QSP modeling of OPB-171775, a phosphodiesterase 3A–Schlafen 12 molecular glue, to predict clinical responses in patients with gastrointestinal stromal tumors
Tomohiro Sasaki, PhD, Senior Manager, Otsuka Pharmaceutical Co.,Ltd., Osaka, Japan
Tomohiro Sasaki is a scientist with a main interest in pharmacometrics. He obtained his PhD in pharmaceutical sciences from Kyushu University (Fukuoka, Japan) in 2011. After working as a clinical pharmacologist in Nippon Boehringer Ingelheim, he joined Otsuka Pharmaceutical in 2015, where he is in charge of modeling & simulation work of several projects. He has experience in clinical pharmacology, pre-clinical, clinical PK/PD analysis, and modeling and simulation in various therapeutic areas.
Live Webinar Recording - in English
Presentation Only - in Japanese
Gastrointestinal stromal tumor (GIST), the most common mesenchymal tumor having KIT or platelet-derived growth factor receptor A activating mutations, is typically treated with tyrosine kinase inhibitors (TKIs), such as imatinib. OPB-171775 (OPB) is a first-in-class anti-tumor agent that selectively kills phosphodiesterase 3A (PDE3A)/Schlafen 12 (SLFN12) double-positive cancer cells. OPB appears to induce PDE3A–SLFN12 complex formation, leading to the downregulation of anti-apoptotic proteins and increased cancer cell death. GIST cells express high levels of SLFN12 and PDE3A, making them particularly sensitive to OPB-induced tumor growth inhibition. Here, QSP modeling characterized OPB’s anti-tumor effects on GISTs and predicted its clinical efficacy to aid in OPB’s therapeutic development.