Ensovibep is a multispecific designed ankyrin repeat protein (DARPin) therapeutic developed as anti-viral therapy to treat symptomatic COVID-19. During clinical development multiple bioanalytical assessments were performed including free and total PK, as well as immunogenicity. The free and total PK assays for this biologic were developed using immunoassay and mass spectrometry platforms, respectively, to assess if ensovibep bound to target (receptor binding domain of SARS-CoV-2) impacted free protein assessments from the ligand binding assay. A direct drug binding immunogenicity assay was used to detect anti-drug antibodies. During immunogenicity tiered testing, a high false negative rate was observed in the confirmatory assay. Therefore, the tiered testing scheme was updated to characterize positive samples from the screening assay directly to the titer assay. Evaluation of the bioanalytical data revealed good agreement between findings in the free and total assay, confirming availability of free drug in serum and confidence in the bioanalytical data.
Learning Objectives:
The participant will understand the unique bioanalytical methodologies used to assess PK and immunogenicity for a DARPin in development and see how decision making was implemented real-time during the pandemic.
Understand DARPins.
Understand integrated Bioanalysis (PK (free and total), PD, and Immunogenicity measurements
Understand rapid drug development in the time of COVID