4D Molecular Therapeutics (4DMT) has announced a strategic shift in its pipeline to prioritize the development of 4D-150 for wet age-related macular degeneration (wet AMD) and diabetic macular edema (DME), and 4D-710 for cystic fibrosis (CF). This decision follows alignment with the FDA and EMA on trial designs for the Phase 3 4FRONT program for 4D-150 in wet AMD. The company anticipates that its current cash reserves will fund operations into 2028.
Phase 3 Trials for 4D-150 in Wet AMD
The Phase 3 4FRONT program includes two trials, 4FRONT-1 and 4FRONT-2, slated to begin in Q1 2025 and Q3 2025, respectively. Both trials will assess the noninferiority of 4D-150 (3E10 vg/eye) compared to aflibercept (2mg Q8W) based on best-corrected visual acuity (BCVA). Each trial aims to enroll 400 patients, with 4FRONT-1 focusing on treatment-naïve patients and 4FRONT-2 including both treatment-naïve and previously treated patients diagnosed within the last six months. Topline data from both trials is expected in H2 2027.
Progress of 4D-150 in DME
4DMT's ongoing SPECTRA Part 1 follow-up for 4D-150 in DME has shown promising results. Interim data at 32 weeks demonstrated that 4D-150 was well-tolerated, with no intraocular inflammation observed. The 3E10 vg/eye dosage led to a sustained BCVA gain of +8.4 letters and a CST reduction of -194 from baseline. Based on SPECTRA and PRISM data, the FDA has indicated that a single Phase 3 trial with 300-400 patients would be sufficient for BLA submission, eliminating the need for SPECTRA Part 2.
Advancing 4D-710 for Cystic Fibrosis
4DMT is also advancing 4D-710, a gene therapy for cystic fibrosis lung disease. The company's proprietary A101 vector has demonstrated successful delivery and expression of the CFTR transgene in the lungs of CF patients following aerosol delivery. Phase 1 AEROW enrollment is complete, and an interim data update is expected in mid-2025, including measurements of ppFEV1, CFQ-R-R, lung clearance index, and airway biopsies. 4DMT plans to approach the FDA with a pivotal trial proposal in mid-2025.
Pipeline Prioritization and Financial Outlook
As part of its strategic refocus, 4DMT will reduce capital allocation for 4D-175 for geographic atrophy and terminate the development of 4D-110 for choroideremia and 4D-125 for X-linked retinitis pigmentosa. With $506 million in cash, cash equivalents, and marketable securities as of December 31, 2024, 4DMT expects to fund operations into 2028, including the execution of the 4FRONT-1 and 4FRONT-2 Phase 3 trials and ongoing development for DME and CF. The company will also explore partnership opportunities and strategic financing options.
