CRISPR Therapy Shows Proof-of-Concept in Preventing Antibiotic-Resistant E. Coli Infection in Patients With Cancer

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The proof-of-concept trial was in healthy volunteers, and additional studies are being planned in patients with blood cancers undergoing hematopoietic stem cell transplants.

SNIPR001 CRISPR therapy has demonstrated proof of principle in reducing E. coli levels in the human gastrointestinal tract of patients with antibiotic-resistant E. coli at risk of fatal infections in vulnerable patients with hematological cancers, according to new data from a phase 1 clinical trial (NCT05277350).

“We are thrilled with these positive interim results from our Phase 1 clinical trial of SNIPR001, which provide clinical validation for this innovative treatment. 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. This is a significant milestone in our mission to develop groundbreaking solutions in the fight against antimicrobial resistance, and we look forward to advancing SNIPR001 through further clinical studies to learn more and ultimately, we hope, to improve patient outcomes,” Christian Grøndahl, MD, PhD, DVM, chief executive officerand cofounder, SNIPR Biome, said in a statement.

The trial enrolled 36 healthy participants, 24 of which received 1 of 3 dose levels of SNIPR001 dosed orally over 7 days and 12 of which received placebo. The trial was supported by CARB-X, a global nonprofit partnership trying to address the issue of drug-resistant bacteria. The seminal research leading to the design of SNIPR001 was published in Nature Biotechnology earlier in May 2023. The trial aimed to evaluate the safety profile, pharmacodynamics, and SNIPR001 recovery.

READ MORE: Intellia’s CRISPR Gene Editing Therapy Significantly Reduces Swelling in Hereditary Angioedema, New Data Show

Investigators found that SNIPR001 was able to be recovered in feces from treated participants in a dose-dependent matter, and SNIPR001 treatment lowered E. coli levels in the gut. Based on these findings,future studies are now being planned to evaluate SNIPR001’s ability to reduce the rate of infections in cancer patients at high risk of E. coli gut translocation into the bloodstream, with an initial indication in patients with hematological malignancies who are undergoing hematopoietic stem cell transplants. The standard-of-care of fluroquinolone administration is ineffective against antibiotic-resistant bacteria and thus another optionis needed. SNIPR Biome also plans to develop an intravenously administered version of SNIPR001 and investigate that route of administration.

SNIPR001 is a cocktail of 4 CRISPR-armed phages that selectively target and eliminate E. coli that are resistant to fluoroquinolone. It has been granted fast track designation by the FDA and is being evaluated for use alone or in combination with fluoroquinolone as a decolonization strategy.

REFERENCE
SNIPR Biome reports positive clinical interim results for groundbreaking, first-in-human, CRISPR-based microbial gene therapy. News release. SNIPR Biome. May 31, 2023. https://static1.squarespace.com/static/5bacc67990f9041ab0d5b0c1/t/6476ee0c6181141d414b9ec3/1685515789399/230529+SNIPR+Phase+1+Data+Release.pdf
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