BIOTECH & LIFE SCIENCES
b❝CN Bio’s approach has een recognised by the US
FDA CDER (Centre for Drug Evaluation and Research) group
The company has created a webinar that aims to help people reduce their DILI risk
crucial for maintaining liver function and tissue-specific inflammatory responses. They are cultured under perfusion to simulate the liver’s microenvironment, including blood flow and shear stress, which are essential for promoting high metabolic activity and prolonged culture longevity to discover latent effects. Liver-on-a-chip technology delivers
deep mechanistic insights to elucidate the pathways through which drugs induce liver injury, such as oxidative stress, mitochondrial dysfunction, steatosis, dysregulation of bile acid synthesis or transport and importantly, immune-mediated damage to identify more indirect or idiosyncratic DILI events[1,2,3,4]. Additionally, by incorporating genetic variations and the presence or absence of common diseases such as metabolic disorders, these models can help to identify factors that increase susceptibility.
THE PHYSIOMIMIX APPROACH CN Bio’s PhysioMimix DILI assay utilises liver-on-a-chip technology to deliver exceptional performance, according to the company, as exemplified in a study using reference compounds from the IQ MPS Consortium DILI validation set and human-specific gene-therapies (antisense oligonucleotides), which are less-suited to animal testing. The
assay, cultured using PhysioMimix OOC Systems, delivered 100% sensitivity, 85% accuracy, and 100% precision, measuring six different biomarkers to produce a ‘signature of hepatotoxicity’, identifying hepatotoxicants that passed traditional in vitro tests [5]. CN Bio’s approach has been
recognised by the US FDA CDER (Centre for Drug Evaluation and Research) group, which cited superior performance versus standard approaches in the first publication between the organ-on-a-chip (OOC) provider and the regulator [1]. Importantly, the utility of both the highly metabolically active hepatocytes and immune-competent Kupffer cells in the PhysioMimix assay were shown to be crucial in identifying hepatotoxic risk. Recent technological advances
have increased the assay’s throughput, enabling its use within lead optimisation, in addition to investigative toxicology, to justify the progression of promising drugs into in vivo studies by providing go/ no go or reengineer decisions at the tipping point between discovery and development.
THE IMPORTANCE OF ACTING QUICKLY The process of discovering and developing drugs is inefficient and costly. Change is required to reduce attrition rates and improve return on investment. OOC technology is becoming a lab essential because it provides the capacity to flag more liabilities than before and better inform next-step decisions [6]. CN Bio aims to help clients future proof their safety toxicology workflows, starting with DILI research, to help them reduce cost and time spent on projects.
REFERENCES 1.
https://doi.org/10.1111/cts.12969 2.
https://doi.org/10.1016/j. tiv.2022.105540
3.
https://doi.org/10.1016/j. tiv.2017.09.012
4.
https://doi.org/10.1124/ dmd.116.074005
5.
https://cn-bio.com/resource/ human-liver-microphysiological- system-for-predicting-the-drug- induced-liver-toxicity-of-differing- drug-modalities/
6.
https://doi.org/10.1038/s41573-022- 00633-x
For more information visit:
www.cn-bio.com
www.scientistlive.com 29
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