AUG-3387, a Human-Derived Monoclonal Antibody Neutralizes SARS-CoV-2 Variants and Reduces Viral Load from Therapeutic Treatment of Hamsters In Vivo

Emig, C. J.; Mena, M. A.; Henry, S. J.; Vitug, A.; Ventura, C. J.; Fox, D.; Nguyenla, X. H.; Xu, H.; Moon, C.; Sahakijjpijarn, S.; Kuehl, P. J.; Revelli, D.; Cui, Z.; Williams, R. O.; Christensen, D. J.

doi:10.1101/2021.10.12.464150

bioRxiv · 10.1101/2021.10.12.464150

AUG-3387, a Human-Derived Monoclonal Antibody Neutralizes SARS-CoV-2 Variants and Reduces Viral Load from Therapeutic Treatment of Hamsters In Vivo

Emig, C. J.·Mena, M. A.·Henry, S. J.·Vitug, A.·Ventura, C. J.·Fox, D.·Nguyenla, X. H.·Xu, H.·Moon, C.·Sahakijjpijarn, S.·Kuehl, P. J.·Revelli, D.·Cui, Z.·Williams, R. O.·Christensen, D. J.

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Abstract

Infections from the SARS-CoV-2 virus have killed over 4.6 million people since it began spreading through human populations in late 2019. In order to develop a therapeutic or prophylactic antibody to help mitigate the effects of the pandemic, a human monoclonal antibody (mAb) that binds to the SARS-CoV-2 spike protein was isolated from a convalescent patient following recovery from COVID-19 disease. This mAb, designated AUG-3387, demonstrates a high affinity for the spike protein of the original viral strains and all variants tested to date. In vitro pseudovirus neutralization and SARS-CoV-2 neutralization activity has been demonstrated in vitro. In addition, a dry powder formulation has been prepared using a Thin-Film Freezing (TFF) process that exhibited a fine particle fraction (FPF) of 50.95 {+/-} 7.69% and a mass median aerodynamic diameter (MMAD) and geometric standard deviation (GSD) of 3.74 {+/-} 0.73 {micro}m and 2.73 {+/-} 0.20, respectively. The dry powder is suitable for delivery directly to the lungs of infected patients using a dry powder inhaler device. Importantly, AUG-3387, administered as a liquid by intraperitoneal injection or the dry powder formulation delivered intratracheally into Syrian hamsters 24 hours after intranasal SARS-CoV-2 infection, demonstrated a dose-dependent reduction in the lung viral load of the virus. These data suggest that AUG-3387 formulated as a dry powder demonstrates potential to treat COVID-19.

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Emig, C. J., Mena, M. A., Henry, S. J., Vitug, A., Ventura, C. J., Fox, D., Nguyenla, X. H., Xu, H., Moon, C., Sahakijjpijarn, S., Kuehl, P. J., Revelli, D., Cui, Z., Williams, R. O., Christensen, D. J.. 2021-10-13. AUG-3387, a Human-Derived Monoclonal Antibody Neutralizes SARS-CoV-2 Variants and Reduces Viral Load from Therapeutic Treatment of Hamsters In Vivo. https://doi.org/10.1101/2021.10.12.464150

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