On September 28, 2021 Artios Pharma Limited (Artios), a leading biotech company pioneering the development of novel small molecule therapeutics that target the DNA Damage Response process in order to treat patients suffering from a broad range of cancers, reported it has dosed the first patient in its Phase 1/2a study with its polymerase theta (Polθ) inhibitor, ART4215 (Press release, Artios Pharma, SEP 28, 2021, View Source [SID1234590357]). The Polθ project was originally in-licensed from Cancer Research UK in 2016 as part of the initial formation of Artios.
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The open label, multi-center study will assess the safety, tolerability, pharmacokinetics, and clinical activity of ART4215 administered orally as a monotherapy and in combination with other anticancer medicines in patients with advanced or metastatic solid tumors. The study will enroll up to 206 patients and will be conducted at multiple oncology centers across the USA and Europe. The trial is led by principal investigators Erika P. Hamilton, M.D., Director of the Breast Cancer and Gynecologic Cancer Research Program, Sarah Cannon Research Institute at Tennessee Oncology, and Timothy Yap, M.B.B.S., Ph.D., Associate Professor of Investigational Cancer Therapeutics and Medical Director of the Institute for Applied Cancer Science at The University of Texas MD Anderson Cancer Center. Interim safety and tolerability data is expected in 2022. Full details can be found at www.clinicaltrials.gov under the identifier NCT04991480.
Dr. Niall Martin, Chief Executive Officer at Artios, said: "The initiation of our Phase 1/2a study is an important milestone for Artios and the DNA Damage Response field in general, launching the first evaluation of a specifically designed Polθ inhibitor in the clinic. Polθ is an important tumor-specific DDR target which we believe has the potential to exploit certain genetic vulnerabilities of cancer cells with defective DNA repair processes, while sparing healthy tissue. We have brought forward to the clinic a new and exciting inhibitor class where preclinical data shows the possible clinical utility that a potent, selective Polθ inhibitor may have as a single agent in patients who have progressed on PARP inhibitors, in combination with PARP inhibition in PARPi naïve patients and in combination with DNA damaging therapies such as ionizing radiation and cytotoxic chemotherapy. The progress of ART4215 supports Artios’s approach to leverage our internal expertise in identifying promising new DDR targets, developing novel molecules, working with our collaborators at Cancer Research UK, and advancing these molecules into the clinic. It has been a very productive year at Artios with the execution of our $153M Series C financing in July and now the expansion of our clinical pipeline, building upon our ongoing clinical development of ART0380, an ATR inhibitor, and our collaborations with Merck KGaA and Novartis."
Principal Investigator for the trial, Dr. Erika P. Hamilton, Director of the Breast Cancer and Gynecologic Cancer Research Program, Sarah Cannon Research Institute at Tennessee Oncology, said: "I am encouraged by the preclinical data for ART4215 that demonstrates the molecule’s potential to address areas of high unmet need such as overcoming de novo and acquired resistance to PARP inhibitors and DNA damaging therapy. We look forward to advancing these important studies for an entirely new class of inhibitors for patients who need more effective treatment options."
ART4215 is the first selective, orally bioavailable, small molecule inhibitor of the Polθ polymerase domain to enter the clinic. Polθ, a DNA polymerase, is a tumor-specific DDR target involved in microhomology mediated end joining (MMEJ) that is overexpressed in many tumors and found in low levels in healthy tissue. Extensive preclinical studies have demonstrated that ART4215 has broad potential clinical utility, as described in Artios’s recent Nature Communications publication, Zatreanu et al., 2021.