Iterion Therapeutics Announces Promising Phase 1b Data for Tegavivint in Combination with Osimertinib in First-Line EGFR-Mutated Non-Small Cell Lung Cancer

• Combination demonstrating 79% objective response rate (ORR), including complete responses (CRs) in 16% of patients (compared to 1% historically for osimertinib alone)
• Median progression-free survival (mPFS) of 19.9 months and median overall survival (mOS) of 48.8 months observed in the dose-escalation cohort (compared to 37.6 months OS historically for osimertinib alone)
• Combination was well tolerated, with no dose-limiting toxicities
• Data provide clinical support for targeting β-catenin-mediated drug-tolerant persister cells as a strategy to improve the depth and durability of response to EGFR-targeted therapy

HOUSTON, Sept. 22, 2026 /PRNewswire/ -- Iterion Therapeutics, a clinical-stage biopharmaceutical company dedicated to advancing the treatment of Wnt-driven cancers, today announced promising results from an investigator-sponsored Phase 1b study conducted at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute evaluating tegavivint in combination with osimertinib as first-line therapy for patients with metastatic EGFR-mutated non-small cell lung cancer (NSCLC). The study, NCT04780568, is led by principal investigator Regan Memmott, M.D., Ph.D., of the Ohio State University Comprehensive Cancer Center.

"These promising results provide important early clinical evidence supporting tegavivint's differentiated mechanism of action and its potential to address one of the fundamental limitations of targeted cancer therapy: the persistence of drug-tolerant tumor cells," said Rahul Aras, Ph.D., President and Chief Executive Officer of Iterion Therapeutics. "We are particularly excited by the depth of tumor reduction, complete responses and survival observed in this study, together with the favorable tolerability profile of the combination. We believe these data provide important clinical validation for targeting β-catenin signaling and support the continued development of tegavivint in combination with targeted cancer therapies."

EGFR tyrosine kinase inhibitors (TKIs) have transformed treatment of EGFR-mutated NSCLC but are not curative in the metastatic setting; slow-cycling, drug-tolerant persister (DTP) cells can survive treatment and drive resistance. Preclinical research suggests EGFR-mutated NSCLC cells enter this persistent state via increased β-catenin transcriptional activity, and combining an EGFR TKI with β-catenin pathway inhibition improved depth and duration of response in xenograft models. Tegavivint, a small-molecule inhibitor of β-catenin transcriptional activity, was evaluated in combination with osimertinib in this study to test whether targeting DTP cells could improve the depth and durability of response to EGFR inhibition.

"The biology underlying the persistence of cancer to EGFR-targeted therapy provides a rationale for combining osimertinib with tegavivint," said Regan Memmott, M.D., Ph.D., Assistant Professor in the Division of Medical Oncology at The Ohio State University Comprehensive Cancer Center – James Cancer Hospital and Solove Research Institute, and principal investigator of the Phase 1b study. "Increased β-catenin transcriptional activity appears to play an important role in allowing a population of tumor cells to persist despite EGFR inhibition. The clinical activity observed in this study is consistent with our hypothesis that targeting these DTP cells may deepen responses and delay the emergence of resistance."

Phase 1b Clinical Results
The dose-escalation portion of the study, conducted at Ohio State, enrolled 15 evaluable patients with metastatic EGFR-mutated NSCLC who had not previously received an EGFR TKI; four additional patients were enrolled at the highest dose in a dose-expansion cohort. Patients received osimertinib 80 mg orally once daily in combination with escalating weekly intravenous doses of tegavivint (3–8 mg/kg) for the first four months, after which tegavivint was discontinued and osimertinib monotherapy was continued until disease progression. Patient demographics were similar to Phase 3 1L EGFR TKI studies (e.g. FLAURA) regarding sex, histology, and prevalence of EGFR mutation type, but there was a higher incidence of CNS and liver metastases and greater median tumor burden.

Combination treatment was well tolerated, with no dose-limiting toxicities, Grade 4 or 5 events, drug related serious adverse events or pneumonitis of any grade. The most common drug-related adverse events were those typically associated with osimertinib treatment, including diarrhea, maculopapular rash, anemia and fatigue, most Grade 1 or 2. Pharmacokinetic analyses showed dose-proportional tegavivint exposure with no evidence of a drug-drug interaction with osimertinib. Additional results include:

• Amongst all evaluable patients treated, the Overall Response Rate (ORR) was 79%, with complete responses (CR) observed in 3 of 19 patients (16%), including a CR in the one patient enrolled whose lung cancer harbored a Wnt-pathway activating mutation (WPAM).
• In the doses escalation portion of the study, the median progression free survival (mPFS) for all evaluable patients was 19.9 months and median overall survival (mOS) was 48.8 months, only 6 events have occurred.
• Preliminary results suggest combination of osimertinib and tegavivint has the potential to improve the depth and durability of response through targeting drug-tolerant persister (DTP) cells and may be better tolerated than current FDA-approved combinations.

Data from the dose-escalation portion of the study were shared in an oral presentation at ASCO 2026 (Abstract #547976).

About Tegavivint
Tegavivint is a potent and selective small molecule that functions as a downstream inhibitor of the Wnt/β-catenin signaling pathway by binding to TBL1. By disrupting the nuclear β-catenin complex, tegavivint aims to inhibit the expression of genes that drive tumor growth, survival and resistance to therapy across multiple cancer types.

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. 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. The Company has received $26 million in Product Development Awards from the Cancer Prevention and Research Institute of Texas (CPRIT). For more information, visit www.iteriontherapeutics.com.

Investor Contact:
Laurence Watts
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Media Contact:
Ryan Walker
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SOURCE Iterion Therapeutics