Translational pharmacokinetic and pharmacodynamic modelling of the anti-ADAMTS-5 NANOBODY^® (M6495) using the neo-epitope ARGS as a biomarker.

ABSTRACT: M6495 is a first-in-class NANOBODY^® molecule and an inhibitor of ADAMTS-5, with the potential to be a disease modifying osteoarthritis drug. In order to investigate the PK/PD (pharmacokinetic and pharmacodynamic) properties of M6495, a single dose study was performed in cynomolgus monkeys with doses up to 6 mg/kg, with the goal of understanding the PK/PD properties of M6495. The neo-epitope ARGS (Alanine-Arginine-Glycine-Serine) generated by cleavage of aggrecan by ADAMTS-5 was used as a target-engagement biomarker. A long-lasting dose-dependent decrease in serum ARGS could be observed after a single dose of M6495 in cynomolgus monkeys. The serum biomarker ARGS decreased to levels below the limit of quantification of the assay in animals which received doses of M6495 of 6 mg/kg

SUBMITTER: Pereira JNS 

PROVIDER: S-EPMC11662058 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature