INmune Bio's INB03 Shows Promise in Overcoming HER2-Positive Breast Cancer Drug Resistance
核心洞察
INmune Bio announced new preclinical data at AACR 2026 showing that INB03 (XPro1595) significantly enhances anti-tumor activity when combined with tyrosine kinase inhibitors in HER2 (搜索)-positive breast cancer models.
The combination therapy demonstrated statistically superior inhibition of cell proliferation and migration compared to TKIs alone, with p-values ranging from p < 0.05 to p < 0.0001.
INB03 significantly reduced metastatic spread to brain, lung, and liver organs, addressing a critical unmet need in advanced HER2 (搜索)-positive breast cancer treatment.
INmune Bio Inc. has unveiled promising preclinical data demonstrating that its investigational therapy INB03 (XPro1595) can overcome drug resistance and reduce metastases in HER2 (搜索)-positive breast cancer models. The findings, presented at the American Association for Cancer Research (AACR) Annual Meeting 2026 in San Diego, suggest a potential breakthrough for patients who develop resistance to standard tyrosine kinase inhibitors.
Overcoming Treatment Resistance
The study, conducted by collaborators from the Instituto de Biología y Medicina Experimental (IBYME-CONICET) in Buenos Aires, Argentina, examined INB03's ability to enhance the effectiveness of existing HER2 (搜索)-targeted therapies. INB03 is a first-in-class dominant-negative soluble TNF (搜索) (sTNF) inhibitor that works differently from current TNF inhibitors by selectively neutralizing soluble TNF without affecting trans-membrane TNF or TNF receptors.
In laboratory studies, the combination of INB03 (10 µg/mL) with either lapatinib (1 µM) or tucatinib (10 µM) produced statistically superior inhibition of cell proliferation and migration in both HER2 (搜索)+ JIMT-1 and brain-metastatic JIMT-1 Br3-luc cell lines compared to TKIs alone, with significance levels ranging from p < 0.05 to p < 0.0001.
Significant Reduction in Metastatic Spread
Perhaps most notably, the preclinical data revealed that INB03 significantly reduced the incidence of metastases to critical organs including the brain, lungs, and liver. This was quantified using ex-vivo IVIS luminescence imaging in female nude mice bearing JIMT-1 or JIMT-1 Br3-luc tumors. The combination therapy markedly slowed tumor growth compared to TKIs alone and further enhanced tucatinib's effect on lung metastases with statistical significance of p < 0.05 to p < 0.0001.
"The ability of INB03 to overcome TKI resistance and limit metastatic dissemination, including to the brain, highlights its potential to address key unmet needs in advanced HER2 (搜索)-positive breast cancer," said Roxana Schillaci, Ph.D., the study's lead investigator.
Mechanism of Action
The therapeutic benefit appears to stem from INB03's ability to down-regulate MUC4 (搜索), a protein that shields the HER2 (搜索) molecule and prevents therapies from binding effectively. By selectively neutralizing soluble TNF (搜索), INB03 restores sensitivity to HER2-targeted therapies, potentially offering a solution for patients who have exhausted current treatment options.
"These results build on our prior work showing that selective sTNF neutralization with INB03 down-regulates MUC4 (搜索), restoring sensitivity to HER2 (搜索)-targeted therapies," Schillaci explained.
Clinical Implications
David Moss, CEO of INmune Bio, emphasized the broader therapeutic potential of the approach. "INB03 continues to demonstrate broad therapeutic potential across solid tumors by targeting the soluble TNF (搜索) pathway. These AACR data reinforce our confidence in advancing INB03 combinations in the clinic for patients who have developed resistance to standard TKIs or who are at high risk for brain metastases."
The company's XPro platform represents a next-generation approach to TNF (搜索) inhibition, currently in clinical trials with potential applications extending beyond oncology to neurologic diseases through its anti-neuroinflammatory effects.
Research Presentation
The complete findings are detailed in a poster titled "Soluble TNF (搜索) blockade overcomes tyrosine kinase inhibitors resistance in HER2 (搜索)-positive breast cancer," which was made available for viewing during the AACR 2026 meeting on April 21st. The research adds to the growing body of evidence supporting combination approaches to overcome treatment resistance in HER2-positive breast cancer, particularly for patients at high risk of brain metastases.