EXT-4U

EXT-4U is a structurally unique, potent, and highly selective small-molecule agonist of the Peroxisome Proliferator-Activated Receptor-alpha (PPAR-α), currently in development by Excitant Therapeutics. Designed for oral administration, it is being investigated for the treatment of retinal diseases, specifically Diabetic Macular Edema (DME), Diabetic Retinopathy (DR), and neovascular Age-related Macular Degeneration (nAMD). EXT-4U exhibits cellular potencies below 50 nM and demonstrates more than 2,700-fold selectivity for PPAR-α over other PPAR isoforms (β/δ and γ). The therapeutic mechanism involves the activation of PPAR-α in retinal Müller cells, endothelial cells, and the retinal pigment epithelium (RPE), which helps ameliorate inflammation, vascular leakage, neurodegeneration, and neovascularization. It is positioned as a potential oral alternative to traditional intravitreal anti-VEGF therapies.