Chen Yang, an intern reporter of this newspaper, and Cao Xueping, reported from Shanghai
In 2016, the world's first blockbuster small nucleic acid drug spinraza (nusinersen) was approved for marketing by the US FDA. Since then, small nucleic acid drugs have frequently appeared in people's field of vision.
Recently, sirnaomics ltd., an innovative company dedicated to the research and development of small nucleic acid drugs, submitted a prospectus to the Hong Kong Stock Exchange, with CICC as the sole sponsor. 49.6% of the net proceeds from the IPO will be used for the development and commercialization of the core product candidate, stp705. With the withdrawal of Ruibo Bio's application for the IPO of the Science and Technology Innovation Board, Shengnuo Pharmaceutical may become the first stock of domestic small nucleic acid drugs.
At present, Only the core candidate product stp705 of Sunno Pharmaceutical has entered Phase II clinical trials, and there are great variables in whether it can be successfully listed in the future.
In fact, Roche, Pfizer, Abbott and Merck all invested heavily in the development of the first generation of RNAI drugs. However, the early clinical trials of related drugs were not satisfactory, and the giants had to stop the loss and exit.
Only one product entered Phase II clinical trials
Sunno Pharma claims to be the first and currently the only clinical-stage RNA therapy biopharmaceutical company with a significant market position in both China and the United States, and the first company to achieve positive Phase Iia clinical results in the field of oncology RNAI treatment. Its core product, stp705, is used to treat cholangiocarcinoma, non-melanoma skin cancer (NMSC) and hypertrophic scarring.
Since its development, small nucleic acid drugs have been hampered by delivery systems.
Professor Hua Yimin, the inventor of the small nucleic acid drug Spinraza and the founder of Antian Shengshi Medicine, told the reporter of China Business Daily: "Now the target organs of small nucleic acid drugs are mostly concentrated in the liver. Because the liver itself has an enrichment effect, coupled with an efficient and stable gallnac delivery system, it can meet the requirements of druggability. The key behind is whether the delivery system can act on targets outside the liver. ”
Sunno Pharma's prospectus shows that the company leverages transformative proprietary peptide nanoparticles (PNPs) and the new Gallac RNAI delivery platform. The former allows for local or intravenous administration, is lowly toxic, easy to manufacture, and has the ability to reach target organs other than the liver; the latter enables highly efficient specific delivery of liver cells. At the same time, the two delivery platforms are also able to knock down two different target genes to create a synergistic effect.
The prospectus shows that the core product, stp705, uses pnp enhanced delivery technology to directly knock down the expression of tgf-β1 and cox-2. At present, STP705 has successfully completed a phase IIA interim clinical study in the United States for the treatment of NMSCs( especially in situ squamous cell carcinoma ISSCC). The company launched a phase Iib study of ISSCC in the U.S. in May 2021 and expects to achieve interim results in the second half of 2021 and a Phase II study of non-melanoma basal cell carcinoma (BCC) treatment in the fourth quarter of 2020.
Meanwhile, the company was admitted to an IND review by the FOOD and Drug Administration in June 2021 as part of a global multi-center study conducted in China for the ISSCC clinical Iib phase. The Phase II clinical trial of stp705 for the prevention of keloidscar has completed the first patient administration, and the study for the treatment of hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) has also entered the phase I clinical phase.
At present, There is no commercial marketing of Products for Shengnuo Pharmaceuticals. According to the prospectus, in 2019, 2020 and the first five months of 2021, the other revenue of Shengnuo Pharmaceutical was $440,000, $771,000 and $85,000, respectively, and the corresponding losses for the period were $17.127 million, $46.428 million and $23.339 million, respectively. During the reporting period, Shengnuo Pharmaceutical incurred R&D expenses of US$10.213 million, US$14.894 million and US$9.766 million, respectively.
On July 2, 2021, the company announced the completion of a $105 million Series E funding round. According to the prospectus, the company's valuation after the e-round financing is US$657 million, or about 4.2 billion yuan.
The industrial chain needs to be further improved
In fact, the global research and development of small nucleic acid drugs has gone through more than 20 years of history. At present, small nucleic acid drugs mainly include small interfering RNA (sirna) and antisense oligonucleotide (ASO). Unlike small molecules and antibody drugs that target proteins, small nucleic acid drugs directly intervene in the expression of disease-related genes from the MNA level, which has the characteristics of short research and development cycle, more accurate and effective, and long-lasting efficacy.
Hua Yimin believes: "There is a large market for small nucleic acid drugs as the third type of drugs after small molecules and antibody proteins. In the future, we can try different drug types to compare, some indications may have an advantage in nucleic acid drugs, and some may have an advantage in proteins. ”
According to the data of the CCI Consulting Report, the current global market size of RNAI therapy has increased from US$12 million in 2018 to US$362 million in 2020, with a compound annual growth rate of 449.2%, and it is estimated to reach US$21 billion by 2030. By 2030, the market size of RNAI therapy applied to common diseases and oncology will account for 49% of the total market size.
Compared with foreign veteran small nucleic acid pharmaceutical companies such as alkylam and ionis, there is still a gap in the field of domestic small nucleic acid drug creation. As Lu Yang, founder and CEO of Sunno Pharmaceutical, said in an interview with the Science and Technology Innovation Board Daily reporter: "There are almost 10 listed companies in this field in the United States, and the market value of flagship company arnylam has exceeded 15 billion US dollars, but there is no listed company specializing in nucleic acid interference pharmaceuticals in China." ”
At present, there are more than 20 sirna drugs and 50 aso drugs in the clinical research stage worldwide, and the therapeutic fields cover the central nervous system, cardiovascular, anti-infection and tumor. A total of 4 sirna drugs and 9 ASO drugs have been approved for marketing. Among them, spinraza reached sales of $2.097 billion in 2019, becoming the first "blockbuster" in the field of small nucleic acid drugs.
Relevant data show that as of 2020, there are 10 small nucleic acid drugs that have been clinically studied in China, including 5 sirna drugs and 5 ASO drugs, involving antiviral, hereditary blood diseases, metabolic diseases and cardiovascular diseases. At present, except for spinraza, which is listed as an orphan drug, no other small nucleic acid drugs have been approved for marketing.
In addition, Hua Yimin mentioned to reporters that the domestic small nucleic acid drug industry chain needs to be further improved. "Two or three years ago, only a handful of companies in China could provide ASO synthesis services, the price was very expensive, and the quality was uneven. But this year the situation has changed significantly, with several companies offering high-quality synthesis services and prices gradually falling. ”
In addition, Ruibo Biotech, another small nucleic acid head enterprise in China, completed a C+ round of financing of 250 million yuan in September 2020, with a cumulative financing of more than 1.3 billion yuan, and submitted a prospectus for the Science and Technology Innovation Board on December 29, 2020, but withdrew its application for the IPO of the Science and Technology Innovation Board in May this year.
(Editor: Yan Qiaoru Proofreader: Yan Jingning)