In 2020 Cyprotex hosted two complimentary webinar series alongside colleagues from across the industry. Each series was presented over four weeks with a different presenter and topic each week.
Originally broadcast in October and November 2020, this article is focussed on the second series, New Approaches in Toxicology. To read our review of the first webinar series: A Focus on Drug Transporters click here.
Four topics were presented in the New Approaches in Toxicology webinar series:
- Drug Discovery and Development: Challenges and Opportunities in Toxicology, presented by Prof Ruth Roberts from ApconiX
- Understanding the Applicability and Limitations of In Silico and In Vitro Safety Models Towards the Design and Selection of the Safest Drug Candidates, presented by Takafumi Takai PhD from Takeda
- Development of an In Vitro T-cell Assay to Assess the Intrinsic Immunogenicity of Drugs and Chemicals, presented by Monday Ogese PhD from the University of Liverpool
- Seizure Prediction using MEA: Importance of Receptor Expression, Cell Type and Maturity, presented by Chris Strock PhD from Cyprotex
The series began with Prof Roberts discussing the complexities of toxicology in drug discovery. The webinar covered small molecule development, including navigating the regulatory framework for general toxicology testing. With accelerated approval processes, early registrations and orphan drugs all on the rise, it is becoming clear that many therapies no longer fit within the standardised development framework, and a customised approach is often required. By starting with a science driven approach to drug discovery and development and asking specific questions about a programme, many regulatory studies may not be needed and can be approached using in vitro, in silico or novel in vivo testing. The ongoing challenges of safety being the number one reason for early stage failure opens the door to science-led design as a way to overcome costly late-stage failures. Several case studies were presented during the webinar to demonstrate the advances made using new technologies and approaches.
The second webinar focussed on analysing and understanding in vitro and in silico models and their applicability towards chemical toxicology. Dr Takafumi presented two different case studies, examining a phototoxicity in silico model to predict in vitro toxicity, and an analysis of how in vitro cytotoxicity assays can predict in vivo toxicity. In order to ensure an effective screening paradigm, the webinar emphasised the importance of selecting assays and models on a case by case basis, taking into account the unique chemical properties of a compound and the inherent limitations of each model.
In the third presentation in the series, Dr Ogese described a novel in vitro naïve T-cell priming assay, which has been developed to better characterise the risk factors of immune tolerance during drug development. Roughly one third of all drugs withdrawn postmarket are due to hepatotoxicity, which suggests that current in vitro models do not sufficiently characterise the adverse off-target reactions seen in the clinic. The role of T-cells is known to be a contributing factor in hypersensitivity, and the webinar discussed the development of an optimised immunogenicity screening platform with a view to develop an industry ready assay that could be used during routine screening.
Cyprotex’s own Dr Strock closed out the series by discussing the importance of receptor expression, cell type and maturity in seizure prediction using the MEA platform. The MEA platform is ideal for neurotoxicity assays as it is able to identify sub-cytotoxic responses which are indicative of many observed liabilities. The research was discussed in detail, in addition to how advancements in human induced pluripotent stem cell derived neurones (hiPSC) have addressed the early challenges seen through the lack of complex burst organisation. The presentation described the insights gained throughout the assay development process and how the expression levels, cell type, and maturity can significantly affect the outcome of seizure prediction.
All of the webinars are now available to view on demand and can be accessed using the following links:
To find out more about our toxicology service offerings click here.