Molecular and clinical responses observed across multiple cancer types, including those with high replication stress
Predictable and manageable safety profile with reliable pharmacokinetics offers combination flexibility and continuous and intermittent dosing regimens
Initial Phase 2 data from ongoing trial for ART0380 in platinum resistant ovarian cancer is expected for the gemcitabine combination in H1 2025 and for the irinotecan combination in ATM deficient cancers in H2 2024
CAMBRIDGE, UK and NEW YORK, USA, 23 October 2023: Artios Pharma Limited (Artios), a clinical-stage biotech company led by pioneers of DNA damage response (“DDR”) drug development, 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. ART0380 is a clinically advanced, oral, highly potent, and selective ATR inhibitor with best-in-class potential. The Phase 1/1b portion of the trial presented at ESMO assessed the safety and tolerability, pharmacokinetics (PK), pharmacodynamics, and preliminary efficacy of ART0380 monotherapy in patients with advanced or metastatic solid tumors. The patient population was enriched for cancers harboring DNA damage response deficiencies as identified by the Artios DcoDeR platform (n = 49).
Dr. Niall Martin, Chief Executive Officer at Artios, said: “As a master regulator of replication stress, ATR inhibition can increase DNA damage and powerfully suppress tumor growth across broad cancer types harboring genetic defects. However, durability and long-term use with first-generation ATR inhibitors has been limited by challenges with toxicity and tolerability. Our next-generation ATR inhibitor ART0380 has demonstrated highly encouraging molecular and clinical responses as a monotherapy particularly in patients with DDR deficiency and high replication stress alterations. We believe the predictable and manageable safety profile and reliable pharmacokinetics of ART0380 offers combination flexibility as well as continuous and intermittent dosing regimen options. We look forward to further evaluating the therapeutic potential of ART0380 alone and in combination with chemotherapies in patients with selected cancer biologies as part of the ongoing Phase 2 trial. 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.”
Key Phase 1/1b efficacy data support ART0380 is active across tumor types:
- 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
- Potent tumor-specific DNA damage detected by selective increases in γH2Ax in circulating tumor cells but not normal cells in DDR deficient tumors predicted through Artios’ DcoDeR platform
Key Phase 1/1b safety and PK data demonstrate ART0380 is well-tolerated and predictable:
- Safe and well tolerated at intermittent and continuous doses
- Predictable, manageable, and reversible on-target anemia
- Dose proportional increases in exposure with rapid absorption and relatively rapid elimination and low variability
The global, open-label, multi-center, Phase 1/2a study is evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of ART0380 as a monotherapy or in combination with gemcitabine or irinotecan in patients with advanced or metastatic solid cancers. In the Phase 1/1b portion of the trial, patients with advanced solid cancers receiving escalating doses of ART0380 on a continuous daily (QD) or intermittent (3 days on, 4 days off) schedule will be evaluated. Patient enrollment was enriched for those with cancers harboring DNA damage response deficiencies as identified by the Artios DcoDeR platform. The Phase 2 portion will evaluate intermittent dosing of ART0380 in combination with gemcitabine in patients with platinum-resistant high grade serious ovarian, primary peritoneal or fallopian tube carcinoma, and in combination with irinotecan in ATM deficient cancers. Up to 250 patients are expected to be enrolled in the Phase 1/2a study which will be conducted at multiple oncology centers across the United States and Europe.
ART0380 is being developed as an oral anti-cancer agent for the treatment of cancers that harbor defects in DNA repair and in combination with agents including those that cause DNA damage. ART0380 was originally in-licensed by Artios from The University of Texas MD Anderson Cancer Center and ShangPharma Innovation in 2019. The molecule was jointly developed as part of a collaboration between ShangPharma and MD Anderson’s Therapeutics Discovery Division.
To view and download our ESMO poster, please click on the link below:
For more information about Artios Pharma Ltd., please contact:
Media & Investor Relations Contact:
Ligia Vela Reid
Artios is on a mission to kill cancer by exploiting DNA damage response (DDR) and repair pathways that are leveraged by cancer cells to promote their survival. Our specialized DcoDeR platform integrates Artios’ leadership capabilities, expertise and experience in DNA damage biology and drug discovery to systematically discover and develop medicines targeting the totality of the DDR. We have built an extensive DDR focused pipeline designed to address areas of high unmet needs across solid tumour indications including our ATR inhibitor, ART0380, and our Polθ inhibitors, ART4215 and ART6043, as monotherapies and with combination treatments. Together with our strategic partnerships with Merck KGaA and Novartis, and research collaborations with premiere institutions like Cancer Research UK, The Institute of Cancer Research, The Netherlands Cancer Institute, and the Crick Institute we are pioneering validated approaches to DDR drug discovery.
ART0380 is a competitive, potentially best-in-class, oral, highly potent, and selective ATR inhibitor. Ataxia telangiectasia and Rad3-related (ATR) is a master regulator of DNA replication stress response that promotes cell death by destabilizing replication forks, inducing DNA damage, or inhibiting checkpoint activation. ART0380 has broad clinical potential and is being investigated alone and in combination with other targeted therapies, chemotherapies and radiosensitiser opportunities in DDR deficient and high replication stress tumors. ART0380 was in-licensed from MDACC and ShangPharma in 2019.
About the DcoDeR platform
Artios has developed a specialized DcoDeR platform which exploits its expertise and experience in DNA damage biology and drug discovery to systematically discover and develop medicines targeting the totality of the DDR. Our world class DNA damage response discovery platform allows us to understand disease biology, identify novel targets, develop new medicines, and select and treat patients who will benefit most. DcoDeR is being leveraged in ongoing research collaborations and licensing agreements with Merck KGaA to identify novel DDR nuclease inhibitors and with Novartis to identify DDR targets to use in combination with radioligand therapies.