 million people across the US, EU, and Japan within five years, with roughly 200,000 new US diagnoses annually. Left untreated, the disease can progress to irreversible central vision loss.¹ With durability data now extending past 2 years and Phase 3 readouts on the horizon, 4DMT continues to position 4D-150 as a candidate that could meaningfully reduce that burden for retina specialists and their patients.

References

1. 4DMT Announces Positive 2-Year Data from PRISM Phase 2b Clinical Trial in a Broad Wet AMD Population. 4D Molecular Therapeutics. Published July 18, 2026. Accessed July 20, 2026. https://www.globenewswire.com/news-release/2026/07/18/3329368/0/en/4DMT-Announces-Positive-2-Year-Data-from-PRISM-Phase-2b-Clinical-Trial-in-a-Broad-Wet-AMD-Population.html

2. 4DMT Announces Presentation at 44th Annual Scientific Meeting of the American Society of Retina Specialists. 4D Molecular Therapeutics. Published June 30, 2026. Accessed July 20, 2026. https://www.globenewswire.com/news-release/2026/06/30/3320101/0/en/4DMT-Announces-Presentation-at-44th-Annual-Scientific-Meeting-of-the-American-Society-of-Retina-Specialists.html

3. Harp MD. 4DMT completes enrollment in 4FRONT-2, global phase 3 trial of 4D-150 in wet AMD. Ophthalmology Times. Published July 6, 2026. Accessed July 20, 2026. https://www.ophthalmologytimes.com/view/4dmt-completes-enrollment-in-4front-2-global-phase-3-trial-of-4d-150-in-wet-amd

4. 4DMT announces positive 52-week data from phase 2b cohort of PRISM wet AMD study. Ophthalmology Times. Published February 10, 2025. Accessed July 20, 2026. https://www.ophthalmologytimes.com/view/4dmt-announces-positive-52-week-data-from-phase-2b-cohort-of-prism-wet-amd-study

5. 4DMT releases positive interim 1.5- to 3.5-year data from phase 1/2 PRISM trial. Ophthalmology Times. Accessed July 20, 2026. https://www.ophthalmologytimes.com/view/4dmt-releases-positive-interim-1-5--to-3-5-year-data-from-phase-1-2-prism-trial

6. 4DMT announces positive results from SPECTRA trial evaluating 4D-150 in patients with DME. Ophthalmology Times. Accessed July 20, 2026. https://www.ophthalmologytimes.com/view/4dmt-announces-positive-results-from-spectra-trial-evaluating-4d-150-in-patients-with-dme

7. Harp MD. 4DMT completes enrollment in 4FRONT-1, phase 3 trial of 4D-150 in AMD. Ophthalmology Times. Published February 9, 2026. Accessed July 20, 2026. https://www.ophthalmologytimes.com/view/4dmt-completes-enrollment-in-4front-1-phase-3-trial-of-4d-150-in-amd