Can CRISPR—a gene editing mechanism born from a bacterium’s antiviral system—be used as an antibiotic? That’s what SNIPR Biome wants to know, and new interim data from an early phase 1 study seem to show that a CRISPR-based therapeutic can in fact reduce levels of antibiotic resistant E. coli in humans.
SNIPR001 lowered levels of E. coli in the gut of healthy individuals, the small Danish biotech reported Wednesday. The 36-person phase 1 trial tested three different doses of the CRISPR-armed phage therapeutic in 24 participants, with the remaining 12 getting placebo. The main goal was safety, recovery of the medicine and pharmacodynamics.
The study showed that oral dosing over seven days was well tolerated with mild to moderate side effects and no patients withdrawing. The treatment was also able to be recovered from feces of the treated individuals in a dose-dependent manner, the company said.
SNIPR said the early data show proof of concept for CRISPR-based therapies to combat bacterial infections, however, more research is needed to confirm the findings. The biotech is planning additional studies to evaluate SNIPR001’s ability to reduce the rate of infections in cancer patients who are at high risk of E. coli gut translocation into the bloodstream.
The data also support advancement of a trial for an intravenous version of the therapy, which is in the planning stages.
“With the combined killing effects of bacteriophages and CRISPR-Cas technology, SNIPR001 has demonstrated the ability to target and eliminate antibiotic-resistant E. coli strains in the gut, providing a safe alternative to traditional treatments that do not work against antibiotic-resistant strains, while sparing the rest of the gut microbiome,” SNIPR CEO Christian Grøndahl said in a Wednesday release.
SNIPR is initially targeting SNIPR001 at patients with hematological malignancies who are undergoing hematopoietic stem cell transplants and are vulnerable to bloodstream infections caused by E. coli. These patients are typically treated with fluoroquinolone antibiotics, which are ineffective against antibiotic-resistant bacteria.
SNIPR001, meanwhile, is a cocktail of four different CRISPR-armed phages that target E. coli that resist fluoroquinolone. SNIPR said that the cocktail could be used on its own or in combination with fluoroquinolone.
The FDA granted SNIPR001 a fast-track designation in January 2022. The therapy is being developed with support from CARB-X, or Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator, a global nonprofit partnership that aims to accelerate the development of treatments for drug-resistant bacteria. SNIPR was awarded up to $3.9 million in May 2021 to develop the E. coli treatment, with a further $6.3 million available down the line if certain milestones were met.
SNIPR raised $50 million back in 2019 to fund its work in CRISPR-based microbiome drugs.