Marks first randomized Phase 2/3 trial of CRISPR-enhanced bacteriophage precision medicine
Research Triangle Park, N.C., September 13, 2022 – Locus Biosciences, Inc. (“Locus”), a clinical-stage biotechnology company developing a new class of precision engineered bacteriophage treatments for a diverse set of bacterial diseases, announced that the ELIMINATE trial has begun enrolling patients and the first patient has been treated. ELIMINATE is a registration-enabling Phase 2/3 clinical trial of lead candidate LBP-EC01, a CRISPR-enhanced bacteriophage (crPhage®) precision medicine, for the treatment of urinary tract infections (UTIs) caused by Escherichia coli (E. coli) bacteria.
Worldwide, an estimated 150 million people are affected by UTIs each year. Approximately 80 percent of these are caused by E. coli, often including difficult-to-treat strains that are resistant to commonly used antibiotics. Nearly 40 percent of patients with UTIs experience a recurrence within months of the first episode. Both the U.S. Centers for Disease Control and Prevention (CDC) and World Health Organization (WHO) have identified antibiotic-resistant E. coli as an urgent and serious public health threat requiring development of new treatments.
“Treatment of recurrent UTIs is complicated by increasing antimicrobial resistance, drug adverse events, formation of biofilms, and lack of newer antibiotic therapies for resistant uropathogens,” said Sonali Advani, MBBS, MPH, Assistant Professor of Medicine-Infectious Diseases and board-certified infectious disease physician with extensive research into and clinical experience treating UTIs. “These challenges have led to a renewed interest in exploring bacteriophage therapy for treatment of resistant and recurrent infections. Use of bacteriophages as an alternative or adjunct to conventional antibiotics presents a novel opportunity for tackling recurrent UTIs in an era of increasing antimicrobial resistance.”
The Phase 2/3 trial of LBP-EC01 in combination with a commonly used antibiotic will enroll female patients between 18-65 years of age who have UTIs caused by multi-drug resistant (MDR) E. coli and have a history of prior UTIs caused by E. coli. Locus plans to enroll approximately 800 patients at up to 27 sites across the U.S. and the EU.
“This trial represents a significant milestone for Locus’ CRISPR-Cas3-enhanced bacteriophage, as we work to realize the potential of our precision medicines for bacterial-related diseases, and for the field as this is the first statistically powered registration-enabling trial for a bacteriophage therapy,” said Paul Garofolo, Co-founder and CEO of Locus. “Locus and our partner, the Biomedical Advanced Research and Development Authority (BARDA), believe LBP-EC01 may offer a potentially first-in-class treatment to address the emerging worldwide public health crisis of MDR bacteria and we hope to be able to confirm and build upon the positive results seen in our prior Phase 1b trial in this Phase 2/3 trial.”
Locus completed a Phase 1b clinical trial of LBP-EC01, the world’s first randomized, placebo-controlled trial of recombinant bacteriophage therapy, which met all primary and secondary endpoints and demonstrated safety and tolerability for LBP-EC01.
In 2020, Locus and BARDA, part of the Administration for Strategic Preparedness and Response (ASPR) at the U.S. Department of Health and Human Services (HHS), announced an agreement to co-fund development of LBP-EC01. Under the partnership agreement, contract number 75A50120C00169, BARDA will provide up to $77 million in funding to Locus as part of a $144 million program to support Phase 2/3 clinical trials and other activities required to seek marketing approval from the U.S. Food and Drug Administration (FDA) for LBP-EC01.
Locus anticipates completing enrollment of the trial in 2024. For more information, visit clinicaltrials.gov using the identifier NCT05488340.
LBP-EC01 is a Locus crPhage® therapy in development for the treatment of urinary tract infections and other infections caused by the pathogen Escherichia coli (E. coli). It is a bacteriophage cocktail engineered with a CRISPR-Cas3 construct targeting the E. coli genome. The precision medicine product works through a unique dual mechanism of action utilizing both the natural lytic activity of the bacteriophage and the DNA-targeting activity of CRISPR-Cas3. Laboratory tests and small animal models of urinary tract infection have demonstrated LBP-EC01 is significantly more effective at killing E. coli than corresponding natural bacteriophages, and LBP-EC01 met all primary and secondary endpoints and demonstrated safety and tolerability in a Phase 1b trial. LBP-EC01 is currently being evaluated in a registrational Phase 2/3 trial for the treatment of UTIs caused by E. coli.
About Locus Biosciences
Locus Biosciences is creating a new class of precision biotherapeutics with clinical-stage, engineered bacteriophage treatments for a diverse set of bacterial and microbiome/inflammatory diseases. A world-leading bacteriophage discovery, synthetic biology, and manufacturing platform powers the company. Locus engineers bacteriophage – naturally occurring viruses that target bacteria – to: 1) kill pathogenic bacteria, while sparing good bacteria, through programmable, precision anti-bacterials with CRISPR-Cas3; and 2) utilize bacteria resident in the body to deliver therapeutic molecules to reduce inflammation or induce other biotherapeutic effects. Its artificial intelligence and machine-learning based discovery engine is targeting bacteria across therapeutic areas including infectious disease, immunology, and oncology. Multiple non-dilutive strategic partnerships validate the company’s platform and programs. These include anti-bacterial alliances with Biomedical Advanced Research and Development Authority (BARDA) for its lead Phase 2/3 asset; and Combatting Antibiotic Resistant Bacteria Accelerator (CARB-X). For more on the Research Triangle Park, N.C.-based company, visit www.locus-bio.com.