ART6043 / Artios Pharma - LARVOL DELTA

First data disclosure of the first-in-class DNA polymerase theta inhibitor, ART6043, as monotherapy and in combination with olaparib, in patients with molecularly-selected advanced solid tumors (ESMO 2025) - P1/2 | "In combination with ola, there were 3 responses: 2 partial responses per RECIST (ovary [ BRCA1 mutation], breast [ CHK2 mutation]) and 1 PCWG3 tumor marker response (prostate [ CHK2 and RAD51 mutations]). Conclusions This represents the first data disclosure of the first-in-class DNA Polθi, ART6043, which shows that the combination with ola is tolerable, has promising PK/PD data, and for the first time in humans shows encouraging clinical activity in pts with cancers haboring DDR defects."

Clinical • Combination therapy • Metastases • Monotherapy • Oncology • Solid Tumor • BRCA1 • CHEK2 • POLQ • RAD51

The pharmacological profile of ART6043, a first-in-class clinical DNA polymerase theta polymerase domain inhibitor potentiating PARP inhibitor efficacy. (PubMed, Clin Cancer Res) - P1/2 | "The data demonstrate strong potential for ART6043 as an anti-cancer therapeutic for HRD tumours in combination with PARP inhibitors. Based on this, combination therapy of ART6043 with PARP inhibitor treatment is being tested in an ongoing Phase I/IIa clinical trial (NCT05898399)."

Journal • Oncology • HRD • POLQ

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

Phase IIa, open-label, multi-center study of the DNA polymerase theta inhibitor ART6043 administered orally in combination with olaparib to patients with HER2-negative breast cancer with a germline BRCA1/2 mutation (randomized expansion of study NCT05898399). (ASCO 2026) - P1/2 | "Cell free DNA samples will be collected to assess stratification biomarkers, response and compare the occurrence of resistance mechanisms (eg BRCA reversion) between the two arms. Enrollment will continue until Q4-2027."

Clinical • Combination therapy • P2a data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • BRCA • BRCA1 • BRCA2 • HER-2 • POLQ

Artios Announces First Patient Dosed in Randomized Phase 2 POLKA Study Evaluating DNA Polymerase Theta Inhibitor ART6043 in gBRCA-mutated HER2-Negative Breast Cancer (GlobeNewswire) - "The global, multicentre, Phase 2 trial is enrolling 80 patients randomized 1:1 with gBRCAm HER2-negative, locally advanced or metastatic breast cancer who received up to three prior lines of chemotherapy and no or ≤ 1 month of prior treatment with a PARP inhibitor."

Trial status • HER2 Negative Breast Cancer

ART6043C001: Study of ART6043 in Advanced/Metastatic Solid Tumors Patients (POLKA) (clinicaltrials.gov) - P1/2 | N=181 | Recruiting | Sponsor: Artios Pharma Ltd | Active, not recruiting ➔ Recruiting | Trial completion date: Dec 2026 ➔ Sep 2028 | Trial primary completion date: May 2026 ➔ Jun 2028

Enrollment open • Monotherapy • Trial completion date • Trial primary completion date • Breast Cancer • HER2 Negative Breast Cancer • Oncology • Prostate Cancer • Solid Tumor • BRCA • HER-2

Micronuclei (MN) dynamics in preclinical models and in patient reticulocytes as a pharmacodynamic biomarker for the first in class DNA polymerase theta (PolΘ) inhibitor ART6043 (AACR 2026) - P1/2 | "These data demonstrated the utility of MN-RET as a target engagement biomarker for ART6043 in preclinical studies and in the subsequent clinical study (NCT05898399). In preclinical xenograft models ART6043 monotherapy and ART6043 in combination with olaparib induces MN-RET at doses where tumor regressions occurred. The MN-RET data evaluated in the phase 1 trial of ART6043 mirrored the preclinical data."

PK/PD data • Preclinical • Oncology • POLQ

DNA polymerase theta inhibitor, ART6043, potentiates the efficacy of 177Lu- and 225Ac-based radioligand therapies in vitro and in vivo (AACR 2025) - "This potential is pertinent to cancer therapy, as radioligand therapy (RLT), where a radionuclide is targeted to tumour cells by linking to peptides binding tumour-specific receptors, has had recent clinical success, in particular with 177Lu-PSMA-617 for prostate cancer. Key findings were confirmed for the combination of ART6043 with 225Ac-RLT.Furthermore, in vivo studies in mouse prostate cancer xenografts showed that the combination of ART6043 with 177Lu-RLT induced significant tumour growth inhibition and a significant improvement in median survival with regimens that were well tolerated. This work supports the clinical development of the combination of ART6043 with RLT to improve the clinical efficacy of RLT."

Preclinical • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • POLQ

Artios Receives U.S. FDA Fast Track Designation for DNA Polymerase Theta (Polθ) Inhibitor ART6043 for Treatment of gBRCA-mutated HER2-Negative Breast Cancer (GlobeNewswire) - "Artios is launching a global randomized Phase 2 study to evaluate ART6043 in patients with BRCA-mutant HER2-negative breast cancer who are eligible to receive a PARP inhibitor....The designation was granted based on data from the ongoing, first-in-human, Phase 1/2a study (NCT05898399), evaluating ART6043 in combination with olaparib in patients with advanced solid tumors harboring mutations in DDR pathways, including gBRCAm HER2-negative breast cancer."

Fast track • New P2 trial • HER2 Negative Breast Cancer

A patent review of DNA polymerase theta (Polθ) targeted therapies (2019-2025). (PubMed, Expert Opin Ther Pat) - "Artios' Polθ inhibitor ART6043 has excellent clinical data. The results of these trials will influence the future development of Polθ inhibitors for HR-deficient cancers."

Journal • Review • Oncology • POLQ

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

ART6043C001: Study of ART6043 in Advanced/Metastatic Solid Tumors Patients (clinicaltrials.gov) - P1/2 | N=220 | Active, not recruiting | Sponsor: Artios Pharma Ltd | Recruiting ➔ Active, not recruiting

Enrollment closed • Monotherapy • Breast Cancer • HER2 Negative Breast Cancer • Prostate Cancer • Solid Tumor • HER-2

Artios Announces Phase 1/2a Data for DNA Polymerase Theta Inhibitor ART6043 at ESMO Congress 2025 (GlobeNewswire) - "ART6043 demonstrated an expected, benign tolerability profile as a monotherapy, with no additional toxicity to that of olaparib when combined. Pharmacokinetic data support convenient and oral once-daily dosing, and no drug-drug interaction (DDI) between ART6043 and olaparib was observed. Pharmacodynamic engagement of ART6043 alone was enhanced in combination with olaparib in patients, and was similar to preclinical models where tumor regressions were seen."

P1/2 data • Solid Tumor

Polymerase Theta (Polθ) Inhibitor ART6043 in Advanced Solid Tumors in Oral Presentation at ESMO (GlobeNewswire) - "The presentation will feature the first clinical results for ART6043 from the Phase 1/2a study (NCT05898399), including safety, tolerability, pharmacokinetics, and preliminary efficacy in patients with advanced solid tumors."

P1/2 data • Solid Tumor

Artios Pharma Announces Details of Presentations at the American Association for Cancer Research (AACR) Annual Meeting 2025 (GlobeNewswire) - "Artios Pharma Limited...today announced that the company’s abstract featuring clinical trial results from its ongoing Phase 1/2a study of ART0380 in combination with low dose irinotecan has been selected for an oral presentation at the American Association for Cancer Research ('AACR') Annual Meeting 2025, taking place in Chicago from April 25 to 30, 2025."

P1/2 data • Preclinical • Solid Tumor

ART6043: a first-in-class clinical DNA Polymerase Theta polymerase domain inhibitor for potentiating PARP inhibitor efficacy (EORTC-NCI-AACR 2024) - P1/2 | "The data presented demonstrate strong potential for ART6043 as an anti-cancer therapeutic for HRD tumours in combination with PARP inhibitors."

Clinical • Oncology • POLQ

Study of ART6043 in Advanced/Metastatic Solid Tumors Patients (clinicaltrials.gov) - P1/2 | N=250 | Recruiting | Sponsor: Artios Pharma Ltd | Not yet recruiting ➔ Recruiting

Enrollment open • Metastases • Monotherapy • Breast Cancer • HER2 Breast Cancer • Oncology • Prostate Cancer • Solid Tumor • HER-2

Study of ART6043 in Advanced/Metastatic Solid Tumors Patients (clinicaltrials.gov) - P1/2 | N=250 | Not yet recruiting | Sponsor: Artios Pharma Ltd

Metastases • Monotherapy • New P1/2 trial • Breast Cancer • HER2 Breast Cancer • Oncology • Prostate Cancer • Solid Tumor • HER-2