Science Pool

BMS-986094 (INX-08189) is a prodrug of a guanosine nucleotide analogue which was developed to treat hepatitis C virus but was discontinued during clinical trials due to cardiotoxic effects.

In this poster, we focus on:

• the mechanism of BMS-986094 cardiotoxicity 
• the impact of chronic dosing over multiple time points
• evaluation of data from an MEA platform, a cardiac mitochondrial protein biogenesis assay, a calcium flux assay and a cardiac cytotoxicity assay 

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BMS-986094 (INX-08189) is a guanosine nucleotide analogue prodrug which was developed to treat hepatitis C virus (HCV). However, BMS-986094 was discontinued in Phase III clinical trials with 1 death and 8 people hospitalised with significantly reduced left ventricular ejection fraction (LVEF). Cardiotoxic effects were observed in 14 out of the 34 patients with left ventricular dysfunction, with ST depressions, T-wave inversions or loss of T-wave amplitude.

In this poster, we focus on:

• investigating the mechanism behind the cardiotoxicity of BMS-986094
• the use of MEA and human iPSC-derived cardiomyocytes in long term incubations with BMS-986094

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In vitro 3D microtissue models are transforming our understanding of cardiotoxicity.

In this poster, we focus on:

• the use of a 3D cardiac triculture model consisting of iPSC-derived cardiomyocytes, cardiovascular endothelial cells and cardiac fibroblasts in cardiotoxicity prediction
• the detection of functional and structural mechanisms of cardiotoxicity
• calcium flux as a sensitive detection method for cardiac contraction as well as microtissue area for identifying cardiac hypertrophy
• HCS detection of cell health markers such as mitochondrial function, calcium homeostasis and nuclei/DNA structure

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Download this fact sheet to learn more about Huntingtin quantitation assays including: 

• Immunoassay platforms
• HTT assay menu
• Case studies

Download this fact sheet to learn more about Evotec's capabilities in AAV and LV application including:

• Case studies
• AAV production, QC and in vitro / in vivo
• High quality virus production and purification

Download this fact sheet to learn more about structural biology services at Evotec including:

• Rapid gene-to-structure process & versatile protein production
• Novel structure elucidation by X-ray and cryo-EM
• Experience with major target families including membrane proteins
• Rapid access to facilities at Diamond light source, UK

Download this fact sheet to learn more about cellular assays and stem cell research for HD including: 

• Case studies
• High-content screening/imaging
• Biochemical assays
• Specifically designed HD in vitro platforms