A validated ligand binding assay for the determination of etalanetug, a novel anti-tau therapeutic antibody, in rats and monkeys for nonclinical pharmacokinetic studies.

Etalanetug (E2814) is a novel human monoclonal antibody targeting tau that is currently being developed as a biotherapeutic for Alzheimer's disease. To inform pharmacological and toxicological evaluations in nonclinical settings and to guide dose selection for the first-in-human study, it is critical to characterize the pharmacokinetics (PK) of etalanetug. We have developed and validated a ligand-binding assay (LBA) for quantifying etalanetug in rat and monkey serum for use in nonclinical PK studies. Tau protein and anti-human immunoglobulin G antibody served as the capture and detection reagents, respectively. Using 10 µL of serum at a minimum dilution of 2000, etalanetug was quantifiable from 0.1 µg/mL in monkeys and 0.3 µg/mL in rats. Assay accuracy and precision, together with multiple serum stability assessments, demonstrated the robustness and reliability of the method. The assay was applied to PK studies in rats and monkeys. Following an intravenous dose of 30 mg/kg, etalanetug exhibited a biphasic decline in serum concentration with half-lives of 150-193 h in rats and monkeys. Incurred sample reanalysis further confirmed assay reproducibility. These results support the suitability of the developed LBA for nonclinical PK studies of etalanetug in both rats and monkeys.