Purple Biotech Ltd. announced it has determined 100mg/kg is the recommended Phase 2 dose (RP2D) for NT219 in combination with cetuximab in the treatment of head and neck cancer based on its Phase 1/2 dose escalation study (NCT04474470). NT219 is a first-in-class small molecule dual inhibitor of IRS1/2 and STAT3. The RP2D was determined based on data from the open-label dose escalation study designed to assess the safety, pharmacokinetics, pharmacodynamics and efficacy of NT219 in combination with Erbitux® (cetuximab), in previously treated recurrent and/or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN) patients.

The Company recently reported that NT219, in combination with cetuximab, demonstrated a dose dependent anti-tumor activity with confirmed partial responses. No dose-limiting toxicities were reported. The additional supporting data used for this determination was pharmacokinetics of NT219 across all dose levels.

Further dose optimization is planned for future studies. The Phase 1 dose escalation study is being concluded and the remaining patients? data are expected to be reported during the first half of 2024.

The Company is now advancing its upcoming Phase 2 Proof of Concept study of NT219 for the treatment of R/M SCCHN. NT219 is a first-in-class, small molecule that promotes Insulin Receptor Substrates 1/2 (IRS) degradation and inhibits Signal Transducer and Activator of Transcription 3 (STAT3) phosphorylation, two major complementary signalling pathways that play a key role in the tumor and its microenvironment. IRS1/2 acts as scaffolds, organizing signalling complexes that mediate mitogenic, metastatic, angiogenic, and anti-apoptotic signals from IGF1R and other oncogenes, consisting of an important driver in multiple cancers and is highly involved in triggering drug resistance.

STAT3 is a transcription factor that is broadly hyperactivated in many cancers, promoting proliferation, survival, angiogenesis, metastasis, and tumor immune evasion. Feedback activation of STAT3 plays a prominent role in mediating drug resistance to various anti-cancer therapies. As an inhibitor of both IRS1/2 and STAT3, NT219 has the potential to prevent the development of resistance to multiple approved therapies.