– Clinical Candidate Designed for the Treatment of Acute Myeloid Leukemia (AML) –
UTRECHT, The Netherlands I June 17, 2013 I 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.
“The data we have generated with MCLA-117 so far clearly show that the compound can efficiently eradicate AML tumor cells. Most importantly, the compound can also destroy tumor-inducing cancer stem cells which are the main cause for relapse,” said Lex Bakker, Chief Development Officer of Merus. “In addition, we have designed MCLA-117 to prevent undesired side-effects triggered by cytokine release, which makes it a safe candidate for potent, targeted cancer therapy.”
“Based on the favorable research and preclinical data, we are looking forward to moving MCLA-117 into clinical development next year,” added Ton Logtenberg, Chief Executive Officer of Merus. “As MCLA-117 was selected from large panels of common light chain human monoclonal antibodies that were screened for both functional and developmental characteristics, we are convinced that we have identified the best clinical candidate for AML.”
About Acute Myeloid Leukemia (AML)
Acute myeloid leukemia (AML) is a cancer of the blood and bone marrow. It is the most common type of acute leukemia in adults, with 54% of AML patients diagnosed at age 65 or older. It is estimated that every year, more than 13,000 new cases of AML occur in the United States and more than 10,000 patients die from the disease. In Europe, the annual mortality rate is 4-6 cases per 100,000 individuals. At present, standard treatments for AML include chemotherapy, radiation therapy and stem cell transplants. Targeted therapies, such as monoclonal antibodies, are also being evaluated in clinical trials. AML is generally associated with a poor prognosis. Despite of initial complete remissions with available therapies (60-80% in patients younger than 60 years and 40-55% in older patients), the long-term disease survival is only about 20-30 % (see footnotes 1,2,3).
About MCLA-117
MCLA-117 is based on Merus´ proprietary 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.
About Merus B.V.
Merus is a biotechnology company building a pipeline of innovative, human bispecific antibodies (Biclonics™) and single cell-derived combinations of antibodies (Oligoclonics®) for cancer therapy. Through the use of a common antibody light chain and CH3 heterodimerization technology, these full-length IgG antibody therapeutics can be robustly produced at high yields from a single clonal manufacturing cell line using standard approaches. Biclonics™ and Oligoclonics® bind to multiple disease-associated targets, such as growth factor receptors expressed by tumor cells. Synergy is achieved by addressing multiple pathways/mechanisms simultaneously, thereby eliminating tumor cells more efficiently and preventing treatment escape. In the Biclonics™-ENGAGE approach, full-length, human, bispecific IgG antibodies are used to induce the cytotoxic activity of T cells to kill cancer cells.
Merus meets a significant need in the oncology field: the discovery and development of bispecific antibodies and single-cell derived antibody combinations with improved clinical efficacy to address the limited potency of conventional antibodies. For further information, please visit Merus´ website at www.merus.nl
Footnotes:
1- National Cancer Institute. General Information About Adult Acute Myeloid Leukemia.
http://www.cancer.gov/cancertopics/pdq/treatment/adultAML. Accessed January 2, 2013.
2- NCCN clinical guidelines, Acute Myeloid Leukemia. v.2, 2012, www.NCCN.com
3- ESMO clinical practice guidelines- Acute Myeloblastic Leukemia- M. F. Fey& M. Dreyling, Annals of Oncology 21 (Supplement 5): v158–v161, 2010.
SOURCE: Merus
Post Views: 130
– Clinical Candidate Designed for the Treatment of Acute Myeloid Leukemia (AML) –
UTRECHT, The Netherlands I June 17, 2013 I 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.
“The data we have generated with MCLA-117 so far clearly show that the compound can efficiently eradicate AML tumor cells. Most importantly, the compound can also destroy tumor-inducing cancer stem cells which are the main cause for relapse,” said Lex Bakker, Chief Development Officer of Merus. “In addition, we have designed MCLA-117 to prevent undesired side-effects triggered by cytokine release, which makes it a safe candidate for potent, targeted cancer therapy.”
“Based on the favorable research and preclinical data, we are looking forward to moving MCLA-117 into clinical development next year,” added Ton Logtenberg, Chief Executive Officer of Merus. “As MCLA-117 was selected from large panels of common light chain human monoclonal antibodies that were screened for both functional and developmental characteristics, we are convinced that we have identified the best clinical candidate for AML.”
About Acute Myeloid Leukemia (AML)
Acute myeloid leukemia (AML) is a cancer of the blood and bone marrow. It is the most common type of acute leukemia in adults, with 54% of AML patients diagnosed at age 65 or older. It is estimated that every year, more than 13,000 new cases of AML occur in the United States and more than 10,000 patients die from the disease. In Europe, the annual mortality rate is 4-6 cases per 100,000 individuals. At present, standard treatments for AML include chemotherapy, radiation therapy and stem cell transplants. Targeted therapies, such as monoclonal antibodies, are also being evaluated in clinical trials. AML is generally associated with a poor prognosis. Despite of initial complete remissions with available therapies (60-80% in patients younger than 60 years and 40-55% in older patients), the long-term disease survival is only about 20-30 % (see footnotes 1,2,3).
About MCLA-117
MCLA-117 is based on Merus´ proprietary 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.
About Merus B.V.
Merus is a biotechnology company building a pipeline of innovative, human bispecific antibodies (Biclonics™) and single cell-derived combinations of antibodies (Oligoclonics®) for cancer therapy. Through the use of a common antibody light chain and CH3 heterodimerization technology, these full-length IgG antibody therapeutics can be robustly produced at high yields from a single clonal manufacturing cell line using standard approaches. Biclonics™ and Oligoclonics® bind to multiple disease-associated targets, such as growth factor receptors expressed by tumor cells. Synergy is achieved by addressing multiple pathways/mechanisms simultaneously, thereby eliminating tumor cells more efficiently and preventing treatment escape. In the Biclonics™-ENGAGE approach, full-length, human, bispecific IgG antibodies are used to induce the cytotoxic activity of T cells to kill cancer cells.
Merus meets a significant need in the oncology field: the discovery and development of bispecific antibodies and single-cell derived antibody combinations with improved clinical efficacy to address the limited potency of conventional antibodies. For further information, please visit Merus´ website at www.merus.nl
Footnotes:
1- National Cancer Institute. General Information About Adult Acute Myeloid Leukemia.
http://www.cancer.gov/cancertopics/pdq/treatment/adultAML. Accessed January 2, 2013.
2- NCCN clinical guidelines, Acute Myeloid Leukemia. v.2, 2012, www.NCCN.com
3- ESMO clinical practice guidelines- Acute Myeloblastic Leukemia- M. F. Fey& M. Dreyling, Annals of Oncology 21 (Supplement 5): v158–v161, 2010.
SOURCE: Merus
Post Views: 130
