Gene therapy on the vent – a list of 157 companies worldwide

In recent years, gene therapy has been listed one after another, allowing us to see the possibility of gene therapy landing, we have inventoried the gene therapy pipelines of 157 gene therapy companies and some companies around the world one by one, starting from the clinical stage, technical path, and technological frontier, in order to explore the technical overview
of the entire gene therapy field.

1 Look at the stage

Define gene therapy first: intervention at the DNA level, including gene addition or gene editing, excluding cell therapy (CAR-T, etc.
).

Companies with a primary business in gene therapy and some pharmaceutical companies with gene therapy pipelines were included in our analysis
.
First, the company is divided into the highest clinical trial stages of its gene therapy pipeline to briefly summarize the stage in which the company is located
.
(Figure 1)

As can be seen from the figure, there are very few companies in clinical phase III and beyond, more than half of the companies are in the mechanism exploration and preclinical research stage, but at the same time, nearly 1/3 of the companies are about to enter or have entered the early clinical stage
.
It can be seen that the vast majority of gene therapy companies are still in the early stage of technology and clinical exploration, and the opportunities and risks are the
same.
The overall situation can be said to be the stage of large-scale seeding, and technical research and clinical exploration will be the main theme
of the future development of gene therapy.

The vast majority of gene therapy companies are still in the early stage of technology and clinical exploration, and the opportunities and risks are the
same.

Figure 1 Overview of the highest stage of the pipeline of gene therapy companies (source: the official website of each company; Fengshuo Venture Capital finishing)

2 Look at the technology

In recent years, gene editing technology has gradually matured, and companies with gene editing as the core technology have entered the field of gene therapy to strongly promote gene therapy
.
Looking at the technology path of all companies, in vivo editing is the mainstream, AAV technology has almost become the standard for gene therapy companies, 101 of the 157 companies have laid out AAV platforms, compared to the number
of companies that use lipid nanoparticles (LNP) as the carrier to achieve gene editing.
At the same time, the target parts of in vivo editing are relatively concentrated, mainly targeting CNS, eye and liver, and a small number of companies layout in vitro editing to achieve delivery
by lentiviral (LV) and other means.

In vivo editing is the mainstream, AAV technology has almost become the target site of in vivo editing as a standard for gene therapy companies, mainly targeting the CNS, eye and liver

Figure 2 Technology profile of gene therapy companies (Source: official websites of each company; Fengshuo Venture Capital finishing)

We have listed the clinical stage III and later as a mature stage and have seen past successful experiences; Listing the proof-of-concept and preclinical research phases as early stages to see current trends
.
Mature stage companies are mainly AAV delivery, multi-targeted CNS, eye, liver and other fields, basically representing the main trend of all gene therapy companies; In the early stages of the company, AAV is still the mainstream but the proportion has declined, and many other delivery methods have been explored and new targeting locations have emerged (Figure 3
).
It can be seen that more mature companies in the field of gene therapy mostly use AAV and LV vectors, mainly targeting CNS, eyes and liver; In addition to the layout of AAV vectors, emerging gene therapy companies have explored some new vectors and new
targets.

It can be seen that more mature companies in the field of gene therapy mostly use AAV and LV vectors, mainly targeting CNS, eyes and liver; In addition to the layout of AAV vectors, emerging gene therapy companies have explored some new vectors and new
targets.

Figure 3 Technical layout of companies in the initial stage and mature companies (source: the official website of each company; Fengshuo Venture Capital finishing)

3 Look at the frontier

After gaining a basic understanding of technology, we summarize some of the representative companies
that are at the forefront of technology.

1.
AAV carrier frontier company - grasp the targeting

1.
AAV carrier frontier company - grasp the targeting

Askbio is a pioneer of AAV gene therapy, and its founders used AAV for gene therapy for the first time, making the concept of gene therapy truly land.

At present, the company's AAV technology platform has three development priorities: capsid, promoter, and production, which basically represents the current research trend
in the field of AAV.
The capsid section is designed to enhance AAV targeting and develop a new generation of chimeric carriers; The promoter section aims to effectively control gene expression and enhance the selectivity of tissues and cells, and develop some tissue-specific synthesis promoters and inducible promoters; The production part aims to increase AAV capacity, and the company has developed the Pro10™ - HEK293-based suspension cell line, which claims to be the largest and yield platform
for AAV vector production.
The company is currently acquired
by Bayer.
The Glybera developed by UniQure is the world's first marketed AAV vector gene therapy product, and the safety and efficacy of its AAV technology have been initially verified clinically
.
In addition, BioMarin, Spark (Roche acquisition) and AveXis (Novartis acquisition) have also developed AAV vector gene therapy products
that have been listed.
Regenxbio is a cutting-edge AAV gene therapy company with a NAV technology platform focused on developing novel AAV vectors to improve targeting
.
At present, more than 100 new AAV carriers have been developed, and more than 10 companies and more than 20 pipelines
have been authorized to cooperate.
2.
Lentiviral vector frontier company - Bluebird bio company with mature technology has listed two lentiviral vector gene therapy products in succession: Skysona and Zynteglo, which are also the only lentiviral vector gene therapy products
on the market.
These two products are in vitro therapy, with lentivirus as the carrier of the gene of interest, in vitro integrated into the hematopoietic stem cells taken out by the patient, and then infused back into the patient, the safety and efficacy of the technology have also been preliminarily verified clinically
.
3.
Gene editing frontier company - CRISPR technology, providing a new platform for gene therapy, has opened the era of
gene editing.
CRISPR/Intellia/Editas are the three giants of CRISPR technology, and it is worth mentioning that Editas has developed Sleek technology to improve the efficiency of gene knock-in, further optimizing gene editing technology
.
Beam has developed base editing technology, and its gene therapy products using base editing technology have also entered the clinical stage
.
There is also Sangamo's exclusive zinc finger enzyme technology, and the fastest growing pipeline has also entered clinical phase
III.
The chart below is a summary
of the list of gene therapy companies in this study.

AskbioAAV gene therapy pioneer The company's AAV technology platform has three development priorities: capsid, promoter, and production, which basically represents the current research trend
in the field of AAV.
UniQure's world's first marketed AAV vector gene therapy product has been preliminarily verified
in clinical terms for the safety and efficacy of AAV technology.
BioMarinSparkAve XisRegenxbio has developed more than 100 new AAV carriers, authorized more than 10 companies and more than 20 pipelines
.
2.
Lentiviral vector frontier company - mature technology Bluebird bio has listed two lentiviral vector gene therapy products on the market The safety and efficacy of the only lentiviral vector gene therapy product on the market have also been preliminarily verified clinically
.
3.
Gene editing frontier company - CRISPR/Intellia/EditasBeamSangamo, a new platform for gene therapy

Figure 4 Summary of gene therapy companies/pipeline technologies (Source: official websites of each company; Fengshuo Venture Capital finishing)

epilogue

The most fascinating but also dangerous thing about gene therapy is that it is genetically modified
.
One treatment, a lifetime cure, but it is also possible to go to the other extreme
.
Looking at the pipeline situation of these companies recently, most of the companies are still in the same running line, and the technical means and layout areas are gradually increasing
.
Gene therapy has just opened its doors, with broad directions, opportunities and risks
.