Junshi Biosciences, a leading innovation-driven biopharmaceutical company, announced that the first healthy volunteer has been dosed in the phase I clinical study of JS016 at Huashan Hospital Affiliated to Fudan University in China.
JS016 is the first SARS-CoV-2 neutralizing antibody to enter clinical trials in China. Junshi and Eli Lilly and Company are collaborating to co-develop JS016 globally, with Junshi leading clinical development in China and Lilly leading clinical development in the rest of the world.
The trial is a randomized, double-blind and placebo-controlled study to evaluate the tolerability, safety and pharmacokinetic and immunogenicity of JS016 in healthy subjects. Should phase 1 results show the antibody can be safely administered, the company intends to move to the next phase of testing to study the antibody’s ability to prevent and treat COVID-19. The study researchers are Prof. Zhang Jing and Prof. Zhang Wenhong from Huashan Hospital.
COVID-19 is an acute respiratory infectious disease caused by the SARS-CoV-2 virus that has infected 6.8 million people, with a current death toll of over 390,000 worldwide. There are currently no approved vaccines or specific drugs that target COVID-19.
Neutralizing antibodies may have the potential to prevent and treat COVID-19. Previous clinical trials of agents developed to treat Ebola have shown that monoclonal neutralizing antibodies can reduce viremia, attenuate virulence, substantially improve clinical symptoms and reduce the mortality of those infected.
JS016 was jointly developed by Junshi Biosciences and Institute of Microbiology, Chinese Academy of Sciences (IMCAS). The fully human monoclonal antibody was identified by screening blood samples of patients who recovered from COVID-19. A preclinical study shows that JS016 expresses extremely high specific affinity (on a level of nM) to the SARS-CoV-2 receptor-binding domain (RBD) on the spike protein blocking the virus from invading host cells. A recent publication in Nature (Shi et al. Nature) detailed the findings from a study showing JS016 protected rhesus monkeys from COVID-19 infection, suggesting a potential for prophylactic use in humans.
Professor Zhang Wenhong from Huashan Hospital, head researcher of the clinical study, said: "Neutralizing antibodies can precisely target the SARS-CoV-2 virus which may quickly prevent the virus from replicating in the human body. We hope to demonstrate the safety and tolerability of JS016 in phase I and provide supporting data for additional clinical trials.”
Dr. Yan Jinghua, a co-developer of JS016 and a researcher at IMCAS, said: “Preclinical studies have shown that JS016 has strong neutralizing and blocking ability, as well as prophylactic and treatment effect. We anticipate that JS016 could be further tested in clinical trials.”
Dr. Feng Hui, chief operation officer of Junshi Biosciences emphasized that speed is the key in this campaign against COVID-19 and that “over years of accruing expertise and experience, Junshi has established a research and technology platform for antibody development, enabling us to accomplish the vital steps of protein expression, pharmaceutical research, screening and engineering modification, as well as the technical development for clinical batches and GMP 2000L stable pool manufacturing.”
Dr. Ning Li, chief executive officer said: “We are very pleased that we have achieved this key milestone through joint efforts. Our R&D and manufacturing teams have been working diligently, aiming to help the infected and the vulnerable as quickly as possible.”
JS016 is specific to the SARS-CoV-2 surface spike protein receptor binding domain and can effectively block the binding of viruses to host cell surface receptor ACE2. The project is jointly developed by Junshi Biosciences and Institute of Microbiology, Chinese Academy of Science.
At the beginning of the COVID-19 outbreak, Junshi Biosciences rapidly launched the research and development program of neutralizing antibodies to combat COVID-19. Within two months, the company has completed IND enabling pre-clinical studies, the process development and production for GLP toxicity study and GMP production of clinical material by leveraging the company’s platform technology.
JS016 is a derivative antibody that originated from single B cells of a recovered patient. Screened by the human immune system, JS016 should not bind to human antigens. Researchers also introduced LALA mutations to the Fc portion to potentially lower the risk of antibody-dependent enhancement, antibody-dependent cell-mediated cytotoxicity, and antibody-dependent cellular phagocytosis. Preclinical toxicological experiments of the Maximum Tolerated Dose and No-observed-adverse-effect level are higher than the recommended starting dose for a human clinical trial.