tegavivint (BC2059) / Iterion Therap, Apollomics - LARVOL DELTA

Iterion Therapeutics Expands Clinical Development of Tegavivint, a First-in-Class Wnt/β-Catenin Inhibitor, into Colorectal Cancer with First Patient Dosed (PRNewswire)

Trial status • Colorectal Cancer

Tegavivint directly targets TBL1 to inhibit b-catenin nuclear oncogenic activity (AACR 2026) - "Similar to tegavivint, these series bind directly to TBL1, disrupt the β-catenin/TBL1 interaction, inhibit β-catenin dependent transcription, and promote nuclear β-catenin degradation. These findings establish the oncogenic driver gene TBL1 as a novel, druggable target in the WNT/ β- catenin signaling pathway and highlight tegavivint as a differentiated therapeutic strategy for Wnt-driven cancers."

Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • TBL1XR1

Tegavivint, a first-in-class TBL1 inhibitor demonstrates potent activity in WNT-driven colorectal cancers (AACR 2026) - "Tegavivint demonstrated synergistic activity when combined with VEGF-TKIs and pan-RAS inhibitors, while combination with other Wnt-inhibitors yielded no added activity.Conclusion. These findings underscore the translational promise of Tegavivint as a therapeutic strategy in colorectal cancer, supporting its advancement toward clinical development to improve outcomes in WNT-driven disease subsets."

Colorectal Cancer • Hepatocellular Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ANXA5 • APC

Safety and Efficacy of Tegavivint in Patients With Metastatic Colorectal Carcinoma (clinicaltrials.gov) - P1/2 | N=126 | Recruiting | Sponsor: HonorHealth Research Institute

New P1/2 trial • Colorectal Cancer • Oncology • Solid Tumor • BRAF

Tegavivint With Gemcitabine in Patients With Relapsed or Refractory Osteosarcoma (clinicaltrials.gov) - P1 | N=24 | Recruiting | Sponsor: Emory University | Not yet recruiting ➔ Recruiting

Enrollment open • Oncology • Osteosarcoma • Sarcoma • Solid Tumor

Tegavivint for Treating Patients With Relapsed or Refractory Large B-Cell Lymphoma (clinicaltrials.gov) - P1 | N=18 | Recruiting | Sponsor: Lapo Alinari | Trial completion date: Mar 2027 ➔ Mar 2028 | Trial primary completion date: Mar 2027 ➔ Mar 2028

Trial completion date • Trial primary completion date • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • High-grade B-cell lymphoma • Indolent Lymphoma • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • BCL2 • BCL6 • MYC

Iterion Therapeutics Announces First Patient Dosed in Clinical Study of Tegavivint, a First-in-Class Wnt/β-Catenin Inhibitor, in Relapsed/Refractory Osteosarcoma (PRNewswire) - "The trial is sponsored by Emory University, conducted at the Aflac Cancer and Blood Disorders Center of Children's Healthcare of Atlanta and supported by funding from the Peach Bowl LegACy Fund, reflecting strong academic, clinical and philanthropic commitment to advancing new therapies for this rare pediatric cancer."

Trial status • Osteosarcoma

A Phase Ib Study of Osimertinib and Tegavivint as First-Line Therapy in Patients with Metastatic EGFR-Mutant Non-Small Cell Lung Cancer (NSCLC) (IASLC-WCLC 2024) - P1 | "Once the dose escalation phase of this trial is complete, the dose expansion phase will include a total of 12 patients at the RP2D to further assess clinical outcomes, including response rate, progression free survival, duration of response, and overall survival. Correlative studies include PK analysis, the evaluation of pharmacodynamic markers of β-catenin pathway activity, assessment of the clearance of EGFR-mutant ctDNA, and CT tumor volumetric studies."

Clinical • Metastases • P1 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

Tegavivint for the Treatment of Relapsed or Refractory Leukemia (clinicaltrials.gov) - P1 | N=9 | Active, not recruiting | Sponsor: M.D. Anderson Cancer Center | Trial completion date: Dec 2025 ➔ Feb 2027 | Trial primary completion date: Dec 2025 ➔ Feb 2027

Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Tegavivint With Gemcitabine in Patients With Relapsed or Refractory Osteosarcoma (clinicaltrials.gov) - P1 | N=24 | Not yet recruiting | Sponsor: Emory University | Initiation date: Oct 2025 ➔ Jan 2026

Trial initiation date • Oncology • Osteosarcoma • Sarcoma • Solid Tumor

OSU-20298: Osimertinib and Tegavivint as First-Line Therapy for the Treatment of Metastatic EGFR-Mutant Non-small Cell Lung Cancer (clinicaltrials.gov) - P1 | N=24 | Recruiting | Sponsor: Ohio State University Comprehensive Cancer Center | Trial primary completion date: Jul 2025 ➔ Jul 2026

Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Actionable Findings from an Unbiased Drug Screen for Novel Single Agent and Combination Therapies Against AML with Mecom Re-Arrangement (ASH 2023) - "This was consistent with previous reports that BET inhibitors (e.g., OTX015, mivebresib or ABBV-075 and JQ1) are effective against 3q26.2-r AML cell lines, patient-derived (PD) AML cells and PDX models...In follow-up experiments, XIAP/cIAPs inhibitors birinapant (10-1000 nM) or SM-164 (30-1000 nM), chosen based on the MIPE screen outcomes, induced significantly more dose-dependent apoptosis in 3q26.2-r versus the other AML cell lines...Treatment with the dual mTOR/PIK3CA inhibitor NVP-BGT226 (1-30 nM) or navitoclax or Bcl-xL-specific BH3 mimetic A-1155463 also exerted lethality and synergistically induced apoptosis with mivebresib in AML cells with inv3/t(3; 3)...Co-treatment with birinapant and tegavivint also synergistically induced apoptosis in 3q26.2-r AML cells...Additionally, compared to each drug or vehicle control, co-treatment with birinapant and the BETi OTX015 (30 mg/kg/day, by oral gavage) was more effective in reducing AML burden in the xenograft model...."

Combination therapy • Acute Myelogenous Leukemia • Oncology • BCL2L1 • BRD4 • CASP3 • CDK4 • CTNNB1 • GATA2 • HEXIM1 • MCL1 • MECOM • MYC • PIK3CA • SF3B1 • XIAP

WNT16 mediates mesenchymal transition and resistance in Glioblastoma (SNO 2025) - "BC2059 also sensitized GBM tumors to IR, reduced tumor growth and improved animal survival in both syngeneic and orthotopic xenograft mouse models. Collectively, our findings highlight a key role for WNT16 in mediating therapy-induced GSC plasticity and resistance."

Brain Cancer • Glioblastoma • Solid Tumor

EXAMINING THE THERAPEUTIC EFFECT OF TBL1/ β-CATENIN TARGETED COMBINATION THERAPIES ON METASTATIC OSTEOSARCOMA (CTOS 2025) - "Targeting the TBL1/β-catenin axis with Tegavivint in combination with Ponatinib or Vorinostat may offer a more effective treatment strategy for high-risk OS. These combinations show promise in overcoming drug resistance and improving outcomes for patients with limited options."

Combination therapy • Metastases • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • CTNNB1 • MYC • TBL1XR1

WNT16 mediates mesenchymal transition and resistance in Glioblastoma (WFNOS 2025) - "BC2059 also sensitized GBM tumors to IR, reduced tumor growth and improved animal survival in both syngeneic and orthotopic xenograft mouse models. Collectively, our findings highlight a key role for WNT16 in mediating therapy-induced GSC plasticity and resistance."

Brain Cancer • Glioblastoma • Solid Tumor

TBL1 Inhibition Eradicates Drug Resistant Leukemia Initiating Cells in T-ALL (ASH 2024) - "This approach aims to sensitize T-ALL cells to standard chemotherapy agents (vincristine, dexamethasone, L-asparaginase, referred to as VDL) in both in vitro and in vivo settings, as part of the preclinical evaluation of tegavivint in T-ALL treatment. These findings support our hypothesis that inhibiting TBL1-β-catenin is a viable target in T-ALL. Further preclinical studies are ongoing to evaluate the potential of this approach for clinical use."

Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • T Acute Lymphoblastic Leukemia • T-cell Acute Lymphoblastic Lymphoma • ANXA5 • CD1a • CD7

Targeting the DNA Damage Response through TBL1X in Mantle Cell Lymphoma (ASH 2024) - "Moreover, proteasomal inhibitor MG132 restored RAD51 protein levels when combined with tegavivint suggesting that TBL1X is involved in controlling RAD51 protein stability rather than its transcription. We believe these findings support further exploration of targeting of TBL1X in MCL with tegavivint. To leverage this finding of TBL1X-mediated DDR regulation, we are currently exploring novel drug combinations targeting genomic instability to maximize the therapeutic potential of tegavivint in this disease."

IO biomarker • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • ANXA5 • CUL1 • MYC • PLK1 • RAD51

Activity of Tegavivint in Hepatocellular Carcinoma with Aberrant Wnt/β-catenin Signaling and Evaluation of Biomarker Response (AACR-NCI-EORTC 2025) - P1/2 | "CTNNB1-mutant models showed enhanced responses, including growth inhibition, differentiation, and transcriptomic reprogramming. These data support the use of Wnt/β-catenin pathway inhibitors as a precision medicine strategy in CTNNB1-mutant HCC and highlight the need for further studies in immune-competent models and biomarker-enriched clinical trials."

Biomarker • Desmoid Tumors • Hepatocellular Cancer • Oncology • Sarcoma • Solid Tumor • AFP • ANXA5 • AXIN2 • GLUL • LGR5

Calcium Channel Blockers and Irreversible EGFR TKIS. Opportunities Missed? (IASLC-WCLC 2025) - "Study in cell lines concluded that β-Catenin could become a novel therapeutic target in combination with irreversible EGFR-TKIs, such as Afatinib, but not with reversible EGFR TKIs such as Erlotinib...An ongoing (2024) study of Osimertinib and Tegavivint, a novel ß-catenin / Wnt inhibitor indicate that β-catenin could be a relevant target with Osimertinib, an irreversible EGFR TKI. Another study showed that irreversible EGFR TKI Afatinib and Ethacrynic Acid, a diuretic agent, have strong antitumor effects in vitro and in mice models of EGFR/T790M NSCLC by inhibiting WNT/ß-catenin pathway...Amlodepine or Verapamil are candidates for clinical trials with Afatinib or Osimertinib...Repurposing of existing medications can save patients' time and provide safe, affordable and effective treatments that improve SOC. Industry sponsorship of repurposed drugs and clinical trials are not readily achievable and other mechanisms for financial incentives and sponsorship..."

Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • Thoracic Cancer • ABCB1

Osimertinib Combined With Tegavivint Is Safe and Tolerable as First-Line Therapy in Patients With Metastatic EGFR-Mutated NSCLC (IASLC-WCLC 2025) - P1 | "This novel combination has the potential to improve the durability of response through targeting DTP cells and may be better tolerated than current FDA-approved combinations that use chemotherapy or antibody-based therapies. These data provide support for a phase 2 head-to-head study comparing the efficacy of osimertinib versus osimertinib plus tegavivint."

Clinical • Metastases • Desmoid Tumors • Hepatocellular Cancer • Lung Cancer • Non Small Cell Lung Cancer • Sarcoma • Solid Tumor • EGFR

Tegavivint With Gemcitabine in Patients With Relapsed or Refractory Osteosarcoma (clinicaltrials.gov) - P1 | N=24 | Not yet recruiting | Sponsor: Emory University

New P1 trial • Oncology • Osteosarcoma • Sarcoma • Solid Tumor

Tegavivint, a downstream Wnt/ß-catenin inhibitor: Interim results from a phase I/II trial in advanced hepatocellular carcinoma (aHCC) (ESMO-GI 2025) - P1/2 | "Tegavivint is tolerable and demonstrates preliminary efficacy in aHCC, with more pronounced benefits observed in pts with β-catenin activating mutations."

Metastases • P1/2 data • Hepatocellular Cancer • Oncology • Solid Tumor • AFP • AXIN1

Tegavivint triggers TECR-dependent nonapoptotic cancer cell death. (PubMed, Nat Chem Biol) - "TECR is canonically involved in the synthesis of very-long-chain fatty acids but appears to promote nonapoptotic cell death in response to CIL56 and tegavivint via the synthesis of the saturated long-chain fatty acid palmitate. These findings outline a lipid-dependent nonapoptotic cell death mechanism that can be induced by a drug candidate currently being tested in humans."

Journal • Oncology • Sarcoma • Solid Tumor

A Study of Tegavivint (BC2059) in Patients With Advanced Hepatocellular Carcinoma (clinicaltrials.gov) - P1/2 | N=178 | Recruiting | Sponsor: Iterion Therapeutics | N=108 ➔ 178

Enrollment change • Hepatocellular Cancer • Oncology • Solid Tumor • AXIN1

Tegavivint Demonstrates Preliminary Antitumor Activity, Safety in Advanced HCC (OncLive) - P1/2 | N=108 | NCT05797805 | Sponsor: Iterion Therapeutics | "Administration of tegavivint at doses of up to 6.5 mg/kg weekly demonstrated early signs of efficacy and safety, with primarily low-grade treatment-related adverse effects (TRAEs), in patients with advanced hepatocellular carcinoma (HCC), according to data from a phase 1/2 trial (NCT05797805) presented at the 2025 AACR Annual Meeting....Regarding efficacy, 11% of evaluable patients on the study achieved an overall response rate (ORR) per mRECIST criteria. Best responses included partial response (PR; 8%), stable disease (SD; 42%), progressive disease (PD; 29%), and not evaluable (NE; 21%). The disease control rate (DCR) in the overall patient population was 63%."

P1/2 data • Hepatocellular Cancer