CARB-X is funding Locus Biosciences to develop an innovative CRISPR Cas-3-enhanced bacteriophage targeting antibiotic-resistant Klebsiella pneumoniae infections

CARB-X is funding Locus Biosciences to develop an innovative CRISPR Cas-3-enhanced bacteriophage targeting antibiotic-resistant Klebsiella pneumoniae infections

Locus’ new phage therapy designed to precisely target and kill K. pneumoniae bacteria causing recurrent urinary tract infections (rUTI)

(BOSTON: November 10, 2020) – CARB-X is awarding up to US$2.05 million to Locus Biosciences, based in Morrisville, North Carolina, USA, to develop a new precision medicine to treat serious recurring urinary tract infections (rUTI) caused by the bacterial pathogen Klebsiella pneumoniae. K. pneumoniae are bacteria belonging to the Enterobacteriaceae family of pathogens, that includes Escherichia coli (E. coli), and are commonly the cause of antibiotic-resistant infections in healthcare settings.

Under the award, Locus will be eligible for an additional $10.5 million in non-dilutive funding from CARB-X if project progression milestones are met, subject to available funds. The Locus project, LBP-KP01, is a CRISPR Cas3-enhanced bacteriophage (crPhage™). CARB-X funding will support preclinical development of LBP-KP01 and potential progression to Phase 1 development.

“Locus’ approach combines the bacteria-hunting activity of bacteriophages with the DNA targeting activity of CRISPR-Cas3 to treat recurring UTI infections caused by K. pneumoniae,” 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 products to address antibiotic-resistant bacterial infections. “This approach has the potential to kill with laser-sharp precision the bacteria causing an infection without causing damage to other cells. If successful, this could transform the treatment of these serious life-threatening infections and save lives.”

LBP-KP01 is a bacteriophage cocktail that has been engineered with a CRIPSR-Cas3 construct targeting the K. pneumoniae genome. The treatment works through a unique dual mechanism of action utilizing the natural lytic activity of the bacteriophage along with the DNA-targeting activity of CRISPR-Cas3. This dual mechanism makes LBP-KP01 significantly more effective at killing K. pneumoniae cells than corresponding natural bacteriophages. The mechanism also makes LBP-KP01 effective in killing K. pneumoniae strains regardless of whether they are resistant to antibiotics.

“We are very excited to partner with CARB-X to advance LBP-KP01 into clinical trials,” said Paul Garofolo, CEO of Locus Biosciences. “This funding is another important validation of Locus’ rapid development of innovative CRISPR-Cas3 enhanced bacteriophage products, enabling Locus to advance a robust pipeline that includes products targeting four of the most common bacterial pathogens as well as products targeting microbiome-related disorders such as inflammatory bowel disease, pharmaceutical response to immune-oncology therapies, infections associated with immune checkpoint inhibitors and colorectal cancer.”

The LBP-KP01 project is part of an arsenal of products under development by Locus designed to address serious infections irrespective of underlying drug-resistance within the species, with funding from the US Biomedical Advanced Research and Development Authority (BARDA), for a bacteriophage cocktail directed against E. coli also for the treatment of UTIs, and in partnership with Johnson & Johnson for respiratory infections. Together, the E. coli and K. pneumoniae cocktails have the potential to treat more than 90% of UTIs.

There is a large need for new precision antibacterial therapies that selectively kill targeted bacteria while leaving good bacteria in the body unharmed. Worldwide, an estimated 150 million people are affected by UTIs each year. Up to 40 percent of UTI patients experience a recurrence within months of the first episode from difficult-to-treat strains that are resistant to commonly used antibiotics. Both the US Centers for Disease Control and Prevention (CDC) and World Health Organization (WHO) have identified antibiotic-resistant K. pneumoniae as an urgent and serious public health threat requiring development of new treatments.

Supporting global antibacterial innovation to address drug resistance

The 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 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.

The CARB-X portfolio is the world’s largest and most diverse antibacterial R&D portfolio with 46 active projects 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, vaccines, rapid diagnostics and other life-saving products. 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 regulatory approval for use in patients.

Since its launch in 2016, CARB-X has announced 72 awards worth $257 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 news release is supported by the Cooperative Agreement Number IDSEP160030 from ASPR/BARDA and by awards from the 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 Administration for Strategic Preparedness and Response, or other CARB-X funders.


Jennifer Robinson

Locus Biosciences:
Evan Burkhart

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 funding is provided 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, 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 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.  Follow us on Twitter @CARB_X.

About Locus Biosciences
Locus Biosciences is a clinical-stage biotechnology company developing CRISP-enhanced precision antibacterial products (crPhageTM) to address critical unmet medical needs in bacterial infections and microbiome indications in oncology, immunology and neuroscience therapeutics areas. The Locus platform combines CRISPR-Cas3, which permanently degrades target DNA within a bacterial cell, with bacterial viruses called bacteriophage to specifically kill target pathogens while leaving non-target bacteria (i.e., the rest of the patient’s microbiome) unharmed. For more information about Locus visit

About Bacteriophage Therapy
Bacteriophage are viruses that specifically attack bacterial cells. They are ubiquitous in the environment and are the most common organisms on the planet, outnumbering bacteria by an estimated 10 to 1. When a phage targets a bacterial cell, it injects its genetic material into the cell that hijacks the cell’s machinery and uses it to create new copies of itself. The infected bacterium is killed in the process of releasing tens or hundreds of new phages, which go on to infect additional bacteria. Bacteriophage have been used as antibacterial therapy since shortly after they were discovered in the early 20th century. Bacteriophage therapy has enjoyed renewed interest from the medical community in recent years as antibiotic resistance has emerged as a serious global public health threat.

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