elimusertib (BAY 1895344) / Bayer - LARVOL DELTA

Pharmacological inhibitors of the nonsense-mediated RNA decay identified by high-throughput screening. (PubMed, RNA) - "CF patients carrying a nonsense mutation in the CFTR gene are insensitive to CFTR modulators and cannot benefit from the pharmacological therapy with Kaftrio®...At the end of the screening, we identified and validated by secondary assays three possible candidates acting as NMD inhibitors/modulators that could increase CFTR rescue in patients with PTCs, namely CC-115, samotolisib and elimusertib. The study also provides new insights into the changes occurring to cells transcriptome after the inhibition of the physiological NMD pathway, improving our knowledge of possible side effects of NMD inhibitors. This could help in the development of new compounds with more efficacy and less toxicity, that could be useful for the treatment of different genetic disorders caused by PTCs."

Journal • Cystic Fibrosis • Genetic Disorders • Immunology • Pulmonary Disease • Respiratory Diseases • CFTR

Mechanistic insights into phosphorylation-driven activation and therapeutic inhibition of human ATR-ATRIP. (PubMed, Nat Struct Mol Biol) - "Here, we present high-resolution cryo-electron microscopy structures of the human ATR-ATRIP complex in distinct functional states, including two ATPγS-bound precatalytic states, a Chk1-bound catalytic state, a TopBP1-bound activated catalytic state and four inhibitor-bound states with gartisertib, berzosertib, ceralasertib and elimusertib. In addition, inhibitor-bound structures reveal how potent and selective ATR inhibition is achieved through multipocket engagement and exploitation of active-site conformational plasticity. Together, our findings provide a structural framework for understanding multiple routes of ATR activation and inhibition, offering insights for developing next-generation ATR-targeted cancer therapies."

Journal • Oncology • CHEK1 • TOPBP1

ETCTN 10406: Testing the Addition of an Anticancer Drug, BAY 1895344, to the Usual Chemotherapy With FOLFIRI in Advanced or Metastatic Cancers of the Stomach and Intestines (clinicaltrials.gov) - P1 | N=10 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Jul 2026 ➔ Jul 2027

Trial completion date • Colorectal Cancer • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor

Testing the Addition of an Anti-cancer Drug, BAY 1895344, With Radiation Therapy to the Usual Pembrolizumab Treatment for Recurrent Head and Neck Cancer (clinicaltrials.gov) - P1 | N=7 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Dec 2025 ➔ Jan 2027

Trial completion date • Tumor mutational burden • Head and Neck Cancer • Hypopharyngeal Cancer • Laryngeal Cancer • Oncology • Oral Cancer • Oropharyngeal Cancer • Otorhinolaryngology • Salivary Gland Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Squamous Cell Skin Cancer • Thyroid Gland Carcinoma • CD4

Elimusertib exhibits strong synergy with olaparib in ovarian cancer organoids through replication fork interference. (PubMed, Sci Rep) - "Screening identified elimusertib (ATR inhibitor), proteasome inhibitors (ixazomib, carfilzomib), and dinaciclib (Cdk1/2/5/9 inhibitor) as synergistic agents with olaparib. These results demonstrate that elimusertib is a very potent ATR inhibitor for combination with olaparib and provide mechanistic insight into this synergy through replication fork interference. Because this synergy spanned both HRD and HRP organoids, these findings support further preclinical optimization and well-designed clinical evaluation of the olaparib-elimusertib combination in HGSC, with attention to dose-finding, hematologic safety, and patient selection."

Journal • Hematological Disorders • High Grade Serous Ovarian Cancer • Oncology • Ovarian Cancer • Solid Tumor • BRCA1 • CDK1 • HRD

ETCTN 10406: Testing the Addition of an Anticancer Drug, BAY 1895344, to the Usual Chemotherapy With FOLFIRI in Advanced or Metastatic Cancers of the Stomach and Intestines (clinicaltrials.gov) - P1 | N=10 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Apr 2025 ➔ Jul 2026

Trial completion date • Colorectal Cancer • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor

Testing the Addition of an Anti-cancer Drug, Elimusertib (BAY 1895344) ATR Inhibitor, to the Chemotherapy Treatment (Gemcitabine) for Advanced Pancreatic and Ovarian Cancer, and Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=14 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: May 2026 ➔ May 2027

Trial completion date • Fallopian Tube Cancer • High Grade Serous Ovarian Cancer • Oncology • Ovarian Cancer • Pancreatic Adenocarcinoma • Pancreatic Cancer • Peritoneal Cancer • Solid Tumor

ATR Targetting Enhances Craniospinal Irradiation Response in SHH-Activated TP53-Mutant Medulloblastoma (ISPNO 2026) - "SHH-3/TP53mut MED813FH and MED314FHmCL PDOX mice were treated with fractionated craniospinal irradiation (CSI) at onset of clinical tumour symptoms using a 5-days-on, 2-days-off treatment cycle where mice received 10 x 1 Gy fractions (10 Gy total) either alone or in combination with concurrent prexasertib (CHKi), ceralasertib (ATRi) or second-generation ATRi, elimusertib. Using gold standard PDOX models and methodology with high clinical fidelity, we demonstrate that ATR inhibitors significantly enhance survival when combined with CSI. These data provide a strong preclinical rationale for the clinical translation of ATR inhibitors for patients with SHH-3/TP53mut MB, a population with significant unmet clinical need."

Brain Cancer • Medulloblastoma • Solid Tumor • MYC • TP53

ATR inhibition overrides radiation-induced G2 arrest to drive post-mitotic death in medulloblastoma cells (ISPNO 2026) - " Medulloblastoma cells were treated with ATR inhibitors (elimusertib, ceralasertib) and IR, alone and in combination. Taken together, these data indicate that ATR inhibition converts radiation-induced checkpoint arrest into a lethal mitotic transition, providing a mechanistic basis for its potent radiosensitising activity and rationale for clinical evaluation."

Brain Cancer • Medulloblastoma • Solid Tumor

Decoding drug-tolerant persisters in neuroblastoma: insights into resistance to DDR inhibitors (EACR 2026) - "While DTPs have been described for other targeted therapies, their formation in response to DDR inhibition has not been characterised in NB.Material and NB cell lines SK-N-AS and SH-SY5Y, were treated with high-dose (100X GI50) CHK1 inhibitor SRA737 or ATR inhibitor elimusertib for 7 days to generate DTPs. These data demonstrate that DDR inhibitors induce a plastic, epigenetically reprogrammed persister state in NB. Its dynamic and reversible nature, together with drug-specific memory, highlights an early adaptive mechanism that may drive resistance. This work has laid the foundation for further investigation of DTP responses in NB with the final goal of identifying novel therapeutic strategies to limit the emergence of drug resistance."

Tumor mutational burden • Neuroblastoma • Solid Tumor • TMB

Testing the Addition of an Anti-cancer Drug, BAY 1895344, to the Usual Chemotherapy Treatment (Cisplatin, or Cisplatin and Gemcitabine) for Advanced Solid Tumors With Emphasis on Urothelial Cancer (clinicaltrials.gov) - P1 | N=74 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Jun 2026 ➔ Jun 2027 | Trial primary completion date: Jun 2026 ➔ Jun 2027

Trial completion date • Trial primary completion date • Biliary Cancer • Biliary Tract Cancer • Breast Cancer • Cervical Cancer • Cholangiocarcinoma • Endometrial Cancer • Esophageal Cancer • Gastric Cancer • Genito-urinary Cancer • Head and Neck Cancer • Hormone Receptor Positive Breast Cancer • Lung Cancer • Malignant Pleural Mesothelioma • Mesothelioma • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Penile Cancer • Small Cell Lung Cancer • Solid Tumor • Triple Negative Breast Cancer • Urothelial Cancer • ER • HER-2 • PGR

Transient ATR inhibition following ionizing radiation enhances immune-mediated antitumor response and survival. (PubMed, bioRxiv) - "In vivo and in vitro studies have shown enhanced tumor cell radiosensitivity with the ATRi ceralasertib, elimusertib, and berzosertib, however, the potentiating effect of ATRi on ionizing radiation (IR) through immune-based mechanisms has only been studied with ceralasertib. ATRi elicited differential inflammatory gene induction and dose-dependent unique cytotoxicity profiles in vitro . The immune mediated antitumor effect of ATRi combined with radiation is dose and schedule dependent, and while likely a class effect, may differ between ATRi compounds."

Journal • Oncology • CD8

ETCTN 10402: Testing the Addition of an Anti-cancer Drug, BAY 1895344, to Usual Chemotherapy for Advanced Stage Solid Tumors, With a Specific Focus on Patients With Small Cell Lung Cancer, Poorly Differentiated Neuroendocrine Cancer, and Pancreatic Cancer (clinicaltrials.gov) - P1 | N=29 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Mar 2026 ➔ Mar 2027

Trial completion date • Endocrine Cancer • Lung Cancer • Neuroendocrine Carcinoma • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Small Cell Lung Cancer • Solid Tumor

Lumit® hKi-67 immunoassay for cell proliferation with optimized performance for screening applications (AACR 2026) - "The reagent also delivered stable glow kinetics, with a signal half-life of ~6 h. Assay robustness was demonstrated by treating Jurkat cells for 48 h with palbociclib (CDK4/6 inhibitor) or BAY-1895344 (ATR kinase inhibitor). Under these conditions, anti-CD3/CD28 stimulation of primary human CD8⁺ T cells increased Ki-67 levels by 57-fold after 72 h, whereas total ATP levels increased by ~2-fold, highlighting the superior sensitivity of Ki-67 to changes in proliferative activity. The assay also performed robustly in 3D models: HCT116 spheroids generated over 3 days displayed >90% reductions in Ki-67 following 48-h treatment with BAY-1895344 or nutlin-3a (MDM2/p53 inhibitor), with the ATR kinase inhibitor demonstrating ~20-fold greater potency.Together, these results demonstrate that the Lumit® hKi-67 immunoassay is a stable, scalable, and automation-friendly platform suitable for high-throughput screening and for profiling proliferative and antiproliferative..."

Oncology • CD8

Mechanistic studies of fibroblast activation protein activated prodrug AVA6000 in pancreatic and liposarcoma models (AACR 2026) - P1 | "In addition, we studied the effects of the FAP inhibitor Talabostat (PT100) in reversing the effects of AVA6000 in co-culture conditions. Further, we tested the effects of the combination of an ATR inhibitor BAY1895344 in combination with AVA6000 in the coculture system. The GI50 of AVA6000 in two pancreatic cancer cell lines ASPC-1 and Mia-Paca-2 in the co-culture system with PSCs was 58±21.4nM, (Stdev,n=3) and 66.5±16.3nM (Stdev, n=3)... AVA6000, is selectively activated by FAP expressing PSCs and is active in pancreatic and liposarcoma co-culture models. It also exhibits synergistic growth inhibition activity with ATR inhibitors in liposarcoma co-culture models. Clinical trials of AVA6000 are ongoing (NCT04969835)."

Liposarcoma • Oncology • Pancreatic Cancer • Sarcoma • Solid Tumor • CAFs • FAP

Ataxia telangiectasia and Rad3 related kinase inhibitors and gemcitabine induce synergistic killing of uterine leiomyosarcoma cells (AACR 2026) - "Therefore, we investigated the potential for ATR inhibitors to enhance the potency and efficacy of chemotherapy for uLMS in vitro. CellTitre Glo, Bliss Independence analysis, and Multidimensional Synergy of Combinations (MuSyC) assessed synergy between three ATRi (elimusertib, ceralasertib, berzosertib) and SOC chemotherapy (gemcitabine, doxorubicin, docetaxel) in three commercially available (SK-LMS-1, SK-UT-1B, SK-UT-1) and two patient-derived uLMS cell lines (ACI-44A, ACI-44B). Elimusertib strongly synergizes with gemcitabine in vitro across uLMS cell lines by potentiating DNA damage and apoptosis. The lack of synergy with docetaxel or doxorubicin underscores gemcitabine as the most effective combination with ATR inhibitors. These finds support further preclinical and clinical evaluation of elimusertib + gemcitabine as a promising novel therapy for uterine leiomyosarcoma."

Gynecologic Cancers • Leiomyosarcoma • Oncology • Sarcoma • Solid Tumor • Uterine Leiomyosarcoma • ANXA5 • ATR • CASP3 • CHEK1

Targeting replication stress promotes immunogenic cell death in chordoma (AACR 2026) - "To assess the effects of exacerbating replication stress in chordoma, a panel of 14 cell lines was treated with the DNA synthesis inhibitor gemcitabine or the ATR inhibitor elimusertib (BAY 1895344). Moreover, treatment with either drug resulted in the accumulation of double-stranded DNA in the cytoplasm, along with upregulation of type I interferon, immunomodulatory chemokines CXCL10 and CCL5, and cell surface PD-L1. These findings are consistent with a model where ATRi or gemcitabine treatment promotes lethal DNA damage and immunogenic cell death in chordoma, which may be further augmented by PD-1 checkpoint blockade."

Immunogenic cell death • Chordoma • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • CHEK1 • CXCL10 • PD-L1

YF550 is a potent and selective inhibitor of KIF18A, specifically targeting CIN+ cancer cells (AACR 2025) - "In contrast to the Eg5 inhibitor Ispinesib, YF550 does not inhibit normal PBMC proliferation...YF550 has demonstrated synergistic effects when combined with various agents, including Olaparib (PARP inhibitor), PF-07104091 (CDK2 inhibitor), Elimusertib (ATR inhibitor), Volasertib (PLK1 inhibitor), and MMAE, in cellular proliferation assays. In the OVCAR3 ovarian cancer xenograft model, YF550 has shown superior efficacy compared to KIF18A inhibitor AMG650 at a 5 mg/kg dose, with no significant impact on body weight. Furthermore, YF550 induced tumor regression in both the OVCAR8 ovarian and JIMT-1 HER2 positive breast cancer xenograft models. YF550 exhibits superior ADME and PK property suitable for clinical development for CIN+ cancers with high aneuploidy score and has the potential for combination therapy with PD-1/L1 antibodies, PARP1 inhibitors, and MMAE based ADC."

IO biomarker • Late-breaking abstract • Breast Cancer • Head and Neck Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Ovarian Cancer • Solid Tumor • Triple Negative Breast Cancer • HER-2 • KIF18A

ATR and PKMYT1 inhibition re-sensitize a subset of TNBC patient-derived models to carboplatin inducing mitotic catastrophe. (PubMed, Cancer Res Commun) - "Inhibiting ATR with BAY1895344 or AZD6738 re-sensitized carboplatin-resistant PDXCs and PDXs to carboplatin, resulting in an increase in DNA damage, and apoptosis. Molecular factors associated with response to the ATR inhibitor/carboplatin combination included low RNA levels of PKMYT1. These results underscore the pivotal roles of ATR and PKMYT1 in mediating resistance to carboplatin in TNBC and support targeting these pathways to overcome carboplatin resistance in this disease."

Journal • Ataxia • Breast Cancer • Immunology • Movement Disorders • Oncology • Primary Immunodeficiency • Solid Tumor • Triple Negative Breast Cancer • CDK1 • FOXM1 • PKMYT1

Morphology-guided classification of oral cancer using patient-derived organoids and its therapeutic implications (AACR 2025) - "As a result of evaluating 14 drugs by organoid subtype in a high-throughput drug evaluation system using a 384-well plate, normal-like or grape-like organoids showed a good response to single drug treatment. We observed that dense organoids, which exhibited resistant responses to single drugs, showed an increased synergistic effect when co-treated with the first-line standard chemotherapy drug, cisplatin, and the ATR inhibitor (bay1895344), compared to other subtypes."

Clinical • Tumor mutational burden • Head and Neck Cancer • Oncology • Oral Cancer • Solid Tumor • TMB

Investigating genes and pathways determining sensitivity or resistance to anti-L1cam ADCs in lymphomas (AACR 2025) - "LOF and GOF CRISPR-Cas9 screenings identified genes related to resistance or sensitivity to anti-L1CAM ADCs that could be potentially used as therapeutic targets or biomarkers."

ADC • IO biomarker • Cutaneous T-cell Lymphoma • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Oncology • Solid Tumor • T Cell Non-Hodgkin Lymphoma • ABCB1 • ARID1A • CASP9 • CD20 • CDKN2B • CHD4 • FBXW7 • L1CAM • MAPK9 • RAD51B • RIF1 • RIPK1 • SOX11 • TP53

Small molecule inhibitor of FEN1 nuclease utilizing a novel metal-binding pharmacophore synergizes with inhibitors of USP1, PARP, PARG and ATR (AACR 2024) - "Synergistic relationships of BSM-1516 and its combination potential were further explored in viability studies with a panel of DDR inhibitors (n=25) in BRCA2-proficient and deficient cell lines. Strong synergy was identified with multiple drug classes that included inhibitors of USP1 (KSQ-4279), PARP (Olaparib, Niraparib, Talazoparib, AZD5305), PARG (PDD 00017273) and ATR (AZD6738, VE-822, Elimusertib).In vitro ADME assays and in vivo PK studies showed that BSM-1516 has properties suitable for in vivo testing, either as a single agent or in combination with synergistic DDR inhibitors, an investigation that is currently underway."

Oncology • BRCA2 • FEN1 • RPA2 • USP1

Harnessing a radiation-resistant organoid platform to propose novel strategies for precision treatment of advanced oral cancer (AACR 2025) - "The ATR inhibitor, BAY1895344, demonstrated synergistic effects...This study aims to address the limitations of existing preclinical models by utilizing patient-derived organoids that preserve tumor heterogeneity, thereby providing a platform and treatment prediction for clinically relevant research. These findings are anticipated to contribute significantly to the development of precision medicine-based therapeutic strategies for advanced oral cancer."

Metastases • Head and Neck Cancer • Oncology • Oral Cancer • Solid Tumor • Squamous Cell Carcinoma

ATR inhibitors synergize with DHFR inhibitors in rhabdomyosarcoma cells by disrupting DNA damage checkpoint (AACR 2024) - "In this study, we aimed to explore a potential synergistic interaction using a combination treatment of ATR inhibitors (elimusertib and ceralasertib) and DHFR inhibitors (pralatrexate, methotrexate, and raltitrexated) in multiple RMS cell lines. Our findings warrant further research into identifying genomic regions where the DNA damage is enriched in combination treatment by using END-sequencing and synthesis-associated with repair sequencing (SAR-seq). In conclusion, this study provides promising rationale for the combination treatment of ATR and DHFR inhibitors to treat RMS patients, including those with advanced, relapsed, and metastatic states."

Late-breaking abstract • Oncology • Rhabdomyosarcoma • Sarcoma • Solid Tumor • CHEK1 • DHFR

Unveiling markers of response to ATR inhibitor and TMZ combinations in rare tumor PDXs (AACR 2025) - "The combination of ATR inhibitors with temozolomide (TMZ) [ATRi+TMZ] enhances the cytotoxic effects of TMZ by targeting DNA damage response pathways, particularly in cancer cells with impaired DNA repair mechanisms, offering a promising therapeutic strategy for tumors resistant to conventional treatments. This study utilized gene expression profiling of 38 rare tumor patient-derived xenograft (PDX) models available in the NCI Patient-Derived Models Repository (PDMR) (https://pdmr.cancer.gov) to identify potential biomarkers that predict responses to TMZ combined with either of two ATR inhibitors, i.e., AZD6738 (Ceralasertib) and BAY1895344 (Elimusertib)...Our findings revealed distinct expression signatures associated with favorable responses to two ATR inhibitors when individually combined with TMZ, highlighting candidate markers that could guide treatment decisions. Additional validation in a larger study would establish the potential utility of these candidate genes..."

Biomarker • Oncology • MCM2 • MGMT