10157734Brigid Bio – Developing novel, safe and life-saving anti-fungal therapies tailored for patients with complex co-morbiditiesActiveCollaborative R&DInnovate UKInvasive fungal infections are a serious global healthcare concern with an urgent unmet clinical need for improved therapeutic efficacy. Limitations in current therapies are reflected in the unacceptably high mortality rates even when patients are given standard of care drugs. The rise of antimicrobial resistance, a consequence of poor antimicrobial stewardship, long term prophylaxis in immunocompromised patients, and the ability of fungi to rapidly adapt and acquire tolerance and resistance, all contribute to poor patient outcomes. Drug resistant fungal pathogens are on the rise, with global organisations including the World Health Organisation (WHO) and Centers for Disease Control and Prevention (CDC, USA) emphasizing the critical impact of fungi on public health. Currently, only three main classes of antifungals are available to treat these infections. The failure of existing antifungal therapies to consistently achieve a successful clinical outcome is due to their inherent limitations including: emergence of multidrug resistance, drug-drug interactions (DDIs) and drug toxicity which together lead to treatment complications, particularly in highly complex patient groups. Brigid Bio has developed a novel, biologics drug discovery platform for the generation of human monoclonal antibodies (mAbs) recognising key cell wall proteins on the surface of pathogenic fungi including drug resistant clinical isolates. Fungal biology, fungal pathology and cell wall proteomics guided the selection of surface exposed protein targets with crucial roles in infection, cell wall remodelling and drug resistance. Our lead mAbs recognise and bind to the surface of a variety of pathogenic species of concern, specifically targeting areas of new growth, and work in combination with standard of care drugs, which result in increased expression of our cell surface targets. Our lead mAbs promote recruitment of immune cells, facilitating fungal clearance. Importantly, our lead mAbs have shown superior efficacy in "clinically predictive" models of infection, increasing survival and decreasing fungal burdens in multiple organs. We propose these mAbs as a first-in-class therapy against invasive fungal infections which currently have poor clinical outcome due to treatment failure and/or emergence of multidrug resistance. Our focus is high risk, critically ill, complex patients that are an ever-increasing clinical challenge with unacceptably high mortality rates.