Testing safety of novel combination therapeutics that overcome antimicrobial resistance in Pseudomonas aeruginosa infections and reduce treatment-associated side effects.

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Since the discovery of Penicillin, antibiotics have transformed lives across the world, making bacterial infections that were lethal just 100 years ago straightforward to treat. However, misuse of antibiotics has resulted in a rapid rise in bacterial infections that are resistant to antibiotics and thus very difficult to combat. Antimicrobial resistant (AMR) infections have the potential to become the next pandemic, predicted to kill 10 million people per year by 2050, making AMR one of the greatest healthcare challenges of our time, calling for an urgent solution. However there is a dangerously low level of R&D activity in this critical space due to the economic difficulty of applying traditional drug discovery approaches, that rely on costly research programmes, to antibiotics which notoriously lack favourable pricing and reimbursement models.Medusa Pharmaceuticals is developing a new approach to tackle AMR. Instead of pursuing the slow, risky and expensive process of attempting to discover new antibiotics, we are repurposing drugs that are already approved and used in the clinic to reinvigorate existing antibiotics and increase their efficacy, presenting powerful synergistic combination therapeutics. By administering these drugs in optimal combinations we can overcome resistance to antibiotics and thereby combat currently untreatable AMR infections. Moreover, our approach means that we will be able to reduce the doses of antibiotics that are required to fight bacteria in chronic infections too, thus reducing their concentration-dependent side effects that are of increasing concern to long term users. Our approach has the potential to define a new paradigm to combat AMR. We will be leveraging decades of data on the already approved component molecules, presenting a substantially reduced R&D cost and accelerated time to clinic, for a de-risked and readily deployable solution to the rising global challenge of AMR, to save lives all around the world.This project will specifically investigate the translational applicability of the compelling academic discovery that forms the basis of our work, determining the safety/toxicity profile of optimally efficacious compounds (against primary target pathogen, _Pseudomonas aeruginosa_) in human cells. We will be testing lead combinations of synergistic compounds to investigate safety in human cell line models, to provide the toxicity profile and indicate potential to take this work forward to pre-clinical _in vivo_ testing. This project is an absolutely crucial early step in an accelerated pathway to clinical development.