Antimicrobial resistance (AMR) is a critical global health threat, associated with approximately 5 million deaths annually and a severe economic burden. To combat this threat, this project aims to advance the development of our de novo designed antimicrobial peptides (AMPs) towards novel therapeutics. These AMPs, developed within our ERC Consolidator project "Peptide Killers of Bacteria", utilize a mechanism distinct from traditional antibiotics, namely the disruption of bacterial cell membranes. This potentially novel class of antibiotics has already achieved nanomolar antibacterial activity, while exhibiting low toxicity to human cells in our in vitro tests. The susceptible bacteria include antibiotic-resistant strains of the Gram-negative A. baumannii, K. pneumoniae, and P. aeruginosa, which are on the CDC's and WHO's list of priority pathogens. Within this project, we aim to perform key preclinical tests with our AMPs. Our goal is five-fold: [1] determine the activity spectrum against genetically diverse bacterial species and strains; [2] evaluate the stability and efficacy of our AMPs in biological fluids, as well as their ADMET properties; [3] expand the scope of our preliminary in vivo data with murine models to include an additional administration route and infected sites; [4] analyze the prevalence and incidence of target infections to better understand the market size and societal impact; and [5] investigate the market potential, secure intellectual property rights, and develop a business strategy for clinical development. Successful implementation of this project will pave the way for future clinical testing and development of our AMPs, which could lead to effective treatments for the emerging AMR crisis of antibiotic-resistant infections.