Toxicology

With safety concerns being the principal cause for phase 1 and 2 clinical trial failures, it is clear that more predictive models are required to improve the translatability of data from the laboratory to the clinic.

Safety toxicology testing traditionally occurs in simple cell culture systems which lack physiological complexity, and animal models that are limited by cross-species differences. Many drugs with clean toxicity profiles in these systems will present with adverse effects in human trials leading to costly late-stage withdrawals and potential harm to study participants.

Toxicology Studies using PhysioMimix™ OOC

PhysioMimix™ Organ-on-Chip studies allow scientists to identify and address potential side effects early in the drug discovery pipeline, using advanced in vitro single-, or multi-organ models, whose phenotype and functions mimic those in vivo. It provides a deep mechanistic, human-specific, understanding of potential drug toxicity that complements data derived from in vivo models for more insightful next step decision making.

Additionally, the PhysioMimix provides researchers with a clear path forward for novel human-specific modalities, where animal models may not be suitable due to gene sequence or immunological response differences.

PhysioMimix™ OOC enables users to:

3D Liver tissues, generated on CN Bio’s PhysioMimix OOC platform, recreate the liver microarchitecture and maintain its phenotype for long period of time (over 4 weeks).

  • Produce highly functional hepatocyte and non-parenchymal co-cultures for up to 4 weeks
  • Model a human environment, generate human- specific metabolites and overcome cross-species issues
  • Report an exponential number of functional liver-specific endpoints (inc. LDH, Albumin, Urea, ATP, WST-1)
  • Quantify clinical markers (AST/ALT, miR122)
  • Generate distinct hepatotoxin signatures
  • Investigate causality and mechanistic aspects of toxicology
  • Research whether a drug intended to treat one organ will have adverse effects on another.

The liver is one of the organs most susceptible to drug toxicity and drug-induced liver injury is a major cause of drug attrition. By allowing researchers to recapitulate the physiological and mechanical microenvironment of the liver, CN Bio’s liver-on-a-chip system represents the ideal solution for the early identification of both acute and chronic human DILI liability.

By adding circulating immune cells into the model, or by interconnecting our liver-on-a-chip with other organs (using the PhysioMimix Multi-Organ Microphysiological System), the following novel insights can now be derived in vitro:

  • inflammatory-mediated toxicity
  • multi-organ toxicity
  • off-target toxicity
  • reactive metabolite-driven toxicity in secondary organs

Need fast-track human-relevant information regarding lead candidate toxicology?

Submit your lead candidates for test using our Safety Toxicology Testing Services

Detecting human specific toxicant signatures – hierarchical cluster analysis of LDH leakage, albumin secretion and Urea production to assess toxicity of compounds

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 Investigating causality – detecting cholestatic injury following treatment with hepatotoxicant

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Patient stratification – comparing healthy and fatty liver-on-chip models susceptibility to drug-induced liver injury

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Collaborating With Regulators

In 2018 CN Bio signed a multi-year deal with the US Food and Drug Administration (FDA), the world’s most prominent pharmaceutical regulatory agency. The first aim of this  collaboration was to evaluate the use of CN Bio’s PhysioMimix Liver-on-a-chip for drug interaction and safety studies.

In 2021, the FDA published the results of their study findings with CN Bio. This co-publication:

  • represents the first co-published, peer-reviewed article between a microphysiological system provider and a regulator
  • demonstrates advantages of PhysioMimix™ in drug safety and metabolism applications

WEBINAR

A Regulators Viewpoint: Establishing Strategies To Evaluate Microphysiological Systems for Drug Development. Join Dr Alexandre Ribeiro, Staff Fellow (Biological Scientist) at the FDA.

Watch webinar

SCIENTIFIC PAPER

Characterizing the Reproducibility in Using a Liver Microphysiological System for Assaying Drug Toxicity, Metabolism and Accumulation

Download paper

APPLICATION NOTE

Human liver microphysiological system for studying acute and chronic drug-induced liver toxicity in vitro

Application note

Human organ
mimics

Powerful new
data

Translatable
results

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