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The prototype of the best-selling book “The Billion-Dollar Molecule” in the pharmaceutical industry is Vertex. The company, which was founded in 1989, started with $10 million in funds and can be said to be a dark horse enterprise in the pharmaceutical industry. Vertex has created three drugs with annual sales of more than $1 billion (Cicumber Incc has been withdrawn). The company’s market value reached $45 billion for the first time in May 2018, ranking among the top 205 of global pharmaceutical companies.

In the latest version of the global pharmaceutical company TOP50, which is ranked according to 2018 prescription drug sales revenue, Vertex ranked 43rd with a revenue of $3,038 million in 2018. Vertex currently has three marketed drugs for the treatment of cystic fibrosis, but only for different types of subdivisions.


Take all CF patients

Cystic fibrosis (CF) is a rare, fatal genetic disease caused by defects or deletions in the CFTR protein caused by mutations in the cystic fiber transmembrane conductance regulator (CFTR) gene. The CFTR protein is a chloride channel located on the cell membrane. Mutations in the CFTR gene cause epithelial cells to fail to transport CI- normally. CI- and water accumulate in the cells, causing a large amount of mucus to block the systemic exocrine glands, leading to chronic obstructive diseases and pancreatic function. Incomplete, the main clinical manifestations are chronic cough, massive mucositis, long-term chronic abdominal, malabsorption syndrome, growth retardation and so on.

CF is an autosomal recessive disorder in which a child must inherit two defective CFTR genes from both parents to become ill. The CFTR gene is currently known to have approximately 2,000 mutations, which are rare in Asian populations and affect approximately 75,000 people in North America, Europe and Australia. The median age of death in CF patients is 25 to 30 years old.

Kalydeco (ivacaftor) was first approved by the FDA on September 20, 2012. It is the world’s first drug directly targeting the CF disease-causing gene and is known as “the most important drug in 2012.” Kalydeco is a CFTR potentiator that enhances the function of defective CFTR proteins by increasing the gated activity of the CFTR protein (the ability of ion transmembrane) to be used in CF patients with g551d mutations, which is available to approximately 4,900 patients worldwide to increase lung function.

Orkambi (ivacaftor / lumacaftor) is a two-component combination of drugs developed on the basis of Kalydeco. The lukaftor component is a CFTR correcting agent that improves the processing and transport functions of CFTR proteins. Orkambi was first approved for 2015/7/2 for CF patients with 2 copies of the F508del mutation, and approximately 25,000 patients worldwide benefit from it.

Another CF drug, Symdeko (ivacaftor / tezacaftor), was approved for FDA approval at 2018/2/12 for 12-year-old and above CFs carrying 2 copies of the F508del mutation or carrying a F508del mutation and a residual CFTR function mutation patients.


Vertex’s three CF drugs worldwide sales (US$ million)

According to Vertex’s external disclosure, these three flagship products have expanded the target population of CF patients from 39,000 to 44,000, and plan to expand the coverage population to 68,000 through three drug combination therapies, with the ultimate goal of genetic editing. The mRNA covers all 75,000 people with CF.


Plus code gene editing field

Vertex is developing new therapies for the treatment of Duchenne muscular dystrophy (DMD) and myotonic dystrophy type 1 (DM1) through a series of transactions to increase its expansion in the field of gene editing. These deals seem to reveal the ambitiousness of this pharmaceutical company that has just entered the age of standing.

Vertex announced on June 11 that it plans to acquire Exonics Therapeutics for approximately $1 billion and will invest an additional $1.175 billion in funding, which will be extended for three and a half years with CRISPR Therapeutics, and may eventually reach more than $2.5 billion in cooperation. The latter’s gene editing therapy was first introduced into human clinical trials.


— $1 billion acquisition of Exonics

Founded in February 2017 and headquartered in Watertown, Massachusetts, Exonics uses the SingleCut CRISPR for gene editing. Dr. Eric N. Olson, co-founder and Chief Scientific Advisor of the company, is a professor and chairman of the Department of Molecular Biology at the University of Texas Southwestern Medical Center (UTSW).

Dr. Eric N. Olson

Dr. Olson published a scientific study in October 2018. Exonics used SingleCut CRISPR to genetically repair and restore dystrophin in children with DMD. The results showed that dystrophin increased by 50% in skeletal muscle and increased by 90 in canine model. %.

Dr. Olson’s original intention to create Exonics was to develop treatments through genetic editing techniques that repair mutations that cause DMD and other hereditary neuromuscular diseases. “The DMD patient population needs new ways to treat and cure this devastating disease, and Exonics technology has the potential to significantly improve the lives of DMD patients.” It has provided seed funding for the establishment of Exonics and is one of the co-founders of Exonics. Debra Miller said.

Vertex said in an external statement that Exonics will become an independent wholly-owned subsidiary of Vertex. Exonics Equity Holders will be eligible for approximately $1 billion, including $245 million in advance payments and potential future payments, primarily related to the development and regulatory milestones for achieving DMD and DM1 programs.

The transaction will be completed in the third quarter of 2019. After Vertex completes the acquisition of Exonics, Olson will continue to serve as the lead scientific advisor to Exonics and provide oversight and guidance for the research and development of innovative gene editing therapies.


– Expanding the scope of cooperation with CRISPR

In addition to announcing the acquisition of Exonics, Vertex recently announced that it will expand its partnership with CRISPR Therapeutics. The two companies have signed an exclusive licensing agreement to discover and develop gene editing therapies for the treatment of DMD and DM1.

Prior to this, the two companies launched a collaboration of up to $2.5 billion in October 2015, and Vertex agreed to use CRISPR’s gene editing technology to discover and develop potential new therapies for CF and sickle cell disease.

In 2017, Vertex announced partial data on the treatment of CF in three triple-stage regimens in Phase I and Phase II clinical trials, and said it will further expand the beneficiaries of CF patients, prompting the company’s share price to soar by 25%.

In October 2018, Vertex/CRISPR launched a phase I clinical trial of gene editing therapy (NCT03655678) in the United States to evaluate CRISPR-Cas9-modified CD34+ human hematopoietic stem and progenitor cells (CTX001) in beta-thalassemia and sputum Safety and efficacy in patients with squamous cell disease.

This collaboration, Vertex has expanded the application of gene editing to the development of potential curative treatments for DMD and DM1. Vertex agrees to pay $175 million in advance payments to obtain exclusive global rights to CRISPR’s existing and future intellectual property, including basic CRISPR/Cas9 technology, novel endonuclease, single- and double-cleavage guide RNA, and DMD and DM1 gene editing AAV carrier for the product.

Vertex will be responsible for all related costs of research, development, manufacturing and commercialization activities in terms of DMD indications. In terms of DM1 indications, Vertex and CRISPR will share the research costs of the specified mRNA, and Vertex will be responsible for all other research, development, manufacturing, and commercialization costs.

In addition, Vertex also agreed to pay an additional $1 billion to CRISPR Therapeutics, including advances and milestones related to research, development, regulatory and business related DMD and DM1 indications. The Cisco fee is eligible for Vertex’s tiered royalties, which are used to extend the future net sales of any products that may result from the partnership.

After applying for the IND, CRISPR can choose to abandon DM1 milestones and royalties to jointly develop and co-commerce all DM1 products worldwide. The two companies said they expect the transaction to be completed in the third quarter of 2019.

In addition to the expansion of the Exonics acquisition and the CRISPR Therapeutics collaboration, Vertex also stated that it intends to strengthen its genetic editing related drug development by:

  • Establish a new genetic editing therapy research base in the Boston area, and develop vector development and CMC related to early research and gene therapy for indications of DMD and DM1.
  • Dr. John T. Gray was appointed Senior Vice President of Gene Therapy and entered into force on June 17. He previously served as CSO and Senior Vice President at Audites Therapeutics, where he and his team focused on rAAV gene therapy for neuromuscular and liver diseases.



Thirty years ago, the chemist Joshua Borg, who had left Mercer, founded Vertex, which had only a dozen scientists, $10 million in wind investment, no scientific research, and burned nearly $100,000 a week. The startup company was listed in just two years after the establishment of Borg.

The landing of pharmaceutical companies in the capital market is only a means, not a success. Until Vertex’s superior performance in the CF field, the capital market further recognized the value of the company. Now Vertex’s extensive layout in the field of gene editing can promote the company’s take-off in the next generation of therapy?

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