elimusertib (BAY 1895344) / Bayer - LARVOL DELTA

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

X-ray preactivated reversible persistent luminescence enables photodynamic immunotherapy of deep tumors. (PubMed, Nat Commun) - "In this study, we report X-ray preactivated elimusertib-loaded tumor-targeted photodynamic nanoparticles (ETPNs), featuring reversible "on-off" afterglow properties...All in vivo experiments were conducted using female mice. Our findings highlight the potential of ETPNs to advance the therapeutic landscape for deep-seated tumors, offering a robust and controllable platform for combined immuno-photodynamic therapy."

Journal • Oncology

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

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

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

ATR inhibitors: from targeting the DNA damage response to exploiting synthetic lethality-A paradigm shift in Cancer therapy. (PubMed, Bioorg Chem) - "We provide a detailed analysis of the structure-activity relationships (SAR) of leading clinical candidates, including berzosertib, ceralasertib, and elimusertib, focusing on strategic chemical modifications such as scaffold hopping and sulfoximine substitution to optimize selectivity and druggability. Critical challenges, specifically dose-limiting hematological toxicities and acquired resistance, are analyzed alongside the search for robust predictive biomarkers. By synthesizing current pharmacological and clinical data, this work outlines the trajectory for next-generation ATR-targeted precision medicine."

Journal • Review • Ataxia • Hematological Disorders • Immunology • Movement Disorders • Oncology • Primary Immunodeficiency • Targeted Protein Degradation • ATR

Recent advances in small molecule ATR kinase inhibitors as anticancer agents. (PubMed, Future Med Chem) - "Over the last decade, intensive medicinal chemistry efforts have generated a broad pipeline of ATR inhibitors, including ceralasertib, elimusertib, camonsertib, berzosertib, ART0380, and gartisertib, many of which are in Phase I/II clinical trials. Incorporating these strategies into adaptive platform trials with pharmacodynamic markers and patient-centered outcomes will speed up translation. Overall, ATR inhibitors highlight progress in DNA damage response therapies, from understanding mechanisms to biomarker-driven clinical use, with the potential to revolutionize treatment across various cancers."

IO biomarker • Journal • Review • Ataxia • Hematological Disorders • Immunology • Movement Disorders • Oncology • Primary Immunodeficiency • Targeted Protein Degradation • RAD51

PEPN2112: Elimusertib for the Treatment of Relapsed or Refractory Solid Tumors (clinicaltrials.gov) - P1/2 | N=31 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Nov 2025 ➔ Mar 2026

Trial completion date • Ewing Sarcoma • Hematological Malignancies • Lymphoma • Oncology • Pediatrics • Rhabdomyosarcoma • Sarcoma • Solid Tumor • ATF1 • ATM • ATRX • BRCA1 • BRCA2 • CDK12 • CHEK2 • FANCA • FOXO1 • MSH2 • PAX3 • POLD1 • RAD51 • WT1 • XRCC2

Targeting the DNA damage response prevents regrowth of colorectal peritoneal metastasis-derived organoids following treatment with mitomycin C. (PubMed, Br J Cancer) - "PMDOs can be completely eradicated if MMC treatment is followed by inhibition of ATR or other DDR kinases. DDR inhibitors may therefore have value in the adjuvant treatment of peritoneal metastases following CRS-HIPEC."

Journal • Colorectal Cancer • Oncology • Solid Tumor • CHEK1

Targeting ATR to overcome cisplatin resistance in hepatoblastoma. (PubMed, J Hepatol) - "ATR mediates cisplatin resistance in HB. The combination of elimusertib and cisplatin demonstrated preclinical efficacy across patient-derived cultures and multiple in vivo HB models, supporting its potential as a promising therapy for cisplatin-resistant HB."

Journal • Hepatoblastoma • Hepatocellular Cancer • Liver Cancer • Oncology • Pediatrics • Solid Tumor

IDENTIFICATION OF A DNA REPAIR INHIBITOR FOR THE COMBINATION WITH LURBINECTEDIN AND RADIOTHERAPY IN SARCOMA CELL LINES (CTOS 2025) - "Objective: Improved multimodal treatment could optimize therapeutic outcomes for sarcoma patients. Our preclinical data suggest that the combination of LU with RT has no sensitizing effect compared to LU treatment alone in sarcoma cell lines. However, combining LU and IR with DNA repair inhibitors such as the ATRi VE-822 is a promising way to improve sarcoma treatment."

Preclinical • Fibrosarcoma • Liposarcoma • Oncology • Rhabdomyosarcoma • Sarcoma • Solid Tumor • Synovial Sarcoma • ANXA5

Differential Response to ATR/Chk1 Inhibition in Preleukemia and Transformed Leukemia in an MLL-ENL Model of Leukemogenesis Reflects Enrichment for Myc-Transcriptional Program (ASH 2024) - "We hypothesize that in preleukemia, ATR/Chk1 DNA damage response (DDR) checkpoint activation serves as part of intrinsic anti-cancer barrier, while in leukemia, ATR-dependent signaling is essential for leukemia cell proliferation and survival.We tested the consequences of ATR/Chk1 inhibition during Mll-ENL leukemogenesis, using ceralasertib (ATRi1, p.o. 25 mg/kg), elimusertib (ATRi2, p.o. 50 mg/kg) and AZD-7762 (Chk1i, i.v. 25 mg/kg), 3-5 times weekly, 1-6 months, using the preleukemic mice...In vitro, MEER cells showed high sensitivity to JAK2i ruxolitinib (RX, IC50 24 nM), higher than to the tested FLT3i...In preleukemia, attenuation of ATR/Chk1 checkpoint promotes the development of leukemia from preleukemia. Combinatory targeting of DDR components and activated oncogenic signaling to induce synthetic lethality in preleukemia stage of MLL remains to be fully elucidated."

Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • AMBRA1 • CHEK2 • FLT3

Dual inhibition of ATR and PARP reverses acquired PARP inhibitor resistance in triple negative breast cancer. (PubMed, Discov Oncol) - "HCC1937 and HCC1937-R Talazoparib (TAL) resistant cells were treated with Elimusertib (ELI) alone as ATR inhibitor (ATRi) and ELI and TAL combination. Therefore, the dual targeting of ATR and PARP is a promising modality to reverse PARPi resistance with the downregulation of ATR-Chk1 based DNA damage response. However, further preclinical and clinical investigations should be required to elucidate the underlying molecular mechanisms behind ATRi and PARPi interactions in TNBC cells."

Journal • Ataxia • Breast Cancer • Immunology • Movement Disorders • Oncology • Primary Immunodeficiency • Solid Tumor • Triple Negative Breast Cancer • ANXA5 • CHEK1

ATR Inhibitor Elimusertib Suppresses Drug Persister Clones in TP53-Mutated Acute Myeloid Leukemia Via CGAS-Sting-Mediated Cell Death (ASH 2024) - "Among these, the ataxia telangiectasia and Rad3-related protein (ATR) inhibitor elimusertib (BAY1895344) effectively inhibited TP53 mut AML DTPCs at low doses, similar to known inhibitors the CHK1 inhibitor (SRA737) and the Wee1 inhibitor (Adavosertib)...Furthermore, the triple combination treatment of cytarabine, idarubicin, and elimusertib effectively suppressed DTPC formation in TP53 mut AML cell lines...This consequently results in cGAS-STING-mediated cell death following irreparable DNA replication stress accompanied by p53 dysfunction. Our findings provide a basis for developing optimized treatment strategies for patients with TP53-mutant AML using the ATR inhibitor elimusertib."

Acute Myelogenous Leukemia • Ataxia • Hematological Malignancies • Immunology • Leukemia • Movement Disorders • Oncology • Primary Immunodeficiency • CDC25C • CDK1 • CDKN1A • CXCL10 • GNRP • IFI27 • IFIT1 • RSAD2 • SIGLEC1 • STAT1 • STING • TP53

YL0712-3, a Novel ATR/ATM Inhibitor, Demonstrates Anti-Tumor Activity in TP53 Mutant DLBCL through Synthetic Lethality and Degradation of Mutant p53 (ASH 2024) - "The in vitro activity of YL0712-3 was assessed across various TP53 mutant and wild-type DLBCL cell lines, with ATR inhibitor Elimusertib and ATM inhibitor AZD1390 as positive controls. Conclusion : The ATR/ATM inhibitor YL0712-3 effectively targets TP53 mutant DLBCL cells by inhibiting the ATM/Chk2 and ATR/Chk1 pathways and inducing proteasome-mediated degradation of mutant p53 protein. YL0712-3 exhibits promising anti-tumor activity in both in vitro and in vivo models, especially when combined with R-CHOP, presenting a potential therapeutic strategy for TP53 mutant DLBCL."

Synthetic lethality • Ataxia • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Immunology • Lymphoma • Movement Disorders • Non-Hodgkin’s Lymphoma • Oncology • Primary Immunodeficiency • Targeted Protein Degradation • CHEK2

TARGETING ATR TO OVERCOME CISPLATIN RESISTANCE IN HEPATOBLASTOMA (SIOP 2025) - "Elimusertib also synergized with other agents, including carboplatin, irinotecan and/or vincristine and demonstrated ability to inhibit mTOR. This study highlights the crucial role of ATR in cisplatin resistance and demonstrates the potent cytotoxic effects of the elimusertib/cisplatin combination in cisplatin-resistant HB models. These findings offer a promising therapeutic option for treating chemoresistant HB."

Hepatoblastoma • Hepatocellular Cancer • Liver Cancer • Pediatrics • Solid Tumor

The ATR inhibitor Elimusertib in Combination with Cisplatin in Patients with Advanced Solid Tumors: a California Cancer Consortium Phase I Trial (NCI10404). (PubMed, Cancer Res Commun) - "Cisplatin combined with elimusertib was associated with hematologic toxicity requiring significant dose de-escalation. Elimusertib PK was consistent with prior studies. Only modest activity was observed. Further clinical evaluation of elimusertib plus cisplatin is not warranted."

Journal • P1 data • Ataxia • Febrile Neutropenia • Hematological Disorders • Immunology • Movement Disorders • Neutropenia • Oncology • Ovarian Cancer • Ovarian Clear Cell Cancer • Primary Immunodeficiency • Solid Tumor • Thrombocytopenia • ATR

HER3 upregulation reduces DS-8201 sensitivity in HER2-positive tumor cells by ATR/CHK1/FoxO1 signaling cascade. (PubMed, Acta Pharmacol Sin) - "Based on this finding, we showed that combining DS-8201 with either a HER3-targeting antibody (SIBP-03) or an ATR inhibitor (BAY1895344) resulted in significant synergistic antitumor efficacy without substantial toxicity in vitro or in vivo. Overall, this study revealed that the ATR/FoxO1/HER3 pathway plays a critical role in modulating the efficacy of DS-8201, suggesting that combining DS-8201 with ATR or HER3 inhibition represents a promising therapeutic strategy for HER2-positive cancers."

Journal • Oncology • CHEK1 • ERBB3 • HER-2

Epigenetic targeting of PGBD5-dependent DNA damage in SMARCB1-deficient sarcomas. (PubMed, J Clin Invest) - "The Polycomb repressive complex EZH2 inhibitor tazemetostat was recently approved for the treatment of SMARCB1-deficient epithelioid sarcomas, based on the functional antagonism between PRC2 and SMARCB1...We leveraged this collateral synthetic lethal dependency to target PGBD5-dependent DNA damage by inhibition of ATR, but not CHK1, using the ATR inhibitor elimusertib. Consequently, combined EZH2 and ATR inhibition improved therapeutic responses in diverse patient-derived epithelioid and rhabdoid tumors in vivo. This advances a combination epigenetic therapy based on EZH2-PGBD5 synthetic lethal dependency suitable for immediate translation to clinical trials for patients."

Journal • Gene Therapies • Oncology • Rhabdoid Tumor • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • CHEK1 • PGBD5 • SMARCB1

Targeting the DNA damage response prevents regrowth of colorectal peritoneal metastasis-derived organoids following treatment with mitomycin C. (EACR 2025) - "We tested whether inhibitors of the DNA damage response (DDR) could prevent recurrence in an in vitro HIPEC model.Material and Peritoneal metastasis-derived organoids (PMDOs; n=10) were treated with inhibitors of ATR (berzosertib, ceralasertib, elimusertib), CHK1 (rabusertib), and WEE1 (adavosertib) alone, and in combination with MMC, oxaliplatin, or irinotecan. PMDOs can be completely eradicated if MMC treatment is followed by inhibition of ATR or other DDR kinases. DDR inhibitors may, therefore, have value in the adjuvant treatment of peritoneal metastases following CRS-HIPEC."

Colorectal Cancer • Oncology • Solid Tumor • CHEK1

Injectable thermosensitive hydrogel co-loading with ATRi and doxorubicin for the treatment of triple-negative breast cancer. (PubMed, RSC Adv) - "Herein, we developed an injectable thermosensitive hydrogel for localized co-delivery of ATRi-BAY-1895344 (BAY) and doxorubicin (DOX), serving as a localized drug depot to minimize systemic toxicity while ensuring sustained tumor-specific drug release exceeding 4 days. This dual-action strategy overcomes chemo-resistance by disabling DDR compensatory mechanisms and prolongs tumor suppression through controlled drug release. The hydrogel platform represents a functional innovation in localized combination therapy, integrating stimuli-responsive drug delivery with DDR pathway disruption for synergistic efficacy."

Journal • Ataxia • Breast Cancer • Immunology • Movement Disorders • Oncology • Primary Immunodeficiency • Solid Tumor • Triple Negative Breast Cancer • ATR

Phase Ib basket expansion trial and alternative-schedule dose-escalation study of ATR inhibitor elimusertib in advanced solid tumors with DNA damage response defects. (PubMed, Cancer Discov) - "There was no association between ATM protein loss or ATM alterations and progression-free survival or overall response. Further studies to define optimal predictive biomarkers for ATR inhibitors as monotherapy and in combination are ongoing."

Journal • P1 data • Breast Cancer • Gynecologic Cancers • Hematological Disorders • Oncology • Solid Tumor • ATM

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 2025 ➔ Jun 2026 | Trial primary completion date: Jun 2025 ➔ Jun 2026

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 • HER2 Breast Cancer • Hormone Receptor 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

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 primary completion date: Oct 2024 ➔ Apr 2025

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

Comparative in vivo toxicology of ATR inhibitors ceralasertib, elimusertib, and berzosertib alone and in combination with ionizing radiation. (PubMed, Toxicol Appl Pharmacol) - "Cardiotoxicity was observed following single-dose ceralasertib, but no other ATRi, possibly due to high unbound plasma drug concentrations. Our results further support and guide clinical development of ATRi in clinic."

Journal • Preclinical • Ataxia • Cardiovascular • Immunology • Movement Disorders • Oncology • Primary Immunodeficiency