The new article “Quantitative Systems Pharmacology Model to Predict Target Occupancy by Bruton Tyrosine Kinase Inhibitors in Patients With B-Cell Malignancies” by Oleg Demin Jr, Ying Ou, Galina Kolesova, Dmitry Shchelokov, Alexander Stepanov, Veronika Musatova, Sri Sahasranaman, Yating Zhao, Xiangyu Liu, Zhiyu Tang, William D. Hanley was published in CPT: Pharmacometrics & Systems Pharmacology Journal on February 12, 2025. The work was supported by BeiGene.

Oleg Demin Jr, Scientific Director, Oncology & Immuno-Oncology, highlights “The aim of this work was to simulate the target occupancy of three approved covalent BTK inhibitors, not only in PBMC but also in tissues such as lymph nodes and bone marrow. Consistent with observed clinical data, the model predicted that zanubrutinib 160 mg twice daily resulted in higher trough BTK occupancy compared with approved doses of ibrutinib and acalabrutinib. Remarkably, due to the mechanistic description of BTK turnover and its inhibition, the model can potentially be used to simulate target occupancy for reversible BTK inhibitors and even BTK protein levels during treatment with targeted protein degraders. Moreover, BTK occupancy in non-oncology indications can also be predicted. The development of this versatile and highly reproducible model was enabled by the application of our established software infrastructure, namely, the Heta compiler and HetaSimulator.”

Learn more about Heta Project: hetalang.github.io

About InSysBio

InSysBio is a group of Quantitative Systems Pharmacology (QSP) companies located in Limassol, Cyprus (INSYSBIO CY Ltd) and Edinburgh, UK (INSYSBIO UK LIMITED). InSysBio was founded in 2004 and has an extensive track record of helping pharmaceutical companies to make right decisions on the critical stages of drug research and development by application of QSP modeling. InSysBio’s innovative QSP approach has already become a part of the drug development process implemented by our strategic partners: there are more than 100 completed projects in collaboration with leaders of pharmaceutical industry. For more information about InSysBio, its solutions and services, visit www.insysbio.com

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