On June 5, Shanghai Junshi Biopharmaceutical Technology Co., Ltd. and the Institute of Microbiology of the Chinese Academy of Sciences and other units jointly developed the recombination of the whole human source anti-new coronavirus monoclonal antibody injection (hereinafter referred to as “JS016”) was approved by the State Drug Administration, entered the Phase I clinical trial stage. This morning, Huashan Hospital, affiliated with Fudan University, completed the first drug administration of the subjects.
This is the world’s first completed non-human primate experiments, in the healthy population to carry out a new coronary pneumonia therapeutic antibody clinical trial, marking with China’s independent intellectual property rights of the new coronavirus-specific antibody drugs successfully entered the human clinical evaluation stage.
The clinical trial, conducted by Professor Zhang Wei and Zhang Wenhong of Huashan Hospital and Zhang Wenhong, was conducted to evaluate the tolerance, safety, pharmacokinetic characteristics and immunogenicity of JS016 intravenous infusion sending in Chinese health volunteers.
Professor Zhang Said introduced that the first dose group of 4 healthy subjects in the morning in good condition, followed by strict lying in accordance with the trial program continued to advance. All obtained healthy subject safety tolerance data will support the selection of the appropriate dose for subsequent clinical trials in patients with new coronavirus infection.
According to Dr. Feng Hui, chief operating officer of Junshi Bio, neutralizing antibodies produced by human B lymphocytes, and when the virus invades the cells, the antibodies can preemptively bind to antigens on the surface of the virus and “neutralise” them. As a “foreign aid” of recombinant expression of genetic engineering, neutralizing antibody drugs injected into the human body can preemptively bind to the new coronavirus protrusion protein (S protein), so that the virus can not infect human cells, and thus by the immune system to remove. Previous clinical trials have shown that monoclonal neutralizing antibodies can reduce the level of virus in Ebola patients, effectively neutralizing the virus, substantially improving clinical symptoms, and reducing the mortality rate of infected people.
Professor Zhang Wenhong said: “Neutralantibodies can be accurate attack against the new coronavirus, with a unique target, can prevent the virus from replicating in the human body, quickly produced.” We hope to demonstrate the good safety and tolerability of JS016 in Phase I, providing data support for subsequent clinical programs. Neutralizing antibody therapy is expected to be the first treatment option to fight the new coronavirus. “
In addition to the potential therapeutic effects, previous studies have also shown that neutralizing antibody drugs has the effect of preventing viral infections. Unlike vaccines, this drug is more suitable for the prevention of emergency intensive care unit medical staff, elderly and other key groups of people, and complements the vaccine. “Preclinical studies have shown that JS016 has a strong ability to moderate and block, as well as the dual role of prevention and treatment of new coronaviruses,” said Yan Jinghua, a researcher at the Institute of Microbiology of the Chinese Academy of Sciences. We very much expect it to be further validated clinically. “
According to reports, JS016 originated from the new coronary pneumonia recovery period patients in the body. Researchers at the Institute of Microbiology of the Chinese Academy of Sciences used single-cell sequencing technology to isolate neutral monoclonal antibodies from single nuclear cells of the patient’s peripheral blood, and used streaming cell technology to perform blocking test analysis, screen edited and active antibodies and recombinator expression in vitro. With the support of the Ministry of Science and Technology and the Shanghai Science and Technology Commission’s Emergency Science and Technology Project, Junshi Bio carried out multi-way parallel development of antibodies screened by the micro-organisms of the Chinese Academy of Sciences, completed the key steps of protein expression, immunoglobulin Fc segment (crystalline segment) engineering transformation, cell line construction and other antibody process development and large-scale production, reducing the stable cell strain that would have taken 4 to 6 months to prepare to 3 months.
Under the overall promotion of the joint prevention and control mechanism of the State Council, antibody research and development has been strongly supported by the Ministry of Science and Technology, the National Health and Health Commission, the State Drug Administration, the Chinese Academy of Sciences, Shanghai and Beijing.
Preclinical studies have shown that JS016’s receptor binding region (RBD) of the new coronavirus S protein exhibits a very specific affinity, reaches the nanomole level, and is able to bind to the virus first, blocking the virus from invading host cells at the source.
In terms of effectiveness, the rhesus monkey animal infection experiment showed the treatment and prevention effect of JS016, the results showed that the neutralizing antibody effectively blocked the infection of the new coronavirus, significantly reduced the load of the new coronavirus in the respiratory tract of rhesus monkeys, and protected the lung damage caused by the virus infection. The data have been published online in Nature, the world’s top technology magazine.
In terms of safety, the JS016 antibody gene comes from a single B-cell in a recovering patient and is an all-human natural antibody, which is expected to have better safety. In addition, in order to reduce the risk of acute lung injury from antibody-mediated and ensure safety in clinical applications, the team modified JS016 for Fc segment modification, effectively reducing possible antibody-dependent enhanced effects (ADE), antibody-mediated cytotoxic effects, and cell phagocytosis effects. In preclinical pre-eating crab monkey toxicology studies, the maximum tolerable dose and the unobserved dose of no significant toxic reaction were dozens of times the recommended starting dose in human clinical trials, meaning that there was a large safety window.
Experts say there is still a long way to go from entering the human clinical trial stage to the final use of antibody drugs.