Pulmocide gave an oral presentation (as a late breaking abstract) at European respiratory society annual meeting 2016, held September 03 – 07, 2016 in London, UK. This is as follows:
Effects of a single treatment with PC786, a novel inhibitor of respiratory syncytial virus (RSV) replication, on viral load and biomarkers in fully differentiated human bronchial epithelial cells
Author(s): D. Brookes1, M. Coates1, H. Allen1, J. Ayrton1, A. Davis1, M. Hows2, P. Strong1, G. Rapeport1 and K. Ito1
1Pulmocide Ltd, London, United Kingdom 2LGC, Fordham, United Kingdom
Addition of respiratory syncytial virus (RSV) A2 to fully-differentiated air-liquid interface cultured human bronchial epithelial cells resulted in a robust infection which generated amplified viral titres and measurable pro-inflammatory biomarkers. The novel anti-RSV agent, PC786, showed a concentration dependent inhibition of RSV A2 replication determined by plaque assay following a single apical treatment on Day 1 post-infection, reducing viral titres to below detectable limits the following day. Viral titres remained undetectable for 2 or 5 days when treated with either 0.1 or 0.5µg/ml of PC786, respectively. PCR products detected using primers targeting RSV N protein showed similar kinetics to the RSV virus titre determined by plaque assay. RSV A2 infection also induced several pro-inflammatory cytokines (RANTES, IL-6, CXCL8, CXCL10), mucin and double stranded DNA, a marker of epithelial cell injury. A single treatment of PC786 on Day 1 post infection delayed the expression of each of these biomarkers. In addition, a good correlation was found between PC786 content within cells and anti‑viral activity determined by PCR in apical wash. Thus, PC786 showed rapid onset of action and produced sustained inhibition of RSV replication and associated biomarker expression following only a single treatment post infection, and the anti-viral activity was correlated well with PC786 content within cells. Therefore PC786 has the potential to be an effective treatment for RSV infection in humans, and the clear PK-PD relationship observed in this study has the potential to help to predict efficacy of PC786 in vivo by measuring local epithelial concentrations of the drug in vivo.