Cantargia reported new preclinical data highlighting how nadunolimab, an IL1RAP-targeting antibody currently in phase II clinical development, may induce antitumor activity in pancreatic cancer by blocking fibrosis. The data will be presented as a poster at the American Association for Cancer Research (AACR) Annual Meeting 2024 in San Diego and were generated in a collaboration with Nordic Bioscience A/S and the group of Dr. Marcus Järås at Lund University. Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease with poor survival prognosis.

Nadunolimab is currently in phase II clinical development in first line PDAC and has shown pronounced effects including a much longer survival than expected from historical controls. One factor that significantly contributes to the poor treatment response in PDAC is the high abundance of tumor-supporting stroma, driven by the excessive activity of cancer-associated fibroblasts (CAFs). The new data now show that in pancreatic cancer-associated fibroblasts, interleukin-1alpha (IL-1alpha) and IL-1beta both induce formation of type III collagen (as measured by PRO-C3), a biomarker which has been found to correlate with poor survival in PDAC.

Similarly, formation of type III collagen could also be induced by pancreatic cancer cells when co-cultured with pancreatic CAFs. Notably, addition of nadunolimab to the in vitro co-cultures potently blocked the induction of type III collagen formation. Thus, the new data strengthen the role of IL-1alpha and IL-1beta in pancreatic tumor fibrosis and highlight the potential for nadunolimab to counter the detrimental, fibrotic microenvironment in PDAC tumors.