BOYU ZHONG

President, CSO​​
Tyligand Bioscience Ltd

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Boyu Zhong was a chemical engineer by training (B.E. Hefei University of Technology). He worked as a petrochemical product engineer for 5 years in Sinopec after an M.E. program (Research Institute of Petroleum Processing, Sinopec, Beijing). His life science career began with an M.S. education in carbohydrate chemistry (Prof. Roger W. Binkley, Cleveland State University, Ohio). He received his Ph.D. in bioorganic chemistry from Northwestern University (Prof. Richard B. Silverman) and completed postdoctoral fellow training in organic synthesis at California Institute of Technology and Harvard University (Prof. Andrew G. Myers). 

Boyu Zhong started his drug discovery adventure at Eli Lilly and Company in 2000, seeking new kinase inhibitors as anticancer agents.  In 2010，he left Lilly and worked with Dr. Joe Chuan Shi to establish the New Drug Discovery Unit at Crown Bioscience (Taicang, Jiangsu), a pioneer of biomedical enterprise in China. Since 2014, he has been leading new drug research in Immune Sensor (Dallas, USA), Gan & Lee (Beijing, China), and Tyligand Bioscience (Shanghai, China), etc. He has over 25-year experience in cancer research, leaving a long track record of drug hunting success. Over 10 candidates to his credit have entered clinical trials, including Bozitinib/Vebreltinib, which was named after him and is the most selective kinase inhibitor drug known so far (approved in China and pending approval in US).

Speech title & Synopsis

Bozitinib: from bench to bedside

Aberrant activity of c-Met can cause abnormal signaling in cells, leading to tumor growth, migration, invasion, and metastasis. Bozitinib (CBI-3103, CBT-101, PLB-1001, Vebreltinib) is an oral and highly selective Type I c-Met inhibitor discovered in Crown Bioscience. After many years of dedication, it is eventually approved for the treatment of c-Met dysregulated NSCLC (2023) and PTPRZ1-MET fusion gene positive high grade GBM (2024) in China (pending approval in USA).
Bozitinib binds to c-Met protein at the kinase catalytic site, competing with ATP. Of a panel of 468 kinases, it interacts with c-Met only, at an affinity of 8 nM. It showed high selectivity and activity in relevant cellular assays, too. It demonstrated excellent antitumor effects in vivo in HGF ligand-dependent (KP4) and ligand-independent (MKN45) Cell-Derived Xenograft (CDX) models. In addition, it exhibited outstanding antitumor effects in many Patient-Derived Primary Xenograft (PDX) models with various c-Met dysfunctional signaling, such as gene amplification, overexpression, mutation, and fusion. In preclinical studies, Bozitinib presented good physical properties (low MW, logD, PSA, and good FasSIF solubility), good in vitro DMPK profile (CYPs and metabolic stability), and excellent oral PK parameters cross species. Furthermore, acute 4-day rat toxicology study demonstrated good exposure and safety properties. Translation medicinal study revealed that genomic alterations in the form of MET exon 14 skipping mutation is an independent prognostic factor associated with poor survival rate in patients with NSCLC. Recently, a study based on the mutational landscape of 188 sGBMs demonstrated that Met-exon-14-skipping, PTPRZ1-MET fusions, and MET amplification promotes glioma progression. In clinical studies, Bozitinib has behaved as a safe and effective treatment for patients of NSCLC or GBM with alterations in c-Met function.