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Medicilon's Interview: See how Dr. Chen Chen from ABM Therapeutics crosses the blood-brain barrier

2023-09-20
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On the way to fight against tumors, we may encounter many "enemies", and most of the time it is difficult to get through.  However, when faced with the formidable enemy of brain metastasis, they often lose.  Relevant data show that about 25%-40% of malignant tumors will develop brain metastasis during the course of the disease. Even with targeted therapy drugs, many will fail before they reach the metastasis.

Why is brain metastasis so common and dangerous?  We have to mention the blood-brain barrier that blocks drugs from entering the brain.

How to allow drugs to break through the blood-brain barrier is a major and important problem in the treatment of tumor brain metastasis.  Fortunately, there are always scientists who are not afraid of war and are bound to attack the blood-brain barrier and lead drugs across the blood-brain barrier. One of the examples is Dr. Chen Chen that we interviewed today.  As a scientist with more than 20 years of experience in central nervous system drug research and development, Dr. Chen Chen was inspired by oncology research expert Professor Ke Yu and chose to develop small molecule drugs for the central nervous system.  Dr. Chen founded ABM Therapeutics in 2015, recruited experts who have successfully developed global new drugs for the central nervous system and cancer, and formed an efficient and capable technical team.  At present, the first drug candidate BRAF inhibitor ABM-1310 independently developed by  ABM Therapeutics has obtained clinical trial approval from the US FDA and NMPA in 2019 and 2021 respectively.  ABM-1310 obtained the FDA orphan drug qualification certification in 2023, which can be described as rapid progress.

Shanghai Medicilon Inc. (Medicilon) has the honor to invite Dr. Chen Chen, Founder and Chairman of ABM Therapeutics, to discuss the unique technical advantages and R&D strategies of ABM Therapeutics in developing brain-targeted drugs, as well as the inner journey and profound insights.

Dr. Chen Chen
Founder & Chairman of ABM Therapeutics

Medicilon's interview: ABM.webp

Dr. Chen Chen is the founder and CEO of ABM Therapeutics.  Before founding ABM Therapeutics, he served as Sandia's General Manager and the company grew from 200 people to nearly 800 people.  Dr. Chen Chen has more than 20 years of experience in central nervous system drug research and development, including 15 years of working experience at Neurocrine Bioscience, a Nasdaq-listed company focusing on neurological drug research and development.  Dr. Chen started out as a researcher and rose to the position of Senior R&D Director of Medicinal Chemistry at the company, where he achieved many impressive achievements in the field of new drug discovery.  He developed two gonadotropin-releasing hormone receptor small molecule antagonists, NBI-42902 and Elagolix, and advanced them into clinical studies.  Elagolix is also the first FDA-approved oral medication to treat moderate to severe pain caused by endometriosis.

Dr. Chen received his bachelor's degree in chemistry from Xiamen University, and then obtained his doctorate from the Shanghai Institute of Organic Chemistry, where he studied under the Academician Yaozeng Huang.  Dr. Chen conducted postdoctoral training with Sir Derek Barton, the Nobel Prize winner in chemistry, at Texas A&M University in the United States.  Dr. Chen has published nearly 130 papers in professional journals such as American Journal of Chemistry, Journal of Organic Chemistry, Journal of Medicinal Chemistry, and Acta Biochimica Sinica.  He is also a co-inventor of 25+ more US patents.

Q1 Medicilon: Hello Dr. Chen Chen, congratulations to ABM Therapeutics for obtaining orphan drug qualification for ABM-1310. Can you introduce ABM-1310 to us?

Dr. Chen: ABM-1310 is a small molecule BRAF inhibitor.  Its greatest advantages are its high selectivity, good water solubility, and excellent blood-brain barrier permeability.  These qualities are very suitable for the treatment of brain diseases such as glioma.  ABM-1310 is currently in Phase I clinical trials for BRAF V600 mutated advanced solid tumors in multiple clinical centers in the United States and China.  Existing data show that ABM-1310 has a good safety profile and has shown very positive signals in patients with primary brain tumors, such as GBM and other gliomas.  Our team is making every effort to advance the clinical development of this compound.

The number of patients with orphan drugs is relatively small. For pharmaceutical companies, the investment is large, development is difficult, the success rate is low, the market potential is relatively small, and the benefits and risks are obviously disproportionate, which makes most companies avoid orphan drugs.  Although it is very difficult for ABM Therapeutics to develop orphan drugs, compared with the gaps in the market, clinical development is relatively low-cost and short-term.  Therefore, for  ABM Therapeutics, we first hope that new drugs can truly meet clinical needs.  In addition, after obtaining orphan drug certification, ABM Therapeutics will receive a series of economic incentives in the research and development of ABM-1310, thereby supporting us to continue to expand the indications of ABM-1310 and benefit more patients.  The current indication of ABM1310 is for brain glioma, and we will continue to conduct research and exploration related to the treatment and prevention of tumor brain metastasis.  I believe that the advantages of ABM-1310 will continue to be demonstrated clinically in the future.

Q2 Medicilon: Since its establishment, ABM Therapeutics has been focusing on the research and development of small molecule drugs that can treat primary brain tumors and other brain metastatic solid tumors, and has built a strong research and development pipeline.  Against the background of such fierce competition in the research and development of small molecule drugs, ABM Therapeutics has precise positioning and rapid development.  What do you think are the advantages of ABM Therapeutics in this field?

Dr. Chen: The brain itself is a very complex organ. Current science actually has a very limited understanding of the entire biological sciences, and even less about the brain.  The blood-brain barrier is like a protective umbrella for the brain. It can prevent foreign matter such as microorganisms and viruses from entering the brain. It also blocks most small molecule drugs and almost 100% of large molecules.  For new drug development, breaking through the blood-brain barrier is extremely challenging.  At present, the scientific community's understanding of the blood-brain barrier is not deep enough. Fortunately, our team has been deeply involved in this field for many years.  I have been engaged in the research and development of central nervous system drugs before, and have a relatively in-depth understanding of the physiological structure and function of the brain.  Such advantages can help our team better understand the limitations of the blood-brain barrier and formulate targeted development strategies so that drugs can cross the blood-brain barrier more effectively and achieve therapeutic targets, thereby providing the opportunity to contribute to solving the difficult problem of drug delivery to the brain.

In addition, ABM Therapeutics independently developed the brain-penetrating kinase drug discovery (BPKdd™) platform, which has well solved the two key issues of drug penetration through membranes and brain.  The entire technology platform has a great leading advantage in the world.  Currently, through this platform, we have established a rich R&D pipeline of drugs that can enter the brain.

Q3 Medicilon: Can you talk about what kind of company you think ABM Therapeutics is?

Dr. Chen: I think ABM Therapeutics is an excellent team that is constantly exploring and moving forward.

Drug research and development is a very complex and long process. On the one hand, we face many scientific challenges and require a lot of experiments and verification.  On the other hand, we must strictly abide by regulatory requirements and ensure clinical drug safety, which also means investing a lot of money and manpower and requiring a team to work together.

Over the past seven years, we have built a very good team that covers the entire process from research and development to clinical management.  In addition, for the team's shortcomings, we will complement each other's strengths through external collaboration.  In collaboration with CRO, the team will rely on their rich successful experience and extensive resources in related fields to obtain new creative inspiration and effective solutions.  For example, during the research and development process of ABM-1310, Medicilon Chemical’s FTE team helped us screen and optimize the candidate compound ABM-1310 during the drug discovery stage.

In the future, ABM Therapeutics will also promote clinical research on multiple pipelines and push existing pipelines forward as quickly as possible.  It is hoped that the team can continue to expand its capabilities and enhance its influence and competitiveness in the field of new drug development.

Q4 Medicilon: You have served as the General Manager of a CRO company. Can you tell us about your understanding of CRO companies?

Dr. Chen: CRO began to sprout in China at the end of the 20th century. From a few small companies in Wuxi, it gradually drove the entire industry, laying a solid foundation for the prosperity of the pharmaceutical industry.

I joined CRO at an early stage and have a deep understanding of this field.  It can be said that CRO is of revolutionary significance to the biopharmaceutical industry and plays a decisive role in drug research and development and accelerating the launch of new drugs.

On the one hand, CRO can reduce the cost of drug research and development.  For example, various expensive instruments and equipment need to be used during the experiment. For a Biotech, the utilization rate of these equipment may not be very high, resulting in a large investment but a waste of resources.  However, CRO companies could have a lot more clients. One instrument can serve hundreds of companies and can support the needs of various drug research and development projects. It also has rich experimental experience and can provide more efficient and professional research and development solutions.  Because of this, ABM Therapeutics has been cooperating with Medicilon since 2016, and has received support in drug design, chemical synthesis, biological testing, pharmacokinetic research and other aspects.

On the other hand, CRO companies have gathered and trained many outstanding talents.  They have rich experience in R&D and clinical trials, as well as a large reserve of scientific knowledge, and can provide high-quality R&D solutions and services to ensure the accuracy and reliability of test results.  Many young people work in CROs after graduation. Starting from basic work, they gradually become independent as they communicate with clients and exchange experiences with colleagues.  Only through accumulation can we make progress, which is a kind of accumulation for the future of the biopharmaceutical industry.  I believe that without CRO companies, there would be no vigorous development of new drug research and development in China in recent years.

Q5 Medicilon: So can you talk about what qualities scientists need to have to start a business?

Dr. Chen: This is very interesting.  Scientists who do scientific research are usually considered to have relatively high IQs.  I often joke that there is an inverse relationship between IQ and EQ. If the IQ is high, the EQ will be low, and if the EQ is high, the IQ will be low.

For R&D personnel with high IQs, they need to pay attention to the cultivation of emotional intelligence in their career development.  As entrepreneurs or decision-makers in a company, in addition to doing good research and development, we must have professional knowledge and skills. We also need good communication skills to better cooperate with team members, customers and other stakeholders.  In a highly competitive business environment, keen insight is even more important.  These capabilities can help us better work with our management teams to attract investment, expand markets and develop our business, and gain an advantage in the competition.

Q6 Medicilon: Currently, the biopharmaceutical investment and financing markets in China and the United States are in difficult condition.  What do you think is the reason for this phenomenon?  In the next decade, what theme do you think will lead everyone out of the difficult condition?

Dr. Chen: The short difficult condition is actually not the biggest problem.  I think it still depends on the overall environment. In fact, I am not particularly worried about this aspect. China's biopharmaceutical industry has accumulated a large number of talents in the past decade, which can be said to be the most important for the entire industry.  There is an old saying in China, "Study mathematics, physics and chemistry well, and you will have no fear of traveling all over the world."  Many universities in China are equipped with chemistry departments and other science majors, which are the core source of strength for the talent pool in the biopharmaceutical industry.

The field of new drugs has grown rapidly over the past few years, but I think that every emerging field will have an uneven process.  It has climbed rapidly in the past few years and has become overheated, which requires adjustment.  This requires us to have firm will and belief, clear goals and strategies, and extensive participation and collaboration.

Health is a fundamental need of human beings.  As economic conditions get better and better, human beings' requirements for health will become higher and higher.  Coupled with talent accumulation, capital attention, and technology iteration, I am very optimistic about the entire industry in the future.

I think the key to leading everyone out of the "difficult condition" is rationality.  As a highly complex and sensitive field, the biopharmaceutical industry needs to rely on scientific, empirical and rigorous methods for R&D, production and management.  The entire industry was very prosperous in the past few years; so many people pursuing hot topics will join in, fall into involutional innovation, and even cause internal friction with each other.  As time passes, maintaining rational thinking can help us better respond to the challenges and opportunities in the biopharmaceutical industry, promote the healthy development of the industry, and bring more welfare and progress to society.

Q7 Medicilon: Do you have any expectations or advice for the new generation in the biopharmaceutical industry?

Dr. Chen: Compared to my job-hunting experience when I was young, young people today have more choices.  Different eras have different situations and topics, but I think the similarity lies in interest and love, which are very important motivations.  When a person is interested in and enjoys the work they do, they are more likely to feel a sense of accomplishment and, in turn, more motivated to continue learning and improving.

When young people choose an industry, I think they need to have a long-term vision, that is, foresight, and not just focus on immediate interests.  Also, it's important to balance personal preferences with family expectations.  As we gradually demonstrate our talents and values, families will realize that their chosen industry can also have good development prospects and achievements.

For young people engaged in scientific research, it is recommended to avoid frequent job-hopping.  R&D work requires long-term accumulation. Frequent job changes will result in only superficial experience in each new position, and not enough time for in-depth learning and growth, which is not conducive to experience accumulation and improvement of professional capabilities.  Of course, changing jobs can provide you with better opportunities, challenges and room for growth, and it is not an absolutely undesirable option.  However, before making a decision, you should fully weigh your career goals, development direction, and the opportunities and challenges provided by the new job.

On August 25, 2023, ABM Therapeutics announced that its independently developed brain-entering MEK1/2 inhibitor ABM-168 has been approved by the National Medical Products Administration (NMPA).  The company agreed to recruit patients with advanced solid tumors, especially brain metastases or primary brain tumors, with the aim of exploring the safety, tolerability, pharmacokinetics and preliminary anti-tumor activity of ABM-168 in such patients.  Looking forward to the future, ABM Therapeutics will bring more exciting news and explore the potential of multi-drug combination use.  We look forward to ABM Therapeutics continuing to make more breakthroughs in the field of medicine and bringing greater hope to human health.

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