LOCUS
Predictive Artificial Intelligence and Robotics Platform
LOCUS
Central to our mission is LOCUS, a powerful technology-led platform that enables us to develop products that selectively remove bacterial species at equivalent or superior levels than antibiotics without the drawback associated with broad-spectrum antibiotics. Instead of employing the age-old approach to building phage therapies, LOCUS industrializes the process by deploying a suite of robotic tools, predictive modeling, and world-class manufacturing to build its precision medicines.
The scale of proprietary data that LOCUS generates enables the development of quality machine learning models. In short, better data results in better predictions. With each product developed, LOCUS becomes better at designing the next one. With five active programs advancing into and through the clinic, LOCUS has become one of the world’s most robust bacteriophage development platforms.
Cloud Core
The computational powerhouse of LOCUS, the Cloud Core not only stores all the data we generate but enables access and learning from natural language processing (NLP)-inspired models and other predictive models used to rapidly advance our engineered phage cocktails.
- 1 petabyte of proprietary genomic, phenotypic, and clinical data
- AI-predictive models like AlphaFold used to predict synthetic payload selections
- 2.2 million images processed through image enumeration pipeline for automated calculation of phage and bacterial titers
- 65,054 cloud pipeline runs process multi-step genomic and phenotypic workflows
- Automated scripts search for new data coming off robots and automatically trigger analyses, directing data flow to appropriate locations
Biobank Core
To enable global sourcing of bacterial strains, mass discovery of bacteriophages, and rapid engineering of target phages, we utilize automated biobanks to store and track the tens of thousands of bacteria, phage, and environmental samples we have on site.
- 5,239 contemporary bacterial strains isolated by Locus or acquired from commercial/academic sources
- 7,673 phages banked + 1,266 engineered phages
- Hundreds of unique payloads enhance phage virulence and provide abundant phage engineering options
- 1,131 environmental samples sourced from 577 providers in all 50 U.S. states
Pangenomics Core
Home to the suite of sequencing capabilities within LOCUS, the data generated by this core feeds the NLP-inspired models that enable our team to build clinically-relevant bacterial training panels that are genomically diverse and to accurately predict optimal engineering sites within phage genomes.
- >30,000 bacterial genomes isolated from humans acquired from the PATRIC database
- Natural-language-processing (NLP) inspired comparative genomics workflows
- NLP-inspired models trained on phage pangenomic data used to predict optimal engineering sites within phage genomes
Robotics Core
To enable conducting experiments at a scale that human hands could not accomplish alone, we built high-throughput robotics capabilities that enable our team to test millions of bacteria-phage interactions for each program and to ensure the efficacy seen in vitro translates to the clinic.
- Rapid high-throughput assays provide model datasets for machine learning prediction of optimized phage cocktails
- Laboratory robotics drive phage discovery, characterization, and cocktail optimization (logging over 10,000 hours)
- 18,295 samples sequenced provide training data for phage, bacteria, and microbiome genome content
- 41 million phage x bacteria reaction datapoints collected by optical density assessment
Viral Vector Core
We built an award-winning 10,000 sq ft clinical- and commercial-scale cGMP manufacturing facility that meets the specifications of the US FDA, EMA, and Japanese Ministry of Health, providing us with a right-sized facility that produces high potency and purity drug product.
- ISPE Facility of the Year Award Winner
- 10,000 sq ft viral cGMP manufacturing facility, commercial launch capable for regulatory authorities in US (FDA), Europe (EMA), and Japan (PMDA)
- Fully internalized formulation, process and analytical development capabilities with capacity for toll manufacturing contracts
- Facility designed for all single-use materials minimizing contamination risk
- Manufactured >60 cGMP batches (over 60% dosed in patients in Ph1 and Ph2 clinical trials)
How LOCUS Builds an Effective Phage Drug Product
Defining the Target
Designing an effective phage therapy starts with optimizing the clinical panel. This ensures that the bacterial strains tested are representative of those that will be encountered in the clinic. This is why we build clinical panels of hundreds of bacterial isolates that are bioinformatically representative of up to 10,000 publicly available genomes.
Finding Phage
Building a fixed phage cocktail that rivals the efficacy of antibiotics requires phage discovery at a scale that has never been attempted before. We discover thousands of phages for each program to feed our cocktail optimization engine.
Biobanking
Automated banking provides an unprecedented level of control, supporting rapid and accurate creation of bacterial strain panels. Barcoded and long-read sequence-validated bacterial isolates ensure that panels are repeatably assembled to consistent specifications. When testing millions of phage-bacteria interactions, having automated processes that maintain the integrity of the panels is essential.
Characterizing Phage & Bacteria
Robust, comprehensive characterization of both isolated phages and target bacteria generates critical genotypic and phenotypic data. These data feed predictive models that drive phage selection, cocktail optimization, and phage engineering.
Predicting Cocktails
To test every isolated and characterized phage in a cocktail of six phages would require trillions of permutations. Even automated robotics can’t deliver that scale, so we turn to in silico computational models that predict the highest-performing cocktails. By leveraging these models, we to turn an impossible challenge into a manageable task.
Testing Cocktails
Computational models are excellent at predicting the highest-performing cocktails, but they still must be evaluated. Testing these cocktails across a variety of conditions ensures that we select cocktails in which all of the phages complement, rather than antagonize, each other, allowing robust bactericidal activity and mitigation of resistance development.
Enhancing Cocktails
Millions of years of co-evolution has produced an ecological balance between phage and their bacterial prey. Synthetic biology allows us to tip the balance in favor of phage killing the target bacteria by enhancing phage with bactericidal payloads.
Manufacturing Drug Product
We built an award-winning manufacturing facility that allows us to strategically control the manufacturing of our products, enabling us to move into and through clinical development at a lower cost and a faster pace than we could if we were relying on external manufacturing partners.
Contact
If you are interested in working with us on developing precision medicines, please reach out below.
