Abstract
Purpose :
NRP1 can make complex with variety receptors such as VEGFR1, VEGFR2 and PDGFR so that it can regulate an angiogenesis induced by several growth factors. If the patients are administrated only anti-VEGFA drug for a long time, alternative angiogenic pathway may promote more aggressive neovascularization and reduce the responsiveness of the drug. Due to IDB0062 has a specific binding activity against hVEGFA and NRP1, it can efficiently block several angiogenic signal from these two targets. The purpose of this study is to investigate whether IDB0062 is able to inhibit angiogenesis which is induced by several growth factors such as VEGFA, VEGFB, PlGF2 and PDGF so that it can treat the patients who have resistance to anti-VEGFA drug.
Methods :
The in-vitro activity of IDB0062 was compared with the conventional therapeutic drugs through tube formation and migration assay after treatment of human retinal endothelial cells(hREC) and HCASMC with several growth factors. In vivo activity of IDB0062 was also evaluated using mouse CNV and OIR model.
Results :
In several in-vitro studies using hREC, ranibizumab couldn't inhibit angiogenesis by VEGFB and PlGF2 at all. IDB0062, on the other hand, was able to completely inhibit hREC migration to VEGFA, VEGFB and PlGF2 and had similar IC50 value for these three growth factors to aflibercept. In transwell assay using HCASMC, we demonstrated that IDB0062 also efficiently inhibited cell migration which was induced by PDGFBB. For in-vitro study using hREC, we have concluded that IDB0062 was superior to ranibizumab and non-inferiority to aflibercept.
In mouse CNV model, we found that CNV was significantly inhibited in mice treated with IDB0062 compared to conventional therapeutic drugs. Similarly, in mouse OIR model, we also confirmed that IDB0062 significantly reduced vascular leakage and contributed to vascular stabilization effectively.
Conclusions :
Due to its NRP1 binding activity, IDB0062 can competitively inhibit of NRP1 related ocular angiogenesis which was induced by several growth factors. Therefore, IDB0062 is a candidate for next-generation ocular biologics that can improve response for resistant patients and non-responders by overcoming the disadvantages of current ocular drugs such as ranibizumab and aflibercept.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.