Wolfgang Moritz

Dr. Wolfgang Moritz, Head of External Collaborations at InSphero AG, graduated in Biochemistry at the University of Zürich and obtained his Ph.D. at the Department of Endocrinology and Metabolism at the University Hospital Zürich. He got his further training as a postdoc at the Massachusetts General Hospital in Boston in the area of diabetes with focus on beta-cell physiology. After a group leader position from 1999-2009 at the Department of Surgical Research, University Hospital Zurich, focusing on research topics related to islet transplantation and liver surgery, he co-founded InSphero AG, at which point he became responsible for early product development. He has profound knowledge in 3D Cell culture platform and model development, in vitro disease modelling and 3D cell-based applications. He is co-inventor of 8 patent applications, acquired and managed several national and European funded projects worth of CHF ~6m and co-authored >40 peer-reviewed publications.

NextGen Basel 1

Versatility of new approach methods – from early drug discovery to risk stratification exemplified by human liver microtissues

In the ever-evolving landscape of drug development, ensuring on-target pharmacological activity and early detection of toxicity in novel chemical entities (NCEs) is crucial to prevent late-stage drug failure. The lack of efficacy and organ toxicity continue to be significant causes of drug failures during clinical trials and post-approval withdrawals. Regrettably, traditional preclinical animal models often fall short in accurately predicting human clinical outcomes due to species differences in drug metabolism and response.

To address this discrepancy, preclinical strategies have advanced, integrating sophisticated human in vitro cell-based models with multi-parametric endpoints. We describe how Micro-physiological systems (MPS), as an integral part of New Approach Methods (NAMs), can be applied throughout the drug development pipeline. This is exemplified by human liver microtissues (hLiMTs). hLiMTs, cultivated from primary hepatocytes and non-parenchymal cells, emulate tissue architecture and function. They facilitate disease modelling and long-term studies, recapitulating disease phenotype, drug metabolism, and toxicity more accurately than traditional monolayer cultures.

We illustrate the use of complex in vitro hLiMTs to study disease progression under a specific induction scheme and the impact of therapeutic intervention by respective drug candidates. We propose a risk stratification strategy through the identification of population-specific susceptibility to adverse drug effects.

In conclusion, the versatility of new approach methods—from advanced cell-based models to risk stratification—offers potential for enhancing drug efficacy and safety assessment. By harnessing human-centric insights and adopting innovative technologies, we can bolster drug discovery and reduce the risk of late-stage attrition.