Science Pool

Learn more about Evotec's long term vision in Kidney Disease therapeutics including:

• Molecular patient databases
• Patient derived disease models
• Molecular profiles turned biomarkers
• Evotec's footprint in chronic kidney disease

PK/PD modelling is an important aspect of dose prediction of antibiotics for both preclinical and clinical development and is a requirement of both the European Medicines Agency (EMA) and US Food and Drug Administration (FDA). This technique facilitates efficient dose-response study designs and assists in identifying optimal dosing regimens to ensure clinical efficacy and to suppress drug resistance.

Cyprotex is increasingly supporting its parent company, Evotec, in the modelling and simulation area. For example, mathematical modelling techniques have been applied in the rational design of antibiotic efficacy studies to reduce the number of animals required to determine the magnitude of efficacy and pharmacodynamic driver and promote acceptance of such data by regulatory authorities.

Our research poster, titled Pharmacokinetic/Pharmacodynamic Modelling of Antibiotic Efficacy, was presented at the Alderley Park 3R’s Poster Event on 17th October 2018. The event was jointly hosted by AstraZeneca, Cancer Research UK and Agenda Life Sciences. The poster was awarded 1st prize in the event for its contribution to the 3R’s concept of Replacement, Reduction and Refinement.

The contemporary definitions of the 3Rs are:
• Replacement: accelerating the development and use of models and tools, based on the latest science and technologies, to address important scientific questions without the use of animals.
• Reduction: appropriately designed and analysed animal experiments that are robust and reproducible, and truly add to the knowledge base.
• Refinement: advancing animal welfare by exploiting the latest in vivo technologies and by improving the understanding of the impact of welfare on scientific outcomes.

In silico modelling and simulations can be used to improve study designs leading to a significant reduction in the number of animals required to achieve experimental objectives.

You can read more in our poster.

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The field of high-throughput ADME (HT-ADME) places a greater demand on the analytical systems supplying end point quantification.

In this review, we focus on:

• recent technological advances in LC–MS/MS which dramatically reduce sample analysis time
• evaluating the impact of reduced sample analysis time on analytical data quality
• the use of appropriate LC-MS/MS systems
• software tools to aid bioanalytical quality

Read our publication to learn more!

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Drug-induced mitochondrial dysfunction has been associated with organ toxicity and drug withdrawal. Highly specific and sensitive in vitro assays have been developed to predict mitochondrial dysfunction.

In this publication, we focus on:

• a background to mitochondrial toxicity
• a comparison of the Glu/Gal mitochondrial assay with the Seahorse assay for the prediction of mitochondrial toxicity
• how the Seahorse assay provides a mechanistic understanding of mitochondrial toxicity

Read our publication to learn more!

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Drug-induced liver injury (DILI) is a leading cause of drug failure due to poor translation between traditional preclinical animal models and human clinical outcome. More sophisticated human in vitro cell-based models with multiparametric endpoints are now being developed to improve DILI prediction.

In this review article, we focus on:

• the evolution of the strategies adopted to improve human hepatotoxicity prediction in drug discovery
• how companies are addressing translational challenges using human relevant cell-based models
• a further insight into the key role of human exposure and hepatic drug uptake transporters (e.g., OATPs, OAT2)

Read our publication to learn more!

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It is almost 50 years since MEA was first developed, however, the power of this technology in toxicology testing has only just been realised due to the introduction of the multi-well MEA allowing for its utility in high throughput
analysis.

In this whitepaper, we focus on:

• the current challenges within the pharmaceutical industry in terms of toxicology prediction
• how companies are addressing these challenges using human relevant cell-based models
• an in-depth evaluation of microelectrode array (MEA) and its key role in in vitro cardiotoxicity and neurotoxicity toxicology testing

Read our whitepaper to learn more!

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