Boan Biotech Publishes Research Results of Self-Developed Neutralizing Antibody Against SARS-CoV-2 Variants in Nature Sub-Journal

Boan Biotech announces recently that the research paper Biparatopic Antibody BA7208/7125 Effectively Neutralizes SARS-CoV-2 Variants Including Omicron BA.1-BA.5, completed by the joint efforts of Boan Biotech, the team led by Professor Jincun Zhao of the State Key Laboratory of Respiratory Diseases(SKLRD), the Cryo-electron Microscopy Center of Southern University of Science and Technology, and the National Institute for Food and Drug Control, was officially published in Cell Discovery(IF:38.079), which is a journal of the Nature Portfolio . The research results revealed that the biparatopic antibody BA7208/7125, self-developed by Boan Biotech, had broad-spectrum neutralization abilities against 18 different SARS-CoV-2 variants including Omicron BA.1-BA.5, suggesting that it has the potential to become a promising candidate as an intervention against COVID-19.

BA7208/7125 is a 1+1 biparatopic antibody engineered by leveraging Boan Biotech’s bispecific antibody technology platform and has excellent druggability. Monoclonal antibodies BA7208 and BA7125 are obtained by sequential immunization and sequential screening of spike proteins of various variants with Boan Biotech’s Human Antibody Transgenic Mice and Phage Display Technology. The pseudovirus neutralization assay in vitro indicated that BA7208/7125 had broad-spectrum neutralization abilities against 18 SARS-CoV-2 variants including early discovered variants and Omicron BA.1-BA.5.

To evaluate the neutralization abilities of BA7208/7125, the team led by Professor Jincun Zhao, Director of SKLRD, carried out both in vitro and in vivo therapeutic potency tests using authentic virus. The research on therapeutic potency against authentic virus in mice indicated that BA7208/7125 administered via intraperitoneal injection, intranasal spray and aerosol inhalation could all effectively prevent or treat Omicron BA.1/BA.2 infection, significantly reduce the viral titer in the lungs of animal infection models, and basically achieve viral clearance, suggesting excellent protective effect.

In the cryo-electron microscopy research conducted by the Cryo-electron Microscopy Center of Southern University of Science and Technology, the reason why this biparatopic antibody has a good neutralizing activity was analyzed from the structural point of view -- BA7208 and BA7125 bind to the conservative epitope of receptor domain(RBD), which avoid most mutation-sensitive sites in the spike protein RBD on the surface of SARS-CoV-2, thus greatly reducing the risk of losing neutralizing activity against SARS-CoV-2 variants.

Figure 1: Broad-spectrum neutralizing antibodies obtained via sequential immunization and sequential screening regimen

Figure 2: Prophylactic or therapeutic efficacies of BA7208/7125 administered via intraperitoneal injection, intranasal spray and aerosol inhalation in mouse infection models

Figure 3: Structure of the trimeric SARS-CoV-2 Spike in complex with BA7208 and BA7125 Fab by Cryo-electron microscopy

The impact of SARS-CoV-2 outbreak on people’s health and economies around the world has continued unabated. Due to the continuous mutation of SARS-CoV-2, the efficacy of existing neutralizing antibodies and vaccines has declined. Therefore, there is an urgent need to develop efficient neutralizing antibodies with broader spectrum. The use of cocktail treatment, involving two or more neutralizing monoclonal antibodies (nmAbs), may lead to increased efficacy and better resistance to viral escape than monotherapy. The bispecific antibody that integrates two monoclonal antibodies has the advantages of low production cost and convenient pre-clinical and clinical development compared with cocktail treatment.

Jincun Zhao, the corresponding author and professor at SKLRD, noted: " The rapid mutation of the SARS-CoV-2 and the coexistence of multiple variants are the main challenges of the current and future COVID-19 prevention and control. Mice in both prevention and treatment groups using the biparatopic antibody BA7208/7125 showed accelerated viral clearance in the lungs, suggests that the antibody can be efficiently delivered and treat pulmonary disease via diverse routes. This research has provided a useful exploration for the subsequent development of more efficient and broad-spectrum neutralizing antibodies to combat the SARS-CoV-2.”

Deyong Song, the co-author and Director of Biopharmaceutical Discovery Research Department of Boan Biotech, said, “This biparatopic antibody integrates the respective merits of the two monoclonal antibodies. Comparing with cocktail treatment, it enjoys the advantages of low production cost and convenient clinical development as single molecule, standing as an effective development strategy to combat the mutation and escape of SARS-CoV-2 variants.”

As one of the innovative biopharmaceutical companies to first develop antibodies against SARS-CoV-2 in China, Boan Biotech has been fully engaged in the research and development of treatments for COVID-19 since the pandemic. With the proprietary Human Antibody Transgenic Mice and Phage Display Technology platform, Boan Biotech has developed a number of neutralizing antibody candidate products against SARS-CoV-2, of which the broad-spectrum neutralizing antibody BA-CovMab injection has been approved for clinical trials in China. Dr. Changlin Dou, President and Chief Operating Officer of Boan Biotech, stated, "We will continue to invest resources in the development and research of broad-spectrum neutralizing antibodies against SARS-CoV-2 variants, and make our own contributions to the fight against the pandemic."