Non-Antibiotic Antimicrobial for Treatment of Respiratory Infections

NUI Galway Background
Antimicrobials, such as antibiotics, have had perhaps the most dramatic impact on modern medicine. Due to overuse and misuse, resistance to conventional antibiotics is rising dramatically. To overcome such resistant strains and to slow the emergence of new resistant microorganisms, there is an urgent pressing need for innovative new classes of antimicrobials.
Antimicrobial resistance is a major health problem which is expected to grow dramatically in the coming years. The CDC in their Antibiotic Resistance Threats Report in 2019 state that over 2.8 million antibiotic-resistant infections occur in the US each year, responsible for greater than 35,000 deaths. Globally over 700,000 people die each year from antibiotic resistance. The O’Neill Report commissioned by the UK government have suggested that if left unchecked this figure could rise to 10 million people by 2050.
Technology Overview
NUI Galway have developed a suite of antimicrobials with a novel mechanism of action. Unlike traditional antibiotics, these technologies do not allow bacteria to become resistant to them; nor can a cross-resistance to other antimicrobials be induced following prolonged exposure. These technologies have demonstrated high efficacy against all bacteria trialled to date: Gram-positive, Gram-negative, Multi-drug resistant strains. They have been shown to have an excellent safety profile following animal studies.
These technologies are subject to a number of preclinical programs, including as use in Respiratory Infections including those caused by drug resistant strains of Pseudomonas aeruginosa. This application of the technology is particularly timely given the current SARS-CoV-2 pandemic, with studies showing secondary infections occurring in 50% of all mortalities (Zhou, F. et al., (2020) Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 395:1054-62). Antimicrobials to tackle respiratory infections are also of strong commercial interest, as evidenced by the recent $190m deal signed between Roche and Forge Therapeutics to develop a novel antibiotic for treatment of P. aeruginosa lung infections.
NUI Galway have developed 2 novel antimicrobial technologies (termed LARS and ITC). These have been extensively tested in vitro and in vivo. These have a number of characteristics:

Effective bactericidal effect against all bacterial strains tested to date (Gram-positive and -negative)
Effective against planktonic and biofilm phenotypes
Effective against antibiotic-resistant strains (single and multi-drug resistant strains)
Do not allow for an increased level of sensitivity
Do not allow for an induction of resistance or cross-resistance following prolonged exposure
Novel mechanism of action
Excellent safety and toxicity profile following animal studies
Multiple routes of delivery: aerosol/nebulisation, oral, topical etc.
Low-cost, readily manufacturable active ingredients
Effective against range of microorganisms (Bacteria, Yeast, Fungi, Viruses)
Based upon prior viricidal studies expected viricidal activity against SARS-CoV-2

The technology has been tested in an in vitro lung infection model. Here the antimicrobial was nebulised against a P. aeruginosa infection, demonstrating a superior bactericidal effect than antibiotics tested (Gentamycin, Levofloxacin, Polymyxin B) (see )
These findings have been published in several papers:

Tonoyan, L., Friel, R. and O’Flaherty, V., 2019. Mutation rate and effux response of bacteria exposed to a novel antimicrobial iodo-thiocyanate complex. J Glob Antimicrob Resist
Tonoyan, L., Fleming, G.T., Friel, R. and O’Flaherty, V., 2019. Continuous culture of Escherichia coli, under selective pressure by a novel antimicrobial complex, does not result in development of resistance. Scientific reports, 9(1), p.2401
Tonoyan, L., Boyd, A., Fleming, G.T., Friel, R., Gately, C.M., Mc Cay, P.H. and O’Flaherty, V., 2018. In vitro comparative cytotoxicity study of a novel biocidal iodo-thiocyanate complex. Toxicology in Vitro, 50, pp.264-273.
Tonoyan, L., Fleming, G.T., Mc Cay, P.H., Friel, R. and O’Flaherty, V., 2017. Antibacterial potential of an antimicrobial agent inspired by peroxidase-catalyzed systems. Frontiers in microbiology, 8, p.680

Benefits
A flexible, highly effective and safe antimicrobial, with superior impact against biofilms and multi-drug resistant strains – suitable for delivery via several methods, including by oral/topical/wipe/ aerosol/nebulisation /wash/spray/– without the concern around the facile emergence of resistance or cross-resistance.
Applications
The technologies have a range of applications. These have been demonstrated and validated to be effective when delivered across a range of delivery formats (oral, aerosol, nebulisation, liquid, powdered, gel, encapsulation, coating etc.).
Opportunity
NUI Galway are seeking an out-licensing opportunity or potential co-development arrangement

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