Tag: Biclonics™ ENGAGE platform
Company News: Merus Presents Preclinical Data on its Novel Bispecific Antibody MCLA-117 at EHA 2013
– Clinical Candidate Designed for the Treatment of Acute Myeloid Leukemia (AML) –
Merus B.V., 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.
MCLA-117 activates the patient’s own immune system by simultaneously binding to the CLEC12A molecule expressed by AML tumor cells and the CD3 molecule expressed by T cells. CLEC12A is a myeloid differentiation antigen that is expressed on 90-95% of de novo and relapsed AML cases and is selectively expressed on leukemic stem cells.
Co-incubation of patients´ resting T cells and AML tumor cells via MCLA-117 resulted in efficient tumor cell lysis, i.e. the potent killing of cancerous AML cells. 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 MCLA-117 antibody is based on Merus’ proprietary Biclonics™ ENGAGE platform. Human bispecific antibodies from this platform can be manufactured and administered like conventional, full-length IgG molecules, thereby providing for high yield, good stability and a long serum half-life.
Company News: OcellO and Merus Sign Agreement for Screening Bispecific Cancer Antibodies
OcellO B.V. and Merus B.V. have entered into a collaboration under which OcellO will provide screening services to Merus. OcellO, a biotech company providing drug discovery screening services using its proprietary high throughput 3D cell culture-based screening platform, will use its platform to profile bispecific antibodies designed by Merus for the treatment of cancer. Financial details of the collaboration have not been disclosed.
Mark Throsby, Chief Operating Officer at Merus, commented: “The strength of our approach is its ability to generate thousands of full-length, bispecific human IgG antibodies addressing combinations of targets expressed by tumor cells. OcellO is able to provide high quality data on the functional properties of large panels of bispecific antibodies. These data can’t be obtained from other in vitro screening assays and are pivotal in identifying antibody leads with unique modes of action.”
Company News: Merus Selects Clinical Candidate for the Treatment of Acute Myeloid Leukemia (AML)
Merus B.V., a biopharmaceutical company focusing on innovative human antibody therapeutics, today announced that it has selected MCLA-117 as lead candidate for clinical studies in patients with acute myeloid leukemia (AML). 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 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. Merus intends to start phase I clinical trials with MCLA-117 in 2014.
The antibody is based on Merus’ Biclonics™ ENGAGE platform. Human bispecific antibodies from this platform can be manufactured and administered like conventional, full-length IgG molecules, thereby providing for high yield, good stability and a long serum half life. In addition, bispecific antibodies from the Biclonics™ ENGAGE platform have a modified constant region to abrogate unwanted clinical cytokine release.
Prof. Gert Ossenkoppele from the department of hematology at the Free University Medical Centre in Amsterdam, The Netherlands, will be the lead investigator of the first MCLA-117 Phase I study.