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Yihan Wang, a technical expert: Where does his confidence to cure blood cancer come from?

2018-11-11 Views:

Fei Ma, Medicine Economic Reporter, November 11,

website: https://mp.weixin.qq.com/s/H5xTfZkb-OMRl7t7rHWnuA

“A box lunch is 20 yuan, and 1160 yuan is for 58 meals. A box of 56 tablets of a targeted drug for the treatment of leukemia is priced at 65,000 yuan, and one tablet is about 1,160 yuan. Xiaozhuo (pseudonym) requires 3 tables per day. His parents decided to sell the family car and exchange for a box of drug, which was only for less than 20 days. Drug resistance has now emerged, and the savings that parents saved from working as tailors have run out and his parents owed huge external debts. " The reality version of Dying to Survive is being performed in an ordinary family in Baoding, Hebei. How many families can face it calmly? Leukemia causes the helplessness and powerlessness of tens of thousands of families.

“Our goal is to cure chronic myelogenous leukemia. In fact, chronic myelogenous leukemia is currently one of the cancers with the best curative effects. The latest generation of BCR-ABL inhibitors under research in the company for chronic myelogenous leukemia has made breakthroughs, and its activity is orders of magnitude higher than that of ponatinib, which helps to achieve a deeper molecular response to eliminate residual lesions.” In Shenzhen Kexing Science Park, Dr. Yihan Wang, the founder, chairman and CEO of Shenzhen TargetRx Inc. took off his lab coat, came out of the lab, and welcomed the reporter into the conference room. This is how he talked about the social concerns raised by the reporter.

Dr. Yihan Wang, Founder, Chairman and CEO of Shenzhen TargetRx Inc.

Today, he his important contribution to the world's leading leukemia drug development. Yihan Wang worked for Ariad, a leading company in biopharmaceutical research in the United States, for 16 years. He led the development of the third-generation drug ponatinib to solve the resistance problem of Gleevec. In 2014, he returned to China and founded TargetRx, and led his young team to develop new drugs for chronic myeloid leukemia. Such new drug is the new hope of thousands of families.

TargetRx's offices in the Kexing Science Park are like square boxes filled with overtime workers with passion and ideal. It’s past dinner, and several researchers in lab coats are still immersing themselves in experiments. Their simplest wish is to try to cure blood cancer. Although the drug safety and efficacy need to be confirmed by clinical trials, Yihan Wang is very confident in achieving the final goal of curing canner. They are preparing for the clinical application for the fourth-generation drug.

;Winning the “Pearl in the Crown”

In the face of malignant tumors, patients are helpless and can only regard themselves as “test mice”. They take great risks and endure various side effects to try approved drugs or drugs in clinical trials. Their only hope is to survive, even if they can only live one more day. How to let patients receive the most effective and most dignified treatment in the balance of benefits and side effects is the goal of the pharmaceutical industry.

Dr. Yihan Wang, as a technical expert, does not seem to have too many attractive stories of returnee entrepreneurs. He calmly said, “The fourth-generation drug for chronic myelogenous leukemia is like the pearl in the crown. Once successful, it will be the curative drug like that for hepatitis C. TargetRx may be the first company in the world to get this pearl. It is like Everest, representing the highest peak of the entire targeted drugs. Fortunately, during my career in the pharmaceutical industry, I became associated with two first-in-class drugs, ponatinib and brigatinib for treating ALK-positive non-small cell lung cancer.” His voice was gentle, not deliberately high-pitched. It did not sound like a top scientist telling the glory of the past, but he was more like a rational pioneer.

Looking back on the course, Yihan Wang said that he was honored, “Modern drug design has great limitations, and structural elements are only limited to common and predictable groups. Ponatinib and brigatinib were successful because of breaking through traditions. Researchers should boldly explore the unknown.”

When a brand-new structure is designed to effectively treat cancer, the sense of accomplishment cannot be expressed in words, and the mechanism of action of the fourth-generation drug is brand new. The reporter can clearly feel that he is most afraid of slack in the competition, just like driving a car, you can occasionally look at the rearview mirror, but cannot stare at the rearview mirror to drive.

TargetRx is currently focusing on two directions: The first one is the fourth-generation drugs for chronic myelogenous leukemia, currently there is no approved drug in the world. The second one is the development of drugs for non-small cell lung cancer. There are more people with lung cancer than leukemia. At present, the incidence and mortality of lung cancer rank the first in China, with 733,000 new cases each year. The cure of lung cancer and blood cancer is equally urgent.

“Leukemia is the urgent disease to be treated by targeted drugs at the moment. Under the action of targeted drugs, patients with this malignant cancer can marry and have children and fight for careers just like normal people. Any breakthroughs in the targeted drugs are of indicator significance.” Yihan Wang revealed that this technology is mature and it can also be used in lung cancer drug development. They are confident that patients with lung cancer can live 10 years longer. The prolongation of their survival period does not rely on radiotherapy and chemotherapy, but the patients can live normally like patients with diabetes and hypertension under the treatment of targeted drugs. In terms of drug design, cure of cancer is not a dream.

The best drug has not yet been developed

Optimized targeted drugs can turn cancer into a chronic disease, which is the ideal of pharmacists. “I have two 95% concepts: one is that 95% of the drugs in the world have not been discovered because there are more than 7,000 rare diseases registered, but fewer than 350 drugs that are registered in FDA and can be used for treatment, accounting for less than 5%; the another is that 95% of the existing drugs can be further optimized.” Yihan Wang often tells his team that the best drug has not yet been developed.

Of course, this involves commercial considerations. To what extent does a drug be improved? From the perspective of developing drugs, there is only better but not the best. Technology and commercialization are like the relationship between “returning to earth and planting potatoes” in the movie The Martian. For example, in 1997, Ariad decided to develop the third-generation drug for chronic myelogenous leukemia, which was a long arduous and tortuous story. There was no progress in the first few years. The cooperation with German companies was terminated around 2000. Funds were almost exhausted. The company laid off a large number of employees. Some colleagues chose to leave because they lost confidence in the project. At that time, both Ariad and Yihan Wang's career fell to the bottom.

A year later, they shifted the direction of development to the structural design of the newly emerging kinase catalytic active domain, using structural elements that are not commonly used by pharmaceutical scientists. At the initial design, it was not certain whether it was stable enough, but after several rounds of optimization, the results were unexpectedly good, and ponatinib was successfully developed. The top American cancer journal Cancer Cell once used their design as the cover story. Dr. Yihan Wang said, “This can be regarded as a textbook case of modern new drug development.”

Of course, the best drug has not yet been developed due to many factors, especially China still lacks an atmosphere and environmental ecology to develop first-in-class drugs. The declaration of major science and technology projects in Shenzhen requires that the enterprise to have a certain amount of income. “This one just got me stuck. Start-up pharmaceutical companies burned a lot of money in the early stage. Where can they get their income? I hope to get more support from the policy in the future. I feel more confident after I come back to start a business day by day.” Yihan Wang smiled happily.

CDE recently released the first batch of clinically urgently needed overseas new drugs including ponatinib, which can be directly marketed in China without clinical trials. This allows patients with drug resistance, especially those with T315I mutations, to finally have better treatments. On November 5, China's clinical trials officially started the tacit approval system. Yihan Wang applauded for the drug evaluation reform in the circle of friends.

Asset-light model ensures patent application

In TargetRx's office area, there are 4 laboratories on both sides of the aisle, but these relatively simple laboratories are equipped with expensive test equipment. “Being original is TargetRx's characteristic.” Holding the experimental equipment imported from Germany next to him, Yihan Wang squinted his eyes and told the reporter that he tried his best to buy the best equipment, because the success of a project hinges on the equipment to some extent.

In addition, he has to read a lot of materials to keep the technology up-to-date. He poured his many years of experience into his hands, so that in-house scientific researchers can all become experts. “The company was an empty shell 4 years ago. Today, we have more than 20 staffs. It is not easy to achieve such a result.” He straightened his chest, and the proud in his words.

In the United States, this is called the asset-light model. Except for the core technology, everything else can be outsourced. “Innovation replies on technology, which cannot be achieved by directly buying or hiring a team and buying the best equipment.” He said categorically, “It is impossible.” Many pharmaceutical companies have funds and believe that the products can be bought. TargetRx is very small, but its technology is in the same generation as that developed by the international pharmaceutical giants. Even because it is more diligent and the staff spends time in the laboratory all the time, certain subdivisions are ahead.

In addition to technology, they attach great importance to intellectual property protection. The independent global intellectual property rights are the core of TargetRx's competition.

“How to understand? Takeda acquired Ariad for US$ 5.2 billion. I have applied for 32 patents in Ariad in 16 years. My patents are basically the patents of the entire team, with an average annual output of 2-3 patents. Since its establishment, in 4 years, TargetRx has 78 international patents, with an average of nearly 20 patents per year. This year, it has obtained 4 international first-in-class drug patents, and there will be more in the future.” He said happily.

“Laziness” is a kind of focus and tenacity

“I had worked in a pharmaceutical company in Boston for 16 years. To make it sound better, I am tenacious and persevering. In my opinion, I am lazy to change jobs.” Yihan Wang is very aware of his such characteristic. He explained with a smile, “if you can't do something on one platform, you may not be able to do it on other platforms.”

Fortunately, before founding TargetRx, he built a R&D team from zero in Ariad, and was responsible for the development of new drugs for leukemia and lung cancer. He was promoted 3 times because of his outstanding scientific research results. The new drug for the treatment of chondrosarcoma developed by his team was purchased by Merck as soon as it was developed. This result caused the company's stock price to soar by more than 10 times in a short period of time.

While he was doing very well in the American workplace, Yihan Wang resigned resolutely. “In 2007, I initiated and founded the Chinese American Biomedical Association (CABA). I had more contact with China peers in the association. I slowly saw the domestic opportunities and simply quit my job. I sold the stock and returned to China to start a business. Fortunately, my wife and family supported me.”

What many people lack in starting a business is not money, but ambition. Starting a business means that the easy life is paused. “I came back with capital and technology, and I was under a lot of pressure. I spend a lot of time in the laboratory and rarely go out. I haven't even been around Shenzhen for more than 4 years.” Yihan Wang said that his life is regular and simple.

In addition, although he has a large team of overseas consultants, and the CABA alone has thousands of PhDs, the existing projects are moved forwards based on his own experience. With the expansion of the product line, employment is something he is considering. On the one hand, TargetRx makes good use of external resources and cooperates with high-quality domestic CRO companies and even adopts cross-border cooperation. On the other hand, TargetRx is also expanding the team, including talents in the application and approval, process, clinical and other links. Although the internal team grows very fast, new talents are urgently needed.

Capital promotes innovation

In July of this year, TargetRx completed a pre-A round financing of tens of millions of yuan, which was jointly invested by Shenzhen Capital Group and other agents. “As the company's product series is becoming more and more abundant, the demand for funds is increasing. I hope to cooperate with the Chinese capitals.” Yihan Wang revealed that they started the next round of financing negotiations.

Yihan Wang spent 10 million yuan at the time and found 3 agents to be angel investors, but the capital fund cannot exceed his. In this way, he pooled up the 40 million yuan start-up capital of the angel round. “I take out all my savings. There are currently 6 projects, and the company's funds are enough for the first two projects. If there are surplus funds, the next 4 projects will be pushed forward simultaneously. If funds are not enough, the next four projects will be suspended first.” You can feel the desire of that this type of innovative start-up company for capital.

However, the early investment has greater risk, and was not liked by the capital community in the past. Few pharmaceutical companies developed first-in-class drugs in China in the past, and the national policy is not as clear as today. The capital is not equipped with professionals and resources, and many agents cannot understand it. The situation has changed drastically in recent years. The reporter is curious that the new shareholders of TargetRx are all people with investment background.

“Most of the other shareholders are not medical professionals. They rarely intervene in the company's daily operations and let the company grow.” Yihan Wang explained that he cares more about whether the company's development philosophy can be recognized by investors. Some investors may pay attention to quick returns, and the capital will ask to spend money to buy products. This model is not their option. “The board of directors recognizes me and the company's direction very much. They have provided a lot of support to the company. For example, Vice Chairman Luo Quanfeng, who is the lead investor in the angel round, started the business earlier than I started, and gave me a lot of help. No matter it is industrial capital or a pure financial investor, as long as it recognizes the company's development philosophy.”

Recently, the state announced the establishment of the science and technology innovation board on the Shanghai Stock Exchange and the pilot registration system. In the CABA Investment and Entrepreneurship WeChat group he initiated, he can feel the inner surge of these entrepreneurs. They are cheering and blessing each other.

Reporter's Notes

See the future that has come

For a person who develops drugs, nothing is more comforting than that a new drug developed by himself can help desperate patients. During the two-hour interview, the reporter observed that each of the low-key TargetRx employees has a higher mountain in their heart, and everyone is a climber. Looking at Yihan Wang's Wechat Moments in the past two years, almost all of them are the advocation for people who are developing new drugs.

He also went to the cinema to watch the movie Dying to Survive, and he was deeply impressed. “The good news is that the situation is getting improved. For example, the patient group is relatively more developed in the United States than in China, and even before the drug is approved, the patient group spreads. This kind of thing is slowly happening in China today. Although it is still in its infancy, some patients have gone further than pharmaceutical companies. Some patients come to us and tell us the most cutting-edge information. I am very pleased to see this situation.” Yihan Wang praised the current changes many times in the interview.

Most people familiar with him commented that he is a low-key doer. However, no matter how low-key he is, no one can ignore the remarkable achievements of the Hubei-born scientist in the field of development of drugs for chronic myelogenous leukemia and non-small cell lung cancer. When Yihan Wang was a child, he was from a poor family, and with the encouragement of his family, he determined to study hard to change his destiny. After graduating from the University of Science and Technology of China (USTC), he entered New York University in 1992 and joined Ariad after graduating with a PhD in Chemistry in 1997 and worked until 2013.

During the interview, he mentioned a short story: Not long ago, he chatted with USTC alumni living overseas, who told him that he might not choose to come to China for the time being, because some conditions in China are not ideal. However, Yihan Wang said, “I walked over and over, there are indeed many problems in the middle, but I prefer to focus on the positive side. China is growing, and there are bound to be many flaws. If you look at all the problems, you will feel that the risks are high, and you may not be able to make the step of returning to China at all. I told him that we might need to look more at the positive side and keep the general direction in mind. In any case, Chinese patients need treatment, and Chinese patients must live with dignity like European and American patients. This rigid need cannot be replaced by anything.” He gives the impression of being very persistent, and what he sees is the future that has come.