On April 5, 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, reported 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 (Press release, Artios Pharma, APR 5, 2022, View Source [SID1234611449]).
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Artios also announces a poster presentation at the upcoming American Association for Cancer Research (AACR) (Free AACR Whitepaper) 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
Abstract LB520 – A pharmacodynamic platform using liquid biopsy to support dose selection for the ATR inhibitor ART0380 (IACS-030380)
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