Introduction

In order to constitute a relevant hepatic in vitro system, cultured hepatocytes need to accurately reflect phenotypes and functionality seen in vivo. Hepa Predict utilizes a cutting-edge 3D liver spheroid system to offer predictive models with high physiological relevance for drug development. Among other successes, the spheroid system has been coupled to Al to accelerate the development from computational hypothesis generation to experimental validation. For instance, our 3D models have validated Al-based repurposing of baricitinib against COvlD-19 from theoretical hypothesis to clinical validation in just 16 months,compared with the many years that such developments typically take. Based in part on our data, baricitinib has received FDA approval and WHO endorsement and has saved billions of dollars and many lives.

Through its Innovative 3D Liver Spheroid System, Hepa Predict Achieves Unprecedented Accuracy in Predicting Drug Response, Metabolism and Toxicity

Hepa Predict has overcome the technical challenge of traditional drug toxicity testing, where 2D cell models lack physiological relevance. Mainly animal studies and2D hepatocyte systems have been used for the examination of human drug metabolism and toxicity. Yet, these models have major limitations due to extensive species differences and because hepatocytes in conventional 2D monolayer cultures rapidly dedifferentiate and lose their phenotype and hepatocyte-specific functions.

Hepa Predict offers a novel, well established long-term stable 3D primary human liver spheroid culture platform. The 3D spheroid system utilizes primary human hepatocytes which are able to maintain a highly physiological phenotype for several weeks in 3D culture. The 3D spheroid system significantly outperforms 2D models that lose their in vivo expression signatures within a short time, and thus provides a novel step into a more physiological hepatic system. The prolonged viability and functionality of the system are an optimal tool for long-term studies, enabling accurate prediction of in vivo metabolism and toxicity. This highly physiologically replicated 3D liver spheroid system enables precise predictions in drug discovery and development, particularly achieving breakthroughs in long-term toxicity assessments, pharmacokinetics, and simulations of inter-individual variability. Importantly, through multi-omics approaches, the 3D spheroid platform is a reliable tool for the generation of comprehensive data sets, which provide cohesive results to enable predictions of large-scale effects on cellular processes. Comprehensive benchmarking in multi-center trials has demonstrated that Hepa Predict's system has its advantages in both sensitivity and specificity, showcasing its international leadership in toxicological analysis. Additionally, its unique technology reduces com-pound absorption and enhances the accuracy of toxicological interpretations, further consolidating its innovativeness.

The Scientific Value of 3D Spheroids Lies in Their Ability to Provide a Closer Approximation to Human Tissue

Novel 3D spheroid systems have revolutionized research by providing more physiologically relevant models for studying human tissues and diseases, significantly advancing our understanding of complex biological processes. Unlike traditional 2D cell cultures.3D spheroid systems better mimic the in vivo environment, allowing for more accurate investigations into cellular behaviors, drug responses, and tissue interactions. This innovation has propelled biomedical research, leading to improved drug discovery and toxicity testing, reducing the reliance on animal models, and accelerating the development of effective therapies. Economically, the use of 3D spheroid systems can lower the costs associated with drug development by increasing the predictability of preclinical studies and reducing high failure rates in clinical trials. Socially, these advancements contribute to public health by fostering the development of safer and more effective treatments, enhancing the overall quality of healthcare, and addressing global health challenges more efficiently.

Besides his work at Hepa Predict, Volker Lauschke is Full Professor for translational pharmacology at Karolinska InstitutetSweden, and Deputy Director of the Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Germany. His research has demonstrated original insights and innovative research methodologies in both theoretical and academic realms. His team's utilization of 3D cell culture systems, microfluidic technology, and bioinformatic approaches to address complex metabolic diseases such as non-alcoholic fatty liver disease and type 2 diabetes and develop novel therapeutic strategies represents an unprecedented advancement in pharmacology. Furthermore, the development of machine learning tools to enhance personalized drug therapy and predict drug toxicity constitutes a methodological breakthrough, significantly supporting precision medicine. Lauschke's achievements have not only propelled the development of pharmacology, molecular biology, and bioinformatics theoretically but also fostered advancements in drug discovery and personalized medicine in practical applications, exerting profound impacts on economic construction and social development.

Hepa Predict's 3D Liver Model has Gained Extensive Recognition in the international Scientific Community Due to Its Remarkable innovation and Ac.curacy

Hepa Predict's 3D liver model has gained significant international recognition in the field of drug discovery and development due to their remarkable innovation and predictive capabilities. Its research achievements have not only been published in numerous top-tier academic journals, but have also received successful application and certification from international regulatory agencies such as the FDA and EFSA, demonstrating its reliability and effectiveness in drug evaluation. Moreover, these models are widely adopted by global pharmaceutical companies and research institutions, showcasing a high level of international acceptance. By providing a more reliable platform for drug testing, 3D spheroid systems have accelerated the approval of new therapies and medical treatments, impacting regulatory frameworks globally. Countries with advanced pharmaceutical industries, such as the United States, Japan, and members of the European Union, have particularly benefited from these innovations enhancing their capacity for cutting-edge research and development. Furthermore, the adoption of 3D spheroid technology in developing nations has the potential to elevate local research standards and integrate these countries into the global scientific community. This international dissemination of 3D spheroid systems fosters a more interconnected scientific ecosystem, where shared knowledge and collaborative efforts can address world.wide health challenges more effectively Through international conferences, publications, and training programs, the influence of 3D spheroid systems continues to grow, bridging gaps and promoting a unified approach to medical research and development.