CB307 is bispecific Humabody, targeting each of PSMA and the potent co-stimulatory molecule CD137 (4-1BB).
CD137 is expressed on T-cells that are already primed to recognize tumour antigen through MHC/TCR interaction. It is a TNFRSF member which requires clustering to deliver an activating signal to T-cells. Monospecific mAbs that can agonise CD137 are in the clinic and known to be potent T-cell activators but suffer from treatment-limiting hepatotoxicity due to Fc-receptor and multivalent format-driven clustering.
CB307 is deliberately monovalent for CD137 and as such is unable to cause CD137 clustering in normal tissue. However, when the bispecific CB307 also binds to PSMA on tumour cells, only then does it cause clustering of co-engaged CD137 on tumour-associated T-cells. This drives a highly potent but tumour specific T-cell activation.
This highly modular format can be re-configured to create a pipeline of multiple therapeutic candidates each treating a different cancer indication, by targeting any of a range of alternative tumour-specific markers. Crescendo is moving CB307 rapidly towards the clinic.