On August 3, 2023 RS Oncology reported exciting new science to patients who will have the best chance of benefiting from new therapies (Press release, RS Oncology, AUG 4, 2023, View Source [SID1234633791]). PRX3 is a novel drug target with potential for treating patients with the asbestos related cancer, mesothelioma. It is a key defense against oxidative stress and is located in the mitochondria, the energy generating factories. Inhibiting PRX targets cancer, not normal cells.
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MITOPE, a first-in-human Phase 1 clinical trial, is investigating a first-in-class PRX3 inhibitor, RSO-021 (clinicaltrials.gov using the identifier NCT05278975, sponsor RS Oncology, LLC [RSO], Boston, USA). Dose escalation is ongoing across four UK sites with a planned enrollment by Q2 2024. Phase 2 expansion will bring on board additional sites in Q4 of 2023.
Early experience with RSO-021 in MITOPE was presented to a global audience of mesothelioma clinicians, scientists, and allied professionals at the 2023 International Mesothelioma Interest Group (iMig) conference hosted in Lille, France in June. The industrial symposium was entitled New Horizons for Cancer Therapy – Targeting Oxidative Stress Vulnerabilities.
Brian Cunniff, Ph.D., Chief Science Officer for RSO, and Assistant Professor of Pathology and Laboratory Medicine at the University of Vermont Cancer Center, explained how tumor cells utilize increased levels of Reactive Oxygen Species (ROS) as a driver of pro-tumor signaling pathways. He also described the discovery of PRX3 as a target to leverage ROS dependency in cancer. RSO-021 irreversibly binds and inhibits PRX3, leading to tumor-specific cell death. Dr. Cunniff stated that "RSO-021 is an exciting new therapeutic option for patients suffering with mesothelioma. RSO-021 exploits a universal vulnerability of tumor cells through a novel mechanism of action, leaving tumor cells unable to clear toxic waste products. We are excited to see our laboratory findings translated to patients in collaboration with RS Oncology."
Dr. Sean Dulloo, a UK investigator based at the University Hospitals of Leicester and University of Leicester, shared early insights in the safety and activity in MITOPE. Three cases were presented demonstrating the impactful tumor responses and reduced MPE levels with disease stabilization and improved quality of life.
Key opinion leader and IMIG 23 research medal winner, Professor Dean Fennell, also from Leicester, summarized the evolving mesothelioma treatment landscape and unmet needs. "PRX3 is a novel and interesting therapeutic drug target with potential for treating cancers, especially those with unmet need such as mesothelioma. We await the first clinical results with interest."
For more information about MITOPE clinical trial visit Mesothelioma UK. The study is supported by NIHR.