alnodesertib (ART0380) / Artios Pharma - LARVOL DELTA

Leveraging H3K27M-Driven ATR Dependency to Enhance the Efficacy of Radiotherapy for Diffuse Midline Gliomas (ASTRO 2026) - "Materials/ To investigate whether ATR inhibition enhances radiation-induced replication stress, DNA damage, and cell death in H3K27M-mutant DMG cells, we treated H3K27M-mutated and H3 wild-type human isogenic pediatric glioma cell line pairs, murine isogenic DMG lines, and patient-derived DMG cell lines in vitro with the brain-penetrant ATR inhibitor alnodesertib, ionizing radiation, or combination thereof... H3K27M-driven DMGs exhibit high levels of replication stress, creating a therapeutically exploitable reliance on ATR. We demonstrate that ATR inhibition sensitizes H3K27M-mutant DMG cells to radiation-induced DNA damage, driving synergistic tumor cell death both in vitro and in vivo. These findings establish ATR inhibition as a promising radiosensitizing strategy, supporting the clinical translation of ATR inhibitor-radiotherapy combinations in children with H3K27M-driven DMGs."

Clinical • Brain Cancer • Diffuse Midline Glioma • Glioma • Oncology • Solid Tumor • CASP3 • CASP7 • RPA2

Alnodesertib (ART0380) potentiates the preclinical efficacy of TOP1 inhibitor-based ADCs across multiple tumour histologies (EORTC-NCI-AACR 2026) - "Abstract will be available as of 4 November (with consent of the author)"

ADC • Preclinical • Oncology • TOP1

STELLA: A Study of ART0380 for the Treatment of Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1/2 | N=542 | Recruiting | Sponsor: Artios Pharma Ltd | Trial completion date: Dec 2027 ➔ Jun 2028 | Trial primary completion date: Dec 2026 ➔ Jan 2028

Monotherapy • Platinum resistant • Trial completion date • Trial primary completion date • Colorectal Cancer • Endometrial Cancer • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer • Peritoneal Cancer • Solid Tumor • BRCA • HRD

Resistance-centered pharmacology of DNA damage response-targeted therapy: Mechanisms, predictive biomarkers, and biomarker-guided adaptive treatment strategies in solid tumors. (PubMed, Biomed Pharmacother) - "Yet inevitable therapeutic resistance limits durability of clinical benefit and now defines the central pharmacological challenge of the field, driving development of next-generation DDR inhibitors including saruparib, ART6043, RP-3467, ART0380/alnodesertib, ceralasertib, and peposertib. We propose a biomarker-guided adaptive treatment algorithm integrating longitudinal circulating tumor DNA monitoring, functional RAD51 foci assays, and AI-driven multi-omics integration to enable real-time resistance detection and mechanism-guided therapy switching. This framework advances DDR-targeted oncology from static biomarker selection toward a dynamic, resistance-aware, mechanism-matched therapeutic strategy for patients with metastatic solid tumors."

Biomarker • Journal • Review • Oncology • Solid Tumor • ABCB1 • BRCA1 • BRCA2 • RAD51 • STING • TP53BP1

STELLA: A dose expansion of the ATR kinase inhibitor alnodesertib (ART0380) administered orally in combination with low-dose irinotecan to patients with advanced or metastatic CRC and PDAC. (ASCO 2026) - P1/2 | "Pts with CRC must have received a maximum of 2 prior chemotherapies excluding prior trifluridine/tipiracil, fruquintinib, or regorafenib, and pts with PDAC must have received a maximum of 1 prior chemotherapy for advanced disease. Prior targeted agents are allowed and do not count as prior lines of therapy. Key objectives include safety, tolerability, and preliminary efficacy."

Clinical • Combination therapy • Metastases • Ataxia • Colorectal Cancer • Immunology • Movement Disorders • Oncology • Pancreatic Ductal Adenocarcinoma • Primary Immunodeficiency • Solid Tumor • ATM

H3K27M-driven hypertranscription leads to a new targetable dependency in diffuse midline gliomas. (PubMed, bioRxiv) - "These findings provide the mechanistic underpinning and preclinical rationale for including alnodesertib as monotherapy and in combination with radiation in clinical trials for children with H3K27M DMGs. The broad implications of our studies highlight ATR inhibition as a therapy for aggressive human cancers displaying hypertranscription."

Journal • Brain Cancer • Diffuse Midline Glioma • Glioma • Oncology • Solid Tumor

Artios Announces Clinical Trial Collaboration with GSK to Evaluate Alnodesertib in Combination with Risvutatug Rezetecan, a B7-H3-Targeted ADC in Gastrointestinal Tumors (The Manila Times) - "Under the terms of the agreement, GSK will sponsor and conduct the Phase 1 study and provide its B7-H3 Topo-1 ADC, while Artios will supply alnodesertib. Each party will maintain rights to its respective products, and the agreement is mutually non-exclusive. The clinical study is expected to open by the end of the year."

Licensing / partnership • New P1 trial • Gastrointestinal Cancer

Alnodesertib (ART0380) in combination with irinotecan is highly efficacious in preclinical models of ATM null pancreatic cancer (AACR 2026) - P1/2 | "Our data highlights that PDAC may represent a highly sensitive tumor type for further development of this new treatment modality exploiting cancer cell specific replication stress* Ulahannan et al. Cancer Res (2025) 85 (8_Supplement_2): CT267"

Combination therapy • Preclinical • Oncology • Pancreatic Cancer • Solid Tumor • ATM • TOP1

Combination of the ATR inhibitor, ART0380, with irinotecan for treating ATM-negative tumors (AACR 2025) - P1/2 | "In a range of CDX and PDX mouse models we show that the combination of ART0380 with irinotecan leads to robust tumor growth inhibition and, in some instances, regressions across diverse ATM negative tumor types and is well tolerated. These findings highlight ART0380 in combination with low-dose irinotecan as a promising therapeutic strategy for ATM negative cancers, which supports the ongoing clinical investigation NCT04657068."

Oncology • ATM

First results of ART0380 (an ATR kinase inhibitor) with low dose irinotecan in advanced or metastatic solid tumors (AACR 2025) - P1/2 | "ART0380 and low dose irinotecan is well tolerated and suitable for long-term dosing. Clinically meaningful activity has been demonstrated and further refined via biomarker selection (45% confirmed RECIST response rate in patients with ATM negative cancers)."

Metastases • Biliary Cancer • Cholangiocarcinoma • Oncology • Solid Tumor • ATM

A novel ATR inhibitor combined with radiation sensitizes an immunologically cold tumor to immunotherapy (AACR 2025) - "Overall, radiation+ART0380 sensitized an immunologically cold tumor to anti-CTLA4, with protons inducing long-lasting tumor regression. Protons combined with ART0380 may be a novel strategy to sensitize radioresistant and immunologically cold tumors to immunotherapy."

IO biomarker • Breast Cancer • Oncology • Solid Tumor • RAD51 • TP53BP1

STELLA: A Study of ART0380 for the Treatment of Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1/2 | N=442 | Recruiting | Sponsor: Artios Pharma Ltd | Trial completion date: Dec 2026 ➔ Dec 2027

Monotherapy • Platinum resistant • Trial completion date • Colorectal Cancer • Endometrial Cancer • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer • Peritoneal Cancer • Solid Tumor • ATM • BRCA • HRD

Artios Reports Randomized Phase 2a Study of Low Dose Alnodesertib Plus Gemcitabine Achieves Primary Endpoint in Platinum-Resistant Ovarian Cancer (GlobeNewswire) - "The results were presented...at the 27th European Society of Gynaecological Oncology (ESGO) Annual Meeting....In the Phase 2a study, 64 patients with platinum-resistant HGSOC were randomized 1:1 to receive a low dose of alnodesertib plus standard-of-care gemcitabine or the same dose of gemcitabine alone....Combining a low dose of alnodesertib with gemcitabine was statistically significant (p<0.1, one-sided test) and improved progression-free survival (PFS) with a 29% reduction in the risk of progression or death compared with gemcitabine alone 6-month PFS rate was 34% with low dose alnodesertib plus gemcitabine compared to 23% with gemcitabine alone.....Key secondary endpoints of overall response rate and overall survival were comparable in both treatment arms, with overall survival analysis confounded by a 41% cross-over rate."

P2a data • Platinum resistant • High Grade Serous Ovarian Cancer

GEICO 114-O: A randomised phase 2a evaluation of the ATR inhibitor alnodesertib (ART0380) combined with gemcitabine for platinum-resistant high-grade serous ovarian cancer (HGSOC) (ESGO 2026) - P1/2 | "There were no treatment-related deaths. Conclusion Combining alnodesertib with standard-dose gemcitabine in an unselected population increased haematological toxicity and showed a 29% reduction in the risk of progression/death, with improved 6-month PFS rate but no difference in median PFS."

Clinical • P2a data • Platinum resistant • High Grade Serous Ovarian Cancer • Oncology • Ovarian Cancer • Solid Tumor

Targeting ATR-CHK1 and ATM-CHK2 Axes in Pancreatic Cancer-A Comprehensive Review of Literature. (PubMed, Int J Mol Sci) - "Preclinical studies demonstrate that ATR inhibition disrupts replication stress tolerance, impairs homologous recombination, and disables checkpoint control, enhancing cytotoxicity from standard therapies including gemcitabine, FOLFIRINOX, fluoropyrimidines, and radiotherapy...Early-phase clinical trials of ATR inhibitors (ART0380, AZD6738, BBI-355) alone or in combination show promising safety, tolerability, and preliminary efficacy. In this review, we summarize current literature on targeting the ATM-CHK2 and ATR-CHK1 pathways in PC, highlighting preclinical evidence, clinical developments, and strategies for biomarker-driven, precision oncology approaches."

Journal • Review • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • ARID1A • CHEK1 • CHEK2

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

The H3K27M oncoprotein induces replication stress and ATR inhibitor sensitivity (SNO 2025) - "It is noteworthy that ART0380 synergizes with radiation to kill H3K27M-mutant DMG cells in vitro and (in preliminary studies) in DMG xenografts. Our findings warrant ART0380 evaluation in pediatric DMGs and the cooperative relationship with radiotherapy, standard-of-care for DMG treatment, may facilitate such future clinical trials."

Brain Cancer • Diffuse Midline Glioma • Glioma • Solid Tumor • CHEK1

The H3K27M oncoprotein induces replication stress and ATR inhibitor sensitivity (SNO 2025) - "It is noteworthy that ART0380 synergizes with radiation to kill H3K27M-mutant DMG cells in vitro and (in preliminary studies) in DMG xenografts. Our findings warrant ART0380 evaluation in pediatric DMGs and the cooperative relationship with radiotherapy, standard-of-care for DMG treatment, may facilitate such future clinical trials."

Brain Cancer • Diffuse Midline Glioma • Glioma • Solid Tumor • CHEK1

The H3K27M oncoprotein induces replication stress and ATR inhibitor sensitivity (WFNOS 2025) - "It is noteworthy that ART0380 synergizes with radiation to kill H3K27M-mutant DMG cells in vitro and (in preliminary studies) in DMG xenografts. Our findings warrant ART0380 evaluation in pediatric DMGs and the cooperative relationship with radiotherapy, standard-of-care for DMG treatment, may facilitate such future clinical trials."

Brain Cancer • Diffuse Midline Glioma • Solid Tumor • CHEK1

The H3K27M oncoprotein induces replication stress and ATR inhibitor sensitivity (WFNOS 2025) - "It is noteworthy that ART0380 synergizes with radiation to kill H3K27M-mutant DMG cells in vitro and (in preliminary studies) in DMG xenografts. Our findings warrant ART0380 evaluation in pediatric DMGs and the cooperative relationship with radiotherapy, standard-of-care for DMG treatment, may facilitate such future clinical trials."

Brain Cancer • Diffuse Midline Glioma • Solid Tumor • CHEK1

Artios Announces Oversubscribed $115 Million Series D Financing to Accelerate Clinical Programs in Indications of High Unmet Need (Artios Press Release) - "The Series D proceeds will expand the clinical evaluation of Artios’ lead program, alnodesertib, to enroll additional ATM-negative patients in each of second-line pancreatic cancer and third-line colorectal cancer...The proceeds from the financing will also be used to initiate a Phase 2 randomized clinical trial for Artios’ second potential first-in-class candidate, ART6043, in patients with BRCA-mutant HER2-negative breast cancer who are eligible to receive a PARP inhibitor...The company is also advancing a first-in-class and highly differentiated DDR inhibitor-Antibody Drug Conjugate (DDRi-ADC) program and expects to name a lead candidate in Q1 2026."

Financing • New P2 trial • Pipeline update • Colorectal Cancer • HER2 Negative Breast Cancer • Pancreatic Cancer

FDA grants fast track designation to drug combo for colorectal cancer (Medical Xpress) - "The drug combination pairs alnodesertib, a targeted therapy that blocks cancer cells' ability to repair DNA damage, and a low dose of irinotecan, a chemotherapy drug that causes that damage....The drug combination's Fast Track Designation is for patients who have already received at least two rounds of other colorectal cancer treatments that have not been effective."

Fast track • Colorectal Cancer

Artios Pharma Limited…announced that the U.S. Food and Drug Administration (FDA) granted Fast Track designation to its ATR inhibitor, alnodesertib, in combination with a low dose of chemotherapeutic agent irinotecan, for the treatment of adult patients with ATM-negative metastatic colorectal cancer (mCRC) in the third-line setting. (GlobeNewswire) - "The designation is supported by encouraging results from the ongoing STELLA Phase 1/2a study..."

Fast track • Colorectal Cancer

A Study of ART0380 for the Treatment of Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1/2 | N=597 | Recruiting | Sponsor: Artios Pharma Ltd | Trial completion date: Jun 2025 ➔ Dec 2026 | Trial primary completion date: Jun 2025 ➔ Dec 2026

Monotherapy • Platinum resistant • Trial completion date • Trial primary completion date • Colorectal Cancer • Endometrial Cancer • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer • Peritoneal Cancer • Solid Tumor • ATM • BRCA • HRD

ARTIST: Study of ART0380 in Patients With Biologically Selected Solid Tumors (clinicaltrials.gov) - P2 | N=36 | Terminated | Sponsor: Artios Pharma Ltd | Active, not recruiting ➔ Terminated; Sponsor decision, not for reasons affecting the benefit-risk balance.

Monotherapy • Pan tumor • Trial termination • Endometrial Cancer • Oncology • Solid Tumor • PD-1 • PD-L1