UQ’s innovative Octapeptin drug would disable the bacteria’s protective wall, creating a path for antibiotics to enter the bacteria and kill them
(BOSTON: February 22, 2021) – CARB-X is awarding up to US$2.2 million to The University of Queensland’s (UQ) Institute for Molecular Bioscience (IMB), Brisbane, Australia, to expand its Octapeptin research program to develop a new drug designed for use in low- and middle-income countries (LMICs) where there are high levels of drug-resistant bacteria.
The new drug – engineered Octapeptin peptides that act as potentiators – would work by disrupting the protective cell membrane of drug-resistant Gram-negative bacteria so that existing antibiotics can once again work to kill the bacteria. The drug would be used in combination with antibiotics that are readily available in LMICs but that have become ineffective in the treatment of drug-resistant bacterial infections.
The LMIC-focused Octapeptin potentiator project is led by Associate Professor Mark Blaskovich, Dr. Alysha Elliott and Dr. Johannes Zuegg at UQ’s IMB. The new award is in addition to funding announced in 2020 of up to $10.86 million – the first-ever Australian project funded by CARB-X – for the Octapeptin research program led by Professor Matthew Cooper and Dr. Karl Hansford, along with Dr. Blaskovich.
“New innovative approaches are urgently needed to treat deadly infections. CARB-X funds and supports a broad diversity of scientific approaches in development around the world,” said Erin Duffy, R&D Chief of CARB-X, a global non-profit partnership led by Boston University and dedicated to funding and supporting the development of innovative antibiotics, vaccines, diagnostics and other products to address antibiotic-resistant bacterial infections. “The UQ IMB project aims to reboot generic antibiotics that have become ineffective against Gram-negative bacterial infections in LMICs. If successful, this approach could provide new treatment options in parts of the world where life-saving options are limited.”
‘Running out of time’
“We are running out of time to outsmart the most dangerous drug-resistant bacteria, and this funding will build on our existing CARB-X funded work developing a new antibiotic class, the Octapeptins,” Dr. Blaskovich, Director of the IMB Centre for Superbug Solutions, said. “We will harness this latest funding injection to investigate which existing antibiotics can be rejuvenated by combining them with compounds from the Octapeptin family.”
“The benefit is that we can potentially restore the use of cheap generic antibiotics that are widely used in LMICs, where there are high levels of drug-resistant bacteria,” Dr Elliott said. She added that with Octapeptins, there is potential to significantly reduce the amount of antibiotics required to treat an infection.
(l-r) Mark Blaskovich, Alysha Elliott and Johannes Zuegg lead the LMIC-focused project
A similar scientific approach has been effective at extending the effectiveness of the beta-lactam class of antibiotics such as penicillin, revitalised by inhibitors that block the beta-lactamase enzymes that bacteria use to defend themselves from these antibiotics.
The new Octapeptin project is in the hit-to-lead phase. Early goals are to identify which types of antibiotics Octapeptins are best at helping, and which of two structural subclasses of Octapeptins are most promising with the best efficacy and least toxicity. The project also includes a capability enhancement to support several hospitals in countries such as Pakistan, Nepal and Nigeria to establish whole genome sequencing and molecular epidemiology protocols so that they can analyse different resistant strains using genetic sequencing onsite in their countries.
Dr. Blaskovich said the team plans to help researchers and health professionals collect and identify resistant bacteria, especially in remote areas, which will contribute to knowledge of how resistance develops.
CARB-X funding supports antibacterial R&D around the world
CARB-X receives its funding from the US Biomedical Advanced Research and Development Authority (BARDA), the Wellcome Trust in the UK, Germany’s Federal Ministry of Education and Research (BMBF), the UK Global Antimicrobial Resistance (AMR) Innovation Fund (GAMRIF), and the Bill & Melinda Gates Foundation. Funding contributions by GAMRIF are earmarked by CARB-X to fund projects that focus on specific antibacterial priorities, and the UQ IMB Octapeptin LMIC project is one such project. GAMRIF funding allocated to CARB-X is focused on innovative research and development in the field of AMR, specifically in underinvested areas for LMICs, where the burden of AMR is greatest.
The World Health Organization (WHO) estimates that 700,000 people die each year from drug-resistant infections, including 35,000 in the US and 33,000 in Europe. CARB-X funds only projects that target drug-resistant bacteria highlighted on the Centers for Disease Control and Prevention (CDC)’s Antibiotic Resistant Threats list, or the Priority Bacterial Pathogens list published by the WHO, with a priority on those pathogens deemed Serious or Urgent on the CDC list, or ranked Critical or High on the WHO list.
52 projects progressing in the CARB-X portfolio
The CARB-X portfolio is the world’s largest and most diverse antibacterial R&D portfolio with 52 active projects, including the UQ IMB Octapeptin program, focused exclusively on drug-resistant bacteria. CARB-X is investing up to $480 million in non-dilutive funding between 2016-2022 to support the early development of new antibiotics and other therapeutics, vaccines and other preventatives, rapid diagnostics. The goal is to support therapeutics projects through the early phases of development including Phase 1 so that they will attract additional private or public support for further clinical development and regulatory approval for use in patients.
Since its launch in 2016, CARB-X has announced 78 awards and has committed more than $285 million, with the potential of additional funds if project milestones are met. These funds are in addition to investments made by the companies themselves. The CARB-X pipeline will continuously evolve, as projects progress and others fail for a variety of reasons.
This research is supported by the Cooperative Agreement Number IDSEP160030 from ASPR/BARDA and by awards from the Wellcome Trust, and the UK Global AMR Innovation Fund (GAMRIF). The contents are solely the responsibility of the authors and do not necessarily represent the official views of the HHS Administration for Strategic Preparedness and Response, or other CARB-X funders.
Contacts:
CARB-X:
Jennifer Robinson
+1.514.914.8974
carbxpr@bu.edu
UQ:
Dr. Mark Blaskovich, m.blaskovich@imb.uq.edu.au, +61 (0) 414 955380
Dr. Alysha Elliott, a.elliott@imb.uq.edu.au, +61 (0) 433 403905
IMB Communications, communications@imb.uq.edu.au, +61 (0) 405 661856
About CARB-X
Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator (CARB-X) is a global non-profit partnership dedicated to accelerating early development antibacterial R&D to address the rising global threat of drug-resistant bacteria. CARB-X is led by Boston University and funded by the Biomedical Advanced Research and Development Authority (BARDA), part of the Administration for Strategic Preparedness and Response (ASPR) in the US Department of Health and Human Services (HHS), the Wellcome Trust, a global charity based in the UK working to improve health globally, Germany’s Federal Ministry of Education and Research (BMBF), the UK Department of Health and Social Care’s Global Antimicrobial Resistance Innovation Fund (GAMRIF), the Bill & Melinda Gates Foundation, and with in-kind support from National Institute of Allergy and Infectious Diseases (NIAID), part of the US National Institutes of Health (NIH). CARB-X is investing up to $480 million from 2016-2022 to support innovative antibiotics and other therapeutics, vaccines and other prevention approaches, and rapid diagnostics. CARB-X supports the world’s largest and most innovative pipeline of preclinical products against drug-resistant infections. CARB-X is headquartered at Boston University School of Law. carb-x.org/. Follow us on Twitter @CARB_X.
About The University of Queensland (UQ)
The University of Queensland has educated and worked with outstanding people to create positive change for society for more than a century. UQ research has global impact and is delivered by an interdisciplinary community of more than 1500 researchers at six faculties, eight research institutes and 100+ research centres.
About UQ’s Institute for Molecular Bioscience
The Institute for Molecular Bioscience is Australia’s #1 research institute, with a track record of translating research discoveries into spinout drug discovery companies with molecules in clinical trials. We are committed to improving the health and sustainability of our local and global communities. Our Centre for Superbug Solutions is dedicated to finding innovative multidisciplinary approaches to combat antimicrobial resistance.
About BARDA and NIAID
The US Department of Health and Human Services works to enhance and protect the health and well-being of all Americans, providing for effective health and human services and fostering advances in medicine, public health, and social services. Within HHS, ASPR’s mission is to save lives and protect Americans from 21st century health security threats. ASPR leads the nation’s medical and public health preparedness for, response to, and recovery from disasters and public health emergencies. BARDA provides a comprehensive, integrated, portfolio approach to the advanced research and development, innovation, acquisition, and manufacturing of medical countermeasures – vaccines, drugs, therapeutics, diagnostic tools, and non-pharmaceutical products for public health emergency threats. These threats include chemical, biological, radiological, and nuclear agents, pandemic influenza, and emerging infectious diseases. NIH is the primary US federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. NIAID conducts and supports research — at NIH, throughout the United States, and worldwide — to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses.
About Wellcome Trust
Wellcome exists to improve health for everyone by helping great ideas to thrive. We’re a global charitable foundation, both politically and financially independent. We support scientists and researchers, take on big problems, fuel imaginations and spark debate. The Wellcome Trust is a charity registered in England and Wales, no. 210183. Its sole trustee is The Wellcome Trust Limited, a company registered in England and Wales, no. 2711000 (whose registered office is at 215 Euston Road, London NW1 2BE, UK).
About the Global AMR Innovation Fund (GAMRIF)
The Department for Health and Social Care (DHSC) is the UK Government department which is responsible for helping people to live more independent, healthier lives for longer.
This research is co-funded by DHSC’s Global AMR Innovation Fund (GAMRIF). GAMRIF was established to provide seed funding for innovative research and development, specifically in neglected and underinvested areas, in the field of antimicrobial resistance (AMR). GAMRIF is a £50m UK aid investment, which means all projects funded must support research primarily and directly for the benefit of people in low- and middle-income countries (LMICs). The Fund takes a ‘One Health’ approach, seeking to invest in potential solutions to reduce the threat of AMR in humans, animals, fish and the environment. The Fund seeks to leverage additional global funding through interaction with international government bodies, public-private partnerships, product development partnerships, global funding mechanisms and global fora.
About Boston University
Founded in 1839, Boston University is an internationally recognized institution of higher education and research. With more than 33,000 students, it is the fourth-largest independent university in the United States. BU consists of 17 schools and colleges, along with a number of multi-disciplinary centers and institutes integral to the University’s research and teaching mission. In 2012, BU joined the Association of American Universities (AAU), a consortium of 62 leading research universities in the United States and Canada. For further information, please contact Jeremy Thompson at jeremy22@bu.edu. www.bu.edu.