Preclinical pharmacokinetics of novel MYDGF for human PK and dose prediction

Aim This study aimed to characterize the pharmacokinetics (PK) of recombinant human myeloid-derived growth factor (hMYDGF), a 15.8 kDa novel therapeutic protein for cardiac repair after myocardial infarction, in various preclinical animal species (mouse, Yorkshire pig and cynomolgus monkey) to guide human PK and dose prediction.Methodology A custom, specific, ultra-sensitive MSD assay was developed to accurately quantitate hMYDGF in plasma. Single-dose pharmacokinetic studies were conducted in mice, Yorkshire pigs, and cynomolgus monkeys, followed by bioanalytical assessment and comprehensive pharmacokinetic analysis. In vitro human serum stability was also assessed using a custom LC-MS/MS-based assay. Plasma time-concentration profiles were fitted to a two-compartment PK model, with allometric scaling used to predict human PK parameters.Results Rapid plasma clearance of hMYDGF was observed across all species, consistent with renal elimination driven by its low molecular weight. Serum stability tests indicate that clearance was not caused by nonspecific proteolytic degradation.Conclusion Pharmacokinetics were accurately characterized in all species, enabling allometric scaling and predicted human PK and efficacious dose. Simulations indicated that a single intravenous bolus of 0.42 mg/kg in humans would achieve plasma levels linked to preclinical efficacy, supporting MYDGF’s potential as a protein replacement therapy for acute myocardial infarction.