On December 6th, Sirnaomics Ltd.-B, a leading international biopharmaceutical company specializing in RNA therapy. (hereinafter referred to as "Sirnaomics") posted a post-hearing information set on the HKEx website, announcing the imminent launch of the public offering. China International Capital Corporation is the exclusive sponsor. This paper notes that Sirnaomics has already obtained five rounds of financing before IPO, and the existing shareholders include famous professional investors such as Xuanshi Capital, Fairy pupil Capital, China Resources Zhengda Life Science Fund, Watson Biology, Sunshine Insurance, Yuexiu Industrial Fund and so on. According to the prospectus, the company completed in July this year.Pre-IPOThe valuation after the round of financing is $657 million, or about 4.2 billion yuan.
With the termination of Ruibo Biology Chuangban IPO this year, Sirnaomics, as the first share of the domestic RNA track, has successfully passed the hearing and is about to be listed in Hong Kong, which may become another important capital breakthrough in the field of RNA.
So, from the perspective of capital markets, what is the advantage of Sirnaomics, the global leader in RNA drug research and development? What are the prospects for the development of the RNA track? What kind of investment logic does it have?
First, the innovative dual target RNAi therapy track has a bright future.
From the perspective of market development potential, the RNA interference (RNAi) track, which has been ploughed deeply by Sirnaomics for more than a decade, is undoubtedly a very popular track.Looking at the three hot directions of RNA therapy at present, mRNA, RNAi and ASO therapy, RNAi technology, which can "silence" disease-causing genes, is one of the most promising and fastest-growing frontier fields in the field of biomedical development.
Simply understood, RNAi is a phenomenon of gene silencing, in which small interference RNA (siRNA) mediates the degradation of target mRNA and inhibits its translation by RNA-induced silencing complex (RISC). Using this mechanism, RNAi can be used to silence the expression of specific genes to treat diseases.
From the development trend of RNAi therapy, after nearly 20 years of continuous development and technological progress after RNAi won the Nobel Prize in 2006, more than 50 RNAi drug development projects have been carried out in clinical trials around the world, of which about 1/3 are in the late clinical stage.
Compared with other small molecular drugs, RNAi therapy has five core advantages: a wide range of proprietary drug targets, accurate and personalized therapy, high safety, long-lasting effect, high success rate of development and low cost.
Note that the current global market for RNAi therapy for all indications has increased from US $12 million in 2018 to US $362 million in 2020.The compound annual growth rate has reached 449.2% and is estimated to reach US $25 billion by 2030.By 2030, the market size of RNAi therapy for common diseases and oncology will account for 54% of the total market size; at the same time, the market size of RNAi therapy in China will increase from about US $4 million in 2022 to more than US $300 million in 2025, with a compound annual growth rate of more than 300%. It is estimated that it will reach about US $3 billion by 2030.From this point of view, the market for RNAi therapy has strong growth and great room for imagination.
Second, multiple core competitive advantages establish the leading position of Sirnaomics RNAi drug research and development.
Nowadays, RNAi has regained the favor of capital, and more and more pharmaceutical giants at home and abroad have entered the RNAi therapy one after another. Sirnaomics, which takes the lead in the capital market, is the first international RNA drug research and development company that uses RNAi technology to obtain IIa phase positive clinical data in the anti-tumor field, and is the leading innovator in the rapidly developing and transformative RNA treatment market, which occupies an important market position in both China and the United States.The author believes that enterprises with excellent genes and development potential can finally gain a foothold in the capital market. This listing in Hong Kong, the company is quite interesting, and then it will reveal the competitive advantages and core investment logic of Sirnaomics.
1) two highly competitive blockbuster products with rich product lines
According to the prospectus, Sirnaomics focuses on exploring the research and development and industrialization of RNAi and mRNA drugs and vaccines, and has built a rich pipeline of more than a dozen products under development, covering a variety of therapeutic areas such as anti-tumor, anti-fibrosis, anti-viral and anti-liver metabolic diseases. Among them, the core products with the fastest clinical progress, STP705 and STP707, are double targeted siRNA therapy for TGF- β 1 and COX-2.
It is reported thatSTP705 is a dual TGF- β 1 / COX-2 inhibitor, which has been proved to be effective and safe in oncology phase I/II clinical trials of non-melanoma skin cancer.The company is further advancing STP705 phase IIb clinical trials for squamous cell carcinoma in situ (isSCC), phase II clinical trials for skin basal cell carcinoma (BCC) and phase II clinical trials for keloids. In addition, the company has also launched a phase I clinical trial of local injection of STP705 in the treatment of liver cancer (basket). Sirnaomics has also obtained the orphan drug certification issued by FDA for three clinical symptoms of primary sclerosing cholangitis (PSC), hepatic cholangiocarcinoma (CCA) and hepatocellular carcinoma (HCC).
Another core product of SirnaomicsSTP707Is to use the company's unique global PNP delivery platform, while targeting TGF- β 1 and COX-2Treatment of hepatocellular carcinoma and multiple solid tumors by intravenous administration、Liver fibrosis和Diseases such as lung cancer.Preclinical studies of GLP in non-human primates have shown that STP707 has obvious efficacy in silencing target genes, and has proved good safety and tolerance. According to the prospectus, the company launched a Phase I clinical trial of STP707 in the United States in November 2021 and plans to submit an IND application to the China Drug Administration in 2022 as part of a global multicenter trial. At the same time, the prospectus also mentioned that Sirnaomics will continue to conduct phase I clinical trials and phase II clinical trials for a variety of tumor types, including metastatic skin squamous cell carcinoma, non-small cell lung cancer (NSCLC), HCC and CCA.
In addition, Sirnaomics has two pre-clinical drug candidates worth paying attention to, which are targeted at factor XI using the GalAhead delivery system.STP122GAnd developed by RNAimmune, a subsidiary of Sirnaomics, which specializes in the development of mRNA drugs and vaccinesRIM730 .Among them, STP122G is used for anti-thrombosis and plans to submit an application for IND to FDA of the United States in the first half of 2022, while RIM730 is a candidate vaccine for prophylactic mRNA, which is targeted by LNP technology and uses Delta mutant protein coding mRNA as an antioriginal to promote the research and development of mRNA SARS-CoV-2 vaccine (this project is currently under pre-IND discussion with FDA of the United States). At the same time, RNAimmune is also promoting the research and development of mRNA tumor vaccines and drugs.
As of the date disclosed in the prospectus, Sirnaomics has a total of six issued patents, including one in Europe and five in the United States and 40 pending patent applications covering these 16 candidate products (including 7 in China, 21 in the United States, 1 in Europe and 2 under the Patent Cooperation Treaty and 9 in other jurisdictions).
In addition, the company has at least 13 other product lines currently undergoing preclinical research, covering a wide range of indications, including influenza, hepatitis B, HPV, pancreatic cancer, colon cancer and many other cancers, cardiovascular and metabolic diseases, as well as medical and aesthetic fat plasticity treatment.
At the same time, it is worth noting that in April this year, Sirnaomics established a research and development cooperation with Watson Biology, a well-known domestic vaccine company. This partnership will combine Sirnaomics's RNAi drug research and development expertise with Watson's production and marketing capabilities to jointly develop a new anti-influenza RNAi drug STP702. Sirnaomics will receive a down payment of about RMB 41.5 million, and will receive a milestone payment of Rmb100m for the drug candidate at a later stage, as well as a share based on product sales in the future. This proves,There is great potential to expand the indications of Sirnaomics products, and the product space is still improving.。
2) solve the problem of constraints and innovate the delivery platform to promote product innovation.
At this stage, the key to the successful development of RNAi/mRNA therapy and vaccine is to find a safe and effective delivery vector, which can deliver the corresponding RNA to the target cell type and the action site in the cell, and protect RNA from degradation before reaching the target cell.
After more than a decade of hard work, Sirnaomics has established a number of innovative and proprietary nucleic acid drug delivery platforms, including its global unique Peptide nanoparticles (PNP) drug delivery platform, new GalNAc RNAi delivery platform and PLNP delivery platform. Compared with the so-called mainstream delivery technologies in the nucleic acid drug industry, such as GalNac (tri-tentacle N-acetylgalactosamine) and lipid nanoparticles (LNP) introduction technologySirnaomicsThe drug delivery system has obvious technical advantages of delivery platform, and has established a high competition barrier, which is expected to become the core competitiveness of commercialization in the future.
Among them, Sirnaomics's Peptide nanoparticles (PNP) drug delivery platform has global patent protection, which can be delivered locally or systemic, with low toxicity, easy to manufacture, can reach a variety of targeted organs and cell types, and can deliver both siRNA and mRNA.
The active clinical trial results of IIa oncology obtained by Sirnaomics have successfully verified the effectiveness of the PNP delivery platform. The company is now going furtherExpand the product pipeline and use PNPThe technology simultaneously promotes the implementation of several clinical trials aimed at different finger symptoms.
On the other hand, Sirnaomics's new GalNAc RNAi delivery platform can achieve high-performance specific delivery of hepatocytes. At present, Sirnaomics is further designing and optimizing other nucleic acid drug delivery platforms, including different methods of siRNA/ chemical drug conjugates, peptide ligand tumor targeting and airway delivery for the treatment of respiratory infections.
The author thinksSirnaomicsContinue to invest in the drug delivery system, constantly expand and improve its product pipelineIt is expected that RNAi drugs will be promoted to the fields of tumor therapy, fibrosis therapy and antiviral therapy.，Construction companyIn the futureIn competitionAn absolute advantage.
3) haveExperienced and visionaryGlobal management team
In addition to the above two core competenciesSirnaomicsBehind the strong independent R & D capability, there is also an experienced and far-sighted global management team that is quite interesting.
According to the prospectus, the senior management team of Sirnaomics has extensive experience and ability in developing, clinical and commercializing RNA therapy.The Sirnaomics management team and the Scientific Advisory Board have an average of more than 20 years of drug research and development experience in the world's leading pharmaceutical companies and research institutions in China and the United States. Dr. Lu Yang, founder, President and CEO, has been involved in the research and development of new drugs for nucleic acid interference for many years, and is one of the earliest researchers and entrepreneurs in the world to enter this field. Dr. Lu has written more than 55 scientific books and 53 patents for inventions, and has been recognized and awarded a number of awards in China and the United States for his innovative research and entrepreneurial spirit.
Dr. Lu has more than 28 years of experience in biomedical research and development in China and the United States. prior to starting his business, Dr. Lu worked in the Novartis Gene Therapy Division, then founded Intradigm Corp., in the United States in 2001 as Executive Vice President of the company and led the company's siRNA therapy research and development until early 2007. After Intradigm left office, Dr. Lu founded Sirnaomics in the spring of 2007, and established Suzhou Sirnaomics and Guangzhou Sirnaomics in 2008 and 2012 respectively, leading the team to build a solid technology platform and enrich the RNA treatment product pipeline.
As of the latest practicable date, Sirnaomics's R & D team consists of 115 employees and consultants, including 27 with doctorates and 30 with master's degrees. And the company spends a lot of money on R & D. the R & D costs of Sirnaomics in 2019, 2020 and the first five months of 2021 are $10.213 million, $14.894 million and $9.766 million, respectively.
Third, speed up commercialization and open the ceiling of value
Like many unprofitable biotech companies, Sirnaomics currently has no products approved for commercial sale, so it does not generate any revenue from product sales.
According to the prospectus, Sirnaomics recorded a total net loss of $17.127 million, $46.428 million and $23.339 million in 2019, 2020 and the five months ended May 31, 2021, mainly due to high upfront R & D costs and some necessary administrative expenses in the treatment area.
However, it is worth noting that Sirnaomics's pipeline products under development will be launched one after another in the next two years.In particular, the profit opportunities and space brought by the launch of STP705 and STP707-related indication products will accelerate the process of commercialization and achieve revenue growth.
In addition, as a clinical RNA pharmaceutical company that has been deeply cultivated in China and the United States for many years, Sirnaomics adopts the clinical development strategy of "complementary advantages". Based on the different medical needs and regulatory systems of the two markets, Sirnaomics maximizes the policy dividends brought by the complementary regulatory policies of the two markets, accelerates clinical development and quickly accumulates market advantages.
At present, Sirnaomics has built its own nucleic acid drug production workshop in Guangzhou and plans to start operation in the first quarter of 2022, when it will further strengthen its production capacity in China and gradually complete the transformation from a pharmaceutical R & D enterprise to a pharmaceutical pharmaceutical enterprise.
The author thinksSirnaomicsBoth China and the United States have strong R & D capabilities, and their strategic clinical development strategy and industrialization layout maximize the advantages of the "China-US double market". Its multiple competitiveness will certainly bring it more room for development and expected benefits.
In addition, according to the investment project raised in the prospectus, the funds raised after the listing of Sirnaomics are mainly used for the research and development and commercialization of the core drug candidate STP705, the development of PNP-STP707, GalNAc plan products such as STP122G, STP133G and STP144G, and the research and development of other mRNA preclinical drug candidates. On the whole, the above direction is consistent with the strategic development direction of Sirnaomics, which is conducive to further consolidate the company's industry position and gain development opportunities in the future market competition.
End
Nowadays, biopharmaceutical companies are accelerating the speed of capitalization and listing, and the door of the RNA track is wide open. It is certain that only the leading companies with real innovation ability and high enough industry barriers can stand out. From this point of view, Sirnaomics, which has hard-core R & D capability and outstanding comprehensive strength, has seized the first opportunity of "the first domestic nucleic acid drug" and has the attribute of absolute scarcity. In the course of its growth, it has successively completed five rounds of equity investment totaling US $270 million, which also confirms that the capital continues to be optimistic about its future development space and growth, or it can grow into a fully integrated international biopharmaceutical company in the near future. it deserves the continuous attention of investors.
