INmune Bio Inc. Presents Data on INB03’s Role as an Immune Check Point Modulator in the Treatment of High-Risk Breast Cancer at AACR 2024

Novel Immunotherapy Approach Targets Soluble Tumor Necrosis Factor to Overcome Resistance and Enhance Therapeutic Outcome in High-Risk Breast Cancer

Boca Raton, Florida, April 08, 2024 (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 tumor necrosis factor (TNF) inhibitor of soluble TNF (sTNF) in the treatment of high-risk MUC4 expressing HER2+ and triple negative breast cancer (TNBC).  INB03 is shown to decrease T cell and macrophage immune checkpoint proteins (PD1, TIGIT, LAG3, CD47 and SIRPa) in a model immunotherapy resistant HER2+ breast cancer and decrease the metastatic potential of TNBC by downregulating cell surface markers of tumor invasion (MUC4, SNAIL and Vimectin).  The two posters will be presented at the annual American Association of Cancer Research in San Diego on April 8, 2024.

The poster, titled, “INB03: a new immune checkpoint inhibitor that reprograms macrophage polarization, boosts ADCP and reverts T-cell exhaustion markers” outlines the use of human macrophages and T cells in a MUC4+HER2+ syngeneic breast cancer model to demonstrate that the combination of INB03 with an anti-HER2 antibody 4D5 has five distinct effects on the tumor biology, which results in decreased tumor growth (p<0.001).  These include:

i.       a decrease in MUC4 expression

ii.      a 3-fold increase in T cell infiltration

iii.     polarization of tumor macrophages from M1 (immunosuppressive) to M2 (anti-tumor macrophages)

iv.     a doubling of antibody dependent cellular phagocytosis (ADCP) and

v.      a decrease in the expression of innate immune checkpoint proteins (CD47 and SIRP-a) and T cell checkpoint proteins (TIGIT, CTLA-4, PD1 and LAG-3)

In the study, the increase in T cell infiltrate did not occur unless both anti-HER2 and INB03 immunotherapy were used in combination.  Decreases in T cell and macrophage immune checkpoint proteins were caused by INB03. All changes in immune parameters are p<0.05 unless otherwise stated.  The authors concluded that INB03 enhances the M1-like phenotype and reprograms already-polarized pro-tumoral M2-like macrophages to antitumoral ones.  Further, it promotes ADCP against HER2+ tumor cells by downregulating the ADCP inhibitory axis CD47-SIRPα-B7H4 in vitro.  Finally, the addition of INB03 to 4D5 treatment promotes T cell infiltration to the TME and downregulates immune checkpoint molecules and T cell exhaustion markers in vitro and in vivo.  The authors speculate that these effects could avoid tumor immune evasion to anti-HER2 targeted therapies by reinvigorating the immune infiltrate. The poster can be found on the Company’s web site.