Securities code: Hybio Pharmaceutical Co.Ltd(300199) securities abbreviation: Hybio Pharmaceutical Co.Ltd(300199) Announcement No.: 2022040 Hybio Pharmaceutical Co.Ltd(300199)
Announcement on the reply to the inquiry letter of Shenzhen Stock Exchange
The company and all members of the board of directors guarantee that the information disclosed is true, accurate and complete without false records, misleading statements or major omissions.
Special risk tips:
1. The covid-19 nasal spray project of the company is different from Pfizer's nimatovir experimental path, and there is still uncertainty in the data and results of animal in vivo and clinical experiments in the future.
2. There are covid-19 preventive and therapeutic drugs in different research and development stages in the world. There are polypeptide membrane fusion inhibitor research and development companies with the same action mechanism in China. It can be found from the public information that there are two companies, of which Jinbo biological disclosure obtained the clinical approval in September 2021; Beijing Youcare Pharmaceutical Group Co.Ltd(688658) disclosed on January 10, 2022 that it cooperated with the Institute of pathogenic biology of the Chinese Academy of Medical Sciences to develop broad-spectrum coronavirus membrane fusion inhibitor polypeptide drugs. The market competition is fierce. Investors are invited to pay attention to investment risks.
3. Covid-19 nasal spray of the company still needs clinical phase I, phase II and phase III studies and registration and application stages in the future. In terms of pharmaceutical research, there are risks of difficulty in the development of API and preparation process and uncertainty of stability. In terms of clinical research, there is a risk that the effectiveness does not meet the expectations. There is uncertainty about the clinical progress and whether it can be approved for listing in the future, There is uncertainty about the future economic benefits and the impact on the company's performance.
4. Affected by the development and control of overseas epidemic situation, the choice of drug use, overseas market promotion and other factors, there is still uncertainty about whether the clinical trial application and products can be successfully approved for listing.
5. The patent applied for by the project is owned by the Institute of Microbiology, Chinese Academy of Sciences. It is licensed to the company for commercial development in the form of global exclusive license. At present, it has been accepted by the State Intellectual Property Office, but it has not finally obtained the patent authorization. Please pay attention to the investment risks.
6. As of September 30, 2021, the company's asset liability ratio was 58.65%. After pre communication with the annual audit accounting firm, the company's net profit loss in 2021 after deducting non recurring profits and losses was 380 million yuan to 430 million yuan. Please make prudent decisions and pay attention to investment risks.
7. China Securities News, Shanghai Securities News, securities times, securities daily and cninfo (www.cn. Info. Com. CN.) As the information disclosure media designated by the company, all information of the company shall be subject to the information published in the above designated media. Investors are invited to invest rationally and pay attention to risks.
Hybio Pharmaceutical Co.Ltd(300199) (hereinafter referred to as "the company" or " Hybio Pharmaceutical Co.Ltd(300199) ") received the inquiry letter on Hybio Pharmaceutical Co.Ltd(300199) issued by Shenzhen Stock Exchange on April 11, 2022 (GEM attention letter [2022] No. 41). The company has carefully verified and implemented the relevant questions asked in the letter one by one, and now replies to the relevant questions in the letter are as follows:
1. Please list the number of live virus inhibition tests of covid-19 nasal spray polypeptide preparation conducted by your company, previous experimental methods, test paths, experimental results, etc., and explain whether each experiment shows that the inhibitory activity of the polypeptide nasal spray developed by your company is about 60 times higher than that of Pfizer covid-19, and whether it is at the nanomolar level, i.e. 100% inhibition of each variant.
Reply: in vitro live virus inhibition test path of API of covid-19 nasal spray project of the company:
Covid-19 nasal spray project preparation in vitro live virus inhibition test path:
Pfizer nimatvir in vitro live virus inhibition test path:
The previous experimental data are as follows:
Assessor WT (original delta)
Test unit sample method cell line IC50 (nm) Omicron IC50 (nm) IC50 (nm)
The minimum concentration of peptide small test sample used in laboratory test is 0.9nm, / 25.99
All inhibition was observed at the lowest concentration of feed drug
The lowest concentration of CPE observed in the polypeptide group scale used in the laboratory Vero test of polypeptide nasal spray is
The large sample was 120.8 40.6 0.0005nm, and all samples were observed at the lowest concentration
inhibition
203.1 58.7 0.26
laboratory
Pilot CPE observation //
Material medicine
Shenzhen third Vero E6
People's Hospital 4.86 5.66 2.82
Preparation focus reduction
Number neutralization 11.7 10.65 13.09
7.6 11.91 12.16
The polypeptide nasal spray project team conducted three experiments through small-scale laboratory test, API test and laboratory scale-up samples
The results showed that the API had inhibitory effect on covid-19 virus in vitro.
When the company conducted the test in Shenzhen Third Institute,
DMSO was used to dissolve the laboratory API without exploring the culture conditions, which could not be observed by CPE
To EC50. There are some differences between covid-19 nasal spray project of the company and nimatway experimental path of Pfizer
The covid-19 nasal spray project and the in vitro antiviral effect of Pfizer's nimatvir were adopted to target the current major epidemic variants
Comparing the data of strain Omicron, the EC50 of nimatovir divided by covid-19 nasal spray EC50 showed in vitro viability
Sex is 60 times higher.
On April 1, 2022, the company obtained the experimental report of Shenzhen Third People's hospital. It showed that covid-19 nasal spray polypeptide preparation had inhibitory effect on the live virus of each variant of covid-19 virus at the drug concentration without obvious cytotoxicity. The half inhibitory concentration of the three preparation prescriptions on the live virus of each variant was at the nanomolar level, The experimental results of covid-19 nasal spray polypeptide preparation showed that the in vitro antiviral effect of Pfizer's nimatvir was higher than 5.67 times.
2. Your company said that "the action mechanism of polypeptide nasal spray drug developed by your company is different from that of Pfizer's recently listed oral tablets, and it is still in the rapid development stage". Please explain the R & D stage of covid-19 nasal spray drug of your company, and show the comparison of R & D progress between your company and other covid-19 drugs produced in China. Combined with the above situation, explain whether your company's "covid-19 nasal spray drug is in the rapid development stage" is accurate.
Reply: on November 12, 2021, the company held the 37th meeting of the Fourth Board of directors, deliberated and approved the proposal on signing technology transfer contract with the Institute of Microbiology, Chinese Academy of Sciences, and agreed to cooperate with the Institute of Microbiology, Chinese Academy of Sciences to carry out polypeptide nasal spray project. As of the disclosure date of this announcement, the company's covid-19 nasal spray project has completed preclinical process research and is in the process of drug efficacy research in animals In vivo pharmacological and toxicological research, safety evaluation research, and sample production under GMP conditions.
Progress of some covid-19 drug research projects in China
Drug name drug type drug delivery route original research unit action target progress latest progress
The project was launched on January 29, 2020
Fb2001 intravenous Frontier Biotechnologies Inc(688221) 3CL protease was approved on the day, and the phase I clinical trial was completed in December 2021
Clinical approval was obtained on January 21
Spike protein the project was launched on January 27, 2020
EK1 polypeptide atomization inhalation Jinbo biological day was approved and phase I clinical HR2 was launched in September 2021
Clinical approval was obtained on September 9
The project was completed on December 24, 2021
Pending small molecule oral Fujian Cosunter Pharmaceutical Co.Ltd(300436) 3CL protease clinical approval day before
Spike protein the project was launched on January 10, 2022
To be determined Youcare Pharmaceutical Group Co.Ltd(688658) pre clinical HR2 project approval
The project was launched on February 18, 2022
Shen26 small molecule oral Shan Dong Kexing Bioproducts Co.Ltd(688136) RNA polymerase was approved the day before the clinical trial
As this drug is developed based on the technology platform of chemical synthetic polypeptide, which is a new target and has a new mechanism, it is difficult to compare with the R & D Progress of neutralizing antibody or small molecule covid-19 drugs. Therefore, the R & D projects of covid-19 specific drugs developed based on the technology platform of polypeptide in China are compared in parallel. The company's polypeptide nasal spray project has lasted five months since the signing of the patent authorization agreement in November 2021. According to the current progress, In vivo pharmacodynamics research, in vivo pharmacology and toxicology research, safety evaluation research and sample production under GMP conditions are being carried out. Based on the above research
