Public Funding for Amprologix Limited

Amprologix is a company developing novel antibiotics to meet the global threat of antimicrobial resistance (AMR). AMR happens when bacteria become resistant to antibiotics and results in treatment failure and increased death from 'drug resistant' infections. These infections killed over 1.2 million people in 2019 and new antibiotics are urgently needed. If we don't develop new antibiotics, our current medical system may fail and things like cancer therapy and routine surgery may result in a fatal infection. In this TOBRADERM project, Amprologix will test a new antibiotic compound, epidermicin NI01, for treating skin infections, which affect millions of people every year in the UK and are the cause of more than 10% of all antibiotic prescriptions. Skin infections can be minor but can also result in severe and fatal outcomes, and they are increasingly complicated by AMR. We will develop epidermicin to be used externally (topical application), being applied directly to infected areas. This increases the killing action but also helps preserve current antibiotics, taken orally or by injection, for use against serious infections, like those in the blood. Epidermicin NI01 is from a new class of antibiotic compound, the bacteriocins (small protein-like molecules). Whilst bacteriocins are not used to treat patients yet, epidermicin has many features that increase the chance of it being a successful drug. These features include properties that minimise any risks that have stopped development of previous bacteriocins: it has very potent activity against globally leading pathogens ('superbugs'), including those that are resistant to current antibiotics and the leading causes of skin infections; toxicity is extremely low, even in recent safety tests in animals; resistance is very unlikely to occur due to the novel way it kills target bacteria; and we have developed an extremely low-cost production system. Epidermicin will also not kill all kinds of bacteria meaning it will target the main pathogens, leaving other skin bacteria unharmed, protecting the 'microbiome'. Epidermicin is an extremely promising new antibiotic and success in the TOBRADERM project will allow Amprologix to access new drug markets, helping it grow into a global leader in 'topical therapeutics'. This will create jobs, generate income for the company and enable development of a new drug to treat skin infections, potentially benefitting over 1 million people a year in the UK.

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.