Undisclosed YAP/TAZ-TEAD inhibitor / Hanmi - LARVOL DELTA

Hippo-YAP/TAZ signaling in gastric cancer: molecular pathogenesis and emerging therapeutic horizons. (PubMed, Med Oncol) - "It explores the crosstalk between Hippo-YAP/TAZ signalling and other oncogenic pathways, including Wnt/β-catenin and PI3K/Akt, as well as the influence of tumour microenvironmental factors such as hypoxia and extracellular matrix stiffness on pathway activation. Additionally, emerging therapeutic strategies targeting YAP/TAZ-TEAD interactions and upstream regulators are discussed, offering potential avenues for improving gastric cancer outcomes in diagnosis and treatment."

Journal • Review • Gastric Cancer • Oncology • Solid Tumor • CTNNB1 • LATS1 • SLK

Targeting Hippo-YAP/TAZ signaling pathway: an updated review demonstrating the therapeutic potential of key plant derived anticancer compounds. (PubMed, Front Pharmacol) - "The upregulation of YAP/TAZ/TEAD complex has been demonstrated to result in cellular proliferation, transformation, and ultimately, carcinogenesis. This article offers extensive insight into plant derived anticancer compounds mainly apigenin, curcumin, EGCG, resveratrol, homoharringtonine, and ursolic acid of the Hippo pathway, specifically YAP/TAZ, in several cancer therapies. This will enhance the discovery of novel Hippo inhibitors and the optimal therapeutic application of Hippo signaling-related pharmaceuticals in synergistic cancer therapies."

Journal • Review • Oncology

Verteporfin, an inhibitor of nuclear YAP, improved multi-ciliated cell differentiation in the airway epithelium. (PubMed, J Transl Med) - "Our findings suggest YAP nuclear localization in human airway MCCs is broadly associated with decreased MCCs regardless of patient condition, and verteporfin improves airway MCC differentiation."

Journal • Gastrointestinal Disorder • Inflammation • Respiratory Diseases

In vitro evaluation of Verteporfin and exploration of TEAD palmitoylation inhibition in Piezo1-YAP/TAZ signaling and ECM remodeling. (PubMed, Sci Rep) - "Fibrosis is characterized by excessive extracellular matrix (ECM) deposition driven by mechanical stress, yet the underlying molecular mechanisms remain incompletely understood. YAP/TAZ-TEAD signaling mediates mechanically induced ECM remodeling. Activation of this pathway drives profibrotic gene expression, and disruption of YAP-TEAD interaction effectively reverses these changes, highlighting a potential therapeutic target for fibrosis."

Journal • Preclinical • Fibrosis • Immunology • ANKRD1 • CCN1 • CTGF • TAFAZZIN

Targeting TEAD in cancer. (PubMed, Front Oncol) - "Advances in understanding the YAP/TAZ-TEAD complex have informed the development of diverse strategies to inhibit downstream transcription of key oncogenic target genes. Finally, we highlight TEAD inhibitors currently in clinical trials, outlining their mechanisms of action, associated adverse effects, and potential impact on the future therapeutic landscape."

Journal • Review • Oncology

TEADES PH1/2 STUDY WITH ODM-212: PRELIMINARY RESULTS IN EHE PATIENTS (CTOS 2025) - "TEAD inhibition with ODM-212 has induced durable tumour regression in EHE, demonstrating proof-of-concept for this targeted approach in a TAZ-fusion driven sarcoma. ODM-212 showed encouraging anti-tumour activity and manageable safety, highlighting the potential of targeting the Hippo–YAP/TAZ–TEAD pathway in EHE."

Clinical • Oncology • Sarcoma • Solid Tumor • CAMTA1 • WWTR1

Epithelial-mesenchymal cell competition coordinates fate transitions across tissue compartments during lung development and fibrosis. (PubMed, Nat Commun) - "Conversely, Yap/Taz-TEAD-Myc binding instructs a myogenic, pro-fibrotic program. Our findings demonstrate that inter-tissue cell competition, governed by a Snail/Yap rheostat, orchestrates lung architecture and provides a framework for targeting the mesenchymal niche to treat fibrotic disease."

Journal • Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases • SNAI1

YAP/TAZ deletion in vascular smooth muscle cells mirrors atherosclerosis-associated transcriptional programs. (PubMed, J Mol Cell Cardiol Plus) - "These findings suggest that YAP/TAZ safeguard VSMC identity by directly repressing pro-inflammatory and osteochondrogenic programs, and that their disruption may contribute to atherogenesis. This positions YAP/TAZ-TEAD axis as a key guardian of vascular homeostasis and a potential therapeutic target for limiting plaque progression."

Journal • Atherosclerosis • Cardiovascular • WWTR1 • YAP1

Targeting YAP/TAZ-TEAD and their protein-protein interaction for precision cancer therapy. (PubMed, Eur J Med Chem) - "Notably, several pioneer TEAD inhibitors and YAP/TAZ-TEAD protein-protein interaction inhibitors have progressed into clinical trials. This review dissects the structure and mechanistic details of YAP/TAZ-TEAD interactions and provides a comprehensive overview of recent advances in chemical compounds targeting YAP, TAZ, TEAD, and YAP/TAZ-TEAD PPI, highlighting the therapeutic potential of YAP/TAZ-TEAD axis as target for precision cancer therapy."

Journal • Review • Oncology • Targeted Protein Degradation

A first-in-human study of oral IAG933 in adult patients with advanced mesothelioma and other solid tumours (ESMO 2025) - P1 | "Conclusions IAG933 is a direct inhibitor of the YAP-TEAD protein-protein interaction. In the dose escalation phase of this trial, IAG933 was well-tolerated and demonstrated clinical efficacy."

Clinical • First-in-human • Metastases • P1 data • Brain Cancer • Malignant Pleural Mesothelioma • Meningioma • Mesothelioma • Oncology • Peritoneal Mesothelioma • Pleural Mesothelioma • Solid Tumor • LATS1

Validation of an AI-powered computational chemistry workflow for streamlined drug discovery (AACR-NCI-EORTC 2025) - "Of the 17 compounds tested in vitro, one molecule demonstrated potent activity (IC₅₀ = 1.31 nM), comparable to the clinically approved PARP1 inhibitor olaparib (IC₅₀ = 1.61 nM)...In the TEAD4 case study, 1 out of 8 selected compounds exhibited superior in vitro performance (IC₅₀ = 13–18 µM) compared to IK-930 (IC₅₀ = 25–158 µM), a known TEAD family inhibitor. Inhibition of canonical YAP/TAZ-TEAD transcriptional targets suggests that this compound acts as a pan-TEAD inhibitor, with strong binding affinity for both TEAD2 and TEAD4...These findings illustrate the power of the DrugAppy to identify and prioritize novel molecular scaffolds for targeted cancer therapy. The platform enables efficient early-stage drug discovery through the integration of AI, docking, and MD simulations, supporting the development of next-generation cancer therapeutics with improved rationality and speed."

Oncology • TEAD2 • TEAD4

ADORA2B Inhibition in Mesothelioma (MMe) cells affects PDL-1 expression, exerts an effective response on Hyppo andAKT signaling and elicits anti-tumor immune response (AACR-NCI-EORTC 2025) - "The effects on the latter were by the increased expression of the YAP/TAZ/TEAD positive modulator 14-3-3 pathway linked to tumor progression. We provide the first evidence ever that A2B inhibition has an anti-tumor effect on both epithelial and non-epithelial MMe cells, decreases PDL-1 expression via AKT inhibition and exerts a significant mixed effect on YAP signaling and immune-mediated MMe growth inhibition"

IO biomarker • Mesothelioma • Oncology • Solid Tumor • ADORA2B • AKT1 • PD-L1 • TAFAZZIN • YAP1

Preclinical characterisation of a novel TEAD inhibitor ODM-212 (ESMO 2025) - P1/2 | "Results ODM-212 binds potently and specifically to all TEAD/TEF transcription factors, inhibiting YAP/TAZ-TEAD complex transcriptional activity. Legal entity responsible for the study Orion Corporation. Funding Orion Corporation."

Preclinical • Mesothelioma • Oncology • Solid Tumor • TEAD1 • TEAD2 • YAP1

Robust efficacy and favorable safety profile of pan-TEAD inhibitors in oncogenic Hippo pathway-dysregulated cancers including mesothelioma (AACR-NCI-EORTC 2025) - "The Hippo pathway regulates cell proliferation and tissue homeostasis through a YAP/TAZ-TEAD transcriptional complex...These findings highlight the potential of our optimized TEAD inhibitor as a therapeutic agent for cancers characterized by genetic alterations in Hippo signaling pathway. Comprehensive preclinical results will be disclosed upon the nomination of a development candidate."

Clinical • Brain Cancer • Head and Neck Cancer • Lung Cancer • Meningioma • Mesothelioma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CCN1 • CTGF • TEAD1

Defining a molecular basis and therapeutic approach for KEAP1-NRF2 mediated resistance to KRAS inhibition in KRAS-mutant pancreatic ductal adenocarcinoma Free (AACRPanCa 2025) - "Recent clinical observations with the approved KRASG12C selective inhibitors sotorasib and adagrasib support the therapeutic value of targeting KRAS in PDAC...This gene set was distinct from transcriptional changes associated with other transcriptional signatures driving resistance to KRAS inhibitors (ERK, MYC and YAP/TAZ-TEAD). Finally, analysis of KEAP1-loss associated genes also identified the activation of glutamine metabolism, and we found the combination treatment with the glutamine antagonist DRP-104 enhanced KRAS inhibitor-mediated growth suppression in PDAC patient-derived organoids. In summary, our studies have established the molecular mechanisms underlying KEAP1-NRF2 pathway-driven resistance to KRAS inhibition and validated a potential therapeutic strategy to overcome this resistance."

Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • KEAP1 • KRAS

the YAP/TAZ-TEAD axis promotes tumor stem cell functionality and cellular heterogeneity in pediatric high-grade gliomas (EANO 2025) - "Our results show that YAP/TAZ-TEAD inhibition may represent a promising therapeutic avenue for pHGGs."

Clinical • Heterogeneity • Brain Cancer • Glioma • High Grade Glioma • Oncology • Solid Tumor

COMBINED TEAD AND RAS INHIBITOR THERAPY ACHIEVES LONG-TERM SURVIVAL IN KRAS-MUTANT CHOLANGIOCARCINOMA (AASLD 2025) - " Bulk and scRNA-seq analysis in mouse CCA models, the TCGA and Fu-iCCA cohorts and human scRNA-seq data revealed a consistent upregulation of YAP/TAZ/TEAD pathway members...VT104 or IAG933 plus KRASG12D-specific inhibitor MTRX1133 or panRAS inhibitors RMC-7977 and RMC-6236 blocked compensatory YAP/TAZ pathway activation, achieved strong synergies in vitro and extended median survival from 2.3 weeks to 9.7 weeks (VT104 + MRTX1133, p<0.0001) and 14.4 weeks (VT104 + RMC7977, p<0.0001) in KRASG12D-driven CCA... Collectively, our study identified TEAD and RAS signaling as convergent and druggable vulnerabilities that can be targeted to prolong CCA survival and delay the development of resistance."

IO biomarker • Biliary Cancer • Cholangiocarcinoma • Oncology • Solid Tumor • CAFs • KRAS • NICD

TEAD INHIBITION BY IAG933 AS A NOVEL THERAPEUTIC STRATEGY FOR CHOLANGIOCARCINOMA (AASLD 2025) - "Cells were treated with IAG933 alone or in combination with either standard chemotherapy (gemcitabine/cisplatin; GemCis) or a pan-KRAS inhibitor (RMC-6236)... IAG933 robustly inhibits TEAD-driven transcription and suppresses CCA growth in vitro and in vivo. Its synergy with GemCis and RMC-6236 supports its potential as a therapeutic candidate for CCA, including KRAS-mutated subtypes. Notably, SOD2 upregulation as a response to TEAD inhibition may represent a general resistance mechanism in CCA."

Biliary Cancer • Cholangiocarcinoma • Liver Cancer • Oncology • Solid Tumor • CCN1 • CTGF • KRAS • SOD2

The multifaceted role of YAP in the tumor microenvironment and its therapeutic implications in cancer. (PubMed, Exp Mol Med) - "Targeting the YAP/TAZ-TEAD axis has shown potential efficacy when combined with immune checkpoint inhibitors, chimeric antigen receptor T cell therapies and tumor vaccines. Although challenges such as tumor selectivity and resistance mechanisms persist, advances in single-cell and spatial transcriptomics are enabling the dissection of YAP/TAZ-regulated networks and guiding the development of more precise therapeutic strategies. Collectively, YAP/TAZ inhibition offers a promising avenue to reprogram the TME and enhance the efficacy of next-generation cancer immunotherapies."

Biomarker • IO biomarker • Journal • Review • Oncology

Endogenous YAP/TAZ partitioning in TEAD condensates orchestrates the Hippo response. (PubMed, Mol Cell) - "Previous works propose the potential role of YAP/TAZ phase separation for transcriptional activation, yet the biomolecular basis of endogenous YAP/TAZ-TEAD condensates remains unclear...Based on this, we revisited a series of recently characterized TEAD inhibitors and identified that VGLL4 represents a critical regulator assisting TEAD central pocket inhibitors. Altogether, we demonstrate a fundamental role of TEAD condensates in spatially regulating YAP/TAZ signaling, underscoring their significance in further deciphering TEAD biology and applications in TEAD-targeted therapy."

Journal • VGLL4

Epidermal Growth Factor Receptor Activation Stimulates SOX9 Expression in Injured Renal Proximal Tubule Epithelial Cells. (PubMed, J Am Soc Nephrol) - "EGFR activation is crucial for SOX9 expression in RPTCs following AKI."

Journal • Acute Kidney Injury • Chronic Kidney Disease • Fibrosis • Immunology • Nephrology • EGFR • HBEGF • SOX9

Pipeline to evaluate YAP-TEAD inhibitors indicates TEAD inhibition represses NF2-mutant mesothelioma. (PubMed, Life Sci Alliance) - "Here, we develop a high-content pipeline that enables a comparative analysis of currently developed YAP/TAZ-TEAD inhibitors...We identify genetic compensation of the Hippo pathway transcriptional module, with implications for therapeutic targeting, and implement Cell Painting to develop a detailed morphological profiling pipeline that enables further characterisation, quantification, and analysis of off-target effects. Our pipeline is scalable and allows us to establish specificity and comparative potency within cancer-relevant assays in a clinically relevant cellular model of pleural mesothelioma."

Journal • Malignant Pleural Mesothelioma • Mesothelioma • Oncology • Pleural Mesothelioma • Solid Tumor • NF2

Hyper-responsiveness of cancer stem cells to microenvironmental cues controls metastasis and therapy response through YAP/TAZ/TEAD. (PubMed, bioRxiv) - "Targeting inputs to the YAP/TAZ/TEAD node reversed chemotherapy-induced enrichment of CSCs in lung metastases. Different population dynamics for breast cancer stem cells (CSCs) and their differentiated progeny in early metastatic colonizationCSCs are hyper-responsive to microenvironmental cues and serve as sensors of local conditions for the tumorMany microenvironmental inputs converge on YAP/TAZ to regulate self-renewal vs differentiation fate decisions in the CSCTargeting YAP/TAZ input pathways blocks chemotherapy-induced enrichment of CSCs."

Journal • Breast Cancer • Oncology • Solid Tumor

miR-127-5p-Enriched Extracellular Vesicles Modulate the Hippo Pathway to Counteract Steroid-Induced Osteonecrosis pathology of the Femoral Head. (PubMed, Free Radic Biol Med) - "Quantitative real-time PCR revealed that miR-127-5p is significantly downregulated in SONFH-hBMSCs, leading to the upregulation of LATS2 and the suppression of YAP/TAZ-TEAD activity, which are crucial for osteogenesis...However, miR-127-5p-enriched EVs reversed these effects, restoring osteogenic differentiation, improving bone microarchitecture, and enhancing gait performance in SONFH models. These findings suggest that miR-127-5p downregulation plays a critical role in SONFH progression and that miR-127-5p-enriched EVs may offer a promising therapeutic strategy to treat SONFH by promoting bone regeneration and improving functional outcomes."

Journal • LATS2 • MIR127

Cytolethal Distending Toxin-increased DNA damage and ploidy involve the YAP/TAZ-TEAD signaling pathway. (PubMed, J Infect Dis) - "Overall, these data show that infection with genotoxin-producing bacteria involves the YAP/TAZ-TEAD signaling pathway to control ploidy following DNA damage in epithelial cells."

Journal • Infectious Disease • Oncology