Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator (CARB-X) is awarding US$1.75 million to the University of Melbourne at the Peter Doherty Institute for Infection and Immunity (Doherty Institute) to develop an oral therapeutic that restores the activity of workhorse antibiotics used to treat community-acquired bacterial pneumonia (CABP).
According to a press release the CARB-X award will support the development of PBT2, an ionophore therapeutic originally pursued as a potential treatment to restore brain activity in patients with neurodegenerative disorders, including Alzheimer’s and Huntington’s diseases. Studies found that PBT2 is also able to disarm key pathways involved in mechanisms by which bacteria become resistant to frontline antibiotics, like amoxicillin and doxycycline.
The Australian research team aims to use the effects of PBT2 on drug-resistant bacteria to restore the ability of common antibiotics to effectively eliminate those bacteria.
“Bacteria that cause community-acquired pneumonia are becoming increasingly resistant to antibiotics on the WHO model list of essential medicines, and so we’ve taken a strategy that embraces both the development of new antibiotics and the pursuit of other products that aim to restore the utility of the ones we already have,” said Erin Duffy, PhD, R&D Chief of CARB-X. “Oral antibiotics enable patients to be treated at home, which can reduce healthcare costs and increase access globally, including in low- and middle-income countries where the burden of antimicrobial resistance is highest.”
Lower respiratory tract infections, including CABP, are among the world’s most deadly communicable diseases. They are estimated to have killed 2.6 million people in 2019 globally, and they cause a substantial mortality, morbidity and economic burden for vulnerable people in low-income countries, where they are the second leading cause of death. Patients with CABP struggle to breathe as their lungs fill with fluid, and they can require hospitalization and intensive care treatment.
More than 400,000 people globally died in 2019 due to lower respiratory tract infections attributable to drug-resistant bacteria, and even in a high-income country like the US, 22percent of CABP cases result in treatment failure due to antibiotic resistance.
An estimated 1.27 million people died due to drug-resistant bacterial infections in 2019, a death toll that exceeded HIV/AIDS (864,000) and malaria (643,000) in that same year. CARB-X is building a pipeline of high-value products to prevent, diagnose and treat bacterial infections, including those that have become resistant to antibiotics. CARB-X emphasizes performance characteristics that will allow the broadest use of these products against infections driving the greatest global morbidity and mortality.
When CARB-X was founded in 2016, the early-stage antibiotic pipeline was stalled. Since then, CARB-X has supported 92 R&D projects in 12 countries, and CARB-X product developers have made tremendous progress: 18 projects have advanced into or completed clinical trials; 12 remain active in clinical development, including late-stage clinical trials; and two diagnostic products have reached the market. Additionally, at least 9 product developers with active R&D projects have already secured advanced development partnerships which can help support their clinical development after leaving the CARB-X portfolio.
Last year, CARB-X launched new funding rounds to support R&D projects and fill critical gaps in the antibacterial pipeline. These include oral therapeutics to replace the workhorse antibiotics that are failing; vaccines for neonatal sepsis, which kills 2.5 million infants annually; and oral therapeutics, vaccines and rapid diagnostics for gonorrhea. Resistant strains of gonorrhea have evaded all but one existing antibiotic
