NIE 2023 | Zehui Biotech Jia Yi: Research on a Pharmaceutical Technology Platform Based on Human Embryonic Stem Cells

Dr. Jia Yi pointed out that traditional drug research often starts with diseases with clear pathogenic mechanisms, first identifying key targets, then screening for suitable compounds or antibodies based on these targets, and finally proceeding with subsequent drug development. Stem cells were discovered during developmental biology research. With further exploration, it has been found that these cells can generate functional cells with special biological activities. Once inside the body, they can respond to complex disease environments, replace or repair cellular physiological functions, and even promote tissue regeneration. Therefore, current research on pharmaceuticals often targets difficult-to-treat diseases with complex pathogenic mechanisms.

According to the different sources of cells, stem cell research for drug development can currently be divided into two main categories: pluripotent stem cells and adult stem cells. Pluripotent stem cells are divided into human embryonic stem cells (hESC) and induced pluripotent stem cells (iPSC). hESC and iPSC lines, as seed cells, originate from a single individual, can replicate indefinitely, and can differentiate into all different functional cells of the germ layers. Functional cells are used for clinical cell therapy; adult stem cells are currently mainly mesenchymal stem cells derived from different tissue sources. The number of mesenchymal stem cells prepared from a single tissue material is relatively limited, and they can only differentiate into cells of the same germ layer as the tissue source.

When choosing the path of developing pharmaceuticals from stem cells, Dr. Jia Yi believes that human embryonic stem cells have advantages: they can continuously proliferate and differentiate as seed cells, allowing for large-scale expansion. This provides a sufficient and biologically consistent source of material for cell drug production, enabling the industrial-scale production of stem cell drugs. Moreover, pluripotent stem cells have the potential to differentiate into all types of functional cells, offering a wide range of therapeutic indications.

Subsequently, Dr. Jia Yi introduced the preparation process of functional cell preparations derived from human embryonic stem cells: extracting inner cell masses from blastocysts formed by the development of fertilized eggs to create human embryonic stem cell lines, then establishing a human embryonic stem cell bank, performing directed differentiation on human embryonic stem cells, and finally forming functional cells, which are combined with excipients to prepare cell preparations. This preparation process is stable and controllable, with the number of cells reaching millions during the entire process, ensuring the commercial production of cell-based drugs.

Dr. Jia Yi introduced the research and development platform for human embryonic stem cell-derived cell drugs at Zehui Biotech, pointing out that the company's stem cell lines are derived from clinical-grade human embryonic stem cells provided by the National Stem Cell Resource Bank. They do not use human or animal serum, do not employ gene editing, and have passed the inspection of the China National Institutes for Food and Drug Control (CNIFDC), effectively ensuring the reliability of the cell-derived drug source. Zehui Biotech has a technology platform for differentiating into various functional cells, capable of conducting preclinical and clinical research related to drug development, and innovative stem cell drug development.

Dr. Jia Yi then introduced the mechanisms of action of different functional cells derived from human embryonic stem cells, including immune regulation, repair and growth, and cell replacement. These have unique advantages for the treatment of immune-inflammatory diseases, degenerative diseases, and injury-related diseases. These are also the three main disease categories currently under development for Zehui Biotech's stem cell drugs. In China, due to the complex pathogenesis of these diseases and the poor efficacy of existing drugs, there is a high clinical demand for them. At the same time, there are also issues such as high prices and low market penetration rates for related therapeutic drugs both domestically and internationally.

Subsequently, Dr. Jia Yi introduced in detail the development of pharmaceuticals using human embryonic stem cells. Currently, major pharmaceutical research and development countries around the world are conducting research on pharmaceuticals using human embryonic stem cells. Neural precursor cells and islet cells derived from human embryonic stem cells have been approved by the US FDA for Phase I/II clinical trials. Nearly 70 new stem cell drugs have been approved by the National Medical Products Administration for registration clinical trials, mainly consisting of adult stem cell drugs. Only about 10% of the approved multi-potent stem cell drugs are undergoing registration trials. As for drugs using functional cells derived from human embryonic stem cells, there are currently only five applications (for indications such as chronic injury, acute inflammation, and blood diseases) approved by Zhehui Biotech. Zhehui Biotech has established a technology platform for pharmaceuticals using human embryonic stem cells, different differentiation processes for functional cells, and quality control systems. From preliminary laboratory research to setting quality research and control standards in GMP workshops, it ensures that cell preparations can be produced in a stable and controllable process according to standards.

According to Dr. Jia Yi, clinical research on different functional cells derived from human embryonic stem cells has been submitted to 19 hospitals in 11 provinces and cities across the country, all of which have obtained approval from the hospital ethics committees. The preliminary animal pharmacodynamic study data conducted by Zehui Biotech's human embryonic stem cell pharmaceutical technology platform show that human embryonic stem cell drugs have significant therapeutic effects in various animal models for degenerative diseases, acute and severe inflammatory diseases, and injury-related diseases. Zehui Biotech will continue to conduct research on different indications around stem cell drugs, continuously exploring new functional cells and new indications, ultimately aiming to achieve the approval and market launch of human embryonic stem cell drugs for the benefit of patients.