4DMT accelerating 4D-150 4FRONT phase 3 program, laying off 25% of staff

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4D Molecular Therapeutics has announced it is accelerating its 4D-150 4FRONT phase 3 program in wet age-related macular degeneration (wet AMD) and will lay off approximately 25% of staff.

The company noted that they will also be streamlining operations to offset additional expenses expected based on the accelerated timelines for the 4FRONT clinical trials and BLA preparation.¹ 4DMT noted that this transition supports the company’s focus on its late-stage pipeline, a strategy previously announced in January 2025.²

In the announcement at the beginning of 2025, the company announced it will terminate its early-stage rare disease clinical programs evaluating 4D-110 for choroideremia and 4D-125 for X-linked retinitis pigmentosa and will not be investing additional capital into new preclinical product candidates at this time. With these changes the company expects its current cash to fund operations into 2028.

4DMT also noted that the initial enrollment and site activation for 4FRONT-1, the North American phase 3 clinical trial of 4D-150 in wet AMD, have exceeded initial projections. As previously reported, the first patient was enrolled in 4FRONT-1³ earlier in March. Topline data from the trial is expected in the first half of 2027, which is an acceleration of the initial projection of the second half of 2027.

The second phase 3 trial of 4D-150 in wet AMD, 4FRONT-2, was initiated in June 2025, which was ahead of schedule according to the company. 4FRONT-2 is a global phase 3 clinical trial of 4D-150 in wet AMD and has an identical design to 4FRONT-1 except for enrolling both treatment-naïve and recently diagnosed, treatment-experienced patients. Topline data is expected in the second half of 2027.

As previously noted, the company plans to lay off 25% of staff in July 2025, primarily in the areas supporting early-stage research and development and support functions. The company notes that the workforce reduction is expected to provide annual cash compensation cost savings of approximately $15 million and offsets additional expenses expected based on the accelerated timelines for the 4FRONT clinical trials and BLA preparation.

David Kirn, MD, co-founder and CEO, and Dhaval Desai, chief development officer of 4DMT, commented on the plans in a press release from the company.

“We are thrilled with the strong interest in 4D-150 from investigators and patients in both 4FRONT Phase 3 studies, reflecting their belief in the Phase 1/2 data demonstrating the tolerability and robust, durable clinical activity of this potential foundational backbone therapy for retinal vascular diseases,” said Desai.

“We have aligned our resources to deliver on our mission of bringing transformative and durable genetic medicines to millions of patients in need, with a focus on 4D-150 for wet AMD, in our ongoing transition to becoming a commercial company. I want to express my deep gratitude and respect for the talented colleagues whose work has been critical to 4DMT’s success to date, who we thank sincerely for their dedication to and passion for our mission,” said Kirn.

References:

1. 4DMT Announces Accelerated 4D-150 Phase 3 Development in Wet AMD and Streamlined Organization to Drive Late-Stage Execution. Published July 2, 2025. Accessed July 7, 2025. https://www.globenewswire.com/news-release/2025/07/02/3109526/0/en/4DMT-Announces-Accelerated-4D-150-Phase-3-Development-in-Wet-AMD-and-Streamlined-Organization-to-Drive-Late-Stage-Execution.html

2. Joy J. 4DMT refocuses pipeline to prioritize 4D-150 trials in wet AMD and DME. Published January 13, 2025. Accessed July 7, 2025. https://www.ophthalmologytimes.com/view/4dmt-refocuses-pipeline-to-prioritize-4d-150-trials-in-wet-amd-and-dme

3. Harp MD. 4DMT enrolls first patient in phase 3 4FRONT-1 evaluating 4D-150 for the treatment of wet AMD. Published March 10, 2025. Accessed July 7, 2025. https://www.ophthalmologytimes.com/view/4dmt-enrolls-first-patient-in-phase-3-4front-1-evaluating-4d-150-for-the-treatment-of-wet-amd