The COVID-19 antibody developed by the VIB-UGent teams of Xavier Saelens and Nico Callewaert has completed the drug development trajectory. Antibody therapeutics will be vital to treat people not yet vaccinated and immunocompromised people. In a preprint publication the scientists show that the antibody neutralizes the newly emerged virus variants. The findings are significant as many other antibodies in development have lost functionality against one or more of the new variants. This makes VIB’s antibody one of the most future-proof antibody therapies for COVID-19 currently under development. VIB spin-off ExeVir Bio will bring this antibody treatment to the clinic.
The coming-of-age story of XVR011
Early in 2020, the labs of Xavier Saelens and Nico Callewaert (VIB-UGent Center for Medical Biotechnology) isolated and developed llama-derived antibodies that neutralize the SARS-COV-2 virus. The antibodies have now been humanized and improved to safely and potently protect against infection by blocking viral entry into cells.
Xavier Saelens says: “While vaccines are a cornerstone of controlling the pandemic, virus-neutralizing antibody-based drugs have an important place in treating people who still fall ill, to head off more severe illness. The therapeutic antibodies can supplement these patients’ immune system, which often fails to mount a sufficiently strong immune response in the first weeks of disease. Especially for people with compromised immune systems, for whom vaccines may not be as effective. On top of that, they can be regarded as a medical insurance policy should coronavirus variants increasingly escape vaccine-induced immunity.“
The antibodies were tested in collaboration with Prof. Johan Neyts (Rega Institute, KU Leuven), as well as with various specialized labs abroad. Today the VIB teams present new developments in a bioRxiv preprint publication, awaiting peer review and formal publication.
Nico Callewaert explains: “We could rapidly further improve the neutralizing activity by enhancing the antibody’s binding affinity to the viral proteins by protein engineering. The drug candidate has entered preclinical development and manufacturing in the Spring of 2020, a time-consuming process that is now completed. This work yielded XVR011, a highly stable anti-COVID-19 biologic with excellent manufacturability that will be tested in patients in the coming months.”
Effective against rapidly spreading variants of the coronavirus
During the last months, US authorities issued an emergency use authorization for several antibody-based drugs to treat non-hospitalized patients. However, most of these antibodies are now reported to be no longer effective against the new virus variants that have emerged. These variants have undergone changes in their spike protein, making it more difficult for these human immune response-derived antibodies to bind the virus. In addition, evidence is growing that particular SARS-CoV-2 variants are less sensitive to immune responses induced by natural infection or vaccines.
VIB’s research in animal models now shows that XVR011 is unaffected by the changes in new variants. The llama antibody that we use is smaller than human antibodies, allowing it to potently target a unique and highly conserved region in the viral spike protein. As this region is difficult to access for the more bulky human antibodies, it is subject to a much lower selective pressure imposed by the human immune system. Furthermore, mutations are less likely to occur in this region as it appears important for the intricate functioning of the virus’ spike protein.
The extensive protective potential against other members of the SARS-CoV-2-like virus family will also make the antibody a vital component of future pandemic readiness.
Ready for human trial
Mid 2020, VIB set up ExeVir Bio to bring this antibody treatment into the clinic. In due time, the spin-off will announce the start of Phase I and II clinical trials to test the drugs for safety and efficacy in Covid-19 patients. ExeVir Bio will continue to collaborate with top academic research groups for further optimization of XVR011.
Jérôme Van Biervliet, managing director at VIB, concludes: “This work towards a COVID-19 drug can be considered as a blueprint for antibody development for next pandemics. The progression these VIB teams made in just 12 months is incredible. Their past year’s activities can serve as points of reference to provide a common orientation and clear picture of what is needed in future pandemic response.”