elesclomol (EO3001) / Edison Oncology - LARVOL DELTA

Elesclomol-mediated cuproptosis overcomes cisplatin resistance by restricting epigenetically activated mitochondrial respiration: Novel therapeutic insights into cisplatin-elesclomol combination therapy. (PubMed, Acta Pharm Sin B) - "Therapeutically, employing zebrafish models, orthotopic xenografts, and patient-derived xenografts (PDXs), we confirmed the therapeutic efficacy of elesclomol in overcoming chemoresistance. Collectively, our study highlights a novel avenue for the development of a combinatorial therapeutic approach employing cisplatin and elesclomol to improve chemotherapy outcomes."

Journal • Eye Cancer • Melanoma • Metabolic Disorders • Oncology • Solid Tumor • Uveal Melanoma • DLAT • FDX1

Inhibiting calreticulin palmitoylation enhances the efficacy of elesclomol-CuCl2 on oxaliplatin-triggered immunogenic cell death in pancreatic cancer. (PubMed, Pharmacol Res) - "This potent ICD response promotes dendritic cell maturation and enhances CD8⁺T cell-mediated cytotoxicity through the TLR4/NF‑κB axis, which single-cell RNA sequencing of clinical PDAC samples supported in neoadjuvant therapy responders. Collectively, our findings identify CALR palmitoylation inhibition as a key driver of L‑OHP/ES‑CU-induced ICD, reshaping the tumor immune microenvironment to provide a promising chemo-immunotherapeutic strategy for PDAC."

CALR • Journal • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CALR • CD8 • TLR4

Inhibition of Jaw Bone Marrow Mesenchymal Stem Cell Cuproptosis Attenuates Bone Loss in Apical Periodontitis via Suppressing the FoxO Signalling Pathway. (PubMed, Int Endod J) - "Cuproptosis acts as a novel driver of alveolar bone loss in AP by impairing the osteogenic potential of JBMMSCs. TTM targeting cuproptosis represents a promising strategy to attenuate bone resorption in AP by the cuproptosis/FoxO/β-catenin pathway."

Journal • Dental Disorders • Infectious Disease • Inflammation • Osteoporosis • Periodontitis

Mechanism of "biaoben acupoint combination" electroacupuncture pretreatment in alleviating cardiomyocyte cuproptosis in rats with myocardial ischemia-reperfusion injury (PubMed, Zhongguo Zhen Jiu) - "Compared with the MIRI group and the ES group, in the EA group and the EA+ES group, disordered arrangement of myocardial mitochondria, mitochondria edema, and mitochondrial outer membrane rupture were improved, the improvement in the EA group was more pronounced. "Biaoben acupoint combination" EA pretreatment can attenuate the structural damage of cardiomyocytes and mitochondria, enhance the expression of mitochondrial respiratory chain complexes Ⅰ-Ⅳ in MIRI rats, and alleviate MIRI by inhibiting elesclomol-induced cardiomyocyte cuproptosis."

Journal • Preclinical • Cardiovascular • Myocardial Infarction • Myocardial Ischemia • Reperfusion Injury • CP • DLAT • DLST • FDX1

Tetrachlorobisphenol A inhibits steroidogenesis in pubertal rat Leydig cells through disruption of copper homeostasis. (PubMed, Ecotoxicol Environ Saf) - "At concentrations that did not affect cell viability, two molecular features of cuproptosis were tested directly: the iron-sulfur cluster protein SDHB was not significantly reduced, and DLAT oligomerisation was not detected, although it was readily produced by the positive control elesclomol-CuCl2. These findings indicate that TCBPA impairs steroidogenesis in rat Leydig cells through suppression of steroidogenic enzymes and copper-dependent mitochondrial dysfunction, without engaging cuproptosis, providing a basis for evaluating the reproductive risk of halogenated bisphenols."

Journal • Preclinical • Metabolic Disorders • ATP7B • DLAT • FDX1 • LIAS • SCARB1 • SDHB

UBE2D4 Upregulation Promotes Cuproptosis Sensitivity in Colorectal Cancer. (PubMed, Mol Genet Genomic Med) - "These findings identify UBE2D4 as a genetically upregulated and functionally significant gene in colorectal cancer. Its upregulation correlates with altered expression of cuproptosis-related genes, particularly DLAT, suggesting that UBE2D4 expression status may represent a genetic determinant of cuproptosis sensitivity in CRC. This study provides a genetic basis for stratifying CRC patients who might benefit from copper-based therapeutic strategies."

Journal • Colorectal Cancer • Oncology • Solid Tumor • DLAT • LIAS

EO3001 (elesclomol), a copper ionophore that exploits ferredoxin-1 (FDX1) to drive cuproptosis in ARID1A-mutant solid tumors: preclinical rationale and design of an all-comer Phase I/II dose-escalation study with prospective ARID1A biomarker stratification (EORTC-NCI-AACR 2026) - "Abstract will be available as of 4 November (with consent of the author)"

P1/2 data • Preclinical • Oncology • Solid Tumor • ARID1A • FDX1

Investigating the potential of EO3001 as a therapeutic agent for clear cell ovarian cancers harboring ARID1A mutations (AACR 2025) - "EO3001 demonstrated significant differential effects against ARID1A-deficient CCOC cells in both in vitro and ex vivo models. However, hypoxic conditions significantly diminished its efficacy, likely due to a metabolic shift between OXPHOS and glycolysis. Furthermore, Cu(II) concentration in the microenvironment remarkably impacts the efficiency of EO3001."

Oncology • Ovarian Cancer • Ovarian Clear Cell Cancer • Solid Tumor • ARID1A • SLC7A11

EO3001: A novel agent for ARID1A mutant cancers (AACR-NCI-EORTC 2025) - "Conclusions and Next Steps These findings suggest that EO3001 holds promise as a targeted therapeutic for ARID1A-mutant cancers, and ongoing work is focused on optimizing its application in clinically relevant settings. A biomarker-driven clinical trial is planed to further evaluate these findings."

Clear Cell Carcinoma • Oncology • Ovarian Cancer • Solid Tumor • ARID1A

Edison Oncology's presentation "EO3001: A novel agent for ARID1A-mutant cancers," highlights the potential of EO3001 as a first-in-class targeted therapeutic for ARID1A-mutant cancers (ACCESS Newswire) - "Edison Oncology Presents...Posters at the 2025 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics....Preclinical studies demonstrate that EO3001 exhibits potent and selective cytotoxicity in ARID1A-deficient ovarian clear cell and endometrioid cancer models, consistent with enhanced reliance on oxidative phosphorylation (OXPHOS) in these tumors."

Preclinical • Endometrial Cancer • Ovarian Cancer

Investigating the therapeutic efficacy of EO3001 in clear cell carcinoma of the ovary (AACR 2023) - "We will use the organoids modeling system -using primary endometrial cells harboring ARID1A mutations- to assess the impact of EO3001 on organoid growth and response to stress conditions and evaluate the effect of EO3001 on cancer metastesis by the ex vivo pulmonary metastasis assay (PuMA). Conclusions Exploiting the vulnerability in reliance on OXPHOS in ARID1A-deficient CCC using EO3001 might represent a promising strategy for the treatment of these patients as well as patients harboring other ARID1A-deficient malignancies."

Clinical • Oncology • Ovarian Cancer • Solid Tumor • ARID1A • PIK3CA • SLC7A11

Edison Oncology Announces Presentation of Two Scientific Posters at AACR Annual Meeting (PRNewswire) - "Edison Oncology Holding Corp....is pleased to announce the presentation of two scientific posters at the annual meeting of the American Association of Cancer Research....In a second presentation...Edison Oncology reported that in CRISPR/Cas9 generated isogenic pairs of ovarian cancer cell lines, EO3001 selectively kills ARID1A mutant cancer cells at low nanomolar concentrations compared to 'wildtype' ovarian cancer cells that do not harbor the mutation....The poster describes that by directly inhibiting the action of certain mitochondrial proteins required for the function of the OXPHOS pathway, EO3001 may result in energy deprivation and apoptosis the of metabolically overactive ARID1A mutant tumor cells."

Preclinical • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor • ARID1A