Looking back again, Yan Feng, founder of Vπ Zhangjiang Science Investment Ecological Fund Zhangke Lead Eagle Investment and Vπ Zhangjiang Pharmaceutical Valley platform graduate company Leadtek Bio, feels that every step he took was just on the drumbeat of the development of the times.
In 2001, Yan Feng went to the University of Michigan for postdoctoral research. This was also the year that Raymond J. Deshaies and Craig M. Crews and others first introduced the concept of protein degradation targeted chimerism (PROTAC).
Mutations in genes can cause mutations in certain proteins, resulting in abnormal activation of signaling pathways that can lead to diseases. The mechanism of action of traditional small molecule drugs is to inhibit the function of target proteins by binding to the active site of the target protein.
However, it is expected that more than 80% of proteins in the human body are difficult to be used as targets for drug development according to traditional drug research methods, so scientists are constantly exploring new technologies to break through these "non-druggable" targets.
"The concept of PROTAC has brought new treatment tools to people. Yan Feng said, general small molecule drugs act on the active site of the target protein, which is equivalent to "unlocking". In the case of PROTAC, it is similar to using a hammer to knock off the "lock" directly, that is, to remove the disease-causing protein.
However, most of the early PROTAC molecules were designed based on peptides with poor membrane permeability and drug-forming properties, so it was difficult to achieve effective degradation of target proteins in vivo, and the development of PROTAC was slow.
Yan Feng also began to wait for the right time.
01
Aiming at "everything can be lowered"
In 2005, after 4 years of training in medicinal chemistry, Yan Feng decided to return to China to contribute to the development of China's biopharmaceutical industry. "I wanted to be able to apply the innovative technologies I learned to unmet clinical needs and solve real problems, instead of just burying my head in R&D and then sending a Paper for everyone to see and that was the end of it. "
Return to the country has been determined, but where to go? That time period, the domestic has not yet formed a perfect environment for innovative drug development, most companies focus on generic drugs.
With the strategic goal of transforming China's drug R&D from generic to innovative, the Shanghai Institute of Pharmaceutical Research opened a new site in 2003 and moved east to Zhangjiang, starting its "fourth venture". Since then, a number of innovative drug R&D companies have emerged in Zhangjiang, becoming the most important infrastructure for new drug R&D and the cradle for new drug R&D talents.
"White Heron Pharmaceuticals was one of them, it was one of the first companies in China to do new drug development, and it was in the second building across from (Zhangjiang Pharmaceutical Valley Building)." Yan Feng has also been associated with Zhangjiang ever since.
The fascinating and dangerous thing about First in Class drugs is the uncertainty. In 2007, Yan Feng left Egret Pharmaceuticals and moved to the United States to continue his research in the field of disease and drug development at Columbia University School of Pharmacy.
Around 2010, a wave of returnees arrived, and a large number of pharmaceutical companies aiming at innovation rather than genericization sprouted in China, including Kangxinuo Bio, Yashang Pharmaceuticals, Junshi Bio, Cinda Bio, and Gloria Bio. Sensing the "smell of spring", Yan Feng returned to Zhangjiang again and joined Sandia.
At Sandia, Yan Feng has witnessed and participated in the development of targeted protein degradation industry. During the cooperation with Celgene (acquired by BMS in 2019), Yan Feng gradually became familiar with and accumulated the theoretical knowledge related to the development of targeted protein degradation drugs, and mastered the "golden key" for the development of various drug molecules through a lot of cooperation and practice with customers. He has also acquired the "golden key" to the development of various drug molecules through extensive collaboration and practice with clients.
In 2019, the company Craig founded, Arvinas, pushed the first PROTAC drug, ARV-110, to the clinic, the first milestone event of clinical trials for PROTAC drugs.
Mechanism of protein degradation mediated by PROTAC molecules
Because protein degradation technologies such as PROTAC can precisely target and degrade target proteins, the industry has come to believe that "everything can be lowered", and in 2019, Nature has directly described the development of new drugs based on PROTAC as "the next big bombshell drug". PROTAC technology for new drug development.
Yan Feng felt that the time had come to start his own business.
02
The first hammer that smashes into self-immunity
Yanhong Zhang, a colleague at the time of Sandia Pharmaceuticals, introduced Yan Feng to his own investment fund, Xiaoyong Yu, the chairman of Zhangke Lead Eagle, after learning of his idea to start a business.
When Yu Xiaoyong and Feng Yan first met, they hit it off immediately, "In Mr. Yu's opinion, whether it was the track development prospect or my personal experience in R&D and work, it was very much in line with his expectations." As an angel investor, Zhang Ke led Eagle to inject tens of millions of dollars into Leadtek Bio.
With the capital, Yan Feng started to consider the venue, "We visited Zhangjiang, Jinqiao and Zhoupu, but after comprehensive consideration, we chose to stay in Zhangjiang." In Yan Feng's opinion, Zhangjiang is the core of the country's pharmaceutical R&D, and it is the preferred place in terms of talent advantage, policy advantage and capital advantage.
Zhangjiang Pharmaceutical Valley Building
But the most difficult part of the entrepreneurial process is its own metamorphosis. "Before the study of chemistry, you know the underlying logic of chemistry, to make a chemical reaction can be, that is, 'know how'. But entrepreneurship is different, you need to complete the 'know how' to 'know why' transformation. You need to answer why you want to do it, for example, to make a drug you need to answer from the mechanism of action of the target."
In addition, as a manager, Yan Feng also needs to think about how to build a team and how to really put the idea in his head on the ground. "Very few companies are doing PROTAC in 2019, and we are globally new, with no reference, so a lot of things need to be figured out by ourselves in the beginning."
What's more, startups can't avoid the question, how to make differentiation and set their own technical barriers? "Differentiation is either in the indication, or in the target, or in the technology platform is different from others."
In the PROTAC field, 99.9% of companies are using oncology as their first pipeline, Yan Feng chose to bring the first hammer down on autoimmunity. "As a small company with relatively little capital and team members, we had to have our own characteristics if we were to break out quickly. Since everyone is doing oncology, we will find another way to do autoimmunity. Compared with tumor, autoimmunity still has many advantages and there are many clinical needs."
R&D corner of Leadingtac
The direction is set, and Yan Feng adopts a two-legged parallel mode to walk fast, while self-researching and collaborating. "For example, there were few CROs providing related services in the early stage of activity screening, so we built our own platform. After establishing our own evaluation platform, we found that the efficiency was not high enough and developed a more efficient screening platform." On the other hand, at the level of in vivo animal models, etc., cooperation with CRO companies was slowly mapped out.
"There was a lot of pain in the middle of this. Fortunately, we also came through step by step. But in retrospect, if you do First in Class, those detours are necessary." Yan Feng said.
03
Competing with global innovation, on the same stage
Leadingtac's R&D staff working scene
In 2021, a number of pharmaceutical companies will enter the clinic with their PROTAC drugs, and protein degradation technology will be in full development. In particular, in 2021, Pfizer will spend over $2 billion on PROTAC and enter into a partnership with Arvinas to accelerate the "ignition" of the industry, and PROTAC will become one of the most popular technologies among researchers and investors.
China is also keeping pace with the international technology frontier - in 2022, the Ministry of Industry and Information Technology and the Development and Reform Commission and other nine departments jointly released the "14th Five-Year Plan" for the development of the pharmaceutical industry, including PROTAC targeted protein degradation technology, cutting-edge core technologies and drugs In the "14th Five-Year Plan", the Ministry of Information Technology and the Development and Reform Commission jointly released the "14th Five-Year Plan", which listed the cutting-edge core technologies and drugs including PROTAC targeted protein degradation technology as the key development objects.
In September 2022, the Shanghai Science and Technology Commission released the announcement of Shanghai 2022 Technology-based SME Technology Innovation Fund Program. The "PROTAC innovative drug LT002 preclinical research" declared by Leadtek was awarded the project.
Experimentation moment of Leadtek Biology
Just recently, Leadtek's IND application for IRAK4 degradation agent was accepted by US FDA, which is the first IRAK4 protein degradation agent in China and the second in the world after Kymera's KT-474 submitted to FDA.
Yan Feng has his own consideration for the synchronous opening of overseas layout, "Innovative drugs are to go to sea, how boring it is to just roll at home, we want to compete with global innovation on the same stage and become the leader in the track of targeted protein degradation." Yan Feng said with a smile.
Next, Leadtek Bio will also extend its pipeline to the oncology field, "In the field of oncology, targeted protein degradation therapy development is also in its infancy. There is no big gap between us and foreign companies. We are looking forward to bringing more possibilities to patients with PROTAC's technical advantages and contributing to the power of Leadtek Bio."
Reprinted from the public account of Zhangjiang Science and Technology Investment
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