Ocular and systemic pharmacokinetics of BI-X, a nanobody targeting VEGF and Ang-2, after intravitreal dosing in cynomolgus monkeys – Evidence for half-life extension by albumin

• DOI: 10.1016/j.exer.2021.108486
• Publication Date: 2021-02-08T06:34:14Z
• Authors: Holger Fuchs; Lin-Zhi Chen; Sarah Low; Hongbin Yu
• Keywords: Human serum albumin; Serum Albumin

Half-life extension strategies to reduce the intravitreal dosing frequency of biomolecules for treatment retinal neovascular diseases are attracting increasing interest. This study investigated ocular and systemic pharmacokinetics trivalent nanobody BI-X (with affinity VEGF, Ang-2 human albumin) in cynomolgus monkeys after injection. concentrations were measured serial samples plasma, vitreous humor, aqueous humor retina. Ocular exhibited two phases. Initially up 2–4 weeks dosing, vitreal, retina declined with half-lives around 3 days, which is comparable macromolecules a similar molecular weight. Thereafter, only vitreal measurable, terminal half-life 13.2 considerably longer than expected based on weight or hydrodynamic radius. It hypothesized that binding low levels intraocular albumin resulted this extension. was detectable plasma 10 post-dosing. Plasma biphasic disposition profile body, 11.8 thus reflecting input kinetics from eye. In conclusion, an important principle could be confirmed primate model, data obtained can potentially translated humans taking into account differing concentrations.