Translational relevance in STAM™ model (NASH-HCC)
One factor that must be considered when selecting models for pre-clinical research is translatability.
As of January 2020, 15 compounds tested in the STAM™ model have progressed to clinical trials.
One such compound is Pegbelfermin, currently being developed in Phase 2 trials by Bristol-Meyers Squibb.
The results of trials using Pegbelfermin have shown an improvement in various NASH biomarkers in both STAM™ and clinical trials.
・Reduction in hepatic fat
When tested in the STAM™ model, Pegbelfermin had a positive effect on most endpoints, with a significant decrease in liver-to-bodyweight ratio, and a reduction in both hepatic TG and cholesterol.
Similarly, in the Phase 2a trial (NCT02413372), treatment with Pegbelfermin showed a robust reduction of hepatic fat content by 5-7%, compared to 1% in the placebo group.
(Cristy R.C. Verzijl et al., EXPERT OPINION ON INVESTIGATIONAL DRUGS, 2019)
・Efficacy against fibrosis
Pegbelfermin’s efficacy against fibrosis is also consistent in both STAM™ and clinical trials, with a reduction in SR positive area in the STAM™ model, and a decrease in serum PRO-C3, a fibrosis marker for collagen formation, in both STAM™ and clinical trials.
While current available clinical data on Pegbelfermin does not include histological endpoints, we look forward to seeing whether the compound achieves the same excellent results in histology in clinical trials as it did in the STAM™ model.
Pegbelfermin is just one example of a compound that has proven it’s efficacy in both STAM™ and clinical trials. We believe the high clinical correlation of this model makes it an excellent platform for NASH and fibrosis targeting pharmacological research.