PBI-4547 is a novel, immunometabolic agent which displays antidiabetic, antihyperlipidemic, anti-inflammatory and anti-fibrotic activity as shown in multiple animal models. PBI-4547 is an orally active small molecule that is a GPR84 antagonist, GPR40 (FFAR1)/GPR120 (FFAR4) agonist, and a partial activator of peroxisome proliferator-activated receptors (PPAR). PBI-4547 treatment significantly improved metabolic regulation of glucose and lipids, and reduced hepatic steatosis, ballooning and overall NAFLD (non-alcoholic fatty liver disease) score in high fat diet (HFD)-fed mice. Fatty acid oxidation and expression of mitochondrial uncoupling proteins were increased by PBI-4547 in the liver. Metabolomic profiling demonstrated that the metabolic dysregulation induced by HFD was abolished by PBI-4547.
Development stage & clinical trial information:
The current clinical study is designed to assess the safety, tolerability and pharmacokinetics of single ascending doses of PBI-4547 in healthy subjects (ClinicalTrials.gov Identifier: NCT04068259). A total of 40 adult participants will sequentially receive 1 of 5 doses of PBI-4547 or matching placebo, with each cohort of 8 participants randomized in a 3:1 ratio to receive PBI-4547 or matching placebo. The Phase 1 clinical study is being conducted by the CRO, Syneos, at locations in Quebec City and Montreal, QC, Canada.
Nonalcoholic Steatohepatitis (NASH) is a multi-faceted disease including metabolic dysregulation, chronic inflammation and fibrosis. In relevant animal models, PBI-4547 displays activity against each of these aspects of the disease.
PBI-4547 is an investigational drug and its safety and efficacy have not yet been established. For information about the Phase 1 clinical study with PBI-4547: please visit http://www.clinicaltrials.gov