Tegatrabetan

HOUSTON, May 16, 2023 /PRNewswire/ -- Iterion Therapeutics, a leading biopharmaceutical company dedicated to the development of innovative treatments for cancer, announced today its collaboration in a Phase 1 clinical trial for tegavivint in patients with relapsed or refractory c-Myc-overexpressing large B-cell lymphomas. The first patient has been enrolled to this National Cancer Institute-funded study, which is being conducted at The Ohio State University Comprehensive Cancer Center, Arthur G. James Cancer Hospital and Richard J. Solove Research Institute in Columbus, Ohio. Continue Reading Diffuse large B-cell lymphomas (DLBCL) are a type of Non-Hodgkin lymphoma (NHL) that originates from white blood cells. It is estimated that each year there are more than 20,000 patients diagnosed with DLBCL resulting in greater than 7,000 deaths annually. In a subset of DLBCL, the oncogene c-MYC is overexpressed through genetic mechanisms. Patients with c-Myc-overexpressing DLBCL are less likely to respond to currently available therapies, with an overall survival (OS) rate of 30% at 2 years compared to 76% in c-MYC negative patients. Patients with relapsed/refractory c-MYC-overexpressing DLBCL represent a significant unmet clinical as their prognosis is particularly poor with very limited effective treatment options. Iterion Therapeutics Announces the Initiation of a Phase 1 Clinical Trial for Tegavivint in Patients with c-Myc-overexpressing Relapsed or Refractory Large B-Cell Lymphomas Tweet this Tegavivint is a first-in-class small molecule inhibitor of Transducin beta-like protein 1 (TBL1), that has demonstrated safety, clinical and pharmacodynamic activity in a Phase 1 study of patients with desmoid tumors. TBL1 is an exchange adaptor protein known to regulate protein stability and acts as a master regulator of the Wnt-signaling pathway by binding to nuclear beta-catenin to protect it from degradation and promote its downstream transcriptional activity. TBL1 is highly expressed in DLBCL compared to normal B cells, with expression inversely correlated with OS in DLBCL patients treated with standard first-line treatment. Pre-clinical studies have shown tegavivint promotes DLBCL cell death in vitro and in vivo through modulating stability of key oncogenic proteins, including c-Myc. "TBL1 and MYC have long been therapeutic targets of interest in DLBCL" states Lapo Alinari, MD, PhD, a hematologist with the OSUCCC – James and assistant professor at The Ohio State University College of Medicine. "Tegavivint provides the first opportunity to treat DLBCL patients with a targeted therapy toward TBL1 and the pre-clinical data suggests that by doing so, we can also impact MYC protein levels resulting in anti-tumor activity". The Phase 1 dose-escalation study will enroll up to 20 patients with relapsed or refractory c-Myc-overexpressing DLBCL, who have failed at least two lines of prior treatment. The primary endpoint for the study will be to assess safety, measure dose limiting toxicities (DLTs), and define a recommended phase 2 dose (RP2D). Patients will also be followed for clinical responses, pharmacokinetics and changes in pharmacodynamic markers. "While there have been significant advances in treatment of DLBCL, the patients targeted in this study are known to have poor prognosis and poor response to the current standard of care", states Casey Cunningham, MD, Chief Medical Officer at Iterion. "The pre-clinical data suggests that tegavivint may provide a therapeutic option where one does not currently exist" For more information about the Phase 1 clinical trial of tegavivint in patients with large B-cell lymphomas, please visit ClinicalTrials.gov using the identifier NCT05755087. This trial is funded by the National Cancer Institute with additional support from Iterion, manufacturer of the study drug, Tegavivint. Patients on this study receive the study drug at no cost while on the clinical trial. 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), as well as investigator-sponsored programs in acute myeloid leukemia (AML), non-small cell lung cancer (NSCLC), and solid tumors. Iterion is the recipient of an up to $18.9 million Product Development Award from the Cancer Prevention and Research Institute of Texas (CPRIT). For more information on Iterion, please visit . SOURCE Iterion Therapeutics

Tegavivint therapy reduced tumor growth and increased T-lymphocyte infiltration in beta-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) 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 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 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 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 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 Research UK's vision is to bring forward the day when all cancers are cured. For further information about Cancer 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