NEW PUBLICATION - 8HUM Humanised Mouse Model Enhances Prediction of Peptide-Small Molecule Drug-drug Interactions
Researchers from the University of Dundee, in collaboration with Novo Nordisk A/S and Aarhus University, have demonstrated that the 8HUM humanised mouse model can more accurately predict drug-drug interactions (DDIs) involving therapeutic peptides, offering a valuable new tool for drug development.
Published in Drug Metabolism and Disposition, the study focused on the glucagon/GLP-1 receptor co-agonist NN1177 and revealed that, while the peptide transiently suppressed key drug-metabolising enzymes CYP3A4 and CYP1A2 in 8HUM mice, this did not translate into clinically significant DDIs – findings consistent with human trial results.
“Therapeutic peptides occupy a unique space between small molecules and biologics, making interaction prediction a complex challenge,” said Carolina Säll, PhD, corresponding author from Novo Nordisk. “Our findings show that the 8HUM model can bridge the gap between traditional in vitro studies and clinical outcomes.”
The 8HUM model, developed by PhaSER Biomedical, is extensively humanised for major cytochrome P450 enzymes and transcription factors CAR and PXR, enabling researchers to obtain in vivo data with much greater translational relevance compared to wild-type mice. The model has applications at all stages of drug development, from early discovery through to clinical phases.
“This model represents a significant advancement in preclinical testing,” added Prof. C. Roland Wolf, Founder and CSO of PhaSER Biomedical. “By improving prediction accuracy, we can reduce unnecessary clinical trials and accelerate the development of safe and effective peptide therapeutics.”
