Abstract
Purpose :
EYS809 dual-gene plasmid encodes Aflibercept and Decorin, an antiangiogenic and anti-fibrotic native protein that targets choroidal neovascularization (CNV), vascular leakage, and subretinal fibrosis. EYS809 is intended to be an alternative to repeated anti-VEGF injections that have been associated with treatment burden and poor long-term visual outcomes in nAMD patients. Herein, we explored the effect of EYS809 in the traditional and the two-stage laser-induced CNV rat models.
Methods :
Laser injury was performed in 8-weeks old Brown Norway rats, once (traditional CNV model) or twice a week apart (two-stage laser model) to induce sustained leakage of vessels and subretinal fibrosis as previously reported in mice (Little et al. 2020). In the traditional CNV model, EYS809 (30 µg/eye) or vehicle electroporation delivery was performed 3 days before laser injury, and compared to IVT Aflibercept (15 µg/eye) or vehicle administered at laser impact (n=8 per group). In the two-stage laser model, treatments were delivered either 3 days before or at the second laser burn (EYS809 or Aflibercept, respectively, n=8 per group). Vascular leakage was assessed at week 2 (traditional and two-stage models) and week 4 (two-stage model) by fluorescein angiography and scoring of leaky lesions. CNV was measured on FITC-Dextran RPE/choroid flat mounts at week 2 in the traditional model.
Results :
In the traditional CNV model, EYS809 or IVT Aflibercept similarly reduced the incidence of leaky CNV lesions and CNV area by about 50% and 40%, respectively, compared with controls. In the two-stage model, angiography showed a 50% reduction in the incidence of leaky CNV lesions in EYS809-treated group at week 2 after the second laser burn while IVT Aflibercept showed no significant effect. EYS809 effects persisted at week 4 after the second laser burn with still 50% reduction in the incidence of leaky CNV lesions compared with controls, in line with sustained expression of transgenes.
Conclusions :
We presented preclinical data from 2 independent CNV rat models suggesting robust and sustained prevention of CNV with EYS809 in preventive and prophylactic conditions. Future studies are underway to determine how EYS809 limits subretinal fibrosis in the two-stage laser CNV model.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.