Tegatrabetan

Tegavivint Is the First Wnt/β-Catenin Inhibitor to Demonstrate Tolerability and Monotherapy Clinical Activity in Complex Solid Tumors Osteosarcoma Program Builds on Clinical Benefit observed in Lead Indication of Advanced Hepatocellular Carcinoma HOUSTON , Feb. 10, 2026 /PRNewswire/ -- Iterion Therapeutics , a clinical-stage, biopharmaceutical company dedicated to revolutionizing the treatment of Wnt-driven cancers, today announced that the first patient has been dosed in a clinical study evaluating tegavivint, a first-in-class inhibitor of the Wnt/β-catenin pathway, in combination with gemcitabine for patients with relapsed or refractory osteosarcoma. The trial is sponsored by Emory University, conducted at the Aflac Cancer and Blood Disorders Center of Children's Healthcare of Atlanta and supported by funding from the Peach Bowl LegACy Fund, reflecting strong academic, clinical and philanthropic commitment to advancing new therapies for this rare pediatric cancer. Osteosarcoma is the most common malignant bone tumor in children and adolescents, and outcomes following relapse remain poor. A growing body of research has shown that Wnt/β-catenin signaling is highly active in relapsed and metastatic osteosarcoma, where it is associated with tumor progression, treatment resistance, and metastasis. Tegavivint is a small-molecule inhibitor of TBL1, a transcriptional co-factor required for oncogenic β-catenin signaling. By selectively disrupting the TBL1/β-catenin transcriptional complex, tegavivint promotes degradation of nuclear β-catenin and suppresses β-catenin-dependent gene transcription, shutting down Wnt-driven tumor growth while avoiding the dose-limiting toxicities historically associated with upstream Wnt inhibition. "Tegavivint represents a novel approach to targeting one of the central biological drivers of osteosarcoma," said Rahul Aras, PhD, President and CEO of Iterion Therapeutics. "This first patient dosed marks an important clinical milestone for a program supported by extensive biological validation and reinforces the broader value of our Wnt/β-catenin platform." Tegavivint has already demonstrated favorable tolerability, pharmacodynamic activity, and encouraging monotherapy clinical responses in Company-sponsored clinical trials in hepatocellular carcinoma and desmoid tumors, two diseases driven by aberrant Wnt/β-catenin signaling. In addition, a Children's Oncology Group (COG)-led study conducted through the National Cancer Institute has established the safety of tegavivint across a broad pediatric population, providing a strong foundation for advancement into disease-focused combination studies in osteosarcoma. "Tegavivint is uniquely positioned for osteosarcoma because it targets a pathway that is consistently active in high-risk and relapsed disease," said Thomas Cash, MD, Principal Investigator of the study at the Aflac Cancer and Blood Disorders Center and Associate Professor of Pediatrics at Emory University. "Evaluating tegavivint in combination with gemcitabine allows us to build on a strong scientific foundation as we seek to improve outcomes for patients with limited treatment options." Tegavivint has received both Orphan Drug Designation and Pediatric Rare Disease Designation from the U.S. Food and Drug Administration for the treatment of osteosarcoma. About Iterion Therapeutics Iterion Therapeutics is a clinical-stage oncology company developing first-in-class therapies that target cancers driven by aberrant Wnt/β-catenin signaling. The Company's lead asset, tegavivint, is the first and only small-molecule inhibitor of TBL1, a critical transcriptional regulator required for nuclear β-catenin stability and oncogenic gene expression. Tegavivint has demonstrated clinical tolerability, target engagement, and monotherapy activity in multiple complex solid tumors, including advanced hepatocellular carcinoma, positioning Iterion at the forefront of Wnt/β-catenin drug development. Iterion is advancing a focused clinical strategy anchored by its lead program in hepatocellular carcinoma, with expansion into additional Wnt-driven cancers, including pediatric and rare oncology indications where Wnt/β-catenin signaling represents a validated disease driver. The Company has received $26 million in Product Development Awards from the Cancer Prevention and Research Institute of Texas (CPRIT) and continues to build a pipeline of differentiation-driven clinical opportunities around its proprietary Wnt/β-catenin platform. For more information on Iterion, please visit . Investor Contact: Laurence Watts laurence@newstreetir.com Media Contact: Ryan Walker ryan@rjwalkerco.com View original content to download multimedia: SOURCE Iterion Therapeutics

HOUSTON, Feb. 20, 2024 /PRNewswire/ -- Iterion Therapeutics, an oncology-focused biopharmaceutical company developing small molecule inhibitors of Transducin beta-like protein 1 (TBL1), a downstream target in the Wnt/beta-catenin signaling pathway, announced today it is actively enrolling a Phase 1b/2a clinical trial of its lead molecule, tegavivint, in patients with advanced hepatocellular carcinoma (HCC) that have failed at least one line of systemic therapy. Activation of the Wnt/beta-catenin pathway is a hallmark of several forms of cancer, including HCC, in which approximately half of patients have tumors with Wnt-activating mutations. Unfortunately, key members of this pathway (including beta-catenin) have either been resistant to conventional drug development or plagued with off-target toxicities. Extensive pre-clinical study results across multiple tumor types suggest that TBL1 is a downstream target that is necessary for Wnt/beta-catenin-activated oncogenesis. TBL1 binds nuclear beta-catenin thus stabilizing the transcription complex necessary to turn on cancer-causing genes. Tegavivint's direct binding to TBL1 displaces beta-catenin and disrupts this complex, allowing the degradation of free nuclear beta-catenin and preventing downstream oncogenic gene transcription. "By targeting TBL1, tegavivint promotes potent inhibition of nuclear beta-catenin oncogenic activity without inducing toxicities observed for other drugs that are upstream in the Wnt-pathway" stated Rahul Aras, Ph.D., President & CEO for Iterion Therapeutics. "HCC is a devastating cancer with a high prevalence of Wnt-activated tumors, and we are committed to developing tegavivint for this patient population that otherwise has very few therapeutic options". HCC is the sixth most commonly diagnosed cancer and the third leading cause of cancer death globally. In 2023, the National Cancer Institute (NCI) estimated 41,210 new HCC cases diagnosed in the US, with 29,380 deaths. The overall prognosis is poor, with a 5-year survival rate of 21.6%. Wnt-activation plays multiple roles in the pathogenesis of HCC by initiating tumorigenesis, promoting metastasis, and enhancing an immunosuppressive tumor microenvironment. Patients with elevated nuclear beta-catenin and TBL1 demonstrate particularly poor outcomes. Despite this, there are no FDA-approved therapies targeting this pathway. "There is a desperate need for novel targeted therapies to address the large unmet clinical need in HCC" expressed Casey Cunningham, M.D., Chief Medical Officer for Iterion Therapeutics. "Tegavivint has demonstrated excellent tolerability and has the potential to address a large portion of this population by directly inhibiting beta-catenin's oncogenic activity". The ongoing clinical trial will enroll approximately 35 patients in dose escalation and optimization cohorts of patients with unresectable locally advanced or metastatic HCC that have failed at least one line of systemic treatment. The study will evaluate safety and clinical efficacy in addition to pharmacokinetic and pharmacodynamic markers to determine a Recommended Phase 2 Dose (RP2D) in HCC. Tegavivint has demonstrated safety, clinical and pharmacodynamic activity in a Phase 1 clinical study of patients with desmoid tumors. For more information about this Phase 1b/2a clinical trial of tegavivint in patients with advanced HCC, please visit using the identifier NCT05797805. 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), a newly characterized target in the Wnt/beta-catenin pathway. TBL1 binds to nuclear beta-catenin, forming an active transcription complex that prevents nuclear degradation of beta-catenin and activates genes necessary for the Wnt/beta-catenin oncogenic activity. Tegavivint binds to TBL1 and disrupts the interaction between beta-catenin and TBL1, thus promoting the degradation of nuclear beta-catenin and preventing the transcription of Wnt/beta-catenin targeted oncogenes. 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 carcinoma (HCC), as well as investigator-sponsored programs in non-small cell lung cancer (NSCLC), diffuse large B-cell lymphomas (DLBCL), and pediatric solid tumors. Iterion is the recipient of combined a $18.9 million in Product Development Awards from the Cancer Prevention and Research Institute of Texas (CPRIT). For more information on Iterion, please visit . SOURCE Iterion Therapeutics