Mazorelvimab, Zamerovimab Approved Mixture of 2

SYN-023 is a mixture of two anti-rabies humanized monoclonal antibodies, CTB-011 and CTB-012, which bind to 2 different antigenic sites on the rabies glycoprotein; CTB011 targets residues near antigenic site III while CTB012 binds to the highly discontinuous conserved residues. SYN-023 is proposed for use in humans following exposure to the rabies virus. The proposed clinical indication is for post-exposure prophylaxis treatment of rabies in conjunction with rabies vaccine. The proposed mechanism of action is for the mAbs to bind to the rabies virus, which results in virus neutralization in a manner similar to an immune response producing neutralizing antibodies. SYN-023 has been shown to neutralize greater than 15 contemporary wildlife isolates of rabies virus collected in China and 10 isolates collected in the North American. The preclinical studies of SYN-023 have been completed. The Phase I study conducted in the US in healthy adult volunteers has been completed in Jun 2016. The phase II study has been conducting in the US since Aug 2016, and will be completed in 2Q 2017. Derived from immunization of mice with rabies vaccines Rabipur (Flury-LEP strain; Chiron Behring GmbH & Co., Liederbach, Germany), and Speeda (PV-2061 strain; Liaoning Chengda) mixed with complete Freund’s adjuvant. Murine MAbs 3D11E3 and 7G11A3 were humanized by CDR grafting, in which human germline sequences homologous to the variable regions of 3D11E3 and 7G11A3 were chosen as the acceptor for humanization. CDR sequences from 3D11E3 were grafted into GenBank sequence DA980102 for VH and CB958542 for VL. Similarly, CDR sequences from 3D11E3 were grafted into GenBank sequence U96282 for VH and X72466 for VL. The final variable sequences were cloned into a mammalian expression vector carrying human gamma-1 and kappa constant regions. Humanized 3D11E3 and 7G11A3 (CTB011 and CTB012) were then produced from stably transfected CHO DG44 cells