Abstract 1799: Harnessing the GlycOBI® enabling technologies: next-generation site-specific glycan ADCs with versatile DAR to enhance therapeutic index

The GlycOBI® enabling technologies represent a novel approach for the development of antibody-drug conjugate (ADC) to achieve site-specific glycan conjugation through the proprietary dual-action enzyme EndoSymeOBI®. This innovative technology is capable of attaining homogeneous ADC at specific drug-to-antibody ratio (DAR) while maintaining antibody integrity and function. A key feature of the technology is its exclusive linker, which has a unique design to enhance payload stability and enable selective release in the tumor microenvironment, thereby potentially broadening the therapeutic index. The ADCs that use the GlycOBI® enabling technologies are shown to be highly homogeneous while achieving uniform DAR configurations. These next generation ADCs, combined with optimized and novel linker designs, exhibit superior pharmacokinetics, stability, and antitumor activity compared to conventional ADCs in various animal models. The technology supports mono-specific and multi-specific antibodies, expanding its versatility for various therapeutic modalities. The flexibility of DAR configurations and proprietary linker design further demonstrate the technologies’ adaptability across diverse payload classes, including cytotoxic agents, immunomodulators, and degraders. In preclinical models, OBI-902 (TROP2 GlycOBI® DAR4 ADC) and OBI-904 (Nectin-4 GlycOBI® DAR8 ADC), both using Exatecan, a potent topoisomerase 1 inhibitor as the payload, have demonstrated promising antitumor activities. Notably, OBI-904, with its DAR8 format, exhibits superior activities in animal models, including in low antigen expressing tumor models, compared to approved and other benchmark Nectin-4 ADCs. Further, both ADCs maintained their stability and avoided antibody aggregation. Both candidates are targeted for IND submissions in 2025, representing an important milestone in advancing the GlycOBI® ADCs to the clinics. The integration of glycan engineering, EndoSymeOBI®, and a novel linker design establishes the GlycOBI® suite of technologies as a robust and adaptable solution to address the current ADC limitations. These advancements underscore its transformative potential in driving the next generation of therapeutics. Citation Format: Teng-Yi Huang, Ka-Shu Fung, Yu-Chao Huang, Chi-Sheng Shia, Chi-Huan Lu, Nan-Hsuan Wang, Ya-Chi Chen, Ming-Tain Lai. Harnessing the GlycOBI® enabling technologies: next-generation site-specific glycan ADCs with versatile DAR to enhance therapeutic index [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 1799.