Text | Dun Yuting
Cell drugs are the third generation of drugs after small molecule chemical drugs and large molecule protein drugs, also known as "living drugs". Its essence is to dedifferentiate and reduce the decomposition of mature human cells into induced pluripotent stem cells (iPSCs) similar to embryonic stem cells, and then further transform them into mature functional cells for treatment. Based on this technique, it becomes a reality to fill in the human body with damaged and or degenerative functional cells.
At present, as a new therapeutic method, iPSC-derived cell drugs have received general attention from the industry. Typically such as Bayer, the company's BlueRock has entered the first phase of clinical trials in this field and achieved positive results, and further proved the effectiveness and safety of iPSC-derived cells in the parkinson's treatment field, and may have great commercial value in the future. It is reported that Parkinson's is one of the most pathological diseases in the field of central nervous system (CNS) and is most suitable for iPSC entry.
This year, this segment also ushered in a favorable policy end. The "14th Five-Year Plan for the Development of the Bioe economy" released in 2022 pointed out that "the development of genetic diagnosis and treatment, stem cell therapy, immune cell therapy and other new technologies, strengthen the synergy between production, education and research, and accelerate the transformation and clinical application of related technology products". Among them, stem cell technology, including iPS, and the industrialization of regenerative medicine are an important part of them.
Wuhan Ruijian Pharmaceutical Technology Co., Ltd. (hereinafter referred to as "Ruijian Pharmaceutical") is a biopharmaceutical company recently learned by 36Kr that focuses on the research of highly efficient chemical small molecules to induce functional cell regeneration, and the company aims to provide new treatment solutions for "incurable" diseases such as Parkinson's disease and blindness. At present, around the research and transformation of cell fate regulation mechanism, the company has built a knowledge graph based on the developmental biological regulation network, as well as a cell drug research and development technology platform based on chemical induction, and carried out a patent layout.
Up to now, Ruijian Pharmaceutical has completed the layout of multiple R&D pipelines: in addition to cytokinesian diseases for Parkinson's disease, spinal cord injury, stroke and other neurodegenerative diseases, it has also explored the possibility of cell drug therapy in the fields of optic neuropathy, diabetic retinopathy, amyotrophic lateral sclerosis, and liver metabolism.
Wei Jun, co-founder and CEO of Ruijian Pharmaceutical, pointed out that the company began communication with regulatory agencies including the FDA as early as 2019, and also participated in the formulation of relevant guidelines in the mainland, "it is very necessary to jointly promote product research and development with regulators in the early stages of drug development." In addition, she also revealed that ruijian pharmaceutical's international R&D center of more than 10,000 square meters is also expected to be put into use this year.
However, as a nascent treatment, the transformation process of iPSC is still challenging. Since the invention of iPSC in 2006, its application safety has been widely concerned, and how to avoid the occurrence of teratoma is a research hotspot in the field. Moreover, both academia and industry have a clear international consensus, the most basic of which is the efficiency of iPSCs into functional cells, and efficient conversion is the basis for iPSCs to industrialize.
Previously, some institutions have caused teratomas in non-standard human iPSC clinical trials, which has aroused industry concern about the safety of iPSC applications. "The biggest bottleneck in the clinical application of iPSC is the efficiency of derived cell transformation, which is also repeatedly emphasized by Professor Shinya Yamanaka, the inventor of iPSC." Wei Jun said that the low conversion efficiency will lead to iPSC cell residue, resulting in subsequent tumor-causing risks, and at the same time affecting the final efficacy of the product. Therefore, efficient functional cell differentiation systems are key to the rapid commercialization of iPSCs.
It is reported that at present, Ruijian is also working with the review agency to actively carry out IND supplementary research in response to the recent concentrated emergencies in the field of iPSC.
From the beginning of its establishment, Ruijian Pharmaceutical has chosen to independently develop a pluripotent stem cell product development platform based on AI screening of small molecule compounds as induction and culture medium, with the purpose of achieving efficient transformation of induced pluripotent stem cells. It is reported that Ruijian Pharmaceutical can use this to complete the analysis of the difference between induced pluripotent stem cells and the target cells of transformation, determine which genes determine the direction of cell differentiation and maturity, and thus determine the induction scheme of derived cells to ensure the efficient differentiation of cells in industrial production volumes, which is also a key issue generally ignored in the industry.
Take iReMeta, one of the company's core platforms, which is based on data and algorithms for developmental biology omics. Using the knowledge graph for target enrichment analysis, and combining the interaction network topology to calculate the impact of each pathway and the importance of each target, Regen Pharma was able to obtain the key pathways and genes in specific developmental pathways, and in-depth determination of the most suitable cell state for treatment, and these factors were used as core screening criteria to help the Ruijian team match and screen small molecule compounds that can play an inducing role, thereby achieving better treatment results.
In addition, Ruijian Pharmaceutical has also established a corresponding reporting system and a high-throughput screening system to quantitatively screen compounds, including organoid verification and a variety of omics analysis, and finally screened for compound molecules and combinations that can be efficiently induced.
After fully understanding the mechanism of iPSC differentiation, Ruijian Pharmaceutical was able to use suitable chemical small molecules to complete the efficient transformation of induced pluripotent stem cells into target cells. That is, with the appropriate chemical small molecule "switch", the standard differentiation process is initiated at the cellular level, so as to solve the difficulty of industrial volume differentiation being out of sync and inefficient, and finally obtaining a stable development process with a target cell purity of more than 99%.
In addition, according to reports, the conversion efficiency is not only closely related to the safety and efficacy of the drug, but also affects the production cycle and cost of the product to a certain extent. Wei Jun pointed out that Ruijian Pharma's chemical induction platform can avoid the use of expensive viral work, while the production cycle and cost are also effectively controlled, which in turn can help develop inclusive cell drugs.
Based on the above technology platform, The future business of Ruijian Pharmaceutical is not limited to cell products. Taking the compound platform as an example, Ruijian Pharmaceutical not only uses a new structural compound to achieve the transformation of the cell state, but also its computational chemistry team has also built a compound design platform based on small nucleic acids and epimodulation, and used these platforms to achieve immunogenic control, and can carry out corresponding pipeline layout in the future.
It is worth noting that Dr. Yonglun Luo, a researcher at the European Molecular Biology Laboratory - Danish Translational Neuroscience Research Center and a professor at the Department of Biomedicine at Aarhus University in Denmark, has recently been officially announced as the company's "International Breakthrough Innovation Science Officer"; As well as the appointment of Mr. Emmanuel Montet, former Vice President of China and Asia of Ipsen Aisa, as the Company's invited international operation consultant.
It is reported that Dr. Luo Yonglun completed important research work in the field of regenerative medicine in the early years of Novo Nordisk, the University of Edinburgh in the United Kingdom, and the George Church Laboratory of Harvard Medical School, and has a deep accumulation in the frontier technology of regenerative medicine, especially in the field of genomics and gene editing tools; Emmanuel Montet has nearly 20 years of experience in the pharmaceutical industry, having served as Vice President of China and Asia at EPSON Asia, Head of Finance and Industrial Control at IPSEN Pharma SAS, and held key positions in GlaxoSmithKline and Sanofi, with extensive experience in corporate governance operations, international business, market access strategy development, product distribution and other areas.
In addition, the founder of the company, Dr. Wei Jun, has been funded by the Rockefeller Foundation of the United States and the Ors of the United Kingdom, and has received master's degree in molecular biology and doctoral education in regenerative medicine in the United States and the United Kingdom, and has successively served as a resident of the Stem Cell Center of union hospital affiliated to Huazhong University of Science and Technology, a senior researcher of embryonic stem cells at the Roslin Institute in the United Kingdom, a head of expert research and development of Axol Bioscience in the United Kingdom, and a visiting researcher at Clinical Neuroscience at the University of Cambridge, the United Kingdom. He has rich experience in the clinical treatment of stem cells, the directional differentiation of pluripotent stem cells and the construction of in vitro disease models.