BIOTECHNOLOGY
To demonstrate
the translatability of cross-species DILI assays, we have been dosing human and cross-species models
and Multi-chip Liver 12 plates, with drugs that have known interspecies diff erences, including sitaxentan. Leveraging clinical markers, including alanine aminotransferase/ aspartate aminotransferase (ALT/AST), this method provides the ability to rank order drugs by safety risk across commonly used species before the preclinical phase.
Confocal image of human liver tissue. Nuclei (blue), albumin (yellow), C-reactive protein (green) and actin (red)
between in-vitro animals and in-vivo animal studies to address this gap?
REGULATORY GUIDELINES In preclinical testing, the drug developer is responsible for the choice of in-vivo species. Factors including the drug target and how closely the animal species mimics human responses infl uence decision-making, as does previous experience from past trials. International guidelines specify the
use of at least one rodent and one non-rodent species. Rats and dogs are most frequently used in toxicology testing, particularly for small molecules, with non-human primates (NHPs) common for newer drug modalities. All pre-clinical data needs to be reported in regulatory fi lings.
USE OF CROSS-SPECIES OOC FOR ENHANCED IVIVT For this reason, CN Bio has been developing preclinical rat and dog liver- on-a-chip models as translational tools. These tools enable comparative studies
to fl ag interspecies diff erences early, better inform in-vivo study design and support go/no decision-making. Insights from these advanced in-vitromodels help to prevent drugs that are potentially safe in humans from being dropped unnecessarily from the pipeline and de-risk those that weren’t adequately fl agged by animals from progressing into preclinical testing. Sitaxentan, a pulmonary
hypertension medication, was removed from the market in 2010 owing to concerns over liver toxicity. A review by Owen et al., 20125 examined preclinical animal species studies where the severity of the toxicity was missed. The authors highlighted that it was not a defi ciency in the preclinical package that resulted in the missed toxicity and translational errors; rather, it was a shortcoming of the preclinical species to predict human outcomes, or the mechanistic details of toxicity. To demonstrate the translatability
of cross-species DILI assays, we have been dosing human and cross- species models, cultured using the PhysioMimix Single-organ System
CROSS-SPECIES OOC MODELS ALIGN WITH 3RS OBJECTIVES The approach also supports 3Rs objectives and ethical considerations, including the length of testing required, cost, and availability of models (especially for NHPs). It facilitates the responsible use of animals as hundreds to thousands of in-vitrotests can be performed per donor and their insights safeguard future animal use. CB Bio continues to qualify these
models to further its understanding of the IVIVT potential of these. Sign up to the company’s newsletter via the website below to receive data comparisons when published.
QR Code: details of the technology here
1.
doi.org/10.1007/s40264-025-01514-z 2. doi:10.1006/rtph.2000.1399 3. doi:10.1016/j.taap.2017.09.006 4.
doi.org/10.3389/fddsv.2025.1536756 5.
doi.org/10.1016/j.yrtph.2012.05.017
For more information visit:
https://cn-bio.com
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