TAXIS’ EPIs would disable a defense mechanism in drug-resistant superbugs that makes them resistant to effects of antibiotics
CARB-X has now invested $179.3 million in 54 projects
(BOSTON, MA) – CARB-X is awarding TAXIS Pharmaceuticals of Monmouth Junction, New Jersey, USA, up to US$3.2 million in non-dilutive funding to develop efflux pump inhibitors (EPI), a new drug class designed to destroy a major mechanism of multi-drug-resistant Pseudomonas aeruginosa bacteria. TAXIS is eligible for an additional funding of up to $11.4 million if the project achieves certain milestones. TAXIS’ EPIs are designed to disable the bacteria’s efflux pumps, which act like bilge pumps to flush out antibiotics from the bacterial cell in order to safeguard the superbug from the effects of antibiotics.
“Pseudomonas aeruginosa is an intrinsically resistant pathogen, with a nearly impermeable outer membrane and with the ability to turn on many efflux pumps to eject antibiotics that make it through,” said Erin Duffy, Chief of Research and Development of CARB-X, which is based at the Boston University School of Law. “The TAXIS project is in the early stages of development but if successful, it would potentially be a leap forward in combating drug-resistance mechanisms and restoring the utility of many existing antibiotics.” CARB-X is led by Boston University and funded by a global partnership.
“We’re extremely gratified that CARB-X has chosen to fund our EPI drug development program,” said Greg Mario, CEO of TAXIS Pharmaceuticals. “This new drug class is designed to enable the reuse of existing generic antibiotics by addressing an elemental form of drug resistance. We believe delivering a durable solution to antibiotic-resistant infections could result in a significant cost-effective societal benefit.”
TAXIS’ EPI project targets multidrug-resistant P. aeruginosa with an emphasis on hospital-acquired and ventilator-associated infections. According to the Centers for Disease Control and Prevention (CDC), there were 32,600 cases of multi-drug-resistant P. aeruginosa infection in hospitalized patients in the US alone in 2017, and these infections caused 2,700 deaths that same year. Infections caused or complicated by P. aeruginosa include pneumonia, urinary tract infections and blood stream infections.
If successful, the TAXIS EPI would enable existing antibiotics to once again be effective against drug-resistant bacterial infections that cannot currently be treated effectively. TAXIS’ EPIs have been shown to potentiate the activity of several antibiotic classes, including against contemporary isolates that also feature other resistance mechanisms, and have the potential for reduced toxicity compared to earlier EPI programs.
Supporting antibacterial innovation
According to the WHO, an estimated 700,000 people die each year worldwide from bacterial infections. In the US, based on 2017 figures, the CDC estimates that 35,000 people die each year from drug-resistant bacterial infections. These US deaths are in addition to 12,800 deaths associated with Clostridioides difficile infections.
CARB-X is investing up to $500 million in antibacterial R&D between 2016-2021. The goal is to support projects through the early phases of development through Phase 1, so that they will attract additional private or public support for further clinical development and approval for use in patients.
The Powered by CARB-X portfolio the world’s largest antibacterial early development portfolio with 35 projects in five countries. Since its inception in 2016, CARB-X has announced 54 awards exceeding $179.3 million, with the potential of additional funds if project milestones are met, to accelerate the development of antibacterial products. 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.
CARB-X is led by Boston University and funding is provided by the Biomedical Advanced Research and Development Authority (BARDA), part of the Office of the Assistant Secretary for Preparedness and Response (ASPR) in the US Department of Health and Human Services, 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).
This news release is supported by the Cooperative Agreement Number IDSEP160030 from ASPR/BARDA and by awards from Wellcome Trust, and Germany’s Federal Ministry of Education and Research. The contents are solely the responsibility of the authors and do not necessarily represent the official views of the HHS Office of the Assistant Secretary for Preparedness and Response, or other CARB-X funders.
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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 funding is provided by the Biomedical Advanced Research and Development Authority (BARDA), part of the Office of the Assistant Secretary for Preparedness and Response (ASPR) in the US Department of Health and Human Services , 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). A non-profit partnership, CARB-X is investing up to $500 million from 2016-2021 to support innovative antibiotics and other therapeutics, vaccines, 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. https://carb-x.org/. Follow us on Twitter @CARB_X.
About TAXIS Pharmaceuticals
TAXIS Pharmaceuticals Inc. is a clinical stage company developing drug candidates that enable the re-use of the most widely prescribed generic antibiotics against antibiotic-resistant ESKAPE pathogens (E. faecium, S. aureus, K. pneumoniae, A. baumannii, P. aeruginosa, and Enterobacter spp). Our science is focused on the disruption of the foundation of bacterial cell wall architecture to address elemental forms of drug resistance. Our most advanced drug candidate, TXA709, is currently enrolling in a Phase I human clinical trial as an oral anti-MRSA treatment. TXA709 targets the filamenting temperature-sensitive mutant Z (FtsZ) bacterial cell division protein and was granted Qualified Infectious Disease Product (QIDP) designation by the FDA. It may also be possible to develop a FtsZ drug candidate targeting Gram-negative bacteria in the future. Our efflux pump inhibitors (EPIs) represent a new drug class against Gram-negative multidrug-resistant (MDR) pathogens. Bacterial efflux pumps act like bilge pumps by flushing antibiotics out of the bacterial cell and are responsible for antibiotic resistance in many Gram-negative strains. TAXIS Pharmaceuticals EPIs have shown that they can resurrect the activity, potency and effectiveness of multiple classes of antibiotics. Our anti-MreB program targets the essential bacterial cytoskeletal structural protein responsible for bacterial cell wall integrity. This MreB research evolved from over a decade of experience associated with the development of our FtsZ bacterial cell division program. www.TAXISpharma.com
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)
Education and research are the foundations for our future. The promotion of education, science and research by the Federal Ministry of Education and Research (BMBF) represents an important contribution to securing Germany’s prosperity. Education and research are a Federal Government policy priority, which is reflected in the development of the funding it is making available to these fields.
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.
The partnership with CARB-X is part of DHSC’s Global Antimicrobial Resistance 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 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 firstname.lastname@example.org. www.bu.edu.