Date: 2013-06-17
Type of information:
phase: 1
Announcement: presentation of pre-clinical results at the Annual 18th Congress of the EHA 2013 (European Hematology Association) in Stockholm.
Company: Merus (The Netherlands)
Product: MCLA-117
Action
mechanism: MCLA-117 is a human, full-length IgG bispecific antibody, which activates the patient’s own immune system by simultaneously binding to the CLEC12A molecule expressed by acute myeloid leukemia (AML) tumor cells and the CD3 molecule expressed by T cells. MCLA-117-mediated co-engagement of CLEC12A and CD3 results in the potent killing of cancerous AML cells and their malignant precursors.
The antibody is based on Merus' Biclonics™ ENGAGE platform. Biclonics™ are full-length, human, bispecific IgG antibodies with a common light chain (cLC) and two different heavy chains. Panels of cLC human antibodies are obtained from MeMo®, a transgenic mouse engineered to generate antibody diversity using a single light chain and diversified heavy chains. Using a proprietary CH3 dimerization technology, the two different heavy chains and the cLC encoding two different specificities are expressed in a single cell to efficiently and stably assemble into Biclonics™. Biclonics™ ENGAGE antibodies bridge T cells and tumor cells through simultaneous binding of CD3 and a tumor associated antigen, thereby inducing potent T cell-mediated tumor cell killing. Bispecific antibodies based on the Biclonics™ ENGAGE platform have IgG constant regions with modified CH2 domains to prevent undesirable cytokine release during therapeutic application.
Disease: acute myeloid leukemia (AML)
Therapeutic area: Cancer - Oncology
Country:
Trial details:
Latest
news: * On June 17, 2013, Merus, a biopharmaceutical company focusing on innovative human antibody therapeutics, has presented preclinical data on its antibody MCLA-117 at the Annual 18th Congress of the EHA 2013 (European Hematology Association) in Stockholm. The compound is being developed for the treatment of acute myeloid leukemia (AML), a disease with very poor long-term prognosis. Co-incubation of patients´ resting T cells and AML tumor cells via MCLA-117 resulted in efficient tumor cell lysis. By introducing mutations in the heavy chain constant region CH2 domain, Merus was able to develop an antibody that in peripheral blood mononuclear cell (PBMC) assays prevented the release of non-specific, pro-inflammatory cytokines, while retaining its full capacity to induce T cell-mediated elimination of AML tumor cells.The company is now looking forward to moving MCLA-117 into clinical development next year.
* On January 7, 2013, Merus, a biopharmaceutical company focusing on innovative human antibody therapeutics, has announced that it has selected MCLA-117 as lead candidate for clinical studies in patients with acute myeloid leukemia (AML). Merus intends to start phase I clinical trials with MCLA-117 in 2014. Prof. Gert Ossenkoppele from the department of hematology at the Free University Medical Centre in Amsterdam will be the lead investigator of the first MCLA-117 Phase I study.
