Iterion Therapeutics Reports First Clinical Validation of Tegavivint as a Targeted Therapy for Wnt-Driven Advanced HCC in Oral Presentation at 2026 ASCO Annual Meeting

Tegavivint was generally well tolerated and demonstrated monotherapy clinical responses with clear on-target Wnt/b-catenin pathway inhibition in patients with Wnt-pathway mutated advanced hepatocellular carcinoma (HCC)

In second- and third-line patients, tegavivint achieved an overall response rate (ORR) of 22%, disease control rate of 89%, and median progression-free survival (mPFS) of 8 months

Tegavivint, the first targeted therapy being developed for the approximately 40% of advanced HCC patients with tumors harboring Wnt pathway–activating mutations (WPAMs), is also in clinical development for mCRC and other Wnt-driven tumors

HOUSTON, June 1, 2026 /PRNewswire/ -- Iterion Therapeutics, a clinical-stage biopharmaceutical company dedicated to advancing the treatment of Wnt-driven cancers, today announced 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) Annual Meeting, and will be featured by David Hsieh, M.D., Associate Professor at UT Southwestern Medical Center.

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.

About Iterion Therapeutics

Iterion Therapeutics is a clinical-stage oncology company developing first-in-class therapies that target cancers driven by aberrant Wnt/b-catenin signaling. The Company's lead asset, tegavivint, is a first-in-class small-molecule inhibitor of TBL1, a critical transcriptional regulator required for nuclear b-catenin stability and oncogenic gene expression. Tegavivint has demonstrated target engagement, clinical tolerability and monotherapy activity in advanced HCC and other Wnt-driven solid tumors.

Iterion is advancing a focused clinical strategy anchored by its lead program in HCC, with clinical development underway in additional Wnt-driven cancers, including mCRC and pediatric osteosarcoma where Wnt/b-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 around its proprietary Wnt/b-catenin platform. For more information, visit www.iteriontherapeutics.com.

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SOURCE Iterion Therapeutics