Precision BioSciences explained

Precision BioSciences, Inc.
Type:Public
Traded As:
Founded: in Durham, North Carolina
Key People:Michael Amoroso (president and CEO)
Owners:-->
Revenue:$115.5 million[1]
Num Employees:192[2]
Num Employees Year:2022

Precision BioSciences, Inc. is a publicly traded American clinical stage gene editing company headquartered in Durham, North Carolina.[3] Founded in 2006, Precision is focused on developing both in vivo and ex vivo gene editing therapies using its proprietary "ARCUS" genome editing platform.

History

Derek Jantz and Jeff Smith met as postdoctoral fellows at Duke University,[4] and in March 2006, they founded Precision BioSciences along with Matt Kane, a student at the Duke Fuqua School of Business at the time. The company went through two rounds of early funding: a Series A round led by venBio to fund development of the genome editing platform,[5] and Series B financing to fund product development efforts.[6] [7] The company completed its initial public offering in 2019, and trades under the Nasdaq ticker DTIL.[8] [9]

Precision entered into a partnership with Eli Lilly in November 2020 to use ARCUS editing for up to six in vivo targets connected to genetic disorders,[10] beginning with Duchenne muscular dystrophy.[11] In September 2021, Precision announced two more collaborations, with UK biotechnology company Tiziana Life Sciences to explore using foralumab to aid chimeric antigen receptor (CAR) T cell therapy,[12] and with Philadelphia-based iECURE to advance candidates into clinical trials and investigate how ARCUS can help treat liver diseases.[10] Michael Amoroso, the former CEO of cell and gene therapy developer Abeona Therapeutics, succeeded Matt Kane as President and CEO in October 2021.[3] That December, Precision announced its entry into an agreement with a syndicate of investors led by ACCELR8 to spin off its subsidiary, Elo Life Systems, and create an independent company focused on food and agriculture business.[13]

ARCUS genome editing

Precision BioSciences' proprietary technology is the ARCUS platform and ARCUS nucleases. ARCUS nucleases are based on a naturally occurring genome editing enzyme, I-CreI, a homing endonuclease that evolved in the algae Chlamydomonas reinhardtii[14] to make highly specific cuts and DNA insertions in cellular DNA.[15] The nuclease is able to deactivate itself once gene edits are made, which minimizes potential off-targeting.[11] [16] An ARCUS nuclease is also much smaller in size than CRISPR spCas9.[17] It can use either adeno-associated virus (AAV) vectors or lipid nanoparticles (LNPs) for delivery to specific tissues and cells.[18] Precision has used ARCUS nucleases to develop multiple ex vivo allogeneic, "off-the-shelf" CAR T cell immunotherapies in early-stage clinical trials.[14] The company also uses ARCUS for in vivo gene editing programs, some of which are in preclinical development as of May 2022.[19]

Similar to I-CreI, ARCUS nucleases generate a unique cleavage site in DNA that is characterized by four-base-pair, 3' overhangs.[14] ARCUS nucleases can perform a range of complex edits, including gene insertion, gene excision, and gene repair.[7] [15] ARCUS nucleases are able to enact all editing operations in one step, which enables efficient multiplexing of edits.

Precision has demonstrated some additional applications of the ARCUS platform, including treating ornithine transcarbamylase deficiency in newborn nonhuman primates and in the use of a LNP to treat chronic Hepatitis B. The company is also pursuing PBGENE-PCSK9, a candidate to treat familial hypercholesterolemia, and PBGENE-PH1, a candidate to treat primary hyperoxaluria type 1.[20] [21]

Clinical trials

Precision is in the process of developing multiple candidates targeting non-Hodgkin lymphoma, acute lymphoblastic leukemia (ALL),[14] [22] and multiple myeloma.[23] The company's lead candidate targeting CD19, PBCAR0191,[22] received orphan drug designation from the U.S. Food and Drug Administration for the treatment of ALL and mantle cell lymphoma, an aggressive subtype of non-Hodgkin lymphoma, as well as fast track designation for the treatment of B-cell ALL.[23] PBCAR0191 began its Phase 1/2a clinical trial of adult subjects in March 2019.[24] [23] In June 2022, Precision reported a 100% response rate, a 73% complete response rate, and a 50% durable response rate, and the company sought to increase enrollment in the study.[25] [26]

Precision is also developing PBCAR19B as an anti-CD19 stealth cell candidate that employs a single gene edit to knock down beta-2 microglobulin, for which a Phase 1 study began in June 2021.[27] [28] The company is also conducting a Phase 1/2a clinical trial evaluating PBCAR269A, its investigational allogeneic B-cell maturation antigen-targeted CAR T cell therapy, for the treatment of multiple myleloma. PBCAR269A began its Phase 1 trials in April 2020,[29] and as of July 2022 had moved onto recruitment for its Phase 1/2a study, which features PBCAR269A in combination with nirogacestat, a gamma secretase inhibitor. In 2020, the FDA granted fast track designation to PBCAR269A for the treatment of relapsed or refractory multiple myeloma, having previously provided orphan drug designation.

Notes and References

  1. Precision BioSciences Reports Fourth Quarter and Fiscal Year 2021 Financial Results and Provides Business Update . 9 August 2022 . Precision BioSciences . 15 March 2022.
  2. News: Form 10-Q: Quarterly report which provides a continuing view of a company's financial position . 9 August 2022 . Precision BioSciences . 30 June 2022.
  3. News: Ezzone . Zac . Executive voice: New leader joins Durham biotech chasing permanent cures . 22 July 2022 . Triangle Business Journal . 24 February 2022.
  4. Graff . Gregory D. . Sherkow . Jacob S. . 2020-08-31 . Models of Technology Transfer for Genome-Editing Technologies . Annual Review of Genomics and Human Genetics . en . 21 . 1 . 509–534 . 10.1146/annurev-genom-121119-100145 . 32151165 . 2142/110346 . 212652569 . 1527-8204. free .
  5. News: Saxena . Varun . Gene editing player gets $25M in Series A round . 8 August 2022 . Fierce Pharma . 12 May 2015 . en.
  6. Web site: Precision BioSciences Closed on a $110 Million Series B Financing . Terry . Mark . 8 August 2022 . BioSpace . en-US . 26 June 2018.
  7. Web site: Taylor . Nick Paul . 26 June 2018 . Precision BioSciences bags $110M to take off-the-shelf CAR-T into humans . 8 August 2022 . Fierce Biotech . en.
  8. Web site: Precision Biosciences S-1 Filing . 1 March 2019 . 2022-08-08 . U.S. Securities and Exchange Commission.
  9. Web site: Precision BioSciences Launches IPO to Raise $126.4 Million . Terry . Mark . 28 March 2019 . 8 August 2022 . BioSpace . en-US.
  10. News: Terry . Mark . Precision Signs Another Collab for ARCUS Genome Editing Platform . 22 July 2022 . BioSpace . 9 September 2021.
  11. News: Idrus . Amirah Al . Lilly, Precision Biosciences team up on Duchenne gene therapy in $135M deal . 22 July 2022 . Fierce Biotech . 20 November 2020 . en.
  12. News: Precision BioSciences and Tiziana Life Sciences partner on foralumab . 16 August 2022 . The Pharma Letter . 2 September 2021.
  13. News: Ezzone . Zac . Durham biotech spins out food, agriculture company . 22 July 2022 . Triangle Business Journal . 27 December 2021.
  14. News: Shaffer . Catherine . Novel Gene Editing Systems Come Into Their Own . 22 July 2022 . Genetic Engineering and Biotechnology News . 5 January 2022.
  15. News: Bayer . Max . Precision BioSciences makes case for 2 gene editing programs over CRISPR with preclinical data . Fierce Biotech . 8 August 2022 . May 23, 2022.
  16. News: Weintraub . Arlene . In vivo gene editing grabs the spotlight after Intellia triumph, but challenges loom . 9 August 2022 . Fierce Biotech . 29 September 2021 . en.
  17. 10.1016/j.ymthe.2020.08.012. Therapy in Rhodopsin-Mediated Autosomal Dominant Retinitis Pigmentosa . 2020 . Meng . Da . Ragi . Sara D. . Tsang . Stephen H. . Molecular Therapy . 28 . 10 . 2139–2149 . 32882181 . 7545001 . "Given that Cas9 genes themselves are approaching the size limit of AAV vectors, usage of long promoters to increase specificity and expression level is prohibited. ... ARCUS meganuclease is much smaller (~300 aa) and does not require gRNAs, making it easier to deliver via a single AAV vector.".
  18. 10.1016/j.ymthe.2022.05.013. Targeting the hepatitis B cccDNA with a sequence-specific ARCUS nuclease to eliminate hepatitis B virus in vivo . 2022 . Gorsuch . Cassandra L. . Nemec . Paige . Yu . Mei . Xu . Simin . Han . Dong . Smith . Jeff . Lape . Janel . Van Buuren . Nicholas . Ramirez . Ricardo . Muench . Robert C. . Holdorf . Meghan M. . Feierbach . Becket . Falls . Greg . Holt . Jason . Shoop . Wendy . Sevigny . Emma . Karriker . Forrest . Brown . Robert V. . Joshi . Amod . Goodwin . Tyler . Tam . Ying K. . Lin . Paulo J.C. . Semple . Sean C. . Leatherbury . Neil . Delaney Iv . William E. . Jantz . Derek . Rhoden Smith . Amy . Molecular Therapy . 30 . 9 . 2909–2922 . 35581938 . 9481990 . 248849628 . free .
  19. News: Sarkar . Anjali A. . Preclinical Study Shows Safety, Efficacy, and Durability of Lowering LDL-Cholesterol Levels Long-Term in Non-Human Primates . 9 August 2022 . GEN - Genetic Engineering and Biotechnology News . 23 February 2021.
  20. News: Haskins . Bryant . Precision Biosciences inks gene editing deal with iECURE . 24 August 2022 . WRAL TechWire . 18 September 2021.
  21. News: Precision and Iecure ink collaboration deal . 24 August 2022 . The Science Advisory Board . 9 September 2021.
  22. News: Amorosi . Drew . One-step gene-editing technique opens door to safe, effective off-the-shelf CAR T cells . 22 July 2022 . Healio . 10 August 2021 . en.
  23. News: CAR T-cell Therapies for the Treatment of Patients with Acute Lymphoblastic Leukemia . 9 August 2022 . Onco'Zine . 13 October 2020.
  24. Precision BioSciences, Inc. . 2022-04-18 . Phase 1/2a, Open-label, Dose-escalation, Dose-expansion, Parallel Assignment Study to Evaluate Safety and Clinical Activity of PBCAR0191 in Subjects With Relapsed/Refractory (r/r) Non-Hodgkin Lymphoma (NHL) and r/r B-cell Acute Lymphoblastic Leukemia (B-ALL) .
  25. News: Bayer . Max . Precision hails phase 1/2 data as proof it could deliver the first approved off-the-shelf CAR-T . 8 August 2022 . June 8, 2022.
  26. Web site: Precision BioSciences Releases Data on CAR T Therapy Candidates . 2022-08-08 . PharmTech . 13 June 2022 . en.
  27. News: McConaghie . Andrew . 'We'll Be First With Off-The-Shelf CAR-T,' Vows Precision Biosciences – And Hopes To Win Over Gene-Editing Skeptics . 9 August 2022 . Informa Pharma Intelligence . 30 March 2022.
  28. Precision BioSciences, Inc. . 2022-03-01 . A Phase 1 Study of PBCAR19B in Participants With CD19-expressing Malignancies .
  29. Precision BioSciences, Inc. . 2021-06-24 . A Phase 1/2a, Open-label, Dose-escalation, Dose-expansion Study to Evaluate the Safety and Clinical Activity of PBCAR269A, With or Without Nirogacestat, in Study Participants With Relapsed/Refractory Multiple Myeloma .

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