Boan Publishes LY-CovMab Research Results in Nature Sub-journal

Luye Pharma Group announced that a research paper on LY-CovMab, an innovative antibody developed by Boan Biotech, a holding subsidiary of the Group, has been published in Communications Biology, a sub-journal of Nature magazine.

The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a tremendous threat to human health and the global economy. LY-CovMab is a human monoclonal neutralizing antibody that binds specifically to the receptor-binding domain in SARS-CoV-2 Spike protein with high affinity, and can effectively block the attachment of the virus to the host cell surface receptor ACE2.

The research demonstrates that LY-CovMab exhibits excellent neutralization potency against pseudovirus and authentic virus infection.

• The FALA mutation introduced to LY-CovMab abrogates the binding with Fc receptors or complement receptors, reducing the antibody-dependent enhancement (ADE) risk. 
• LY-CovMab demonstrates a long half-life, with a terminal half-life (t1/2, λz) of 9.5 days in mice, and 9.3 days in rhesus monkeys.
• LY-CovMab shows therapeutic efficacy in mice challenged with mouse-adopted SARS-CoV-2. LY-CovMab treatment resulted in a 4.5 log reduction of viral titers in the lungs at 3 days post injection. Histopathological examination also showed clear improvement in the lung.
• Structural analysis by cryo-EM revealed that LY-CovMab recognizes an epitope overlapping with angiotensin converting enzyme 2 (ACE2)-binding sites in SARS-CoV-2 RBD in the Spike protein. The 3D structures derived from Spike-CA521FALA Fab or IgG complex show that all three RBDs of the Spike protein trimers bound with antibody regardless of the conformation of RBD. Interestingly, two RBDs were ‘up’ while another one was ‘down’ in S-CA521FALA Fab complex, but all three RBDs were ‘up’ in S-CA521FALA IgG complex. CA521FALA IgG may use a mechanism similar to ACE2 and promote the opening of other closed RBDs to facilitate the binding of CA521FALA after binding the ‘open’ RBD. The 3D structures also showed two of three Fabs in contact with each other, which suggests the bivalent binding of one CA521FALA IgG molecule with two RBDs. All these characteristics contribute to the potent blocking and neutralization ability of CA521FALA. 

▲Structural Analysis of LY-CovMab by Cryo-EM

Dr. Changlin Dou, the corresponding author, R&D President and Chief Operating Officer of Boan Biotech said:

"These results demonstrate the importance of antibody-based therapeutic interventions against COVID-19 and identify CA521FALA as a promising antibody that reacts with SARS-CoV-2 Spike protein to strongly neutralize its activity. Boan Biotech has also conducted additional variants studies and found that LY-CovMab has good neutralization potency against SARS-CoV-2 variant B.1.1.7, which derives from the UK and occurs at a relatively higher frequency."

Boan Biotech is one of the first innovative biopharmaceutical companies in China to develop neutralizing antibodies against SARS-CoV-2. In developing  this candidate, Boan Biotech has shown the efficiency of its antibody development capabilities via its human antibody transgenic mouse technology and phage display technology. BA-huMab are the first human antibody transgenic mice in China and have been used in multiple programs. Antibodies derived from BA-huMab do not require the antibody humanization process. Boan Biotech was able to obtain the lead antibody against SARS-CoV-2 in less than 50 days using this platform. In addition, LY-CovMab adopted a special design for the Fc region, which reduced the ADE risk and improved the safety profile of the antibody.

Currently, LY-CovMab is at the late stage of the phase I clinical trial in China. China’s Ministry of Science and Technology has included LY-CovMab in its COVID-19 Neutralizing Antibody Emergency Projects. Outside of China, Boan Biotech will also carry out clinical research with patients in the United States to support the launch of LY-CovMab in global markets.