Polyphor presents AMR breaker
Swiss Polyphor AG and researchers from the University of Zurich
have presented the mechanism of action of a new class of antibiotics.
In Nature, Anatol Luther et al. from Polyphor AG and the University of Zurich describe the discovery and characterisation of a new class of chimeric peptidomimetic antibiotics they call Outer Membrane Protein Targeting Antibiotics (OMPTA). Derived from a natural product, all OMPTAs including Polyphor’s preclinical lead candidate POL7306, combine a β-hairpin peptide macrocycle linked to the macrocycle found in the polymyxin and colistin family of natural products. POL7306 binds to both lipopolysaccharide (LPS) and the BamA protein within the outer bacterial membrane, which inserts proteins with β-barrel structure in the outer bacterial membrane.
“So far no clinical antibiotics target these key proteins, which is an unprecedented way of specifically combating life-threatening infections caused by Gram-negative bacteria” comments Professor John Robinson at the University of Zurich.
In first tests, Polyphor’s lead compound, which is currently undergoing preclinical toxicity testing, killed all Gram-negative pathogens on the WHO priority list including multi-resistant (MDR), extensively-resistant (XDR) and colistin-resistant bacterial strains.
According to Daniel Obrecht, Chief Scientific Officer at Polyphor, the development of the novel class of potential last resort antibiotics wouldn’t have been possible without the financial support from CTI/Innosuisse, Wellcome Trust (WT), CARB-X, and the Novo REPAIR Impact Fund.
Polyphor will present its findings to the international AMR community at the 4th AMR Conference in Basel, where stakeholders will also put the limelight on new pricing schemes for antimicrobials that incentivise the development and commercialisation of urgently needed compound that break antimicrobial resistance.