Abstract 1886: BRY812, an anti-LIV-1 antibody drug conjugate with novel conjugation method for cancer therapeutics

Abstract

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. The PK studies in rat and monkey demonstrated that the free MMAE released from ADC is 1 to 2 logs lower compared with approved ADCs prepared by the standard conjugation method. BRY812 is well tolerated in cynomolgus monkeys with repeated doses. With best-in-class anti-tumor efficacy in various models, BRY812 demonstrated a wider therapeutic window for cancer treatment. BRY812 is currently in Phase Ia dose escalation stage clinical trial to explore the maximum tolerate dosage (MTD) from 0.25 to 3.6 mg/kg Q3W in patients with advanced malignancies. Citation Format: Xiaobei Zhao, Jie Zhu, Yaqiong Zhou, Jing Li, Lei Nie, Haibin Wang, Gang Chen. BRY812, an anti-LIV-1 antibody drug conjugate with novel conjugation method for cancer therapeutics [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1886.