In 2008, as the first group of pioneers to return to China to conduct research on small molecule anticancer drugs, Dr. Youzhi Tong said, there were not many companies doing new drug research and development in China at that time, and the development of the innovative pharmaceutical industry was still in the early stages.
Before 2008, Dr. Youzhi Tong served as the vice president of a new drug R&D company Angion Biomedica in the United States for six years, leading the team from start-up to maturity. This entrepreneurial experience is of great significance for Dr. Tong to found Kintor Pharmaceutical. “I understand how to build a new drug research and development enterprise from scratch." said Dr. Tong.
In the 1980s, there was a saying in China that “You can conquer everything in the world if you have mastered mathematics, physics and chemistry”. Thus, Dr. Youzhi Tong chose to study chemistry at Peking University. He stayed at Peking University after completing his undergraduate and graduate studies. During his study at Peking University, biology became the most popular subject direction. "When I arrived in the United States, I wanted to move from chemistry to biology." In 1997, Dr. Tong obtained a pharmacology PhD degree at Cornell University and Sloan Kettering Cancer Center. He was then obtained his postdoctoral research there. From 1999 to 2001, Dr. Tong was an assistant professor at the Albert Einstein College of Medicine.
All changed in 2007 when Dr. Tong came back to China because his father was diagnosed with prostate cancer. "At that time, the domestic level of experimental equipment and other hardware has reached a pretty good level, but the gag of new drug R&D level is still high between China and western developed countries. I think this was a good opportunity to go back to China and to do something good for the country." Dr. Tong recalled.
The anti-prostate cancer star medicine Proxalutamide is about to be commercialized
The incidence of prostate cancer has increased year by year. From 2014 to 2018, it has been the second fastest growing cancer type in China, and it ranked first in the ten common cancers in the world, which seriously affects the health of men. "With the changes in people's eating habits and the extension of lifespan, the possibility of elderly men suffering from prostate cancer became very high. This is a 'modern disease'. Thus, I believed that the market will be huge for the development of anti-prostate cancer drug." Dr. Tong Youzhi told to VCBEAT
Excessive androgen levels are one of the causes of prostate cancer. Androgen deprivation therapy has been used as the initial therapy for metastatic prostate cancer, which is castration by removing bilateral testes or combined with androgen blocking therapy. Although the initial remission rate is high, but many patients eventually progressed after androgen deprivation therapy, which is called castration-resistant prostate cancer (CRPC).
The first new drug developed by Kintor Pharmaceutical is Proxalutamide (GT0918), which is for the treatment of metastatic castration-resistant prostate cancer (mCRPC). It is the second-generation androgen receptor (AR) antagonist, belonging to the first-in-class new drug. The research topic of Proxalutamide was listed in the national "12th Five-Year Plane" major new drug creation special project in 2011. It was one of the smallest and shortest established companies among the many companies that undertook the special project at that time. Subsequently, in 2017, the same research topic was once again rated as a national "13th Five-Year Plan" major new drug creation special project.
Proxalutamide is a new compound based on the core structure of Pfizer's new anti-prostate cancer drug Enzalutamide, and computer-aided design using the crystal structure of the target protein as well as repeated optimization. Its chemical structure has many changes compared to Enzalutamide, resulting improved molecular solubility and kinetic properties. It avoids excessive accumulation of the drugs, which may eliminate the central nervous system and other side effects of Enzalutamide clinically exposed.
In addition, Proxalutamide has a dual mechanism of action that is not available in existing second-generation AR antagonists on the market. Through its unique pharmacological effect that can reduce the expression of AR protein, it is expected to overcome the resistance of prostate cancer cells to existing drug treatments. It would become a potential best-in-class drug for mCRPC.
It was reported that Proxalutamide has started clinical trials in China and the United States at the same time. Its second-line therapy and first-line therapy for mCRPC are in phase III clinical stage in China. It is expected to submit a single drug NDA in 2020. In the United States, the trial is in phase II stage and is expected to be completed by 2020.
In addition to the treatment of mCRPC, Kintor Pharmaceutical also actively explores other indications of Proxalutamide. They have completed Phase I/Ib clinical trials of Proxalutamide for the treatment of metastatic breast cancer in China. Kintor is undergoing phase Ic clinical trials in combination with aromatase inhibitor and androgen receptor antagonist-Exemestane, Letrozole and Fulvestrant. Proxalutamide is expected to become the world's first AR antagonist for the treatment of breast cancer.
Dr. Tong is full of hope for the prospects of Proxalutamide: "We will accelerate the clinical and commercialization of Proxalutamide and strive to bring better treatment options to the majority of prostate cancer patients."
Pyrilutamide is a potential prospective treatment for Androgenic Alopecia
According to industry report data, in 2018, more than 92.8 million people in China and more than 31.1 million people in the United States in the 30-70-year-old population suffered from varying degrees of androgenic alopecia (also known as "seborrheic alopecia") ), and the number will continue to rise. The hair loss treatment drug market is huge, but how does Kintor Pharmaceutical expands from cancer to the field of hair loss treatment?
"During the screening process of the company's first project (Proxalutamide), we unexpectedly discovered the candidate compound Pyrilutamide. Because of its short half-life, it is more suitable for development as a topical drug. According to its mechanism of action, Pyrilutamide can just be used for the treatment of androgenic alopecia," said Dr. Tong.
At present, the two hair loss treatment drugs that have been approved for marketing are Minoxidil and Finasteride. Minoxidil is limited in its use due to its lack of a clear mechanism of action and possible adverse reactions (propylene glycol allergy and orthostatic hypotension). Since Finasteride may cause loss of libido, sexual dysfunction and impotence, it has deterred many men.
Pyrilutamide has a local pharmacological effect and a low degree of systemic drug exposure, which is more likely to have better safety than existing treatments. As a potential first-in-class topical AR antagonist, Pyrilutamide has the hope to redefine the market landscape of androgenic alopecia.
Currently, Pyrilutamide is being conducted a phase II clinical trial for androgenetic alopecia in China, and will be completed a phase Ib clinical trial in the United States this year. In March of this year, Kintor Pharmaceutical and Sinopharm Holdings Co., Ltd. reached a strategic cooperation in order to fully prepare for better patient service and market development of Pyrilutamide.
Focusing on androgen receptor (AR)-related diseases and developing multiple new drugs simultaneously
The R&D pipeline of Kintor Pharmaceutical
Besides Proxalutamide and Pyrilutamide in Kintor’s R&D pipeline, the faster progressing project is ALK-1 monoclonal antibody, which is a new antibody candidate drug for the treatment of variety of tumors. Kintor has obtained an exclusive global license from Pfizer for this antibody. This biomacromolecule project is currently being conducted a phase II clinical trial in Taiwan with PD-1 antibody (Nivolumab) for the treatment of metastatic liver cancer.
The company's projects also include clinical stage compounds mTOR1/ mTOR2 dual-target inhibitor Detorsertib (GT0486) and Hedgehog/SMO inhibitor, as well as preclinical stage compounds AR-Degrader, c-Myc inhibitors and IDO inhibitors, etc.
Kintor Pharmaceutical’s historical financing
In terms of financing, Kintor Pharmaceutical has completed five rounds of financing. On December 31, 2019, Kintor Pharmaceutical submitted a listing application to the Hong Kong Stock Exchange, which will become another small-molecule targeted drug company to be listed in Hong Kong this year after InnoCare.
Kintor Pharmaceutical officially obtained the Hong Kong Stock Exchange hearing recently, and is currently actively preparing for listings in Hong Kong. We believe that good news will come soon.