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In 2006, Stanford University professor Andrew Z. Fire and University of Massachusetts Medical Professor Craigc. Mello won the 2006 Nobel Prize in Physiology/Medical for discovering RNA interference (RNAi) and their outstanding contributions in the field of gene silencing.

At the time of the award, they predicted that the application of RNA interference (RNAi) or small interfering RNA (siRNA) would develop a completely new treatment. From the following events, it can be said that 2018 is the tipping point of this prophecy. In other words, it is no exaggeration to call 2018 the year of RNA therapy.

  • In June, Translate Bio (renamed from RaNa Therapeutics last year) completed its own small IPO, raising about $113.4 million;
  • In August, Alnylam’s RNAi drug Onpattro was approved by the US FDA and became the first RNAi drug that was found to have been approved for the entire 20-year period.
  • In early December, the biotech company Moderna Therapeutics raised $604.3 million in its initial public offering (IPO), creating the largest biotech IPO ever;
  • Two more RNA companies were renamed this year: Marina Biotech changed its name to Adhera Therapeutics on October 9th; RXi Pharmaceuticals changed to Phio Pharmaceuticals on November 19.

 

According to Grand View Research, the global market for antisense RNA and RNAi therapeutics will increase at a compound annual growth rate (CAGR) of 8.6% from 2018-2025 and will reach $1.81 billion by 2025. Although the market size is not very large, it also represents a treatment direction.

Recently, the foreign biotechnology website GEN released the list of the top ten RNA therapy companies in 2018, including five listed companies and five non-listed companies. The ranking of listed companies is based on income, and the ranking of non-listed companies is based on raised funds (including financing and cooperation).

Both Alnylam and Moderna are on the list, and Translate Bio is not on the list because it did not generate enough revenue since it was just listed. The following are the top 10 biopharmaceutical companies that specialize in RNA therapy.

 

Listed company

 

01
Ionis Pharmaceuticals

Revenue: $50,766,600 (2017); $407.559 million (Q1-Q3, 2018)

More than half of Ionis Pharmaceuticals’ revenue (55%) is due to research and development, and the rest comes from commercial activities – including Spinal Muscle Atrophy (SMA) drug Spinraza (nusinersen), which was developed in collaboration with Biogen, which has nearly tripled royalties ( $168 million).

On December 6 this year, based on positive data from a Phase I study, Biogen chose to develop BIIB067 for the treatment of a subtype of ALS. Ionis received a $35 million advance payment and a chance to receive a total of $55 million in milestones. The royalties are used.

In August, Ionis and its subsidiary Akcea received a FDA approval letter from the FDA for its familial chylomicron syndrome candidate Waylivra (volanesorsen) NDA, which was temporarily suspended. However, Akcea claims that Waylivra is still expected to be approved in Europe and is continuing to communicate with the FDA on regulatory details.

 

02
Moderna

Revenue: $206 million (2017); $114 million (Q1-Q3, 2018)

On December 7, Moderna was launched on the NASDAQ Global Select Market, creating the largest biotech IPO ever. Although the price of Moderna fell by $4.4 and closed at $18.6, the company raised $604.3 million by selling 26.3 million shares.

Moderna said the proceeds were mainly used for the development of mRNA technology platforms and to further promote the discovery, clinical development and production capacity of its 21 drug candidates.

According to the prospectus, Moderna’s mRNA therapy differs depending on the coding region. Each drug is similar to “life software”. Cells use mRNA to convert DNA into proteins needed for body functioning. This is like implanting a pharmaceutical factory in a patient. To achieve personalized treatment.

 

03
Alnylam Pharmaceuticals

Revenue: $89.912 million (2017); $53.875 million (Q1-Q3 2018)

Alnylam’s RNAi drug Onpattro (patisiran) was approved by the US FDA on August 10 for the treatment of multiple neuropathy caused by hATTR in adult patients. The approval is a milestone because Onpattro is the first RNAi drug that has been approved for marketing in the past 20 years. On August 30th, the EU also approved the drug.

The financial report shows that Alnylam’s revenue this year is almost entirely from cooperation. Although Onpattro has begun to generate revenue, its $500,000 sales in the third quarter accounted for only a small portion of the company’s revenue.

On December 6, Alnylam announced its 2019 R&D program, which includes continuing to promote Onpattro’s global commercialization and launching a phase III clinical trial of the ATTR amyloid candidate vutrisiran.

04
Akcea Therapeutics

Revenue: $55.209 million (2017); $54.67 million (Q1-Q3, 2018)

Akcea’s revenue for the first three quarters of this year was almost the same as last year’s full year, thanks to a $12 million license revenue from the company’s partnership with PTC Therapeutics and a doubling of R&D revenue. Last year, Akcea and Novartis established a partnership. Novartis paid Akcea’s $75 million in research and development amortization and bought shares in Akcea’s parent company Ionis for a premium of $33 million.

In July of this year, Ionis and Akcea’s RNA-targeted therapy Tegsedi (inotersen) was approved by the European Union for RNA targeted therapy for adult hereditary transthyretin-mediated amyloidosis (hATTR) polyneuropathy. Three months later, the drug was also approved by the US FDA.

 

05
Arrowhead Pharmaceuticals

Revenue: US$31.408 million (Fiscal Year ended September 30, 2017); US$16.142 million (Fiscal Year 2018)

Arrowhead’s cooperation agreement reached in 2018 accounted for almost half of the entire RNA therapy industry, shocking peers. In early October, Arrowhead partnered with Johnson & Johnson, a Johnson & Johnson company, to develop RNAi drug candidates for hepatitis B (HBV) and three additional RNAi therapies for Janssen. The total amount of the cooperation agreement exceeds $3.7 billion.

The deal provides Janssen with a worldwide exclusive license to Arrowhead’s ARO-HBV program to develop a third-generation subcutaneous injection of RNAi drug candidates, which is expected to be a potential method for patients with chronic HBV.

On November 9, Arrowhead announced a positive I/II phase of ARO-HBV, saying it “effectively reduces all measurable viruses, including HBsAg [hepatitis B surface antigen].” Arrowhead also announced second-generation RNAi Therapy ARO-AAT treats a phase I outcome of a rare hereditary liver disease associated with alpha-1 trypsin (AAT) deficiency.

 

Unlisted company

 

06
BioNTech

Total funds raised: more than 1 billion US dollars

In December 2017, BioNTech, under the leadership of the Redmile Group, raised $270 million in Series A funding to advance its clinical immunotherapy pipeline, ranking first in the mRNA-based individualized anticancer vaccine (IVAC®) Mutanome and FixVAC® Cancer Vaccine.

In December 2008, BioNTech received $180 million in financing from the seed round. In August, BioNTech and Pfizer reached a strategic partnership to develop an mRNA-based influenza vaccine. The partnership received $120 million in advance payments, equity and recent research funding from Pfizer, and may also bring BioNTech a total of $305 million. Milestone payment. In addition to Pfizer, BioNTech has also entered into strategic partnerships with several other biopharmaceutical giants and biotech companies, including Roche’s Genentech, Eli Lilly, Sanofi, Genmab, and Bayer Animal Health.

 

07
CureVac

Total funds raised: about 450 million euros (about 511 million US dollars)

CureVac released promising data at the 2018 Annual Meeting of the Society for Cancer Immunotherapy (SITC) in November: 1 patient who received his solid tumor candidate CV8102 was observed to have complete regression of injected and non-injected lesions, and 4 The patient achieved stable disease in a phase I clinical study (NCT03291002).

The TLR-/RIG-I agonist CV8102 is one of CureVac’s four clinical stage candidates, and the project has worked with the Gates Foundation, Boehringer Ingelheim, CRISPR Therapeutics, Arcturus Therapeutics, Acuitas, and Lilly.

Last October, CureVac and Lilly reached a total of $1.795 billion in cooperation to develop up to five cancer vaccines. In May of this year, CureVac announced that it will expand its financial and scientific operations in Boston while retaining its global headquarters and manufacturing facilities in Tubingen, Germany.

08
Gradalis

Total funds raised: $89 million

Gradalis has entered an expansion phase, completing a $55 million Series C financing and upgrading its cGMP manufacturing facility in Carrollton, Texas, USA to support its immunotherapeutic platform Vigil in combination with the chemotherapy drug irinotecan and A phase III registration trial of temozolomide for Ewing’s sarcoma (NCT03495921).

Ewing’s sarcoma is one of several advanced oncology indications being developed by the Vigil platform; in addition to this indication, the Vigil platform will also conduct joint studies with immunological checkpoint inhibitors for advanced gynaecology and other female cancers. Gradalis raised $10 million in Series B financing in 2013 and raised $10 million in Series A financing six years ago.

 

09
Quark Pharmaceuticals

Total funds raised: $61.4 million

Since 2010, Quark Pharmaceuticals has not announced public financing, except that it has completed $10 million in private financing for existing investors (ie Japan’s SBI Holdings Group). However, Quark has been busy developing new siRNA therapies to meet unmet medical needs.

On October 20-28, at the 2018 American Society of Nephrology (ASN) in San Diego, Quark published a one-year death follow-up data from a phase II clinical study (NCT02610283), which evaluated p53 gene-targeting siRNA drug teprasiran (formerly known as QPI-1002) The efficacy and safety of patients with high-risk acute kidney injury after cardiac surgery.

QPI-1007, a siRNA candidate targeting the Caspase 2 gene, is being developed for use in the treatment of non-arterial ischemic optic neuropathy (NAION). According to Crunchbase, Quark actually raised $61.4 million in total capital, but the company has not responded to the data as of the date of the posting.
 

10
Gotham Therapeutics

Total funds raised: $54 million

On October 10 this year, Gotham Therapeutics announced the completion of a $54 million Series A financing, which is probably the youngest RNA therapy company. Founding investors include Versant Ventures, Forbion and S.R. One, and two leading investors – biotech giant Shinki and Alexandria Venture Investments of Alexandria Real Estate.

Based on the findings of co-founder Dr. Samie Jaffrey and early seed round funding, Gotham has developed an epitranomics platform to assess the effects of RNA-modified proteins on disease biology and to develop small molecules for priority targets. .

Dr. Samie Jaffrey is a pioneer in epigenetic transcriptomics in the field of RNA metabolism, and his work reveals the role of post-transcriptional mRNA modification in health and disease.

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