There are three major problems in drug discovery: long research cycle, high research cost, low success rate. Organoid technology emerged under such circumstances. Organoid technology is a significant breakthrough in drug discovery which is expected to solve the problems, partially replaces the traditional cell experiments, animal experiments or works as a supplement. It will become the most effective approach for preclinical trial of drugs.
The drug discovery platform of Five Elements is equipped with organoid technology and led by a top academician, famous pharmaceutical scientists and clinical scientists. Five Elements signed 10 renowned scientists engaging in organoid cultures of different areas who are dedicated to building different organoids, such as intestine, liver, lung etc, constructing liver cancer model, non-alcoholic steatohepatitis model, inflammatory bowel disease model and intestinal cancer model that can apply to different stages in drug discovery, such as the identifications and validations of targets and biomarkers, compounds screenings, the evaluations of compounds’ effectiveness and security etc.
Supported by a strong team of scientists, abundant experience and resources in pharmaceutical industry, Five Elements possesses a drug discovery platform with PROTAC technology and different drug discovery pipelines, providing guidance about drug discovery and services of commercialization of intellectual property.
I Organoid Disease Model
An organoid is a miniaturized and simplified version of an organ produced in vitro in three dimensions that shows realistic micro-anatomy. It is capable of recapitulating some specific function of the organ. Organoid disease model is based on organoid technology, which can apply to the researches of pathogenesis, drug screening and drug discovery. Genetic engineering technologies, such as CRISPR/cas9 can be introduced to disease-related gene mutations so as to establish genetically-modified organoid disease models.
I Three-dimensional Liver Cancer Organoid Model
1 Liver Cancer Model
The liver cancer organoid model can be established by using the tumor tissues from patients with primary liver cancer to culture and expand in virto in 3D that can apply to anti-tumor drug sensitivity test and drug discovery. According to the differences in pathological types, differentiation degrees and stages of primary liver cancer, we have established a liver cancer organoid biobank, of which the liver cancer models cover all types of liver cancers. The comparative analyses and basic researches on pathological features, genomics, proteomics and metabolomics of tumor organoids can be used in the screenings of biomarkers and targets of drug treatment and the evaluations of drug effectiveness during the process of drug discovery.
2 Nonalcoholic Steatohepatitis Model
Nonalcoholic steatohepatitis is a syndrome that develops in patients who are not alcoholic. It resembles the alcoholic fatty liver disease and both of them have the features of fatty degeneration, liver cell injury and inflammatory cell infiltration. At present, studies on the pathogenesis and evaluations of treatment effectiveness of NASH are conducted by using animal models, which have the defects of long modeling cycle, high experiment cost, species differences. Five Elements have adopted vitro 3D culture method to build a nonalcoholic steatohepatitis model and conduct researches on biomarkers and drugs screening, thus, overcoming the disadvantages of animal model experiments.
Intestinal Cancer Model and Inflammatory Bowel Disease Model
Tissue sample derived from biopsy or surgery in intestine or IBD patients is minced into several pieces using forceps, scissors, and lancets to isolated crypts(for intestinal biopsy, crypts can also be isolated by EDTA treatment as an alternative). The small pieces of tissue are then incubated with enzymes such as collagenase, elastase to generate a single cell suspension. Single intestinal stem cells or intestinal crypts grow in 3D in Matrigel, in the presence of a defined set of niche factors, to obtain ever-expanding organoids which resemble the structure and the functionality of original intestine. The organoids can then submitted to transcriptome/proteome/epigenome/metabolome analysis, providing better understanding of disease pathogenesis and promote drug target identification.
Human gut microbes perform many metabolic functions that our own bodies cannot carry out, creating a symbiotic relationship. The composition and functions of gut microbiota in humans
and their interactions with a host remain largely unexplored because most microbies cannot be efficiently cultured ex vivo owing to their stringent specificity for human hosts. Organoids might hold promise insolving this dilemma. Microbes can be microinjected into the lumen of organoids, which is equivalent to the intestinal lumen in vivo. These models enable studies of the interaction between host epithelial cells and microbes and help to understand the pathophysiology of various disease states such IBD and intestine cancer.
Source: Trends Mol Med. 2017 May;23(5):393-410.
II Drug Discovery Pipeline
The core team of Five Elements consists of scientists from world-renowned pharmaceutical companies including the former R&D director of China region at J&J and former R&D directors in other multinational companies who involved in a dozen of R&D projects of compound drugs, seven drugs of which were brought to the market. They have six international patents and abundant experience in drug discovery and modern management. Furthermore,there are many famous cell biologists and clinical scientists in our team.
Supported by a strong research team and organoid technology, Five Elements and strategic partners possess 4 valuable product pipelines.
III Valorization of Intellectual Property
Supported by a strong team of scientists and technologies of drug discovery, we have established long-term cooperative partnerships with the big multinational pharmaceutical companies and CRO companies. We possess upstream sellers resources and downstream buyers resources and a professional investment banking team as well as legal advisers. We have purchased intellectual properties of lead compounds with potential research value to further design and optimize the experiments in order to increase the value of the projects.