4DMT completes enrollment in 4FRONT-1, phase 3 trial of 4D-150 in AMD

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

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. While 4FRONT-1 is a multicenter, randomized, double-masked, aflibercept 2 mg (Q8W) comparator-controlled study of intravitreal 4D-150 in treatment-naive patients in North America with wet AMD.¹

According to the company,¹ the primary endpoint of the trial is non-inferiority in the mean change from baseline in best-corrected visual acuity (BCVA) at 52 weeks. Patients in both arms will be eligible for supplemental aflibercept injections.

David Kirn, M.D., co-founder, president, and CEO of 4DMT, commented on the trial in a press release from the company, saying, “The 4D-150 4FRONT-1 phase 3 trial enrolled in 11 months in a treatment-naïve large-market patient population. […] Remarkably, our team achieved this milestone in only 4 years after treating the first patient with 4D-150 in wet AMD.”

Arshad M. Khanani, MD, MA, FASRS, director of clinical research at Sierra Eye Associates, chair of the 4DMT ophthalmology advisory board, and a principal investigator in the 4FRONT-1 clinical trial added, “Based on the long-term PRISM phase 1/2 data, 4D-150 has the potential to significantly reduce treatment burden for patients with wet AMD, with a single in-office intravitreal injection providing sustained disease control. The rapid enrollment of 4FRONT-1 in treatment-naïve patients is particularly encouraging and reflects strong enthusiasm among physicians and patients for therapies that offer potentially safe, effective, and durable long-term disease control.”

As previously reported, the first patient was enrolled in 4FRONT-1 in March 2025. Additionally, topline data from 4FRONT-1 is expected in the first half of 2027.

In addition to the 4FRONT-1 trial, 4DMT is also enrolling in an additional phase 3 trial for wet AMD, 4FRONT-2. This trial is not limited to North America and is instead a worldwide trial of 4D-150 in treatment-naïve and recently diagnosed treatment-experienced wet AMD patients. The trial is expected to complete enrollment in the second half of 2026, with topline primary endpoint data expected in the second half of 2027.

Near the end of 2025,² 4DMT announced a strategic partnership with Otsuka Pharmaceutical to develop and commercialize 4D-150 for the treatment of wet age-related macular degeneration and diabetic macular edema (DME) in the greater Asia-Pacific (APAC) region, including Japan.

According to the company, under the terms of the agreement, 4DMT will grant Otsuka exclusive rights to develop and commercialize 4D-150 for retinal vascular diseases in Japan, China, Australia, and other Asia-Pacific markets. Additionally, Otsuka will lead all regulatory and commercialization activities in its licensed territories.

In July 2025,³ 4DMT announced its intent to accelerate its 4D-150 4FRONT phase 3 program in wet AMD and lay off approximately 25% of staff. 4DMT noted that this transition supported the company’s focus on its late-stage pipeline, a strategy previously announced in January 2025.

References:

1. 4DMT Completes Enrollment for 4FRONT-1 Phase 3 Clinical Trial of 4D-150 in Wet AMD. Published February 9, 2026. Accessed February 9, 2026. https://ir.4dmoleculartherapeutics.com/news-releases/news-release-details/4dmt-completes-enrollment-4front-1-phase-3-clinical-trial-4d-150

2. Harp MD. 4DMT and Otsuka Pharmaceutical partner on 4D-150 in the greater Asia-Pacific region. Published November 4, 2025. Accessed February 9, 2026. https://www.ophthalmologytimes.com/view/4dmt-and-otsuka-pharmaceutical-partner-on-4d-150-in-the-greater-asia-pacific-apac-region

3. Harp MD. 4DMT accelerating 4D-150 4FRONT phase 3 program, laying off 25% of staff. Published July 7, 2025. Accessed February 9, 2026. https://www.ophthalmologytimes.com/view/4dmt-accelerating-4d-150-4front-phase-3-program-laying-off-25-of-staff