CM-24

Purple Biotech believes CM24 helps block pancreatic cancer cells from evading the body’s immune response in addition to developing resistance against drugs like Bristol Myers Squibb’s Opdivo. Purple Biotech hopes its lead asset against metastatic pancreatic cancer will one day show its true colors as a potential first-in-class drug in a larger study—but, for now, it has preliminary, midstage trial results demonstrating measurable gains in overall survival. Presented at the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago, the late-breaking poster data from the company’s phase 2b trial also illustrated improvements in progression-free survival as well as in a diagnostic biomarker linked to pancreatic ductal adenocarcinoma. Purple’s anti-CEACAM1 antibody, dubbed CM24, was offered to previously treated patients in combination with Bristol Myers Squibb’s Opdivo (nivolumab), alongside the physician’s choice between one of two standard-of-care chemotherapy regimens—either gemcitabine and nab-paclitaxel, or liposomal irinotecan plus 5-fluorouracil and leucovorin. Those patients were then compared to those who received either chemotherapy regimen alone. According to the company, the randomized, open-label study was not powered for hypothesis testing. While the interim findings delivered at ASCO consider 31 patients split between the two arms—with a data cutoff of May 8—the trial as a whole enrolled 63 participants across the U.S., Spain and Israel. Broader top-line results are expected in the latter half of this year. The study is also open to patients with other solid tumors, including colorectal cancer, non-small cell lung cancer, ovarian cancer and melanoma. The addition of CM24 and Opdivo was able to extend median overall survival in pancreatic cancer by 2.1 months and median progression-free survival by 1.9 months. According to the company, this also resulted in about a 26% reduction in the risk of death.  Purple believes that by blocking the checkpoint protein CEACAM1 on white blood cells with CM24, tumor cells will have a harder time evading the body’s immune responses as well as developing resistance to other checkpoint inhibitors such as Opdivo, which has struggled to succeed as a monotherapy in other studies against advanced pancreatic cancer, a notoriously recalcitrant disease. “These patients face very limited time with their families, and the prospect of potentially lengthening their lives while delaying their disease progression by approximately two months overall is clinically meaningful,” principal investigator Michael Cecchini, M.D., an assistant professor of medicine at Yale Cancer Center, said in a statement. “These data justify further investigation of CM24 in combination with nivolumab together with standard-of-care chemotherapy to potentially improve outcomes for patients facing a very poor prognosis from this type of tumor.” The initial data captured a total median OS of 7.72 months compared to 5.62 months in the control arm, as well as median PFS times of 3.8 months and 1.9 months, respectively. In addition, overall response rates were logged as 25% versus 7%—with four partial responses, plus one in the control arm—while disease control rates reached 63% compared to 40%. The study also noted patients’ levels of CA19-9, a common clinical serum biomarker used to help predict pancreatic tumor stages and responses to therapy, radiation and surgery. Purple said there was “a consistent and continuous decrease of CA19-9” over a span of 16 weeks, amounting to 61% on average among the second-line patients that received CM24 and Opdivo, compared to an increase of 34% within the control arm. In terms of safety, 15 out of the 16 patients in the experimental arm reported serious side effects, listed as grade 3 and above, compared to 10 out of 15 in the control arm. The most common included diarrhea and fatigue, and the company described the adverse events as manageable. Both sides of the study recorded patients’ median time from their initial diagnoses as 18 months. “We are highly encouraged by the meaningful results of our primary endpoint, overall survival, as well as by the concordant and consistent improvement in all secondary endpoints including PFS, ORR, DCR and CA19-9,” said Gil Efron, CEO of Purple, which picked up CM24 through the 2020 acquisition of FameWave when the company was known as Kitov Pharma.

REHOVOT, Israel, Feb. 01, 2024 (GLOBE NEWSWIRE) -- Purple Biotech Ltd. ("Purple Biotech" or "the Company") (NASDAQ/TASE: PPBT), a clinical-stage company developing first-in-class therapies that harness the power of the tumor microenvironment to overcome tumor immune evasion and drug resistance, today 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.” About NT219 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. About Purple Biotech 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, please visit . 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, statements that are not statements of historical fact, and may be identified by words such as "believe", "expect", "intend", "plan", "may", "should", "could", "might", "seek", "target", "will", "project", "forecast", "continue" or "anticipate" or their negatives or variations of these words or other comparable words or by the fact 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 views, expectations, beliefs or intentions with respect to 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 that may cause our actual results, performance or achievements to be significantly 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: the plans, strategies and objectives of management for future operations; product development for NT219, CM24 and IM1240; the process by which such early stage therapeutic candidates could potentially lead to an approved drug product is long and subject to highly significant risks, particularly with respect to a joint development collaboration; the fact that drug development and commercialization involves a lengthy and expensive process with uncertain outcomes; our ability to successfully develop and commercialize our pharmaceutical products; the expense, length, progress and results of any clinical trials; the impact of any changes in regulation and legislation that could affect the pharmaceutical industry; the difficulty in receiving the regulatory approvals necessary in order to commercialize our products; the difficulty of predicting actions of the U.S. Food and Drug Administration or any other applicable regulator of pharmaceutical products; the regulatory environment and changes in the health policies and regimes in the countries in which we operate; the uncertainty surrounding the actual market reception to our pharmaceutical products once cleared for marketing 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 decision or recover damages in any such action; and the exposure to litigation, including patent litigation, and/or regulatory actions, and other factors that are discussed in our Annual Report on Form 20-F for the year ended December 31, 2022 and in our other filings with the U.S. Securities and Exchange Commission ("SEC"), including our cautionary discussion of risks and uncertainties under "Risk Factors" in our Registration Statements and Annual Reports. These are factors that we believe could cause our actual results to differ materially from expected results. Other factors besides those we have listed could also adversely affect us. Any forward-looking statement in this press release speaks only as of the date which it is made. We disclaim any intention or obligation to publicly update or revise any forward-looking statement or other information contained herein, whether as a result of new information, future events or otherwise, except as required by applicable law. You are advised, however, to consult any additional disclosures we make in our reports to the SEC, which are available on the SEC's website, . CONTACTS: Company Contact: Lior Fhima Chief Financial Officer IR@purple-biotech.com