Guizhou bailing Group Pharmaceutical Co., Ltd. announcement on the progress of tifentai project

The board of directors and all directors of the company guarantee that the contents of this announcement do not contain any false records, misleading statements or major omissions, and shall be jointly and severally liable for the authenticity, accuracy and completeness of the contents Risk tip: in view of the complexity, risk and uncertainty of new drug development, the development of tiffingtai (original Y101) project has a long cycle and large investment, and the research at all stages is risky The company will timely perform the obligation of information disclosure, and invite investors to pay attention to the investment risk 1 The company's tifentai project has the possibility of failure in clinical trials and long clinical trial cycle in the process of new drug approval The clinical study of the project will be carried out according to the approved clinical trial scheme, and the study will be divided into multiple stages The company will timely disclose the information about the cycle time, and there are risks and major uncertainties in each stage; 2 There is a risk that the company's tifentai project cannot obtain the new drug certificate and the drug production approval Guizhou bailing Enterprise Group Pharmaceutical Co., Ltd (hereinafter referred to as "the company" or "Guizhou bailing") cooperates with the Key Laboratory of natural product chemistry of Guizhou Academy of Sciences, Tianjin Pharmaceutical Research Institute and 302 Hospital of the people's Liberation Army to develop a new chemical drug of category 1.1 named "tifentai" (the original Y101) on January 21, 2014, it received the approval for clinical trials of drugs issued by the State Food and drug administration On March 17, 2014, the company signed the technology development (entrustment) contract with Beijing bonoway Pharmaceutical Technology Development Co., Ltd (hereinafter referred to as "bonoway pharmaceutical"), and the company will entrust bonoway pharmaceutical agent to carry out the phase I clinical trial of tifentai tablets On December 14, 2015, the company cooperated with Key Laboratory of natural product chemistry of Chinese Academy of Sciences, Guizhou Province, Tianjin Pharmaceutical Research Institute, 302 Hospital of Chinese people's Liberation Army, the First Affiliated Hospital of Suzhou University, Beijing bonowi Pharmaceutical Technology Development Co., Ltd., etc on chemical medicine 1.1 The research summary has been formed since the phase I clinical trial of the class I new drug "tifentai" project was carried out The interim summary of the phase I clinical trial is made Now the relevant information is announced as follows: 1 The interim summary of the class I new drug "tifentai" project: 1 The clinical trial verifies that the single dose range of 25 mg to 900 mg of tifentai is safe 2 According to the pharmacological experiment completed according to the requirements of clinical approval document, it is proved that tifental can inhibit the production of HBV by inhibiting the calcium Pyk2 signal pathway in cccDNA transcription RNA and up regulating p21 gene At the same time, through the immune regulation of IL-21R, Bcl-2 and other factors, inhibiting the apoptosis of hepatocytes to protect hepatocytes and prevent virus invasion In addition, tifental can also inhibit the content of HBsAg (hepatitis B surface antigen) in the supernatant of cells, have a strong inhibitory effect on HBV DNA in the supernatant of cells, and have an anti drug resistance effect on nucleoside resistance genes 3 The results of grinding to crystal transformation and heat cycle treatment showed that there was no change of crystal form and polymorph in the process of grinding and heat cycle treatment 4 The preparation research shows that the powder with D90 of 44 μ m and normal distribution can be obtained by the airflow pulverizer once, which meets the requirements of the draft quality standard As the FIH test of innovative drugs, since the first phase of the clinical trial of tifentai tablet, in order to ensure the scientificity and ethics of the trial scheme, the research unit has carried out many discussions and scheme updates for the trial design, and the time for ethical review and filing has been extended At the same time, in order to better protect the rights and interests of volunteers, the trial has improved the health requirements of healthy volunteers and reduced the The range of volunteers can be selected, thus prolonging the recruitment time of healthy volunteers, resulting in a delay in the experimental progress compared with the original time According to the current progress of the experiment, if it is approved by the ethics committee in December, it is difficult to recruit volunteers because of the pre experiment design and the special situation of the lunar new year in the middle, so the preliminary estimated completion time of phase I clinical trial is: before May 31, 2016 Later stage plan: 1 The First Affiliated Hospital of Suzhou University and the later stage clinical trial development plan of bonoway medicine: ① there is no adverse reaction in the current tolerance test (up to 900MG), and AUC and Cmax are linearly related to the dosage within the dose range of 25mg-900mg In the next stage, food impact test will be carried out firstly Based on this test, multiple drug administration tests will be carried out ② After the food impact test and multiple drug administration test, POC test is recommended, and the efficacy and effective dose of the drug are confirmed early ③ The urine samples of the 400mg dose group in the single dose trial were continuously detected to calculate the cumulative excretion of human body, so as to provide the preliminary material balance data At the same time, it is suggested that the study of material balance should be carried out after the efficacy of the drug has been confirmed 2 The Key Laboratory of natural product chemistry, Chinese Academy of Sciences, Guizhou Province is responsible for the preparation of the internal standard of tifentai isotopes The type and quantity of isotopes should be confirmed with bonoway pharmaceutical or the First Affiliated Hospital of Suzhou University Complete the synthesis of metabolites M8 and M9 3 302 Hospital of Chinese people's Liberation Army and Tianjin Pharmaceutical Research Institute provided the safety and effectiveness research report of metabolites M8 and M9 4 Guizhou bailing through the air flow grinding test to verify the appropriate air pressure, accurate measurement of D90 44 μ m powder size, control the size range, develop dissolution time, in order to achieve better dissolution effect It is hereby announced Board of directors of Guizhou bailing Group Pharmaceutical Co., Ltd December 14, 2015