Figure 4: Efficacy of ranibizumab and LAVA1 in the cynomolgus monkey laser-CNV model.

Laser photocoagulation to induce CNV lesions was applied 1–5 weeks after drugs were dosed. Late-phase fundus images from cynomolgus monkey eyes injected with ranibizumab or LAVA1 taken approximately 5 min post-intravenous fluorescein injection. The fundus images are shown as negatives (black and white reversed) to highlight the CNV-induced vascular leakage of fluorescein during fluorescein angiography. Cynomolgus monkeys 1–9 were imaged 22 days after dosing, whereas cynomolgus monkeys 10–15 were imaged 49 days after dosing. Each eye received four laser burns producing neovascular tufts (CNV) that appear as dark spots in the images; the darkness corresponds to the degree of vascular leakage from the CNV lesions. When dosed 8 days before laser, a single dose of ranibizumab only partially inhibited laser-induced CNV, whereas a single dose of LAVA1 completely inhibited laser-induced CNV. The plot (bottom left) shows average terminal levels of free (unbound to VEGF) LAVA1 and free ranibizumab in the cynomolgus monkey eyes 22 and 49 days post-intravitreal injection. Drug concentrations less than the lower limit of quantification (0.1 ng per eye) were categorized as ‘not detected’. At both day 22 and 49, free LAVA1 levels in the vitreous, retina and RPE-choroid were markedly higher than free ranibizumab. Error bars represent 1 s.d. Measurements were done in triplicates.