With a unique approach, Eligo engineers natural predators of bacteria to deliver CRISPR systems that kill antibiotic-resistant superbugs in the gut microbiome.
(BOSTON) – CARB-X announced today that it is awarding up to US$1.82 million to Eligo Bioscience in Paris, France, with additional funding for a total award of up to US$7.05 million if project milestones are met, for the development of a new generation of highly-specific antimicrobials to prevent multi-drug-resistant bacterial infections in organ transplant patients. Eligo’s bacteriophage- and CRISPR-based therapeutics are designed to selectively eliminate extended-spectrum beta-lactamase-producing (ESBL) and Carbapenem-resistant E. coli and K. Pneumoniae (CRE) from the microbiome of transplant patients before their procedure, thereby preventing the onset of these often-fatal infections.
Many patients enter hospitals pre-colonized by drug-resistant bacteria without symptoms. Transplant patients colonized by these superbugs have up to a 40% chance of developing postoperative infections due to surgery itself, and studies have shown up to 70% of such infections can be fatal. This high mortality rate is due to the fact that multi-drug-resistant infections do not respond to most commonly used antibiotics, and can even be resistant to all available antibiotics, leaving doctors with no treatment options. Indeed, transplant patients who had CRE infections after their procedure were five times as likely to die as those whose infections were not caused by these superbugs.
“The Eligo EB004 project is the first CRISPR-based phage project funded by CARB-X,” said Erin Duffy, Chief of Research and Development at CARB-X, a global non-profit partnership focused on supporting the early development of new vaccines, rapid diagnostics, antibiotics, and other life-saving therapeutic products to address the rise of drug-resistant bacteria. “Eligo is developing a new class of targeted biotherapeutics to selectively eliminate certain multidrug-resistant bacteria by combining the specificity of CRISPR and the ability of bacteriophages to deliver DNA into bacteria. This innovative approach, if successful, offers additional benefits in that it can prevent multi-drug-resistant infections while not harming bacteria in the microbiome.”
“We are extremely enthusiastic about our collaboration with CARB-X, which will bring our platform technology one step closer to addressing the critical problem of antibiotic resistance, starting with organ transplant patients, a population at extremely high risk of developing multi-resistant infections,” said Xavier Duportet, CEO of Eligo Bioscience.
“Our CRISPR-based approach is the first one that aims to specifically kill antibiotic-resistant bacteria before an infection has a chance to occur, thereby significantly reducing the risk of antibiotic treatment failures (and subsequent deaths) in organ transplant patients. We strongly believe that antibiotic resistance should be tackled from multiple fronts, and that our technology, which can be used to selectively remove bacteria that are linked to diseases from the microbiome, can significantly contribute to addressing this issue. If successful, this program could lead to a wide range of applications for pre-surgery decolonization to eliminate the risk of postoperative antibiotic-resistant infections for anyone undergoing surgery.”
Innovative and transformative science
Bacteriophages are bacterial predators that have been used to treat bacterial infections, such as Shigella dysenteriae, for more than a century. Renewed interest in bacteriophage therapy is growing with the emergence of antibiotic resistance, but the biology of bacteriophages limits the scope of natural phage therapy applications. Phages kill their bacterial hosts by infecting them, replicating themselves, and then bursting the bacteria. Not only have bacteria naturally evolved a wide range of defense mechanisms to shut down this replication cycle, but also, this mode of infection cannot discriminate between pathogenic or antibiotic-resistant bacteria and harmless commensal bacteria from the same species.
Eligo’s technology transforms bacteriophages into safe, non-replicative DNA-delivery vectors. The vectors are programmed to inject a synthetic DNA payload directly into the target bacterial populations of the patient’s gastrointestinal tract. The DNA payload is optimized to circumvent bacterial defense mechanisms and enables the expression of a CRISPR-Cas system that creates double strand DNA breaks only in antibiotic resistance genes carried by the targeted bacteria. This mechanism leads to the selective killing of bacteria carrying these genes, while a patient’s bacteria that do not carry these genes are left unharmed. If successful, the EB004 program could pave the way for personalized decolonization treatments to improve patient care, antibiotic stewardship, and patient prognosis, without disrupting the patient’s beneficial microbiota.
Supporting innovation to address the global superbug crisis
The World Health Organization (WHO) estimates that 700,000 people die each year from drug-resistant infections. The CARB-X portfolio is the world’s largest and most diverse antibacterial development portfolio with 43 active R&D projects focused exclusively on drug-resistant bacteria. CARB-X is investing up to $500 million in non-dilutive funding between 2016-2021 to support the early development of new antibiotics, rapid diagnostics, vaccines and other life-saving products that address drug-resistant bacteria. The goal is to support projects through the early phases of development so that they will attract additional private or public support for further clinical development and approval for use in patients.
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 Critical or High on the WHO list.
Since its launch in 2016, CARB-X has announced 65 awards exceeding $240 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.
This news release is supported by the Cooperative Agreement Number IDSEP160030 from ASPR/BARDA and by award from Wellcome Trust and Germany’s Federal Ministry of Education and Research (BMBF). 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. carb-x.org/. Follow us on Twitter @CARB_X.
About Eligo Bioscience
Eligo Bioscience is a French preclinical-stage biotechnology company pioneering microbiome gene therapy. Their EligobioticsTM platform enables the delivery of synthetic therapeutic DNA payloads to bacterial populations of the microbiome. Eligo is advancing programs to modulate host-microbiome interactions either via the delivery of CRISPR-based therapeutic DNA payloads for the precise elimination of deleterious bacterial strains or by leveraging ubiquitous commensal bacteria to produce therapeutic compounds directly in the gastrointestinal tract and on other host-microbiome interfaces. Eligo was founded in 2014 by Dr. Xavier Duportet (CEO), Dr. David Bikard (Institut Pasteur), Professor Timothy Lu (MIT) and Professor Luciano Marraffini (Rockefeller University); has raised $24 million and was selected as a Technology Pioneer by the World Economic Forum. https://eligo.bio/ @eligobio
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 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.