BiomX’s Phage Cocktail Seen to Kill Resistant P. aeruginosa in Studies
BX004, a phage therapy candidate for Pseudomonas aeruginosa infections in people with cystic fibrosis (CF), was able to effectively kill a range of antibiotic-resistant bacterial strains under laboratory conditions, new data show.
These findings were shared in the poster “Phage therapy for chronic Pseudomonas aeruginosa infections in Cystic Fibrosis patients,” presented at the 44th European Cystic Fibrosis Conference (ECFC) earlier this month.
P. aeruginosa is the most common cause of bacterial lung infections in people with CF. While antibiotics can kill bacteria, many bacteria — including P. aeruginosa — have evolved to become resistant to them, complicating disease management.
Bacteriophages, or phages for short, are viruses that can infect and kill bacteria. BiomX developed a platform called BOLT (BacteriOphage Lead to Treatment) that aims to rapidly develop phages to combat bacterial infections. BX004 is the company’s investigational phage treatment for CF.
These new data highlight “the capability of our BOLT platform to design phage cocktail candidates that can efficiently and selectively target pathogenic [disease-causing] bacteria,” Jonathan Solomon, CEO of BiomX, said in a press release.
At ECFC, researchers with BiomX shared data that led to the development of BX004. The researchers isolated P. aeruginosa in sputum samples from 122 CF patients in the U.S. and 24 in Europe. Genetic sequencing of these bacteria revealed that nearly all of the strains — 141 out of 146 — were resistant to multiple antibiotics.
They screened hundreds of samples, looking for phage candidates with an ability to infect bacteria. The phages also were analyzed for the presence of other traits, such as their ability to target multiple bacterial strains.
Ultimately, the researchers selected three phages for use in BX004. Collectively, these phages were able to infect and kill about 80% of the 146 P. aeruginosa strains in the laboratory tests.
All three phages are part of the Caudovirales order. This group of viruses are also called tailed bacteriophages, named for their structure that consists of a round “head-like” structure where the viral DNA is stored, and a “tail” that the virus uses to attach to the bacterial cell it is infecting.
In addition to antibiotic resistance, another common obstacle in treating bacterial infections arises when bacteria form a biofilm — a mesh of slimy proteins and sugar molecules that allows a group of bacteria stick to a surface. Biofilms help to protect individual bacteria from external threats, like antibiotics.
In subsequent experiments, the scientists tested the ability of their three-phage cocktail to kill P. aeruginosa that had been allowed to grow biofilms. The phage cocktail reduced the number of bacteria in these biofilms by about 1,000-fold, the researchers reported.
Notably, the phage cocktail outperformed two antibiotics commonly used against bacteria in a biofilm. However, the most potent effect was seen when the phages were combined with the antibiotic aztreonam, resulting in a roughly 100,000-fold decrease in bacterial numbers. This finding indicated “a synergistic interaction may exist between the phages and aztreonam,” the researchers wrote.
“The 3-phage cocktail comprised of natural phages demonstrated broad host range, potent antimicrobial activity even in the presence of biofilms, and synergistic activity with antibiotics against clinical P. aeruginosa isolates and should be further explored for the treatment of P. aeruginosa pulmonary [lung] infections in patients with CF,” they concluded.
The safety and efficacy of BX004 in people with CF are currently being evaluated in an early clinical trial.
“We look forward to advancing BX004 in CF to a Phase 1b/2a trial with results from Part 1 expected in the first quarter of 2022,” Solomon said.