Antibody Developability

Overview

Framework of in vitro biophysical assays — selectivity, HIC behavior, insect cell binding, long-term stability — used to predict clinical attrition from discovery; a Wittrup/Adimab study of 137 clinical-stage antibodies demonstrated approved drugs are nearly always flag-free while Phase 2 candidates routinely carry multiple flags. Prior to approximately 2010, antibodies were discovered in HEK293 transient expression with protein A purification and minimal characterization before being handed to manufacturing, which then discovered problems requiring months of remediation; a concrete example was an antibody with multiple SEC peaks that no formulation work could resolve, returning to discovery after six months. A landmark study by Dane Wittrup at MIT and Adimab analyzed 137 antibodies across clinical development stages with in vitro assays for selectivity, HIC behavior, insect cell binding, and long-term stability; Phase 2 antibodies frequently carry three or four flags while approved molecules are almost entirely flag-free. (Discovery Process Evolution (20:00-25:00))