Locus Biosciences Reports Positive Phase 2 ELIMINATE Trial Results for LBP-EC01 in The Lancet Infectious Diseases

Locus Biosciences, Inc., a clinical-stage biotechnology firm, has announced promising results from Part 1 of its Phase 2 ELIMINATE trial. This trial is assessing LBP-EC01, a CRISPR-Cas3 engineered bacteriophage therapy aimed at treating uncomplicated urinary tract infections (uUTIs) caused by antibiotic-resistant and multi-drug-resistant Escherichia coli (E. coli). The findings from this phase were published in The Lancet Infectious Diseases, and dosing for Part 2 of the trial has now commenced.

Uncomplicated UTIs are a significant global health issue, affecting approximately 150 million individuals annually, with E. coli being the cause in about 80% of cases. The prevalence of antibiotic-resistant strains complicates treatment, leading to high recurrence rates. Both the U.S. Centers for Disease Control and Prevention and the World Health Organization have flagged antibiotic-resistant E. coli as a severe public health threat.

The open-label Part 1 of the ELIMINATE trial enrolled 39 adult female participants across six clinical centers in the United States. The primary aim was to establish a safe and effective dosing regimen for LBP-EC01 and oral trimethoprim/sulfamethoxazole (TMP/SMX) for advancement to Part 2. Primary outcomes included pharmacokinetics (PK) in urine and blood, while secondary outcomes focused on safety. An additional exploratory outcome evaluated pharmacodynamic (PD) assessments in 16 patients.

According to Dr. Juvenal E. Martinez, a trial investigator, the growing impact of antibiotic-resistant pathogens emphasizes the need for new targeted antibacterial therapies. ELIMINATE is the first Phase 2 trial utilizing engineered bacteriophage therapy to tackle serious multi-drug-resistant infections. The initial data from Part 1 supports the use of bacteriophages and indicates the potential effectiveness of LBP-EC01 in treating drug-resistant bacterial infections, such as UTIs, which have a high recurrence rate.

Part 1 revealed that the primary and secondary objectives were met, identifying a dosing regimen that was well-tolerated and resulted in high drug exposure at the infection site. No serious adverse events were reported, and exposure to LBP-EC01 did not lead to any genetic resistance in recovered E. coli samples. The initial treatment groups focused on intravenous (IV) delivery were modified due to mild adverse events, leading to a revised regimen that included intra-urethral and lower exposure IV dosing. This updated approach showed a rapid reduction of E. coli in urine within four hours of treatment, maintained up to the day 10 test of cure (TOC).

In Part 1, all 16 evaluable patients experienced complete resolution of UTI symptoms, and 87.5% demonstrated a microbiologic cure or significant reduction in bacterial infection by the day 10 TOC. The finalized regimen for Part 2 involves a 3-day course of LBP-EC01 combined with oral TMP/SMX.

Part 2 of the ELIMINATE trial has begun, focusing on evaluating the efficacy, safety, tolerability, and pharmacokinetics of LBP-EC01 with TMP/SMX. This phase will enroll up to 288 female patients with uUTIs, who will be randomized to receive either LBP-EC01 or a placebo. The primary objective is to assess the therapy's effectiveness in treating acute UTIs in patients with a history of recurrence. The trial will also explore the impact on UTI recurrence over a six-month follow-up period.

Paul Garofolo, Co-founder and CEO of Locus, highlighted the significant progress made in developing their engineered bacteriophage platform, designed to target over 95% of current uropathogenic E. coli strains. He expressed gratitude for the support from participating sites, clinicians, patients, and their funding partner, BARDA, as they move forward with Part 2 of the trial.

LBP-EC01, enhanced with CRISPR-Cas3, is a promising therapy for treating UTIs and other infections caused by E. coli. It works through a dual mechanism utilizing both lytic activity and DNA-targeting. The therapy previously demonstrated safety and efficacy in a Phase 1b trial and is now undergoing further evaluation in Phase 2.

Locus Biosciences, based in Research Triangle Park, N.C., is a leader in precision biotherapeutics, developing bacteriophage treatments for various bacterial diseases, supported by advanced AI and machine-learning technologies.