Announcing the completion of its Phase 1b study of LBP-EC01, a CRISPR-Cas3-enhanced bacteriophage (crPhage) product targeting Escherichia coli (E. coli) bacteria that cause urinary tract infections (UTIs), the biotech said all primary and secondary endpoints were met.
The results, it said, indicated LBP-EC01 exposure can decrease the level of susceptible bacteria in patients infected with E. coli in the bladder. The trial found no drug-related adverse effects, underscoring the safety of the company’s precision approach, added Locus.
Locus’ crPhage technology works by targeting the DNA of specific bacteria, destroying their cells while leaving non-target bacteria in the human body unaffected. It has dual mechanism of action, utilizing the natural lytic activity of the bacteriophage along with the DNA-targeting activity of CRISPR-Cas3, said the developer.
That dual mechanism makes LBP-EC01 significantly more effective at killing E. coli cells than corresponding natural bacteriophages, as shown both in laboratory tests and in small animal models of urinary tract infection, said Locus. The mechanism also makes LBP-EC01 effective in killing such bacterial strains regardless of whether they are resistant to antibiotics, it said.
Threat of antibiotic-resistant E. coli
Both the US Centers for Disease Control and Prevention (CDC) and World Health Organization (WHO) have identified antibiotic-resistant E. coli as an urgent and serious public health threat requiring development of new treatments.
Worldwide, an estimated 150 million people are affected by UTIs each year. About 80% of these are caused by E. coli, often including difficult-to-treat strains that are resistant to commonly used antibiotics. Up to 40% of UTI patients experience a recurrence within months of the first episode.
The company is now set to advance the technology to a Phase 2 study, which is funded under a collaboration with BARDA.
A Phase 3 trial, evidently, would also need to be conducted ahead of the company seeking marketing approval from the US Food and Drug Administration (FDA) for LBP-EC01.
What kind of timeline to commercialization does the company anticipate?
“There are a lot of uncertainties in drug development, so it is too early to say for sure when crPhage products will reach the market. However, if all goes well, we anticipate that we could submit a BLA to the FDA for approval as early as 2025, crPhage could be commercially available in 2026,” Joseph Nixon, senior vice president of business development, Locus, told BioPharma-Reporter last October.
Unmet medical needs
As well as targeting UTIs, the company says it is looking to address, though the use of this phage technology, unmet medical needs in bacterial infections and microbiome indications in oncology, immunology, and neuroscience therapeutic areas.
In collaboration with Johnson & Johnson, it is also working on crPhage products targeting two common pathogens that cause infections of the respiratory tract and other body sites.
In addition, the biotech has a research program evaluating potential treatments for inflammatory bowel disease, improving patient responses to immune-oncology therapies, fighting infections in patients receiving immune checkpoint inhibitors, and colorectal cancer.