Cocrystal Pharma announces preclinical data for CC-42344
Cocrystal Pharma announced that Sam Lee, Ph.D., President of Cocrystal, presented positive preclinical data of CC-42344 at the ISIRV: Options X for the Control of Influenza Conference being held August 28-September 1, 2019 in Singapore. As part of his oral presentation, Dr. Lee provided an overview of the Company's distinct class of PB2 inhibitors developed utilizing its structure-based technology. Cocrystal's novel, potent, broad spectrum anti-influenza preclinical lead molecule, CC-42344, targets the cap-binding PB2 domain and is active against a panel of seasonal, pandemic, and Tamiflu-resistant influenza A strains. Additionally, Dr. Lee presented in vitro characterization and mechanism of action of these novel PB2 inhibitors. The in vitro characterization and mechanism of action was obtained through a process in which seven different influenza A PB2 domains were purified for protein crystallization and biochemical assays. PB2 crystals and cocrystals were diffracted to 1.0 - 2.5 A. Cytopathic effect assays measured antiviral activity. Results from the preclinical study demonstrated high resolution X-ray cocrystal structures of CC-42344 and other PB2 inhibitors, and further revealed a channel connected to the high conserved m7GTP binding site. These novel PB2 inhibitors showed broad spectrum activity, excellent anti-influenza activity, and a strong synergistic effect with approved influenza antivirals including Tamiflu and Xofluxa. In addition to the in vitro studies, the Company also obtained favorable pharmacokinetic and ADMET profiles of these PB2 inhibitors. Cocrystal is applying its proprietary platform technology to develop novel, broad spectrum influenza antivirals that are specifically designed to be effective against all significant A strains of the influenza virus and to have a high barrier to resistance due to the way they target the virus's replication machinery. CC-42344, the Company's lead molecule for the treatment of influenza A, binds to a highly conserved PB2 site on the influenza polymerase complex and exhibits a novel mechanism of action that inhibits viral replication. CC-42344 is currently being evaluated in preclinical IND-enabling studies for the treatment of influenza.