On the wall behind Zhu Yi's office chair hangs a woodblock print of color, "Sunshine on the Plateau", a 1984 work by artist Xu Kuang. A Tibetan man in the prime of life, leaning over and facing sideways, wears a heavy sheepskin-lined Tibetan robe, and the hard, smooth upper limb muscle lines exposed on the side of the empty sleeve tube contrast sharply with the figure's unkempt and lush hair in the scorching sun. Together, these visual elements convey a vigorous signal of life.
Zhu Yi has made many risky decisions, such as starting to invest all of the company's profits in research and development in 2013, and launching clinical trials of several products in 2020, which has almost forced the company's cash flow into a dangerous situation. But it just so happens that Zhu Yi is the kind of person who will accurately calculate the risk and move forward step by step even if he is standing on the edge of the cliff and his legs and feet are weak. You won't be surprised that he likes such a work, because the exuberant vitality has helped him to travel through a lot of "no man's land", and at the same time, it has also turned some of the impossible in common sense into possible.
Judging from the company's financial report data, although the performance of Baili Tianheng in 2023 is not satisfactory, in February this year, the company successfully signed a contract with Bristol-Myers Squibb and successfully received a down payment of 800 million US dollars, which also injected strong financial impetus into its next innovation.
In 2013, spring came late in Chengdu, 10 years after Zhu Yi decided to make an innovative drug, and another full decade after the record-breaking overseas licensing deal with BMS (Bristol-Myers Squibb).
But now that I think about it, this year is a critical moment for 50-year-old middle-aged people who have done scientific research, done real estate, and made "a lot of money" because of generic drugs, but are still not satisfied, really have the opportunity to embrace their inner "obsession".
In fact, Zhu Yi's 2013 was not easy. His previous R&D projects for liver cancer drugs and lymphoma fusion proteins imported from Shanghai and Alzheimer's disease treatment drugs from Japan have all failed. This year, the team members of Baili Tianheng may also spend it in a kind of dazed and complacent. On the one hand, the company's generic drug factory can bring nearly 100 million yuan in profits every year, and in Zhu Yi's words, it seems that there is enough money to "burn". On the other hand, in the face of drugs that have not yet been successfully developed by foreign pharmaceutical companies, almost no one knows how China should "burn" them.
Zhu Yi ranks 661st on the list of the world's richest people with a fortune of $4.7 billion
Zhu Yi's anxiety is still the same as in previous years. In 2010, he mentioned in an internal speech at the company: "There are only two drugs in the world: innovative drugs and others. In the future, the margins of other drugs will be as thin as a blade. Most of the VCs who invested in China in those years were not really aware of this judgment, but these investors did not realize that they had won a lot of "paper wealth" first.
At that time, Baili Tianheng had already started the establishment of the Shanghai R&D base, and some people suggested that Zhu Yi should focus on the second and third phase clinical products of overseas big pharmaceutical companies, and avoid patent barriers through fine-tuning of technical means. They believe that in the current domestic environment, it is more prudent to strive to follow closely. However, Zhu Yi feels that such "innovative drugs" are essentially no different from generic drugs, but they are "involuted" in a market with a higher investment threshold. This was what he was "good at" at one time, but it was also something he desperately wanted to get rid of now.
In 2013, Zhu Yi's biggest gain may be that after a long parabola, Zhu Yi's life trajectory finally brought him back to his original path: to engage in "scientific research" and do something different from others. That's how he planned for himself, at least as a teenager.
His attention is more radically focused on innovative drugs that "penetrate the frontier of cognition". Regarding the word "penetrating the frontier of cognition", which he invented, it is more commonly said that relying on limited annual net profits to do things that even Pfizer and Merck spent more than a billion dollars to do. Even if this kind of story is told in today's medical circle, it is no less fantastical than hearing Musk say that he will use a starship to send humans to Mars.
And what these two stories have in common is that there is no way to judge the authenticity, just that it is difficult to know and the success rate is low.
This year, he shifted his attention from Shanghai to the United States. Zhu Yi visited the San Francisco Bay Area. In Boston, he saw the top pharmaceutical centers in the United States around Harvard University in the Cambridge and Kendall Square areas and innovative drug teams of more than 10 or 20 people, which also broke the stereotype of multinational pharmaceutical companies in Shanghai as expensive and bloated.
Zhu Yi was shocked by two discoveries during his trip to the United States.
First, the global highland of innovative drugs is not as leading as he previously expected. In fact, if one follows his harsh definition of innovation, truly revolutionary innovation is extremely scarce even in the United States.
Second, the biggest advantage of the United States is the high efficiency of talent and industry information flow, which is more suitable for the development of research teams than Shanghai at that time.
Soon after returning to China, he wrote a 10-year plan, including what kind of company to establish in the United States, what kind of team of scientists to recruit, what kind of underlying core technology platform to build, and how to coordinate the Chinese and American teams in the future.
After 30 years of entrepreneurship, Zhu Yi has proven his ability in business and operation very early, but the real phenomenal definition of his contribution to the global innovative drug industry only began in 2013, when he decided to bend his waist lower, take out all the profits, and do research and development if he is not successful.
01 Opportunities are in the impossible
"The choice of drug research direction is gradually clarified through long-term observation and thinking. Zhu Yi told Forbes China that through many in-depth investigations in the United States, he will take the cutting-edge technologies that he has been tracking in China for a long time and confirmed in the United States to the international stage for verification to ensure the correctness of the selected drug types, and finally screen out the targets with real research and development potential.
But his ideas seemed too ahead of his time, even in the United States at the time. In 2014, when he was about to set foot in the field of bispecific antibody ADC, scientists in the United States also thought that Zhu Yi's idea was quite aggressive, and in 2015, when he proposed to make multi-specific antibodies, no company in the United States dared to do it. Even Baili Tianheng's own scientists are skeptical, "It's a joke, it's a joke, it's unlikely to happen." ”
At that time, the U.S. biotechnology industry was experiencing a trough, and many companies were laying off employees or even closing their R&D centers due to the cold market. Among them, Amgen, a well-known biopharma company, laid off 4,522 employees as the largest number of pharmaceutical companies that year, and its R&D center in Seattle and Bother's small manufacturing plant were also closed. But such an environment suits Zhu Yi's "radical plan". He has encountered little resistance to renting a laboratory in Seattle at a low price, buying second-hand equipment, and recruiting talent.
Zhu Yi did not blindly follow the "license-in" route, he is well aware that most of the overseas products available for Chinese generic drug companies in the market have been screened layer by layer, and the remaining options are already limited. In particular, the price of high-quality products with great market potential and innovative value is often prohibitive. At the same time, he did not choose to follow the example of other Chinese pharmaceutical companies and rapidly expand his team and acquire technology by acquiring innovative American pharmaceutical companies.
On the contrary, he established a unique strategic layout for Baili Tianheng - the front-end discovery in the United States and the back-end development in China.
In 2014, Systimmune was officially established in Seattle. In the following five years, Zhu Yi built a technology platform including monoclonal antibodies, bispecific antibodies, multispecific antibodies, ADCs and fusion proteins.
This is a strong example of Zhu Yi and Baili Tianheng's efforts to cross the "generic drug company" and open the innovative drug business, the earliest, unlike many innovative pharmaceutical companies that rely on external investment, Baili Tianheng's efficient generic drug system, like a steady stream of "golden egg hens", provides stable financial support for Baili Tianheng in the research and development of innovative drugs, and is not swayed by external capital.
In the past ten years, Zhu Yi has devoted himself to the research and development of innovative drugs with a determination to become a beneficiary if he does not succeed. However, the fluctuation of generic drug profits has always been a concern for the research and development of new drugs. In 2017, Zhu Yi began to seek external financial support to reserve resources for possible failures in the research and development of innovative drugs. OrbiMed was quick to cast a vote of confidence in it.
Looking back on this journey, he admitted: "It's really a bit reckless. Because in 2020, when our drug enters the clinical stage, we will really feel the huge pressure of capital consumption. ”
On January 6, 2023, Baili Tianheng successfully landed on the Science and Technology Innovation Board, ushering in a new stage of the company's development. Zhu Yi sighed: "Thanks to the listing on the Science and Technology Innovation Board and the opening of fundraising channels, we can carry out high-intensity R&D investment in 2023 and accumulate rich clinical data. ”
02 The road to "going to sea" is gradually getting better
At the end of 2023, in the cold winter of biopharmaceuticals, the largest licensing transaction in China's innovative drug field was born: an initial payment of US$800 million (about 5.74 billion yuan), and the total contract transaction value could reach up to US$8.4 billion (about 59.9 billion yuan). The protagonist of this transaction is Baili Tianheng, and the cooperation with it is a world-renowned multinational pharmaceutical company: Bristol-Myers Squibb.
Six months ago, Baili Tianheng was invited to participate in the annual meeting of the American Society of Clinical Oncology (ASCO) and presented five important clinical research results, including the bispecific antibody ADC drug BL-B01D1. Among them, BL-B01D1 is the bispecific antibody ADC drug that Baili Tianheng insisted on developing when it was not optimistic in 2014.
According to Zhu Yi's recollection, the venue was full of about 6,000 attendees, most of whom were clinical scientists or early research scientists. The chairman of the conference made a detailed comparison of the early clinical study data published by Baili Tianheng with other ADC data, and found that BL-B01D1 showed promising anti-tumor activity in patients with non-small cell lung cancer and breast cancer whose disease progressed after standard therapy. In terms of the performance of non-small cell lung cancer, the data of BL-B01D1 was also the best in the world at that time.
"We have proven our strength and worth with real and powerful data. Zhu Yi said. As a result, BL-B01D1 has been labeled as a "new concept of bispecific antibody ADC" and a "first-in-class" drug. During the ASCO meeting, 8 of the world's top 10 multinational companies communicated with Baili Tianheng, and BMS was one of them.
When the news of the deal with BMS came out, foreign industry media commented: Bristol-Myers Squibb urgently needs to open up a new ADC front to compete with competitors such as Gilead and Pfizer.
The R&D of innovative drugs is like a "gold mine" buried deep underground, and if you want to successfully dig out the gold, you can't do without partners with strong infrastructure capabilities.
"BMS is an ideal partner. Zhu Yi said. As a global leader in the field of oncology, BMS's position and influence in the industry are self-evident. According to the financial reports disclosed by major pharmaceutical companies, the oncology drug market will reach about US$160 billion in 2023, and BMS ranks second in the world with oncology business revenue of US$26.47 billion.
"The collaboration with BMS is a co-development and co-commercialization transaction. For BMS, they have found a strategic asset that matches their strategy, and for Baili Tianheng, we have obtained an important and heavyweight partner to achieve globalization overseas. Zhu Yi is very satisfied with this cooperation, and Baili Tianheng has more sufficient funds for research and development.
In addition to BL-B01D1, the company's other innovative drug pipelines have also made significant progress. Among them, SI-B001, a bispecific antibody for the treatment of epithelial tumors such as non-small cell lung cancer, is advancing to phase III clinical studies, and is the fastest advancing bispecific antibody drug based on EGFR×HER3 targets in the world. At the same time, Baili Tianheng has also made important breakthroughs in the field of four-specific antibodies, and the three drugs GNC-038, GNC-039 and GNC-035 have entered phase Ib/II, phase Ib and phase Ib clinical trials respectively, and it is planned to explore the treatment of a variety of malignant tumors in the future.
Talking about his role in the company, Zhu Yi said humbly but firmly: "If I can, I just want to be the company's CSO (Chief Scientific Officer). My biggest responsibility is to provide innovative methodological guidance to the team and build a solid and efficient R&D framework for them. ”
Zhu Yi has always been the one in the company who asks the right questions. It is precisely with these questions that the impossibility of everything begins to become concrete. Today, Baili Tianheng has gone through 28 spring and autumn steadily. And Zhu Yi is closer to his next critical moment!
The following is an excerpt from Forbes China's conversation with Zhu Yi:
Forbes China: Around 2010, you and the company were ready to start officially entering the field of innovative drugs. But this is a difficult road to take, and once you choose the wrong direction or entry point, the opportunity cost is very large. Did you have a target or target company at that time?
Zhu Yi: At the beginning, we were actually mentally prepared to take 10 years or even longer to innovate. So when we first started, we weren't impatient.
Although our generic drugs are chemical drugs and Chinese patent medicines, when choosing the direction of innovative drugs, we choose the direction of anti-tumor macromolecule drugs in the field of biological drugs. This decision was not accidental, but based on my past education and experience in the biomedical field, as well as my years of experience in making generic drugs. I have always maintained a continuous focus on the field of innovative drugs, and I did not start thinking about the direction when I decided to devote myself to the research and development of innovative drugs.
Forbes China: What is the biggest feeling or gain from visiting the United States?
Zhu Yi: During my visit to the United States, I was deeply aware of two important issues. First of all, true innovation is scarce, regardless of industry or field. Even in a tech powerhouse like the United States, most of the innovation is limited to micro-innovation, and breakthrough innovation is rare. However, the U.S. has an abundant pool of scientists with deep expertise and experience in their respective fields, providing a strong support for innovation. In contrast, at that time, it was not easy to recruit a systematic team of scientists in China, which limited our progress in the development of innovative drugs to a certain extent.
Second, innovation is high-risk, so incentives need to be given accordingly. The U.S. system, especially in the field of biologics, provides a strong incentive for innovators to pay generously for innovative drugs.
In contrast, Chinese consumers and businesses tend to be more inclined to choose lower-priced products when purchasing products or services, rather than paying a high price for professional services. This consumption concept and market environment limit the value embodiment of innovation to a certain extent.
Forbes China: If you want to be at the forefront of the industry, the key is to find and gather those outstanding talents. How do you find the right talent?
Zhu Yi: There is a saying in China: "Three stinkers are the top of Zhuge Liang". But in terms of innovation, even if there are 10,000 or 100 million "stinkers", it is difficult to match a real "Zhuge Liang".
Focus is the key to success. Because resources are limited, we have to focus on a specific point and not try to do it all. If you can "penetrate the front line" at one point, it is already a great success. If you try to make efforts in multiple fields at the same time, under the constraints of limited money, it is difficult to gather talents who have breakthrough and innovation capabilities in various fields, so it is often difficult to achieve real in-depth analysis and breakthroughs in various fields. For a company like ours, the direction should be clear, for example, in the field of oncology. However, even in the field of oncology, the scope is quite broad. We chose a more specific research direction - antibody drugs, and then according to our direction, we found and attracted scientists with deep attainments in the field.
Forbes China: In addition to bringing strong support to the company on the capital side, what kind of synergy or help will there be in this cooperation with BMS?
Zhu Yi: Our cooperation with BMS is not only to obtain a funding, but more importantly, to learn from such industry giants, so as to build the strong infrastructure we need to become a MNC (large multinational pharmaceutical company).
In terms of 0-to-1 early R&D, we have been running in the United States for ten years, accumulating rich experience and leading technology, through the cooperation with BMS, we will further consolidate and expand our R&D advantages, in terms of clinical development capabilities, through cooperation with BMS, we will learn more experience and knowledge about clinical development, improve the efficiency and quality of clinical development, and in terms of commercialization, through cooperation with BMS, we will learn commercialization strategies and skills, and understand how to promote and sell our products globally。 This will provide valuable experience and guidance for our future commercialization path.
There are two core reasons behind this cooperation. First of all, this cooperation is highly compatible with BMS's global development strategy, which is the basis for their strong interest in us. Secondly, the amount and structure of the transaction proposed by BMS were in line with our expectations, which enabled the two parties to reach a smooth cooperation. Prior to signing, we presented data from more than 800 patients to BMS, the largest dataset provided by a single project in ADC's historical deals.
What I would like to emphasize here is that such a large sample size is due to the fact that we have explored the results of the accumulation of more than a dozen tumors, and through continuous exploration in new indications, we have further verified the effectiveness of the molecule, and effectively identified and managed the safety of the drug, so as to remove more risks for the future development of drugs.
Forbes China: Is there any other option for "going global" besides license-out?
Zhu Yi: If we are an industry giant like BMS, we don't need to choose license-out, and we can do it ourselves. Unfortunately, however, most companies in China have not yet reached this level. Chinese companies can be divided into four quadrants according to two dimensions: one is the global competitiveness of product innovation, and the other is the global competitiveness of team operations.
Enterprises in the first quadrant have the ability to introduce foreign products to the Chinese market, which may be competitive in the world, but the team operation ability is only in the domestic market, that is, enterprises in the license-in model; enterprises in the third quadrant are enterprises in the license-out model, whose products have entered the international market, but the team cannot go out, and the operation ability is still limited to the domestic market; teams like Baili Tianheng, which have both internationally competitive products and global vision and operational capabilities, belong to the fourth quadrant。 For companies that aspire to become global companies, the way forward lies in continuously improving their own strength, and when they reach the global leading level, they may no longer need to be license-out, but carry out global license-in like BMS, showing real global competitiveness.
Forbes China: Finally, what do you think about wealth?
Zhu Yi: Some time ago, our employees told me that some media reported that I was the "richest man" on the Science and Technology Innovation Board. I'm still very happy and proud to hear it, because I think it shows one thing: we're really committed to innovation, and we're really creating wealth. Of course, I know that this "wealth" is actually a verbal compliment, because it can't be realized, but it does affirm your efforts.