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Anti-CD160, Alone or in Combination With Bevacizumab, Is a Potent Inhibitor of Ocular Neovascularization in Rabbit
Thierry Menguy1, Anne Briaux2, Elisabeth Jeunesse3
1Elsalys Biotech, Lyon, France.
Purpose:
To assess the efficacy of the murine first-in-class CL1-R2 monoclonal antibody (mAb) targeting human CD160 (alone or in combination with bevacizumab) by using the rabbit corneal neovascularization (CNV) model, and determine the safety and efficacy of ELB01101, a novel CL1-R2-derived humanized IgG4 mAb, in a monkey model of choroidal neovascularization (ChNV).
Methods:
Comparison of effect of CL1-R2, bevacizumab, or aflibercept or IgG1 (control) injections in early and late treatment schemes on evolution of VEGF- or FGF2-induced rabbit CNV was performed. In the combination setting, bevacizumab was coinjected with different doses of CL1-R2. ELB01101 or vehicle was administered intravitreally in monkeys after laser-induced ChNV. Individual laser-induced lesions were semiquantitatively graduated by using fluorescein angiography to determine leakage.
Results:
In the rabbit model, early and late treatments with CL1-R2 significantly decreased both area and length of CNV neovessels. The effect was as potent as produced with anti-VEGF comparators. When combined with bevacizumab, an additive effect of CL1-R2 was measured at all doses tested. In the ChNV model, on day 29, eyes treated with ELB01101 showed a statistically significant reduction in clinically relevant lesions compared to vehicle-treated eyes (∼50%; χ2 test, P = 0.032001).
Conclusions:
The additive effects of anti-CD160 and bevacizumab in the CNV model suggest that these compounds could act via different pathways, opening new therapeutic pathways for cotargeted or combination therapies. In the ChNV model, ELB01101 was well tolerated and prevented approximately 50% of clinically relevant lesions, validating CD160 targeting as a safe approach for treatment of retinal diseases in the most relevant animal model of wet AMD.
Insights
CL1-R2 monoclonal antibody shows promise in treating neovascularization in rabbit and monkey models. Combination therapy with bevacizumab demonstrated additive effects, suggesting new therapeutic avenues for retinal diseases like wet age-related macular degeneration.
Area of Science:
- Ophthalmology
- Immunology
- Vascular Biology
Background:
- Neovascularization, a key process in retinal diseases, involves complex signaling pathways.
- Targeting specific molecules like CD160 offers potential for novel therapeutic strategies.
- Current treatments for neovascular eye diseases often target vascular endothelial growth factor (VEGF).
Purpose of the Study:
- To evaluate the efficacy of CL1-R2 monoclonal antibody (mAb), alone and with bevacizumab, in a rabbit corneal neovascularization (CNV) model.
- To assess the safety and efficacy of ELB01101, a humanized CL1-R2 mAb, in a monkey choroidal neovascularization (ChNV) model.
Main Methods:
- Comparison of CL1-R2, bevacizumab, aflibercept, and control IgG1 in rabbit CNV models with early and late treatment schemes.
- Combination therapy involved co-injecting bevacizumab with varying doses of CL1-R2.
- ELB01101 or vehicle was administered intravitreally in monkeys with laser-induced ChNV, with leakage assessed via fluorescein angiography.
Main Results:
- CL1-R2 treatment significantly reduced CNV area and length in rabbits, comparable to anti-VEGF agents.
- Combination therapy with bevacizumab showed additive effects with CL1-R2 across all tested doses.
- ELB01101 treatment in monkeys resulted in a statistically significant reduction (approximately 50%) in clinically relevant ChNV lesions.
Conclusions:
- The additive effects suggest CD160 and bevacizumab may act via different pathways, supporting combination therapies.
- ELB01101 was well-tolerated in monkeys and validated CD160 targeting as a safe approach for retinal diseases.
- CD160 targeting presents a promising therapeutic strategy for wet age-related macular degeneration and other retinal vascular conditions.
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