Delving into the Latest Updates on ZKA-190 with Synapse

Overview

Basic Info

Drug Type

Monoclonal antibody

Synonyms

Target

Mechanism

NS1 inhibitors(non-structural protein 1 inhibitors), syncytin inhibitors(endogenous retrovirus group W member 1, envelope inhibitors)

Therapeutic Areas

Infectious DiseasesOther Diseases

Active Indication-

Inactive Indication

Zika Virus Infection

Originator Organization

Humabs LLC

Active Organization-

Inactive Organization

Humabs LLC

Drug Highest PhasePendingPreclinical

First Approval Date-

Regulation-

Author: Varani, Luca ; Espinosa, Diego A ; Lanzavecchia, Antonio ; Fibriansah, Guntur ; Foglierini, Mathilde ; Graham, Victoria ; Barca, Taylor ; Simonelli, Luca ; Broccoli, Vania ; Ng, Thiam-Seng ; Lok, Shee-Mei ; Stettler, Karin ; Jaconi, Stefano ; Harris, Eva ; Bardelli, Marco ; Shi, Jian ; Pedotti, Mattia ; Pullan, Steven ; Bianchi, Siro ; Pagani, Isabel ; Beltramello, Martina ; Dowall, Stuart ; Cameroni, Elisabetta ; Wang, Jiaqi ; Lim, Elisa X Y ; Hewson, Roger ; Zerbe, Oliver ; Rubio, Alicia ; Jurt, Simon ; Zatta, Fabrizia ; Cavalli, Andrea ; Sallusto, Federica ; Corti, Davide ; Vicenzi, Elisa

Zika virus (ZIKV), a mosquito-borne flavivirus, causes devastating congenital birth defects. We isolated a human monoclonal antibody (mAb), ZKA190, that potently cross-neutralizes multi-lineage ZIKV strains. ZKA190 is highly effective in vivo in preventing morbidity and mortality of ZIKV-infected mice. NMR and cryo-electron microscopy show its binding to an exposed epitope on DIII of the E protein. ZKA190 Fab binds all 180 E protein copies, altering the virus quaternary arrangement and surface curvature. However, ZIKV escape mutants emerged in vitro and in vivo in the presence of ZKA190, as well as of other neutralizing mAbs. To counter this problem, we developed a bispecific antibody (FIT-1) comprising ZKA190 and a second mAb specific for DII of E protein. In addition to retaining high in vitro and in vivo potencies, FIT-1 robustly prevented viral escape, warranting its development as a ZIKV immunotherapy.

100 Deals associated with ZKA-190

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