On December 24, 2018, it was exclusively learned that Zhejiang Huoyi Bioengineering Co., Ltd. (abbreviation: Huoyi Bio) had completed the A round of financing of tens of millions of yuan. This round of financing was led by Shanghai Datai, and probe capital acted as the exclusive financial advisor. The funds raised will be used for pre-clinical trials related to cell therapy, as well as fixed inputs and pre-market development such as production and R&D. Due to the superiority of technology, Hod Bio has obtained 12 million yuan from Hangzhou Jingchuang Investment, Heli Investment and Sai Bole since its establishment in 2017. From basic research to technology entrepreneurship If he does not choose to start a business, Dr. Fan Jing will obtain a professorship in a US research institution in accordance with his original life trajectory and continue basic medical research. In 2012, after receiving a Ph.D. in neurology from the University of British Columbia, Canada, Fan Jing entered the laboratory of Professor Ted Dawson and Valina Dawson of Johns Hopkins University in the United States to continue his postdoctoral research on the pathogenesis of neurological diseases. Thinking about it now, this should be a crucial turning point in her life. At the top neurological disease laboratory of the Hopkins Neurology and Cell Engineering Institute, Fan Jing and other scientists have sufficient laboratory research funding and are ranked first in the United States for 21 consecutive years, the highest federally funded medicine. Under the platform environment of the hospital, I am concentrating on the most advanced disease research in the neurological field. The biggest pain point in the research of neurological diseases is that it is almost impossible to obtain human living nerve cells or brain tissue for neurological disease research, and animals as a neurological disease model are very different from human mechanisms and phenotypes. The reprogramming of human induced pluripotent stem cells (human iPSCs) and the induction of differentiation from pluripotent stem cells (including iPSCs and embryonic stem cells ESCs) to the emergence of nerve cells and other technologies have greatly facilitated the study of neurological diseases. Dawson Laboratories was trying to use human brain nerve cells to validate important findings from previous laboratory models in animal diseases, and tried to use human cells to screen and validate targeted small molecule drugs, as well as signaling pathways and new drug targets. The discovery. However, all the neural cells obtained by the mainstream neural differentiation methods at the time had defects of insufficient maturity and functionality. In order to solve this problem, Xu Jinxi of Dawson Labs (formerly the Ph.D. in Neurology at the University of Hamburg, Germany, and the founder of Hod Biosystems), through two years of exploration, established a new, induced differentiation of pluripotent stem cells. The RONA method of obtaining extremely pure human neural stem cells and various mature and stable nerve cells is obtained. After Fan Jing joined the research group, he rented the RONA technology with the help of Xu Jinxi, and independently applied this technology to produce human cerebral cortical cells, and constructed the stroke and neurodegenerative disease models and confirmed the downstream pathways. Verification of small molecule drugs. Subsequently, Fan Jing applied the in vitro disease model and mouse model obtained by the differentiation method to independently discover and confirm the important missing link in the neuronal death pathway, filling the gaps that have been unknown in the laboratory and scientific circles. Fan Jing is excited to write the second academic paper of his post-Bao period and submit it to Nature Cell Biology. After receiving the article "Science Translational Medicine", which was jointly contributed by Dr. Xu Jinqi in 2016 (50% contribution), Fan Jing was able to produce another 95% contribution in a short period of time, which was the result of Professor Dawson's couple. Great recognition. At the end of 2016, after communicating with peers and companies at the International Stem Cell and Neurology Annual Meeting, Fan Jing was clearly aware of the commercial potential of this technology. This technology can obtain a large number of human neural systems with human six-layer cerebral cortical cells in vitro. The ratio of excitatory and inhibitory neurons, and the subtypes of interneurons are almost the same as those of human brain. Batch stability, maturity and functionality far exceed the current mainstream methods of Harvard, Stanford, Wisconsin Madison and other similar companies on the market. Even more exciting, the laboratory colleagues injected the neural precursor cells differentiated by RONA into the damaged area of ​​the brain of immunodeficient mice with cerebral infarction. The cells of these transplanted humans were in the brain of mice one month later. 80% differentiate into functional cerebral cortical cells, and the rest differentiate into brain cells such as glial cells. Differentiated into but the nerve bundle growth can reach the contralateral brain as well as the moving nuclear region, and the mice's hemiplegia symptoms showed a significant continuous improvement compared with the control group without the injection of these cells. The results of this experiment made the entire group very excited, because the brain cell death caused by stroke and the resulting hemiplegia are currently without any treatment. Cell therapy, which means "replacement of your own functional brain cells and the formation of neural connections again" will be a real breakthrough! Not only that, they expect that the same cell therapy strategy will have similar therapeutic effects on hemiplegia caused by cerebral hemorrhage, craniocerebral injury, etc., and cognitive and motor disorders caused by diseases such as Alzheimer's, Parkinson's, and autism. There will be some effect. Xu Jinyu and Fan Jing realized that this technology has the potential to bring about real changes in the treatment of neurological diseases. “At the end of 2016, we began to realize the huge industrialization value of this technology. We hope that the vast research and development departments, pharmaceutical research and development departments and patients with neurological diseases can enjoy the product benefits brought by this technology, not just for us to close. The door is doing research," Fan Jing said. During this period, many companies want them, or hope to reach a technology transfer agreement with them. But these invitations also make them feel worried: just transferring technology or joining a company can ensure that this superior technology truly transforms and realizes the ultimate value? As a neurological disease scientist, both of them have a very strong sense of mission and hope to finally realize the ideal of providing treatment for patients with neurological diseases. After nearly half a year of discussion, and seeing that the environment for domestic biomedical R&D and investment and financing is getting better and better, they finally decided to return to China by Dr. Fan Jing to set up a company full-time to ensure technology. Therefore, Fan Jing, 35 years old, a researcher who has worked in the field of scientific research for 14 years, opened the door of the laboratory and bravely went to the magnificent entrepreneurial world. Cell therapy, new ideas for the treatment of neurological diseases Stem cell technology, also known as regenerative medicine technology. In theory, it is possible to separate and dry cells in vitro, and finally obtain new cell tissues and organs to achieve treatment of clinical diseases. Since the 2009 EMA approved Chondro Celect for knee cartilage defects, there are nine stem cell products available worldwide. Most of these products are used for bone repair and arthritis diseases, but they are still a market gap in the field of neurological diseases in which Fan Jing is involved. More than just stem cell therapy, there are few treatment options in the entire neurological field. Giant pharmaceutical companies continue to pour a lot of money into it, but until now, most of the new drug research and development of neurological diseases have not achieved substantial success. 2016 Eli Lily's company solanezumab clinical trial failed Intepirdine Phase III clinical trial failed by Axovant in September 2017 Lundbeck's idalopirdine clinical trial failed in early 2018 Pfizer Announces Stopping Alzheimer's and Parkinson's Therapeutics in 2018 In particular, Alzheimer's disease, the cause of the disease is not clear, and it is still incurable. Now the drug can only relieve its symptoms, and there are no new drugs for more than 14 years. Nobel Prize-winning technology to help research on neurological diseases According to WHO statistics, there are hundreds of millions of people with neurological diseases worldwide, including more than 200 diseases of stroke, brain injury, spinal cord injury, Alzheimer's disease, Parkinson's disease, autism, schizophrenia, depression and other major diseases. More than the sum of people with diabetes, cardiovascular disease and cancer. In 2017, Ness-China published the latest statistics on Circulation. The number of stroke (stroke) survivors in China is as high as 11 million, and 1.3 million people are added each year. Because most of the lack of effective treatment, the treatment needs of neurological diseases and their sequelae are very urgent. However, the development cycle of new drugs such as chemical drugs and drug drugs is long and it is difficult to achieve substantive breakthroughs. With the promotion of the market and society, scientists from all over the world have begun to seek other treatment options including cell therapy. Whether there are a very small number of neural stem cells in the adult brain is still controversial, considering that its inaccessibility and quantity efficacy are also insufficient to meet the needs of neurological treatment. Before the differentiation of neural differentiation technology, most clinical research and neural stem cell treatment companies used fetal-derived neural stem cells. These fetal neural stem cells not only have ethical problems (mainly glial precursors), but due to different developmental stages and individual differences, it is difficult to achieve homogeneity and batch stability, thereby affecting functional stability and drug-forming properties. Therefore, when the technology of different, uniform and stable neural stem cells and functional nerve cells differentiated from pluripotent stem cells gradually emerged and matured after 2012, the research of new cell replacement therapy gradually emerged. iPSC differentiation by Kyoto University in Japan resulted in retinal epithelial cells (RPE) for the treatment of senile macular degeneration, and differentiation of dopaminergic neuronal transplantation for Parkinson showed good safety and efficacy in clinical phase I. Professor Lorenz Studer of the United States also used iPSC to differentiate dopamine nerve cells and treat Parkinson's disease by intracranial injection. The trial has been successful in monkey experiments in preparation for FDA clinical Phase I trials. The Chinese Zhou Qi academician team also applied cell transplantation for embryonic stem cell differentiation to treat these two diseases. The early results of Phase I clinical studies also showed the same good safety and efficacy. In addition, studies on the differentiation of pluripotent stem cells from insulin-producing β-islet cells for the treatment of type 1 diabetes and other fields are also emerging. Due to the high technical barriers, it appears late, and most of the similar new cell replacement treatments are currently in the pre-clinical animal testing phase. However, the scientific community is very optimistic because it is not limited to the paracrine function to help the regeneration of existing cells, but to supplement a large number of functional new cells. The principle of neural stem cell and nerve cell replacement transplantation therapy induced by differentiation is different from that of traditional stem cells, and its technical barrier is very high, which is called second generation stem cell technology. Extracting individual blood or skin cells After reprogramming "rejuvenation" as autologous iPSC pluripotent stem cells, neural stem cells or functional nerve cells can be cultured in vitro by differentiation to moderate to severe strokes (including cerebral infarction and cerebral hemorrhage). Brain damage (a large number of nerve cells die, and the neurons themselves are not regenerative), the prepared neural precursor cells should be delivered to the vicinity of the injured area by intracranial 3D stereotactic injection, so that these precursor cells spontaneously in the brain. Differentiation into various functional cerebral cortical neurons (accounting for more than 80% of viable cells) and glial cells, etc., slowly re-established connections with the original neural network. In addition, these neural stem cells or precursor cells themselves can secrete a variety of neurological factors, promoting the survival of transplanted cells and the connection with peripheral nerve cells at an early stage. Among many stem cells, neural stem cells differentiated from induced pluripotent stem cells (iPSCs) and embryonic stem cells have advantages in yield and quality in all aspects, and are more suitable for the development of clinical therapeutic products. In 2006, Shinya Yamanaka of Kyoto University in Japan was the first to report on the induction of pluripotent stem cells in the world-famous academic journal Cell, and Yamanaka won the 2012 Nobel Prize in Physiology and Medicine. The advantages of iPSCs are their multi-directional differentiation potential and autologousness, which are similar to embryonic stem cells in terms of morphology, gene and protein expression, epigenetic modification status, cell doubling ability, embryoid body and malformation ability, and differentiation ability. And in terms of difficulty and ethics, it is more feasible than embryonic stem cells. The in vitro human genetic disease model based on iPSC and differentiated cells and organoids can directly simulate human diseases, providing a new way for scientists and pharmaceutical companies to study disease pathogenesis and drug screening. Hod Bio's unique RONA neural cell differentiation technology can multiply and stably differentiate iPSC and embryonic stem cell cells into the highest purity neural stem cells, brain subtypes of nerve cells and 3D mini brains, and is truly capable of fully simulating the human brain. The composition and methods of achieving mature functionality. The world's leading technology platform layout industry 1, downstream: cell therapy overcomes difficult to cure neurological diseases Neural stem cells and related treatments have already entered many clinical applications, such as Parkinson's disease, stroke, head injury, and spinal cord injury. A large number of preclinical experiments, clinical Phase I and Phase II trials at home and abroad have shown good transplantation efficacy. In addition to the use of iPS stem cells to treat Parkinson as mentioned above, neural stem cell therapy is also being tried for currently untreated neurological diseases such as Alzheimer's disease, amyotrophic lateral sclerosis (gradual freezing). It is understood that the team of researchers such as Dr. Feldman of the University of Michigan is currently trying to treat amyotrophic lateral sclerosis with human spinal-derived neural stem cell transplantation. The FDA approved a study of HSSC injection into the spinal cord of the C3-C5 segment, which involves diaphragmatic motor neurons. Although there is no product on the market, iPS neural stem cell therapy has shown potential in neurological diseases, especially in the field of neurological diseases without current measures. Based on the world's leading innovative RONA cell differentiation technology and Johns Hopkins University Medical School's "Industry-University Research" platform, Hod Bio is also actively deploying neural stem cell treatment pipelines. In the treatment of stroke, experimental data on the treatment of stroke mice by neural precursor cell transplantation has been obtained at Johns Hopkins University, and the article is currently being submitted. At present, in addition to serving as the scientific advisor to China's Hod, Professor Dawson and his wife also decided to join Hong Kong and the United States Hoard Company to jointly promote the double report of stroke and other cell therapy pipelines. At present, Hod Bio's therapeutic cell products will use HLA-matched large-scale universal cells, and are currently in preclinical trials. "Although the second-generation stem cell technology will be later than the first-generation technology, there are direct cell replacement and batch stability advantages in the treatment of the disease, and it is possible to catch up with the products of the first-generation neural stem cell technology company." Jing said firmly. 2, the middle reaches: cooperative pharmaceutical companies, providing a powerful tool for the development of new drugs In addition to direct access to the field of stem cell therapy, Hod Bio is also in the midstream through the use of nerve cells and brain-like organs that provide iPSC differentiation for pharmaceutical companies for disease research and drug screening. Global R&D investment in the central nervous system disease industry is about 80 billion US dollars per year. However, due to the complexity of human brain structure and mechanism, human brain tissue is difficult to obtain, human and animal species are different, and the research on neurological diseases is lacking. Disease model. These reasons have made the development of difficult new drugs more confusing. Although they continue to invest every year, the development of neurological drugs has not made a substantial breakthrough, and the failure rate is extremely high. There are differences between animal cells and human cells, which is a clearer cognition in the development of new drugs, but it is difficult to obtain human brain tissue cells before the emergence of neural differentiation technology. Therefore, when iPSC and differentiation technology are applied to obtain various human cells in vitro, scientific research institutions begin to use these people's cells to study disease mechanisms, and international large pharmaceutical companies have also established their own iPSC differentiation departments, using differentiation to obtain human liver, Cardiac and nerve cells are used for preclinical drug screening and drug toxicity testing. The proposed CiPA proposal also considers that the genetic background of different populations has a great impact on drug toxicity prediction, and advocates the iPSC-differentiated myocardium to be included in the evaluation of myocardial toxicity. Using the existing RONA technology platform, Hod Bio can solve the problem that the existing differentiated nerve cells and 3D brain organs are not mature enough to simulate the stable composition of the brain, and the batch yield and stability are difficult to meet the drug screening needs. And research institutions provide the best nerve cells, differentiation kit products, and other ancillary services. For hospitals, they can also use these technologies and products for cell transplantation therapy or animal experiments with neural stem cell exosomes. At present, the company has trial orders for Vertex and Genentech, and is negotiating cooperation with Novartis, Eli Lilly, Merck and GlaxoSmithKline for drug research and development. In addition, the company and the National Institutes of Health, the United States Johns Hopkins University, Peking University, Zhejiang University, Chinese Academy of Sciences and many other domestic and foreign laboratories will also launch a number of research cooperation projects. 3, upstream: cell storage In the extension of drug development and cell therapy, Hod Bio completed the layout of the midstream and downstream industries. However, upstream of new autologous stem cell therapy relies first on the preparation and storage of patient iPSC stem cells, that is, first stored in the patient's stem cells. Induced pluripotent stem cells (iPSCs) possess readily available, pluripotent differentiation (including hematopoietic stem cells, mesenchymal cells, skin, cartilage, cardiomyocytes, hepatocytes, retinal cells, brain nerve cells, hair follicle cells, etc.), no limit And so on, it is very suitable as a seed stem cell for autologous stem cell storage. Using the latest iPSC and differentiation technology, Hod Bio can be safe, efficient, GMP-compliant and long-term storage, as well as help to differentiate into the desired tissue stem cells and cells for storage, which can be quickly extracted in acute diseases. Used for approved clinical or clinical research to gain valuable life and reduce sequelae. "The cell storage business has not yet begun, but it is indeed an area we want to enter," she said. She told the arterial network that although the current market penetration of stem cell storage is only 1%, they still hope to promote the concept of iPSC cell storage, so that everyone can access the most cutting-edge and more choices of technology. Second generation stem cell technology and opportunities of the times In order to quickly advance the project, Fan Jing returned to China after resigning from Hopkins University. From scratch, he found money, recruited employees, and found a venue. Compared to entrepreneurship, the university environment is like the ivory tower of researchers. After coming out of the ivory tower, Fan Jing learned to change from a simple researcher to a full-fledged entrepreneur. Since resigning after resigning, she talked about financing and talks, and at the beginning she borrowed money from many friends. "The most difficult time is that all the money in the family is 2,000 US dollars, and with two children in kindergarten and house, the monthly expenses of the American family are 6,000 US dollars." Fan Jing recalls, "all rely on Mr. With the support of family and friends." “Thank you very much for the trust and support of the investors, we have the opportunity to establish a workshop and platform that conforms to the production specifications of stem cell clinical preparations, and to transform innovative technologies. I am also very grateful to be willing to work hard with me and lead a low salary to work hard but partners. She can't help but sigh, without firm belief, lasting patience, and making innovative drugs is almost impossible, not to mention the first innovative cell drug that wants to be a stroke. †"We are fortunate, just in time for domestic cell therapy to enter the normative development period, various policies and norms have been introduced." Fan Jing told the arterial network. Such an opportunity allows them to have a formal advantage and many meridian and other treatment projects that have been conducting clinical research for many years to stand on the same starting line for fair competition. It is understood that the company has reached a cooperation intention with the General Hospital of the Army General Hospital Bayi Brain Hospital, Run Run Shaw Hospital, and Xiangya Hospital with clinical trials of stem cell clinical trials. Next, Hod Bio's main task is to get the clinical records of cell products and enter clinical trials. "We hope to be able to conduct clinical trials in the next 2020," Fan Jing said. Fan Jing recently represented Hod Bio in the 6th "Dongsheng Cup" International Entrepreneurship Competition and also won a special prize of 1 million yuan and entrepreneurial venues. “For an innovative company with the right direction and real technical barriers, I think this is a good entrepreneurial era,†she added. Pain Relief Patch(Pain Areas)
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