Purple Biotech Initiates Phase 2 Study for NT219 in R/M SCCHN Patients

Purple Biotech has initiated a Phase 2 clinical study to evaluate NT219 in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). The study will assess the efficacy of NT219 in combination with pembrolizumab or cetuximab to overcome tumor resistance. NT219 is a small molecule that targets IRS1/2 and STAT3 pathways, blocking their signaling pathways. The study aims to evaluate the potential of NT219 as a first-in-class therapy to overcome tumor immune evasion and drug resistance.

Rehovot, Israel — June 17, 2025 — Purple Biotech Ltd. (NASDAQ/TASE: PPBT) has announced the initiation of a Phase 2 clinical study to evaluate NT219 in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). The study aims to assess the efficacy of NT219 in combination with either pembrolizumab or cetuximab to overcome tumor resistance.

NT219 is a novel small molecule designed to target two key oncogenic pathways: IRS1/2 (Insulin Receptor Substrates 1 and 2) and STAT3 (Signal Transducer and Activator of Transcription 3). By inducing the degradation of IRS1/2 and inhibiting the phosphorylation of STAT3, NT219 blocks these signaling pathways, potentially reversing drug resistance and improving outcomes for patients with R/M SCCHN.

The Phase 2 study, led by Dr. Antonio Jimeno at the University of Colorado Anschutz Medical Campus, will evaluate NT219 in two single-arm cohorts. One cohort will assess NT219 in combination with pembrolizumab, while the other will evaluate NT219 in combination with cetuximab. Each cohort will follow a Simon 2-stage design, beginning with 10 patients per arm and potentially expanding to a total of 29 patients per arm.

This Phase 2 study builds upon encouraging results from the Phase 1 study, which demonstrated the safety and anti-tumor activity of NT219 in combination with cetuximab. The study also aims to evaluate potential biomarkers identified in a previous clinical study of NT219.

The SCCHN treatment market is projected to reach $5 billion by 2030, driven by the need for more effective treatments for R/M SCCHN. The development of such treatments is hindered by tumor heterogeneity, therapeutic resistance, and a lack of reliable biomarkers.

Purple Biotech is a clinical-stage company developing first-in-class therapies to overcome tumor immune evasion and drug resistance. Its oncology pipeline includes CM24, NT219, and CAPTN-3. CM24 is a humanized monoclonal antibody that blocks CEACAM1, supporting tumor immune evasion and survival through multiple pathways. NT219 is a dual inhibitor that simultaneously targets IRS1/2 and STAT3. CAPTN-3 is a preclinical platform of conditionally activated tri-specific antibodies that engage both T cells and NK cells to induce a strong, localized immune response within the tumor microenvironment.

For more information, please visit [Purple Biotech's website](https://purple-biotech.com/).

References:
[1] https://www.nasdaq.com/press-release/purple-biotech-announces-initiation-phase-2-study-nt219-patients-head-and-neck-cancer