Abstract
Pathological retinal and choroidal neovascularization is a hallmark of several blinding diseases, including diabetic retinopathy and age-related macular degeneration. While intravitreal anti-VEGF therapies remain the standard of care, they necessitate frequent injections, posing risks such as endophthalmitis and elevated intraocular pressure, alongside economic and adherence challenges. Here, we present Pene/LQ015, a novel eye drop formulation comprising the anti-VEGFA nanobody (LQ015) and a proprietary penetratin analog for noninvasive delivery. LQ015 demonstrates superior VEGF-blocking activity, broad binding specificity across species, and robust stability and scalability using a yeast expression system. Topical administration of Pene/LQ015 achieved effective retinal-choroid complex drug levels and suppressed neovascularization in preclinical models. Notably, in the cynomolgus monkey laser-induced choroidal neovascularization model, 30 days of continuous topical application significantly reduced neovascularization and vascular leakage, with excellent safety and tolerability. These findings highlight Pene/LQ015's potential as a game-changer in treating neovascular eye diseases. It offers a groundbreaking, noninvasive alternative to intravitreal injections, addressing key limitations of current therapies by enabling continuous dosing, improving patient adherence, and reducing treatment burden. These findings underscore its potential to transform the management of neovascular retinal and choroidal diseases, with promising implications for clinical application.