Earlier this year, the company completed what it described as the world’s first placebo-controlled Phase 1b clinical trial of a CRISPR Cas3-enhanced bacteriophage product targeting E. coli in UTIs.
“The results demonstrated safety and tolerability for LBP-EC01, and the trial met all of its primary and secondary endpoints. We are currently moving towards initiating the phase 2 study with LBP-EC01 with an anticipated trial initiation in early 2022,” said Paul Garofolo, CEO of Locus.
Once Locus started the very first recombinant phage phase 1b clinical trial, it was in need of a larger cGMP facility to continue that study and future clinical trials. Because the drug substance is a bacterial phage and incorporates virulent bacterial in its production process, contract manufacturing was impossible. Locus was forced to build its own facility
The company set about building a 10,000 sq ft modular biologics manufacturing facility in Morrisville, North Carolina, with it being substantially completed in August 2020. The facility is said to meet the standards of the US, European and Japanese regulators, among others, to enable the manufacture of its precision medicines while providing the capability to also manufacture gene therapy vectors and other advanced biologics.
Garofolo told BioPharma-Reporter that the financial backing from Hercules will allow the company to expand the production capacity of that site. “The modular design allows us to change-out or upgrade existing equipment that moves Locus from being able to produce clinical trial material to producing multiple early-stage commercial products in parallel, all while maintaining the same footprint.”
Bacteria-related diseases
Locus is also looking to address, though the use of its phage technology, unmet medical needs in bacterial infections and microbiome indications in oncology, immunology, along with neuroscience therapeutic areas.
“Bacteria are directly associated with many human diseases and Locus believes its precision engineered bacteriophage platform has the potential to fundamentally change the way bacteria-related diseases are treated.
“Through our bacteriophage discovery, synthetic biology and manufacturing platform, Locus is developing two innovative categories of biotherapeutics to address significant unmet medical needs: precision products to fight deadly infections, including those caused by multi-drug resistant bacteria; and engineered bacteriophage therapies that utilize bacteria resident in the body to deliver therapeutic molecules.
“We use a bacteriophage to deliver Type I CRISPR-Cas3 systems into bacterial cells that target and kill pathogens while leaving all of the other species of bacteria in the microbiome – many of which are necessary for human health - unaffected," said the CEO.
AMR: the silent pandemic
Antimicrobial resistance (AMR) is considered by many within the field, he continued, as ‘the silent pandemic’.
“This is not a concern for the future, it is clearly affecting people today. Locus’ precision medicines work regardless of AMR status and are specifically designed to overcome resistance.
“Should LBP-EC01 become so widely used that it causes epidemiological shift - a global change in the E. coli strains that infect people - then our platform is designed to rapidly evolve the drug product.
“Furthermore, the one bug, one drug precision approach our platform employs has significant implications for bacterial infections in patients receiving novel therapeutics for conditions such as cancer. Lifesaving checkpoint inhibitors, for example, which are used across several cancer types, are negatively impacted by antibiotic use in these fragile patients. By specifically targeting only the pathogen of interest, Locus precision medicines avoid negatively affecting patient responses to these important therapies.”
Leveraging the microbiome
Within immunology and oncology, the association between disease and bacteria is becoming clearer, continued Garofolo.
“Our platform enables the company to directly remove bacteria driving or exacerbating disease while delivering biotherapeutics that can ameliorate disease pathogenesis. We leverage the microbiome to manufacture the biotherapeutics inside the human body at the site of the disease, increasing the effective dose while decreasing systemic exposure - all designed to improve outcomes while decreasing side effects.”