From Concept to Clinic: How Monash Researchers Developed a New Antibiotic Candidate to Fight Deadly Bacterial ‘Superbugs’

Associate Professor LR Tony Velkov, Professor Philip Thompson, Professor Jian Li, Dr Kade Roberts, Professor Roger Nation

A new paper led by Monash researchers outlines the exciting journey from “concept to clinical trial” of QPX9003, a much-needed new antibiotic targeting drug-resistant Gram-negative “superbugs”. Considered a global health crisis, Gram-negative bacteria can cause life-threatening infections, including pneumonia, bloodstream infections, urinary tract infections, peritonitis and meningitis.

QPX9003 is a synthetic lipopeptide administered intravenously – no new peptide antibiotics have been approved against Gram-negative pathogens since polymyxin B and colistin became available in the late 1950s.

The newspaper, published in Nature Communication and led by researchers from the Monash Institute of Pharmaceutical Sciences (MIPS) and Monash Biomedicine Discovery Institute (BDI) in collaboration with Qpex Biopharma Inc. (Qpex), details the research that led QPX9003 to become a clinical candidate currently in Phase 1 of clinical trials.

This is the first time that the end-to-end story of how the team developed a new peptide antibiotic candidate has been published.

The research presented in the article describes a range of in vitro and in vivo studies that demonstrate the superior safety and efficacy of QPX9003 over existing polymyxin antibiotics. The researchers also describe work that demonstrates the mechanism of action and decreased toxicity of QPX9003 at the molecular level using state-of-the-art transcriptomics and mass spectrometry imaging.

Monash’s research team includes Professor Jian Li, Associate Professor Tony Velkov, Professor Roger Nation, Professor Phillip Thompson and Dr. Kade Roberts. In 2019, the American biopharmaceutical company Qpex licensed QPX9003 and is currently conducting phase 1 clinical trials.

First author Dr. Kade Roberts said taking a drug from concept to clinical trial is a remarkable achievement for an academic group involving two decades of hard work in pharmacology, medicinal chemistry, computational biology, microbiology and drug discovery.

“This article highlights the incredible journey of taking a drug from concept to lab through the drug discovery pipeline and into clinical trials. Our work has made timely contributions to the global fight against priority multidrug-resistant ‘superbugs’ and helped rebuild the antibiotic pipeline.

Professor Li, who leads the Monash Antibiotic Drug Discovery Programme, said: “We have successfully disentangled the therapeutic efficacy of polymyxins from toxicity and adverse disposition in the body. QPX9003 has the potential to be the first new peptide antibiotic approved for Gram-negative “superbugs” since the introduction of polymyxin B and colistin over 60 years ago. We are excited to share our story and look forward to the next chapter when Phase 1 clinical trials are complete later this year. »

“The novel QPX9003 synthetic lipopeptide potentially represents a significant advance in the treatment of multidrug-resistant pathogens that the World Health Organization (WHO) has identified as a critical need for new drugs,” said Michael Dudley, PharmD, President and CEO. from the management of Qpex. “The Nature Communication article and our Phase 1 progress establishes that QPX9003 has an improved profile that is needed for patients with limited treatment options.

Single escalating dose studies in healthy adults have been completed in the Phase 1 trial, with excellent safety and tolerability results. The results will be presented at the European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) in Lisbon in April 2022.

Financial support for the discovery program was provided by the National Institute of Allergy and Infectious Diseases of the US National Institutes of Health (R01 AI098771 and AI132154). The program would also not be possible without the support of Monash Innovation, the Biomedical Advanced Research and Development Authority, the Australian National Health and Medical Research Council (NHMRC, GNT157909) and the productive collaboration with Qpex.

To read the full article, go to: https://www.nature.com/articles/s41467-022-29234-3

Structure-activity model of polymixins

About the Monash Institute of Pharmaceutical Sciences The Monash Institute of Pharmaceutical Sciences is a dynamic, innovative and ambitious research institute, made up of more than 400 scientists committed to research in drug discovery, design, delivery and use. Part of the top-ranked faculty of pharmacy in Asia-Pacific, MIPS’ therapeutic strengths lie in neuroscience and mental health, cardiovascular and metabolic health, and global health. The MIPS team is committed to translating research and has made major contributions to collaborative drug discovery programs that have advanced more than 30 new drug candidates into clinical development.

About Monash Biomedicine Discovery Institute Committed to making the discoveries that will alleviate the future burden of disease, the newly established Monash Biomedicine Discovery Institute at Monash University brings together more than 120 internationally renowned research teams. Spanning six discovery programs in cancer, cardiovascular disease, development and stem cells, infection and immunity, metabolism, diabetes and obesity, and neuroscience, Monash BDI is one of Australia’s largest biomedical research institutes. Our researchers are supported by world-class technology and infrastructure, and partner with industry, clinicians and researchers around the world to improve lives through discovery.

About Qpex Biopharma Qpex Biopharma has three clinical-stage programs focused on treating extended-spectrum beta-lactamase (ESBL) and carbapenemase-producing pathogens that the CDC considers serious or urgent antimicrobial resistance threats, including Acinetobacter spp.., Pseudomonas aeruginosa, and Enterobacteriaceae. Development of Qpex’s portfolio products is supported in part by federal funds from the Office of the Assistant Secretary for Preparedness and Response of the United States Department of Health and Human Services, BARDA, under OTA number HHSO100201600026C.