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International Society for Antiviral Research

ICAR2020 Abstracts

Development of REGN-COV2, an anti-spike antibody cocktail for treatment and prevention of COVID-19

Alina Baum, PhD

Regeneron, Tarrytown, New York, United States of America

Antibodies targeting the spike protein of SARS-CoV-2 present a promising approach to combat the COVID-19 pandemic. Through a large screen of thousands of anti-spike monoclonal antibodies from humanized mice and convalescent humans we selected multiple pairs of highly potent neutralizing antibodies that simultaneously bind the receptor-binding domain of the spike protein. Escape studies with individual antibodies and two antibody combinations revealed that novel spike mutants rapidly appeared following in vitro passaging in the presence of individual antibodies, resulting in loss of neutralization. Such escape also occurred with combinations of antibodies binding diverse but overlapping regions of the spike protein but not with antibodies binding to non-overlapping epitopes. A combination of two non-competing highly potent neutralizing mAbs (REGN-COV2) was selected for clinical development. We evaluated the in vivo efficacy of this antibody cocktail in both rhesus macaques and golden hamsters and demonstrated that REGN-COV2 can greatly reduce virus load in lower and upper airway and decrease virus induced pathological sequalae when administered prophylactically or therapeutically, thus providing strong evidence for potential clinical benefit in both treatment and prophylaxis of COVID-19.

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