Purple Biotech Reaches Recommended Phase 2 Dose for NT219

Purple Biotech Ltd. recently 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.

Detailed clinical results from the dose escalation portion of the study are intended to be presented at the European Society of Medical Oncology Targeted Anticancer Therapies (ESMO TAT) Congress 2024 in Paris on February 26, 2024, in an Oral Presentation titled Interim results of a Phase 1/2 trial of NT219 in combination with cetuximab in patients with advanced/metastatic Squamous Cell Carcinoma of the Head and Neck (SCCHN).

“This is a major milestone for the development of NT219 for an indication in need of more effective therapies. As we progress into a Phase 2 study, our goal is to establish NT219 as standard of care for squamous cell carcinoma of the head and neck for patients who have not responded to first line treatments,” stated Gil Efron, Chief Executive Officer of Purple Biotech. “We look forward to treating more patients with NT219 in a Phase 2 study.”

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 signaling pathways that play a key role in the tumor and its microenvironment. IRS1/2 acts as scaffolds, organizing signaling 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.

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 NT219, CM24 and IM1240. NT219 is a dual inhibitor, novel small molecule that simultaneously targets IRS1/2 and STAT3. A phase 2 study of NT219 at its recommended Phase 2 level in combination with cetuximab in patients with recurrent and/or metastatic SCCHN is planned. CM24 is a humanized monoclonal antibody that blocks CEACAM1, an immune checkpoint protein that supports tumor immune evasion and survival through multiple pathways. The company is advancing CM24 as a combination therapy with anti-PD-1 checkpoint inhibitors in a Phase 2 study for the treatment of pancreatic ductal adenocarcinoma (PDAC). The company has entered into a clinical collaboration agreement with Bristol Myers Squibb for the Phase 2 clinical trials to evaluate the combination of CM24 with the PD-1 inhibitor nivolumab in addition to chemotherapy. The company is advancing a preclinical platform of conditionally-activated tri-specific antibody that engages both T cells and NK cells to mount a strong, localized immune response within the tumor microenvironment. The cleavable capping technology confines the compound’s therapeutic activity to the local tumor microenvironment, and thereby potentially increases 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 5T4 expressed in a variety of solid tumors and is correlated with advanced disease, increased invasiveness and poor clinical outcomes. The company’s corporate headquarters are located in Rehovot, Israel. For more information, visit https://purple-biotech.com/.