The China National Medical Products Administration (NMPA) has accepted the Investigational New Drug (IND) application for BRY812, a novel antibody-drug conjugate (ADC) targeting human LIV-1 for the treatment of advanced malignant tumors (Acceptance No. CXSL2300366). The investigational drug is being developed by Shanghai-based BioRay Pharmaceutical Co.
LIV-1, also known as SLC39A6 or ZIP6, is a multi-pass transmembrane protein that belongs to a subfamily of proteins group that displays structural specifications of zinc transporters in the cell membrane. Over-expression of this protein is observed in breast, prostate, and kidney tumor cells. 
As a multi-pass transmembrane protein with zinc transporter and metalloproteinase activity, the involvement of LIV-1 in the homeostatic metabolism of zinc in cells and its role in promoting cell growth make it a key factor in tumor metastasis and the epithelial-mesenchymal transformation (EMT) process.
BRY812 is a LIV-1 targeting ADC developed on BioRay’s CysLink™ technology platform where highly stable conjugation is created through irreversible chemistry. By binding to LIV-1 on the surface of tumor cells, the ADC-target complex enters the tumor cell’s lysosome through endocytosis, releasing small molecule toxins that selectively kill tumor cells. In pre-clinical pharmacological studies, BRY812 demonstrated significant antitumor activity in various tumor models.
Compared to other ADCs targeting the same pathway, BRY812 has higher stability in circulation by eliminating payload exchange, delivering toxins more selectively to tumor tissue, which resulted in a superior safety profile in pre-clinical toxicology studies. Globally, no LIV-1 targeting ADC has received marketing approval yet, and BioRay’s BRY812 is anticipated to be the second LIV-1 ADC that reaches the clinical stage.
“Since this January, we have obtained the IND approval of two innovative antibody-drug candidates, BR108 and BRY805,” noted Haibin Wang, MD, Chief Executive Officer of BioRay.
“We are committed to finding better therapeutic options for patients living with cancers and immune-mediated diseases. We will continue the research in exploring innovative targets, technologies, and therapeutic modalities, including ADCs, Wang added.
 Bagheri S, Hashemi M, Alirahimi E, Habibi-Anbouhi M, Kazemi-Lomedasht F, Behdani M. Recombinant Expression of Zinc Transporter SLC39A6 and Its Functional Antibody Production. Monoclon Antib Immunodiagn Immunother. 2019 Apr;38(2):70-74. doi: 10.1089/mab.2018.0045. PMID: 31009334
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