Iterion Therapeutics Announces Results from Preclinical Study of Tegavivint in Beta-Catenin Mutant Hepatocellular CarcinomaBeta-Catenin Mutant Hepatocellular Carcinoma to be Presented at the 34th EORTC-NCI-AACR Symposium 2022

18 Oct 2022
www.biospace.com
AntibodyCollaborateFirst in ClassSmall molecular drugAACR
Tegavivint therapy reduced tumor growth and increased T-lymphocyte infiltration in beta-catenin activated hepatocellular carcinomabeta-catenin activated hepatocellular carcinoma models Iterion intends to initiate a company-sponsored clinical program investigating tegavivint in the treatment of hepatocellular carcinoma HOUSTON, Oct. 18, 2022 /PRNewswire/ -- Iterion Therapeutics, Inc., a venture-backed, clinical-stage biotechnology company developing novel cancer therapeutics, announced that results from a preclinical murine study of tegavivint in beta-catenin activated hepatocellular carcinoma (HCC)beta-catenin activated hepatocellular carcinoma (HCC) will be featured in a poster presentation and discussion session at the 34th European Organisation for Research and Treatment of Cancer (EORTC), National Cancer Institute (NCI), and American Association for Cancer Research (AACR) Symposium (ENA 2022). ENA 2022 is being held October 26-28, 2022, in Barcelona, Spain. Tegavivint is a potent and selective first-in-class small molecule inhibitor of Transducin Beta-like Protein One (TBL1), a novel downstream co-factor in the Wnt/beta-catenin signaling pathway. Increased expression of beta-catenin and TBL1 are associated with metastasis and poor prognosis in a broad range of tumor types, including HCC. Up to 50% of HCC patients have tumors driven by activating beta-catenin and canonical Wnt pathway mutations. Tegavivint targets TBL1 and prevents TBL1/beta-catenin complex formation, specifically inhibiting nuclear beta-catenin's oncogenic transcriptional activity without disrupting key cell membrane functions that are linked to toxicity common to other drugs in this pathway. The poster presentation, entitled, "The TBL1 inhibitor, Tegavivint, suppresses tumour growth and enhances T-cell infiltration in preclinical murine β-Catenin mutant hepatocellular carcinomaβ-Catenin mutant hepatocellular carcinoma," will be presented on Wednesday, October 26, 2022, between 12:00-20:00 CET, during the Molecular Targeted Agents 1 session (poster board number PB043; abstract number 53) by Thomas Drake, M.B.Ch.B., B.Med.Sci, principal investigator of the study from the Cancer Research UK Beatson Institute. The poster reports on research studying the therapeutic potential for tegavivint in a genetically engineered C57BL/6J mouse model (GEMM) of beta- cateninexon3 mutant HCC (reference) in both early and late-stage disease. The results include evidence for direct anti-tumor activity and immunomodulatory effects on the 'cold' immune microenvironment. The study found that inhibition of TBL1 in early-stage disease significantly reduced the number of tumor-initiating clones compared with vehicle controls. Treatment of established beta-cateninexon3 activated tumors with tegavivint inhibited tumor growth and resulted in a reduced tumor burden compared with vehicle controls. Additionally, in mice with established tumors, tegavivint treatment increased CD3+ T-lymphocyte tumor infiltration, with prominent increases in intratumoral CD8+ T-cells. Importantly, no off-target effects were observed in intestinal tissue, which is dependent on canonical Wnt signaling to maintain tissue homeostasis. "Hepatocellular cancer is the third leading cause of death worldwide with approximately half of all patients harboring a Wnt/beta-catenin mutation that is correlated with poor prognosis and resistance to checkpoint inhibitor therapy," said Rahul Aras, Ph.D., CEO of Iterion. "The research presented at ENA 2022 suggests that tegavivint's ability to inhibit TBL1 and thereby nuclear beta-catenin's oncogenic activity has the potential to reduce tumor growth and activate an immune response in previously 'cold' HCC tumors. These data add to a growing body of literature suggesting nuclear beta-catenin inhibition may be beneficial in treatment of HCC and Iterion is now planning to initiate a company-sponsored clinical trial investigating the potential for tegavivint in this patient population." About Iterion Therapeutics Iterion Therapeutics is a clinical-stage biotechnology company developing novel cancer therapeutics. The company's lead product, tegavivint, is a potent and selective small molecule that binds to Transducin Beta-Like Protein 1 (TBL1) in the nucleus, inhibiting nuclear beta-catenin signaling and oncogenic activity. Increased expression of beta-catenin and TBL1 are associated with metastasis and poor prognosis in a broad range of tumor types, making TBL1 an emerging, high-value cancer target of interest. Iterion is currently advancing multiple clinical programs investigating tegavivint in cancer indications where nuclear beta-catenin overexpression is a known factor. These include Iterion-sponsored programs in hepatocellular cancer (HCC) and osteosarcoma, as well as investigator-sponsored programs in acute myeloid leukemia (AML), non-small cell lung cancer (NSCLC), and pediatric sarcomas, lymphomas and other solid tumors. Iterion is the recipient of an up to $18.9 million Product Development Award from the Cancer Prevention and Research Institute of TexasCancer Prevention and Research Institute of Texas (CPRIT). For more information on Iterion, please visit . Contact: Madeleine Lu PR@iteriontx.com About Cancer Research UK Cancer Research UK is the world's leading cancer charity dedicated to saving lives through research. Cancer ResearchCancer Research UK's pioneering work into the prevention, diagnosis and treatment of cancer has helped save millions of lives. Cancer Research UK has been at the heart of the progress that has already seen survival in the UK double in the last 40 years. Today, 2 in 4 people survive their cancer for at least 10 years. Cancer ResearchCancer Research UK's ambition is to accelerate progress so that by 2034, 3 in 4 people will survive their cancer for at least 10 years. Cancer Research UK supports research into all aspects of cancer through the work of over 4,000 scientists, doctors and nurses. Together with its partners and supporters, Cancer ResearchCancer Research UK's vision is to bring forward the day when all cancers are cured. For further information about Cancer ResearchCancer Research UK's work or to find out how to support the charity, please call 0300 123 1022 or visit . Follow us on Twitter and Facebook
For more details,please visit the original website
The content of the article does not represent any opinions of Synapse and its affiliated companies. If there is any copyright infringement or error, please contact us, and we will deal with it within 24 hours.
Organizations
Indications
Targets
Drugs
Get started for free today!
Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.
Start your data trial now!
Synapse data is also accessible to external entities via APIs or data packages. Leverages most recent intelligence information, enabling fullest potential.