4DMT's gene therapy cuts wet AMD injections 78% in 2-year trial

A single injection of 4D Molecular Therapeutics' gene therapy 4D-150 reduced the need for supplemental eye injections by 78% over two years in a broad wet age-related macular degeneration population, Phase 2b data show.

"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," Carl Awh, a retina specialist at Tennessee Retina who presented the data at the American Society of Retina Specialists meeting, said.

Patients in the overall cohort required a mean of 2.7 supplemental injections over two years, compared with 12.0 projected for on-label aflibercept dosed every eight weeks. In a subgroup of patients diagnosed within six months — the population most comparable to the ongoing 4FRONT Phase 3 trials — the burden fell 87% to 1.6 mean injections. Best-corrected visual acuity and central subfield thickness were maintained consistently across both dose groups.

The durability data strengthen the case for 4D-150 as a potential backbone therapy for wet AMD, a disease affecting more than 4 million patients in major markets. 4DMT is also developing the therapy for diabetic macular edema, which together represent a multi-billion-dollar market currently dominated by Regeneron's Eylea and Roche's Vabysmo. The company has selected the 3E10 vg/eye dose for its Phase 3 program.

The Phase 2b trial enrolled 45 patients across two dose levels, with 30 receiving the 3E10 vg/eye dose selected for Phase 3 and 15 receiving a lower 1E10 vg/eye dose. The dose response favoring the higher dose was maintained through the full two-year period.

4D-150 uses the company's proprietary R100 vector, an evolved intravitreal AAV capsid designed to deliver genes encoding aflibercept and an anti-VEGF-C biologic directly to retinal cells. The approach aims to turn the eye into a sustained production site for anti-VEGF proteins, eliminating the need for the frequent intravitreal injections that define current standard of care.

Safety profile supports chronic use

Safety data from 71 patients across the Phase 1/2a and Phase 2b trials showed no new concerns with up to four years of follow-up. Two patients (2.8%) experienced transient mild intraocular inflammation within the first 28 weeks, each resolving after a single timepoint. No cases of hypotony, endophthalmitis, vasculitis, or choroidal effusions were reported.

The safety record is particularly important for a gene therapy targeting a chronic disease in an elderly population. Current treatments require patients to visit retina specialists every four to eight weeks for injections, a schedule that imposes significant logistical and financial burdens.

4DMT shares have rallied as the data de-risks the program ahead of Phase 3 readouts. The company has not disclosed its cash runway, but with a Phase 3 program underway for wet AMD and a second Phase 3 program for DME expected to follow, the capital requirements are substantial. Barclays rates the stock Overweight with a $33 price target, implying upside from current levels.

If approved, 4D-150 would compete in a wet AMD market that analysts estimate at more than $10 billion annually. Regeneron's Eylea generated $5.8 billion in 2025, while Roche's Vabysmo has been gaining share with a longer dosing interval. A one-and-done gene therapy that maintains disease control for years would represent a structural shift in treatment economics.

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