Medicilon interview with Dr. Yingfu Li - With the innovation ability in the left hand and the growth ability in the right hand, what does Hyperway Pharmaceuticals, which has only been established for 4 years, rely on it?

Recently, HBW-004285, a Nav1.8 inhibitor independently developed by Chengdu Hyperway Pharmaceutical (Hyperway), obtained an implied license for clinical trials and is intended to be used for the treatment of acute/chronic pain.

Currently, Nav1.8 has become a rising star target for the development of non-addictive analgesic drugs.  The most advanced is VX-548 developed by Vertex, which just started Phase III clinical research in the United States in January 2023.  It has not yet been applied for clinical trials in China, and there are also very few Nav1.8 inhibitors in the clinical research stage.  In China, HBW-004285, which is safe, efficient and non-addictive, is expected to lead this track.

▲Hyperway Pharmaceuticals' lab

Just as amazing as HBW-004285 is the growth rate of Hyperway.  In 2019, Dr. Yingfu Li, who has more than 20 years of experience in drug R&D and management in well-known worldwide pharmaceutical companies, founded Hyperway, focusing on the research and development of small molecule innovative drugs.  In just 4 years, the team led by Dr. Li has applied for 26 invention patents, deployed more than 10 innovative drug R&D pipelines, and identified 7 PCCs, 4 of which have been declared for IND, and 3 of which have obtained implicit approval for new drug clinical trials.
What kind of secret does Hyperway have in its innovation and growth?  To this end, Shanghai Medicilon Inc. (Medicilon), as a partner of Hyperway, invited Dr. Yingfu Li, the founder of Hyperway, to reveal the secrets of Hyperway’s innovation and growth.

Dr. Yingfu Li

Dr. Yingfu Li has more than 20 years of experience in drug R&D and management in well-known domestic and foreign pharmaceutical companies. Dr. Li is the only Chinese scientist who has been engaged in new drug R&D and management for more than ten years in Bayer's German headquarters drug research center, Japanese research center, and American research center.  After returning to China, Dr. Li successively served as Chief Scientific Officer of Yangtze River Pharmaceutical Group, General Manager and Vice President of Chempartner, Dean of Drug Research Institute and VP of Chengdu Brilliant Pharmaceutical Co., Ltd.  He is the first inventor and overall project leader of several clinical drug candidates.  In 2019, he founded Chengdu Hyperway Pharmaceuticals, and established a research and development platform for brain-through innovative drugs and distinctive technology platforms such as blockbuster anti-tumor targeted innovative drug development platform, which drive innovation.  Dr. Li was awarded "2020 Tianfu Jingrong Entrepreneurship Star" in 2020 and "Chengdu New Economy Top 100 Talents" in 2021.  In 2022, Dr. Li got the national high-tech enterprise certification and the Sichuan Province "Special" enterprise certification.

Q1 Medicilon: Dr. Li, congratulations to HBW-004285, a class 1 new drug of Hyperway for its clinical approval!  Currently, most Nav1.8 inhibitors have failed in research and development. Why do you choose this track that few people have gone through, and few people have completed it?

Dr. Li: Pain is the third largest health problem after cardiovascular and cerebrovascular diseases and tumors.  The addiction and abuse of opioid analgesics are serious. As many as 69,000 people worldwide die from opioid overdose every year, and 15 million people are dependent on opioids.  There is a huge unmet clinical demand for analgesics, especially in the European and American markets.

Sodium channels are one of the most popular targets for non-opioid analgesics research.  From Nav1.7 to Nav1.8 and even Nav1.9, there is no shortage of successive studies, including Pfizer, Abbott and GSK, but unfortunately most of them failed in the second phase of clinical trials.

In 2020, Hyperway has just been established, and one of the areas we consider is tumor, a battleground for pharmaceutical companies.  At that time, I wanted to choose another field to balance the company's development.  I have been paying attention to the field of pain, and just saw that VX-150 was awarded the breakthrough therapy designation in the United States. After further investigation, I felt that Nav1.8 is a target with research value.  In fact, Vertex has been cultivating this target for many years. After GSK failed to obtain the transfer research, it took over again and launched VX-150. After the clinical phase II failed, it launched VX-548.  Although the target Nav1.8 is difficult to achieve a balance between activity, pharmacokinetics, and safety; however, Vertex was able to take care of this balance by improving the prodrug, allowing us to see opportunities and hopes, and entered the track of pain, making a relatively large improvement on the basis of VX-150.
Currently, apart from Hengrui Medicine's HRS4800 and Jemincare's JMKX000623 (both in phase 1 clinical trials), HBW-004285 are another one that IND in China.  It can be said that challenges and opportunities coexist on this track, as well as difficulties and hopes.

  Q2 Medicilon: HBW-004285 ranks among the first echelons of global Nav1.8 inhibitor drug development.  Can you share its unique advantages and therapeutic potential?

Dr. Li: HBW-004285 is a safe, highly effective and non-addictive Nav1.8 inhibitor, which can meet the needs of clinical development without the need for prodrug modification.  We tested 200 enzymes and more than 40 receptors, except for Nav1.8, there is almost no inhibitory effect on other targets, which shows that HBW-004285 is a highly selective Nav1.8 inhibitor.  At the same time, the toxicology test done in Medicilon showed good safety.  In addition, preclinical head-to-head comparative studies have shown that the activity of HBW-004285 is about 10 times higher than that of the positive control VX-150, and its pharmacokinetics are about 10 times higher, which has significant advantages in key druggability such as safety and effectiveness.  Moreover, HBW-004285 has more obvious advantages in the persistence of pain relief.

Whether it is for acute pain or chronic pain, HBW-004285 is very promising to become a new generation of best-In-class Nav1.8 inhibitor.

  Q3 Medicilon: Looking forward to the next few years, what progress do you expect Hyperway Pharmaceuticals to make in its R&D pipeline?

Dr Li: At present, we have deployed more than ten innovative R&D pipelines.  Now the fastest progress and the key push is HBW-3220 capsule.  Judging from the preliminary data of preclinical and clinical phase I, the drug has obvious advantages in clinical differentiation and is expected to become the third-generation BTK inhibitor of best-In-class.  At the same time, the clinical results have also been valued by worldwide Big Pharma, and may be authorized for international R&D in the later stage.  We plan to apply for breakthrough therapy designation, so that HBW-3220 can be launched in China soon.

▲Hyperway Pharmaceuticals' lab

In the field of pain, the above-mentioned Nav1.8 inhibitor HBW-004285 has the opportunity to complete Phase III clinical trials in about three years and submit NDA.  In addition, there are two other new target drugs in the field of pain, which are expected to be pushed to the IND stage next year.
In addition, we also have a relatively new PAK4 inhibitor HBW-008-A, a targeted drug for tumor immunotherapy, which changes the cell morphology and tumor microenvironment from a "cold tumor" to a "hot tumor", thus making it easier for T cells to attack it, it is expected to double the therapeutic effect of PD-1 and CAR-T, and become an anti-tumor drug with First-In-Class potential.

Q4 Medicilon: Hyperway has achieved outstanding results in the pharmaceutical industry only 4 years after its establishment. What is the secret for innovation and growth?

Dr. Li: The first thing to say is the team.  Hyperway has a young and energetic team with great learning and innovation ability. The management team has worked and collaborated with me for more than ten years, forming a high degree of tacit understanding.  At the same time, many of our technicians have practical experience in worldwide well-known pharmaceutical companies, and have accumulated rich experience in the fields of synthesis, preparation, and analysis.  Just talking about chemical synthesis, we have more than 30 technicians, most of them have experienced more than ten years, therefore the synthesis efficiency is very high.

Secondly, our company implements a full-staff shareholding model, and every employee is a shareholder.  Hyperway is not only a place for them to achieve their careers, but also a home, which will give them a stronger sense of belonging and responsibility.  If you are happy at work, your efficiency will naturally increase.

In addition, it is also related to my personal experience.  I have been engaged in new drug R&D and management in Bayer's German headquarters, Japan, and the United States for more than ten years. I have the experience of supervising the entire project as the general manager of strategic projects, which is very helpful for today's topic selection, design, and judgment of key nodes.  For example, all of our projects will benchmark against globally recognized compounds in the clinical stage with known structures, we will move forward when three to five important druggability indicators are achieved, and therefore more than half of them can be significantly surpassed.  It is precisely because of the height of the initial positioning, in addition of hard work of Hyperway, that it has achieved today's outstanding results.  

At last, our rapid growth is also inseparable from the help of CRO.  For example, we do not have our own biological and toxicology teams, so we entrust Medicilon to do the pharmacokinetics and safety assessment of the Nav1.8 inhibitor HBW-004285.  The two parties exerted their respective advantages and promoted the quality and efficiency of the entire R&D to be optimal, thereby smoothly advancing the IND filing and obtaining the approval of the CDE.
These are the indispensable and important factors for Hyperway Pharmaceuticals to get to where it is today.

Q5 Medicilon: Today, the homogeneity of China drug research and development targets is intensified, and the involution is serious.  How does Hyperway Pharmaceutical achieve characteristic and differentiated research and development?
Dr. Li:I have the following points to share with you.  The first point is to analyze the current status of target research and development.  For example, in the field of tumors with serious involution, dozens of BTK inhibitors are working, but most of them are working on second-generation BTK.  The third-generation BTK has done better mainly because Eli Lilly's LOXO-305, which was just launched in January this year, is the first and only third-generation BTK approved by the FDA, and the other is Merck's ARQ-531 in the third phase of clinical trials.  From the pre-clinical head-to-head comparison, HBW-3220 has better inhibitory activity than LOXO-305 and ARQ-531 not only against wild BTK, but also against various drug resistance mutations after taking the first and second generation BTK, such as C481S, C481R, and T316A.  HBW-3220 also has a good inhibitory effect on another major mutation, L528W, which is also resistant to drugs after taking the first and second generation BTK or LOXO-305.  In addition, HBW-3220 can also inhibit PLCγ2 mutation downstream of BTK, and LOXO-305 may be ineffective against this mutation.  In terms of safety, we have done a head-to-head toxicological comparison with ARQ-531, and the safety of HBW-3220 is much better than that of ARQ-531.  In general, HBW-3220 has a wider range of clinical applications than LOXO-305, better safety than ARQ-531, broader market prospects, and a greater possibility of becoming Best-In-Class.  Identifying the correct positioning and making some differentiated advantages, the competition of the three generations of BTK inhibitors is relatively unremarkable.

     

▲Hyperway Pharmaceuticals' lab

The second point is to look at clinical needs from an international perspective.  In the field of pain, there is very little done in China, but there is a great clinical demand internationally.  As Nav1.8 is a promising target, so we chose Nav1.8 and chose the field of pain.
The last point is to find our own position.  When we were doing BTK, we discovered a strong brain-penetrating BTK inhibitor, so we built a "Brain-Penetrating Drug Development Platform".  Therefore, we could further expand into this field, and made our own characteristics on the basis of differentiation.

Q6 Medicilon: Dr. Li, you have more than 20 years of experience in drug development and management in well-known worldwide pharmaceutical companies and your career has witnessed the development of the global biomedical industry.  As a successful person, how do you think the younger generation can make the leap in the era of involution?

Dr. Li:There is a high demand for lying flat in China, but I find that many young people around me are very ambitious.  It's like we have a group of young people who refuse to lie down on our team.  If their achievements can compete with the best drugs in the world, they will have continuous motivation to work hard.  In fact, it is the same for other young people. We must first do what we like.  If you didn't like it very much at first, but you are determined to do this line of work, then you must let yourself like it.  Because only if you like it, you will have passion and motivation to continuously improve yourself and deepen the industry.  When you have a certain sense of accomplishment, you will become more confident, more passionate, and more fruitful.  This process is like a snowball and is a very lucky thing.

In addition, we must have the desire for lifelong learning and the ability to learn, age and industry are never the reasons to limit the possibility of life.  In fact, you can try many things, and if you work harder, you will succeed more.

About Hyperway Pharmaceuticals

Hyperway Pharmaceuticals, a startup biotech company located in Chengdu High Tech Development Zone, was founded in January 2019 by a group of high caliber biotech entrepreneurs and industry veterans. Hyperway, adhering to a concept of "embrace all advances, attract all talents, benefit all people", is committed to discover and develop new medicines to address unmet medical needs using our state-of-art drug discovery technology platforms.

Currently, Hyperway has focused on establishing a unique and differentiated brain-through innovative drug development platform for the pharmaceutical industry.  More than 10 innovative drug R&D pipelines have been deployed, involving many fields such as tumors, pain, fungal infections, autoimmune diseases, and central nervous system diseases.  7 PCCs have been identified, 4 INDs have been declared, 3 of which have obtained implicit approval for new drug clinical trials, and the research results of many projects have been selected into the international academic annual meeting.  Among the 2 foreign collaborative innovative drug projects, one has been successfully delivered in October 2022 in accordance with the collaboration agreement, and the other is planned to submit IND filing in 2023.  Hyperway Pharmaceuticals will give full play to the company's advantages in innovative drug research and development, increase the investment in research and development, deepen collaboration, and adopt an open, multi-level, and multi-faceted collaborative model.  Through multi-dimensional collaborative methods such as regional equity transfer of innovative drugs, technical collaboration and technology transfer of innovative drugs and improved new drugs, we will seek external partners to jointly develop Chinese good drugs with better quality and better price!

About Medicilon

Since the founding of our company in 2004, Medicilon (Stock Code: 688202.SH) has grown into one of the professional drug discovery contract research organizations (CRO) in China.  Over the years, Medicilon keeps improving their services in biotechnology and pharmaceutical research.  Their services now span across medicinal chemistry, process chemistry, in vitro and in vivo DMPK, preclinical development and bioanalytical support.  By the end of 2022, Medicilon has provided new drug R&D services to more than 1,800 clients around the world, and participated in the R&D of 300 new drug projects that have been approved for clinical trials.  Medicilon is proud to contribute to human health in the globe.