The official announcement of the approval of the IND resulted in the stock price falling three times in a row, and it also fell out of a new low since its listing. In recent trading days, Sirnaomics may not be in a good mood.
Zhitong Financial APP learned that on December 18, Sirnaomics announced that its subsidiary Da Mian Biologics' innovative mRNA vaccine RV-1770 for human respiratory syncytial virus (RSV) has been approved by the US FDA, and plans to carry out phase I clinical research trials.
The clinical approval of a new drug is undoubtedly a good thing for an innovative pharmaceutical company, but it does not seem to be the case for Sirnaomics. After the news was disclosed, the company's stock price closed down 4 on the 18th and 19th19% and 250%。On December 20, the company once again ** nearly 5% intraday, and the lowest share price touched 37HK$45, this share price has hit a new low since the company's listing. Since December, the company's stock price has fallen by 1857%。
For this 18A company that has not yet achieved commercialization and is strapped for cash flow, investors may prefer to commercialize it as soon as possible rather than opening a new R&D line to increase the financial burden.
RSV tracks that players flock to.
Recently, respiratory infectious diseases such as mycoplasma and influenza have entered a period of high incidence. Respiratory syncytial virus (RSV) has also entered the epidemic period, which has also made RSV vaccines quickly become a hot spot in the market, attracting many players from all over the world.
According to Zhitong Financial APP, respiratory syncytial virus (RSV) is the main cause of respiratory diseases in young children, and the risk of serious infection in the elderly is high. In addition to acute mortality and morbidity, RSV infection is associated with long-term sequelae, such as impaired asthma and pulmonary function in the pediatric population, and exacerbations of chronic obstructive pulmonary disease in older adults.
In April this year, the journal NEJM published data on the flow of RSV infections in the United States for the 2022-2023 epidemic season. The data shows that in the 2022-2023 epidemic season, RSV shows a trend of early onset and high incidence. Stimulated by market demand, a number of multinational pharmaceutical companies have accelerated the research and development of RSV vaccines.
In fact, before May this year, there was still a gap in the commercialization of global RSV vaccines. In terms of global competition, only Moderna, GlaxoSmithKline and Pfizer are listed in Racing products.
In April, Moderna announced that it expects to submit a marketing application for its investigational RSV vaccine candidate, mRNA-1345, in Q1. But while Moderna pinned its hopes on this, it was then preempted by GSK and Pfizer.
In the following May and June, GSK and Pfizer's RSV vaccines were approved by the FDA for marketing. It wasn't until July that Moderna announced that it had submitted marketing authorization applications for mRNA-1345, a respiratory syncytial virus (RSV) vaccine, for people aged 60 years and older, to the European Medicines Agency, the Swiss Medicines Regulatory Agency, and the Medicines Australia Regulatory Agency, and a rolling biologics license application for mRNA-1345 to the U.S. Food and Drug Administration (FDA).
At present, Pfizer's AbrySVO and GlaxoSmithKline's Arexvy, as the first batch of RSV vaccines on the market, have enjoyed the dividends of the relevant indication market one step ahead of schedule.
From the perspective of market space, the overall global market size of RSV drugs (including first-class drugs and preventive drugs) is expected to grow from US$1.8 billion in 2020 to US$12.8 billion in 2030, with a compound annual growth rate of 214%。China's RSV drug market is expected to grow significantly from $5.2 million in 2020 to $1.5 billion by 2030, growing at a CAGR of 75.58%。Among them, RSV drugs for children are expected to account for about 89% of the entire Chinese RSV drug market4%。
According to the latest 2023Q3 financial report disclosed by Pfizer and GSK, AbrySVO contributed 3$7.5 billion in sales, and GlaxoSmithKline's Arexvy is a FIC product, with sales of up to 70.9 billion pounds, or about 8$700 million, it is clear that it will easily step into the billion club.
In fact, in addition to the above three, Sanofi, Merck, Johnson & Johnson, AstraZeneca and other multinational pharmaceutical companies have invested in the RSV field. Take AstraZeneca as an example, after it announced a high-profile acquisition of a vaccine research and development company ICOS**AX for a consideration of $1.1 billion to enter the RSV track.
In the domestic market, Advexin's RSV vaccine ADV110 BARS13 is in the phase II clinical stage, which is the fastest R&D product in China, and the phase II clinical data has been disclosed. In addition to Advexin, there are also domestic companies including Baike Biotech, Walvax Biotech and Jiachen Xihai that are developing RSV vaccines. In contrast, Sirnaomics, which has just been approved for IND, is not in the first echelon in terms of the development progress of RSV vaccines.
"Gnaw hard bones" when you are short of money
Because Sirnaomics has its own small polypeptide lipid delivery (PLNP) technology, it is also a professional counterpart when it involves mRNA vaccines, but the reason why the secondary market is "not cold" may be that investors believe that Sirnaomics is now "gnawing hard bones" when it is short of money.
As can be seen from the 2023 interim results disclosed by Sirnaomics, the sales revenue from 2019 to the first half of 2023 is zero because the company still does not have a commercial product.
At present, the company is also consciously cutting back on expenses. According to the data, the company's R&D expenses increased from 3210 in the first half of 2022$90,000 to $3,070 for the same period in 2023$90,000, with a reduction in administrative costs. The reason for the company's voluntary fee reduction may come from the company's cash flow pressure. As of the first half of this year, the company had only 5,729 cash and cash equivalents on its books90,000 US dollars, a year-on-year decrease of 6623%。That is, in the first half of the year, the company's net loss was 4110With a total of $60,000, the cash on the account is only enough for Sirnaomics to burn for half a year.
Therefore, for Sirnaomics, the top priority should be to accelerate the commercialization of core products as soon as possible, rather than opening new R&D projects, and the RSV vaccine is still a "difficult bone to gnaw".
As mentioned earlier, there is a gap in the global RSV vaccine until May this year. But in fact, relevant research began as early as the 60s of the last century, but because of many difficulties in the development of RSV vaccines, various research and development failures have been repeated.
The key pain point is the change in the conformation of the F protein of RSV before fusion. According to Zhitong Financial APP, the F protein of RSV is metastable in its conformation before fusion, and there are two conformations. If the immune system is able to encounter the F protein in the first conformation, it is able to produce strong antibodies, but if the F protein is in the second conformation, it will hardly stimulate the production of antibodies, and the excitation of antibodies will not be very effective. Traditional methods of developing RSV vaccines often result in the F protein being in the second conformation, so the provoked antibody response is not strong.
On the other hand, in the process of research and development of RSV vaccines, there is a lack of good animal test models and serological markers, and different development strategies need to be developed for different populations.
It is not until recent years that researchers have revealed the mechanism by which RSV vaccines activate Th2-CD4+ T cells to secrete-related cytokines to mediate the occurrence of pneumonia, that many companies have begun to restart the development of RSV vaccines, but the process is still tortuous and there are many failures.
For example, in July this year, B**Arian Nordic released the latest data of the Phase III clinical trial of the RSV vaccine, which showed that the study was 59% effective for more than two LRTD symptoms and 42% against more than three LRTD symptoms9%, i.e., only one primary endpoint was met. Based on this, B**arian Nordic decided to abandon the RSV project. The partner, UniPharmaceutical, will also abandon development in select Asian countries.
Although Sirnaomics' RV-1770 is said to have a unique skeleton design of AI-enhanced sequences, uses the sequences of recently isolated clinical strains of RSV, and has demonstrated immune response and neutralization effect against both subtype A and subtype B of RSV in preclinical studies in cotton mouse models, it is not possible to determine the risk and cost of successfully advancing from Phase I to Phase III clinical trials alone, and the risks and costs are difficult to accurately estimate.
For Sirnaomics, the current rapid decline in stock prices may be mainly due to its lack of hematopoietic capacity and the possibility of running out of cash flow. Against this backdrop, launching a project with an unpredictable success rate can be a burden. At present, finding financing to stabilize the pre-commercialization stage and ultimately commercialize the product may be an immediate matter for Sirnaomics.