Micromet's BiTE Antibodies Reveal Unique Mode of Action
BETHESDA, Md., November 06, 2007 /PRNewswire-FirstCall/ -- Micromet, Inc. , a biopharmaceutical company developing novel, proprietary antibodies for the treatment of cancer, inflammation and autoimmune diseases, announced the publication of two new studies describing a unique mode of action of Micromet's bispecific BiTE antibody therapeutics. The studies were published in the Journal of Immunotherapy(1) and in Cancer Immunology Immunotherapy(2), respectively.
BiTE antibodies are designed to transiently connect cytotoxic T cells with cancer cells leading to a tightly controlled and serial elimination of cancer cells. In this process, cytotoxic T cells are activated, which causes them to proliferate, recharge their toxins and increase their adhesiveness.
The two new studies have shown that BiTE antibodies activate T cells only when cancer cells are present, but not when they are given to T cells in the absence of cancer cells. The studies have also shown that initial cytokine release by activated T cells is not required for elimination of cancer cells, and that anti-inflammatory steroid hormones can efficiently quench the initial cytokine release by BiTE-activated T cells without reducing their capacity to kill cancer cells.
"The highly conditional, target cell-dependent activation of killer T cells by our BiTE antibodies is a very important safety feature in patients," commented Patrick Baeuerle, Micromet's Chief Scientific Officer. "Unlike other T cell-activating agents, BiTE antibodies activate T cells in a highly controlled fashion that is intimately linked to the desired therapeutic activity."
"We have observed depletion of circulating B lymphoma cells and have confirmed partial and complete responses in the clinical trials with MT103. At the same time, only very low systemic cytokine levels, if any, were detected," commented Carsten Reinhardt, Micromet's Chief Medical Officer. "The side effect profile of MT103 seen in the ongoing phase 1 study is consistent with the conditional T cell activation observed in the newly published studies."
References 1 Brischwein K, Parr L, Pflanz S et al. Strictly target cell-dependent activation of T cells by bispecific single-chain antibody constructs of the BiTE class. J Immunother. Vol. 30 (8):798-807, November/December 2007. 2 Brandl C, Hass C, d'Argouges S et al. The effect of dexamethasone on polyclonal T cell activation and redirected target cell lysis as induced by a CD19/CD3-bispecific single-chain antibody construct. Cancer Immunol Immunother. Vol. 56:1551-1563 (2007).
About BiTE(R) 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 product development 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 advanced non-Hodgkin's lymphoma patients. Three other BiTE antibodies, targeting EpCAM (CD326), CEA and MCSP, are in pre-clinical 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 in clinical development. MT103 (MEDI-538), the first antibody developed utilizing the BiTE(R) technology platform in Micromet's product pipeline, is being evaluated in a phase 2 clinical trial for the treatment of patients with acute lymphoblastic leukemia and 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 to eliminate cancer cells. Micromet is developing MT103 in collaboration with MedImmune, a subsidiary of AstraZeneca plc.
The second clinical stage antibody is adecatumumab (MT201), a human monoclonal antibody targeting EpCAM expressing tumors. Adecatumumab is being developed by Micromet in collaboration with Merck Serono in a phase 1b clinical trial evaluating MT201 in combination with docetaxel for the treatment of patients with metastatic breast cancer. The third clinical stage antibody is MT293 (formerly D93), also known as TRC093, a first-in-class humanized monoclonal antibody that inhibits angiogenesis and tumor cell growth by binding cleaved collagen. MT293, which is currently being tested in a phase 1 clinical trial, is licensed to TRACON Pharmaceuticals, Inc. and is being developed for the treatment of patients with cancer and age-related macular degeneration. In addition, Micromet has established a collaboration with Nycomed for the development and commercialization of MT203, Micromet's 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.
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.
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Posted: November 2007