4DMT completes enrollment in 4FRONT-2, global phase 3 trial of 4D-150 in wet AMD

4D Molecular Therapeutics (4DMT) has completed enrollment in 4FRONT-2, the second phase 3 trial in its global program evaluating 4D-150 in patients with wet age-related macular degeneration (AMD).¹

According to the company, global enrollment finished approximately 4 months ahead of initial projections, and the trial over-enrolled past its anticipated target of more than 500 patients. Final patient randomization is expected in the third quarter of 2026. The company attributed the pace to investigator and patient interest in a durable, vision-preserving alternative to repeated anti-VEGF injections.

Trial design

4FRONT-2 is a global, multicenter, randomized, double-masked, aflibercept 2 mg (Q8W) comparator-controlled study of intravitreal 4D-150 in wet AMD. Unlike its North American counterpart, the trial enrolled both treatment-naïve and recently diagnosed treatment-experienced patients. The primary endpoint is non-inferiority in the mean change from baseline in best-corrected visual acuity (BCVA) at 52 weeks. The key secondary endpoint is treatment burden reduction, comparing the number of aflibercept injections received in the 4D-150 arm versus the comparator arm over 52 weeks. Patients in both arms are eligible for supplemental aflibercept injections. 4FRONT-2 52-week topline data is expected in the second half of 2027.¹

4FRONT-1, the first 4D-150 wet AMD phase 3 trial, is being conducted in North America in treatment-naïve patients with an otherwise identical design. As previously reported, 4DMT completed enrollment in 4FRONT-1 earlier this year, with topline data from that trial anticipated in the first half of 2027.²

A backbone therapy approach

4D-150 is a potential backbone therapy designed to provide multi-year, and potentially lifelong, sustained delivery of anti-VEGF biologics—aflibercept and anti-VEGF-C—within the retina following a single intravitreal injection. The candidate uses R100, a customized and evolved intravitreal adeno-associated virus vector invented at 4DMT through its proprietary Therapeutic Vector Evolution platform. Beyond wet AMD, the company is developing 4D-150 for diabetic macular edema (DME) and has reported positive results from the SPECTRA trial in that indication.^1,3

David Kirn, MD, co-founder, president, and CEO of 4DMT, commented on the milestone in a press release from the company. "Completing global enrollment in both 4FRONT-1 and 4FRONT-2 phase 3 trials with over-enrollment and ahead of initial projections further validates 4D-150 as the potential cornerstone of a transformative, category-defining retina franchise at 4DMT," he said. Kirn noted that the high enrollment rate, predominantly in treatment-naïve patients, reflects enthusiasm among patients and retina physicians as well as the unmet need for a durable backbone therapy. He added that a phase 3 trial in DME is slated to begin in the third quarter of this year.¹

Julie Clark, MD, chief medical officer of 4DMT, framed the completion in terms of treatment burden. "Wet AMD remains a leading cause of vision loss worldwide, and despite important advances in bolus anti-VEGF therapy, most patients still continue to face the real-world burden of frequent, lifelong injections and the associated risk of undertreatment and vision loss," she said. Completing enrollment, she added, brings the program closer to confirming whether 4D-150 can meaningfully reduce treatment burden while preserving vision outcomes.¹

Patricio G. Schlottmann, MD, director of the research department at the Charles Ophthalmic Center in Buenos Aires, Argentina, a member of the 4DMT retinal advisory board and a principal investigator in 4FRONT-2, said the candidate's appeal lies in moving wet AMD care beyond repeated bolus injections toward durable, continuous disease control from a single administration. "Based on the clinical data generated to date, I believe 4D-150 has the potential to represent an important paradigm shift for patients and physicians if the ongoing phase 3 program is successful," he said.¹

Program context

The 4FRONT program builds on the phase 1/2 PRISM trial, which produced positive 52-week data from its phase 2b cohort and has continued in long-term follow-up.⁴ In July 2025, 4DMT announced its intent to accelerate the 4D-150 4FRONT phase 3 program and lay off approximately 25% of staff, a move it tied to a pipeline strategy first outlined in January 2025 that prioritizes its late-stage retinal candidates.^5,6

Wet AMD, in which abnormal blood vessels grow into the macula and cause swelling, bleeding, and scarring, is expected to affect more than 4 million individuals across the US, EU, and Japan within five years, with an estimated 200,000 new diagnoses annually in the US alone. With two phase 3 readouts now expected in 2027 and a DME trial set to launch later this year, 4DMT continues to position 4D-150 as a potential backbone therapy across large-market retinal vascular diseases.¹

References

1. 4DMT Completes Enrollment for 4FRONT-2 Global Phase 3 Clinical Trial of 4D-150 in Wet AMD. 4D Molecular Therapeutics. Published June 29, 2026. Accessed June 29, 2026. https://www.globenewswire.com/news-release/2026/06/29/3318897/0/en/4DMT-Completes-Enrollment-for-4FRONT-2-Global-Phase-3-Clinical-Trial-of-4D-150-in-Wet-AMD.html

2. Harp MD. 4DMT completes enrollment in 4FRONT-1, phase 3 trial of 4D-150 in AMD. Ophthalmology Times. Published February 9, 2026. Accessed June 29, 2026. https://www.ophthalmologytimes.com/view/4dmt-completes-enrollment-in-4front-1-phase-3-trial-of-4d-150-in-amd

3. 4DMT announces positive results from SPECTRA trial evaluating 4D-150 in patients with DME. Ophthalmology Times. Published February 6, 2026. Accessed June 29, 2026. https://www.ophthalmologytimes.com/view/4dmt-announces-positive-results-from-spectra-trial-evaluating-4d-150-in-patients-with-dme

4. 4DMT announces positive 52-week data from phase 2b cohort of PRISM wet AMD study. Ophthalmology Times. Published February 10, 2025. Accessed June 29, 2026. https://www.ophthalmologytimes.com/view/4dmt-announces-positive-52-week-data-from-phase-2b-cohort-of-prism-wet-amd-study

5. Harp MD. 4DMT accelerating 4D-150 4FRONT phase 3 program, laying off 25% of staff. Ophthalmology Times. Published July 7, 2025. Accessed June 29, 2026. https://www.ophthalmologytimes.com/view/4dmt-accelerating-4d-150-4front-phase-3-program-laying-off-25-of-staff

6. 4DMT refocuses pipeline to prioritize 4D-150 trials in wet AMD and DME. Ophthalmology Times. Accessed June 29, 2026. https://www.ophthalmologytimes.com/view/4dmt-refocuses-pipeline-to-prioritize-4d-150-trials-in-wet-amd-and-dme