From concept to clinic: How Monash researchers developed a novel antibiotic candidate to tackle deadly bacterial ‘superbugs’
A new paper led by Monash researchers describes the exciting ‘concept-to-clinical-trial’ journey of QPX9003, a much-needed novel antibiotic targeting drug-resistant Gram-negative ‘superbugs’. Deemed a global health crisis, Gram-negative bacteria can cause life-threatening infections including pneumonia, bloodstream infections, urinary tract infections, peritonitis and meningitis.
QPX9003 is an intravenously-administered synthetic lipopeptide - no new peptide antibiotics have been approved against Gram-negative pathogens since polymyxin B and colistin became available in the late 1950s.
The paper, published in Nature Communications 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 to QPX9003 becoming a clinical candidate now in Phase 1 clinical trials.
This is the first time that the end-to-end story of how the team developed a novel peptide antibiotic candidate has been published.
The research presented in the paper describes an array of in vitro and in vivo studies that highlight the superior safety and efficacy of QPX9003 over the existing polymyxin antibiotics. The researchers also describe the work that highlights the mechanism of action and decreased toxicity of QPX9003 at a molecular level using cutting-edge transcriptomics and mass spectrometry imaging.
The team of Monash researchers includes Professor Jian Li, Associate Professor Tony Velkov, Professor Roger Nation, Professor Philip Thompson and Dr Kade Roberts. In 2019, the US-based biopharmaceutical company Qpex licenced QPX9003 and they are now conducting the Phase 1 clinical trials.
First author, Dr Kade Roberts, said that taking a drug from concept to clinical trial is a remarkable achievement for an academic group involving two decades of hard work across pharmacology, medicinal chemistry, computational biology, microbiology, and drug discovery.
“This paper highlights the amazing journey of taking a drug from concept in the lab right along the drug discovery pipeline and into clinical trials. Our work has made timely contributions to the global act to combat top-priority multidrug-resistant ‘superbugs’, and help rebuild the antibiotic pipeline.”
Professor Li who heads up the Monash antibiotic drug discovery program said “We have successfully disconnected the therapeutic efficacy of polymyxins from the toxicity and unfavourable 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 thrilled to share our story and we are looking forward to the next chapter when the Phase 1 clinical trials are completed later this year.”
“The new synthetic lipopeptide QPX9003 potentially represents a marked advance in the treatment of multidrug-resistant pathogens which the World Health Organization (WHO) has identified as a critical need for new drugs,” said Michael Dudley, PharmD, president and chief executive officer of Qpex. “The Nature Communications paper and our progress in Phase 1 establishes that QPX9003 has an improved profile that is needed for patients for whom there are limited treatment options.”
Single ascending 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.
Funding support for the discovery program was provided by the US National Institute of Allergy and Infectious Diseases of the 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 visit: 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, comprising over 400 scientists engaged in research in drug discovery, design, delivery and use. As part of the top ranked Pharmacy Faculty in the Asia Pacific, MIPS’ therapeutic strengths lie in neuroscience and mental health, cardiovascular and metabolic health and global health. The team at MIPS are committed to research translation and have made major contributions to collaborative drug discovery programs that have progressed more than 30 novel drug candidates into clinical development.
About the Monash Biomedicine Discovery Institute Committed to making the discoveries that will relieve 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 across Cancer, Cardiovascular Disease, Development and Stem Cells, Infection and Immunity, Metabolism, Diabetes and Obesity, and Neuroscience, Monash BDI is one of the largest biomedical research institutes in Australia. Our researchers are supported by world-class technology and infrastructure, and partner with industry, clinicians and researchers internationally to enhance lives through discovery.
About Qpex Biopharma Qpex Biopharma has three clinical-stage programs focused on the treatment of 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 Enterobacterales. The development of the products in Qpex’s portfolio is funded in part with federal funds from the U.S. Department of Health and Human Services’ Office of the Assistant Secretary for Preparedness and Response, BARDA, under OTA number HHSO100201600026C.