CTX-009 is a bispecific antibody that simultaneously targets Delta-like ligand 4 (DLL4) and vascular endothelial growth factor A (VEGF-A). This next generation angiogenic inhibitor has completed Phase 1 dose escalation and expansion study, and a Phase 1b in combination with chemotherapy is ongoing. As a monotherapy, CTX-009 has demonstrated clinical benefit in heavily pre-treated patients who have progressed after prior VEGF, EGFR, HER2, and PD1/L1-targeted therapies. Multiple, deep clinical responses were observed in patients with advanced colorectal cancer and in patients with gastric cancer. Multiple durable responses were also observed in the ongoing combination study in patients with cholangiocarcinoma and pancreatic cancer.
We plan on initiating clinical studies in the U.S. in several solid tumor indications, including biliary tract cancer, colorectal cancer, and ovarian cancer.
CTX-471 is an agonistic antibody directed against the co-stimulatory molecule CD137 (4-1BB).
CD137, a member of the TNF receptor superfamily of proteins, provides a potent costimulatory signal to activated T cells and other effector cells within the innate and adaptive arms of the immune system. A CD137 signal can potentiate cytotoxic T cell and proinflammatory anti-tumor activity.
CTX-8371 is a bispecific antibody that targets simultaneously the program death receptor (PD-1) and the programmed death ligand receptor (PD-L1) that are expressed on immune cells and cancer cells respectively. CTX-8371 is currently undergoing IND-enabling preclinical development. In pre-clinical studies, CTX-8371 demonstrated superior anti-tumor efficacy compared to marketed monoclonal antibodies targeting PD-1 or PD-L1 across several solid tumor animal models, including large syngeneic tumors as well as immunologically resistant melanoma metastases. Investigation into the molecular mechanism of action showed that binding of CTX-8371 to both PD-L1 and PD-1 resulted in cell-to-cell bridging and PD-1 shedding that is sustainable. This mechanism indicates that CTX-8371 has the potential to eliminate PD-1 from the surface of effector cells rather than transiently reduce the ability of PD-1 to bind to its ligands, thus providing additional advantage over existing anti PD-1 and anti-PD-L1 monoclonal antibodies.