A world first: Triangle’s Locus Biosciences to launch gene editing trial involving therapy ‘cocktail’

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Morrisville-based Locus Biosciences, a developer of precision antibacterial therapies, will conduct the world’s first clinical trial of a recombinant bacteriophage therapy, a major milestone for the field, the company announced.

Locus has opened enrollment for a Phase 1b trial of a potential treatment for urinary tract infections caused by Escherichia coli (E. coli) bacteria. The study will evaluate LBP-EC01, a bacteriophage “cocktail” that has been engineered with the gene editing technology CRISPR Cas3 to target the E. coli genome.


“This trial represents a major step toward proving that CRISPR recombinant phage can reach into the human body and precisely remove a specific pathogen,” Paul Garofolo, chief executive officer of Locus, said.  “We could not be more pleased with the team and partners who helped us advance from bold vision to the clinic.”

To accommodate the specialized early manufacture of its product candidate, the company has also taken out a $15 million loan from Signature Bank to fund a 12,000-square-foot expansion.

The investment will enable biosafety level 1 and 2 production of both oxygen-loving aerobic organisms and anaerobic microbes grown without oxygen. As a result, Locus will be able to manufacture the materials in what it calls a “vaccine-like” environment capable of meeting U.S. Food and Drug Administration and European Union regulations.

That will handle production of supplies needed for global clinical trials and a small-scale commercial launch.


About 150 million people worldwide are affected by UTIs each year, with 80 to 90 percent of the infections caused by E. coli, sometimes including difficult-to-treat strains that are resistant to commonly used antibiotics. The need for new antibacterial therapies is widely recognized, particularly those that selectively kill certain bad bacteria while leaving the many species of good bacteria in the body unharmed.

Locus is enrolling patients for the clinical trial for LBP-EC01 across several clinical sites in the United States. The company received clearance from the U.S. Food and Drug Administration for its Investigational New Drug application in the fourth quarter of 2019 and began activating its study sites.

The trial will assess the safety, tolerability and pharmacokinetics of LBP-EC01 in patients with indwelling urinary catheters, or requiring intermittent catheterization, and/or patients with asymptomatic bacteriuria caused by E. coli. About 30 adult patients will be enrolled in the multi-center randomized, double-blind, placebo-controlled study.

Additional information on the trial can be found online at https://clinicaltrials.gov/ct2/show/NCT04191148


Bacteriophages, or phages for short, are viruses that specifically attack bacterial cells. They are ubiquitous in the environment and are the most common organisms on earth, outnumbering bacteria by an estimated 10 to 1.

When a bacteriophage targets a bacterial cell, it injects DNA 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.

Bacteriophages have been used as antibacterial therapy since shortly after they were discovered in the early 20th century. Bacteriophage therapy has seen renewed interest from the medical community in recent years as antibiotic resistance has emerged as a serious global public health threat.

Locus’s product works by using both the natural reproductive activity of phages along with the DNA-targeting activity of CRISPR-Cas3. This dual mechanism makes LBP-EC01 significantly more effective at killing E. coli cells than natural corresponding phages, as shown both in laboratory tests and in small animal models of urinary tract infection, the company said.


Locus’s pipeline of CRISPR-enhanced precision antibacterial products, trademarked as crPhage, are for bacterial infections and microbiome indications in oncology, immunology and neuroscience therapeutic areas.

CRISPR is a relatively new gene-editing technology that uses enzymes to cut, edit and replace DNA at specific places in the genome. It was adapted from the natural immune systems of bacteria, which use CRISPR to chew up invading pathogens such as bacteriophages.

Various CRISPR systems have been repurposed for precise genome engineering with big commercial potential for biomedical, agricultural and research applications.

While most CRISPR technology uses an enzyme known as Cas9, Locus uses a Cas3 enzyme. Cas3’s ability to irreversibly destroy DNA differentiates it from the more widely known Cas9 enzyme used for gene editing and repair.

The Locus platform combines the DNA-shredding CRISPR-Cas3 with bacteriophages to specifically kill target pathogens while leaving non-target bacteria in the body unharmed.


Locus, a 2015 spinout of N.C. State University, was started with the help of a $75,000 Company Inception Loan from the North Carolina Biotechnology Center. The Biotech Center followed that with a $250,000 Small Business Research Loan a year later.

Three of the four scientific founders of Locus have also received Biotech Center grants totaling more than $300,000.

Locus went on to raise $19 million in Series A venture capital in 2017. The round was led by Artis Ventures of San Francisco with additional financing from institutional investors Tencent Holdings, the Chinese internet conglomerate, Abstract Ventures of San Francisco and others.

A year ago this month, Locus Biosciences signed an exclusive collaboration and license agreement with Janssen Pharmaceuticals, owned by Johnson & Johnson, to develop, manufacture and commercialize crPhage products targeting two key bacterial pathogens for the potential treatment of infections of the respiratory tract and other organ systems.  Locus received a $20 million upfront fee with an additional $798 million in payments if it meets certain development milestones.

(C) N.C. Biotech Center


Original Article Source: WRAL TechWire