Transplanted human organoids empower PK/PD assessment of drug candidate for the clinic

Pharmacokinetic/pharmacodynamic (PK/PD) studies are an essential component of pre-clinical drug discovery. Current best approaches for PK/PD studies, including the analysis of novel kidney disease targeting therapeutic agents, are limited to animal models with unclear translatability to the human condition. To address this challenge, we developed a novel approach for PK/PD studies using transplanted human kidney organoids. We performed PK studies with GFB-887, an investigational new drug now in Phase 2 trials. Orally dosed GFB-887 to athymic rats that had undergone organoid transplantation resulted in measurable drug exposure in human transplanted organoids. Importantly, we established the efficacy of orally dosed GFB-887 in PD studies, where quantitative analysis showed significant protection of kidney filter cells in human organoids and endogenous rat host kidneys. This widely applicable approach demonstrates, for the first time, feasibility of using transplanted human organoids in PK/PD studies, empowering organoids to revolutionize drug discovery. scRNAseq profiles of in vitro and in vivo matured IPSC derived organoids