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A drug discovery collaboration between Japanese pharma and a UK SME CRO successfully developed novel small molecule inhibitors of the Kv1.3 channel to treat autoimmune disease

The Best of Both Worlds: Innovation, Collaboration and Synergy between CROs and their Customer Partners, Stevenage, 2018

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Functional characterisation of human iPSC-derived atrial cardiomyocytes

Atrial fibrillation (AF) is the most common arrhythmia observed in the clinic, considerable effort has been made to identify the cellular mechanisms of AF and develop new safe and effective antiarrhythmic drugs(1). However, preclinical studies using non-cardiac cells and non-human animal models may not replicate the physiology of human atrial cardiomyocytes or predict patient efficacy and safety.

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Utility of human iPSC-derived CMs for preclinical safety assays and disease modelling

This talk was presented by Dr Sarah Williams at the Axol Metrion Interactive Stem Cell Forum held in May 2018. This project received funding from the Eurostars-2 joint program with co-funding from the European Union Horizon 2020 Research and Innovation Program.

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Refining in vitro QPatch cardiac ion channel QPatch and MEA iPSC cardiomyocyte assays for CiPA

The Comprehensive in vitro Proarrhythmia Assay (CiPA) initiative is a new cardiac safety testing proposal sponsored by the FDA to refine the current ICH S7B and E14 guidelines. Two components of CiPA utilise in vitro electrophysiological assays that require validation using a toolbox of compounds with defined clinical proarrhythmic risk. Here we outline our progress to optimise these electrophysiological assays to meet the CiPA goal of predicting human cardiac liability.

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SR Live event during Metrion’s 2018 Syndicate Room finance round

Presentation by Marc Rogers (Metrion CSO) at the 8th February 2018 SR Live event during Metrion’s 2018 Syndicate Room finance round.

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Therapeutic potential of activators of two-pore domain ion channels

Presentation from Metrion Biosciences’ external speaker series, Professor Alistair Mathie, Medway School of Pharmacy, 13th October 2017.

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Electrophysiological characterisation of Cellular Dynamics International ventricular iCell2 iPSC-derived cardiomyocytes

To provide a more thorough and predictive cardiac safety profile of new chemical entities, the FDA is introducing the Comprehensive in vitro Proarrhythmia Assay (CiPA) initiative. To allow the successful integration of human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CM) as a translational model of human cardiac tissue their physiology needs to be fully characterised.

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Differentiation and validation of human iPSC-derived atrial cardiomyocytes

There is a growing trend for utilisation of native human cells in drug discovery to overcome common translational disconnects between in vitro screening data, preclinical animal models, and clinical trials in man. Translational assays using cardiomyocytes derived from human induced pluripotent stem cells (hiPSC) are increasingly appreciated as an accessible cell source for cardiac disease modelling, drug screening, and safety pharmacology.

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Comprehensive profiling of Axiogenesis ventricular vCor.4U iPSC-derived cardiomyocytes – from electrophysiology to phenotypic assays

The FDA’s Comprehensive in vitro Proarrythmia Assay (CiPA) initiative aims to provide a thorough preclinical cardiac safety profile of new chemical entities that enables prediction of human clinical proarrhythmia risk. To allow the successful utilisation of commercial human iPSC-derived cardiomyocytes (iPSC-CM) as models of human CM in the CiPA safety paradigm, their biophysical and pharmacological profile needs to be fully characterised. Here we will highlight our work to assess the utility of Axiogenesis vCor.4U iPSC-CM for CiPA-relevant cardiotoxicity screening.

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Development of native and stem cell-derived electrophysiological assays for neurotoxicology screening and translational drug discovery

Neurotoxicological effects now rank second behind cardiovascular events as adverse events impeding the development and safety of new drug candidates. Accordingly, Metrion has developed assays that can be used to predict seizurogenic and neurotoxic compound activity in the peripheral and central nervous system using native neurons, and are now building similar assays with human stem-cell derived neurons. Both approaches provide a translational step for development of anticonvulsant compounds and safe and effective treatments for other central nervous system diseases.

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