AZD9773, a novel anti-TNFα immune Fab in development for severe sepsis and septic shock: demonstration of safety and efficacy in a murine CLP sepsis model

TNFα is thought to play a central role in the pathogenesis of sepsis and septic shock. AZD9773 is an ovine polyclonal anti-human TNFα immune Fab comprising TNFα-directed and nonspecific Fab populations. AZD9773 potency and pharmacokinetic attributes such as a shorter half-life distinguish it from anti-TNF monoclonal antibodies, which have been assessed previously in clinical sepsis models. Here we explore the preclinical safety/efficacy of AZD9773 in a mouse cecal ligation puncture (CLP) model. There are currently no reports of anti-TNF agent efficacy in mouse CLP; rather, TNFα neutralization is associated with minimal/no effect or increased mouse mortality. As AZD9773 is differentiated from other anti-TNFα agents based on neutralizing potency and pharmacokinetic attributes, we studied both the safety and efficacy of this product in mouse CLP models.