nir-vana innovation network

Pharmaceutical or biotech companies who develop new drugs for liver, kidney, colon, intestine, stomach disease or cancer need to screen them in predictive tests. They need to evaluate drug effects on each cell type, the further interactions between cells, and cell fate. For all novel compounds showing early promise as potential therapeutics, the rate of failure is high, with less than 10% of drugs that enter phase 1 clinical trials ever achieving product licencing. The disparity between the preclinical success of novel cancer therapeutics and high failure rates in the clinic suggests that the models by which pharma test such therapeutics need improvement. A French SME has developed a know-how in preparing 3D organoids, powerful tools for research experiments. This 3D technology allows to test drug candidates in a more accurate and reliable way than in 2D in vitro tests first because the model is made of human cells and second because of the 3D structure, that is more physiological for cells behavior. 3D organoids mimics human tissues. Hence, researchers will save money compared to some in vivo tests, in particular in rodents which cannot reflect human cells behavior. For pre-clinical test of new molecules, big pharma generally subcontract classical and regulatory tests realized on 2D, and on cell lines, by high throughput screening. High throughput is a technology not adapted to complex 3D currently (size, numbers of samples, fluorescence, etc). The tests done with primary cells, or models like Patient-Derived Xenograft (PDX), are internally treated by big pharma. On the contrary, strategically smaller companies like mid caps and SMEs biotechs, which don’t have such encyclopedias, need to have other competitive ways to screen efficiently their innovative molecules. Organoid drug screening is fully appropriate to this target. Organoids can be made of cell lines, or human primary cells or monkey primary cells from safe or diseased tissues coming from the same donor when possible. Several cell types can be included: tumoral, fibroblasts, immune cells and/or endothelial cells upon partner’s request and as represented in the tissue. Primary cells are characterized by their specific markers before being included in organoids. Liver, kidney, colon, intestine, stomach are tissues from which organoids can be provided. Models from several diseases may be obtained according to the tissue: - liver: NASH (Nonalcoholic steatohepatitis) / safe, tumor/safe, - kidney: Renal cell carcinoma (RCC) /safe - colon - intestine - stomach: tumoral/safe Age, sex and previous treatments before surgery can be provided or included in conditions for biopsy. For other diseases, a feasability study will be required. Organoids are supplied cryopreserved. Protocole for organoid culture is provided to ensure the best conditions for partner’s experiments. The expertise allows 3D evaluation of the different cell responses (for T cell: proliferation, activation by IFN-g, cytotoxicity by Granzyme B, and caspase 3/7 to drug tested), protein expression, mutation analysis, cytogenetic analysis, target validation. Organoids can be delivered after 21 days of culture, ready to use. The company has the authorization for selling products made from human residues after surgery (GDPR), for research use. The company is seeking commercial agreements with technical support with drug discovery companies willing to test their leads. The company may also provide the 3D models for R&D institutions and academics.