Facile’s new oral drug would disable toxins that enable C. difficile infections to recur
(BOSTON) – CARB-X is awarding Facile Therapeutics, based in Belmont, California, USA, up to $1.26 million to develop a new orally bioavailable drug to treat recurring infections caused by Clostridium difficile. Facile could receive up to $17 million more in additional funding from CARB-X if the project achieves certain development milestones, for a potential total of $18.26 million.
“C. difficile represents an urgent global health threat and CARB-X is funding and supporting innovative R&D projects, like Facile’s Ebselen project, to address this growing threat,” said Erin Duffy, Chief of Research and Development of CARB-X, a non-profit partnership based at Boston University School of Law, dedicated to supporting early development antibacterial research around the world. “This is a terrific example of an attempt to repurpose a compound for use in the infectious-disease arena. If successful and ultimately approved for use in patients, Facile’s project could represent tremendous progress in the prevention of recurrent C. difficile infections, and save many lives.”
C. difficile infections can be cleared with antibiotics, but those antibiotics can disrupt or create an imbalance in the patient’s microbiome, which can lead to recurring infections. Facile’s small molecule drug, Ebselen, is an anti-toxin that has been shown to be a potent inhibitor of a key biochemical function of C. difficile toxins A and B, which drive the damage done by the infection. By neutralizing C. difficile toxins, the risk of recurrence is reduced.
Marc Navre, CEO and co-founder of Facile Therapeutics, said: “CARB-X’s support greatly enhances our ability to underscore Ebselen’s use for prevention of recurrent C. difficile infections so that we may continue its forward progression, ultimately, to human clinical trials. Ebselen is unique in two ways. First, it is de-risked with respect to human safety thanks to its development in other non-related areas. Second, Ebselen is a small molecule anti-toxin and therefore does not expose the patient to further antibiotic therapy, which benefits stewardship efforts as well as favoring the early recovery of a healthy microbiota.”
Ebselen has been previously evaluated in tests with hundreds of patients in Phase 2 and 3 clinical trials for stroke. While the molecule was not approved for that indication, it was shown to have a favorable safety profile. Other clinical studies have recently validated C. difficile toxin neutralization as an approach to preventing infection recurrence in humans. In recent studies, mice orally dosed with Ebselen after exposure to virulent C. difficile were protected in a dose-dependent manner from the dramatic intestinal damage that occurs from antibiotic use. This work has been published in Science Translational Medicine.
If successful in the preclinical proof-of-concept, Facile Therapeutics aims to bring Ebselen into a proof-of-concept clinical trial in patients with C. difficile, to be given to patients following their completion of standard of care antibiotic therapy, and thus reduce their risk for recurrence. Ebselen is being developed as an oral therapeutic, and the company will also examine its potential for use in a colonic-delivery formulation.
A new study published in the New England Journal of Medicine estimates that more than 20,000 deaths in the US are caused yearly by C. difficile infections, many of which are contracted in health-care centers. Those deaths are in addition to an estimated 35,000 Americans who die each year from drug-resistant Gram-negative bacterial infections.
Supporting innovation to address the global superbug crisis
The CARB-X portfolio is the world’s largest and most diverse antibacterial development portfolio with 39 active projects – antibiotics, vaccines, rapid diagnostics and other life-saving products – in five countries focused on addressing the global rise of drug-resistant bacteria.
CARB-X is a consortium led by Boston University and funded by a global partnership. CARB-X is investing up to $500 million between 2016-2021 to support the development of new antibiotics, rapid diagnostics, vaccines and other life-saving products. The goal is to support projects through the early phases of development – from hit-to-lead through Phase 1 for therapeutics – so that they will attract additional private or public support for further clinical development and approval for use in patients.
Funding for the Facile project is provided by the Biomedical Advanced Research and Development Authority (BARDA) and the Wellcome Trust.
Since its launch in 2016, CARB-X has announced 61 awards exceeding $222.06 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 an award from Wellcome Trust. 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.
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 Facile Therapeutics
Facile Therapeutics is Silicon Valley based biotech company founded to demonstrate that the anti-toxin Ebselen can be used to treat Clostridium difficile recurrence. The approach of using anti-toxins to reduce recurrence rates has been validated in humans in Phase 3 trials. Moreover, extensive data from over 20 years of late stage trials of Ebselen (for indications not related to infectious disease) in over 500 subjects and patients in Japan and the United States have yielded a favorable safety profile in humans. Clostridium difficile infection (CDI) is a life-threatening colon infection, with hundreds of thousands of cases per year in the US. The CDC has designated CDI as an urgent infectious disease threat. Although antibiotics are effective at clearing the infection, they also increase the risk of disrupting the normal bacteria that live in the gut, leading to infection recurrence. In fact, 25-60% of treated patients experience a recurrence of the infection within 2-8 weeks. Thus, prevention of recurrence remains the overwhelming challenge in treating CDI, and Ebselen represents a promising new option to treat this debilitating disease. www.faciletx.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).
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.