Abstract 6027: Translational medicine studies of BRY812, an anti-LIV-1 antibody drug conjugate for cancer therapeutics

Abstract LIV-1, also known as SLC39A6 or ZIP6, belongs to the zinc transporter family and was initially identified as an estrogen-inducible gene in breast cancer. Immunohistochemical (IHC) analysis have revealed escalated LIV-1 expression in estrogen receptor-positive (ER+), hormone-treated tumors (both primary and metastatic sites) as well as ER-/PR-/Her2- (triple-negative) breast cancers. Notably, healthy human tissues exhibit limited LIV-1 expression, primarily in hormone regulated organs (prostate, uterus, and breast). The escalated expression of LIV-1 in breast and prostate cancer, as well as melanoma and other tumors, positions LIV-1 as an excellent target for ADC therapeutics. BRY812 is a monomethyl auristatin E (MMAE)-conjugated humanized IgG1 ADC against LIV-1. With Bioray’s irreversible conjugation method CysLinkTM, BRY812 enables superior in vivo stability and eliminates off-target payload migration. Recent translational medicine studies have shown that BRY812 exhibits favorable efficacy in in vitro models of Breast cancer and Endometrial cancer. Additionally, BRY812 has demonstrated synergistic efficacy when combined with PD-1/L1 antibodies in a series of in vitro and in vivo models. Finally, BRY812 has shown improved efficacy in DS-8201 resistant cell line compared to the parental cell line. These results showed that BRY812, either as a monotherapy or in combination with other drugs, has a significant potential for application in various solid tumor indications, as well as in patients who are resistant to existing therapies. Citation Format: Qinqin Zhuang, Qianqian Tao, Xiaobei Zhao, Jie Zhu, Lei Nie, Gang Chen, Haibin Wang. Translational medicine studies of BRY812, an anti-LIV-1 antibody drug conjugate for cancer therapeutics [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6027.