Pre-clinical validation of a potent candidate in the fight against AMR HCAI

Antimicrobial resistant (AMR) bacteria kill over 25,000 people a year in Europe and resistance rates are climbing rapidly worldwide. There is a critical need for novel classes of antibiotics to tackle the rise of antibiotic resistant bacteria and serve as scaffolds for derivatisation, diversification and enhancement of efficacy, a strategy proven successful with previous generations of drugs such as penicillin. Amprologix Ltd is using machine learning, bioinformatic peptide design strategies and high-throughput biological assays to develop an exciting new class of antimicrobial biologics (ABs) focused around a family called epidermicins. These ABs have no known resistance liabilities and rapidly kill bacteria at very low doses. Amprologix is currently developing narrow-spectrum epidermicins that are specifically active against either Gram positive or Gram-negative AMR pathogens. In recent work, Amprologix has shown unique benefits of epidermicin NI01, our lead compound, over current gold-standard therapy (mupirocin: Bactroban) in a key animal infection model for MRSA; a single dose of NI01 was as effective as six doses of mupirocin. This level of efficacy, combined with the broader properties of epidermicin NI01 mean it has excellent potential for use as a topical therapy for prevention and treatment of infections caused by bacteria like Staphylococcus aureus and MRSA, which are leading causes of skin and soft tissue infections in Europe. MRSA is also one of the leading causes of healthcare associated infections (HCAI) in the UK and Europe and has been designated as a high priority target pathogen. In both hospital and community settings, the rate of infections caused by MRSA and S. aureus are increasing and resistance to front-line therapies is growing. Consequently, there is an urgent need for new agents to prevent and treat infection caused by these organisms. In this SBRI-funded project, Amprologix will fast-track the pre-clinical development of NI01, the first anti-MRSA/S. aureus epidermicin. We will optimise the formulation of epidermicin and demonstrate its safety in a pre-clinical evaluation of toxicity in a topical application. Building on our previous successes in developing a high-yield manufacturing process for epidermicin antibiotics in a commercially-scalable yeast production system, we will deliver a GMP compliant pre-master cell bank, ready for manufacture of clinical grade epidermicin. Success in this project will allow rapid progression to a phase-1 human clinical trial investigating the topical application of the antibiotic to prevent MRSA infections. If successful, this will de-risk NI01 for human use and allow Amprologix to raise sufficient venture capital to bring its lead compound to market and fund the development of other 'narrow spectrum' epidermicins from the same class of antibiotics. Ultimately this will bring a powerful new platform of highly effective and adaptable antibiotic drugs to market, greatly benefiting the NHS and other healthcare systems worldwide.