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
Dosing has begun in Part 2, the controlled, double-blind portion of the trial triggered by the success in Part 1
Data support potential of Locus’ engineered bacteriophage platform in combatting the global health crisis of infections caused by multidrug-resistant (MDR) pathogens
RESEARCH TRIANGLE PARK, N.C., Aug. 12, 2024 (GLOBE NEWSWIRE) -- 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, today announced positive results from Part 1 of its two-part Phase 2 ELIMINATE trial. This Phase 2 trial is evaluating LBP-EC01, a CRISPR-Cas3 genetically engineered bacteriophage therapy designed to treat patients with uncomplicated urinary tract infections (uUTIs) caused by antimicrobial-resistant (AMR) and multi-drug-resistant (MDR) Escherichia coli (E. coli).
Data from the randomized, uncontrolled, open-label Part 1 portion of the trial were published in The Lancet Infectious Diseases. Locus also announced that dosing has begun in the randomized, controlled, and blinded Part 2 portion of this Phase 2 study. This clinical trial is supported by the Biomedical Advanced Research and Development Authority (BARDA), part of the Administration for Strategic Preparedness and Response within the U.S. Department of Health and Human Services.
Worldwide, an estimated 150 million people are affected by UTIs each year. Approximately 80% of these are caused by E. coli, often including difficult-to-treat strains that are resistant to commonly used antibiotics. Up to 40% of UTI patients experience a recurrence, often within months of the first episode. Both the U.S. Centers for Disease Control and Prevention and the World Health Organization have identified antibiotic-resistant E. coli as an urgent and serious public health threat requiring the development of new treatments.
Part 1 of ELIMINATE enrolled 39 adult female patients, across six United States-based clinical centers and had an overall objective of defining a dosing regimen of LBP-EC01 and oral trimethoprim/sulfamethoxazole (TMP/SMX) to advance to Part 2 of the trial. This overall objective was supported by analysis of the primary outcome of pharmacokinetics (PK) in urine and blood, and the secondary outcome of safety, which were assessed on randomized patients dosed at least once with LBP-EC01. In addition, an exploratory outcome of pharmacodynamic (PD) assessments was performed on 16 evaluable patients.
“The need for new targeted antibacterial therapies is urgent given the increasing impact of antibiotic-resistant pathogens, which we see in our clinic every day,” said Juvenal E. Martinez, M.D., an investigator in the trial. “As the first Phase 2 engineered bacteriophage trial, ELIMINATE is breaking new ground in the quest to address increasingly prevalent serious MDR infections. This encouraging initial data support the possible utility of bacteriophages and the potential of LBP-EC01 as a therapeutic option to address drug-resistant bacterial infections, such as UTIs, which have a high recurrence rate due to MDR pathogens.”
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 and which led to high drug exposure at the site of infection. No serious 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 was 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 updated treatment groups, which focused on a short, 3-day course of intra-urethral (i.e., IU or direct to 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 given for 2 days IU (2×1012 PFU/dose) and given concurrently for 3 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.
ELIMINATE Trial Part 2 underway
Part 2 of the ELIMINATE trial has been initiated with patient dosing underway. This randomized, controlled, double-blind portion of the trial will evaluate the efficacy, safety, tolerability, and pharmacokinetics of LBP-EC01 with TMP/SMX. Up to 288 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 of time to the next 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.
“These milestones represent a huge step forward in the critical fight against MDR. Over the past eight years, we have invested significant resources to build the Locus engineered bacteriophage platform. We developed our high-throughput robotics and AI technology to optimize a fixed set of precisely engineered phages that target over 95 percent of current uropathogenic E. coli strains, including MDR strains. We also built a world-class viral vector manufacturing facility that produces GMP materials at potency and purity levels higher than any others we have seen in the field to date. These Part 1 data validate our platform and support the advancement of a potential first-in-class therapy,” said Paul Garofolo, Co-founder and CEO of Locus. “We are grateful for the participating sites, clinicians, and patients, and our funding partner BARDA. We are eager to build on this positive momentum as we continue Part 2 of the ELIMINATE trial.”
For more information on Part 1 of the ELIMINATE trial, visit clinicaltrials.gov using the identifier NCT05488340. Patients interested in participating in Part 2 can visit www.eliminateuti.com.
About LBP-EC01
LBP-EC01 is a CRISPR-enhanced bacteriophage therapy in development for the treatment of urinary tract infections 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 along with the DNA-targeting activity of CRISPR-Cas3. LBP-EC01 previously met all primary and secondary endpoints and demonstrated safety and tolerability in a Phase 1b trial. LBP-EC01 is currently being evaluated in a Phase 2 trial for the treatment of UTIs caused by E. coli.
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 $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.
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 kill pathogenic bacteria, while sparing good bacteria, through programmable precision anti-bacterials with CRISPR-Cas3 and other therapeutic payloads. Its artificial intelligence and machine-learning based discovery engine targets bacteria that are associated with disease across multiple therapeutic areas including infectious disease, immunology, and oncology. Locus has secured multiple non-dilutive partnerships to support development of the company’s platform and programs. These include anti-bacterial partnerships with Biomedical Advanced Research and Development Authority (BARDA) for its lead asset targeting E. coli and Combatting Antibiotic Resistant Bacteria Accelerator (CARB-X) for its asset targeting K. pneumoniae. For more on the Research Triangle Park, N.C.-based company, visit www.locus-bio.com.
Media Contact:
Gina Mangiaracina
6 Degrees
gmangiaracina@6degreespr.com
