A Breath of Fresh Air: Delivering Novel Respiratory Syncytial Virus (RSV) Inhibitors

Abstract

Pulmocide Ltd., a VC-funded biotechnology company, was founded to discover more effective and safer inhaled treatments for serious viral and fungal infections of the respiratory tract. Human respiratory syncytial virus (hRSV) is the leading cause of lower respiratory tract infections in infants and young children, and a significant pathogen in both the elderly and in immuno-compromised patients. Current therapies are limited to high risk patients due to safety and efficacy concerns. Herein, we disclose the results of a collaboration, in which Sygnature Discovery was selected as the sole provider of medicinal chemistry to the Pulmocide discovery enterprise.

Taking a lead from the published literature, a series of thienobenzazepines was discovered that showed enhanced activity against the pathogenic organism and a more balanced profile against the two principal viral strains responsible for infection.

PC786, a non-nucleoside RSV L-protein polymerase inhibitor, demonstrated potent and selective anti-viral activity against laboratory and clinical isolates of both RSV-A and RSV-B, as determined by inhibition of their cytopathic effects in HEp-2 cells, without causing detectable cytotoxicity. The persistence of the anti-viral activity of PC786 was also revealed in human bronchial epithelial cells and in an industry accepted, ‘gold standard’ RSV model, in the cotton rat. The NCE is now in clinical development.

Sygnature’s industry standard data capture and recording of laboratory work greatly facilitated the subsequent filing of patent applications. This shared activity has matured into an IP portfolio in which patents covering the principal inventions have already been granted. Beyond the complementary technical skills of Pulmocide and Sygnature, key determinants of success have been a strong sense of shared purpose, ‘intellectual ownership’ of the programme by Sygnature scientists and the strong interpersonal relationships that have arisen from frequent face-to-face meetings.