——Interview with Dr. Yihan Wang, Chairman of Shenzhen TargetRx Inc.

Yihan Wang was born in Hubei, China in 1966. After graduating from high school, he was admitted to the University of Science and Technology of China. In 1992, he went to the Department of Chemistry of New York University to study for a doctorate. After receiving his doctorate in 1997, he joined ARIAD Pharmaceuticals, Inc. in Boston. In 2014, he returned to China to establish Shenzhen TargetRx Inc., focusing on the R&D of internationally advanced targeted new drugs.

The movie Dying to Survive reveals the living conditions and cruel social reality of patients with chronic myelogenous leukemia, and also reflects the helplessness and powerlessness of the families of tens of thousands of patients with chronic myelogenous leukemia in China. However, the “magic drug” Gleevec still has drug resistance problem. In April 2021, the author interviewed Dr. Yihan Wang, the founder, chairman and CEO of Shenzhen TargetRx Inc. He led his team to participate in the development of the third-generation drug ponatinib and successfully solved the resistance problem of Gleevec. Yihan Wang has a bachelor's degree from the University of Science and Technology of China and a PhD degree in Chemistry from New York University. After graduation, he has been engaged in the R&D of new drugs in Ariad Pharmaceuticals, Inc. (Cambridge, Massachusetts, USA) for 16 years. He is the core inventor of multiple international class 1 anti-cancer drugs such as Ponatinib for CML and Brigatinib for lung cancer. He participated in the founding of the Chinese American Biomedical Association (CABA) in 2007, and is also one of the main sponsors of the Alliance of Chinese-American Biotechnology and Pharmaceutical Associations (All-CABPA). His main research results have been awarded a number of patents, and nearly 200 papers and conference abstracts have been published.

No national boundaries in academia, but clear barriers in the pharmaceutical industry

Yihan Wang was born in a poverty-stricken Hubei farmhouse, and with the encouragement of his family, he determined to study hard to change his destiny. In the age of “learning mathematics, physics and chemistry, not afraid to travel all over the world”, he worked hard and graduated from the Department of Chemistry at the University of Science and Technology of China, and later obtained a Ph.D. from the Department of Chemistry at New York University. During his Ph.D. study, he focused on organic solid-phase synthesis, nanomaterials and other researches. His related research results had been published in the top American and international chemical journals. In 1997, Dr. Yihan Wang joined Ariad Pharmaceuticals Inc. in Boston, USA, and was engaged in the R&D of new drugs.

During his 16 years at Ariad, Dr. Yihan Wang worked with pharmaceutical R&D elites in the United States. They developed a new drug for the treatment of chronic myeloid leukemia, which turned blood cancer into a chronic disease; and they also developed a new drug for the treatment of chondrosarcoma, which was purchased by the multinational pharmaceutical company Merck & Co. (MERCK) in 2010, and purchase caused MERCK's stock price to soar more than 10 times in a short period of time.

No national boundaries in academia, but clear barriers in the pharmaceutical industry. Although his career in the United States was booming, but with the fact that the new anti-cancer drug he developed has not been able to treat Chinese patients with chronic myelogenous leukemia, Dr. Yihan Wang was very distressed and his intention to return to China was growing. With more and more reports in the media that cancer patients cannot afford the expensive drugs and the people are worried about cancer, Yihan Wang could no longer sit still. He resolutely gave up the favorable conditions in the United States and resigned to return to China, hoping to turn his experience accumulated in the American pharmaceutical industry into anti-cancer drugs that can alleviate the pain of Chinese patients and save their lives.

"For many years of research on anti-cancer drugs, I want to allow Chinese cancer patients to have the same treatment rights as American patients, and to take the same anti-cancer drugs as American patients." He returned to China in 2014 and came to Shenzhen as a talent of the Shenzhen “Peacock Program” and founded Shenzhen TargetRx Inc.

Not a dream to cure leukemia

Chronic myeloid leukemia is one of the four main types of leukemia, accounting for 15-20% of all leukemias. After the first-generation classic targeted anticancer drug Gleevec was launched in the early 20th century, it was hailed as a silver bullet against chronic myeloid leukemia. Clinical studies showed that the patient's 5-year cumulative best complete hematological remission was as high as 98%, and the 5-year survival rate was increased to 89%. This is the “magic drug” mentioned in the movie Dying To Survive - Gleevec.

However, with the long-term use of Gleevec by patients, some patients have gradually discovered that the "magic drug" is no longer useful, and the condition has deteriorated again, that is, the problem of drug resistance has appeared. In order to solve this problem, Dr. Yihan Wang led the team to overcome difficulties and research and develop new drugs for 16 years. Finally, the third-generation drug ponatinib was developed, which successfully solved the drug resistance problem of Gleevec. As a result, blood cancer is turned into a chronic disease. Cancer Cell, the top American cancer journal, used their design as the cover story. Dr. Yihan Wang said: “This can be regarded as a textbook case of modern new drug development.”

Facing the honor of the successful research and development of new drugs, Dr. Yihan Wang did not stop there. He has a bigger dream - to completely cure leukemia. “I decided to return to China to start a business, not repeating my previous work, but standing on the shoulders to take another step forward to benefit more leukemia patients.” Since the founding of TargetRx in Shenzhen in 2014, Dr. Yihan Wang has continued to focus on chronic myeloid leukemia. In just four years, he has developed the fourth-generation product with the best-in-class drug potential in the world. Due to its unique mechanism, this product is expected to functionally cure chronic myeloid leukemia. It is currently at the clinical preparation stage.

In addition to the fourth-generation anti-cancer drug for leukemia, Dr. Yihan Wang is also actively developing new drugs against lung cancer and breast cancer, and has made major breakthroughs. Dr. Yihan Wang said excitedly, “By April 2020, TargetRx expects to obtain two clinical approvals. By then, patients will be able to use these drugs. These are their life-saving drugs.”

Building an excellent anti-cancer team

No hero is fighting alone. At TargetRx, there is a team of young people from home and abroad who have the same patriotic sentiment. They are called the anti-cancer dream team. It is precisely such a R&D team with an average age of less than 30 years old, that, under the leadership of Dr. Yihan Wang, had overcome difficulties on the road of new drug research and development. In just a few years, the team had obtained more than 70 PCT international new drug patents, and their drug research and development had also made breakthroughs in key technical difficulties.

The road of innovation has always been tortuous. Dr. Yihan Wang recalled: "I remember that when I first returned to China to start a business, it was really difficult. In China, we did not even have a place to find cell lines for experiments, but our team had such a spirit of adversity. For more than four years, the difficulties of the new drug development process cannot be expressed in words, but these difficulties have been overcome by us one by one.”

In order to stimulate the enthusiasm of young researchers in the R&D of new drugs, Dr. Yihan Wang, as the leader of the team, not only imparted his years of research experience, but also instilled the wandering intentions and wishes to save lives to every young and vigorous heart. Dr. Yihan Wang organized all the company's R&D staff to watch the movie Dying to Survive, which greatly stimulated the team's sense of mission and urgency, and it is duty-bound to devote themselves to the R&D of new drugs.

Doing it personally is better than just worrying about the country and the people

Entering Dr. Yihan Wang's office, what you see is a whole wall of data racks, on which are full of pharmaceutical R&D materials. Dr. Yihan Wang said, “Every day after the work off, when the employees leave one after another, that's when I focus on studying.”

In the movie Dying to Survive, the patient had to take a huge risk to buy "magic drug" in India in order to survive. In reality, some patients even directly buy the active intermediates of the drugs and make the raw materials into preparations to take. In order to survive, they can only treat themselves as mice to test the drugs.

There is also a report impressed Dr. Yihan Wang, I want to live to the day when the life-saving drugs are included in the scope of medical insurance. Zhang Wan, a Shanghai officer, is 31 years old. Her life should have been beautiful and bright, but after being diagnosed with myelofibrosis (a relatively rare malignant hematological tumor), she instantly fell into a low life. Rucotinib is a targeted drug developed by Novartis for the treatment of myelofibrosis, and it is also the only effective targeted drug for the treatment of myeloproliferative neoplasms (MPNs) in the world. The price is 8,000 yuan a box, which is only enough for 10 days, and it will cost about 24,000 yuan in a month, which is very expensive and difficult for ordinary families to afford. It was the only anti-cancer drug that was failed to be included in the scope of medical insurance among the 18 anti-cancer drugs to be included in medical insurance after special negotiation announced by the government on August 17, 2018. For the country and ordinary people, this is just a project that has not been successfully negotiated. However, for Zhang Wan, the news made her fall into the abyss. This is her only hope for survival, but the high prices make these drugs out of reach. As a result, patients can only count down the days to live.

Just because of too many similar cases, Dr. Yihan Wang thinks that the only thing he can do is to focus on the R&D of innovative anti-cancer drugs that are low in price, high in curative effect, can prolong the patient’s life cycle or even cure cancer, and patients with advanced cancer can't wait. TargetRx's TGRX-678 for the treatment of advanced leukemia with drug resistance and TGRX-326 for the treatment of ALK-positive non-small cell lung cancer are both life-saving drugs. In the medical insurance negotiations, both ALK's first-generation drug crizotinib and the second-generation drug ceritinib have been successfully included in the medical insurance. After patients are resistant to these two drugs, new drugs that can last for a later period are needed. In pre-clinical studies, TargetRx’s TGRX-326 can effectively deal with the problem of crizotinib and ceritinib resistance, and is expected to allow some lung cancer patients to survive for a long time and turn cancer to be a chronic disease.

“I’m very happy to see that the price of Novartis’ second-generation drug Dashna for chronic myelogenous leukemia has been dramatically reduced by 68% in medical insurance, which reduces most of the drug expenses of CML patients. I hope that the government can include more such life-saving drugs and orphan drugs into medical insurance.” Dr. Yihan Wang said with satisfaction.

Keep making efforts to be the leader of R&D of targeted anti-cancer drugs

“As a corporate scientific researcher, I have experienced the country’s emphasis on the biopharmaceutical industry and technological innovation. In particular, the seven actions to reduce the burden on scientific researchers issued by the Ministry of Science and Technology in 2018 have released the creativity of scientific researchers and made us more enthusiastic to concentrate on scientific research.” Dr. Yihan Wang said that the innovation of new drugs is an extremely high-end industry, which requires a large amount of capital and talents, and has a long R&D cycle. However, with the continuous release of favorable new policies in China, as long as we persevere in tackling difficulties, more effectively drugs for curing diseases and saving people’s lives will be eventually developed.

The birth of a new drug can save thousands of lives, but the R&D road of new drugs is full of thorns and bumps. The United States has strong scientific research strength and financial guarantees in drug research and development, and has a mature system and incentive mechanism in encouraging original innovative drugs and supporting new drug research and development. Dr. Yihan Wang said, “I hope to use my own practical actions to drive the R&D of domestic original innovative drugs, improve the industrial chain of new drug R&D, and more scientific research personnel can participate in to jointly improve the R&D level of new drugs in China.”

I decided to start a business in Shenzhen because it was the right time. “I think I'm at the forefront of the trend, and all levels from the government to the society are paying great attention to biopharmaceuticals, especially innovative drugs. Shenzhen has a strong atmosphere of innovation and entrepreneurship. I believe that the entire Guangdong-Hong Kong-Macao Greater Bay Area will have a big development in biopharmaceuticals.” Dr. Yihan Wang is very proud, “We are fortunate to be at such an innovative bridgehead, and TargetRx is also confident to make the development and progress together with the biopharmaceutical industry in the Guangdong-Hong Kong-Macao Greater Bay Area. Through the efforts of all of our researchers, TargetRx aims to be a leader of anti-cancer drugs, practicing what Premier Li Keqiang said for the sake of cancer patients, and truly realizing the healthy China strategy proposed by General Secretary Xi Jinping.”