Purple Biotech Reports Positive NT219 Data for Colorectal & Head & Neck Cancers

Purple Biotech Ltd. recently announced two posters reporting new NT219 data presented at the American Association for Cancer Research (AACR 2025) 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 (R/M HNSCC) in combination with pembrolizumab (anti-PD1) and in combination with cetuximab (anti-EGFR).

“The poster presents a significant upregulation of STAT3, IRS1/2 and b-catenin in HNSCC tumors and tumor microenvironment as compared to normal tissues, and a similar trend per tumor stage. Together with the unique mechanism of NT219 as a suppressor of STAT3 and a degrader of IRS1/2, which blocks IGF1R/IRS and downstream AKT and b-catenin signaling, we revealed that the activated forms of STAT3 and IGF1R are associated with the patient response to NT219-based therapy, suggesting these targets as potential biomarkers,” stated Purple Biotech VP R&D Dr. Hadas Reuveni. “STAT3 and b-catenin, as well as cancer stem cells, are major immune evasion and tumor recurrence mechanisms, suppressed by NT219. This mechanistic rationale and preclinical in-vivo and ex-vivo results demonstrating repression of anti-PD1 refractory tumors, support NT219 and anti-PD1 combination therapy that will be administered to R/M HNSCC patients in our Phase 2 clinical study.”

“Activation of b-catenin or loss of its negative suppressor APC play a key role in colorectal cancer, and we have previously shown that NT219 efficiently blocks the IRS2 to b-catenin pathway, inhibiting CRC metastasis and chemo-resistance,” added Hadas Reuveni. “Here we reveal that these elements may serve as potential biomarkers for NT219-based therapy in CRC, based on extended in-vivo and ex-vivo patient-derived screens.”

“These biomarker and mechanism data are important guides for study design, patient selection, and combination therapy strategies for NT219,” stated Purple Biotech CEO Gil Efron. “This new data is highly encouraging and support our current NT219 Phase 2 study in head and neck cancer. We were pleased to share these data at the prestigious AACR annual meeting.”

Key highlights from the posters included the following:

Poster Title—NT219 overcomes immune evasion mechanisms in head and neck squamous cell carcinoma (HNSCC)

• 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-β-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 (PDX) models and colorectal (CRC) patient-derived explants (PDE), along with genomic and transcriptomic analysis, suggest that the response to NT219 is associated with enhanced wnt/β-catenin signaling or loss of function mutation of its negative regulator APC (APC-loss).
• The results suggest APC-loss or upregulated β-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 β-catenin.

The NT219’s posters are available at the Publication section on Purple Biotech’s website following its presentation at the conference.

Purple Biotech Ltd. (NASDAQ/TASE: PPBT) is a clinical-stage company developing first-in-class therapies that seek to overcome tumor immune evasion and drug resistance. The Company’s oncology pipeline includes CM24, NT219, and CAPTN-3. CM24 is a humanized monoclonal antibody that blocks CEACAM1, which supports tumor immune evasion and survival through multiple pathways. CEACAM1 on tumor cells, immune cells and neutrophil extracellular traps is a novel target for the treatment of multiple cancer indications. As proof of concept of these novel pathways, the Company completed a Phase 2 study for the treatment of pancreatic ductal adenocarcinoma (PDAC) with CM24 as a combination therapy with the anti-PD-1 checkpoint inhibitor nivolumab and chemotherapy, demonstrating clear and consistent improvement across all efficacy endpoints and the identification of two potential serum biomarkers. NT219 is a dual inhibitor, novel small molecule that simultaneously targets IRS1/2 and STAT3. A Phase 1 dose escalation study was concluded as a monotherapy and in combination with cetuximab, in which NT219 demonstrated anti-tumor activity in combination with cetuximab in second-line patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). The Company is advancing NT219 into a Phase 2 study in collaboration with the University of Colorado, to treat R/M SCCHN patients in combination with cetuximab or pembrolizumab. The Company is advancing CAPTN-3, a preclinical platform of conditionally activated tri-specific antibodies, which engage both T cells and NK cells to induce a strong, localized immune response within the tumor microenvironment. The cleavable capping technology confines the compound’s therapeutic activity to the local tumor microenvironment, thereby potentially increasing the anticipated therapeutic window in patients. The third arm specifically targets the Tumor Associated Antigen (TAA). The technology presents a novel mechanism of action by unleashing both innate and adaptive immune systems to mount an optimal anti-tumoral immune response. IM1240 is the first tri-specific antibody in development that targets the 5T4 antigen, which is expressed in a variety of solid tumors and is associated with advanced disease, increased invasiveness, and poor clinical outcomes. The Company’s corporate headquarters are located in Rehovot, Israel. For more information, please visit https://purple-biotech.com/.