Abstract 6728: Preclinical development of QL325, a novel T cell engager targeting CLEC12A-positive AML

Abstract Despite advancement in targeted therapies, treatment options for patients with acute myeloid leukemia (AML) that provide a tolerable and durable response remain elusive. We have developed a CD3 bispecific antibody, QL325, targeting CLEC12A, a c-type lectin protein that is highly expressed on AML blasts. Normally, CLEC12A expression is mostly confined to the CD34+CD38- progenitor population and largely absent on normal and regenerating bone marrow stem cells. Our bispecific antibody is configured in a 2 + 1 format, with bivalent avidity binding to CLEC12A, monovalent low affinity binding to CD3, and an effector-null Fc for extending half-life. In our preclinical studies, QL325 induced CLEC12A -dependent activation and proliferation of T cells. Redirected T cell-dependent cytotoxicity mediated by QL325 was restricted to AML cancer cells expressing CLEC12A. QL325 demonstrated dose dependent suppression of tumor growth in xenograft models of AML, significantly more potent than a clinical benchmark antibody. In non-human primates, QL325 was tolerated up to 0. 03 mg/kg for IV dosing and under 0. 1 mg/kg for SC dosing, well above the predicted effective therapeutic dose. A phase 1 clinical trial is currently ongoing to determine the safety and early efficacy in patients with refractory or relapsed AML. Citation Format: Shenda Gu, Hieu V. Tran, Shihao Chen, Ke Liu, Xin Zhang, Linchao Jia, Ruixue Ma, Jiayu Fu. Preclinical development of QL325, a novel T cell engager targeting CLEC12A-positive AML abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts) ; 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84 (6Suppl): Abstract nr 6728.