Anti-cancer Drug Candidates Create Commercial and Health Benefits
Prof. Thomas Leung, Prof. Larry Chow, Prof. Zhao Yanxiang
Impact Highlights
Ranked third as the leading cause of death worldwide, cancer accounts for approximately one in six deaths annually. The global market needs for oncology medicines keep surging and its market value is estimated to increase by triple in 2027. PolyU drug inventions stapled peptide (Tat-SPs), clicked flavonoid heterodimers, BCA-PEG20 and ABarginase are potential pre-clinical and clinical trial candidates to be exploited by two pharmaceutical companies and a city government.Stapled Peptides - Cancer cells are frequently reprogrammed to become over-proliferative. To disrupt related pathways, manipulation of autophagy (cellular degradation process) was employed. Since 2018, Prof. Zhao Yanxiang utilizes a key autophagic protein as structural template to design and synthesized a series of all-hydrocarbon stapled peptides (Tat-SPs). These peptides were found to interfere with the dimerization process on the autophagy protein, causing mitochondrial stress and enhanced autophagy, leading to cancer cell death. Profound anti-proliferative effects are observed towards several cancer type which brings these peptides patented in both U.S. and Mainland China.
Flavonoids - Overexpression of membrane transporter permeability-glycoprotein (P-gp) diminishes cancer drug efficacy and causes treatment failure by the expulsion of intracellular drug molecules. The blood-brain-barrier is a P-gp rich area which prevents drug penetration and give rise to poor treatment outcomes in glioblastoma patients. Prof. Larry Chow and Prof. Tak-hang utilized click chemistry to create a flavonoid heterodimer with dual inhibitory functions towards P-gp and Breast Cancer Resistance Protein (BCRP) in combating glioblastoma. The heterodimer exhibits promising anti-cancer effect under combination therapy with sorafenib in an orthotopic and a temozlomide-resistant relapse animal model, leading to its patency in 2019.
Arginine depletion - Arginine is an essential amino acid for the survival of cancer cells where its depletion can inhibit growth and eventually leads to death via multiple cellular mechanisms, such as apoptosis and autophagy. Adopting enzymatic degradation to cease external supply of arginine in cancer cells, while leaving normal cells unharmed, provides a new cancer treatment approach. With major success in previous clinical trial during 2017, Prof. Thomas Leung expanded his research and developed a new generation of thermostable mono-PEGylated Bacillus caldovelox arginase (BCA-PEG20) with enhanced stability, efficacy and safety. BCA-PEG20 is proven to exert long lasting effectiveness towards various cancer types. Since 2021, Prof. Leung collaborates with Prof. Godfrey Chan Chi-fung of HKU to investigate the use of BCA-PEG20 in treating brain cancer.
With potent anti-proliferative activities to several cancer types, Tat-SPs has attractedintentional investor Simcere Pharmaceutical Group Limited in 2022. As a “Top Innovative Pharmaceutical Enterprises in China” and “Top 100 Pharmaceutical Manufacturing Enterprises of China”, SEHK possesses over ten recommended products in a number of clinical practice guidelines and pathways issued by the Chinese government and prestigious associations in China. In addition, over forty products are enlisted within the Chinese National Reimbursement Drug List (NRDL). Together with the expertise in R&D and commercialization, Simcere is now having initial discussions with Prof. Zhao in translating Tat-SPs into a pre-clinical trial candidate. Successful liaison is expected to generate investment capitals and new job positions.
In concomitance to the licensing achievement in 2014 with previous generation of flavonoid dimers, FD18; a new clicked flavonoid heterodimer combating glioblastoma leads to the approach by Xiamen Municipal People's Government delegates in 2023. The delegates are having positive impressions on the drug candidate and currently arranging with Prof. Chow in commencing a clinical trial program. Patients’ recruitment is expecting to begin in Q4 of 2023. Government investments as well as career opportunities are foreseeable to generate through the program. The team has also developed another heterodimer in combating cancer stem cells (CSCs) which is now in progress of application for a PolyU Micro fund (HK$0.1M) to set up a startup company at IncuBio in HKSTP. Other than this, the invention is now in preparation for filing a patent.
With the support from the ITF fund (HK$0.5 M) and PolyU Angel Fund (HK$0.5 M), Prof. Leung and his team have taken a step forward to form a startup company, PolyMedTech, aiming at the development of BCA-PEG20 for therapeutic purposes. The company is now discussing with a potential investor, Shanghai Pharmaceuticals for funding support to conduct pre-clinical trials on brain cancer. With no current FDA-approved drug in treating NAFLD and limitations arisen from prescribed medicines in treating metabolic syndrome, ABarginase has created positive impact on global health. The research team is now in preparation for manufacturing at Good Manufacturing Practices (GMP) facilities for future clinical trials.
Contact the Researcher
Prof. Thomas Leung, Professor
thomas.yun-chung.leung@polyu.edu.hk
Prof. Larry Chow, Professor
Prof. Zhao Yanxiang, Professor
Related Start-up Company
ABRAM Therapeutics Limited
Cancer Stem Therapeutics Ltd.
PolyMedTech