QSP modeling of a transiently inactivating antibody-drug conjugate highlights benefit of short antibody half life.

ABSTRACT: Antibody drug conjugates (ADC) are a promising class of oncology therapeutics consisting of an antibody conjugated to a payload via a linker. DYP688 is a novel ADC comprising of a signaling protein inhibitor payload (FR900359) that undergoes unique on-antibody inactivation in plasma, resulting in complex pharmacology. To assess the impact of FR inactivation on DYP688 pharmacology and clinical developability, we performed translational modeling of preclinical PK and tumor growth inhibition (TGI) data, accompanied by mechanistic Krogh cylinder tumor modeling. Using a PK-TGI model, we identified a composite exposure-above-tumorostatic concentration (AUC_TSC) metric as the PK-driver of efficacy. To underpin the mechanisms behind AUC_TSC as the driver of efficacy, we perform

SUBMITTER: Khera E 

PROVIDER: S-EPMC11652588 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature