Iterion Therapeutics Doses First Patient in Colorectal Cancer Trial for Wnt Inhibitor Tegavivint

Iterion Therapeutics has dosed the first patient in a phase 1/2 clinical trial evaluating its first-in-class Wnt/β-catenin pathway inhibitor, tegavivint, for the treatment of metastatic colorectal cancer. The milestone expands the clinical development of the small molecule inhibitor into mCRC, a disease with significant unmet need and limited progress in developing targeted therapies.

The mCRC study builds on encouraging clinical benefit observed in patients with advanced hepatocellular carcinoma, including partial responses and durable disease control in heavily pre-treated patients. The level of monotherapy activity observed with tegavivint in complex solid tumors is unprecedented for a Wnt/β-catenin pathway inhibitor.

Colorectal cancer is one of the most common cancers worldwide, with over 1.9 million new cases annually and is the second leading cause of cancer-related death in the U.S. after lung cancer. While greater than 90% of colorectal cancer patients harbor Wnt-pathway activating mutations, there are no FDA-approved drugs targeting the pathway.

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.

The drug 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.

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 has received $26 million in Product Development Awards from the Cancer Prevention and Research Institute of Texas and continues to build a pipeline of differentiation-driven clinical opportunities around its proprietary Wnt/β-catenin platform.