BiTE antibodies are designed to direct the body’s cytotoxic, or cell-destroying, T cells against tumor cells, and represent a new therapeutic approach to cancer therapy
BETHESDA, MD, USA | April 14, 2008 | Micromet, Inc. (Nasdaq: MITI), a biopharmaceutical company developing novel antibodies for the treatment of cancer, inflammation and autoimmune diseases, today presented at the Annual Meeting of the American Association for Cancer Research (AACR) in San Diego, CA, preclinical data of two new human BiTE(R) antibodies targeting CD33 and MCSP, for the treatment of acute myelogenous leukaemia (AML) and melanoma (1). BiTE antibodies are designed to direct the body’s cytotoxic, or cell-destroying, T cells against tumor cells, and represent a new therapeutic approach to cancer therapy.
Generation of human anti-CD33 and anti-MCSP BiTE antibodies used a novel human BiTE antibody platform that is cross-reactive with non-human primates. In cell-based assays, CD33-specific and MCSP-specific BiTE antibodies were equally potent in eliminating tumor cells expressing the respective target antigens. While CD33 is present and well accessible on many normal blood cells, MCSP is barely accessible on normal cells, but is exposed and highly expressed on melanoma cells. Consistent with the accessibility of the respective target antigen, the CD33-specific BiTE antibody showed in macaques a dose-dependent depletion of CD33-expressing blood cells, whereas the MCSP-specific BiTE antibody did not show any activity, even at very high doses.
"We are very encouraged by the first in vivo results of these two new BiTE antibodies that continue to expand our novel BiTE antibody pipeline," comments Patrick Baeuerle, chief scientific officer of Micromet. "The data indicate highly target-specific activities of the two BiTE antibodies in primates, and suggest appropriate therapeutic windows for elimination of target cells in vivo."
Reference
(1) Kischel, R. et al. Characterization of Novel CD33- and MCSP-specific BiTE Antibodies for the Treatment of Acute Myeloid Leukaemia and Melanoma, Respectively, that Are Fully Human in Sequence. Annual Meeting of AACR, San Diego, 2008, Abstract No. 2404.
About BiTE Antibodies
BiTE(R) antibodies are designed to direct the body’s cytotoxic, or cell- destroying, T cells against tumor cells, and represent a new therapeutic approach to cancer therapy. BiTE antibodies have been shown to induce an immunological synapse between a T cell and a tumor cell in the same manner as observed during physiological T cell attacks. These cytolytic synapses enable the delivery of cytotoxic proteins from T cells into tumor cells, ultimately inducing a self-destruction process in the tumor cell referred to as apoptosis, or programmed cell death. In the presence of BiTE antibodies, T cells have been demonstrated to serially eliminate tumor cells, which explains the activity of BiTE antibodies at very low concentrations and at very low ratios of T cells to target cells. Through the process of killing cancer cells, T cells proliferate, which leads to an increased number of T cells at the site of attack.
Several antibodies in Micromet’s product pipeline are BiTE antibodies and have been generated based on Micromet’s proprietary BiTE antibody platform. The most advanced BiTE antibody is MT103 (MEDI-538), targeting CD19, and has provided proof-of-concept in an ongoing phase 1 clinical study in patients with advanced non-Hodgkin’s lymphoma. MT110, which is targeting EpCAM (CD326) and is the first BiTE antibody with potential applications in the treatment of solid tumors, has completed preclinical development. Two additional BiTE antibodies, targeting CEA and MCSP, are in preclinical development.
About Micromet, Inc. (www.micromet-inc.com)
Micromet, Inc. is a biopharmaceutical company developing novel, proprietary antibodies for the treatment of cancer, inflammation and autoimmune diseases. Three of its antibodies are currently in clinical trials, while the remainder of the product pipeline is in preclinical development. The BiTE(R) antibody MT103 is in a phase 2 clinical trial for the treatment of patients with acute lymphoblastic leukemia and in a phase 1 clinical trial for the treatment of patients with non-Hodgkin’s lymphoma. BiTE antibodies represent a new class of antibodies that activate a patient’s own cytotoxic T cells, considered the most powerful "killer cells" of the human immune system, to eliminate cancer cells. Micromet is developing MT103 in collaboration with MedImmune, Inc., a subsidiary of AstraZeneca plc. The second clinical stage antibody is adecatumumab, also known as MT201, a human monoclonal antibody which targets epithelial cell adhesion molecule (EpCAM)-expressing solid tumors. Micromet is developing adecatumumab in collaboration with Merck Serono in a phase 1b clinical trial evaluating adecatumumab in combination with docetaxel for the treatment of patients with metastatic breast cancer. The third clinical stage antibody, MT293 is licensed to TRACON Pharmaceuticals, Inc. and is being developed in a phase 1 clinical trial for the treatment of patients with cancer. In addition, Micromet has established a collaboration with Nycomed for the development and commercialization of MT203, a human antibody neutralizing the activity of granulocyte/macrophage colony stimulating factor (GM-CSF), which has potential applications in the treatment of various inflammatory and autoimmune diseases, such as rheumatoid arthritis, psoriasis, or multiple sclerosis.
Forward-Looking Statements
This release contains certain forward-looking statements that involve risks and uncertainties that could cause actual results to be materially different from historical results or from any future results expressed or implied by such forward-looking statements. Factors that may cause actual results to differ materially from any future results expressed or implied by any forward-looking statements include the risk that product candidates that appeared promising in early research, preclinical studies or clinical trials do not demonstrate safety and/or efficacy in subsequent clinical trials, the risk that encouraging results from early research, preclinical studies or clinical trials may not be confirmed upon further analysis of the detailed results of such research, preclinical study or clinical trial, the risk that additional information relating to the safety, efficacy or tolerability of our product candidates may be discovered upon further analysis of preclinical or clinical trial data, the risk that we or our collaborators will not obtain approval to market our product candidates, the risks associated with reliance on outside financing to meet capital requirements, and the risks associated with reliance on collaborators, including MedImmune, Merck Serono, TRACON and Nycomed, for the funding or conduct of further development and commercialization activities relating to our product candidates. You are urged to consider statements that include the words "ongoing," "may," "will," "would," "could," "should," "believes," "estimates," "projects," "potential," "expects," "suggests," "plans," "anticipates," "intends," "continues," "forecast," "designed," "goal," or the negative of those words or other comparable words to be uncertain and forward-looking. These factors and others are more fully discussed in our periodic reports and other filings with the SEC.
Any forward-looking statements are made pursuant to Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, and, as such, speak only as of the date made. Micromet, Inc. undertakes no obligation to publicly update any forward-looking statements, whether as a result of new information, future events or otherwise.
SOURCE: Micromet, Inc.
Post Views: 107
BiTE antibodies are designed to direct the body’s cytotoxic, or cell-destroying, T cells against tumor cells, and represent a new therapeutic approach to cancer therapy
BETHESDA, MD, USA | April 14, 2008 | Micromet, Inc. (Nasdaq: MITI), a biopharmaceutical company developing novel antibodies for the treatment of cancer, inflammation and autoimmune diseases, today presented at the Annual Meeting of the American Association for Cancer Research (AACR) in San Diego, CA, preclinical data of two new human BiTE(R) antibodies targeting CD33 and MCSP, for the treatment of acute myelogenous leukaemia (AML) and melanoma (1). BiTE antibodies are designed to direct the body’s cytotoxic, or cell-destroying, T cells against tumor cells, and represent a new therapeutic approach to cancer therapy.
Generation of human anti-CD33 and anti-MCSP BiTE antibodies used a novel human BiTE antibody platform that is cross-reactive with non-human primates. In cell-based assays, CD33-specific and MCSP-specific BiTE antibodies were equally potent in eliminating tumor cells expressing the respective target antigens. While CD33 is present and well accessible on many normal blood cells, MCSP is barely accessible on normal cells, but is exposed and highly expressed on melanoma cells. Consistent with the accessibility of the respective target antigen, the CD33-specific BiTE antibody showed in macaques a dose-dependent depletion of CD33-expressing blood cells, whereas the MCSP-specific BiTE antibody did not show any activity, even at very high doses.
"We are very encouraged by the first in vivo results of these two new BiTE antibodies that continue to expand our novel BiTE antibody pipeline," comments Patrick Baeuerle, chief scientific officer of Micromet. "The data indicate highly target-specific activities of the two BiTE antibodies in primates, and suggest appropriate therapeutic windows for elimination of target cells in vivo."
Reference
(1) Kischel, R. et al. Characterization of Novel CD33- and MCSP-specific BiTE Antibodies for the Treatment of Acute Myeloid Leukaemia and Melanoma, Respectively, that Are Fully Human in Sequence. Annual Meeting of AACR, San Diego, 2008, Abstract No. 2404.
About BiTE Antibodies
BiTE(R) antibodies are designed to direct the body’s cytotoxic, or cell- destroying, T cells against tumor cells, and represent a new therapeutic approach to cancer therapy. BiTE antibodies have been shown to induce an immunological synapse between a T cell and a tumor cell in the same manner as observed during physiological T cell attacks. These cytolytic synapses enable the delivery of cytotoxic proteins from T cells into tumor cells, ultimately inducing a self-destruction process in the tumor cell referred to as apoptosis, or programmed cell death. In the presence of BiTE antibodies, T cells have been demonstrated to serially eliminate tumor cells, which explains the activity of BiTE antibodies at very low concentrations and at very low ratios of T cells to target cells. Through the process of killing cancer cells, T cells proliferate, which leads to an increased number of T cells at the site of attack.
Several antibodies in Micromet’s product pipeline are BiTE antibodies and have been generated based on Micromet’s proprietary BiTE antibody platform. The most advanced BiTE antibody is MT103 (MEDI-538), targeting CD19, and has provided proof-of-concept in an ongoing phase 1 clinical study in patients with advanced non-Hodgkin’s lymphoma. MT110, which is targeting EpCAM (CD326) and is the first BiTE antibody with potential applications in the treatment of solid tumors, has completed preclinical development. Two additional BiTE antibodies, targeting CEA and MCSP, are in preclinical development.
About Micromet, Inc. (www.micromet-inc.com)
Micromet, Inc. is a biopharmaceutical company developing novel, proprietary antibodies for the treatment of cancer, inflammation and autoimmune diseases. Three of its antibodies are currently in clinical trials, while the remainder of the product pipeline is in preclinical development. The BiTE(R) antibody MT103 is in a phase 2 clinical trial for the treatment of patients with acute lymphoblastic leukemia and in a phase 1 clinical trial for the treatment of patients with non-Hodgkin’s lymphoma. BiTE antibodies represent a new class of antibodies that activate a patient’s own cytotoxic T cells, considered the most powerful "killer cells" of the human immune system, to eliminate cancer cells. Micromet is developing MT103 in collaboration with MedImmune, Inc., a subsidiary of AstraZeneca plc. The second clinical stage antibody is adecatumumab, also known as MT201, a human monoclonal antibody which targets epithelial cell adhesion molecule (EpCAM)-expressing solid tumors. Micromet is developing adecatumumab in collaboration with Merck Serono in a phase 1b clinical trial evaluating adecatumumab in combination with docetaxel for the treatment of patients with metastatic breast cancer. The third clinical stage antibody, MT293 is licensed to TRACON Pharmaceuticals, Inc. and is being developed in a phase 1 clinical trial for the treatment of patients with cancer. In addition, Micromet has established a collaboration with Nycomed for the development and commercialization of MT203, a human antibody neutralizing the activity of granulocyte/macrophage colony stimulating factor (GM-CSF), which has potential applications in the treatment of various inflammatory and autoimmune diseases, such as rheumatoid arthritis, psoriasis, or multiple sclerosis.
Forward-Looking Statements
This release contains certain forward-looking statements that involve risks and uncertainties that could cause actual results to be materially different from historical results or from any future results expressed or implied by such forward-looking statements. Factors that may cause actual results to differ materially from any future results expressed or implied by any forward-looking statements include the risk that product candidates that appeared promising in early research, preclinical studies or clinical trials do not demonstrate safety and/or efficacy in subsequent clinical trials, the risk that encouraging results from early research, preclinical studies or clinical trials may not be confirmed upon further analysis of the detailed results of such research, preclinical study or clinical trial, the risk that additional information relating to the safety, efficacy or tolerability of our product candidates may be discovered upon further analysis of preclinical or clinical trial data, the risk that we or our collaborators will not obtain approval to market our product candidates, the risks associated with reliance on outside financing to meet capital requirements, and the risks associated with reliance on collaborators, including MedImmune, Merck Serono, TRACON and Nycomed, for the funding or conduct of further development and commercialization activities relating to our product candidates. You are urged to consider statements that include the words "ongoing," "may," "will," "would," "could," "should," "believes," "estimates," "projects," "potential," "expects," "suggests," "plans," "anticipates," "intends," "continues," "forecast," "designed," "goal," or the negative of those words or other comparable words to be uncertain and forward-looking. These factors and others are more fully discussed in our periodic reports and other filings with the SEC.
Any forward-looking statements are made pursuant to Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, and, as such, speak only as of the date made. Micromet, Inc. undertakes no obligation to publicly update any forward-looking statements, whether as a result of new information, future events or otherwise.
SOURCE: Micromet, Inc.
Post Views: 107
