DiosCURE to Develop Highly Specific Single-Chain Antibodies Against SARS-CoV-2
- Core technology includes promising bivalent single-domain antibodies simultaneously targeting two surface structures of the viral spike protein.
- Lead candidates DIOS-202 and DIOS-203 are engineered for high potency and their potential to avoid the emergence of escape mutants.
- DIOS-202 and DIOS-203 entered into accelerated development to initiate clinical studies later this year.
DiosCURE Therapeutics SE announced a publication in Science describing its core technology of multivalent single-chain antibodies with a unique molecular mode-of-action to inactivate SARS-CoV-2 virions. An international team led by scientists at the University of Bonn developed and characterized the lead candidates, which are exclusively licensed by DiosCURE.
“This global pandemic requires an arsenal of therapeutic and preventative tools and our lead candidates will allow us to contribute to what will be an ongoing battle,” stated Klaus Wilgenbus, Chief Executive Officer at DiosCURE. “DiosCURE was established with the goal of developing novel, best-in-class immunotherapies to protect a significant population which will remain at risk, including exposed healthcare workers, immunocompromised patients, non-responders to vaccines and patients experiencing post-acute COVID-19 syndrome. The data now published provides a solid foundation to continue our development efforts with the goal of entering the clinic later this year.”
The company’s lead candidates, DIOS-202 and DIOS-203, are synergistic combinations of single-domain antibodies derived from camelid heavy chain-only antibodies. These next-generation immunotherapies against SARS-CoV-2 were designed based on detailed structural information of the antibodies’ interaction with its viral target protein and result from functional and evolutionary experiments. The discovery and promising early preclinical data were published in an article in Science entitled “Structure-guided multivalent nanobodies block SARS-CoV-2 infection and suppress mutational escape” on January 12, 2021. The study details the identification of DiosCURE’s lead candidates out of millions of potential structures, as well as the rational design of multivalent constructs, which increased neutralizing activity more than 100-fold. Preclinical studies demonstrated that DIOS-202 and DIOS-203 selectively target two distinct epitopes of the SARS-CoV-2 spike protein at once, which largely prevents the emergence of escape mutants. The dual targeting induces the premature activation of the fusion machinery, rendering the virions non-infectious. These discoveries were accomplished through a collaborative effort of research groups at the University Hospital of the University of Bonn (led by the Institute of Innate Immunity and the Core Facility Nanobodies), The Scripps Research Institute and the Karolinska Institutet.
The lead candidates are expected to be highly efficacious, well-tolerated, cost-efficient in production and are amenable to a wide range of clinical applications. As immunotherapies, DIOS-202 and DIOS-203 are suitable as prophylactic and to treat infected patients to avoid severe COVID-19 disease.
“The structure-based multivalent single-chain antibodies we discovered have strong potential for clinical applications. This is owed to their highly potent neutralizing activity and in-built protection from the rapid emergence of escape mutants. The emergence of SARS-CoV-2 escape mutants will remain an ongoing challenge in this pandemic, and novel therapies are urgently needed to address this problem,” stated Eicke Latz, Director of the Institute of Innate Immunity at the University of Bonn, co-founder and Board member of DiosCURE. “Our understanding of the short- and long-term consequences of SARS-CoV-2 is rapidly evolving, and rational therapeutics targeting the virus are needed to curb the potentially devastating consequences of COVID-19.”