tezacitabine (EO-4426) / Edison Oncology - LARVOL DELTA

EO-4426: A brain-penetrant dual DNA-polymerase α and ribonucleotide reductase inhibitor for high-grade gliomas and other aggressive cancers (SNO 2025) - "This dual-targeting mechanism induces replication fork collapse and accumulation of DNA damage, selectively impacting rapidly proliferating tumor cells. EO-4426 has been studied in over 400 patients across multiple Phase 1 and Phase 2 trials as both i.v. and oral formulations, alone and in combination with 5-FU or cisplatin...Importantly, EO-4426 overcomes resistance related to cytidine deaminase (CDA)-mediated deactivation, a known mechanism of resistance to FDA-approved RNR inhibitors such as gemcitabine and hydroxyurea. EO-4426 represents a novel oral, brain-penetrant dual inhibitor of Pol α and RNR with promising preclinical and clinical evidence of activity in aggressive cancers, including CNS malignancies. Its ability to bypass CDA-related resistance and its biomarker-driven development strategy position EO-4426 as a first-in-class precision therapy for CNS malignancies."

Brain Cancer • CNS Tumor • Glioma • Hematological Malignancies • High Grade Glioma • Microsatellite Instability • Neutropenia • Oncology • Solid Tumor • MSI • RRM2

EO4426: A CDA-Resistant, Dual-Mechanism Agent Designed for Highly Resistant Solid Tumors (ACCESS Newswire) - "Edison Oncology Presents New...Data...at SNO 2025....In comparative preclinical biochemical studies, EO4426 was shown to be ~30-fold more resistant to CDA-mediated degradation than gemcitabine, enabling potent antitumor activity in CDA-high cancers such as non-small cell lung cancer (NSCLC), triple negative breast cancer (TNBC), ovarian cancer, and head and neck squamous cell carcinoma. Across multiple intracranial and systemic tumor models-including GBM, neuroblastoma, and metastatic TNBC-EO4426 delivered significant survival extension, robust intracranial tumor control, and durable complete responses."

Preclinical • Glioblastoma • Neuroblastoma • Non Small Cell Lung Cancer • Ovarian Cancer • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer

EO-4426: A brain-penetrant dual DNA-polymerase α and ribonucleotide reductase inhibitor for high-grade gliomas and other aggressive cancers (WFNOS 2025) - "This dual-targeting mechanism induces replication fork collapse and accumulation of DNA damage, selectively impacting rapidly proliferating tumor cells. EO-4426 has been studied in over 400 patients across multiple Phase 1 and Phase 2 trials as both i.v. and oral formulations, alone and in combination with 5-FU or cisplatin...Importantly, EO-4426 overcomes resistance related to cytidine deaminase (CDA)-mediated deactivation, a known mechanism of resistance to FDA-approved RNR inhibitors such as gemcitabine and hydroxyurea. EO-4426 represents a novel oral, brain-penetrant dual inhibitor of Pol α and RNR with promising preclinical and clinical evidence of activity in aggressive cancers, including CNS malignancies. Its ability to bypass CDA-related resistance and its biomarker-driven development strategy position EO-4426 as a first-in-class precision therapy for CNS malignancies."

Brain Cancer • Hematological Malignancies • Microsatellite Instability • Neutropenia • Solid Tumor • MSI • RRM2

Development of EO-4426: A brain-penetrant dual DNA polymerase-α and ribonucleotide reductase inhibitor (AACR-NCI-EORTC 2025) - "Background: Resistance associated with cytidine deaminase (CDA)-mediated deactivation, a key limitation of existing ribonucleotide reductase (RNR) inhibitors such as gemcitabine and hydroxyurea...This unique dual-targeting mechanism induces replication fork collapse and accumulation of DNA damage, selectively impacting rapidly proliferating tumor cells. EO-4426 has been evaluated in over 400 patients across multiple Phase 1 and Phase 2 clinical trials, using both intravenous and oral formulations as monotherapy and in combination with standard chemotherapies such as 5-FU and cisplatin... EO-4426 represents a novel oral, brain-penetrant dual inhibitor of Pol α and RNR with promising preclinical and clinical evidence of activity in aggressive cancers. Its ability to bypass CDA-related resistance and its biomarker-driven development strategy position EO-4426 as potential a first-in-class precision therapy for CNS malignancies."

Brain Cancer • Hematological Malignancies • Microsatellite Instability • Oncology • Solid Tumor • CDA • MSI • RRM2

Edison Oncology also presented an abstract titled “Development Overview of EO4426: A Brain-Penetrant Dual DNA Polymerase α and Ribonucleotide Reductase Inhibitor,“ which details the clinical and preclinical evaluation of EO4426 in over 400 patients across multiple Phase 1 and Phase 2 trials (ACCESS Newswire) - "Edison Oncology Presents...Posters at the 2025 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics....EO4426 has shown broad preclinical activity across both solid tumors and hematologic malignancies, including models of microsatellite instability (MSI) and RRM2 overexpression, with a favorable tolerability profile. Reversible neutropenia was identified as the primary dose-limiting toxicity, consistent with on-target RNR inhibition....Forthcoming biomarker-guided clinical studies planned to evaluate its therapeutic potential, including in central nervous system (CNS) malignancies..."

Clinical data • Preclinical • CNS Tumor • Colorectal Cancer • Esophageal Cancer • Gastric Cancer • Hematological Malignancies • Microsatellite Instability