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.
Forward-Looking Statements and Safe Harbor Statement
Certain statements in this press release that are forward-looking and not statements of historical fact are forward-looking statements within the meaning of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements include, but are not limited to to, statements which are not statements of historical fact and which can be identified by words such as “believe”, “expect”, “intend”, “plan”, “may”, “should”, “could”, “could”, “seek”, “target”, “will”, “project”, “plan”, “continue” or “anticipate” or their negatives or variations of these words or other comparable words or that these statements do not relate strictly to historical matters. You should not place undue reliance on these forward-looking statements, which are not guarantees of future performance. Forward-looking statements reflect our current opinions, expectations, beliefs or intentions regarding future events, and are subject to a number of assumptions, involve known and unknown risks, many of which are beyond our control, as well as uncertainties and other factors. which may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements. Important factors that could cause or contribute to such differences include, among others, risks relating to: management’s plans, strategies and objectives for future operations; product development for NT219 and CM24; the process by which early-stage therapeutic candidates such as NT219 and CM24 could potentially lead to an approved drug is long and subject to very significant risks, especially in the context of a joint development collaboration; the fact that the development and commercialization of drugs involves a long and expensive process with uncertain results; our ability to successfully develop and commercialize our pharmaceutical products; the expenses, duration, progress and results of any clinical trial; the impact of any changes in regulations and legislation that could affect the pharmaceutical industry; difficulty in obtaining the regulatory approvals required to market our products; the difficulty of predicting the actions of the United States Food and Drug Administration or any other regulatory agency applicable to pharmaceuticals; the regulatory environment and changes in healthcare policies and regimes in the countries in which we operate; uncertainty surrounding the actual market reception of our pharmaceutical products once approved for sale in a particular market; the introduction of competing products; patents obtained by competitors; dependence on the effectiveness of our patents and other protections for innovative products; our ability to obtain, maintain and defend issued patents; the commencement of any patent interference or infringement action against our patents, and our ability to prevail, obtain a favorable judgment or recover damages in such action; and exposure to litigation, including patent litigation and/or regulatory actions, and other factors which are discussed in our Annual Report on Form 20-F for the fiscal year ended December 31, 2020 and in our other filings with the United States Securities and Exchange Commission (“SEC”), including our cautionary note about risks and uncertainties under the heading “Risk Factors” in our registration statements and our annual reports. These are factors that we believe could cause our actual results to differ materially from expected results. Factors other than those we have listed could also negatively affect us. Any forward-looking statement in this press release speaks only as of the date on which it is made. We disclaim any intention or obligation to publicly update or revise any forward-looking statements or other information contained herein, whether as a result of new information, future events or otherwise, except as required by applicable law. . You are, however, advised to review any additional disclosures we make in our reports to the SEC, which are available on the SEC’s website, https://www.sec.gov.
Company Contact:
Gil Efron
President and Chief Financial Officer
IR@purple-biotech.com
Contact with Investor Relations:
Chuck Padala
chuck@lifesciaadvisors.com
+1 646-627-8390
Media Contact:
Megan Humphreys
megan@mlhconsulting.com
