Locus Biosciences is a clinical-stage biotechnology company developing precision biotherapeutics using engineered bacteriophage technology to target and eliminate specific pathogenic bacteria.
Could you update us on the positive results from your Phase 2 trial for the treatment of urinary tract infections (UTIs)? What about Crohn’s disease?
Part 1 of our two-part Phase 2 trial for UTIs, especially in an antibiotic-resistant population, yielded remarkable results. We achieved a 100% clinical cure rate and an 87.5% microbiological cure rate in the evaluable population of patients. The outcomes from Part 1 of this study, published in The Lancet Infectious Diseases, helped us secure $24 million from our collaboration with BARDA, part of the U.S. Department of Health and Human Services, enabling us to proceed with the blinded portion of this Phase 2 trial. We aim to complete patient enrollment by mid-2025, targeting a release of data potentially demonstrating superiority—a major milestone for us.
Regarding Crohn’s disease, our insights from the UTI study revealed a link between adherent invasive E. coli (AIEC), a pathogen often found intracellularly that antibiotics cannot easily eliminate, and the reservoirs of uropathogenic E. coli (UPEC) associated with recurrent UTIs. AIEC is also suspected of contributing to Crohn’s disease. To address this, we have developed a second-generation drug for oral delivery aimed at reducing AIEC in the gastrointestinal tract, potentially alleviating or preventing Crohn’s symptoms. We are excited about this discovery, as it could lead us into immunology, a field we have been eager to explore.
Have your successes spurred a greater interest in precision antibiotic treatments?
Yes, there is certainly a growing recognition, especially following our Lancet publication, that we are leading in well-designed, controlled studies for engineered phage therapies. Within the infectious disease field, though it is a challenging therapeutic area largely driven today by government and academic initiatives, our trial has garnered significant attention. We are proud that our work may set a precedent for addressing multi-drug resistance, and there is a high level of anticipation for our upcoming data, which could potentially illuminate a new approach to curing these tough-to-treat infections.
Your pipeline is unique in that all the drugs in your pipeline are developed via AI. Could you explain how this came about?
The integration of AI into our drug development approach began when we acquired EpiBiome in 2018. EpiBiome pioneered high-throughput phage discovery and characterization, and machine learning for phage cocktail design and optimal phage engineering. We then invested heavily, including over $100 million in scaling what we believe is one of the world’s most advanced AI-driven drug development platforms in existence today and in developing the resulting products. This platform allows us to identify novel phages in vast quantities, with approximately 7,500 unique phages discovered across 14 bacterial species.
Our approach combines AI with robotics to simulate interactions between bacteria and phages at an unprecedented scale. Using large-scale simulations, we can predict phage behavior in various combinations, assessing factors like receptor diversity, synergy, and stability. This modeling is crucial for developing optimized cocktails that maximize effectiveness while minimizing antagonistic interactions.
We rely on “cocktail calculators” that perform millions to billions of simulations to select phage combinations for our drugs. Our AI-directed robotics platform continuously refines these predictions by comparing clinical outcomes to in vitro results, verifying that our in-clinic findings align with laboratory predictions. This alignment strengthens our confidence in using AI-driven discovery to push the limits of phage therapy, making our pipeline one of the most advanced in this emerging field.
What are your thoughts on the potential applications of this platform beyond phage therapy?
We have considered applying our AI-driven technology to broader fields, such as gene editing with CRISPR-Cas3 or optimizing targeting of other viruses like AAVs and adenovirus. However, expanding into these areas would require a substantial amount of diverse and unbiased data, which is essential for training AI models accurately. In the past, few companies have collected this type of data at scale, making it a slower journey for AI integration in synthetic biology outside our specific field.
For now, our focus remains on bacterial targets where we can leverage our existing data and expertise. However, if the opportunity arises to acquire or merge with a group that has relevant data in areas beyond phage therapy, we might explore expanding the applications of our platform further.
Have you considered licensing out your AI platform?
Yes, we are in the early stages of discussing licensing with several industry players. These conversations take time, and we anticipate potential partnerships by 2025. Our technology is positioned to target bacterial precision medicine, which we believe will be central to future treatments for conditions like Crohn’s disease, psoriasis, rheumatoid arthritis, and even neurological conditions potentially influenced by bacterial factors.
In precision medicine, selectively removing specific pathogenic bacteria instead of wiping out the patient’s microbiota with broad-spectrum antibiotics marks a significant shift. Our platform could be instrumental in creating a new field of bacterial precision medicine, allowing us to address the underlying causes of various diseases by selectively targeting and removing harmful bacteria.
Looking ahead, what advancements do you hope to achieve in the next year?
Our top priority is a positive outcome from our blinded study on recurrent urinary tract infections. Achieving success in microbiological and clinical cure rates would continue to validate our platform’s capabilities in a rigorous, randomized study, potentially opening doors for strategic partnerships.
Additionally, we aim to secure funding to advance our Crohn’s disease program, which is moving through critical stages, including preparing for FDA IND submission along with manufacturing process development and scale-up. We expect to enter the clinic with this asset by late 2025. We are also working to secure the funding needed to advance into clinical development for two assets, targeting Staphylococcus and Pseudomonas infections that we developed in collaboration with Johnson & Johnson before J&J exited infectious disease R&D in 2023. Success in these areas would transform Locus Biosciences and set us up for a pivotal 2026.
