Abstract 6022: YH006: a next-generation CTLA-4×OX40 Treg antagonist, demonstrates superior tumor-infiltrating Treg-depletion efficacy and favorable manufacturability

Abstract Immune checkpoint inhibitors have revolutionized the treatment of early and advanced cancer. Especially combination of anti-cytotoxic T lymphocyte associated antigen 4 (CTLA-4) antibody and anti-programmed death-1 (PD-1) antibody, has shown remarkable efficacy against various cancers and approved for 7 indications by the US FDA. However, there are still limitations with regard to response rates and dose-dependent immune related adverse events (irAEs) caused by CTLA-4 antibody for fully achieve the optimal therapeutic effect for the combination strategy. YH006 is a monovalent bsAb with effector enhanced Fc domain, generated from Biocytogen RenLiteTM common light chain mice, designed to deplete tumor-infiltrating Treg cells with better specificity, based on tumor-infiltrating Treg cells consistently exhibit higher expression levels of both CTLA-4 and OX40 compared to T cells in the periphery across multiple cancer types. YH006 potent to selectively depletion of tumor-infiltrating Tregs and increase the intra-tumoral CD8/Treg ratio, outperform the first and other next generation of anti-CTLA-4 agents in vivo efficacy at low dose. Notably, the antitumor activity of PD-1 mAb was significantly enhanced when combined with YH006 in syngeneic MC38 models at high tumor burden. Ongoing CMC process development has a titer of over 6 g/L at the 20 L scale, and the overall purification yield of >80%. YH006 also has consistent quality from research cell bank to passage 90, suggesting excellent developability. Citation Format: Sarah Chan, Baihong Liu, Bahetiyaer Huwatibieke, Jing Zhang, Yang Chen, Minjuan Meng, Wenchao Zheng, Lei Zhang, Yi Yang. YH006: a next-generation CTLA-4×OX40 Treg antagonist, demonstrates superior tumor-infiltrating Treg-depletion efficacy and favorable manufacturability [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 6022.