Overview and Mechanism of Action

CM24 is a first-in-class clinical stage mAb targeting CEACAM1, a novel immune checkpoint inhibitor with significant potential to treat multiple cancers. CEACAM1 is associated with angiogenesis, and is an inter-cellular adhesion regulator of Fas-mediated apoptosis via interaction with β-catenin that enhances natural killer cell cytotoxicity against tumor cells. High CEACAM1 expression is known to be associated with poor disease prognosis in a number of tumor types. CEACAM1- CEACAM1 and CEACAM1-CEACAM5 immune checkpoint pathways prevent the death of tumor cells through the inhibition of the immune activity of TILs, lowering phosphorylation of immuno-receptors, and reducing SHP1/2 phosphorylation level in T and NK cells. CM24 (Humanized IgG4 mAb) binds specifically to the extracellular domain of CEACAM1 with nano-molar affinity. Blocking CEACAM1- CEACAM1 and CEACAM1-CEACAM5 interactions with CM24 is associated with anti-angiogenic, immune access, and checkpoint release mechanisms and enables cytotoxic activity of lymphocytes and the killing of tumor cells by T and NK cells.

Neutrophil extracellullar trap-associated CEACAM1 as a putative therapeutic target to prevent metastatic progression:

CEACAM1 creates a pro-angiogenic tumor microenviroment that supports tumor vessels maturation. CM24 is proposed to attenuate/block tumor growth anbd metastatic processes.

Clinical Studies

In a Phase 1 dose-escalation study, CM24 demonstrated a good safety profile and promising efficacy signals. We are developing CM24 in collaboration with Bristol Myers-Squibb via a Phase 1/2 trial combining CM24 with nivolumab in NSCLC and pancreatic cancer patients expressing high CEACAM1 levels.

CM24 - References (Download) NCT04731467 - A Phase 1/2 Study of CM24 in Combination With Nivolumab in Adults With Advanced Solid Tumors