2019 Global Top 10 Gene Editing Companies: CRISPR Pioneers Zhang Feng, Jennifer Doudna, and Emmanuelle Charpentier All Represented

There are currently three main types of gene editing in use: Zinc Finger Nucleases (ZFNs), Transcription Activator-Like Effector Nucleases (TALENs), and Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR). All three types target specific DNA sequences and excise them from the genome. ZFNs are the oldest gene editing method, dating back to the 1990s. This was the only gene editing method available until the discovery of TALENs in 2009, which offered more precise targeting of DNA sequences.

The year 2012 can be regarded as the inaugural year of gene-editing technology, as CRISPR was discovered in that year. CRISPR is considered the most accurate, effective, rapid, and simple gene-editing tool, enabling scientists to edit or modify the genomes of nearly any organism with greater precision than ever before. In recent years, the term “CRISPR” has continued to generate significant excitement across both scientific and non-scientific communities.

Recently, GEN, the most authoritative global magazine in biotechnology, released the “Top 10 Gene Editing Companies of 2019.” The list includes five publicly traded companies and five privately held companies in the gene editing sector. The publicly traded companies were ranked based on their 2018 revenues, which encompassed income from product sales or services, as well as collaborations and research and development activities. The privately held companies were ranked according to their total disclosed capital raised.

Compared with the 2018 list, companies associated with the “three pioneers” of CRISPR—Feng Zhang, Jennifer Doudna, and Emmanuelle Charpentier—still appear on the 2019 list. What has changed is that CRISPR Therapeutics, co-founded by Emmanuelle Charpentier, dropped out of the Top 5 listed companies due to its revenue performance, while Casebia, a joint venture established by CRISPR Therapeutics and Bayer, made it onto the Top 5 private companies list.

The following is the list of the top 10 gene editing companies worldwide in 2019:

Top 5 Listed Companies

#1.Sangamo Therapeutics

Established in: 1995

2018 Revenue: $84.452 million

Sangamo Therapeutics is a clinical-stage biopharmaceutical company engaged in drug development through gene editing technologies, with a focus on the research, development, and commercialization of zinc finger protein (ZFP) technology. As the global leader in the application of zinc finger protein technology, the company is advancing a series of clinical-stage therapies for human diseases. Leveraging a multi-platform approach based on gene therapy—including gene therapy, genome editing, cell therapy, and gene regulation—Sangamo has built a product pipeline targeting hemophilia, hemoglobinopathies, central nervous system disorders, and HIV/AIDS.

Sangamo’s 2018 revenue more than doubled compared to the $36.567 million reported in 2017, thanks to collaborations with Kite (a Gilead company) and Pfizer. Recently, Sangamo researchers have focused on enhancing genome editing using zinc-finger nucleases (ZFNs). On July 29, the Sangamo team published an article in Nature Biotechnology stating that they engineered two key functional domains within the ZFN structure: modulating the binding affinity of the zinc-finger array responsible for DNA recognition, and slowing the catalytic rate of the FokI cleavage domain. These two complementary approaches can be combined to achieve nearly 100% target modification with no detectable off-target effects. In March of this year, the Sangamo team reported in Nature Communications that they had developed new ZFN architectures through a series of protein engineering efforts. These modifications included reversing the order of the DNA-binding domain and the nuclease domain, as well as employing novel linkers to skip bases between adjacent zinc fingers. Through this strategy of structural diversification, they aimed to substantially improve the targeting precision of ZFNs.

#2. Horizon Discovery Group

Year Established: 2005

2018 Revenue: £58.7 million ($71.186 million)

Horizon Discovery is headquartered in Cambridge, UK. Its technological core lies in gene editing, with over a decade of experience in the field. Horizon holds patent licenses for technologies ranging from early recombinant adeno-associated virus (rAAV) techniques and zinc finger nucleases (ZFNs) to the widely adopted CRISPR technology in recent years.

Horizon Discovery’s 2018 revenue increased by 68% compared to 2017. This growth was also driven by its recent collaborations: Celyad is developing the first non-gene-edited allogeneic CAR-T clinical program using Horizon Discovery’s SMARTvector™ short hairpin RNA (shRNA) technology platform. In 2018, AstraZeneca adopted Horizon Discovery’s Edit-R crRNA library as part of its functional genomics discovery platform. Furthermore, Biocartis’ Idylla™ microsatellite instability (MSI) assay is supported by cell line-derived reference standards developed by Horizon Discovery.

#3. Editas Medicine

Established in: 2013

2018 Revenue: $31.977 million

Headquartered in Massachusetts, USA, Editas Medicine was co-founded by Zhang Feng, a luminary in the CRISPR field. The company is developing a genome-editing platform based on CRISPR/Cas9 technology patents, dedicated to treating diseases by modifying patients’ disease-causing genes. Currently, the company has established a diverse pipeline, including products targeting ocular diseases, muscular disorders, blood disorders, pulmonary diseases, hepatic diseases, and cancer.

Driven by collaborations with Beam Therapeutics, Juno Therapeutics (acquired by Celgene last year), and particularly Allergan, Editas Medicine more than doubled its collaboration and other research and development revenue in 2018 compared to the $13.7 million reported in 2017. In April, Editas Medicine and Allergan announced that the first-in-human clinical trial of in vivo CRISPR therapy would commence in the second half of 2019. This initiative is also a top priority for Cynthia Collins, who was appointed Interim Chief Executive Officer in March of this year and named permanent President and Chief Executive Officer on August 6.

#4. Intellia Therapeutics

Establishment Year: 2014

2018 Revenue: $30.344 million

Intellia Therapeutics, headquartered in Massachusetts, USA, focuses on leveraging the CRISPR/Cas9 system as a biological tool to develop proprietary, potentially curative therapies. As the strongest competitor of Editas Medicine, Intellia has licensed relevant intellectual property from Jennifer Doudna, a pioneering female scientist in the field of CRISPR.

Intellia’s collaborations with Novartis and Regeneron Pharmaceuticals drove a 16.5% increase in the company’s revenue, rising from $26.117 million in 2017. Meanwhile, Intellia and Regeneron are collaborating on the Intellia-led NTLA-2001 program, building on their partnership initiated in 2016. In December 2018, Intellia expanded its cell therapy collaboration with Novartis to include ocular stem cells (for which Novartis paid Intellia $10 million) and secured expanded access to Novartis’ lipid nanoparticle (LNP) library.

#5. Precision BioSciences

Establishment Year: 2006

2018 Revenue: USD 10.883 million

Precision BioSciences, headquartered in North Carolina, USA, is dedicated to developing applications of its next-generation genome editing technology platform, ARCUS, in cancer immunotherapy, genetic diseases, and the food sector. In the field of cancer immunotherapy, the company aims to use genome editing technology to excise genes that cause patients’ immune systems to attack donor T cells and that cause donor T cells to attack patients’ healthy tissues in CAR-T or TCR cell therapies. This approach enables cancer patients to receive T-cell therapies derived from healthy donors, thereby no longer being limited to relying on their own T cells.

Since completing its initial public offering (IPO) on April 1 this year, Precision BioSciences has begun patient dosing in the Phase I/IIa trial (NCT03666000) of PBCAR0191. PBCAR0191 is the company’s first gene-edited allogeneic anti-CD19 CAR T-cell product, developed in collaboration with Servier. In July, Precision established the Manufacturing Center for Advanced Therapies (MCAT) in Durham, North Carolina. The company states that this is currently the first cGMP-compliant in-house manufacturing facility in the United States dedicated to off-the-shelf CAR-T cell therapies based on genome editing. Following completion of commissioning, qualification, and validation, MCAT will commence cGMP production in the fourth quarter.

Top 5 Private Companies

#1. Casebia

Established: 2016

Total Amount of Funds Raised: $300 million

Casebia Therapeutics is a 50-50 joint venture established by CRISPR Therapeutics and Bayer, aimed at leveraging gene-editing technology to develop treatments for blood disorders, as well as autoimmune, metabolic, and congenital heart diseases.

Upon the establishment of Casebia, Bayer agreed to invest at least $300 million in R&D in CRISPR Therapeutics over the next five years, plus an additional $35 million in cash to acquire a minority stake in CRISPR Therapeutics. Last month, at the 2019 Congress of the International Society on Thrombosis and Haemostasis, Dr. Alan Brooks, Chief Scientific Officer of Casebia, reported on research into a gene-editing approach that uses CRISPR-Cas9 to achieve stable, titratable factor VIII expression in mice, thereby managing the production of factor VIII for the treatment of hemophilia A.

#2.Poseida Therapeutics

Year Founded: 2014

Total Amount of Funds Raised: $226.5 million

Poseida Therapeutics is a clinical-stage biopharmaceutical company dedicated to translating best-in-class non-viral gene engineering technologies into life-saving therapies for the treatment of various challenging diseases. The company is independently developing autologous and allogeneic CAR-T cell therapy candidates for the treatment of hematologic malignancies, solid tumors, and certain rare genetic disorders.

In April this year, Poseida Therapeutics announced the completion of a $142 million Series C financing round, led by Novartis with a $75 million investment. Poseida stated that it would use these funds to comprehensively advance its ongoing CAR-T programs, including gene therapies for rare genetic diseases. In May this year, Poseida received orphan drug designation from the FDA for its CAR-T candidate drug, named P-BCMA-101, for the treatment of relapsed and/or refractory multiple myeloma (r/rMM).

#3. Beam Therapeutics

Year Established: 2018

Total Funds Raised: $222 million

Beam Therapeutics is the first company to leverage CRISPR single-base editing technology to develop novel therapies, co-founded by three luminaries in the CRISPR field: Feng Zhang, David Liu, and J. Keith Joung. At its inception, the company announced the completion of an $87 million Series A financing round. In March of this year, it further announced the closing of a $135 million Series B financing round. The funds will be used to advance the development of next-generation CRISPR technologies, expand its leadership in base editing technology, and propel its product pipeline into clinical development.

In May, Beam and the Japanese biotechnology company Bio Palette announced an exclusive cross-licensing agreement regarding their respective base editing intellectual property (IP). Meanwhile, Beam also licensed its technology to Harvard University, the Broad Institute, MIT, and Editas Medicine through multiple platforms.

#4.Synthego

Establishment Date: 2012

Total amount of funds raised: USD 158 million

Headquartered in Silicon Valley, California, Synthego is a company that provides genetically engineered cells to scientists and researchers. The company was founded by brothers Paul Dabrowski and Michael Dabrowski, who previously worked at SpaceX, the company established by Elon Musk, before formally entering the bioscience sector.

One month before being listed on Forbes’ 2019 Billion-Dollar Startup Club, Synthego announced a groundbreaking development—the launch of its Gene Knockout Kit v2. Designed to ensure robust gene knockout by leveraging a novel bioinformatics-driven multi-guide strategy that employs up to three modified single-guide RNAs (sgRNAs) targeting the same gene, the kit enables scientists to avoid extensive trial-and-error optimization in CRISPR experiments, thereby accelerating research. In October 2018, Synthego completed a $110 million Series C financing round led by Founders Fund, raising more than two-thirds of its total capital.

#5.Inscripta

Year Established: 2015

Total Amount of Funds Raised: US$134.5 million

Inscripta is a gene-editing technology company headquartered in Colorado, USA, dedicated to creating revolutionary gene-editing technologies and tools that bring transformation to human food, fuel, and healthcare.

At the 2019 Synthetic Biology: Engineering, Evolution & Design (SEED) conference, Inscripta publicly unveiled its latest CRISPR-based technology for the first time, which aims to achieve multiplexed, trackable cell editing at an unprecedented scale. Leveraging cutting-edge principles of CRISPR gene editing, the company has developed a family of CRISPR enzymes known as MADzymes. These enable researchers and commercial partners to customize nucleases as needed, along with a comprehensive suite of gene-editing tools—including software, instruments, and reagents—that significantly enhance the speed and efficiency of gene editing. In April this year, Inscripta announced an additional $20 million in funding, bringing the total for this round to $105.5 million, building upon its $85.5 million Series C financing raised in 2018.

[1] Top 10 Companies Leveraging Gene Editing in 2019

[2] Top 10 Companies Leveraging Gene Editing in 2018

[3] 5 Top Gene-Editing Stocks for 2019

[4] Top 10 Global Gene Editing Companies: The Youngest Was Founded Just One Year Ago

[5] GEN Inventory: Top 10 Global Gene Editing Companies, with All Three CRISPR “Pioneers” Included