4D Molecular Therapeutics Accelerates Phase 3 AAV Program for 4D-150 in Wet AMD

EMERYVILLE, Calif., July 02, 2025 – 4D Molecular Therapeutics (4DMT) (Nasdaq: FDMT), a leading late-stage biotechnology company advancing durable AAV gene therapy, today announced a significant acceleration of its AAV-based 4D-150 4FRONT Phase 3 program for wet age-related macular degeneration (wet AMD). This strategic move, part of the company’s intensified focus on its late-stage AAV pipeline, also includes operational streamlining to support an extended cash runway into 2028.

Key Program Accelerations & Operational Adjustments for AAV Program:

Accelerated 4FRONT-1 Topline Data for AAV-150: Initial enrollment and site activation for 4FRONT-1, the North American Phase 3 clinical trial of their AAV therapeutic 4D-150 in wet AMD, have exceeded projections. Consequently, 52-week topline data is now anticipated in H1 2027, a significant acceleration from the previous guidance of H2 2027.

Early Initiation of 4FRONT-2 for AAV-150: The second global Phase 3 trial, 4FRONT-2, commenced in June 2025, ahead of schedule. This trial, also evaluating the AAV vector 4D-150 in wet AMD, has an identical design to 4FRONT-1 but includes both treatment-naïve and recently diagnosed, treatment-experienced patients. 52-week topline data for 4FRONT-2 is still expected in H2 2027.

Workforce Reduction: To offset additional expenses from the accelerated AAV clinical trial timelines and BLA preparation, 4DMT implemented a workforce reduction of approximately 25% in July 2025. This reduction primarily impacts early-stage research and development and support functions.

Cost Savings & Cash Runway: The workforce reduction is projected to provide annual cash compensation cost savings of approximately $15 million, maintaining the company’s previously guided cash runway into 2028.

Financial Position: As of March 31, 2025, 4DMT reported $458 million in cash, cash equivalents, and marketable securities. The Company believes this is sufficient to support planned expenses to deliver 52-week topline data from both 4FRONT-1 and 4FRONT-2 Phase 3 AAV trials and BLA preparation for AAV150 in wet AMD, continue Phase 1/2 and pre-Phase 3 planning activities for AAV150 in diabetic macular edema (DME), and continue ongoing Phase 1/2 development of AAV710 in cystic fibrosis (CF).

About 4D-150 (an AAV Therapeutic):4D-150 is a potential backbone therapy designed to provide multi-year sustained delivery of anti-VEGF (aflibercept and anti-VEGF-C) from the retina with a single, safe, intravitreal injection. 4D-150 utilizes the Company’s customized and evolved intravitreal AAV vector, R100, which was invented at 4DMT through the Company’s proprietary Therapeutic Vector Evolution platform. 4D-150 is being developed for wet AMD and DME, which both affect millions of patients globally, with the goal of freeing patients from burdensome injections while preserving vision through AAV delivery.

About Wet AMD:Wet AMD is a highly prevalent disease, projected to affect over 4 million individuals in major markets within the next five years, with an estimated 200,000 new diagnoses annually in the U.S. alone. It involves abnormal blood vessel growth (macular neovascularization or MNV) leading to swelling, bleeding, and scarring, which can severely distort or destroy central vision and lead to blindness if untreated. This process is stimulated by VEGF.