INmune Bio Inc. Presents Preclinical Data at SITC 2023 Showing INB03 is an Innate Immune Check Point Inhibitor that Downregulates SIRPα

SIRP-CD47 is an innate immune checkpoint known as the “don’t eat me” signal. INB03 downregulates expression of SIRPα on macrophages promote increased cancer cell death by antibody dependent cellular phagocytosis (ADCP).

Boca Raton, Florida, Oct. 30, 2023 (GLOBE NEWSWIRE) --   INmune Bio, Inc. (NASDAQ: INMB) (the “Company”), a clinical-stage immunology company focused on developing treatments that harness the patient’s innate immune system to fight disease, is presenting data on the use of INB03, a dominant-negative inhibitor of soluble TNF in the treatment of high-risk MUC4 expressing HER2+ breast cancer. Roxana Schillaci Ph.D. of Instituto de Biología y Medicina Experimental in Buenos Aries, Argentina, will present her work at the 38^th annual Society of Immunotherapy in San Diego, California which runs from November 1-4.

The poster entitled “INB03: a new immune checkpoint inhibitor that reprograms polarization and promotes ADCP in human macrophages,” shows that INB03 is an innate immune checkpoint inhibitor working through the SIRPα-CD47 pathway to promote ADCP. SIRPα is a surface protein expressed by macrophages that binds to CD47 expressed by tumor cells. SIRPα-CD47 is known as the “don’t eat me” signal that prevents phagocytosis of tumor cells and promotes resistance to immunotherapy. INB03 downregulates SIRPα expression to eliminate the “don’t eat me signal” and promote ADCP. Inhibition of the SIRPα-CD47 pathway has focused predominately on targeting CD47 with anti-CD47 therapeutics. Targeting SIRPα may provide differentiated pharmacokinetic, safety, and efficacy profiles.

“Macrophages play an important role in the control of tumors, but cancer cells have developed very efficient ways to evade attack by the patient’s immune system,” said Roxana Schillaci, Ph.D. of CONECIT and senior author of this work. “TNF promotes expression of SIRPα on macrophages that bind to CD47 on tumor cells to prevent ADCP.  Neutralization of sTNF with INB03 downregulates the expression of SIRPα to promote ADCP that should help control tumor growth and prevent resistance to immunotherapy.”

The research presented in the poster examines animal models and human macrophages. INB03 neutralizes sTNF, repolarizing tumor protecting M2 macrophages to M1 anti-tumor macrophages, enhances ADCP with trastuzumab, and reduces SIRPα expression. In mice with trastuzumab resistant breast cancer, INB03 treatment polarizes splenic and tumor-infiltrating macrophages to M1 type macrophages that phagocytize tumor cells and decreased immune checkpoint expression (PD-L1, TIM3, LAG3) in tumor-infiltrating CD8+ T cells.