Core Insights - Purple Biotech Ltd. presented new preclinical data on its CAPTN-3 tri-specific antibody platform at the EACR 2025, showcasing its potential to overcome tumor immune evasion and drug resistance [1][2] Group 1: CAPTN-3 Platform Overview - The CAPTN-3 platform enables the creation of tri-specific antibodies that activate both innate and adaptive immune systems, enhancing anti-tumor responses [2][6] - The lead product, IM1240, targets the 5T4 antigen and has shown robust in vivo anti-tumor activity, particularly in triple negative breast cancer models [7][10] - The design includes an anti-NKG2A arm that synergizes with the anti-CD3 arm, demonstrating significant cytotoxic effects against solid tumor cells [3][4][5] Group 2: Mechanism of Action - The CAPTN-3 platform features a conditional activation mechanism, where the CD3 arm is activated only in the tumor microenvironment, minimizing systemic effects [6][7] - The anti-NKG2A arm plays a crucial role in reinvigorating exhausted T cells, enhancing their ability to kill tumor cells [4][5] - The platform's design allows for a modular approach, enabling the development of various tribodies with different target combinations [7][10] Group 3: Clinical Implications - Preclinical data indicate that the CAPTN-3 platform can lead to sustained tumor regression in animal models, highlighting its therapeutic potential [5][7] - The platform's ability to engage both T cells and NK cells suggests a promising avenue for developing effective cancer therapies [6][10] - The company is advancing multiple candidates within its oncology pipeline, including CM24 and NT219, alongside CAPTN-3 [10]

Company Overview - Purple Biotech Ltd. is a clinical-stage company focused on developing first-in-class therapies to overcome tumor immune evasion and drug resistance [6] - The company's oncology pipeline includes NT219, CM24, and CAPTN-3, with NT219 being a dual inhibitor targeting IRS1/2 and STAT3 [6][7] Clinical Study Initiation - A Phase 2 clinical study has been initiated to evaluate NT219 in combination with either pembrolizumab or cetuximab for patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) [1][4] - The study is led by Dr. Antonio Jimeno at the University of Colorado Anschutz Medical Campus and structured into two single-arm cohorts [3] Mechanism of Action - NT219 is designed to induce degradation of IRS1/2 and inhibit phosphorylation of STAT3, blocking their signaling pathways [2] - Previous Phase 1 studies showed safety and anti-tumor activity of NT219 in combination with cetuximab, with two partial responses and five patients with stable disease [4] Market Potential - The SCCHN treatment market is projected to reach $5 billion by 2030, highlighting the need for more effective treatments due to challenges like tumor heterogeneity and therapeutic resistance [5]

Core Insights - Purple Biotech Ltd. is a clinical-stage company focused on developing first-in-class therapies to combat tumor immune evasion and drug resistance [1][3] - The company will present its novel CAPTN-3 tri-specific antibody platform at the EACR 2025 Annual Congress in Lisbon, Portugal [1][2] Company Overview - Purple Biotech's oncology pipeline includes CM24, NT219, and CAPTN-3, with CM24 being a humanized monoclonal antibody targeting CEACAM1, which is involved in tumor immune evasion [3] - A Phase 2 study of CM24 in combination with nivolumab and chemotherapy for pancreatic ductal adenocarcinoma showed significant improvement across all efficacy endpoints [3] - NT219 is a dual inhibitor targeting IRS1/2 and STAT3, with a completed Phase 1 study demonstrating anti-tumor activity in combination with cetuximab for recurrent and/or metastatic squamous cell carcinoma of the head and neck [3] - CAPTN-3 is a preclinical platform utilizing conditionally activated tri-specific antibodies to engage T cells and NK cells, aiming to enhance localized immune responses within the tumor microenvironment [3] - The first tri-specific antibody, IM1240, targets the 5T4 antigen, which is associated with various solid tumors and poor clinical outcomes [3]

Core Viewpoint - Purple Biotech Ltd. is advancing its clinical-stage therapy NT219, which targets tumor immune evasion and drug resistance, with promising data presented at the AACR 2025 Annual Meeting [1][3][10] Group 1: NT219 Overview - NT219 is a novel dual inhibitor of IRS1/2 and STAT3, currently in a Phase 2 study for recurrent and/or metastatic head and neck squamous cell carcinoma (R/M HNSCC) in combination with pembrolizumab and cetuximab [2][10] - The mechanism of NT219 involves suppression of STAT3 and degradation of IRS1/2, which blocks IGF1R/IRS and downstream AKT and β-catenin signaling pathways [3][7] Group 2: Clinical Data and Biomarkers - Significant upregulation of STAT3, IRS1/2, and β-catenin was observed in HNSCC tumors compared to normal tissues, indicating potential biomarkers for NT219-based therapy [3][7] - The data suggest that activated forms of STAT3 and IGF1R correlate with patient response to NT219 treatment, supporting their role as potential biomarkers [7][12] Group 3: Efficacy in Colorectal Cancer - NT219 has shown anti-tumor efficacy in colorectal cancer (CRC) models, with APC-loss and activated β-catenin identified as potential biomarkers for treatment response [5][12] - The therapy has demonstrated the ability to reverse chemo-resistance and enhance the efficacy of existing chemotherapy regimens [12] Group 4: Future Directions - The findings from the AACR meeting are expected to guide study design, patient selection, and combination therapy strategies for NT219 [3][7] - Purple Biotech is committed to advancing NT219 in collaboration with the University of Colorado for R/M HNSCC patients [10]

Core Insights - The study identifies IRS2 as a significant driver of brain metastasis in colorectal cancer, suggesting that targeting IRS2 with NT219 may provide a new therapeutic strategy [1][2][4] - The combination of NT219 and 5-fluorouracil (5-FU) has been shown to inhibit the formation of colorectal cancer brain metastasis and extend survival in preclinical models [2][5] - Approximately 20% of colorectal cancer patients present with distant metastasis at diagnosis, with an additional 50% developing metastasis later, highlighting the potential impact of NT219 on patient outcomes [2] Company Overview - Purple Biotech Ltd. is a clinical-stage company focused on developing first-in-class therapies to overcome tumor immune evasion and drug resistance, with a pipeline that includes NT219, CM24, and CAPTN-3 [7] - NT219 is a novel small molecule designed to degrade IRS1/2 and block downstream signaling pathways, currently advancing into a Phase 2 study for recurrent and/or metastatic squamous cell carcinoma of the head and neck [1][7] - The company aims to leverage NT219's unique mechanism of action to expand clinical development opportunities in colorectal cancer and other malignancies [2][7] Research Findings - The study analyzed over 35,000 colorectal cancer samples, revealing a distinct genomic profile associated with brain metastasis and highlighting the role of IRS2 in this process [4] - Elevated IRS2 expression is linked to the promotion of brain metastasis through modulation of the β-catenin pathway and oxidative phosphorylation [4][5] - The findings support the potential of NT219 as a therapeutic strategy against colorectal cancer brain metastasis, offering new avenues for treatment [5]

Company Overview - Purple Biotech Ltd. is a clinical-stage company focused on developing first-in-class therapies to overcome tumor immune evasion and drug resistance [2] - The company's oncology pipeline includes CM24, NT219, and CAPTN-3, targeting various cancer indications [2] Pipeline Details - CM24 is a humanized monoclonal antibody that blocks CEACAM1, demonstrating improvement in a Phase 2 study for pancreatic ductal adenocarcinoma when combined with nivolumab and chemotherapy [2] - NT219 is a dual inhibitor targeting IRS1/2 and STAT3, showing anti-tumor activity in a Phase 1 study and advancing to a Phase 2 study in collaboration with the University of Colorado [2] - CAPTN-3 is a preclinical platform of conditionally activated tri-specific antibodies designed to induce a strong immune response within the tumor microenvironment [2] Upcoming Events - The CEO of Purple Biotech, Gil Efron, will participate in a panel discussion at the Canaccord Genuity Horizons in Oncology Virtual Conference on April 7, 2025 [1]