Bispecific VEGF-A and Angiopoietin-2 Antagonist RO-101 Preclinical Efficacy in Model of Neovascular Eye Disease

Abstract

ObjectiveTo investigate preclinical data regarding efficacy and biocompatibility of a bispecific protein, RO-101, with effects on Vascular Endothelial Growth Factor-A (VEGF-A) and Angiopoietin-2 (Ang-2) for use in retinal diseases. Study DesignExperimental study. SubjectsBrown Norway rats, New Zealand White Cross rabbits. MethodsPreclinical study data of RO-101 in terms of target-specific ELISA binding affinity to VEGF-A and Ang-2, vitreous half-life, inhibition of target-receptor interaction, laser Choroidal Neovascular Membrane (CNVM) animal model, Human Umbilical Vein Endothelial Cell (HUVEC) migration, and biocompatibility was obtained. Where applicable, study data was compared to other anti-VEGF agents. Main Outcome MeasuresBinding affinity, half-life, biocompatibility, and efficacy of RO-101. Neovascularization prevention by RO-101. ResultsRO-101 demonstrated a strong binding affinity for VEGF-A and Ang-2 and in vitro was able to inhibit binding to the receptor with higher affinity than faricimab. The half-life of RO-101 is comparable or longer than current VEGF inhibitors used in retinal disease. RO-101 was found to be biocompatible with retinal tissue in Brown Norway rats. RO-101 was as effective or more effective than current anti-VEGF therapeutics in causing regression of neovascular growth in vivo. ConclusionRO-101 is a promising candidate for use in retinal diseases. In preclinical models, RO-101 demonstrated similar or higher regression of neovascular growth to current anti-VEGF therapeutics with comparable or longer half-life. It also demonstrates strong binding affinity for VEGF-A and Ang-2. It also was shown to be biocompatible with retinal tissue in animal studies, indicating potential compatibility for use in humans.