DiosCURE’s drug candidates are based on highly specific neutralizing single-domain antibodies or nanobodies that target two distinct binding surfaces of the SARS-CoV-2 spike protein.

Unlike conventional antibodies, single-domain antibodies can be combined into multivalent formats that incorporate several binding specificities into a single therapeutic molecule.

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We use structural, biophysical, and functional information to engineer multivalent nanobodies with substantially improved properties. The combination of synergistic nanobodies that simultaneously attack the viral fusion protein on two unique surfaces, improved the neutralizing activity of our lead candidates by several orders of magnitude.

With this unique mechanism of action, the spike protein gets prematurely trapped and undergoes critical structural changes. This process strips the virus of the energy it would otherwise need in order to fuse with target cells, rendering it non-infectious. Evolutionary experiments show that the beneficial combination of two target sites also avoids the rapid emergence of escape mutants, indicating optimized long-term efficacy.

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Our candidates represent the latest generation of immunotherapeutics against SARS-CoV-2, and have the potential to be highly efficacious, well-tolerated and cost-efficient.

PIPELINE

Best-in-class approach

The Company’s lead candidates, DIOS-202 and DIOS-203, represent a novel generation of single-domain antibodies, specifically targeted against SARS-CoV-2. The most promising candidates have been carefully selected based on structural information and analyses. DIOS-202 and DIOS-203 have demonstrated their ability to effectively target two different parts of the SARS-CoV-2 spike protein, with the potential to be highly efficacious. Beyond optimizing for potency, DIOS-202 and DIOS-203 have the potential to successfully avoid emerging escape mutants of the virus.

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Our therapeutic candidates can be applied to prevent infection and to treat infected patients avoiding severe COVID-19 disease progression. Lacking the fragment crystallizable (Fc) part of the antibody structure, our novel design allows production in non-eukaryotic manufacturing systems, thereby reducing costs and allowing the production of high protein yields. Our approach is based on scientific discoveries by scientists at the Institute of Innate Immunity of the University Hospital Bonn in collaboration with the Scripps Research Institute and the Karolinska Institutet and exclusively in-licensed by DiosCURE for further rapid development.

We are accelerating our preclinical development and expect to enter the clinic in 2021.

SARS-CoV-2 with intact spike – infectious

S1/S2 complex

viral membrane

nucelocapsid

geonomic RNA+N protein

SARS-CoV-2 with post-fusion spike – non-infectious

S2

viral membrane

nucelocapsid

geonomic RNA+N protein