Novel TBL1 targeting strategy drives nuclear β-catenin degradation, inhibits oncogenic transcription, and demonstrates potent anti-tumor activity in complex solid tumors

The company continues to build clinical momentum in hepatocellular carcinoma while expanding development into colorectal cancer, as well as other Wnt-driven cancers

HOUSTON, April 13, 2026 /PRNewswire/ -- Iterion Therapeutics announced that two abstracts featuring its first-in-class TBL1 inhibitor, tegavivint, will be presented at the 2026 American Association for Cancer Research (AACR) Annual Meeting. Each will highlight the company's approach to targeting the Wnt/β-catenin pathway, one of the most frequently dysregulated signaling programs in cancer.

Despite its role in an estimated 25–30% of solid tumors, the Wnt/β-catenin pathway has historically proven difficult to target therapeutically. Earlier efforts focused on inhibiting upstream components of the pathway and were often limited by bone and gastrointestinal toxicities.

Tegavivint takes a differentiated approach by targeting TBL1, a transcriptional regulator required for β-catenin–mediated gene expression. By disrupting the TBL1–β-catenin transcriptional complex, tegavivint promotes degradation of nuclear β-catenin, inhibits oncogenic transcriptional programs driven by Wnt signaling, and has demonstrated potent anti-tumor activity in preclinical models and clinical studies.

"These data further support our strategy of targeting TBL1 as a novel approach to treating Wnt-driven cancers," said Rahul Aras, Ph.D., President and Chief Executive Officer of Iterion Therapeutics. "As clinical momentum builds in hepatocellular carcinoma and our program expands into colorectal cancer and pediatric osteosarcoma, we see the potential for tegavivint to play an important role across multiple cancers where Wnt signaling drives disease."

Iterion recently completed a Phase 1 study of tegavivint in patients with advanced hepatocellular carcinoma (HCC), where the therapy demonstrated encouraging clinical responses and durable disease control in heavily pre-treated patients, along with a favorable tolerability profile. Detailed results from the study are expected to be presented at a scientific conference later this year as the company prepares to advance tegavivint into Phase 2 development in HCC.

The two presentations highlight both the mechanistic basis of tegavivint's activity and its emerging potential across multiple Wnt-driven cancers.

Building on a recently initiated Phase 1 clinical study in colorectal cancer, one presentation describes the activity of tegavivint in Wnt-driven colorectal cancer models, demonstrating potent anti-tumor activity in preclinical models characterized by activation of the Wnt/β-catenin pathway. These findings support the continued clinical development of tegavivint and exploration of combination strategies in colorectal and other cancers.

A second presentation further characterizes the mechanism of action of tegavivint and the characterization of TBL1 as a druggable therapeutic target within the Wnt/β-catenin pathway. The work highlights how targeting TBL1 can selectively disrupt β-catenin–dependent transcriptional activity and supports the broader potential of this approach across Wnt-driven cancers.

AACR Presentation Details

• Poster 1: Tegavivint, a first-in-class TBL1 inhibitor demonstrates potent activity in WNT-driven colorectal cancers
  • Presenter: Stephen Horrigan, Ph.D., Chief Scientific Officer
  • Session Title: CL07.02 – Molecular Targeted Therapy
  • Abstract Number: 3900/6
  • Date / Time: Monday April 20^th, 2026, 2:00-5:00pm
  • Location: Section 47
• Poster 2: Tegavivint directly targets TBL1 to inhibit β-catenin nuclear oncogenic activity
  • Presenter: Aundrietta Duncan, Ph.D., Sr. Director of Translational Research and Non-Clinical Development
  • Session Title: ET05.01 – Mechanisms of Anticancer Drug Action
  • Abstract Number: 5669/15
  • Date / Time: Tuesday April 21^st, 2:00-5:00pm
  • Location: Section 12

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 www.iteriontherapeutics.com.

Investor Contact:
Laurence Watts
laurence@newstreetir.com

Media Contact:
Ryan Walker
ryan@rjwalkerco.com

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SOURCE Iterion Therapeutics