On April 11, 2023 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, reported that it 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+ and triple negative breast cancer (Press release, INmune Bio, APR 11, 2023, View Source [SID1234629948]). Roxana Schillaci Ph.D. of Instituto de Biología y Medicina Experimental in Buenos Aries, Argentina, will present data at the American Association of Cancer Research Annual Meeting 2023 in Orlando Florida and has published a paper in Cancers as part of the Special Issue: Targeted Therapeutic Options and Future Perspectives for HER2-Positive Breast Cancer.
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MUC4, an easily measured glycoprotein on the cell surface of approximately one third of women with HER2+ or TNBC, predicts poor survival and treatment resistant disease with increased metastatic potential. Several resistance mechanisms are active in MUC4-expressing tumors including resistance to trastuzumab-based antibody drug conjugates such as trastuzumab-deruxtecan (Enhertu). Neutralizing soluble TNF with INB03, a dominant negative inhibitor of sTNF, decreases MUC4 expression, improves function of trastuzumab based immunotherapies, increases anti-tumor macrophage function, increases tumor infiltrating lymphocyte populations, and decreases the metastatic potential of these high-risk tumors. These changes should improve the response to immunotherapy.
"We understand how MUC4 causes resistance to HER2-targeted therapies and have developed a strategy to overcome this resistance," said Roxana Schillaci Ph.D., lead scientist on the program from the Instituto de Biología y Medicina Experimental in Buenos Aires, Argentina. "We believe reversing expression in MUC4 in TNBC may provide therapeutic benefits. Reversing drug therapy resistance mechanisms by targeting soluble TNF alpha with INB03 may be a more efficient and safer way to improve response to therapy in women with relapsing breast cancer."
"Despite recent innovations in the treatment of HER2+ and triple-negative breast cancer, an unacceptably high number of women have resistant disease," said RJ Tesi M.D., CEO of INmune Bio. "MUC4 expression can be determined before treatment is initiated. Modifying the treatment to account for this new resistance mechanism may make is difference in the care of these woman."
Session title: Immune Response to Therapy
Poster Title: Soluble TNFα blockade enhances trastuzumab deruxtecan antitumor effect in HER2-positive breast cancer
Session Date/Time: Monday April 17, 2023 / 9.00 am to 12.30pm
Poster Board Number/Abstract Presentation Number: 20 / 2273
Location/Poster Board Number: Section 43 / 20
Session title: Metastasis Promoting and Suppressing Genes
Poster Title: New Therapeutic approach for triple negative breast cancer: TNF blockade and MUC4 expression as a prognostic biomarker
Session Date/Time: Monday April 17, 2023 / 9.00 am to 12.30pm
Poster Board Number/Abstract Presentation Number: 29/1306
Location/Poster Board Number: Section 4/29
About INB03
INB03 is a DN-TNF inhibitor that neutralizes soluble TNF (sTNF) without affecting trans membrane TNF (tmTNF) or TNF receptors. Compared to currently available non-selective TNF inhibitors, INB03 preserves the immune response to cancer by decreasing immunosuppressive cells in the TME including TAM and MDSC while promoting recruitment of anti-tumor immune cells including cytolytic CD8+ lymphocytes, NK cells and anti-tumor macrophages. INB03 has completed an open label dose-escalation Phase I trial in patients with advanced cancer. In that trial, INB03 was found to be safe and well tolerated – no dose limiting toxicity was found. INB03 decreased blood biomarkers of inflammation in patients with advanced cancer. INMB is planning a Phase II trial that uses IN03 as part of combination therapy.