Abstract
Purpose :
SKG0106 is a novel recombinant AAV vector developed by Skyline Therapeutics for the treatment of neovascular age-related macular degeneration (nAMD) via intravitreal (IVT) delivery. SKG0106 comprises a proprietary capsid and a novel transgene genome that encodes an anti-vascular endothelial growth factor (VEGF) protein, Vb24. Upon delivery, the vector transduced retinal cells resulting in effective expression of Vb24, which potently and specifically suppressed the action of VEGF in the studies with a chronic rabbit retinal neovascularization (RNV) model and a monkey choroidal neovascularization (CNV) model.
Methods :
The efficacy of SKG0106 was quantified in the rabbit RNV model based on the improvement rate of fluorescein leakage area (FLA) and evaluated in the monkey CNV model based on grade 4 laser spot rate, mean FLA, and thickness of subretinal hyperreflective material (SHRM). The local tolerance in eyes was assessed by slit lamp microscopy.
Results :
In the rabbit DRF study, multiple doses of SKG0106 were administered and observed for 6 wks. SKG0106 in the dose-range of 1E9 to 3E10 vg/eye showed comparable efficacy profiles vs. that of Eylea®. In addition, SKG0106 inhibited fluorescein leakage until the end of the study, while Eylea® lost its activity. In the monkey DRF study, 6 doses of SKG0106 were injected and observed for 6 wks. SKG0106 exhibited a dose-dependent effect in reducing CNV grade 4 spot rate and mean FLA at 1-2 wks post-modeling, the SHRM thickness was significantly reduced. The efficacy of SKG0106 at 8E9, 4E10, 2E11 and 1E12 vg/eye were comparable to that of Eylea®, and the vector showed excellent tolerance profiles. In the prophylactic long-term study with CNV model, monkeys were dosed with 6E10 vg/eye for observations of 6, 13 or 26 wks. SKG0106 exhibited comparable efficacy to that of Eylea® at 6, and 13 wks following treatment. SKG0106 showed strong efficacy in the 26-wks groups, in contrast, Eylea® did not show the inhibitory effect on the lesions. The thickness of SHRM in SKG0106 group was significantly thinner than that of vehicle group and Eylea® group. Importantly, there was no AE detected in the study. In addition, no systemic abnormal findings were detected in all PD studies and a GLP toxicity study in monkeys.
Conclusions :
With the support from all these data, INDs for the vector have been approved in both the US and China, and the clinical trial is on-going.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.