In 2017, the company closed a $19 million Series A led by Artis Ventures, Tencent Holdings Ltd, and Abstract Ventures.[7][8] In 2020, the company sold convertible notes in a debt raise to roll into its next equity round in 2021.[9]
In 2018, Locus acquired a high-throughput bacteriophage discovery platform from San Francisco-based phage therapy company Epibiome, Inc.[10][11]
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.[7][12][13][14] Locus received $20 million upfront and up to $798 million in milestones and royalties on net sales.[15]
In 2020, the company signed a $12.5 million partnership with the global non-profit, Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator (CARB-X).[9] In November 2020, Locus had 52 employees;[9] by the end of 2021, it had about 80 employees.[4] As of January 2022, the company and all employees were contained in a single 25,000 square foot research and manufacturing facility.[4]
In 2022, the company closed a $35 million Series B funding round, with participation from Artis Ventures, Tencent, Viking Global Investors, and Johnson & Johnson.[16] Locus announced in September 2022 that it had begun patient treatment in its trial of LBP-EC01, in partnership with the BARDA, for the treatment of UTIs caused by E coli bacteria.[17]
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.[7] CRISPR–Cas3 destroys the targeted DNA in either prokaryotic or eukaryotic cells.[12][18] 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".[19]
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.[20] The 6 system types are divided into 19 subtypes.[21] Many organisms contain multiple CRISPR-Cas systems suggesting that they are compatible and may share components.[22][23]
Difference between CRISPR-Cas3 and CRISPR-Cas9
Class
Cas type
Signature protein
Function
Reference
1
I
Cas3
Single-stranded DNA nuclease (HD domain) and ATP-dependent helicase
Nucleases RuvC and HNH together produce DSBs, and separately can produce single-strand breaks. Ensures the acquisition of functional spacers during adaptation.
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.[28] Twenty patients will get a phage cocktail, and 10 will get a placebo.[29] The trial completed before March 2021 and a Phase II trial is expected to start within two years.[2] The company has an agreement the US government's Biomedical Advanced Research and Development Authority which began in 2020 and provides funding to support Phase II and Phase III trials.[2][9]
Publications
Kim, Paul; Sanchez, Ana M.; Penke, Taylor J. R.; Tuson, Hannah H.; Kime, James C.; McKee, Robert W.; Slone, William L.; Conley, Nicholas R.; McMillan, Lana J.; Prybol, Cameron J.; Garofolo, Paul M. (August 9, 2024). "Safety, pharmacokinetics, and pharmacodynamics of LBP-EC01, a CRISPR-Cas3-enhanced bacteriophage cocktail, in uncomplicated urinary tract infections due to Escherichia coli (ELIMINATE): the randomised, open-label, first part of a two-part phase 2 trial". The Lancet Infectious Disease. 24 (12): 1319–1332. doi:10.1016/S1473-3099(24)00424-9. PMID39134085.
