p align = "center" [core view]
Covid-19 epidemic situation will not disappear in the short term or not. The closed loop of "vaccine + detection + therapeutic drugs" prevention and control in the medium and long term has been basically formed, and covid-19 epidemic situation is moving towards normalization.
We believe that covid-19 antigen detection may become an important supplementary means for epidemic prevention and control in China, mainly based on: 1 Chinese antigen detection products are mature. 2. The product capacity is sufficient. 3. Specific application scenarios require rapid response to antigen detection.
The enhanced vaccination of covid-19 vaccine in China will be accelerated. At present, sequential vaccination and homologous vaccination are free of charge. We expect that the manufacturers of covid-19 vaccine will be in a competitive state.
Covid-19 oral drugs are in short supply. At present, two covid-19 oral drugs have been approved for marketing, including molnupiravir of MSD and paxlovid of Pfizer Pfizer is actively promoting production capacity. Chinese domestic covid-19 drug RdRp inhibitor has entered phase 3 clinical trial.
investment suggestions: covid-19 epidemic is expected to coexist with humans in the medium and long term, and the trend of the epidemic is highly uncertain. It is suggested to screen theme investment opportunities from three dimensions: 1) good demand sustainability, 2) excellent competition pattern, and 3) traditional business has certain valuation support. It is recommended to pay attention to the relevant subjects:
1) covid-19 antigen detection: Zhejiang Orient Gene Biotech Co.Ltd(688298) , Guangzhou Wondfo Biotech Co.Ltd(300482) , anxiu biology, Hangzhou Biotest Biotech Co.Ltd(688767) , Hangzhou Alltest Biotech Co.Ltd(688606) ;
2) vaccine booster: Chongqing Zhifei Biological Products Co.Ltd(300122) , Cansino Biologics Inc(688185) , Shenzhen Kangtai Biological Products Co.Ltd(300601) ;
3) covid-19 drug: Shanghai Junshi Biosciences Co.Ltd(688180) , Shijiazhuang Yiling Pharmaceutical Co.Ltd(002603) ;
Supply chain: ,
\u3000\u3000 1. Under the new situation of covid-19 prevention and control, antigen may be an important supplementary means of detection
\u3000\u3000 11. The application of overseas antigen detection is mature, and China may gradually improve the prevention and control means
At present, overseas covid-19 detection is mainly antigen detection. Covid-19 detection methods include nucleic acid, antigen and antibody. Nucleic acid detection is the gold standard, but it needs professional PCR instrument detection, and the waiting time is long; Antigen detection is suitable for detecting patients within 7 days of illness. The reaction speed is faster, but the sensitivity is lower than that of nucleic acid, and there are false negative results; Antibody detection mainly determines whether covid-19 virus has been infected by detecting IgM or IgG, but it is unable to detect the early stage of covid-19 virus infection. There is a window period for antibody detection. At present, China mainly focuses on nucleic acid detection, and overseas developed countries in Europe and America mainly focus on antigen detection.
The sensitivity of antigen detection is lower than that of nucleic acid, which can be detected quickly in case of pandemic and help the epidemic prevention and control. According to the research of science, the effect of covid-19 prevalence on antigen detection is different. When the prevalence of covid-19 in the population decreases, the number of false positives and false negatives of antigen detection kits increases and decreases. At the initial stage of the general screening of antigen detection in Slovakia, the prevalence of covid-19 was as high as 3.9%. According to Pavelka's statistical model, the general screening of antigen detection and other epidemic prevention and control measures reduced the spread of the epidemic by 70%.
There are many antigen detection products, and the sensitivity is the core index of product performance judgment. According to incomplete statistics, at present, there are 94 Chinese antigen detection products certified by EU CE and 3 products certified by us EUA. There are many certified products for covid-19 antigen detection. The index to judge the quality of products is mainly sensitivity, i.e. false negative, and the sensitivity of nucleic acid detection is 99%. According to Hvidovre Hospital's research on different antigen detection kits and a large number of samples, there are 9 antigen detection reagents with sensitivity of more than 90%, accounting for less than 20%, and only 2.5% have the lowest sensitivity. The sensitivity of covid-19 rapid detection reagent produced by Aikang biology is as high as 94%, and the sensitivity of Guangzhou Wondfo Biotech Co.Ltd(300482) and lumiradx is 93%.
Figure 4: number of Chinese enterprise antigen self-test kits certified in various countries
Antigen detection may be an important supplement for covid-19 epidemic prevention and control in China. We believe that antigen detection or gradual release is mainly based on the following three points: 1 The antigen detection product is mature and the sensitivity can reach 90%; European antigen testing has been implemented for more than a year and has been verified for epidemic prevention and control. 2. The production capacity of products is sufficient. In 2021, China exported covid-19 test kits worth 66.893 billion yuan overseas, and the production expansion cycle of enterprises is relatively short. 3. Specific application scenarios require rapid response to antigen detection. For example, places such as ports, airports and sea transportation are places with high risk of covid-19 virus infection, and migrant workers such as takeout and taxi drivers are high-risk transmission sources. If covid-19 virus infection spreads widely in these places and populations, the epidemic situation is easy to spread quickly, the cost of nucleic acid detection is high and the detection speed is slow, Antigen detection or provide more convenient control.
\u3000\u3000 12. Future antigen self inspection market: Overseas tracking epidemic diagnosis, China's tracking policy liberalization
Looking back on the year 2021, there was a large demand for overseas covid-19 testing. At present, the testing volume is gradually released or decreased. According to the annual detection volume in 2021, the average daily detection volume per 1000 people in most overseas countries is about 2-5 times. The epidemic situation is serious and the detection demand is large. The significant increase in autumn and winter (January March and October December) is mainly due to the increase in the number of infections caused by covid-19 virus mutation. Covid-19 testing in the UK has been free since April 2020. In 2021, the average daily testing volume per 1000 people was about 13.67 times, and the annual covid-19 testing demand was high, about 331 million people. On April 1, 2022, the UK will cancel covid-19 testing free of charge, and the demand for covid-19 testing may decline.
At present, the requirements for overseas testing are liberalized, and the national testing demand represented by the UK is declining. The main variable for the increase of testing demand in the future is the severity of covid-19 epidemic, the surge in the number of confirmed cases in a single day, and the testing policy may change.
In the overseas market, the United States has a large demand and high barriers, and the Chinese antigen self-test kit has not been approved. According to the average of 2-5 tests per 1000 people per day in 2021 and the neutral assumption of 3 tests per 1000 people per day in 2022, the annual testing demand of the U.S. market is about 324 million, that of the European market is about 484 million and that of the overseas market is about 6.588 billion. The continuity of covid-19 detection mainly depends on the variation of covid-19 virus. Omicron virus caused another pandemic of covid-19 epidemic in the world, and the demand for detection surged.
\u3000\u3000 2. Covid-19 booster vaccination may accelerate
According to wind, as of March 4, 2022, China had received about 3.152 billion doses of covid-19 vaccine. As of February 25, 2022, the total number of vaccinations was 1.269 billion, of which 1.234 billion had completed the whole course of vaccination, and about 554 million had completed the third booster vaccination. In the future, about 680 million people will need the third booster covid-19 vaccine, accounting for 55% of the basic immunization. At present, sequential vaccination is the same as homologous vaccination, which is free of charge. It is preferred to be implemented in key areas such as ports and borders. Other people carry out sequential and enhanced vaccination according to their needs. We expect that manufacturers of covid-19 vaccine for the third injection will be in a relatively fierce competition.
\u3000\u3000 3. Covid-19 oral drugs are in short supply, and domestic products are under clinical trial
At present, two covid-19 oral drugs have been approved for marketing, including molnupiravir of MSD and paxlovid of Pfizer Mosadong molnupiravir has obtained license / emergency use authorization in the UK, the United States and Japan. Recently, molnupiravir was recommended by who to treat mild covid-19 patients with high risk of hospitalization. Molnupiravir's EUA application is based on the phase 3 move-out clinical trial. Among patients treated with molnupiravir, patients treated with molnupiravir were hospitalized or had a mortality rate of 7.3% (vs 14.1%) on day 29, and the relative risk reduction was 30% in all randomized subjects. Pfizer's paxlovid has obtained approval / emergency use authorization in the UK, Canada, the United States and Japan. It was approved for import registration with conditions in China in February 2022. In the phase II / III epic-hr trial (nct04960202), paxlovid reduced the risk of hospitalization or death for any reason in patients who developed symptoms and received treatment within 5 days by 88%, the probability of hospitalization or death during 28 day follow-up decreased from 6.3% to 0.8%, and the overall death rate decreased from 1.1% to 0.
In addition, the oral covid-19 drug s-217622 of yanyeyi, Japan, has submitted a conditional approval application to PMDA based on phase IIB clinical data. Phase IIB clinical results showed that s-217622 could rapidly reduce virus titer and virus RNA. In the s-217622 treatment group, the proportion of subjects with positive virus titer decreased by about 60-80%, and the average time of negative new coronavirus titer was shortened by 2 days. At the same time, it also showed good safety.
Because covid-19 oral drug has clear curative effect, convenient use and strong accessibility, it has gradually become the mainstream trend of anti epidemic procurement of governments all over the world. It can be seen from the data of covid-19 drug procurement of the U.S. government that since covid-19 oral drugs came into the market, the number of antibody drugs purchased by the U.S. government has decreased, and the procurement trend of covid-19 oral drugs has increased significantly. According to government reports, the United States, the United Kingdom and Japan have purchased 20 million, 2.75 million and 2 million courses of Pfizer paxlovid respectively; For molnupiravir, the United States, the United Kingdom and Japan have purchased 9.5 million, 2.3 million and 1.6 million courses respectively.
domestic covid-19 drug is in clinical trial
1) progress of domestic covid-19 RdRp inhibitors
The main mechanism of RdRp inhibitor is to block coronavirus by blocking the synthesis of RNA polymerase (RdRp). At present, many pharmaceutical enterprises in China have actively carried out the R & D layout of covid-19 oral drugs, among which Shanghai Junshi Biosciences Co.Ltd(688180) , real organisms have entered the phase III clinical trial stage Shanghai Junshi Biosciences Co.Ltd(688180) vv116 has obtained the emergency use authorization (EUA) of Uzbekistan. The phase I clinical study of vv116 completed in China and the previous clinical study on moderate and severe patients in Uzbekistan have shown its expected safety and effectiveness. At present, an international multicenter phase III trial is being carried out. The trial of mild and moderate patients is planned to enroll 2000 people. Azvudine, a real organism of another RdRp inhibitor, is conducting phase III trials in China, Brazil and Russia respectively. Among them, the phase III trial for patients with moderate and severe covid-19 pneumonia in Brazil (nct04668235) is expected to be completed in April 2022, and the trial for patients with mild illness (nct05033145) is expected to be completed in July 2022. GOLLY pharmaceutical asc10 plans to declare ind in China, the United States and other places in H1 2022.
2) progress of domestic covid-19 3clpro inhibitors and other types of drugs
3CL protease inhibitor can inhibit the activity of 3CL protease and block the replication process of coronavirus. It has significant advantages in the treatment of covid-19 virus infection Frontier Biotechnologies Inc(688221) , Shanghai Junshi Biosciences Co.Ltd(688180) , Xiansheng pharmaceutical and other pharmaceutical enterprises have arranged the research and development of 3clpro inhibitors with the same mechanism as Pfizer paxlovid. At present, except Frontier Biotechnologies Inc(688221) (fb2001, injection), other pharmaceutical enterprises are still in the stage of preclinical research. According to Shanghai Junshi Biosciences Co.Ltd(688180) investor relations records, according to the preclinical and antiviral research data of vv993, vv993 single drug showed good efficacy and safety. Sim0417 of Xiansheng pharmaceutical showed good antiviral activity and safety in animal models Fujian Cosunter Pharmaceutical Co.Ltd(300436) announced that it had obtained pre selected preclinical candidate compounds with considerable efficacy; Yunding Xinyao is authorized to introduce covid-19 oral drug eddc-2214 of Singapore a ccelerate, and the clinical trial is expected to be carried out in 2022; Ge Li pharmaceutical asc11 plans to declare ind in China, the United States and other places in 2022.
Prochloramide, an androgen receptor antagonist pioneering the pharmaceutical industry, was approved as EUA in Uruguay, but the interim analysis of its phase III trial for non hospitalized patients with mild and moderate diseases did not reach the end point.
At present, the company is carrying out phase III clinical research on critically ill inpatients and phase III global clinical trial on mild and moderate diseases. On February 14, the global phase III clinical trial of covid-19 for the treatment of mild and moderate diseases completed the administration of the first subject in China.
\u3000\u3000 4. Investment proposal
Covid-19 epidemic is expected to coexist with humans in the medium and long term, and the trend of the epidemic is highly uncertain. It is suggested to screen theme investment opportunities from three dimensions: 1) good demand sustainability, 2) excellent competition pattern, and 3) traditional business has certain valuation support. Relevant subject matter:
1) covid-19 antigen detection: Zhejiang Orient Gene Biotech Co.Ltd(688298) , Guangzhou Wondfo Biotech Co.Ltd(300482) , anxiu biology, Hangzhou Biotest Biotech Co.Ltd(688767) , Hangzhou Alltest Biotech Co.Ltd(688606) ;
2) vaccine booster: Chongqing Zhifei Biological Products Co.Ltd(300122) , Cansino Biologics Inc(688185) , Shenzhen Kangtai Biological Products Co.Ltd(300601) ;
3) covid-19 drug: Shanghai Junshi Biosciences Co.Ltd(688180) , Shijiazhuang Yiling Pharmaceutical Co.Ltd(002603) ;
4) cdmo supply chain: Wuxi Apptec Co.Ltd(603259) , Asymchem Laboratories (Tianjin) Co.Ltd(002821) , Porton Pharma Solutions Ltd(300363) .
Risk tips: covid-19 virus mutation risk, covid-19 antigen detection release is less than expected, covid-19 vaccination is less than expected, covid-19 drug research and development is less than expected, covid-19 drug preparation process is uncertain, which is the subjective expectation of analysts, covid-19 drug industry chain company's participation is uncertain, etc.
Note: the report section in the text is selected from the research report publicly released by Tianfeng Securities Co.Ltd(601162) Research Institute. See the full version of the report for the specific contents and relevant risk tips.
