Abstract 5591: Development of a novel anti-CD19 x BCMA dual targeted T cell engager for the treatment of autoimmune diseases and B cell malignancies

Abstract Rationale B cells and autoantibodies drive the progression of autoimmune diseases. Targeting B cells or plasma cells alone is often insufficient to eliminate both pathogenic B cells and autoantibody. Here, we generated HXN-1031, a novel trispecific T cell engager (TCE), simultaneously targeting CD19 and BCMA. Methods: Affinity, cell-binding and cytotoxicity were evaluated in vitro. In vivo efficacy was investigated in mice bearing CD19+ or BCMA+ tumor cells, and in non-human primates. Results: HXN-1031 has sub-micromolar CD3 affinity and nanomolar CD19/BCMA affinity. Against CD19+ targets, it showed weaker potency (IC50) but similar maximum killing efficacy versus Blinatumomab, with significantly reduced T cell activation and cytokine release. For BCMA, HXN-1031 shows high potency in in vitro cytotoxicity. HXN-1031 effectively kills both CD19+ and BCMA+ cells simultaneously within a mixed cell population while maintaining moderate T cell activation and cytokine release. In contrast, CD19-TCE and BCMA-TCE only selectively target B cells (CD19+BCMA-) or H929 (CD19-BCMA+) cells, respectively. In vivo, HXN-1031 demonstrated superior efficacy to Blinatumomab against CD19+ tumors, and significantly suppressed BCMA+ tumor growth, matching Teclistamab analogue efficacy. In non-human primates, HXN-1031 potently depleted, both in peripheral and bone marrow, B cells and plasma cells, leading to significantly reduced serum immunoglobulin, for a prolonged period of times. Conclusion: HXN-1031 is an innovative TCE with finely tuned activity, designed to reset immune system by simultaneously depleting pathogenic B cells and plasma cells. It holds great potential in the treatment of various B cell and plasma cell related autoimmune diseases and malignancies. Citation Format: Lin Huan, Hao Ran, Shiyi Wang, Xiaoping Zhang, Bing Yang, Yang He, Dandan Liu, Chenpeng Su, Chuan Chen, Xiaoqian Chen, Kezhen Ye, Liang Tian, Jian Peng, Zhenping Zhu. Development of a novel anti-CD19 x BCMA dual targeted T cell engager for the treatment of autoimmune diseases and B cell malignancies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 5591.