P126 Oral treatment with PBI-4050 ameliorates bleomycin-induced pulmonary fibrosis by reducing serum and lung anti-inflammatory/fibrotic biomarkers.

PBI-4050 is a first-in-class orally active compound which displays antifibrotic activities in kidney, heart, liver, pancreas and lung models. PBI-4050 was found to be safe and well tolerated in healthy volunteers and in patients with CKD and Type 2 diabetes without any SAEs. Translation of pharmacological efficacy in humans has been confirmed. PBI-4050 is presently in phase II in idiopathic pulmonary fibrosis (IPF). The aim of this study is to identify serum biomarkers regulated by PBI-4050. Intratracheal instillation of bleomycin (0.025 U) was administered on day 0. At day 7, mice were randomized according to their bleomycin-induced body weight loss and then treated with PBI-4050 (200 mg/kg) from day 7 to 21. A Multiplex analysis was performed on serum and expression of key inflammatory markers was quantified by qPCR in lung tissue at day 21. Ashcroft score was significantly decreased with PBI-4050 treatment. A Multiplex analysis showed a significant increase of many biomarkers (G-CSF, IFNγ, IL-17, IL-3, IL-6, IL-9, IL-13, MCP-1, MIP-1α, MIP-1β, RANTES, TNFα, KC, IL-1α and IL-1β) in serum of bleomycin-induced mice, which were all reduced with PBI-4050 treatment. These results correlated with gene expression analysis in lung tissue where PBI-4050 reduced the overexpression of TNF-α, IL-6 and MCP-1 mRNA expression.