Locus’ therapy is actually a cocktail of six phages. The company used artificial intelligence to predict which combination would be effective against E. coli. Three of the phages are “lytic,” meaning they work through infection E. coli cells and causing them to open. The other three have been engineered to contain Crispr to enhance their effectiveness. Once inside their target cells, these phages use the Crispr system to home to a key site in E. coli genome and begin to destroy the bacteria’s DNA.
Some phages are really good at entering bacterial cells but not good at killing them. “That’s where gene editing comes in,” explains Paul Garofolo, CEO of Locus. He said the therapy is meant to “reach the human body and eliminate a targeted bacterial species without touching anything else.”
In a Phase 2 trial, 16 women received a three-day course of the phage cocktail, along with Bactrim, a commonly prescribed antibiotic for UTIs. Within four hours of the first treatment, levels of E. coli in the urine decreased rapidly, and was maintained until the end of the 10-day study period. By that time, UTI symptoms in all participants had been eliminated, and levels of E. coli was low enough in 14 of the 16 women that they were considered cured.
The findings were reported Aug. 9 in the journal The Lancet Infectious Diseases. The Biomedical Advanced Research and Development Authority, or BARDA, part of the US Department of Health and Human Services, is collaborating on the development of the therapy.
UTIs are incredibly common, and about half of women will develop a UTI in their lifetime. More than 80 percent of infections are caused by E. coliand in a 2022 report, the World Health Organization found that one in five UTI infections is caused by E. coli showed reduced susceptibility to common antibiotics such as ampicillin, co-trimoxazole, and fluoroquinolones.
Although phage therapy is common in the Republic of Georgia and Poland, it is not licensed in the US. However, it is used experimentally in certain cases with permission from the US Food and Drug Administration. A major challenge in commercializing phage therapy is that it is often personalized to individual patients and thus difficult to scale. Finding the right phage for treatment can take time, and then batches of phage need to be grown and purified. But using a fixed cocktail like Locus’s means the therapy can be scaled up more easily.
And there’s another potential benefit. “Crispr-enhanced phages allow the destruction of the bacterial genome and bypass some mechanisms by which bacteria can become phage-resistant,” said Saima Aslam, a professor of medicine at the University of California, San Diego, who studies phages but was not involved in the development of Locus therapy. “Theoretically, this could prevent the regrowth of phage-resistant bacteria and thus lead to more effective treatment.”
Photo: Locus Biosciences
