A Novel Multi-Lineage Human Intestinal Organoid Screening Platform for Drug Discovery and Preclinical Testing

About This Grant

ABSTRACT Over 90% of drug candidates fail in clinical trials, resulting in high costs and delayed access to therapies. These failures are driven by the limitations of current preclinical models, which rely on animal systems that do not fully capture human biology or simple cell monolayers that lack the complexity of native tissues. There is an urgent need for human-relevant models that better predict drug toxicity and efficacy. Intero Biosystems has developed the first stem cell–derived Human Intestinal Organoid (HIO) platform that incorporates multiple cell types of the native intestine. This multicellular architecture enables modeling of both normal intestinal function and disease processes that are not possible in traditional systems. In Phase I, we successfully established robust assays for intestinal toxicity and fibrosis with strong reproducibility and focus of this Phase II proposal is to scale production methods and validate assay readouts to meet the market needs for high-throughput screening projects. The efforts of this project will establish standardized quality control, shelf life, and cryopreservation benchmarks to ensure consistent performance and enable distribution for industrial use. Additionally, we will expand cytotoxicity screening to detect compounds with selective or partial effects on different intestinal cell types. To complement overt cytotoxic assessments, we will evaluate antifibrotic efficacy in models of acute, chronic, and immune-mediated fibrosis, testing FDA-approved and experimental therapies. Successful completion of this project will position the HIO platform as a scalable, predictive, and commercially viable tool for drug discovery. By capturing the cellular diversity and functional complexity of the intestine “in a dish,” this system offers the potential to transform preclinical testing, reduce reliance on animal studies, and accelerate the development of safe and effective therapies.