New preclinical data from Israel-based Can-Fite BioPharma Ltd. (NYSE American: CANF) show that namodenoson, an oral A3 adenosine receptor (A3AR) agonist, enhances the pro-apoptotic effect of gemcitabine in pancreatic cancer cells — findings the Israel-based company says support the design of its planned Phase IIb combination study in advanced pancreatic adenocarcinoma.
In preclinical experiments, the combination of namodenoson and gemcitabine elevated levels of cleaved caspase-3, a central executioner protein in the apoptotic cascade, relative to either agent alone. Can-Fite said this indicates namodenoson suppresses survival pathways in pancreatic cancer cells, increasing their susceptibility to cytotoxic chemotherapy. The company did not disclose quantitative preclinical data, such as fold-changes or dose-response relationships, in the announcement.
The findings arrive as Can-Fite prepares to move namodenoson into a randomized Phase IIb trial evaluating the drug in combination with gemcitabine and nab-paclitaxel in patients with advanced pancreatic adenocarcinoma. The new data provide mechanistic support for combining namodenoson with the gemcitabine component of that regimen, although the preclinical experiments disclosed by Can-Fite did not test the full three-drug combination
The clinical backdrop matters for interpreting the combination rationale. Can-Fite's completed Phase IIa monotherapy study enrolled 20 patients with advanced pancreatic ductal adenocarcinoma who had progressed on prior therapy. The study met its primary safety endpoint, with no new signals identified. An updated survival analysis reported median OS exceeding five months among eight evaluable third-line patients who survived at least two months after treatment initiation; six other third-line patients with rapidly progressive disease were excluded from that analysis. Those results were accepted for poster presentation at ESMO Congress 2026. Though potentially encouraging in a treatment setting where outcomes are uniformly poor, the single-arm, open-label design and small patient numbers preclude efficacy conclusions.
Namodenoson binds selectively to A3AR, a G protein-coupled receptor that is overexpressed on tumor cells relative to normal tissue. Receptor activation is proposed to deregulate downstream Wnt/β-catenin, NF-κB, and RAS signaling, leading to GSK-3β upregulation, cyclin D1 suppression, and tumor cell apoptosis. Can-Fite has previously highlighted the RAS pathway component as particularly relevant in pancreatic cancer, where KRAS mutations drive approximately 90% of cases. The new caspase-3 data add a direct apoptotic readout to that mechanistic picture, suggesting the drug may prime cancer cells for chemotherapy-induced death rather than simply acting in parallel.