Tegavivint Targets the Central Oncogenic Driver in Colorectal Cancer as First-in-Class Clinical-Stage Wnt/β-Catenin Inhibitor
CRC Expansion Builds on Promising Monotherapy Activity and Favorable Safety Profile Observed in Advanced Hepatocellular Carcinoma
HOUSTON, March 25, 2026 /PRNewswire/ — Iterion Therapeutics, a clinical-stage, biopharmaceutical company dedicated to advancing the treatment of Wnt-driven cancers, today reported that the first patient has been dosed at HonorHealth Research Institute in a phase 1/2 clinical trial (NCT07463599) evaluating tegavivint, a first-in-class, small molecule inhibitor of the Wnt/β-catenin pathway, for the treatment of metastatic colorectal cancer (mCRC). This milestone expands Iterion’s clinical development into mCRC, a disease with significant unmet need and limited progress in developing targeted therapies.
“The mCRC study builds on the encouraging clinical benefit we’re observing in patients with advanced hepatocellular carcinoma, including partial responses and durable disease control in heavily pre-treated patients,” said Rahul Aras, PhD, President and CEO of Iterion Therapeutics. “The level of monotherapy activity observed with tegavivint in complex solid tumors is unprecedented for a Wnt/β-catenin pathway inhibitor and we’re excited to expand development into other hard-to-treat Wnt-driven cancers.”
Colorectal cancer is one of the most common cancers worldwide, with over 1.9 million new cases annually and a pressing need for novel therapies. After lung cancer, colorectal cancer is the second leading cause of cancer-related death in the U.S.
Despite advances in early detection, treatment options for advanced or metastatic CRC remain inadequate, highlighting the urgency for targeted approaches like tegavivint.
“While greater than 90% of colorectal cancer patients harbor Wnt-pathway activating mutations, there are no FDA-approved drugs targeting the pathway. This first patient dosed represents a critical step forward in addressing this therapeutic gap,” said Sunil Sharma, MD, Chief of Translational Research and Drug Discovery at HonorHealth Research Institute. “Based on tegavivint’s excellent tolerability profile and demonstrated clinical activity in other solid tumors, we’re optimistic about its potential in colorectal cancer, including future combination strategies.”
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, inhibiting Wnt-driven tumor growth while avoiding the dose-limiting toxicities historically associated with upstream Wnt inhibition.
Tegavivint has demonstrated favorable tolerability, pharmacodynamic activity, and encouraging monotherapy clinical responses in clinical trials in hepatocellular carcinoma and desmoid tumors, two diseases driven by aberrant Wnt/β-catenin signaling. These findings provide a robust foundation for expansion into mCRC, and underscore the drug’s broad applicability across a substantial portion of newly diagnosed cancers worldwide in which aberrant Wnt/β-catenin signaling is a fundamental oncogenic driver.