Accelerating antibiotics

Polyphor and the University of Zurich examine new class of drugs inhibiting the LPS transport pathway

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ZURICH—Polyphor and the University of Zurich (UZH) in Switzerland recently announced that Innosuisse, the Swiss Innovation Agency, has awarded a significant grant for the innovation project “Development of a new class of antibiotics inhibiting the lipopolysaccharide (LPS) transport pathway.”
The Innosuisse award will finance the salaries and material costs of Polyphor's project partner UZH, whereas Polyphor will provide an additional contribution, of which a substantial part will be in kind. The research is independent from the project recently funded by Carb-X and the Novo Repair Fund.
The project funded by Innosuisse is based on a novel discovery of Prof. John Robinson and Prof. Oliver Zerbe from UZH concerning the molecular target and mode-of-action of the natural antimicrobial peptide thanatin. Thanatin inhibits the lipopolysaccharide transport protein A (LptA), which is critically involved in the transport of LPS from the periplasm to the outer membrane and of vital relevance to the bacteria.
Polyphor has discovered, through leveraging its macrocycle platform, a new class of antibiotics against gram-negative bacteria with a novel mode of action, which are called outer membrane protein targeting antibiotics, or OMPTAs. The most advanced drug candidate of this new class is murepavadin (POL7080), an antibiotic in clinical development targeting Pseudomonas aeruginosa, including its most resistant strains. It is followed by the next-generation OMPTAs (lead candidate: POL7306), now in advanced preclinical testing, which are medium-spectrum antibiotics targeting the most important gram-negative pathogens, including extensively drug-resistant and multidrug-resistant strains.
“This collaboration is a unique opportunity for the UZH and Polyphor to jointly develop antibiotics against priority 1 gram-negative bacteria to treat infections with high unmet medical need,” said Oliver Zerbe, chief investigator of the project.
“We are delighted to have obtained the support from Innosuisse, which is a further proof of the potential of our technology platform,” added Daniel Obrecht, chief scientific officer and co-founder of Polyphor. “This project will allow us to continue a highly fruitful collaboration with the UZH which started in 2000 with a first grant from Innosuisse to develop the protein epitope mimetics technology, from which all of Polyphor's current drug portfolio has been developed. Thanatin analogues may lead to another family of compounds inhibiting the outer membrane assembly through a different mechanism than other OMPTAs developed so far.”

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