Posters

A novel CD160-targeted first-in class humanized IgG4 monoclonal antibody, ELB01101, prevents laser-induced choroidal neovascularisation in a cynomolgus non-human primate model

Poster Details

First Author: T.Menguy FRANCE

Co Author(s):    A. Calcei   H. Haegel   V. Dugong   J. Mizrahi   A. Bensussan   P. Le Bouteiller              

Abstract Details



Purpose:

Efficacy and tolerability, after a single bilateral intravitreal injection, were tested with ELB01101, a novel therapeutic humanized anti-human CD160 human IgG4 mAb, in the experimental laser-induced choroidal NV (ChNV) model in cynomolgus Non-Human Primate (NHP).

Setting:

Tolerability and preventive effect of intravitreal delivery of ELB01101 on Laser-Induced Choroidal Neovascularization in Cynomolgus Monkeys

Methods:

The novel humanized anti-CD160 mAb ELB01101 was tested by single bilateral intravitreal injection of 1 mg/eye in a NHP ChNV model (Charles River, Canada). On day 1, the eyes of 6 animals per group were successfully subjected to a 9-spot laser wound pattern for the evaluation of ChNV. Fluorescein angiography was performed on days 1, 14 and 29. The individual laser spots were evaluated for leakage semi-quantitatively on a scale of 0-4 by 2 independent readers. The number of clinically relevant lesions (grade 3 and 4 corresponding to moderate and substantial leakage respectively) were combined. Laser spots were also individually evaluated semi-quantitatively for positive von Willebrand (vWF) staining on NHP flat mounted eyes and a score was given to the size and nature of the lesion of the laser spot.

Results:

In the NHP ChNV model, there was a greater combined number of clinically relevant lesions in the vehicle group on days 14 and 29 than for the novel ELB01101 anti CD160 mAb. At day 29, the incidence of clinically relevant lesions relative to the total number of laser spots was 12% (13 out of 108) in eyes administered with ELB01101 compared to 23% (25 out of 108) for the vehicle group. When evaluating the retinal pigment epithelium (RPE) coverage status of the spot lesion, the anti-CD160 treated group had higher number of completely RPE-covered total spots (32 to 16 spots) with scar while the vehicle control group had higher number of open spots with or without central scar (26 to 19 spots).

Conclusions:

The administration of the novel humanized anti-CD160 ELB01101 IgG4 therapeutic mAb, by single bilateral intravitreal injection, was well-tolerated in cynomolgus monkeys at 1 mg/eye. ELB01101 was associated with a reduction of ChNV compared to the vehicle control, which correlated well with a slightly higher vascularization at the centre of the induced lesion and a higher incidence of lesions with RPE scaring, suggesting an accelerated healing process in these eyes. Humanised ELB01101 therapeutic IgG4 monoclonal antibody (mAb) targeted against human CD160 receptor is a novel first-in class anti-angiogenic therapy.

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