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Almost everyone did not notice that the cumulative market value of the three CRISPR listed companies tripled between June 2017 and June 2018, with a cumulative market value of nearly $6 billion. However, in the past six months, the market value of these three companies has fallen by nearly half due to the unsatisfactory clinical trial progress.

The three companies are Editas Medicine (about $1.3 billion) founded by Zhang Feng and others; the Swiss drug research and development company CRISPR Therapeutics (about $1.9 billion) co-founded by Emmanuelle Charpentier and others, and the Intellia Therapeutics of Jennifer Doudna (about $700 million).

Although the research community has frequently published good news about the third generation of genetic editing CRISPR technology. But so far, no compliant human clinical trial results have been published to prove the value promised. This article reviews the recent developments of three star companies.

 

01
CRISPR Therapeutics

Founded in Switzerland in 2013, Therapeutics is the only company in the three celebrity listed companies that has been approved for entry into the clinical trial phase.

In October 2015, Vertex announced that it will pay $75 million in cash and $30 million in equity investments, working with the company’s four-year contract to develop CRISPR-Cas9 drugs for existing human genetic confirmation targets. Mainly cystic pulmonary fibrosis and sickle type anemia.

In December 2017, Vertex and CRISPR began working together to develop CTX001. CTX001 is an experimental in vitro autologous hematopoietic stem cell CRISPR gene editing therapy. The preparation and treatment steps include: collecting hematopoietic stem cells from patients, introducing CTX001, using gene editing technology to generate a genetic alteration, and causing hematopoietic stem cells to produce HbF. These genetically edited hematopoietic stem cells are returned to the patient to produce red blood cells containing high levels of HbF, thereby overcoming the hemoglobin deficiency leading to these diseases, alleviating the transfusion needs of patients with beta thalassemia and the pain and decay of patients with sickle cell disease. Sickle cell crisis.

In May of this year, Vertex/CrisPR obtained permission to conduct CTX001 Phase I/II clinical studies on beta thalassemia and sickle cell disease in Europe. This is the world’s first human clinical research in CRISPR gene editing initiated by pharmaceutical companies.

 

CRISPR company product pipeline

Currently, European Phase I/II studies for the treatment of beta thalassemia are recruiting patients with transfusion-dependent beta thalassemia, and both said they will begin CTX001 for European Phase I/II clinical studies of sickle cell disease by the end of 2018.

The FDA treats genetic editing more carefully than the EU. At the end of May, the FDA suspends the IND application for CTX-001, saying that some questions about the clinical trial need to be answered by the applicant. Until October 10, the FDA released the clinical shelving of the experimental gene editing therapy CTX001 and has accepted the experimental new drug application (IND) for the treatment of sickle cell disease. This will also be the first human clinical trial in the United States for CRISPR gene editing therapy.

However, in a brief statement announcing the clinical suspension, the two companies did not specify what concerns the FDA had before, nor how the two sides resolved them.

 

02
Editas Medicine

Founded in 2013, Editas Medicine is a biotechnology company that is co-founded by MIT’s Zhang Feng and others. It was once thought to be the first pharmaceutical company to conduct human clinical trials of gene editing technology. In 2017, a CRISPR gene editing therapy was initiated to treat a rare type of blindness clinical trial (LCA10, also known as EDIT-101).

Editas product pipeline

However, due to CMC issues, the timetable for submitting the IND was postponed until 2018. The company’s third quarter report showed that the clinical trial application of EDIT-101 was submitted to the FDA in October for the treatment of Leber congenital amaurosis type 10 (LCA10).

LCA10 (EDIT-101) gene editing process

One of the founders of Editas Medicine also attended the second International Summit on Human Gene Editing in Hong Kong. He pointed out that “there are still many problems in gene editing technology. Experimenting on humans should not be done.” Supporting the suspension of transplants through editing embryos, he believes that the practices in the CCR5 trial will need to be opened until a set of well-considered security measures have been established.

 

03
Intellia Therapeutics

The pioneer of the company, Jennifer Doudna, is one of the founders of Intellia. The company was founded in 2014. In the same year, it completed a $15 million financing for the A round, and completed the B round of $70 million financing in the following year. Investors include the Atlas Venture Capital Fund. Aobo Capital and so on.

Intellia product pipeline

In January 2015, Intellia and the leading position in CAR-T, Novartis, launched a five-year R&D cooperation program to jointly study hematopoietic stem cell-related diseases including sickle cell disease and β-thalassemia. To accelerate the development of CRISPR/Cas9 technology in CAR-T cell therapy and hematopoietic stem cells.

On April 11, 2016, Intellia and Regeneron reached a six-year collaborative development protocol for CRISPR gene editing therapy. Regeneron paid Intellia a prepayment of $75 million and agreed to invest $50 million in Intellia’s next round of equity financing. The two sides developed a total of 10 drugs during the cooperation period, and Regeneron can select 5 targets outside the field of liver disease.

It is not difficult to find out from the company pipeline. To this day, the company’s rapid progress is in the treatment of transthyretin amyloidosis project with Regeneron, and the sickle cell disease project in cooperation with Novartis. stage. At the same time, the company’s Q3 financial report showed that the time to submit the IND in 2019 was postponed to 2020.

 

04
Conclusion

From the perspective of the number and quality of papers: The new generation of CRISPR technology is easier and cheaper to operate than the previous two generations, which is very helpful for the commercial development of gene editing technology. However, in the middle of the year, there were academic papers saying that “some CRISPR cells may lack a key anti-cancer mechanism, so they can cause tumors.” The news caused the market value of these three companies to shrink rapidly.

In addition to the three main CRISPR companies listed above, there are some genetic editing companies in the United States that deserve attention. For example, Horizon Discovery, which has been involved in the early rAAV technology to ZFN and the hot CRISPR technology in recent years, has been edited using zinc finger nuclease (ZFN) gene and has several projects in Phase I/II clinical Sangamo Therapeutics. Precision BioSciences, etc., a new generation of ARCUS genome editing platform.

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