INmune Bio to present data on INB03, trastuzumab-deruxtecan combination

INmune Bio has been invited to present data on the combination of INB03 and trastuzumab-deruxtecan, or TDxd, for treatment of HER2 positive breast cancer. The data suggests INB03, a dominant-negative TNF inhibitor that selectively sequesters soluble TNF, or sTNF, may provide a novel mechanism for reversing resistance to HER2 targeted immunotherapy, and through this mechanism, may further enhance efficacy and reduce toxicity associated with TDxd treatment in some patients. TDxd is a trastuzumab-based antibody drug conjugate used to treat certain patients with HER2 breast cancer. Mucin 4, or MUC4, an easily measured glycoprotein on the cell surface of some HER2 positive breast cancer, is a biomarker of resistance to immunotherapy, including trastuzumab, and is also a biomarker of poor survival in women with HER2+ breast cancer. Expression of MUC4 is believed to be driven by soluble TNF produced by breast cancer cells. MUC4 is at the root of therapy resistance as it causes steric hinderance and prevents binding of trastuzumab to HER2 receptors and further promotes an immunosuppressive tumor microenvironment, or TME. Schillaci has previously shown that INB03 downregulates MUC4 and reverses resistance to trastuzumab in MUC4 expressing HER2+ breast cancers. Prior to this data, it was not known if MUC4 expression by HER2 positive breast cancer has an impact on response to TDxd. Using the nude mouse model of HER2 resistance in mice with MUC4 expressing HER2+ breast cancer, JIMT-1 tumors exhibit decreased growth when treated with TDxd. The combination of TDxd with INB03 improved anti-tumor immunology of the TME with fewer myeloid derived suppressor cells and more antitumor tumor macrophages, which further decreased tumor growth compared to TDxd alone. Importantly, the addition of INB03 did not increase the toxicity of TDxd in these animals.