Scientific Approach

Our unique pathogen-targeted approach uses genetics, state-of-the-art molecular and dynamic model and medicinal chemistry to design novel antibacterials that overcome mechanisms of resistance

At Entasis, our drug discovery platform combines the use of genetics tools, molecular dynamics simulations and modeling to enable exploration of novel therapies in a highly directed, focused manner to design compounds with improved efficacy for these very challenging pathogens.  This differs from the historical antibiotic discovery model that has largely focused on screening high volumes of natural and synthetic compounds for activity against multiple bacterial pathogens and advancing these molecules toward clinical development - a process that provides limited predictability of safety and efficacy profiles.

Novel strategies for developing antibiotics are needed, as infections caused by multidrug-resistant organisms are a leading threat to public health. Along with industry partners, academia and regulators, Entasis Therapeutics is committed to the concept of streamlined development programs focused on pathogen-directed antibacterials that may target only a single species of highly resistant bacterial pathogens in areas of high unmet medical need. The emergence of new, non–culture-based, rapid diagnostic testing makes the strategic shift towards pathogen-directed therapies much more feasible. As a leader in this area, we have focused on one of the most concerning antibiotic-resistant pathogens: carbapenem-resistant Acinetobacter baumannii.

Our strong knowledge of chemistry and structural biology, together with a deep understanding of the genetics and genomics of Gram-negative bacteria, have helped us advance early leads and identify novel, differentiated pre-clinical and clinical candidates.

Our ability to leverage lab-based automation, in vitro hollow-fiber technologies and mass spectrometry to define exposure-efficacy relationships rapidly led to an early understanding of clinical dose setting – a key aspect of a streamlined development strategy.