Purple Biotech Announces Publication in the Neuro Oncology Journal Demonstrating the Potential of NT219 to Suppress Brain Metastasis of Colorectal Cancer
Purple Biotech (NASDAQ/TASE: PPBT) announced the publication of a study in Neuro Oncology journal demonstrating NT219's potential to suppress brain metastasis in colorectal cancer. The research, conducted at Tel Aviv University and Sourasky Medical Center, reveals that NT219 combined with 5-flourouracil (5-FU) effectively inhibits colorectal cancer brain metastasis through the IRS2 pathway.
The study analyzed over 35,000 colorectal cancer samples, identifying IRS2 as a key driver of brain metastasis. NT219, a first-in-class small molecule drug, works by degrading IRS1/2 and blocking downstream signaling. The research shows particular promise for colorectal cancer patients, of whom 20% have distant metastasis at diagnosis and 50% develop metastasis later.
Purple Biotech is advancing NT219 into a Phase 2 study for recurrent/metastatic squamous cell carcinoma of the head and neck, with potential expansion into colorectal and other cancers.
Purple Biotech (NASDAQ/TASE: PPBT) ha annunciato la pubblicazione di uno studio sulla rivista Neuro Oncology che dimostra il potenziale di NT219 nel sopprimere le metastasi cerebrali nel cancro colorettale. La ricerca, condotta presso l'Università di Tel Aviv e il Sourasky Medical Center, rivela che NT219 combinato con 5-fluorouracile (5-FU) inibisce efficacemente le metastasi cerebrali del cancro colorettale attraverso la via IRS2.
Lo studio ha analizzato oltre 35.000 campioni di cancro colorettale, identificando IRS2 come un fattore chiave nello sviluppo delle metastasi cerebrali. NT219, un farmaco innovativo di prima classe, agisce degradando IRS1/2 e bloccando la segnalazione a valle. La ricerca mostra un particolare potenziale per i pazienti con cancro colorettale, di cui il 20% presenta metastasi a distanza alla diagnosi e il 50% sviluppa metastasi successivamente.
Purple Biotech sta portando avanti NT219 in uno studio di Fase 2 per il carcinoma squamoso ricorrente/metastatico della testa e del collo, con possibile estensione a tumori colorettali e altri tipi di cancro.
Purple Biotech (NASDAQ/TASE: PPBT) anunció la publicación de un estudio en la revista Neuro Oncology que demuestra el potencial de NT219 para suprimir las metástasis cerebrales en el cáncer colorrectal. La investigación, realizada en la Universidad de Tel Aviv y el Centro Médico Sourasky, revela que NT219 combinado con 5-fluorouracilo (5-FU) inhibe eficazmente las metástasis cerebrales del cáncer colorrectal a través de la vía IRS2.
El estudio analizó más de 35,000 muestras de cáncer colorrectal, identificando a IRS2 como un factor clave en el desarrollo de metástasis cerebrales. NT219, un fármaco innovador de primera clase, actúa degradando IRS1/2 y bloqueando la señalización downstream. La investigación muestra un gran potencial para los pacientes con cáncer colorrectal, de los cuales el 20% presenta metástasis a distancia al diagnóstico y el 50% desarrolla metástasis posteriormente.
Purple Biotech está avanzando con NT219 hacia un estudio de Fase 2 para carcinoma de células escamosas recurrente/metastásico de cabeza y cuello, con posible expansión a cáncer colorrectal y otros tipos de cáncer.
Purple Biotech (NASDAQ/TASE: PPBT)가 Neuro Oncology 저널에 NT219가 대장암 뇌전이를 억제할 수 있는 잠재력을 입증한 연구를 발표했습니다. 텔아비브 대학교와 소라스키 의료센터에서 진행된 연구에 따르면 NT219와 5-플루오로우라실(5-FU)의 병용이 IRS2 경로를 통해 대장암 뇌전이를 효과적으로 억제합니다.
이 연구는 35,000건 이상의 대장암 샘플을 분석하여 IRS2가 뇌전이의 주요 원인임을 밝혔습니다. NT219는 최초의 소분자 약물로 IRS1/2를 분해하고 하위 신호 전달을 차단하는 방식으로 작용합니다. 연구 결과는 진단 시 20%가 원격 전이를 가지고 있고 50%가 이후 전이를 겪는 대장암 환자들에게 특히 희망적입니다.
Purple Biotech는 재발성/전이성 두경부 편평세포암에 대해 2상 임상시험을 진행 중이며, 대장암 및 기타 암종으로의 확대 가능성도 모색하고 있습니다.
Purple Biotech (NASDAQ/TASE : PPBT) a annoncé la publication d'une étude dans la revue Neuro Oncology démontrant le potentiel de NT219 à supprimer les métastases cérébrales dans le cancer colorectal. La recherche, menée à l'Université de Tel Aviv et au Centre Médical Sourasky, révèle que NT219 combiné au 5-fluorouracile (5-FU) inhibe efficacement les métastases cérébrales du cancer colorectal via la voie IRS2.
L'étude a analysé plus de 35 000 échantillons de cancer colorectal, identifiant IRS2 comme un moteur clé des métastases cérébrales. NT219, un médicament innovant de première classe, agit en dégradant IRS1/2 et en bloquant la signalisation en aval. La recherche est particulièrement prometteuse pour les patients atteints de cancer colorectal, dont 20 % présentent des métastases à distance au moment du diagnostic et 50 % développent des métastases par la suite.
Purple Biotech fait progresser NT219 dans une étude de Phase 2 pour le carcinome épidermoïde récidivant/métastatique de la tête et du cou, avec une possible extension aux cancers colorectaux et autres.
Purple Biotech (NASDAQ/TASE: PPBT) gab die Veröffentlichung einer Studie im Journal Neuro Oncology bekannt, die das Potenzial von NT219 zur Unterdrückung von Hirnmetastasen beim kolorektalen Krebs zeigt. Die Forschung, durchgeführt an der Universität Tel Aviv und dem Sourasky Medical Center, zeigt, dass NT219 in Kombination mit 5-Fluorouracil (5-FU) Hirnmetastasen beim kolorektalen Krebs über den IRS2-Signalweg effektiv hemmt.
Die Studie analysierte über 35.000 kolorektale Krebsproben und identifizierte IRS2 als Schlüsselfaktor für Hirnmetastasen. NT219, ein neuartiges Small-Molecule-Medikament, wirkt durch den Abbau von IRS1/2 und die Blockade der nachgeschalteten Signalwege. Die Forschung zeigt besonderes Potenzial für Patienten mit kolorektalem Krebs, von denen 20 % bei Diagnose Fernmetastasen aufweisen und 50 % später Metastasen entwickeln.
Purple Biotech treibt NT219 in einer Phase-2-Studie für rezidivierenden/metastasierten Plattenepithelkarzinom des Kopf- und Halsbereichs voran, mit möglicher Ausweitung auf kolorektale und andere Krebsarten.
- First successful preclinical combination treatment for colorectal cancer brain metastasis
- Novel drug mechanism showing effectiveness in treating resistant cancers
- Advancing to Phase 2 clinical trials
- Large addressable market with 70% of colorectal cancer patients developing metastasis
- Still in early clinical development phases
- Efficacy in human subjects yet to be proven
- Competition from established cancer treatments
Insights
This publication represents a significant scientific advancement for Purple Biotech's NT219 drug candidate. The research identifies IRS2 as a previously unrecognized driver of brain metastasis in colorectal cancer and demonstrates that NT219's unique mechanism—covalently binding to IRS2 to trigger its degradation—can effectively suppress this metastatic pathway in preclinical models.
The combination of NT219 with standard chemotherapy (5-FU) showed impressive results in animal studies, inhibiting the formation of colorectal cancer brain metastasis and extending survival. This is particularly noteworthy as brain metastasis represents one of the most challenging treatment scenarios in oncology, with few effective options currently available.
The mechanistic insights are compelling: NT219 appears to modulate the β-catenin pathway and oxidative phosphorylation downstream of IRS2, potentially addressing cancer stem cells and drug resistance—two critical challenges in advanced cancer treatment. The validation from respected researchers at Tel Aviv University and Sourasky Medical Center adds substantial credibility to these findings.
While NT219 is currently advancing to Phase 2 for head and neck cancer, these findings could justify expanding clinical development into colorectal cancer, which represents a much larger market with approximately 70% of patients eventually developing metastasis. The identification of a novel mechanistic target in an otherwise treatment landscape positions NT219 as a potentially valuable addition to colorectal cancer therapy, particularly for patients with brain metastasis.
This peer-reviewed publication significantly strengthens Purple Biotech's scientific foundation by validating NT219's novel mechanism targeting the IRS2 pathway in colorectal cancer brain metastasis. The preclinical data showing extended animal survival when combining NT219 with standard chemotherapy represents a meaningful proof-of-concept for this small-cap biotech.
The strategic implications are substantial. While Purple Biotech is currently advancing NT219 into Phase 2 for head and neck squamous cell carcinoma, this publication provides scientific rationale for potential expansion into colorectal cancer—the third most diagnosed cancer globally. This represents a significant market opportunity expansion, as colorectal cancer affects millions worldwide with 20% having distant metastasis at diagnosis and another 50% developing it later.
The company's approach targeting IRS2 degradation represents a differentiated mechanism that could address treatment resistance. NT219's demonstrated ability to modulate β-catenin, AKT and metabolic pathways suggests potential applications beyond the currently studied indications.
For a company with a market cap of just $6.65 million, this scientific validation from independent researchers at respected institutions provides material support for the platform technology. While still in early clinical development, this publication enhances Purple Biotech's scientific credibility and suggests their lead compound may have applications in multiple high-need oncology indications, potentially increasing the company's overall value proposition.
Findings show combination therapy of NT219 and 5-flourouracil (5-FU) inhibits colorectal cancer brain metastasis through the IRS2 pathway
IRS2, a novel target of NT219, is identified as a driver of brain metastasis in colorectal cancer, by comprehensive research conducted by Prof. Wolf and Dr. Rubinek team at Tel Aviv University and Sourasky Medical Center
REHOVOT, Israel, April 16, 2025 (GLOBE NEWSWIRE) -- Purple Biotech Ltd. ("Purple Biotech" or "the Company") (NASDAQ/TASE: PPBT), a clinical-stage company developing first-in-class therapies that overcome tumor immune evasion and drug resistance, announced today the publication of an independent study titled “IRS2 as a driver of brain metastasis in colorectal cancer: a potential target for novel therapeutic strategies” in the peer reviewed journal, Neuro Oncology. NT219 is a first-in-class small molecule drug designed to target key cancer resistance mechanisms by degrading IRS1/2 and blocking downstream signaling towards AKT and b-catenin, as well as STAT3 survival pathways.
“Most cancer-associated deaths occur due to metastasis. Exploring how cancer cells choose where to metastasize, we reveal IRS2 as a major target in brain metastasis of colorectal cancer,” said the research’s Principal Investigator Dr. Tami Rubinek. “Furthermore, our findings suggest that suppressing IRS2 by NT219 may serve as a powerful strategy to suppress brain metastasis and overcome chemo-resistance. Our study shows that a combination of 5-FU and NT219 inhibited the formation of colorectal cancer brain metastasis and extended animal survival. To our knowledge, this is the first successful preclinical use of drug combination to treat colorectal cancer-associated brain metastasis.”
“These compelling findings suggest a potential opportunity to make a significant impact on prolonging the life of colorectal cancer patients, approximately
Background and Mechanism of Action
Colorectal cancer (CRC) has become the fourth leading cause of brain metastasis (BM), yet the mechanisms driving CRC BM formation remain largely elusive. CRC is the third most diagnosed cancer and the second-leading cause of cancer deaths worldwide.
The study analyzed over 35,000 CRC samples, providing insight into the biology of CRC BM. The study identifies a distinct genomic profile associated with CRC BM, highlighting the possible role of IRS2 in promoting BM formation. Additionally, the study found that heightened levels of IRS2 expression are more prevalent and clinically significant phenomenon in CRC BM. At the mechanistic level, the study suggests that IRS2 facilitates CRC BM through modulation of the β-catenin pathway and oxidative phosphorylation.
“The impact of NT219 on the b-Catenin, AKT and metabolic pathways downstream to IRS2 may correspond with its potential to suppress cancer stem cells, delay tumor recurrence and overcome drug resistance, as demonstrated in multiple preclinical models, and opens new opportunities to patients whose disease involves upregulation of these pathways,“ said Dr. Hadas Reuveni, VP R&D at Purple Biotech. “The unique mechanism by which NT219 covalently binds to IRS2 and triggers its degradation and elimination from cancer cells, introduces a novel modality of treatment that may address drug resistance in advanced tumors where other treatments have not succeeded.”
Importantly, the study demonstrates that combining 5-FU with NT219, an IRS2 inhibitor currently in early-phase clinical trials, may significantly impede the development of brain metastasis and extend survival rates. These findings advocate for the utilization of the novel IRS2 degrader NT219 as a potential therapeutic strategy against CRC BM, offering possible avenues for improved treatment strategies.
The study was conducted and published by a team of researchers led by Dr. Tami Rubinek, Head of the Oncology Research Lab, and Prof. Ido Wolf, MD, Head of Oncology Division, Tel Aviv Medical Center, Head of Tel Aviv University Medical School, and Head of Israeli National Council for the Prevention, Detection and Treatment of Malignant Diseases, in collaboration with Purple Biotech.
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 CM24, NT219, and CAPTN-3. CM24 is a humanized monoclonal antibody that blocks CEACAM1, which supports tumor immune evasion and survival through multiple pathways. CEACAM1 on tumor cells, immune cells, and neutrophil extracellular traps is a novel target for the treatment of multiple cancer indications. As proof of concept of these novel pathways, the Company completed a Phase 2 study for the treatment of pancreatic ductal adenocarcinoma (PDAC) with CM24 as a combination therapy with the anti-PD-1 checkpoint inhibitor nivolumab and chemotherapy, demonstrating clear and consistent improvement across all efficacy endpoints and the identification of two potential serum biomarkers. NT219 is a dual inhibitor, novel small molecule that simultaneously targets IRS1/2 and STAT3. A Phase 1 dose escalation study was concluded as a monotherapy and in combination with cetuximab, in which NT219 demonstrated anti-tumor activity in combination with cetuximab in second-line patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/N SCCHN). The Company is advancing NT219 into a Phase 2 study in collaboration with the University of Colorado, to treat R/M SCCHN patients in combination with cetuximab or pembrolizumab. The Company is advancing CAPTN-3, a preclinical platform of conditionally activated tri-specific antibodies, which engage both T cells and NK cells to induce a strong, localized immune response within the tumor microenvironment. The cleavable capping technology confines the compound's therapeutic activity to the local tumor microenvironment, thereby potentially increasing 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 the 5T4 antigen, which is expressed in a variety of solid tumors and is associated with advanced disease, increased invasiveness, and poor clinical outcomes. The Company's corporate headquarters are located in Rehovot, Israel. For more information, please visit https://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, 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, 2024 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, https://www.sec.gov.
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