12 January 2021 - - A recent publication in Science describes Germany-based DiosCURE Therapeutics SE's core technology of multivalent single-chain antibodies with a unique molecular mode-of-action to inactivate SARS-CoV-2 virions, the company said.

An international team led by scientists at the University of Bonn developed and characterized the lead candidates, which are exclusively licensed by DiosCURE.

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.

DiosCURE is developing next-generation immunotherapies focused on a novel approach against SARS-CoV-2.

The company's proprietary bi- and trivalent variable domains of heavy chain-only antibodies are synergistic combinations of single-domain antibodies, constructed following structural information and optimized for potency as well as their potential to avoid the emergence of escape mutants.

DiosCURE designed lead candidates that target two different epitopes of the SARS-CoV-2 spike protein with the potential to be highly efficacious, well-tolerated and manufactured at a large-scale standardized process.