 | |
| Industry | |
|---|---|
| Founded | 2006 in Durham, North Carolina |
| Founders |
|
Key people | Michael Amoroso (President and CEO) |
| Revenue | $115.5 million [1] |
Number of employees | 192 [2] (2022) |
| Website | precisionbiosciences |
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. [4]
Derek Jantz and Jeff Smith met as postdoctoral fellows at Duke University, [5] and in March 2006, they founded Precision BioSciences along with Matt Kane, a student at the Duke Fuqua School of Business at the time. [3] The company went through two rounds of early funding: a Series A round led by venBio to fund development of the genome editing platform, [6] and Series B financing to fund product development efforts. [7] [8] The company completed its initial public offering in 2019, and trades under the Nasdaq ticker DTIL. [9] [10]
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, [11] beginning with Duchenne muscular dystrophy. [12] 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, [13] and with Philadelphia-based iECURE to advance candidates into clinical trials and investigate how ARCUS can help treat liver diseases. [11] 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. [14]
Precision BioSciences' proprietary technology is the ARCUS platform and ARCUS nucleases. [4] [8] ARCUS nucleases are based on a naturally occurring genome editing enzyme, I-CreI, a homing endonuclease that evolved in the algae Chlamydomonas reinhardtii [4] [12] 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. [12] [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. [4] [19] The company also uses ARCUS for in vivo gene editing programs, [4] some of which are in preclinical development as of May 2022. [20] [18]
Similar to I-CreI, ARCUS nucleases generate a unique cleavage site in DNA that is characterized by four-base-pair, 3' overhangs. [4] ARCUS nucleases can perform a range of complex edits, including gene insertion, gene excision, and gene repair. [8] [15] ARCUS nucleases are able to enact all editing operations in one step, which enables efficient multiplexing of edits. [19]
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. [15] The company is also pursuing PBGENE-PCSK9, a candidate to treat familial hypercholesterolemia, and PBGENE-PH1, a candidate to treat primary hyperoxaluria type 1. [21] [22]
Precision is in the process of developing multiple candidates targeting non-Hodgkin lymphoma, acute lymphoblastic leukemia (ALL), [4] [19] and multiple myeloma. [23] The company's lead candidate targeting CD19, PBCAR0191, [19] 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 [26] 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. [26] 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. [26] 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. [23]
Gene therapy is a medical technology that aims to produce a therapeutic effect through the manipulation of gene expression or through altering the biological properties of living cells.
In biology, chimeric antigen receptors (CARs)—also known as chimeric immunoreceptors, chimeric T cell receptors or artificial T cell receptors—are receptor proteins that have been engineered to give T cells the new ability to target a specific antigen. The receptors are chimeric in that they combine both antigen-binding and T cell activating functions into a single receptor.
B-lymphocyte antigen CD19, also known as CD19 molecule, B-Lymphocyte Surface Antigen B4, T-Cell Surface Antigen Leu-12 and CVID3 is a transmembrane protein that in humans is encoded by the gene CD19. In humans, CD19 is expressed in all B lineage cells. Contrary to some early doubts, human plasma cells do express CD19, as confirmed by others. CD19 plays two major roles in human B cells: on the one hand, it acts as an adaptor protein to recruit cytoplasmic signaling proteins to the membrane; on the other, it works within the CD19/CD21 complex to decrease the threshold for B cell receptor signaling pathways. Due to its presence on all B cells, it is a biomarker for B lymphocyte development, lymphoma diagnosis and can be utilized as a target for leukemia immunotherapies.
Adoptive cell transfer (ACT) is the transfer of cells into a patient. The cells may have originated from the patient or from another individual. The cells are most commonly derived from the immune system with the goal of improving immune functionality and characteristics. In autologous cancer immunotherapy, T cells are extracted from the patient, genetically modified and cultured in vitro and returned to the same patient. Comparatively, allogeneic therapies involve cells isolated and expanded from a donor separate from the patient receiving the cells.
André Choulika is a biotechnologist, the inventor of nuclease-based genome editing and a pioneer in the analysis and use of meganucleases to modify complex genomes.
Genome editing, or genome engineering, or gene editing, is a type of genetic engineering in which DNA is inserted, deleted, modified or replaced in the genome of a living organism. Unlike early genetic engineering techniques that randomly inserts genetic material into a host genome, genome editing targets the insertions to site-specific locations. The basic mechanism involved in genetic manipulations through programmable nucleases is the recognition of target genomic loci and binding of effector DNA-binding domain (DBD), double-strand breaks (DSBs) in target DNA by the restriction endonucleases, and the repair of DSBs through homology-directed recombination (HDR) or non-homologous end joining (NHEJ).
The NK-92 cell line is an immortalised cell line that has the characteristics of a type of immune cell found in human blood called ’natural killer’ (NK) cells. Blood NK cells and NK-92 cells recognize and attack cancer cells as well as cells that have been infected with a virus, bacteria, or fungus. NK-92 cells were first isolated in 1992 in the laboratory of Hans Klingemann at the British Columbia Cancer Agency in Vancouver, Canada, from a patient who had a rare NK cell non-Hodgkin-lymphoma. These cells were subsequently developed into a continuously growing cell line. NK-92 cells are distinguished by their suitability for expansion to large numbers, ability to consistently kill cancer cells and testing in clinical trials. When NK-92 cells recognize a cancerous or infected cell, they secrete perforin that opens holes into the diseased cells and releases granzymes that kill the target cells. NK-92 cells are also capable of producing cytokines such as tumor necrosis factor alpha (TNF-a) and interferon gamma (IFN-y), which stimulates proliferation and activation of other immune cells.
Kite Pharma is an American biotechnology company that develops cancer immunotherapy products, with a primary focus on genetically engineered autologous CAR T cell therapy, a cell-based therapy which relies on chimeric antigen receptors and T cells. Founded in 2009, and based in Santa Monica, California, it was acquired by Gilead Sciences in 2017.
Juno Therapeutics Inc was an American biopharmaceutical company founded in 2013 through a collaboration of the Fred Hutchinson Cancer Research Center, Memorial Sloan-Kettering Cancer Center and pediatrics partner Seattle Children's Research Institute. The company was launched with an initial investment of $120 million, with a remit to develop a pipeline of cancer immunotherapy drugs. The company raised $300 million through private funding and a further $265 million through their IPO.
Editas Medicine, Inc.,, is a clinical-stage biotechnology company which is developing therapies for rare diseases based on CRISPR gene editing technology. Editas headquarters is located in Cambridge, Massachusetts and has facilities in Boulder, Colorado.
Tisagenlecleucel, sold under the brand name Kymriah, is a CAR T cells medication for the treatment of B-cell acute lymphoblastic leukemia (ALL) which uses the body's own T cells to fight cancer.
Intellia Therapeutics is a clinical-stage biotechnology company focused on developing novel, potentially curative therapeutics leveraging CRISPR-based technologies. The company's in vivo programs use intravenously administered CRISPR as the therapy, in which the company's proprietary delivery technology enables highly precise editing of disease-causing genes directly within specific target tissues. Intellia's ex vivo programs use CRISPR to create the therapy by using engineered human cells to treat cancer and autoimmune diseases.
Sangamo Therapeutics, Inc. is an American biotechnology company based in Brisbane, California. It applies cell and gene therapy to combat haemophilia and other genetic diseases.
Locus Biosciences is a clinical-stage pharmaceutical company, founded in 2015 and based in Research Triangle Park, North Carolina. Locus develops phage therapies based on CRISPR–Cas3 gene editing technology, as opposed to the more commonly used CRISPR-Cas9, delivered by engineered bacteriophages. The intended therapeutic targets are antibiotic-resistant bacterial infections.
bluebird bio, Inc., based in Somerville, Massachusetts, is a biotechnology company that develops gene therapies for severe genetic disorders.
Michel Sadelain is an genetic engineer and cell therapist at Memorial Sloan Kettering Cancer Center, New York, New York, where he holds the Steve and Barbara Friedman Chair. He is the founding director of the Center for Cell Engineering and the head of the Gene Transfer and Gene Expression Laboratory. He is a member of the department of medicine at Memorial Hospital and of the immunology program at the Sloan Kettering Institute. He is best known for his major contributions to T cell engineering and chimeric antigen receptor (CAR) therapy, an immunotherapy based on the genetic engineering of a patient's own T cells to treat cancer.
BeiGene is a global biotechnology company that specializes in the development of drugs for cancer treatment. Founded in 2010 by Xiaodong Wang and chief executive officer John V. Oyler, the company has offices in Asia, North America, Australia and Europe. BeiGene has developed several pharmaceuticals, including tislelizumab, a checkpoint inhibitor, and zanubrutinib, a Bruton's tyrosine kinase inhibitor.
Mammoth Biosciences is a biotechnology company based in Brisbane, California developing diagnostic tests using CRISPR-Cas12a and CRISPR-based therapies using its proprietary ultra-small CRISPR systems. Several CRISPR-Cas systems identified through the company's metagenomics-based protein discovery platform, including members of the Casφ and Cas14 families of CRISPR-associated enzymes, have demonstrated potential for therapeutic genome editing in in vivo settings.
Regenerative Medicine Advanced Therapy (RMAT) is a designation given by the Food and Drug Administration to drug candidates intended to treat serious or life-threatening conditions under the 21st Century Cures Act. A RMAT designation allows for accelerated approval based surrogate or intermediate endpoints.
Cellular adoptive immunotherapy is a type of immunotherapy. Immune cells such as T-cells are usually isolated from patients for expansion or engineering purposes and reinfused back into patients to fight diseases using their own immune system. A major application of cellular adoptive therapy is cancer treatment, as the immune system plays a vital role in the development and growth of cancer. The primary types of cellular adoptive immunotherapies are T cell therapies. Other therapies include CAR-T therapy, CAR-NK therapy, macrophage-based immunotherapy and dendritic cell therapy.
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.
{{cite journal}}: Cite journal requires |journal= (help){{cite journal}}: Cite journal requires |journal= (help){{cite journal}}: Cite journal requires |journal= (help)