ART0380 / Artios Pharma - LARVOL DELTA

ARTIST: Study of ART0380 in Patients With Biologically Selected Solid Tumors (clinicaltrials.gov) - P2 | N=36 | Active, not recruiting | Sponsor: Artios Pharma Ltd | Trial completion date: Mar 2025 ➔ Jul 2025

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

Ruthenium-Catalyzed Enantioselective Alkylation of Sulfenamides: A General Approach for the Synthesis of Drug Relevant S-Methyl and S-Cyclopropyl Sulfoximines. (PubMed, J Am Chem Soc) - "Alternatively, sulfoximine alkylation with dibromoethane followed by acid-mediated decarboxylation provided the S-cyclopropyl sulfoximine. The efficient asymmetric synthesis of the preclinical candidate LTGO-33 and the formal asymmetric synthesis of the phase II clinical candidate ART0380 demonstrate the utility of the disclosed approach."

Journal

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 • Colorectal Cancer • Oncology • Solid Tumor • ATM

Artios Pharma Reports Differentiated Clinical Activity in STELLA Phase 1/2a Study for Lead Program ART0380 at the American Association for Cancer Research (AACR) Annual Meeting 2025 (GlobeNewswire) - P1/2a | N=547 | STELLA (NCT04657068) | Sponsor: Artios Pharma Ltd | "As of the data cut-off in February 2025, 87 patients with advanced/metastatic solid tumors who had no satisfactory alternative therapy available to them were treated with ART0380 in combination with low-dose irinotecan, of which 58 patients were treated at the RP2D....37% confirmed overall response rate (cORR) in patients with ATM-negative1 and ATM-low1 cancers (14/38), according to RECIST. 50% cORR in ATM-negative cancers (10/20) with a median duration of response (mDoR) of 5.7 months (several responses ongoing). 22% cORR in ATM-low cancers (4/18) with the median duration of response not reached. Responses were observed in 8 different solid tumor types. The combination had a favorable safety profile, was well tolerated, and was shown to be suitable for long-term dosing."

P1/2 data • Solid Tumor

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

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

Discovery of ART0380, a Potent and Selective ATR Kinase Inhibitor Undergoing Phase 2 Clinical Studies for the Treatment of Advanced or Metastatic Solid Cancers. (PubMed, J Med Chem) - P1/2, P2 | "Herein, we describe the discovery and characterization of ART0380 (6), a potent and selective ATR inhibitor with a compelling in vitro and in vivo pharmacological profile currently undergoing Phase 2 clinical studies in patients with advanced or metastatic solid tumors as monotherapy and in combination with DNA-damaging agents (NCT04657068 and NCT05798611). ART0380 (6) has a favorable human PK profile suitable for both intermittent and continuous once-daily (QD) dosing, characterized by a dose-proportional increase in exposure and low variability."

Journal • Metastases • P2 data • Ataxia • Immunology • Movement Disorders • Oncology • Primary Immunodeficiency • Solid Tumor

ARTIST: Study of ART0380 in Patients With Biologically Selected Solid Tumors (clinicaltrials.gov) - P2 | N=37 | Active, not recruiting | Sponsor: Artios Pharma Ltd | Recruiting ➔ Active, not recruiting | N=60 ➔ 37 | Trial primary completion date: Mar 2025 ➔ Nov 2024

Enrollment change • Enrollment closed • Metastases • Monotherapy • Pan tumor • Trial primary completion date • Endometrial Cancer • Oncology • Solid Tumor • PD-1 • PD-L1

A Study of ART0380 for the Treatment of Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1/2 | N=372 | Recruiting | Sponsor: Artios Pharma Ltd | N=242 ➔ 372

Enrollment change • Metastases • Monotherapy • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Peritoneal Cancer • Prostate Cancer • Solid Tumor • ATM • BRCA • HRD

A phase II, open-label, multicenter, basket study of the ATR kinase inhibitor ART0380 administered orally as monotherapy to patients with biologically selected advanced or metastatic solid tumors (ARTIST) (SGO 2024) - P2 | "If ≥3 objective responses are observed in a cohort of 15 patients, additional patients may be enrolled at that dose regimen. The study is open with 1 patient dosed at time of submission."

Clinical • Metastases • Monotherapy • P2 data • Pan tumor • Colorectal Cancer • Endometrial Cancer • Gynecologic Cancers • Microsatellite Instability • Oncology • Solid Tumor • CCNE1 • FBXW7 • MSI • TP53 • WRN

Ataxia-Telangiectasia Mutated (ATM) loss of function displays variant and tissue-specific differences across tumor types. (PubMed, Clin Cancer Res) - "These data help to better define ATM LOF across tumor types in order to optimize patient selection and improve molecularly targeted therapeutic approaches for patients with ATM LOF cancers."

Journal • Ataxia • Immunology • Movement Disorders • Oncology • Primary Immunodeficiency • ATM

First results from the phase I trial of the ATR inhibitor, ART0380, in advanced solid tumors (ESMO 2023) - P1/2 | "ART0380 has a PK profile conducive with both intermittent and continuous dosing. The DcoDeR platform enabled the successful identification of pts with cancers sensitive to ATR inhibition."

Metastases • P1 data • Anal Carcinoma • Biliary Cancer • Cholangiocarcinoma • Endometrial Adenocarcinoma • Endometrial Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • CTCs

Artios Presents Positive Initial Phase 1/1b Clinical Monotherapy Data for ATR Inhibitor ART0380 in Advanced Solid Tumors at the European Society of Medical Oncology Congress 2023 (GlobeNewswire) - P1/2a | N=242 | NCT04657068 | Sponsor: Artios Pharma Ltd | "Artios Pharma Limited...presented promising monotherapy data from the Phase 1/1b portion of the ongoing Phase 1/2a study (NCT04657068) of its ataxia telangiectasia and Rad-3 related ('ATR') kinase inhibitor ART0380 in advanced or metastatic solid tumors as part of a poster presentation at the European Society of Medical Oncology Congress (ESMO) 2023....'We expect initial Phase 2 combination data with gemcitabine in patients with platinum resistant ovarian cancer in the first half of 2025, and with irinotecan in ATM deficient cancers in the second half of 2024'....Molecular responses and reduction in tumor size observed in multiple cancer types, including those harboring molecular alterations or biology consistent with high replication stress; Molecular responses were associated with longer progression free survival (PFS); Durable confirmed responses in all enrolled patients with high grade endometrial cancer."

P1 data • Endometrial Cancer • Fallopian Tube Cancer • Gynecologic Cancers • Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor

Artios to Present Initial Phase 1 Clinical Monotherapy Data for ATR Inhibitor ART0380 in Advanced Solid Tumors at the European Society of Medical Oncology Congress 2023 (GlobeNewswire) - "Artios Pharma Limited (Artios)...announces the Company will unveil data from the initial Phase 1 study of its ataxia telangiectasia and Rad-3 related ('ATR') kinase inhibitor ART0380 as part of a poster presentation at the European Society of Medical Oncology Congress (ESMO) 2023 taking place October 20 to 24, 2023 in Madrid, Spain....Monotherapy data presented will include safety and tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy."

P1 data • Fallopian Tube Cancer • Gynecologic Cancers • Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor

ARTIST: Study of ART0380 in Advanced/Metastatic Solid Tumors Patients (clinicaltrials.gov) - P2 | N=60 | Recruiting | Sponsor: Artios Pharma Ltd | Not yet recruiting ➔ Recruiting | Initiation date: Apr 2023 ➔ Sep 2023

Enrollment open • Metastases • Monotherapy • Pan tumor • Trial initiation date • Endometrial Cancer • Oncology • Solid Tumor • PD-1 • PD-L1

The ATR inhibitor ART0380 shows preclinical efficacy in monotherapy or in combination with gemcitabine, aPD1, PARP inhibitors and topoisomerase 1 poisons (AACR 2023) - "As monotherapy, ART0380 exhibits tumour PD (γH2AX) effects and efficacy comparable to the ATR inhibitor BAY-1895344 but causing less toxicity to the gut. Here we show strong synergy when combining ART0380 with gemcitabine, the PARP inhibitor olaparib, the topoisomerase 1 poison irinotecan as well as the immuno-oncology therapeutic aPD1. Overall, these data demonstrate the high potential of ART0380 as an anti-cancer agent given as monotherapy or in combination"

Combination therapy • Monotherapy • Preclinical • Oncology • ATM

ARTIST: Study of ART0380 in Advanced/Metastatic Solid Tumors Patients (clinicaltrials.gov) - P2 | N=60 | Not yet recruiting | Sponsor: Artios Pharma Ltd

Metastases • Monotherapy • New P2 trial • Pan tumor • Endometrial Cancer • Oncology • Solid Tumor • PD-1 • PD-L1

A pharmacodynamic platform using liquid biopsy to support dose selection for the ATR inhibitor ART0380 (IACS-030380) (AACR 2022) - P1/2 | "In addition, we are now expanding our analysis into a multiplexed assay where we will measure pKAP1 as well as γH2AX to build a more detailed assessment of PD activity in patients. Updated data will be presented."

Late-breaking abstract • Liquid biopsy • PK/PD data • Oncology • CTCs

A Study of ART0380 for the Treatment of Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1/2 | N=242 | Recruiting | Sponsor: Artios Pharma Ltd | Trial completion date: Dec 2023 ➔ Jun 2025 | Trial primary completion date: Dec 2023 ➔ Jun 2025

Metastases • Monotherapy • Trial completion date • Trial primary completion date • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Peritoneal Cancer • Prostate Cancer • Solid Tumor • ATM • BRCA • HRD

Artios Announces Initiation of Phase 2 Randomized Trial for ATR Inhibitor ART0380 plus Gemcitabine in Patients with Platinum Resistant Ovarian Cancer (GlobeNewswire) - "Artios Pharma Limited (Artios)...announces the initiation of a randomized, Phase 2 expansion cohort in the ongoing Phase 1/2 trial evaluating its ataxia telangiectasia and Rad3-related ('ATR') Inhibitor, ART0380, in combination with gemcitabine for the treatment of platinum resistant ovarian cancer....The randomized, Phase 2 portion is designed to evaluate intermittent dosing of ART0380 in combination with gemcitabine in 21-day cycles in patients with high grade serous ovarian, primary peritoneal or fallopian tube carcinoma. The Phase 2 expansion in combination with gemcitabine is expected to enroll up to 60 patients....Initial Phase 2 data in patients with platinum resistant ovarian cancer expected in 1H 2025."

P2 data • Trial status • Fallopian Tube Cancer • Gynecologic Cancers • Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor

Artios Announces ATR Inhibitor, ART0380, Development On Track and Progressing Into Phase 1b Evaluation (GlobeNewswire) - P1/2a | N=232 | Sponsor: Artios Pharma Ltd | "Melissa Johnson...Principal Investigator for the trial, said: 'Following the successful completion of the intermittent monotherapy dose escalation, ART0380 has progressed to the dose expansion phase for evaluation in patients with cancers expressing low levels of the ATM protein. We also continue to explore the therapeutic potential of ART0380 in combination with gemcitabine and irinotecan.'...Initial dose escalation evaluating intermittent dosing of ART0380."

Media quote • P1 data • Oncology • Solid Tumor

Artios Announces ATR Inhibitor, ART0380, Development On Track and Progressing Into Phase 1b Evaluation (GlobeNewswire) - P1/2a | N=232 | NCT04657068 | Sponsor: Artios Pharma Ltd | "Initial dose escalation evaluating intermittent dosing of ART0380. Key safety findings (i) An encouraging safety profile with no unexpected safety findings (ii) Predictable, manageable, and reversible hematological toxicities expected from an ATR inhibitor (iii) No evidence of off target toxicity. Key pharmacodynamic and pharmacokinetic findings (i) γH2AX DNA damage biomarker data supports dose-dependent target engagement in tumor cells but not normal mononuclear cells (ii) Dose proportional increases in exposure with rapid absorption and elimination (iii) Low interpatient variability...'We look forward to additional data from the dose expansion Phase 1b study targeting ATM deficient tumors in the first half of 2023'"

P1 data • Oncology • Solid Tumor

Artios Pharma Announces Collaboration with Novartis to Create Next Generation DDR Cancer Therapies (GlobeNewswire) - "Artios Pharma...today announced a global research collaboration with Novartis to discover and validate next generation DDR targets to enhance Novartis' Radioligand Therapies (RLT)...'We look forward to continued momentum as a clinical-stage precision medicine company, building upon our recently initiated Phase 1 study of ART0380...with the expected entry of our first-in-class Pol Theta program into the clinic before year end.'....Under the terms of the agreement, Novartis will make an up-front payment of US$20 million and provide near term research funding to support the collaboration."

Licensing / partnership • Oncology

A Study of ART0380 for the Treatment of Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1/2; N=180; Recruiting; Sponsor: Artios Pharma Ltd; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Monotherapy • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Solid Tumor