Locus Biosciences
Locus Biosciences is a clinical-stage pharmaceutical company, founded in 2015 and based in Research Triangle Park, North Carolina which to develop phage therapies based on CRISPR–Cas3 gene editing technology, as opposed to the more commonly used CRISPR-Case9, delivered by engineered bacteriophages. The intended therapeutic targets are antibiotic-resistant bacterial infections. History. The company was founded as a spin-off from North Carolina State University (NCSU) in 2015 with licensed CRISPR patents from NCSU. The company started with a $5 million convertible note from Tencent Holdings and North Carolina Biotechnology Center. In 2017, the company  closed a $19 million Series A led by Artis Ventures, Tencent Holdings Ltd, and Abstract Ventures. In 2020, the company sold convertible notes in a debt raise to roll into its next equity round in 2021. In 2018, Locus acquired the high-throughput bacteriophage discovery platform from San Francisco-based phage therapy company Epibiome, Inc. In 2019, the company entered into a strategic collaboration with Janssen Pharmaceuticals (a Johnson & Johnson company) worth up to $818 million to develop CRISPR-Cas3 drugs targeting two bacterial pathogens. Locus received $20 million upfront and up to $798 million in  milestones and royalties on net sales. In 2020, the company signed a $12.5 partnership with the global non-profit, Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator (CARB-X). In 2020 the company signed a $144 million partnership with BARDA. In November 2020, Locus had 52 people and planned to expand to 85 by 2021. CRISPR CAS3. CRISPR-Cas3 is more destructive than the better known CRISPR–Cas9 used by companies like Caribou Biosciences, Editas Medicine, Synthego, Intellia Therapeutics, CRISPR Therapeutics and Beam Therapeutics. CRISPR–Cas3 destroys the targeted DNA in either prokaryotic or eukaryotic cells. Co-founder, Rodolphe Barrangou , said "Cas3 is a meaner system...but if you want to cut a tree and get rid of it, you bring a chain saw, not a scalpel". CRISPR-Cas systems fall into two classes. Class 1 systems use a complex of multiple Cas proteins to degrade foreign nucleic acids. Class 2 systems use a single large Cas protein for the same purpose. Class 1 is divided into types I, III, and IV; class 2 is divided into types II, V, and VI. The 6 system types are divided into 19 subtypes. Many organisms contain multiple CRISPR-Cas systems suggesting that  they are compatible and may share components. Clinical trial. The company enrolled its first patient in a Phase 1b clinical trial in January 2020. The trial intends to evaluate LBP-EC01, a CRISPR Cas3-enhanced bacteriophage against "Escherichia coli" bacteria which cause urinary tract infections. Twenty patients will get a phage cocktail, and 10 will get a placebo.