In 2008, after nearly 20 years studying and working in the US, Dr. Youzhi Tong made a momentous decision to return to China and start a new drug discovery company. “People who choose to start a business have great ambitions and are not satisfied with the status quo. I always aspire to make a difference and achieve something new in drugs R&D,” he said.
Kintor Pharma which is devoted to the research and development of small molecule anti-cancer drugs was formally established in March 2009. At that time, there were few novel drug discovery companies in China. Drug R&D drew little attention from the financial market, and Kintor struggled for five to six years after its founding, remaining as an “one-drug” company for a long time.
However, Kintor’s fortune took a turn for the better in 2015. As the pharmaceutical industry in China grew, Kintor Pharm started to draw more and more investors’ attention due to its core candidate—the anti-cancer drug Proxalutamide. The company has expedited the development of Proxalutamide while enriching the variety of products in its pipeline.
Over the past five years, Kintor experienced rapid growth and had five new drug candidates that are undergoing phase I-III clinical trials both in China and the United States, including the second-generation androgen receptor (AR) antagonist Proxalutamide (GT0918), topical androgen receptor antagonist Pyrilutamide (KX-826)，Angiogenesis inhibitor ALK-1 monoclonal antibody (GT90001), mTOR kinase inhibitor Detrosertib (GT0486) and Hedgehog/SMO inhibitor GT1708F. In addition, the company’s R&D pipeline includes a few pre-clinical stage products, such as androgen receptor degrader (AR-Degrader), c-Myc inhibitor, IDO inhibitor, etc.
Looking back at the past ten years, Dr. Youzhi Tong commented, “Through a decade’s unceasing introspection and learning, Kintor has formulated its unique new drug development path. In disease-related areas, we concentrate on cancer and androgen receptor (AR) related disease as our core. Meanwhile in the novel drug target aspect, a high quality clinical project group around AR has been established. In the transition from a “one-drug” company to a multi products company, Kintor seized the opportunity.
What are Kintor Pharma’s goals for the next decade? Dr. Tong aims to become an “close loop” innovative company that includes every parts of pharmaceutical industry. In addition to further improvement of research and development strength, the company will make efforts to achieve international standing and be self-sufficient in each aspect in the product chain of pharmaceutical industry, such as clinical development, manufacturing, marketing and sales etc. This target cannot be accomplished without the support of capital. With this in mind, Kintor Pharma has submitted its IPO application to HKEX on December 31st, 2019, and its hearing was set for April 26th, 2020.
“Drug R&D is accompanied by raising funds. The decision to be listed in Hong Kong stock exchange reflects the hope that Kintor will be connected with the capital platform suitable for the company’s developmental demand. This is to expedite new drugs’ approval as soon as possible, generate main business cash flow, and then in turn be able to develop more new drugs. Our mission is that our innovative drugs will be recognized world-wide for the treatments various ailments with unmet medical needs including cancer, alopecia, etc. We hope that Kintor will eventually turn into a leading biopharmaceutical company benefiting everybody in the world” said Dr.Youzhi Tong.
Establishing Kintor Pharma in the emerging field of Chinese pharmaceuticals
Kintor Pharmaceuticals, Inc. established in 2009, is a typical overseas returnee start-up. Dr. Youzhi Tong, founder of Kintor, has nearly 20 years of experience in the US.
After undergraduate and graduate study in the Department of Chemistry at Peking University, Dr. Youzhi Tong went to the US in 1990, received Ph.D degree in pharmacology from Cornell University/Memorial Sloan-Kettering Cancer Center in 1997, and then undergone postdoctoral research. He was an assistant professor at the Albert Einstein College of Medicine from 1999 to 2001.
“I started in the chemistry department of Peking University in 1980 and then turned to Biological Medicine while studying in the US. I’ve honed my skills in scientific research for nearly 20 years. All the work I’ve done is related to cancer drugs. Somewhere deep down in my heart, I’ve always wanted to discover new drugs, but actually producing and distributing a drug requires entering the pharmaceutical industry,” said Dr. Youzhi Tong.
Dr. Youzhi Tong was greeted by an opportunity in 2002, his department head had founded a new drug R&D start-up Angion Biomedica(“Angion”) and invited him to join as the vice president responsible for the company’s operations. As the day-to-day manager of Angion, Dr. Youzhi Tong handled everything from outsourcing materials, project management, pre-clinical research, IND applications, and carrying out clinical trials. That experience helped him gain knowledge in starting a new drug R&D company from ground zero. He said, “The six years during 2002 to 2008 in the US meant a lot to my career, and my work at Angion especially resulted in precious entrepreneurial experience.”
The idea of leaving Angion came up in 2007. Dr. Youzhi Tong returned to China that year and stayed a long time as his father was suffering from prostate cancer. He left with the feeling that there were huge changes coming to China. He said, “I had a strong premonition that it was time to return to China to start my own company.”
Dr. Youzhi Tong resigned form Angion and returned to China while there were very few novel drug R&D companies in China at the time.
The first time presenting his entrepreneurship program officially was in the first ChinaBio venture capital investment forum held by Suzhou Biological Park (currently Suzhou Industrial Park Biobay). According to him, the roadshow was in a tiny room in a library. Eight competitors presented their novel drugs R&D projects, and eventually, his project won the “Most Promising Company Award” from the judges.
After winning the prize, Dr. Youzhi Tong established his company in Suzhou Industrial Park BioBay. In March 2009, Suzhou Kintor was officially founded.
After a decade of persistent effort, core project Proxalutamide is nearing completion
The second generation androgen receptor (AR) antagonist Proxalutamide (GT0918) is Kintor Pharma’s first project. Regarding the reason as why he chose to start with this project, Dr. Youzhi Tong said, “It was nearly impossible to make First-in-Class drugs domestically in 2009. Therefore, we decided to use R&D projects that were in the mid to late clinical stage in US as the reference and improve upon them. Proxalutamide’s benchmark is the second generation androgen receptor antagonist Enzalutamide for prostate cancer treatment, which was undergoing phase II clinical trials in the US at that time.”
To be specific, Proxalutamide is a novel chemical entity discovered via computer-aided analysis of target protein’s crystal structures and repeated optimizations based on the core structure of Enzalutamide
Proxalutamide’s chemical structure has several modifications that improve the solubility and pharmacokinetics of the molecule and avoid excessive drug accumulation, which eliminates seizure, the main central nervous system side effects of Enzalutamide.
Dr. Youzhi Tong and his team completed pre-clinical studies of Proxalutamide at the end of 2013 and submitted the clinical trial application of Proxalutamide to the Jiangsu Drug Administration. 14 months later, Kintor received approval to conduct phase I-II clinical trials in China. In June 2015, Proxalutamide began clinical trials in China. In August that year, Kintor also received approval from the U.S. FDA to commence phase I-II clinical trials.
At this moment, monotherapy of Proxalutamide as a second-line therapy has commenced phase III clinical trials for mCRPC in China, and is about to be submitted to NDA later this year, while the phase II clinical trials in the US are being conducted simultaneously. Meanwhile, the phase III clinical trial for Proxalutamide in combination with Abiraterone (which blocks the synthesis of androgen, a treatment of mCRPC with Prednisone) as a first-line therapy for prostate cancer in China is also ongoing.
On Proxalutamide’s outlook and effectiveness, Dr. Youzhi Tong indicated that “Proxalutamide not only improves the solubility, pharmacokinetics and safety of molecule and target activity, but also more importantly has the pharmacological effect of down-regulating AR expression on top of efficient inhibition of AR. It has a “dual-action mechanism” that is unique among AR antagonists. Due to the fact that overexpression and mutation of AR are the main mechanism of prostate cancer cell developing resistance to Enzalutamide and Abiraterone, Proxalutamide is expected to conquer the resistance from prostate cancer cells by down-regulating AR expression, which will become a more efficient and safer second-generation AR antagonist for mCRPC treatment. Combining those facts, when Proxalutamide successfully reaches the market, it will be a best-in-class blockbuster product for prostate cancer treatment from a local drug discovery company who also has its full proprietary intellectual right.
Prostate cancer is one of the most common cancer types in the male population, with over 1.2 million new cases globally in 2018, second only to lung cancer. Current treatments are characterized by long treatment time and limited medication options; therefore, there is a large market space for Proxalutamide to explore. According to some analysis, the global prostate cancer treatment market is expected to grow at a CAGR of 8.7% from 2018 to nearly US$18 billion in 2023, among it over 12 billion yuan is in the Chinese market. Proxalutamide is also undergoing phase Ic clinical trials in combination with other treatments for metastatic breast cancer, which also has a large market size.
It’s worth mentioning that, following the NDA approval of Enzalutamide in November 2019, Proxalutamide is likely to compete head-on with it in the Chinese market very soon. In response to this, Dr.Youzhi Tong expressed that although Kintor obtained positive results in both pre-clinical and clinical stage, due to the significant influencing factor of price in the Chinese market, Kintor will carry out patient-centered payment in order to help more Chinese patients in need to receive treatment with Proxalutamide. He also indicated that the educational efforts on the application of second generation AR antagonist from Enzalutamide’s initial market penetration in China will benefit the market access of Proxalutamide.
In order to keep the momentum going, multiple products are in R&D
Besides Proxalutamide, Kintor has four other new drug candidates that are undergoing clinical trials, including topical androgen receptor antagonists Pyrilutamide (KX-826)，ALK-1 monoclonal antibody (GT90001), mTOR kinase inhibitor Detorsertib(GT0486) and Hedgehog/SMO inhibitors(GT1708F). The company also has diverse ongoing preclinical programs, such as androgen receptor degraders (AR – Degrader), c - Myc inhibitors and IDO inhibitors, etc.?
According to Dr.Youzhi Tong, Kintor began expanding R&D pipelines on a massive scale in 2015, when its leading project Proxalutamide achieved initial clinical success?and gained phase II/III approval in both China and the US. At the same time, the company received a US$10 million investment from Highlight Capital, which is fund focused on the health industry.
“With improvement in the field and the increasing enthusiasm for novel drugs R&D from investment institutions, I believe that we should seize the opportunity to drive multiple R&D projects at the same time,” he said.
2015 to 2019 was the critical period for Kintor Pharma in expediting development. Besides expediting development of Proxalutamide, Pyrilutamide, and Detorsertib, the company also launched new independent research and development projects, such as drugs based on PROTAC technology, androgen receptor degraders and IDO inhibitors, etc. In the meantime, Kintor licensed in projects from other sources, including fully human monoclonal antibody therapeutic drug ALK-1 from Pfizer, Hedgehog/SMO inhibitors from Suzhou Yunxuan Pharmaceutical Co. Ltd. and c-Myc inhibitors from Peking University.
Regarding Kintor Pharma’s general strategy on product pipeline establishment, Dr.Youzhi Tong emphasized two principles. First, cancer is the core disease area. There are seven R&D projects related to cancer indications including prostate cancer, breast cancer, HCC, blood cancer, etc. Second, androgen receptors (AR) are the main focus.
There are around 100 people devoted to research and development among the over 160 person-team of Kintor. Dr. Youzhi Tong emphasized that the lifeline of a novel drug discovery company is research and development. And as such, Kintor Pharma always adheres to independent research and development as its core. Even with the external introductions, we mainly introduced them from the very early “Lead Compound” stage, and would optimize them into “Candidates” by independent research and development.
Dr.Youzhi Tong said in his reasoning for introducing monoclonal antibody ALK-1 GT90001 for HCC treatment from Pfizer: “It is a very common mode of cooperation in novel drugs R&D for big pharmaceutical companies like Pfizer with many projects in the pipeline to license early stage projects to local companies. In choosing Kintor Pharma among all the available Chinese novel drug developers, Pfizer acknowledged Kintor’s R&D abilities. There is also a strong tendency for small molecule drugs to be combined with large biological drugs to achieve the best therapeutic result. Kintor expects to accumulate experience with biological drugs R&D through the development of this monoclonal antibody ALK-1.
Emphasizing R&D, directions for the next decade
In the next decade, how will Kintor forge ahead? The first step: be listed on the Main Board of the Hong Kong Stock Exchange.
On April 26th 2020, Kintor officially passed the hearing from HKEX. Explaining his reasoning, Dr.Youzhi Tong said, “We are not the favorite of large VC funds in the beginning. During the most difficult times, I used my own money to renovate labs, buy reagents, pay employee, and bring back second-hand equipment to China from the US. Although there have been some improvements in investing in the past few years, the company has to be connected to the capital market in order to expand, especially when the number of projects is increasing. Therefore, by going public on HKEX, we expect to have a more suitable capital platform in order to support the company’s consistent development.”
As to the next decades’ concrete targets and development strategy, Dr. Youzhi Tong specified 3 goals:
First of all, getting products on the market. Currently, Kintor has two ongoing phase III clinical trials for Proxalutamide in China, and the company will finally achieve a “from zero to one” breakthrough in new drug approvals on the market in near future.
With the launch of our new drugs, we will have more funds to expand our product pipeline, improve novel drug R&D, and provide more effective treatment for patients.
Secondly, commit to R&D.
With the growing capacity to take more risks, Dr. Youzhi Tong deemed that the company should take on tougher projects and aim the R&D on more challenging targets like c-Myc. “Since c-Myc is a natively disordered protein, it lacks a uniform active site for medicine to target. Because of this, no companies have been able to successfully develop a drug for this protein. In the future, rather than concentrating on lower-risk and higher-druggable targets, I expect Kintor to aim at higher-risk targets. Only in this way will the company get the opportunity to develop first-in-class novel drugs and become a globally recognized competitor in R&D,” he explained.
Thirdly, be a novel close-loop company that has every sector of industry chain, including innovative R&D, manufacturing, and marketing. Dr.Youzhi Tong considered that in order to improve the company’s anti-risk capabilities, we have to not only ensure the core competence in R&D, but also possess strength in manufacturing and commercialization. In preparation, Kintor has already constructed its own manufacturing base, covering an area of approximately 20,000 square meters, which will officially be put into use in 2020. Additionally, the company plans to construct an API manufacturing base in Zhejiang Province. Kintor has also appointed a head of sales and marketing team and will soon run its own independent commercialization team.
In the past decade, Kintor concentrated on targets such as Androgen Receptor (AR), ALK-1, etc., excogitated novel treatment in prostate cancer, breast cancer, androgenetic alopecia, acne, etc. all with a large market potential, and gained approval for clinical trials both in China and the US. In the next decade, we will continue to expand into the US and China market and exploit more novel treatments both in mono- and combo-therapy in order to become a global leader in the treatment of diseases with unmet medical needs.