- Phase 1a dose escalation of ART0380 defined initial regimen to be evaluated in Phase 1b setting.
- Phase 1a dose escalation demonstrated a predictable safety profile and no unexpected safety findings supported by data from over 35 patients.
- Dose-dependent target engagement in tumor cells but not normal mononuclear cells supported by gH2AX DNA damage biomarker data (poster presentation at AACR 2022 will feature biomarker and pharmacokinetic data supporting clinical dose selection of ART0380).
- Rapid absorption and elimination with dose proportional increases in exposure provides dosing flexibility across different administration schedules.
- Dose escalation shows ART0380 to have clinical activity and supports initiation of Phase 1b dose expansion study targeting ATM deficient tumors. Data from the Phase 1b dose expansion study is expected in the first half of 2023.
CAMBRIDGE, UK and NEW YORK, USA, 5 April 2022: Artios Pharma Limited (Artios), a clinical-stage biotech company pioneering the development of novel small molecule therapeutics that target the DNA damage response (“DDR”) process in order to treat patients suffering from a broad range of cancers, announces that the development of its ataxia telangiectasia and Rad3-related (“ATR”) Inhibitor, ART0380, has progressed into a Phase 1b dose expansion study targeting ATM deficient tumors.
Artios also announces a poster presentation at the upcoming American Association for Cancer Research (AACR) Annual Meeting, taking place April 8-13, 2022, in New Orleans, Louisiana featuring biomarker and pharmacokinetic data supporting the clinical dose selection of ART0380.
Dr. Niall Martin, Chief Executive Officer at Artios, said: “As a strong regulator of DNA repair, ATR inhibition can effectively suppress tumor growth across a broad range of cancers harboring genetic defects. However, durability and long-term use with first-generation ATR inhibitors has been limited by challenges with toxicity and tolerability. The pharmacokinetic profile of ART0380 has the potential to allow reliable and predictable dosing. We are highly encouraged with the initial dose escalation data which demonstrates that ART0380 is engaging the desired cancer pharmacodynamic targets, has a predictable and manageable safety profile and is clinically active in tumors predicted to be sensitive to ATR inhibition. We look forward to additional data from the dose expansion Phase 1b study targeting ATM deficient tumors in the first half of 2023.”
Melissa Johnson, MD, Program Director, Lung Cancer Research, Sarah Cannon Research Institute at Tennessee Oncology, 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
Key safety findings
- An encouraging safety profile with no unexpected safety findings
- Predictable, manageable, and reversible hematological toxicities expected from an ATR inhibitor
- No evidence of off target toxicity
Key pharmacodynamic and pharmacokinetic findings
- gH2AX DNA damage biomarker data supports dose-dependent target engagement in tumor cells but not normal mononuclear cells
- Dose proportional increases in exposure with rapid absorption and elimination
- Low interpatient variability
The global, open-label, multi-center, Phase 1/2a study is evaluating the safety, tolerability, pharmacokinetic profile, and preliminary efficacy of ART0380 as a monotherapy or in combination with gemcitabine or irinotecan. The dose expansion portion of the trial will evaluate the potential of ART0380 monotherapy in patients who have cancers with low expression of ATM protein kinase, and the combination with gemcitabine in patients with high grade serous ovarian, primary peritoneal or fallopian tube carcinoma. The study is expected to enroll up to 180 patients and will be conducted at multiple oncology centers across the United States and Europe.
ART0380 is an inhibitor of ATR that is being developed as an oral anti-cancer agent for the treatment of participants with 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.
AACR 2022 Poster Presentation Details
Date/Time: April 8, 2022, 12:00 PM – 1:00 PM
Session: OPO.ET05.01; Pharmacology, Pharmacogenetics, and Pharmacogenomics
Presenter: Manish Patel
Location: E-Poster Website
For more information, please contact:
Abid Ansari, Chief Financial Officer
Ligia Vela Reid
Artios is a clinical-stage biotech company pioneering the development of novel small molecule therapeutics that target the DDR process to treat patients suffering from a broad range of cancers. Artios is led by an experienced scientific and leadership team with proven expertise in DDR drug discovery, including the discovery and early development of the poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitor Olaparib. It has a unique partnership with Cancer Research UK, and collaborations with leading DNA repair researchers worldwide, such as The Institute of Cancer Research, London, the Netherlands Cancer Institute and the Crick Institute, London. Artios is building a pipeline of next-generation DDR programs to target hard to treat cancers, including its ATR inhibitor, ART0380, and the Polθ inhibitor, ART4215, as a monotherapy and with combination treatments. In December 2020, Artios entered into a collaboration agreement with Merck KGaA, Darmstadt, Germany to identify and develop precision oncology medicines targeting nucleases. Merck KGaA, Darmstadt, Germany has the right to opt into exclusive development and commercialization of compounds on up to eight targets and Artios is to receive up to US$860 million in total milestones per target. In April 2021, Artios entered into a collaboration agreement with Novartis to identify DDR targets to use with Novartis’ proprietary radioligand therapies, with Artios receiving a US$20 million up-front payment in addition to near-term research funding to support the collaboration. Artios is eligible to receive up to $1.3 billion in discovery, development, regulatory and sales-based milestones in addition to royalty payments. Artios has raised US$320 million to date from investors and strategic partners, including the US$153 million Series C financing announced in July 2021. Artios is based at the Babraham Research Campus in Cambridge, UK, with an office in New York City, USA.