Synergistic action of synthetic D-peptides with vancomycin against major Gram-negative pathogens

The spreading of bacterial pathogens that are resistant to numerous antibiotics is a global public health threat. Here, designed small peptides (in L-form or in D-form) with modest activity against gram-negative bacteria when used alone, were shown to be highly active against five selected important Gram-negative pathogens when combined with vancomycin. This project used the NADP Value Proposition Voucher to develop a thorough research plan to do further preclinical evaluation of peptide D8 with vancomycin, including ADME, PK, PD, toxicity, haemolysis, rate of resistance development and animal infection models, i.e. mouse experiments, guided by a professional pharma advisor. The plan is now being executed, partly supported by a subsequent NADP Lead Development Voucher. The researchers have founded Omnicin Therapeutics Company in 2019, and investors are being approached. The University research is continuing with the NACTAR grant and a ZonMW grant. We have also acquired a Take-Off grant of 50k Euro from NWO. This also provides for some dose-finding and pre-clinical studies. A NACTAR clinical study grant proposal was also submitted to NWO, but unfortunately was not approved. Some variant peptides are currently being investigated because a toxic effect is visible in mice at high doses of D8.

Prof. dr. Oscar Kuipers, University of Groningen