On June 1, 2026 Iterion Therapeutics, a clinical-stage biopharmaceutical company dedicated to advancing the treatment of Wnt-driven cancers, reported positive initial data from the dose-escalation portion of its ongoing Phase 1/2 study evaluating tegavivint in patients with advanced HCC. The data will be shared in a rapid oral presentation titled "Tegavivint, a downstream Wnt/b-catenin inhibitor: Dose-finding results from a phase 1/2 trial in advanced hepatocellular carcinoma (aHCC)," at the 2026 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, and will be featured by David Hsieh, M.D., Associate Professor at UT Southwestern Medical Center.

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Tegavivint is a first-in-class, clinical-stage downstream Wnt/β-catenin inhibitor designed to disrupt the TBL1:β-catenin transcriptional activation complex, promote nuclear β-catenin degradation, and block oncogenic transcription in Wnt-driven tumors.

"These data provide important clinical validation of tegavivint’s mechanism as a downstream inhibitor of Wnt/β-catenin signaling and support its development as a targeted therapy in HCC and other Wnt-driven cancers," said Rahul Aras, Ph.D., President and CEO of Iterion Therapeutics. "We are particularly encouraged by the depth and durability of monotherapy responses observed in heavily pretreated patients, and by the concentration of clinical benefit in a molecularly selected population of patients with Wnt-pathway activating mutations".

Key Findings from the Study

A total of 40 patients were enrolled. Patients had received a median of two prior lines of systemic therapy, and 29 patients (73%) had tumors with WPAMs, including alterations in AXIN1, CTNNB1, CREBBP, and APC, as assessed by ctDNA testing.

Tegavivint was generally well tolerated across dose levels. Treatment-related adverse events (TRAEs) occurred in 27 of 40 patients (68%) and were mostly Grade 1 or 2, with fatigue, hyperbilirubinemia, anemia, decreased appetite, and myalgia as the most common TRAEs. Grade 3 anemia at the 8 mg/kg dose level was dose-limiting but reversible, supporting a recommended dose range of 3 to 6.5 mg/kg.

Clinical activity among efficacy-evaluable patients treated with tegavivint at the recommended dose range was observed primarily in patients with WPAM+ tumors:

Tegavivint produced tumor shrinkage in approximately 40% of evaluable patients with WPAM+ tumors and achieved a 72% disease control rate (DCR); no tumor shrinkage was observed in patients without WPAMs.
In second- and third-line patients with WPAM+ tumors, tegavivint achieved a 22% overall response rate (ORR), an 89% DCR and a median progression-free survival (mPFS) of 8 months.
Paired tumor assessments showed reductions in active b-catenin protein levels following tegavivint treatment. Dose-proportional decreases in alpha-fetoprotein (AFP) and reductions in WPAM ctDNA variant allele frequency were also observed.
"Patients with advanced HCC whose tumors harbor Wnt/β-catenin pathway mutations represent a large, genetically defined population with significant unmet need and no approved targeted therapy targeting this biology," said David Hsieh, M.D., Associate Professor at UT Southwestern Medical Center and presenting author of the study. "The clinical activity observed with tegavivint is encouraging and supports further development of this investigational therapy as a potential novel treatment option for biomarker-selected patients."

About Tegavivint

Tegavivint is a potent and selective first-in-class small molecule designed to inhibit the downstream Wnt/b-catenin signaling pathway by binding to TBL1. By disrupting the nuclear TBL1:b-catenin complex, tegavivint is designed to promote degradation of nuclear b-catenin and inhibit expression of genes that drive tumor growth, survival and resistance to therapy in multiple cancer types, while sparing cytoplasmic and membrane-bound b-catenin pools that are necessary for normal cellular function.

(Press release, Iterion Therapeutics, JUN 1, 2026, View Source [SID1234666331])