RESEARCH TRIANGLE PARK
For generations, antibiotics have been a boon to humanity, saving untold numbers of people from deadly infections and bacteria.
But as those antibiotics have been overused across the world — both in humans and in animals — they have created a new threat: antibiotic-resistant bacteria that have evolved immunity to those life-saving drugs.
It’s a potentially dire problem. The World Health Organization warns minor infections and common injuries could once again become deadly without changes to how we use antibiotics. The WHO forecasts that drug-resistant diseases could kill 10 million people a year by 2050.
Locus Biosciences, a Research Triangle Park-based biotechnology, believes it could provide one solution to the looming crisis.
The company, founded in 2015, is using CRISPR gene-editing technology to create what are called bacteriophage therapies.
Bateriophages, also known simply as phages, are viruses that can attack and neutralize bacteria. Phages were once popular choices before the rise of antibiotics, and they are still popular in some Eastern European countries.
But they had some disadvantages. They could be unpredictable and hard to manage, unlike antibiotics which were consistent.
“Phages have been around for over 100 years. You can find them in pharmacies in Eastern European countries,” Locus Chief Scientific Officer Dave Ousterout said in a telephone interview. “But then Penicillin came around and was cheap and was widely available, and it became the de facto drug in western medicine.
“The problem is that while those drugs work well and became quite cheap, you are starting to see what nature does, which is evolve and resist.”
With the use of gene-editing technology, Locus believes it can make phages more reliable and effective. It could also be less disruptive to the microbiome of an individual’s gut.
STARTING WITH FOCUS ON UTIS
The company just completed its first Phase 1 clinical trial testing out its technology, targeting E. coli bacteria causing urinary tract infections. The company claims it’s the world’s first clinical trial for a CRISPR-enhanced phage.
UTIs are one of the most common infections on the planet, and there is a rise in UTIs becoming resistant to antibiotics. A report from Harvard Medical School called UTIs the “canary in the coal mine” for antibiotic resistance.
Phase 1 trials help determine the safety of experimental drugs and therapies. Locus said that its gene-edited phage was safe and tolerated in the trial, which included 30 patients. Locus said the trial also showed its phage can decrease the level of susceptible bacteria in patients infected with E.coli in the bladder, though it will still need to go through larger clinical trials.
But the company doesn’t plan to stop with UTIs. By using CRISPR, Ousterout said, the company could make a variety of different phages that are micro targeted for certain bacteria.
Locus is also studying how its technology might be used in respiratory infections.
“We are advancing other drugs to other indications as well,” Ousterout said. “We are building the platform over time.”
That could be wide ranging. “We could go anywhere where bacteria impacts the immune system,” he added.
It could also add to that platform quickly. Creating a new antibiotic can be resource intensive, Ousterout said. But CRISPR allows them to work faster. The company went from petri dishes to human trials for its UTI phage in just four years, Ousterout said, and its turnaround on other phages could be similar.
LOOKING AHEAD TO MORE TRIALS
Locus was founded by Paul Garofolo, a former executive at Valeant Pharmaceuticals. He came up with the idea for Locus while working as a visiting professor at N.C. State University. The company now has around 60 employees, and it is creating its own manufacturing capabilities.
Outserout said that its UTI phage will likely enter a Phase 2 trial sometime in the next 12 to 24 months.
“Where it goes from there is a product of how the data and trial goes,” he said.
Those next trials will be funded in part by the government. Locus signed a contract with the Biomedical Advanced Research and Development Authority (BARDA), which will provide $144 million to support Phase 2 and 3 trials.
BARDA’s purpose is to help fund potential solutions that could be helpful for public health medical emergencies such as pandemics and emerging infectious diseases.
Ousterout said the BARDA funding shows how much of a threat drug-resistant bacteria is to the future.
“Everyone is starting to know someone who has a drug-resistant infection that had to go through multiple rounds of antibiotics to find what works,” he said. “What we don’t see yet is how much antibiotics will affect our everyday lives.”
That could soon change, and basic cuts could once again be the source of a dangerous infection, Ousterout said.