LBP-EC01 CRISPR-Enhanced Bacteriophage UTI Therapy Clinical Trials, Indication, Side Effects
Locus Biosciences LBP-EC01 CRISPR-enhanced bacteriophage (crPhage®) therapy in development for treating urinary tract infections (UTI) and other infections caused by the pathogen 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, which are viruses that specifically attack bacterial cells and the DNA-targeting activity of CRISPR-Cas3. The mechanism also makes LBP-EC01 effective in killing E. coli strains regardless of whether they are antibiotic-resistant.
In 2020, Locus and the Biomedical Advanced Research and Development Authority (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 the development of LBP-EC01. Under the partnership agreement, contract number 75A50120C00169, BARDA will provide up to $93 million to Locus as part of a $152 million program to support Phase 2 and Phase 3 clinical trials and other activities required to seek marketing approval from the U.S. Food and Drug Administration (FDA) for LBP-EC01.
As of August 12, 2024, the primary and secondary objectives were met in the open-label randomized Part 1 of the clinical trial to treat uncomplicated UTIs caused by antibiotic-resistant E. coli. Data from the randomized, uncontrolled, open-label Part 1 portion of the clinical trial were published in The Lancet Infectious Diseases on August 9, 2024.
Locus Biosciences is creating a new class of precision biotherapeutics with clinical-stage engineered bacteriophage treatments for diverse bacterial and microbiome/inflammatory diseases. For more information about Locus, visit https://locus-bio.com/
LBP-EC01 Indication
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 the development of new treatments. Worldwide, an estimated 150 million people are affected by UTIs each year. Approximately 80% of these are caused by E. coli. Most UTI patients experience a recurrence within months of the first episode.
LBP-EC01 News
August 12, 2024 - Phase 2 trial evaluating LBP-EC01, a CRISPR-Cas3 genetically engineered bacteriophage therapy designed to treat patients with uncomplicated urinary tract infections (uUTIs) caused by antimicrobial-resistant and multi-drug-resistant E. coli, reported positive news.
January 23, 2024 - Locus Biosciences, Inc. announced the release of $23.9 million from the BARDA to continue the development of Locus’ CRISPR-enhanced bacteriophage therapy, LBP-EC01, for treating UTIs caused by drug-resistant E. coli based on positive results from a Phase 2a clinical trial.
September 13, 2022 – Locus Biosciences, Inc. announced that the ELIMINATE trial has begun enrolling patients, and the first patient has been treated. ELIMINA E is a registration-enabling Phase 2/3 clinical trial of lead candidate LBP-EC01 for treating UTIs caused by E. coli bacteria.
February 24, 2021 - Locus Biosciences announced the completion of its Phase 1b clinical trial of the LBP-EC01 precision medicine product, which targets E. coli bacteria that cause UTIs.
LBP-EC01 CRISPR-Enhanced Bacteriophage UTI Therapy Clinical Trials
LBP-EC01 met all primary and secondary endpoints and demonstrated safety and tolerability in a Phase 1b trial. LBP-EC0 is currently being evaluated in a Phase 2 trial for treating UTIs caused by E. coli.
ELIMINATE Trial Part 1 Results - The primary and secondary outcomes of Part 1 were met, and a dosing regimen was identified that was well-tolerated, which led to high drug exposure at the site of infection. No seri us adverse events were observed in Part 1, and exposure to LBP-EC01 did not lead to any observations of genetic resistance in any subsequently recovered E. coli samples. Part 1, as initiated with three treatment groups, focused on intravenous (IV) delivery of a high 1×1011 plaque forming units (PFU)/dose of LBP-EC01, which was halted after three patients discontinued dosing due to non-serious adverse events of mild tachycardia and afebrile chills. Three u-dated treatment groups, which focused on a short, 3-day course of intra-urethral (i.e., IU or direct to the bladder) and lower exposure IV dosing, replaced the original treatment groups. With this updated dosing approach, a rapid reduction of E. coli in urine was observed four hours after the first treatment, which was maintained to the day 10 test of cure (TOC) evaluation. All (16 of 16) patients in the evaluable population had complete resolution of UTI symptoms, and 14 of 16 (87.5%) patients demonstrated microbiologic cure or reduction of their bacterial infection below 1×103 colony forming units (CFU)/mL in urine by the day 10 TOC. A dosing regimen of LBP-EC01 was given for two days IU (2×1012 PFU/dose) and given concurrently for three days IV (1×1010 PFU/dose) with concomitant oral TMP/SMX (160 mg TMP/800 mg SMX twice daily) has been advanced into Part 2.
Part 2 of the ELIMINATE trial has been initiated, and patient dosing is underway. This randomized, controlled, double-blind trial portion will evaluate the efficacy, safety, tolerability, and pharmacokinetics of LBP-EC01 with TMP/SMX. Up to 2 8 female uncomplicated UTI patients will be enrolled and randomized in a 1:1 ratio where patients will receive LBP-EC01 or placebo for the 3-day dosing regimen selected from Part 1. The primary objective will be to evaluate the effect of LBP-EC01 given with TMP/SMX on its ability to treat acute UTIs in patients with a history of UTI recurrence. The impact of the treatment on reducing UTI recurrence and/or extending the duration to the subsequent UTI recurrence will be examined as an exploratory endpoint in a 6-month follow-up evaluation. This trial is registered with ClinicalTrials.gov, NCT05488340, and is ongoing.