Abstract 1532: Next generation IgM antibody based multimeric platform: ePENDY (engineered pentamer body)

Abstract Among many candidates from the recent diverging research to develop a multivalent platform, IgM has shown potential as a pharmaceutical because of its avidity coming from natural multimeric target binding ability. IgM has a great advantage of naturally forming multimers, however, there are some unfulfilled needs to become a good pharmaceutical platform, such as limited biological activity, short half-life, safety concerns, and difficult purification steps compared to IgG. Here, we developed an antibody platform, ePENDY, by engineering IgM to improve efficacy, safety, and convenience of manufacturing process. ePENDY has a self-assembling decavalent pentameric structure and it is an improved IgM with maximized biological activity as therapeutics by using flexible linkers. In addition, ePENDY was engineered one of the effector functions of antibodies, ADCC, was greatly increased compared to IgG as well as IgM which does not have this function. More importantly, the presence or absence of effector functions can be controlled depending on the MoA (Mode of action) of the target. Serum half-life of ePENDY was significantly increased compared to natural IgM, and ePENDY showed similar PK profiles as the IgG Fc-based molecules through FcRn recycling. Unlike natural IgM, ePENDY does not bind to any IgM receptors, such as pIgR, FcμR, and Fcα/μR, thereby eliminating possible side effects. In addition, it has been confirmed that ePENDY showed a comparable expression level to that of IgG, and since the purification process can also be set up in a process like IgG, thus production of ePENDY can be facilitated. Based on these results, we are researching ePENDY which are applying various therapeutic molecules, such as antibodies, protein ligand-based active molecules and therapeutic cancer vaccines. We expect that our versatile applicable platform, safe and long acting ePENDY, can be a superior tool for the various therapeutic targets. Citation Format: Sungmuk Kang, Hyeonju Kang, Jihye Koo, Yoojin Kim, Suho Park, Inyoung Lee, Jiye Yi, Hong Jai Lee, Yonghyun Cho, Hyunju Hwang, Kyunggi Hyun, Chungmin Lee, Gyongsik Ha. Next generation IgM antibody based multimeric platform: ePENDY (engineered pentamer body) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1532.