b'Case Study BREAKING BIOFILM AMRHelping to support biofilm models to assess novel(PDT) greatly enhanced the activity against Staphylococcus interventions aureus. The compound also showed some efficacy against Pseudomonas aeruginosa strains, achieving a Biofilms are a major cause of antimicrobial resistance90% reduction in viability. 3-dimensional Confocal laser (AMR) and are recognised as a key factor in thescanning microscopic (CLSM) imaging was also carried inability of antibiotics (and other antibacterial agents)out to evaluate the killing of Staphylococcus aureus in to treat many types of chronic, recurring infectionsbiofilms. The project evolved as planned, although e.g., diabetic foot ulcers and cystic fibrosis-associatedoptimisation of the wound model was required to avoid pneumonia. Bacterial biofilms are communities ofcomplete overgrowth of Pseudomonas aeruginosa and bacteria embedded within a self-secreted, mainlyStaphylococcus aureus in the model during infection. The polysaccharide, slime matrix. This matrix acts as awork supported an existing platform of Destiny Pharma protective mechanism against a range of externalIP including three families of patents with a total of threats, including antibiotics. The development of new95 granted patents and two pending patents. Destiny agents which can overcome biofilm-associated AMRPharmas Chief Strategy Officer Dr Bill Love said,thus represents a considerable unmet clinical need.NBIC have been entirely supportive of the research Previous studies have shown the efficacy of a novel XF- programme, particularly in regard to the impact of drug activity against Methicillin-resistant StaphylococcusCOVID-19, allowing for timeline extensions which take aureus (MRSA) biofilms in laboratory in vitro models.this impact into consideration.With the support of NBIC Proof of Concept funding, a project led by Destiny Pharma sought to expandThe project is now complete, however future studies the knowledge of XF-drug activity against clinicallycould explore efficacy against complex multi-species relevant biofilms, including those formed by other highcommunities of bacteria, for example, containing priority, multidrug resistant (MDR) bacterial species onPseudomonas aeruginosa and Staphylococcus aureus and the World Health Organisation priority pathogen list,potentially other pathogens in co-culture as might be including Pseudomonas aeruginosa. Since XF-drugs havemore representative of a wound infection.two distinct mechanisms of antimicrobial action, innate and photodynamic, both of these modes of activityNo Treatment + XF-73 (2 g/ml) PDT+ XF-73 (2 g/ml)were explored in this study. NBIC also supported the project by providing expertise in the skin explant wound model, biofilm growth and experiments and imaging methodologies, as well as access to clinically relevant microorganisms from ex vivo clinical samples.The compound was highly effective at killing biofilms formed by clinical Staphylococcus aureus strains in theKilling of Staphylococcus aureus by XF-73, with and without PDT pig skin explant model, achieving complete kill (notreatment. Bacteria labelled with Live/Dead stain (live bacteria fluoresce green and dead bacteria fluoresce red). Confocal laser remaining viable bacterial cells). Photodynamic therapyscanning microscopy, scale bar = 20 m.Dr Bill LoveDr Love is a former scientist at Novartis, focused on novel drug delivery technologies. Dr Love founded Destiny Pharma and leads the development of XF-73 (exeporfinium chloride) and NTCD-M3 (naturally occurring non-toxigenic strain of C. difficile bacteria). He is an expert advisory board member of the UK governments Global AMR Innovation Fund as well as its COVID-19 Research and Innovation Taskforce. He has experience in drug R&D from discovery through to Phase 1, 2 and 3 clinical development in the UK, EU and USA.42'