Efficacy and durability of GB10, a novel bispecific VEGF/Ang-2 neutralizing fusion protein, in ocular neovascularization models
- 1Drug Discovery, Center for Research and Development, Kexing Biopharm Co., Ltd. Shenzhen
Abstract
Purpose: To evaluate the preclinical efficacy, durability, and ocular biodistribution profiling of GB10, a novel bispecific vascular endothelial growth factor/angiopoietin 2 neutralizing fusion protein, compared with faricimab in models of choroidal and retinal neovascularization.
Methods: Cynomolgus monkeys (cyno) with laser-induced choroidal neovascularization (CNV) received intravitreal GB10 (0.07, 0.7, or 7 mg/eye), faricimab (6 mg/eye), or vehicle. Dutch belted rabbits with DL-alpha-aminoadipic acid-induced retinal neovascularization (RNV) received GB10, faricimab, or vehicle. Chinchilla rabbits were used for biodistribution. Efficacy and durability were assessed by fluorescein fundus angiography in cyno CNV model and rabbit RNV model. Tissue concentrations were quantified by ELISA.
Results: In the CNV model, GB10 at 0.7 mg/eye achieved similar anti-leakage inhibition at a 9-fold lower dose relative to faricimab at 6 mg/eye (grade 4 incidence: 54.17% vs. 76.39% at week 1). By week 2, GB10 (0.7 and 7 mg/eye) achieved 0% incidence of grade 4 leakage, sustained through week 4. In the RNV model, GB10 sustained inhibitory activity for ≥12 weeks, whereas faricimab showed effects up to 4 weeks for FFA score and 8 weeks for grade 4 leakage. GB10 demonstrated high distribution in retina/choroid (≈35% of total exposure) and minimal systemic exposure (serum proportion 0.02%).
Conclusion: In preclinical ocular neovascularization models, GB10 shows desirable efficacy at a 9-fold lower dose versus faricimab in cyno CNV model, alongside extended durability of ≥12 weeks (faricimab: 4 weeks for FFA score and 8 weeks for grade 4 leakage area) in rabbit RNV model. These preclinical findings demonstrate GB10’s encouraging prospects as a next-generation therapeutic candidate, with efficacy profiles to be confirmed in clinical investigations.
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BibTeX
@article{hao2026efficacy,
title = {{Efficacy and durability of GB10, a novel bispecific VEGF/Ang-2 neutralizing fusion protein, in ocular neovascularization models}},
author = {Meiqi Hao and Qiongying You and Xiling Wei and Suofu Qin},
journal = {Frontiers in Pharmacology},
year = {2026},
month = oct,
doi = {10.3389/fphar.2026.1974368},
url = {https://www.frontiersin.org/articles/10.3389/fphar.2026.1974368/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Efficacy and durability of GB10, a novel bispecific VEGF/Ang-2 neutralizing fusion protein, in ocular neovascularization models
AU - Meiqi Hao
AU - Qiongying You
AU - Xiling Wei
AU - Suofu Qin
PY - 2026
DA - 2026/10/20
JO - Frontiers in Pharmacology
DO - 10.3389/fphar.2026.1974368
UR - https://www.frontiersin.org/articles/10.3389/fphar.2026.1974368/full
AB - Purpose: To evaluate the preclinical efficacy, durability, and ocular biodistribution profiling of GB10, a novel bispecific vascular endothelial growth factor/angiopoietin 2 neutralizing fusion protein, compared with faricimab in models of choroidal and retinal neovascularization. Methods: Cynomolgus monkeys (cyno) with laser-induced choroidal neovascularization (CNV) received intravitreal GB10 (0.07, 0.7, or 7 mg/eye), faricimab (6 mg/eye), or vehicle. Dutch belted rabbits with DL-alpha-aminoadipic acid-induced retinal neovascularization (RNV) received GB10, faricimab, or vehicle. Chinchilla rabbits were used for biodistribution. Efficacy and durability were assessed by fluorescein fundus angiography in cyno CNV model and rabbit RNV model. Tissue concentrations were quantified by ELISA. Results: In the CNV model, GB10 at 0.7 mg/eye achieved similar anti-leakage inhibition at a 9-fold lower dose relative to faricimab at 6 mg/eye (grade 4 incidence: 54.17% vs. 76.39% at week 1). By week 2, GB10 (0.7 and 7 mg/eye) achieved 0% incidence of grade 4 leakage, sustained through week 4. In the RNV model, GB10 sustained inhibitory activity for ≥12 weeks, whereas faricimab showed effects up to 4 weeks for FFA score and 8 weeks for grade 4 leakage. GB10 demonstrated high distribution in retina/choroid (≈35% of total exposure) and minimal systemic exposure (serum proportion 0.02%). Conclusion: In preclinical ocular neovascularization models, GB10 shows desirable efficacy at a 9-fold lower dose versus faricimab in cyno CNV model, alongside extended durability of ≥12 weeks (faricimab: 4 weeks for FFA score and 8 weeks for grade 4 leakage area) in rabbit RNV model. These preclinical findings demonstrate GB10’s encouraging prospects as a next-generation therapeutic candidate, with efficacy profiles to be confirmed in clinical investigations.
SN - 1663-9812
ER -