From fanaticism to calmness, pharmaceutical stocks will return to rationality in 2021. This year, the pharmaceutical index fell - 9.97%, superimposed on the continuous release of the company's performance, and the valuation level of the sector has been significantly digested. Looking forward to 2022, will anti epidemic become an investment hotspot? The answer may lie in the main line of neutralizing antibodies.
On December 8, the State Food and Drug Administration approved the first joint program of covid-19 neutralizing antibody. Ambacizumab / romistumab combination therapy developed by tengshengbo medicine (02137. HK) is approved for the treatment of mild and common adult and adolescent covid-19 patients with risk of progression. In June this year, tengshengbo launched phase 2 Research on neutralizing antibody therapy in China.
More relevant studies of local pharmaceutical companies are also being carried out, such as etsvizumab in Shanghai Junshi Biosciences Co.Ltd(688180) (688180. SH); Baiji Shenzhou (688235. SH) introduced two neutralizing antibodies of danxu biology dxp-593 and dxp-604 through the authorization agreement.
With the approval of China's first covid-19 neutralizing antibody treatment drug, the potential of using neutralizing antibody drugs to treat covid-19 is being continuously tapped, which is expected to become an important supplement after covid-19 vaccine.
first antibody drug
It is not a coincidence that China's first antibody drug "Hualuo" tengshengbo. There are more reliable clinical trial data of ambacizumab / romistuzumab combination therapy, and it has been tested.
According to the disclosure, the FDA approved the combination therapy mainly based on the research results of the phase 3 clinical trial (activ-2) supported by the National Institutes of Health (NIH). The trial data of 847 recruited patients showed that compared with placebo, the number of hospitalizations and deaths were reduced by 80%, with higher safety and statistically significant difference.
Since June this year, tengshengbo has cooperated with government agencies and hospitals to distribute the epidemic situation for emergency use. According to the disclosure, Guangzhou, Shenzhen, Ruili, Kunming, Nanjing, Yangzhou, Zhang Jia Jie Tourism Group Co.Ltd(000430) and other cities have been supplied.
In terms of mechanism, neutralizing antibody can accurately recognize and combine with covid-19 virus surface spike protein, prevent covid-19 virus from entering human cells and achieve the effect of neutralizing the virus. In addition to the emergency use of covid-19 patients, the main increment of neutralizing antibody drugs lies in the government's strategic reserve procurement, which can bring many performance increments to enterprises. However, the variable is that new variants of covid-19 virus have appeared. Some studies have found that there are more than 30 mutations in Omicron spike protein, which may affect the ability of antibody drugs to neutralize the virus.
At present, the purchase price of neutralizing antibody drugs has not been determined. According to previous interface news reports, Li Ankang, chief financial officer of tengshengbo pharmaceutical, said that the pricing of neutralizing antibody drugs is still under discussion with the government, because government orders and supply are related to pricing, while the government purchase price of the same category of drugs in the United States is $2100 / needle. Li Ankang also denied the online price of 8000 yuan per dose.
Even the relatively low purchase price may greatly thicken the performance of tengshengbo pharmaceutical. In the first half of this year, tengshengbo pharmaceutical had no product income, mainly from government subsidies of 45.66 million yuan and bank interest income of 620000 yuan.
Tengshengbo pharmaceutical is a typical R & D biopharmaceutical enterprise. Its products under research are mainly used for the treatment of HBV, HIV, MDR, Gram-negative bacteria and other diseases. In the first half of this year, the R & D expenditure of Tengsheng boyao reached 158 million yuan, which is the largest expenditure project of the company.
more followers
Shanghai Junshi Biosciences Co.Ltd(688180) is also relatively advanced in the field of neutralizing antibodies, and its products have entered the United States. In February this year, the double antibody therapy of etesevimab and bamlanivimab was authorized by FDA for emergency use for covid-19 patients.
Etsvizumab was jointly developed by Shanghai Junshi Biosciences Co.Ltd(688180) and Institute of Microbiology, Chinese Academy of Sciences, Shanghai Junshi Biosciences Co.Ltd(688180) authorized partner Lilly pharmaceutical to protect the rights and interests outside Greater China, and Shanghai Junshi Biosciences Co.Ltd(688180) continued to lead the development of Greater China. Banivir mAb originated from the cooperative development of Lilly pharmaceutical and pharmaceutical enterprise abcellera.
Recently, the scope of application of dual antibody therapy with etcivir monoclonal antibody and banivir monoclonal antibody has been further expanded. According to the disclosure, FDA added dual antibody therapy for the treatment of mild to moderate covid-19 pneumonia and post exposure prevention in specific high-risk pediatric populations (from birth to under 12 years old).
Since the beginning of this year, the demand for antibody therapy in the U.S. market has remained high, and the increase in the shipment of etsvizumab is good for Shanghai Junshi Biosciences Co.Ltd(688180) . According to the disclosure, as of December 6, more than 700000 patients had received dual antibody therapy or banivir monoclonal antibody therapy, potentially preventing more than 35000 hospitalizations and at least 14000 deaths during the most serious period of the epidemic.
The sales share and milestone payment of etsvizumab are the main performance increments. According to the research of securities companies, it is estimated that in 2021 Shanghai Junshi Biosciences Co.Ltd(688180) the income from neutralizing antibody will be 100 million yuan and the income from neutralizing antibody technology license will be 410 million yuan.
The corresponding trend can also be seen from the published results. In the first three quarters of this year, Shanghai Junshi Biosciences Co.Ltd(688180) revenue was 2.718 billion yuan, a significant increase of 168.90% year-on-year, exceeding that of last year; The net profit loss attributable to the parent company was 392 million yuan, which narrowed significantly year-on-year. Shanghai Junshi Biosciences Co.Ltd(688180) reported in the China Daily that the technology license revenue of the company increased significantly in the first half of the year, and the franchise revenue was increased.
There are many neutralizing antibody projects carried out by local enterprises. In August 2020, Baiji Shenzhou announced that it had signed an exclusive license agreement with danxu biology to obtain the rights and interests of the latter's two candidate drugs dxp-593 and dxp-604 in Greater China. Subsequently, in September, Baekje launched the phase I clinical trial of dxp-593 in Australia and the phase I / II clinical trial in many countries in October 2020.
Danxu biology has only been established for two years. In September 2020, it announced the completion of a round of financing of RMB 100 million, with participants including Hillhouse venture capital and Huagai capital. The enterprise is almost entirely set up for the development of covid-19 virus neutralizing antibody drugs.
Recently, Sinocelltech Group Limited(688520) (688520. SH) also announced that the product under development scta01c injection and the combination of scta01c injection and scta01 injection have obtained clinical trial approval. Scta01 is a recombinant monoclonal antibody against sars-cov-2 spike protein, and scta01c is a monoclonal neutralizing antibody against covid-19 virus. According to the disclosure, the combination of the two antibodies has the potential for broad-spectrum treatment of covid-19 infection.
In addition, covid-19 monoclonal antibody 9mw3311 developed by Maiwei biology, an IPO company of Kechuang board, has entered phase 2 clinical stage. In October 2020, Maiwei biology signed an authorization agreement with abpro, a biotechnology company, to complete the overseas authorization of 9mw3311, in which the agreed milestone payment can reach up to US $122 million.
deal with new variants
Delta is the dominant mutant of covid-19 in the world. The Omicron variant, first discovered in South Africa, has become a dominant strain in some areas. The popularity of Omicron is likely to rise and even replace Delta.
The drug mechanism of neutralizing antibody mainly lies in binding to the surface spike protein (s protein) of covid-19 virus, or blocking the changes of spike protein, preventing the spike protein from binding to human cells and "neutralizing" with the virus. Omicron has up to 15 mutations in the RBD region of S protein, which may affect the effect of neutralizing antibody drugs and even covid-19 vaccine.
Maiwei biology expressed "concern" about the change of neutralizing activity of neutralizing antibody drugs. According to the prospectus, Maiwei biological has carried out the neutralization activity detection of 9mw3311 against the mutants of covid-19 virus originating in the UK, South Africa, Brazil, India and California, which confirmed that 9mw3311 maintained the neutralization activity against the UK mutants, but partially or completely inactivated the mutants in South Africa, Brazil, India and California.
Baiji Shenzhou believes that its products may have the potential to avoid drug resistance caused by virus mutation. According to the company's prospectus, dxp-593 and dxp-604 were screened from antigen B cells of more than 60 convalescent patients with covid-19 pneumonia. Dxp-593 showed strong neutralizing activity in pseudovirus and covid-19 virus respectively. The binding epitope of dxp-604 was different from dxp593, and also had high and low neutralizing activity. Dxp-593 and dxp-604 are expected to be options for cocktail therapy (a treatment to reduce drug resistance caused by monotherapy).
Data on the efficacy of neutralizing antibody drugs against Omicron are still scarce. The efficacy will obviously have an impact on the commercialization prospect of the product. Once the popular mutant changes, neutralizing antibody drug development enterprises need to respond faster.
(interface News)
