Abstract
Purpose :
Abnormal angiogenesis underpins vision loss associated with several diseases including wet age-related macular degeneration (AMD), diabetic retinopathy, diabetic macular edema (DME), and macular edema following retinal vein occlusion. Anti-vascular endothelial growth factor (VEGF) therapies have shown consistent success in these pathologies. However, in addition to VEGF, the angiopoietin-Tie2 pathway has also been shown to play a role in angiogenesis. ABP-201, our tetravalent bispecific antibody, was engineered with the goal of inhibiting VEGF and angiopoietin-2 concomitantly. This is the first study assessing the activity of ABP-201 in the eye, using a rat laser-induced choroidal neovascularization (CNV) disease model.
Methods :
Brown-Norway rats received a single 5 µL intravitreal injection of ABP-201 in three concentrations, vehicle, or aflibercept (EYLEA®) in the right eye. Four or five lesions were burned within two discs from the optic nerve using a laser. Fundus imaging and optical coherence tomography (OCT) verified the lesions immediately following challenge. On Days 7 and 15, fluorescein angiography and OCT assessed lesion leakage and volume. Data were expressed as means ± SEM and analyzed using one-way ANOVA.
Results :
On Day 7, all three doses of ABP-201 induced a highly significant reduction in both lesion volume (27%, 27%, and 40%, respectively, for all p<0.01) and in leakage (33%, 35%, and 37%, respectively, for all p<0.0002) when compared to vehicle. On Day 15, the mid and high doses of ABP-201 induced a significant reduction in lesion volume (26% and 27%, respectively, for both p<0.05) and all three doses induced a significant reduction in leakage (28%, 33%, and 36%, respectively, for all p<0.05). For both lesion volume and leakage, the performance of ABP-201 was similar or better than aflibercept.
Conclusions :
Our study demonstrated that ABP-201 was beneficial for reducing neovascular lesion formation and vascular leakage in rat model of laser-induced CNV. These results pave the way to begin to utilize this bispecific antibody, engineered to improve both efficacy and durability compared to current VEGF therapies, for the treatment of wet-AMD and DME, as well as other angiogenic eye diseases.
This is a 2021 ARVO Annual Meeting abstract.