Company:Locus Biosciences

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Short description: Clinical phase American pharmaceutical company
Locus Biosciences
TypePrivately held company
IndustryPharmaceutical company
FoundedMay 22, 2015; 8 years ago (2015-05-22) in Raleigh, NC, USA
Founders
  • Paul Garofolo[1][2]
  • Nick Taylor
  • Dave Ousterout
  • Rodolphe Barrangou[3]
  • Charles Gersbach
  • Chase Beisel
  • Ahmed Gomaa
Headquarters
Morrisville, North Carolina
,
United States
BrandscrPhage
Number of employees
80[4] (2021)
Websitewww.locus-bio.com

Locus Biosciences is a clinical-stage pharmaceutical company, founded in 2015 and based in Research Triangle Park, North Carolina.[2] Locus develops phage therapies based on CRISPR–Cas3 gene editing technology, as opposed to the more commonly used CRISPR-Cas9, delivered by engineered bacteriophages.[5] The intended therapeutic targets are antibiotic-resistant bacterial infections.[1][5]

History

The company was founded as a spin-off from North Carolina State University (NCSU) in 2015 with licensed CRISPR patents from the university.[6][7] The company started with a $5 million convertible note from Tencent Holdings and North Carolina Biotechnology Center.[8]

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]

Phage injecting its genome into bacterial cell

CRISPR CAS3

Main page: Biology:CRISPR

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 [24][25]
2 II Cas9 Nucleases RuvC and HNH together produce DSBs, and separately can produce single-strand breaks. Ensures the acquisition of functional spacers during adaptation. [26][27]

Therapy development

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

As of 2022, there are no peer-reviewed publications that are solely or primarily authored by Locus Biosciences staff.[30]

References

  1. ↑ 1.0 1.1 Buhr, Sarah (December 21, 2018). "Move over Cas9, CRISPR-Cas3 might hold the key to solving the antibiotics crisis". TechCrunch. https://techcrunch.com/2016/12/21/move-over-cas9-crispr-cas3-might-hold-the-key-to-solving-the-antibiotics-crisis/. 
  2. ↑ 2.0 2.1 2.2 2.3 Eanes, Zachery (March 9, 2021). "Locus using gene-editing technology to get ahead of drug-resistant bacteria". The Herald-Sun: pp. B4. https://www.newspapers.com/clip/107926055/locus/. 
  3. ↑ Barrangou, R. (2019). "CRISPR on the Move in 2019". The CRISPR Journal 2: Affiliations. doi:10.1089/crispr.2019.29043.rba. PMID 31021232. https://pubmed.ncbi.nlm.nih.gov/31021232/. Retrieved August 19, 2022. 
  4. ↑ 4.0 4.1 4.2 Eanes, Zachery (January 29, 2022). "Locus Biosciences is eyeing immunology for its CRISPR tech". The News & Observer 158 (29): pp. A6. https://www.newspapers.com/clip/107931372/locus-biosciences/. 
  5. ↑ 5.0 5.1 Gibney, Elizabeth (January 2, 2018). "What to expect in 2018: science in the new year". Nature 553 (7686): 12–13. doi:10.1038/d41586-018-00009-5. PMID 29300040. Bibcode: 2018Natur.553...12G. 
  6. ↑ Brown, Kristen V. (February 24, 2017). "Scientists Are Creating a Genetic Chainsaw to Hack Superbug DNA to Bits". G/O Media. https://gizmodo.com/a-little-known-crispr-technique-could-be-the-key-to-fig-1792689477. 
  7. ↑ 7.0 7.1 7.2 7.3 Shieber, Jonathan (January 4, 2019). "Up to $818 million deal between J&J and Locus Biosciences points to a new path for CRISPR therapies". TechCrunch. https://techcrunch.com/2019/01/04/up-to-818-million-deal-between-jj-and-locus-biosciences-points-to-a-new-path-for-crispr-therapies/. 
  8. ↑ 8.0 8.1 Martz, Lauren (August 31, 2017). "Cutting through resistance". Biocentury. https://www.biocentury.com/bc-innovations/product-rd/2017-08-31/how-locus-biosciences-using-crispr-cas3-tackle-antibiotic-?. 
  9. ↑ 9.0 9.1 9.2 9.3 Maurer, Allan (November 19, 2020). "Gene editing success could turn Triangle startup Locus Biosciences into a billion dollar unicorn". WRAL TechWire (Capitol Broadcasting Company). https://www.wraltechwire.com/2020/11/19/gene-editing-success-could-turn-triangle-startup-locus-biosciences-into-a-billion-dollar-unicorn/. 
  10. ↑ "Locus Biosciences Acquires EpiBiome Bacteriophage Discovery Platform". Genomeweb. July 17, 2018. https://www.genomeweb.com/business-news/locus-biosciences-acquires-epibiome-bacteriophage-discovery-platform. 
  11. ↑ "CRISPR-Cas3 Platform Developer Locus Biosciences Acquires EpiBiome Phage Technology". Genetic Engineering & Biotechnology Nerws. July 17, 2018. https://www.genengnews.com/news/crispr-cas3-platform-developer-locus-biosciences-acquires-epibiome-phage-technology/. 
  12. ↑ 12.0 12.1 Taylor, Phil (January 3, 2019). "J&J takes stake in Locus' CRISPR-based 'Pac-Man' antimicrobials". Fierce Biotech. https://www.fiercebiotech.com/biotech/j-j-takes-stake-locus-crispr-based-pac-man-antimicrobials. 
  13. ↑ Molteni, Megan (January 16, 2019). "Antibiotics Are Failing Us. Crispr is Our Glimmer of Hope". Wired. https://www.wired.com/story/antibiotics-are-failing-us-crispr-is-our-glimmer-of-hope/. Retrieved March 8, 2019. 
  14. ↑ Schmidt, Charles (November 1, 2019). "Is Phage Therapy Here to Stay?". Scientific American: 50–57. https://www.scientificamerican.com/article/phage-therapy-could-beat-drug-resistant-illnesses/. Retrieved October 23, 2019. 
  15. ↑ Brown, Kristen (January 3, 2019). "J&J Bets $20 Million on DNA Tool to Battle Infectious Bacteria". Bloomberg. https://www.bloomberg.com/news/articles/2019-01-03/j-j-bets-20-million-on-dna-tool-to-battle-infectious-bacteria. 
  16. ↑ Jane Byrne (May 19, 2022). "Bacteriophage producer Locus Biosciences raises $35m in financing". BioPharma Reporter. https://www.biopharma-reporter.com/Article/2022/05/19/bacteriophage-producer-locus-biosciences-raises-35m-in-financing. 
  17. ↑ Emily Kimber (September 15, 2022). "Locus Biosciences announces first patient treated in urinary tract infection trial". PM Live. https://www.pmlive.com/pharma_news/locus_biosciences_announces_first_patient_treated_in_urinary_tract_infection_trial_1455586. 
  18. ↑ Reardon, Sara (2017). "Modified viruses deliver death to antibiotic-resistant bacteria". Nature 546 (7660): 586–587. doi:10.1038/nature.2017.22173. PMID 28661508. Bibcode: 2017Natur.546..586R. 
  19. ↑ Marcus, Amy Dockser. "A Genetic 'Chain Saw' to Target Harmful DNA". Wall Street Journal. https://www.wsj.com/articles/a-genetic-chain-saw-to-target-harmful-dna-1477081818. 
  20. ↑ "Biology and Applications of CRISPR Systems: Harnessing Nature's Toolbox for Genome Engineering". Cell 164 (1–2): 29–44. January 2016. doi:10.1016/j.cell.2015.12.035. PMID 26771484. 
  21. ↑ Westra, Edze R.; Dowling, Andrea J.; Broniewski, Jenny M.; van Houte, Stineke (November 2016). "Evolution and Ecology of CRISPR". Annual Review of Ecology, Evolution, and Systematics 47 (1): 307–331. doi:10.1146/annurev-ecolsys-121415-032428. https://zenodo.org/record/3452297. 
  22. ↑ "RNA-guided genetic silencing systems in bacteria and archaea". Nature 482 (7385): 331–8. February 2012. doi:10.1038/nature10886. PMID 22337052. Bibcode: 2012Natur.482..331W. 
  23. ↑ "A novel interference mechanism by a type IIIB CRISPR-Cmr module in Sulfolobus". Molecular Microbiology 87 (5): 1088–99. March 2013. doi:10.1111/mmi.12152. PMID 23320564. 
  24. ↑ "Cas3 is a single-stranded DNA nuclease and ATP-dependent helicase in the CRISPR/Cas immune system". The EMBO Journal 30 (7): 1335–42. April 2011. doi:10.1038/emboj.2011.41. PMID 21343909. 
  25. ↑ "Structures of CRISPR Cas3 offer mechanistic insights into Cascade-activated DNA unwinding and degradation". Nature Structural & Molecular Biology 21 (9): 771–7. September 2014. doi:10.1038/nsmb.2875. PMID 25132177. 
  26. ↑ "Cas9-crRNA ribonucleoprotein complex mediates specific DNA cleavage for adaptive immunity in bacteria". Proceedings of the National Academy of Sciences of the United States of America 109 (39): E2579–86. September 2012. doi:10.1073/pnas.1208507109. PMID 22949671. Bibcode: 2012PNAS..109E2579G. 
  27. ↑ "Cas9 specifies functional viral targets during CRISPR–Cas adaptation". Nature 519 (7542): 199–202. March 2015. doi:10.1038/nature14245. PMID 25707807. Bibcode: 2015Natur.519..199H. 
  28. ↑ "Locus Biosciences initiates world's first controlled clinical trial for a CRISPR enhanced bacteriophage therapy". January 8, 2020. https://www.locus-bio.com/media/locus-biosciences-initiates-worlds-first-controlled-clinical-trial/. 
  29. ↑ "Scientists Modify Viruses With CRISPR To Create New Weapon Against Superbugs". NPR. May 22, 2019. https://www.npr.org/sections/health-shots/2019/05/22/723582726/scientists-modify-viruses-with-crispr-to-create-new-weapon-against-superbugs. 
  30. ↑ "Locus Biosciences[Affiliation - Search Results - PubMed"] (in en). https://pubmed.ncbi.nlm.nih.gov/?term=Locus+Biosciences%5BAffiliation%5D&sort=. 



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