Nanolive at the SPS Annual Meeting September 18-20

Abstract

Speakers: Ambroise Garry, Group Head, Global Investigative Toxicology Sanofi and Thibault Courtheoux, Global Head of Application and Support Nanolive

In the field of drug discovery and development, ensuring the safety and efficacy of potential therapeutic candidates is critical. However, the attrition rate during drug development due to safety concerns remains a major challenge for the pharmaceutical industry. Unexpected toxicities still account for 20–30% of clinical trial failures, despite the use of upstream animal models to derisk compounds. To address this issue, there has been a paradigm shift towards utilizing phenotypic assays based on human cells, which offer a comprehensive and biologically relevant approach to assess safety profiles and reduce late-stage failures.

Human-induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) have been extensively employed to investigate adverse effects on excitation-contraction coupling, shedding light on potential cardiotoxicities. In this context, holotomography stands out as an invaluable complementary technique, enriching our understanding of compound-induced toxicity.

Holotomography offers high-resolution, label-free, and non-invasive imaging capabilities, enabling the real-time monitoring of cellular morphology and function. By extracting information about refractive index variations within cells, holotomography provides valuable insights into cellular architecture, intracellular dynamics, and morphological alterations induced by drug treatments. This label-free nature of holotomography enables real-time monitoring of cellular responses, minimizing the perturbation caused by exogenous dyes or stains.

In this presentation, experts from Nanolive and Sanofi will discuss data acquired in human iPSC-CMs through the use of established drugs known to induce phospholipidosis and trigger cell death. The assessment was carried out utilizing AI-enhanced digital assays and an automated workflow.