College of Medical, Veterinary & Life Sciences

Glox Therapeutics

Development of precision engineered protein bacteriocins to tackle antimicrobial resistance. 

The recent gradual decline in antibiotic discovery and development, and the evolution of antimicrobial resistance (AMR) in many human pathogens poses a major threat to global human health. It is estimated that antibiotic insufficiencies account for around 1.27 million deaths per year. This prediction is expected to increase to 10 million AMR-associated deaths globally per year by 2050, at a cost of $100 trillion. This urgent clinical need inspired Prof. Daniel Walker and his research group to identify alternative solutions to address the current antimicrobial resistance crisis. Fuelled by their drive for innovation and supported by the Translational Research Initiative (TRI) at the University of Glasgow, the biotechnology pioneers developed novel bacteriocin-based therapeutics against resistant pathogenic bacteria. 

Protein bacteriocins (PBs) are a diverse group of antibacterial proteins or peptides produced by bacteria that act against closely related or even unrelated bacterial strains by inhibiting their growth. They act by disrupting the cell membrane of target bacteria, or by interfering with essential cellular processes such as DNA, RNA, or protein synthesis. Many bacteriocins are highly specific, with a narrow spectrum of activity that enables targeting specific species of pathogenic bacteria, while having no effect on other beneficial strains, such as the gut microbiota. 

Initial work was focused on colicins, bacteriocins produced by some strains of Escherichia coli and have the ability to target other E. coli strains. However, the need for further evaluation, along with market shifts and new identified needs, fuelled a shift of focus towards pyocins, similar proteins produced by Pseudomonas aeruginosa. Collaborations with the University of Oxford resulted in a successful application for a 2.15M Wellcome Trust award to further uncover the basic mechanisms by which bacteriocins kill specific bacteria and to develop novel strategies to develop superior bateriocin-based therapeutics. University of Glasgow were also awarded a £1.28M MRC DPFS grant to optimise methods for the formulation, delivery and manufacture of the lead pyocin and to generate preclinical toxicology and safety data for administration via nebulisation. With funding support by a number of UKRI and TRI-awarded development grants, the team performed further experimental work to establish the efficacy, optimal dosage and effects of their developed bacteriocins on a number of pathogenic bacterial strains. 

With a view to developing a product with significant advantages compared to current solutions, the team aspired to steer away from bacteriocin cocktails that require multiple good manufacturing practice (GMP) stages to produce the components and final product and incur a high cost due to the extensive product development process. With further TRI support, the team developed a new platform technology that allowed them to combine multiple PBs of choice within a single, multimeric scaffold, thereby negating the need for the use of PB cocktails. This approach, which exploits the fact that immunity proteins are displaced at the cell surface during translocation, allowed the team to fuse multiple PBs in a single scaffold, and use precise engineering methods to ensure that each PB retained the ability kill the target bacteria. 

Through their focus on impact generation, an ability to adapt to new market needs, and innovative work on the development of their platform, the team have managed to secure 2 patents on the therapeutic components and delivery aspects of their technology. Their successful collaborations with the University of Oxford gave rise to a joint spinout, Glox Therapeutics, between the Universities of Glasgow and Oxford. Since its incorporation in 2023, Glox Therapeutics has secured significant investment from Scottish Enterprise and the Boehringer Ingelheim Venture Fund. In November 2023, the spinout, with support from Glasgow’s IP & Commercialisation Team and Oxford University Innovations, secured £4.3M seed funding for further development of their platform to target drug-resistant bacteria.