Abstract
Purpose :
To assess the effects of DS-7080a, an anti-ROBO4 monoclonal antibody, in an animal model of angiogenesis-related eye disease.
Methods :
Choroidal neovascularization (CNV) was induced in male cynomolgus monkeys by subjecting the eyes to LASER treatment. DS-7080a was injected intravitreally at doses of 0.055, 0.22, and 1.1 mg/eye to assess its anti-angiogenic efficts (N=6 eyes, each group). ROBO4 mRNA expression was assessed in the choroid from patients with wet-AMD by in situ hybridization. The pharmacokinetics of intravitreally injected DS-7080a was analyzed in rabbits and monkeys.
Results :
Three weeks after LASER exposure, mean (SD) of the incidence of Grade 4 CNV leakage was 48.15 (46.97) % in control monkeys but 1.85 (4.53)% in monkeys which received 1.1 mg/eye of DS-7080a. DS-7080a decreased CNV leakage dose-dependently. ROBO4 mRNA was detected the choroid from wet-AMD patients, especially in small vessels extending toward the Bruch’s membrane. Pharmacokinetics analysis showed DS-7080a may persist in the retina upon intravitreal injection for more than a month at effective concentrations.
Conclusions :
DS-7080a may represent a novel therapeutic option for angiogenesis-related eye diseases such as wet AMD.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.