TB202-3

**TB202-3** is a VHH single-domain antibody (nanobody) fused to an Fc domain, discovered using Twist Bioscience's synthetic antibody libraries. It exhibits picomolar-affinity binding to the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein, specifically targeting the conserved epitope involving residues N450, I472, and F490, which enables potent neutralization of ancestral SARS-CoV-2 virus in vitro and in vivo, as well as beta pseudovirus. TB202-3 demonstrates broad binding to variants including Delta and Omicron subvariants (BA.1, BA.2, BA.3, BA.4/5), though with reduced affinity and neutralization against some like Lambda (due to L452Q/F490S) and BA.4/5. In hamster models, it protected against weight loss and reduced lung viral loads when administered post-challenge. It has been evaluated in bispecific formats like RBT-0813 and TB493-011 for enhanced activity against evolving variants.[1][3][4][9][10][11]