Abstract 3520: EM1031, a novel KLK2 x CD3 bispecific T-cell engager with highly effective efficacy in preclinical models

Therapeutic options for metastatic castration-resistant prostate cancer (mCRPC) are limited within hormonal therapies, taxane-based chemotherapies and palliative radiotherapy. Currently available targeted therapies or immunotherapies have limited efficacy and can only benefit a small population of mCRPC patients. Human kallikrein 2 (KLK2) is a membrane-bound trypsin-like serine protease that shares 78% homology with prostate specific antigen (PSA). Directly regulated by androgen receptor (AR), KLK2 is specifically expressed in epithelial cells of prostate and prostate cancer cells and was considered as a promising tumor associated target. In this case, we have developed EM1031, a novel KLK2 x CD3 bispecific T-cell engager (TCE) based on EpimAb’s proprietary CD3 antibody and bispecific antibody platform, adopting optimized CD3 affinity and binding arm valency to achieve potent redirected tumor cell lysis while maintaining minimal cytokine release. In vitro T-cell activation and cytokine release assay showed that EM1031 activates T cells only in the presence of KLK2 positive target cells. A clinical stage reference KLK2 TCE was also generated with published sequences for comparison. In preclinical studies, EM1031 showed less cytokine release against KLK2 positive prostate cancer cell lines than the reference KLK2 TCE, while it maintained comparable in vitro tumor cell killing activity. In xenograft models derived from KLK2 positive prostate cancer cell lines, EM1031 completely eradicated tumors with lower cytokine release compared to the reference TCE. Taken together, these data suggest that EM1031 has the potential in the treatment of prostate cancer. Citation Format: Zelong Ma, Beilei Shi, Zheng Wei, Weiqing Guo, Li Hu, Yixuan Li, Xuan Wu, Shiyong Gong, Danqing Wu, Chengbin Wu. EM1031, a novel KLK2 x CD3 bispecific T-cell engager with highly effective efficacy in preclinical models [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 3520.