Purple Biotech reports NT219 data at AACR meeting

Purple Biotech (PPBT) announced that two posters reporting new NT219 data being presented at the American Association for Cancer Research Annual Meeting on Sunday and Monday, April 27-28, 2025. NT219, a novel dual inhibitor of IRS1/2 and STAT3, is being evaluated in a Phase 2 study in patients with recurrent and/or metastatic head and neck squamous cell cancer in combination with pembrolizumab and in combination with cetuximab. Key highlights from the posters include the following: Poster Title-“NT219 overcomes immune evasion mechanisms in head and neck squamous cell carcinoma”: NT219 mitigates several immune evasion mechanisms including cancer stem cell-mediated resistance and resulting tumor recurrence, and sensitizes resistant HNSCC tumors to PD1 and EGFR therapies. NT219 inhibits major targets and signaling pathways playing a key role in tumor immune evasion, including STAT3 and IRS-to-beta-catenin pathways. In a clinical setting, upregulation of pIGF1R and pSTAT3 were correlated with patient response and suggested as potential biomarkers for NT219 treatment. Immunosuppressive mechanisms such as IL-10 secretion induced by anti-PD1 treatment, were suppressed by NT219, supporting the synergistic anti-tumor activity observed These data demonstrate the potential of NT219 to restore the efficacy of immunotherapies and expand the patient population that can benefit from these drugs. Poster Title-“APC-loss as a potential biomarker for NT219 treatment in colorectal cancer”: The anti-tumor efficacy of NT219 monotherapy in screens of about 30 patient-derived xenograft models and colorectal patient-derived explants, along with genomic and transcriptomic analysis, suggest that the response to NT219 is associated with enhanced wnt/beta-catenin signaling or loss of function mutation of its negative regulator APC. The results suggest APC-loss or upregulated beta-catenin as a potential biomarker for NT219 treatment in CRC. In addition, NT219 reversed chemo-resistance and synergized with approved chemotherapy as demonstrated in multiple models including PDE with APC-loss and activated PI3K mutations, and in-vivo intracranial model with activating mutation in beta-catenin.