INmune Bio, Inc. is presenting data on the use of INB03, a dominant-negative TNF inhibitor of soluble TNF (sTNF) in the treatment of high-risk MUC4 expressing HER2. Roxana Schillaci, Ph.D., of Instituto de Biología y Medicina Experimental in Buenos Aries, Argentina, will present her work at the 46th annual San Antonio Breast Cancer Symposium, which runs from December 5 to 9. INB03 decreases resistance to T-DXd therapy in three ways. INB03 decreases MUC4 expression on the surface of the breast cancer cells increasing the ability of the antibody to bind to the HER2 target on the cancer cell.

The combination of low-dose (1.5mg/kg) T-DXd+INB03 decreases tumor growth as much as full dose (5mg/kg) T-DXd alone suggesting increased binding of the immunotoxin to the cancer cell improves anti-tumor effects. INB03 increases internalization of T-DXd and converts the immunosuppressive TME into one that is more tumor-sensitive by polarizing tumor associated macrophages (TAM) from M2-like to M1-like phenotype with increased expression of IFNg. The poster concludes that the combination of INB03 may allow for lower doses of T-DXd to be effective in women with MUC4 expressing HER2+ breast cancer and that addition of INB03 may improve the response to T-DXd in women with resistant HER2+ disease.