Despite being tagged as a global threat, the pipeline for new therapies against antimicrobial resistance (AMR) is fairly weak, with most candidates in preclinical and early clinical development.
AMR has been identified as a major global threat by the World Health Organization (WHO). One of the reasons for the resistance is the overuse and misuse of antibiotics. Many reasons have been cited for an underdeveloped AMR pipeline, chief among them is a lack of commercial incentives.
The research into the development of new therapies against AMR was a key focus area at the 2024 ELRIG UK’s Research and Innovation – Drug Discovery (RI2024) conference that took place in Manchester from 20-21 March.
One of the most clinically advanced candidates in the lineup that was discussed at the meeting was Roche’s zosurabalpin. It is classified under a new antibiotic class of drugs called tethered macrocyclic peptides. Zosurabalpin targets the lipopolysaccharide (LPS) transport systems, which is important for maintaining bacterial cell structure among other functions.
The drug is being developed for the treatment of carbapenem-resistant acinetobacter baumanni (CRAB), which has been categorised as a ‘priority 1 pathogen’ by the WHO indicating an urgent need for therapies against these pathogens. Zosurabalpin was evaluated in Phase I trials in both healthy volunteers (NCT04605718) and critically ill patients with bacterial infections (NCT05614895) to determine the pharmacokinetics, safety, and tolerability of the drug.
Another potential AMR therapy approach that was discussed at the meeting was patient-derived neutralising antibody therapy. One such therapy is being developed by the University of Cologne, wherein neutralising antibodies derived from patients with cystic fibrosis could be used against multi-drug resistant Pseudomonas aeruginosa, a common hospital infection. Patients with cystic fibrosis are most at risk of acquiring Pseudomonas infections. “We are currently looking for commercial partnerships to advance the therapy to Phase I trials,” said Alexander Simonis, one of the therapy developers and presenters.
Antibody therapies have been very successful as a cancer treatment, with multiple pharmaceutical companies investing in expanding their antibody portfolio.
Another novel AMR therapy was Glox Therapeutics’ bacteriocins, an engineered protein that targets drug-resistant pathogenic gram-negative bacteria such as Pseudomonas aeruginosa and Klebsiella pneumoniae. In November 2023, the University of Glasgow and University of Oxford-spinout raised £4.3m ($5.5m) in seed funding to develop bacteriocins against gram-negative bacteria.
