Expert Profile

Dr. Li Yingfu

       He is the Chairman and President of Hyperway Pharmaceutical Co., Ltd. with more than 20 years of experience in drug R&D and management at well-known pharmaceutical companies at home and abroad. He was successively responsible for the R&D and management of new drugs at Bayer's drug research center in the Germany headquarters, the research center in Japan, and the research center in the United States. After returning to China, he successively served as the Chief Scientific Officer of Yangtze River Pharmaceutical Group, General Manager and Group Vice President of Chengdu Chempartner Co. Ltd., President of the Pharmaceutical Research Institute of Chengdu Brilliant Pharmaceutical Co., Ltd., Vice President of the Group, etc. He served as the first inventor and general project leader of multiple clinical drug candidates. In 2019, he founded Hyperway Pharmaceutical Co., Ltd.

       Given the demand and trend of precision medicine, the mechanisms of diseases are deeply analyzed continuously, and the key drivers of diseases are gradually elucidated. How to respond more accurately to clinical needs is a major challenge we must face.

       Targeting the key targets at the molecular level enables targeted therapeutic effects and generates significant efficacy. The advantage of small-molecule drugs lies in their ability to easily enter cells and reach the intended targets. Furthermore, the R&D of small-molecule targeted drugs can enjoy great potential with gradual breakthroughs in multiple "undruggable" targets.

       In 2022, the U.S. Food and Drug Administration (FDA) successively approved several blockbuster new antineoplastic targeted drugs, such as futibatinib, the second-generation fibroblast growth factor receptor (FGFR) inhibitor for the treatment of cholangiocarcinoma. In addition, multiple indications were added to some approved antineoplastic targeted drugs.

       In the same year, two neurotrophic tyrosine receptor kinase (NTRK) targeted drugs without restrictions on cancer types - larotrectinib and entrectinib were approved and launched in China.

       This time, Dr. Li Yingfu, the Chairman, President, and Founder of Hyperway Pharmaceutical Co., Ltd. (hereinafter referred to as "Hyperway"), a small-molecule innovative targeted drug developer, was invited to introduce the product planning and business model of small-molecule targeted drugs and share his views.

       BioCollaborate

       What was the development direction planning that served as the basis of Hyperway's decision to plan for and develop targeted drugs in the oncology field at the beginning of its establishment?

       Li Yingfu

       The oncology field has always been a "hotly contested spot" for small-molecule drug companies. At present, small-molecule drugs play a significant role in the treatment of tumors and non-tumor diseases. My experience at home and abroad mainly focuses on the promotion of development pipelines of small-molecule drugs for oncology, so I have chosen to enter this field naturally.

       In fact, the oncology field witnesses the fiercest competition among many pharmaceutical fields, and the success rate of new drug development is extremely low. However, we still want to perform well in one or two projects despite the high pressure to prove our strong strength in the development of small-molecule targeted drugs for oncology.

       We have chosen to develop BTK inhibitors based on the continuously expanding market for BTK inhibitors and their significant efficacy in the treatment of various tumors and autoimmune diseases. BTK inhibitors have been developed to the third generation.

       So far, there have been only two major transactions in the third-generation BTK inhibitor market. One was that Lilly in the United States acquired Loxo, an anticancer drug developer, with USD 8 billion in 2019, and obtained LOXO-305, a third-generation BTK inhibitor during phase 1/2 clinical trials at that time. The other was that MSD acquired ArQule, a biotech company, with USD 2.7 billion in 2020, and obtained multiple small-molecule drugs including the third-generation BTK inhibitor ARQ-531. International pharmaceutical giants are optimistic about third-generation BTK inhibitors, so such products enjoy infinite potential.

       In preclinical studies, the third-generation BTK inhibitor HBW-3220 developed by us has shown obvious advantages over LOXO-305 of Lilly and ARQ-531 of MSD. More importantly, LOXO-305, the only third-generation BTK inhibitor currently on the market, causes a new drug-resistant mutation called the L528W mutation. By contrast, Hyperway's HBW-3220 is effective for this mutation and many other mutations, so it has obvious differential advantages.

BioCollaborate

       Hyperway also pays attention to the pain field. Why does it plan for some niche segments?

       Li Yingfu

       Apart from the oncology field, we also want to engage in differential attempts and explorations in some fields with less intense competition.

       Last year, the innovative analgesic drug VX-548 developed by Vertex in the United States succeeded in phase 2 clinical trials for the treatment of patients with neuropathic pain and obtained the Breakthrough Therapy designation of the FDA. VX-548 exerts its efficacy by selectively inhibiting the NaV1.8 target, providing better analgesic effects than opioids while avoiding side effects such as addiction.

       In fact, as early as 2020, VX-150, another NaV1.8 compound of Vertex, succeeded in phase 2 clinical trials and obtained the Breakthrough Therapy designation of the FDA. It was the success of the world's first sodium ion channel analgesic target in phase 2 clinical trials. This significant breakthrough in the field of analgesia attracted our attention and attracted many large international pharmaceutical companies including Pfizer, MSD, and GSK to intervene in this target. However, due to the great development difficulty, only two or three companies in the world have entered clinical trials on their pipelines so far. The competition is not very fierce.

       In addition, the huge analgesic drug market in regions such as Europe and America is far from being satisfied. Considering various factors, we have chosen to develop new analgesic drugs with NaV1.8, a target that can be relatively quickly advanced to the compound stage. We have successfully promoted the project to the clinical stage, ranking among players in the first echelon regarding the same target in the world.

       Furthermore, we are also exploring characteristic directions suitable for Hyperway's development while promoting innovative drug pipelines.

       For example, while developing third-generation BTK inhibitors, we have found that the existing BTK inhibitors have extremely low blood-brain barrier permeability. Only the second-generation BTK inhibitor developed by Ono Pharmaceutical Co., Ltd. in Japan can penetrate the blood-brain barrier, but the compound activity is relatively weak and the probability of drug resistance is high.

       In this context, we have established a professional, efficient, and systematic technical platform for the development and evaluation of drugs that can penetrate the blood-brain barrier featuring the molecular design, synthesis, and screening, pharmacokinetic evaluation, and toxicological research of drugs that can penetrate the blood-brain barrier. Based on this platform, we have embarked on clinical trials on a third-generation BTK inhibitor. Besides, we are promoting the R&D of a multi-target antineoplastic drug with high blood-brain barrier permeability. We also hope to rely on this platform to fully integrate R&D resources, deepen cooperation, improve drug R&D efficiency, and develop as many drugs for brain diseases with high blood-brain barrier permeability as possible in the future.

BioCollaborate

       What do you think of the current game between large-molecule biological drugs and small-molecule chemical drugs? Nowadays, AI attracts much attention in new drug R&D. What do you think of this phenomenon?

       Li Yingfu

       In fact, small-molecule chemical drugs have solved most of the problems in our daily medication. They are very safe and have a high drug absorption rate and obvious price advantages. In my opinion, the vitality of small-molecule drugs will not decline, and they will still play an important role in the biomedical field in the next two decades. The development of targeted drugs involves the selection of targets. The number of suitable targets is limited for both small-molecule and large-molecule drugs. In terms of target druggability or drug development maturity, small-molecule targeted drugs have obvious advantages. They can generate multi-target therapeutic effects in an all-around way and achieve good efficacy.

       At present, AI is very popular. It certainly facilitates the discovery of new targets and the screening of lead compounds. Although AI can improve the overall efficiency of drug discovery, its effects should not be overstated. Especially in the field of small-molecule targeted drugs, several products of AI drug development companies have entered clinical trials, but the clinical performance falls short of expectations. I think AI plays a supplementary role in drug development and is far from making a critical breakthrough.

       BioCollaborate

       What is the business development model of Hyperway?

       Li Yingfu

       Unlike many biotech companies, Hyperway does not seek corporate development through continuous financing. We hope to collect some clinical data and obtain good clinical results in China based on one or two projects and attract the attention of large biopharmaceutical enterprises for technical authorization or joint development cooperation.

       It is very difficult for any domestic enterprise to go alone in the international market. Up to now, in China's small-molecule drug field, only zanubrutinib, a BTK inhibitor independently developed by BeiGene, can compete with other products in the international market through global head-to-head trials. However, we have limited funds, so it is more practical for us to open up foreign markets through the transfer of international interests.

       Of course, we will also consider promoting certain projects in Europe and America subsequently after our products are launched and when we have sufficient financial support. Such a model not only gives full play to our advantages in high R&D efficiency and high product quality at the front end but also enables us to cover the entire process of new drug R&D and enhance our productivity.

       At present, this model is in line with the development of Hyperway. We achieved a revenue of several million RMB in 2021 and more than RMB 10 million last year. If the cooperation goes smoothly this year, our annual revenue will continue to grow steadily.

BioCollaborate

       Based on your more than 20 years of experience in drug R&D and management at well-known pharmaceutical companies at home and abroad, what is your understanding of Chengdu's biomedical environment during the development of enterprises in recent years?

       Li Yingfu

       There is still a gap between Chengdu and places such as Beijing, Shanghai, and Guangzhou in the development of the biomedical field. For example, the investment climate is relatively conservative. The vast majority of investors investing in local projects are venture capital institutions from other places, while Chengdu's local institutions account for a small proportion. The development of innovative drug R&D enterprises or teams will be restricted. The government should continue to strengthen improvement measures in this regard. We also see that the government is taking some measures. The establishment of Orinno Capital's angel mother funds and the industrial investment platform in the Chengdu Hi-tech Industrial Development Zone can serve as a remarkable move. I believe that the financing environment in Chengdu will be effectively improved under the guidance of the government in the future.

       Furthermore, regarding the guarantee of biomedical R&D safety, I also hope that the government and the park can conduct more scientific control. While guiding the settled enterprises to standardize the implementation of environmental protection and work safety responsibilities and implement environmental risk management and control requirements, it is also necessary to strengthen the prevention and control of trial safety risks. However, rationality is required, and the one-size-fits-all approach cannot be adopted. Of course, enterprises that are found to have significant safety hazards and problems during safety inspections should promptly take preventive measures to ensure the safe and stable operation of the park.

       I was born and raised in Chengdu. After I returned from the United States, I worked in Shanghai, Jiangsu, and other places with a developed biomedical industry for more than half a year before returning to Chengdu and devoting myself to biomedicine. At that time, the industrial environment of Chengdu lagged far behind that of Shanghai. However, Chengdu has witnessed rapid progress over the past decade after my return to my hometown.

       Now, in addition to Shanghai, Suzhou, Beijing, and Guangzhou, Chengdu is also gradually becoming one of the biomedical industry clusters in China. The optimistic and inclusive cultural attitude of the Land of Abundance has also made young talents nationwide willing to settle down in such a livable city for business development. With greater governmental support for the biomedical industry, I believe that Chengdu's biomedical industry will show vigorous development momentum in the long term and achieve the trillion-level scale in the future.

       About Hyperway

       Established in January 2019, Hyperway Pharmaceutical Co., Ltd. is a high-tech enterprise specializing in innovative drug R&D with great growth potential. The company has set up a professional and international drug R&D core team with a forward-looking strategic vision. It closely follows the international trend for drug development, takes clinical needs as the orientation, and regards innovation as the core driver. It is committed to developing the first and best original innovative drugs in the international market with independent intellectual property rights to solve the medication problems of patients from various aspects such as efficacy, safety, and accessibility.