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

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

Phase 1/2 trial of the TBL1 inhibitor, tegavivint, in advanced hepatocellular carcinoma (aHCC) (AACR 2025) - P1/2 | "In these early cohorts, weekly tegavivint appears tolerable and demonstrates preliminary efficacy in aHCC."

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

Targeting the DNA Damage Response through TBL1X in Mantle Cell Lymphoma. (PubMed, Blood Adv) - "Combining tegavivint with PARP-1/2 inhibitor talazoparib results in synergistic MCL cell death in vitro, and in vivo this combination significantly prolonging the survival of an MCL PDX. Together, our results define the role of TBL1X in maintaining genomic stability in MCL and establish targeting TBL1X as a novel therapeutic strategy for patients with this incurable disease."

Journal • B Cell Lymphoma • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CCND1 • RAD51

A clinical drug candidate that triggers non-apoptotic cancer cell death. (PubMed, Res Sq) - "TECR is canonically involved in the synthesis of very long chain fatty acids but appears to promote non-apoptotic 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 non-apoptotic cell death mechanism that can be induced by a drug candidate currently being tested in humans."

Journal • Oncology • Sarcoma • Solid Tumor

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 2024 ➔ Dec 2025 | Trial primary completion date: Dec 2024 ➔ Dec 2025

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

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 | N=18 ➔ 24 | Trial completion date: Dec 2024 ➔ Jul 2029 | Trial primary completion date: Dec 2024 ➔ Jul 2025

Enrollment change • Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • NOTCH3

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

A phase 1/2 study of the TBL1 inhibitor, tegavivint (BC2059), in patients (pts) with advanced hepatocellular carcinoma (aHCC) with β-catenin activating mutations. (ASCO 2024) - P1, P1/2 | "If sufficient clinical benefit is observed, the combination of tegavivint plus pembrolizumab will be explored in the second part of the study in aHCC pts previously treated with a PD-1/PD-L1 inhibitor. The first patient began treatment in October of 2023 and the first dose escalation cohort was completed in January. Three institutions are open for enrollment; 5 other sites are pending site activation; all sites are in the United States and Canada."

Clinical • IO biomarker • Metastases • P1/2 data • Desmoid Tumors • Gastrointestinal Cancer • Hematological Malignancies • Hepatocellular Cancer • Hepatology • Lung Cancer • Lymphoma • Non Small Cell Lung Cancer • Oncology • Pediatrics • Sarcoma • Solid Tumor

Inhibition of TBL1 and β-catenin interaction sensitizes acute lymphoblastic leukemia to chemotherapy (AACR 2024) - "We hypothesize that interrupting the binding of TBL1 to β-catenin abrogates leukemia cell survival and test if tegavivint sensitizes these cells to chemotherapeutic agents such as VDL (Vincristine, Dexamethasone, L-asparaginase) as part of preclinical evaluation of tegavivint in T- and B-cell ALL. Four T-ALL cell lines one patient-derived T-ALL case, B-ALL cell lines and eight patient-derived B-ALL cases were used in vitro. Our preliminary data shows that T-ALL and B-ALL are sensitive to TBL1-β-catenin inhibition using tegavivint as a monotherapy. Tegavivint can also sensitize T-ALL and B-ALL to chemotherapy (VDL). As our data supports our hypothesis that TBL-1-β-catenin inhibition is a new target in ALL therapy, further studies are in progress to preclinically evaluate this approach for clinical care."

IO biomarker • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology • T Acute Lymphoblastic Leukemia • ANXA5 • CTNNB1

In Vitro and In Vivo Models for the Development of Hair Growth Materials By Regulating the β-Catenin Signaling Pathways. (PubMed, J Med Food) - "We confirmed that 100 nM tegatrabetan (TG), a β-catenin inhibitor, decreased the proliferation of human hair follicle dermal papilla cells (HFDPCs) at 72 h...Moreover, TG inhibited the expression of cyclin D1, β-catenin, keratin 14, and Ki67. These results suggest that TG-induced inhibition of hair growth can be a promising model for developing new materials for enhancing β-catenin-mediated hair growth."

Journal • Preclinical • Alopecia • Immunology • CCND1 • KRT14

Cytosolic Cadherin 4 promotes angiogenesis and metastasis in papillary thyroid cancer by suppressing the ubiquitination/degradation of β-catenin. (PubMed, J Transl Med) - "CDH4 induces PTC angiogenesis and metastasis via the inhibition of β-TrCP1-dependent ubiquitination of β-Catenin."

Journal • Endocrine Cancer • Oncology • Solid Tumor • Targeted Protein Degradation • Thyroid Gland Carcinoma • Thyroid Gland Papillary Carcinoma • CTNNB1

Iterion Therapeutics Announces First Patient Dosed in Phase 1b/2a Clinical Trial of Tegavivint in Patients with Advanced Hepatocellular Carcinoma Who Have Failed One or More Systemic Treatments (PRNewswire) - "Iterion Therapeutics...announced today it is actively enrolling a Phase 1b/2a clinical trial of its lead molecule, tegavivint, in patients with advanced hepatocellular carcinoma (HCC) that have failed at least one line of systemic therapy....The ongoing clinical trial will enroll approximately 35 patients in dose escalation and optimization cohorts of patients with unresectable locally advanced or metastatic HCC that have failed at least one line of systemic treatment."

Trial status • Gastrointestinal Cancer • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor