4DMT Accelerates Wet AMD Trials, Cuts Workforce by 25%

4D Molecular Therapeutics (4DMT) has announced the acceleration of its 4D-150 4FRONT phase 3 clinical program targeting wet age-related macular degeneration (wet AMD) alongside a strategic move to lay off approximately 25% of its workforce. This decision comes as the company sharpens its focus on advancing its late-stage pipeline.

Streamlining Operations to Support Accelerated Timelines

According to 4DMT, the company will streamline operations to help offset additional costs tied to the faster timelines of the 4FRONT clinical trials and biologics license application (BLA) preparation. This transition aligns with the strategy first announced in January 2025, emphasizing a focus on late-stage programs. At that time, 4DMT shared plans to discontinue early-stage rare disease programs evaluating 4D-110 for choroideremia and 4D-125 for X-linked retinitis pigmentosa. The company also indicated it would pause new preclinical investments, projecting that these adjustments would enable it to fund operations into 2028.

Progress in 4FRONT Phase 3 Trials of 4D-150

4DMT highlighted that enrollment and site activation for 4FRONT-1, the North American phase 3 trial of 4D-150 in wet AMD, have surpassed initial expectations. The first patient in 4FRONT-1 was enrolled in March 2025, and topline data are now anticipated in the first half of 2027—earlier than the initial forecast of late 2027.

Additionally, 4FRONT-2, the global phase 3 trial of 4D-150 in wet AMD, was initiated in June 2025 ahead of schedule. This study mirrors the design of 4FRONT-1 but will enroll both treatment-naïve patients and recently diagnosed, treatment-experienced individuals. Topline results from 4FRONT-2 are expected in the second half of 2027.

Workforce Reduction to Offset Costs and Reallocate Resources

As part of its operational transition, 4DMT plans to reduce its workforce by approximately 25% in July 2025, primarily impacting early-stage research, development, and related support functions. This reduction is expected to deliver about $15 million in annual cash compensation cost savings, helping offset increased expenses from the accelerated phase 3 timelines and BLA work.

Leadership Comments on Strategic Shift

David Kirn, MD, co-founder and CEO, and Dhaval Desai, chief development officer of 4DMT, shared insights into the company’s direction in a press release.

“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.

Kirn added, “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.”