Highlights of research underlying IRS1 phosphorylation status as a memory mechanism that modulates non-genetic cellular resistance to drug therapy
NT219, which targets the IRS, was shown to be highly synergistic with anti-EGFR therapy, leading to tumor regression and delayed recurrence
REHOVOT, Israel, Oct. 22, 2021 (GLOBE NEWSWIRE) — Purple Biotech (NASDAQ/TASE: PPBT), a clinical-stage company developing innovative, effective and sustainable therapies by overcoming tumor immune evasion and drug resistance , today announced a publication in nature cancer which provides novel insights into the underlying mechanism of cancer cell therapy resistance and the important role of insulin receptor substrate 1 (IRS1) pathway on epithelial growth factor receptor inhibition therapy (EFGR). NT219, currently being evaluated in a phase 1/2 clinical trial, is a new small molecule that simultaneously inhibits IRS1/2 and STAT3.
The article is titled “IRS1 Phosphorylation Underlies the Nonstochastic Probability of Cancer Cell Persistence During EGFR Inhibition Treatment” and is available online at: https://www.nature.com/articles/s43018-021-00261-1. The senior author of the publication is Ravid Straussman, MD, Ph.D., Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
The article demonstrated mechanistic evidence for the hereditary therapeutic resistance of cancer cells, called the chance to persist (CTP). EGFR CTP inhibition has been shown in preclinical models to be modulated by serine/threonine phosphorylation of IRS1. Specifically, higher phosphorylation of multiple serine/threonine sites of IRS1, which blocks IRS1 activity, has been shown to lead to increased susceptibility to EGFR inhibitors. A combination of NT219, which triggers serine phosphorylation and subsequent degradation of IRS1 and EGFR inhibitors, resulted in a synergistic effect, resulting in tumor regression and delayed recurrence upon discontinuation of therapy.
“These results provide new insights into the regulation of cell persistence and advance understanding of IRS1 inhibition in cancer phenotype, as well as highlight the potential of NT219 to enhance tumor cell resistance to cancer. apoptosis,” said Hadas Reuveni, Ph.D., VP Research and Development of Purple Biotech. “The results reinforce our previously published data on synergistic effects with certain anti-cancer agents and further support our clinical development strategy of combining NT219 with anti-EGFR inhibitors.”
About Purple Biotech
Purple Biotech Ltd. is a clinical-stage company developing cutting-edge therapies by overcoming tumor immune evasion and drug resistance. The Company’s oncology pipeline includes NT219 and CM24. NT219 is a dual inhibitor, a new small molecule that simultaneously targets IRS1/2 and STAT3. The Company is currently advancing NT219 as a monotherapy treatment for solid tumors, followed by an increased dose of NT219 in combination with cetuximab for the treatment of recurrent and/or metastatic squamous cell carcinoma of the head and neck ( SCCHN) or colorectal adenocarcinoma in a phase 1/2 study, and an expansion phase of NT219 to its recommended phase 2 level in combination with cetuximab in patients with squamous cell carcinoma of the head and recurrent and/or metastatic neck. CM24 is a humanized monoclonal antibody that blocks CEACAM1, an immune checkpoint protein that supports immune evasion and tumor survival through multiple pathways. The Company is advancing CM24 as a combination therapy with anti-PD-1 checkpoint inhibitors in selected cancer indications in a Phase 1b study followed by a Phase 2 study for the treatment of lung cancer non-small cell and pancreatic cancer. The Company has entered into a clinical collaboration agreement, as amended, with Bristol Myers Squibb for phase 1/2 clinical trials planned to evaluate the combination of CM24 with the PD-1 inhibitor nivolumab (Opdivo®) in patients with non-small cell disease. lung cancer and in combination with nivolumab in addition to nab-paclitaxel (Abraxane®) in patients with pancreatic cancer. The Company’s head office is located in Rehovot, Israel. For more information, please visit https://www.purple-biotech.com.
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