Extracellular TAC degraders go bispecific

Extracellular TAC degraders are starting to look and act more like antibody drugs. Two freshly funded companies are using classical bispecific formats to degrade extracellular targets by recruiting membrane-bound E3 ligases, a departure from the internalization receptors that defined the first extracellular degraders.

The trend revives debate about whether targeting chimeras (TACs) are distinct therapeutic modalities or novel applications of existing ones. Just as some construe proteolysis targeting chimeras (PROTACs) that degrade intracellular targets as a type of small molecule, the wave of largely protein-based TACs against extracellular targets may eventually be considered a subset of the bispecific biologics family...