4D-150 - (4SIGHT)

Sept. 28, 2026: 4D Molecular Therapeutics (NASDAQ: FDMT) said the first patients have been enrolled in 4SIGHT, a global Phase 3 trial of 4D-150 in treatment-naïve diabetic macular edema (DME), and reported updated 2-year SPECTRA data. 4SIGHT will randomize 514 patients in a double-masked, aflibercept 2 mg Q8W comparator-controlled study. The primary endpoint is non-inferiority in mean BCVA change at Week 52; key secondary endpoints are treatment burden reduction and the proportion achieving a ≥2-step ETDRS-DRSS improvement at Week 52. All patients receive five aflibercept loading doses, and both arms may receive supplemental aflibercept.

In SPECTRA (data cutoff March 12, 2026), 4D-150 was reported as well tolerated in 22 patients, with no intraocular inflammation, no ocular serious adverse events, and no hypotony, endophthalmitis, vasculitis, choroidal effusions, retinal artery occlusions, proliferative diabetic retinopathy progression, or vitreous hemorrhage. At the Phase 3 dose (3E10 vg/eye; n=9), mean BCVA gain was +10.8 letters and mean CST reduction was -176 µm. After 3 aflibercept loading doses, mean supplemental injections were 5.2 versus 13.0 projected for on-label aflibercept (61% reduction); a retrospective estimate using 4SIGHT criteria suggested 3.2 injections (75% reduction), and 2/9 patients remained injection-free. The company said FDA and EMA are aligned on potential BLA/MAA filings based on 4SIGHT plus prior SPECTRA, PRISM, and 4FRONT wet AMD data.