Recently,CGeneTech successively announced that two new drug products under research and development were approved by both China and the United States, opening the journey of overseas clinical development. In January of this year, the first product ofCGeneTech, the multiple sclerosis treatment drug teriflunomide, was approved for listing, and the company officially entered the commercial development stage. In addition, its new diabetes drug DPP-4 inhibitor Cetagliptin phosphate has entered the phase 3 clinical closing stage.

"ForCGeneTech, the next 5-10 years will be a stage of rapid development." In a recent interview with Wuxi apptec's content team, Dr. Yu Qiang, founder and CEO ofCGeneTech, said:, "CGeneTech is transliterated from CGT. These three letters are taken from the initials of the company's English name chemical genomics technology, which means to find suitable therapeutic methods through systematic screening and optimization from the chemical perspective. With the promotion of product listing and other clinical pipelines, as well as capital support through IPO and other channels, we will embrace more new technologies in the future Including cell gene therapy and becoming a real CGT technology company. "

Dr. Yu Qiang has a solid academic background in the field of chemistry. He has successively obtained bachelor's, master's and doctor's degrees in chemistry from Peking University, Kansas State University and the University of Kansas. After graduation, he followed Professor Ronald Borchardt, a world-famous scientist, to engage in post doctoral research. After that, he worked in pharmaceutical chemical technology company for many years and successfully founded a company to develop new drug molecular modules. After nearly 20 years of overseas career, he returned to China in 2010 and co foundedCGeneTech with Mr. Ding juping, who has rich experience in new drug R & D and application.

Since its establishment,CGeneTech has established a wealth of product pipelines, covering many disease fields such as diabetes, cancer and rare diseases, and is now entering the "fast lane" of new drug research and development. Under the new development stage, what internal and external challenges areCGeneTech facing and how will it overcome? At the beginning of "going to sea" of innovative drugs, what internationalization strategies has the company formulated? What are the future development plans and key R & D directions? Let's follow the interview of the reporter of medical mission hills and listen to Dr. Yu Qiang's in-depth discussion on these issues.

Photo source: provided byCGeneTech, produced by Wuxi apptec content team

Wuxi apptec content team: first of all, congratulations toCGeneTech on the completion of two Sino US double newspaper projects recently. May I ask why the CXCR4 antagonist CGT-1881 was selected for the first "sea going" project? What unique advantages and therapeutic potential does it present?

Dr. Yu Qiang: the choice of CGT-1881 antagonist is related to the global R & D progress and achievements of CXCR4 target. Studies have shown that CXCR4 (chemokine receptor) not only plays a key role in tumors, but also has a close relationship with some immune diseases, genetic diseases and viral diseases. Among them, CXCR4 antagonists have been clinically validated as stem cell mobilization agents. At present, some products have been approved for use in bone marrow transplantation of hematoma. Specifically, by blocking the interaction and signal transmission of SDF-1 / CXCR4, these products can mobilize bone marrow hematopoietic stem cells to enter the peripheral blood circulation, so as to complete the collection of hematopoietic stem cells and autologous transplantation. In terms of genetic diseases, the development of indications of CXCR4 antagonists against whim syndrome, a congenital immunodeficiency disease, has entered the phase 3 trial phase globally. In addition, such products are also expected to be used in combination with PD-1 / L1 inhibitors and chemotherapy for pancreatic cancer and other tumor species, and have been proved in phase 2 clinical trials.

Currently, no oral drug targeting CXCR4 has been approved globally. CGT-1881 is a new generation of CXCR4 antagonist with high efficiency and selectivity under research byCGeneTech, which has certain novelty and differentiation advantages. It is administered orally, which is more convenient and accessible than the injectable drugs on the market. At the same time, this product has obvious advantages in oral bioavailability and blood-brain barrier crossing. In addition to taking the lead in developing the product for stem cell mobilization, the product will be used for other clinical indications in China and the United States in the future, such as whim syndrome, which is a rare hereditary primary autoimmune disease.

Wuxi apptec content team: the "going to sea" of innovative drugs is one of the current focus topics. Can you share the experience of CGT-1881 in overseas application? In your opinion, what are the key capabilities and elements for innovative drugs to go to sea?

Dr. Yu Qiang: in the past, the innovative drugs of many Chinese companies are worthy of admiration and have certain reference and reference significance for the later ones. In the overseas application process of CGT-1881, we have done a solid preclinical research work with the assistance of our partner Wuxi apptec, and found overseas clinical research service teams and excellent clinical PI (main investigator). There are certain differences in thinking modes between China and the United States, so we need to strengthen communication with PI and the regulatory agency FDA. Based on the preclinical experimental results, both parties need to reach a consensus on the future development of products and how to maximize the benefits of patients. For this reason, the team has spent more time and energy to develop a clinical scheme that meets the regulatory requirements and can be accepted and understood by everyone. At the same time, both ethics and innovation should be taken into consideration.

In my opinion, there are three key elements for innovative drugs to go to sea. The first is the innovation of the product. Truly innovative products can not only attract excellent researchers to participate, but also enhance the research ability and academic influence of researchers. The second is whether the preliminary research is solid, that is, whether the product efficacy and safety data obtained through the research are sufficient. Finally, communication with regulatory authorities is also very important. These elements cannot be separated from the support of partners. At the same time, we also hope to cooperate with like-minded overseas biotech companies to jointly promote the clinical development of products overseas.

Wuxi apptec content team: what are the biggest internal and external challenges you and the team are facing at the current stage? How did your company solve this problem?

Dr. Yu Qiang: after more than ten years of development, the company has gradually completed the construction of the whole industrial chain talent team from R & D to industrialization. With the approval of trifluramine, a product for the treatment of multiple sclerosis, the phase 3 clinical trial of Cetagliptin, a hypoglycemic drug, is coming to an end. The company's team has fully covered the whole chain of early target identification, compound design, preclinical and clinical research, registration and commercialization. Next, our internal challenge is how to make the whole team gain more practical experience.

In terms of external challenges, the first is how to maintain competitiveness, which also requires the team to consider the quality and differentiation of products in internal R & D and project selection. The second is financing. When the market environment is good, how to make investors willing to invest capital; When the market environment is not good, it is worth pondering how to keep investors interested. Of course, it is much more difficult to solve external challenges than internal challenges. At present, we are working hard, including fully communicating with investors to gain sufficient trust. However, the most important thing is to do the project well.

Wuxi apptec content team: judging from the current situation of new drug research and development in China, the concentration of targets is still obvious. As the helmsman of an innovative medicine enterprise, how do you think to ensure the competitiveness of R & D products and the innovation vitality of the enterprise?

Dr. Yu Qiang: there is an attribute of capital, which is to seek stability and innovation. However, stability is easy to be homogenized and innovation is risky. Since I started my business, I have been thinking about how to balance stability and innovation in the company's internal projects. Therefore, we have long started to pursue that the products under research have certain advantages over the existing clinical treatments. If they are the same target products, we must achieve high quality and differentiation at the same time. It is worth mentioning that we found that the products developed based on the integrated drug R & D technology platform created by the company have a potential systemic advantage, that is, compared with the existing therapeutic drugs, the dose is significantly reduced under the premise of the same efficacy. Specifically, these compounds have stronger molecular interaction with the target, increasing the specificity and selectivity, and improving the pK (pharmacokinetics) in vivo, thus changing the metabolism in vivo.

Taking the DPP-4 inhibitor Cetagliptin as an example, it has shown the advantages of halving the dose but having the same efficacy as similar products in clinical trials, and is expected to become a "best in class" new hypoglycemic drug. Another example is the new generation ALK inhibitor CGT-9475. Compared with the second generation of the same target product, preclinical studies show that it has certain advantages in efficacy and safety, and the dose can be reduced by half or even to 1 / 3. In addition, it can simultaneously inhibit ALK and RET mutations in non-small cell lung cancer cell lines and show good blood-brain barrier penetration effect, which is expected to bring hope to patients lacking effective solutions in the clinic.

Wuxi apptec content team: how do you view the role and impact of external cooperation in the bio pharmaceutical innovation ecology? How do you think the industry should build and accelerate cooperation to promote innovation and benefit patients? What are your personal suggestions?

Dr. Yu Qiang: external cooperation is very important because no enterprise in the biomedical industry is omnipotent. We should clearly know the professional knowledge of our industry, and at the same time, we should recognize our own shortcomings and understand how to find the best partners. For areas where you are not good at, you need to learn from each other's strengths through cooperation, so as to promote the products better and faster. AtCGeneTech, we have cooperated with many excellent and professional institutions and experts in different stages of clinical development from preclinical to clinical development for treatment products in different disease fields, with a view to fully tap the potential of the products and maximize their value.

In terms of building cooperation, the cooperation ecology of China's biopharmaceutical industry has become increasingly mature. For example, in the cro / cdmo field, there are both small and specialized services and full chain solutions. Therefore, most of the problems encountered in the process of product development can be basically solved. In my opinion, the next step of the industry should be to accelerate cooperation. This not only requires the biomedical companies to maintain an open mind, but also requires continuous capital investment to support innovation and R & D. Our ultimate goal is the same, that is, to enable patients to get better treatment and obtain higher quality of life.

Wuxi apptec content team: what do you think is the most revolutionary next breakthrough in the field of life science? Or what is the upcoming breakthrough that you are most excited about?

Dr. Yu Qiang: I am more optimistic about the world's leading-edge cell and gene therapy. This kind of therapy has a certain early research and development foundation and clinical foundation, and has shown "cure" potential in cancer, rare diseases, genetic diseases and other fields, especially in some diseases lacking real treatment means. In addition, I also like AI (Artificial Intelligence) technology. At present, AI has been widely used in compound design and drug evaluation, but its real potential has not been fully developed. In my opinion, the key capability that AI needs to expand is the research on big data, that is, through comprehensive analysis of the etiology, treatment process, disease progression and other data of all patients, so as to provide better research and development ideas for scientists, and finally promote the industry to enter a real era of accurate treatment.

Wuxi apptec content team: can you describe the future scenario of the development of China's biomedical industry in 5-10 years? At that time, what is the expected development stage ofCGeneTech?

Dr. Yu Qiang: the development of China's biopharmaceutical industry will usher in a phase change every five years, and every five years will lay a good foundation for the next five years. In terms of drug development, from the early "me too" to the later "me better" and then to the current "first in class", the industry has accumulated a lot of important experience in different types of product development, and has also achieved a number of excellent companies and talents. With the progress of scientific research, these resource reserves will promote the next wave of innovation in the industry. It is believed that in the next 5-10 years, China's biomedical industry will usher in better development, just like entering the high-speed "high-speed railway era".

ForCGeneTech, it will also be a stage of rapid development in 5-10 years. At that time, we will complete the whole chain R & D and industrialization of the new hypoglycemic drug Cetagliptin from beginning to end. The team should also get more exercise and accumulate rich experience. With the promotion of product listing and other clinical pipelines, as well as capital support through IPO and other channels, we will embrace more new technologies in the future, including cell and gene therapy. In addition, the company will also participate in the development of AI technology, hoping to witness the real potential of this technology in the future.

Wuxi apptec content team: many of our readers are young people in the front line of R & D. What is the experience or experience you most want to share with them?

Dr. Yu Qiang: the young R & D personnel in the front line are especially motivated, just like infants and young children in understanding the new world in this field. If this vigorous thirst for knowledge is combined with scientific research, it will produce a great explosive force. In the past 10 years, the foundation laid by the industry leaders was like "planting trees". At present, what the younger generation should do is not to "enjoy the cool", but to "water" in a down-to-earth manner, irrigate "towering trees" in China's biomedical industry, and constantly open up new fields, finally forming a dense "forest".