Pipeline

 IMC-001 (anti-PD-L1 mAb)

PD-L1 is a clinically validated immune-checkpoint target which is over-expressed on tumor cells and tumor-infiltrating immune cells in multiple tumor types. PD-L1 is responsible for inhibiting the natural antitumor immune response by deactivating cytotoxic T cells in the tumor microenvironment or preventing priming and activation of new T cells in the lymph nodes thereby preventing their recruitments to the tumor. Antibodies blocking PD-L1 can reactivate T-cell activity and proliferation, leading to enhanced anti-tumor immunity.

IMC-001 is a fully human anti-PD-L1 monoclonal antibody which shows robust efficacy both in vitro and in vivo. We are currently evaluating IMC-001 in Phase I clinical trial in patients with solid tumors.

 IMC-002 (anti-CD47 mAb)

CD47 is a transmembrane protein broadly expressed on cell’s surface and often overexpressed on cancer cells. CD47 on cancer cells interacts with the myeloid inhibitory immunoreceptor SIRPα on macrophages to deliver a “don’t-eat me” signal that inhibits phagocytic activity (cancer cell killing). Blocking CD47-SIRPα interaction restores phagocytic activity of macrophages, which was shown to inhibit tumor growth in mouse xenograft model.

 IMC-002 is a fully human IgG monoclonal antibody that binds human CD47 with an optimal affinity that maximizes efficacy (tumor phagocytosis) without causing hemagglutination. IMC-002 blocks CD47-SIRPα interaction to promote phagocytosis of cancer cells by macrophages. Combinational blockade of PD-L1 and CD47 has been shown to enhance anti-tumor effects in vivo. This presents an interesting opportunity to combine IMC-001 and IMC-002 in the clinic. ImmuneOncia is also developing additional antibodies targeting novel immune-checkpoints.

References

Immunity. 2013;39:1-10 : Oncology Meets Immunology: The Cancer-Immunity Cycle
Clin Cancer Res. 2012;18:6580-6587 : Molecular pathways: next-generation immunotherapy–inhibiting programmed death-ligand 1 and programmed death-1
Annu Rev Immunol. 2008;26:677-704 : PD-1 and its ligands in tolerance and immunity
Clin Cancer Res. 2013; 19: 1021-1034 : Antagonist Antibodies to PD-1 and B7-H1 (PD-L1) in the Treatment of Advanced Human Cancer
Cell, 2009;138, 271–285 : CD47 is upregulated on circulating hematopoietic stem cells and leukemia cells to avoid phagocytosis.
Proc. Natl. Acad. Sci. USA 2012;109, 6662–6667 : The CD47-signal regulatory protein alpha (SIRPα) interaction is a therapeutic target for human solid tumors.
Annu Rev Immunol. 2014;32:25–50 : The interaction between signal regulatory protein alpha (SIRPα) and CD47: Structure, function, and therapeutic target.
Nature. 2017; 25;545(7655):495-499 : PD-1 expression by tumour-associated macrophages inhibits phagocytosis and tumour immunity.