Micromet Receives Regulatory Approval To Conduct A Phase 2 Clinical Trial Investigating MT103 (MEDI-538) In Patients With Leukemia

Main Category: Lymphoma / Leukemia / Myeloma
Also Included In: Clinical Trials / Drug Trials;  Pharma Industry / Biotech Industry
Article Date: 19 Oct 2007 - 0:00 PDT

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Micromet, Inc. (Nasdaq: MITI), a biopharmaceutical company focusing on the development of novel, proprietary antibody-based products for the treatment of cancer, inflammatory and autoimmune diseases, announced today that the Paul-Ehrlich Institute has approved an Investigational Medicinal Product Dossier (IMPD) for the conduct of a phase 2 clinical trial testing MT103 in patients with acute lymphoblastic leukemia (ALL) in Germany. MT103, a BiTE(R) antibody targeting the CD19 antigen, which is expressed on most malignant B lymphoma cells, is also being evaluated in an ongoing phase 1 clinical trial in Europe in non- Hodgkin's lymphoma (NHL). Micromet and MedImmune, a subsidiary of AstraZeneca plc, are currently developing MT103 (also known as MEDI-538). Under a 2003 agreement, Micromet granted MedImmune exclusive rights for MT103 for North America.

Acute lymphoblastic leukemia is a highly aggressive form of B-cell leukemia. Currently, patients are initially treated with complex and toxic chemotherapy regimens that can be followed by bone marrow stem cell transplantation. If patients have low amounts of residual tumor cells after chemotherapy (also known as "minimal residual disease" or MRD) they are at a very high risk of relapse. This phase 2 clinical trial will test whether MT103 can remove residual tumor cells and thereby convert patients from a MRD- positive to a MRD-negative status with an improved time to relapse.

"When MRD is detectable, the median relapse free survival in patients is only 4.1 months. In the German Multicenter Study Group for Adult ALL (GMALL) studies, patients with MRD after induction and the first consolidation treatment are identified as high risk and are candidates for stem cell transplantation. Optimization of treatment and reduction of relapse of patients with MRD-positive ALL represent an absolute medical need especially in patients for whom stem cell transplantation is not an option. Although CD19 is widely expressed in ALL, no antibody against this tumor associated antigen target has been developed thus far. The current clinical trial is set up to address the question of treating MRD positive ALL with a novel anti-CD19 antibody derivative," said Professor Hoelzer, Chairman of the GMALL study group.

Early observations of MT103 clinical activity were recently reported from an ongoing phase 1 clinical trial evaluating MT103 as single-agent therapy in a population of heavily pre-treated patients with NHL. These observations included complete and partial responses confirmed by independent review. In addition, MT103 not only eliminated tumor target cells in peripheral blood but also cleared lymphoma cells from heavily infiltrated bone marrow. These data were presented at the 48th Annual Meeting of the American Society for Hematology in December 2006.

"The upcoming phase 2 clinical trial in ALL is an important step to establish activity of MT103 in aggressive B cell leukemias and lymphomas," said Carsten Reinhardt, Micromet's Senior Vice President and Chief Medical Officer. "Investigating the effect of MT103 on minimal residual disease may open a highly promising new treatment concept in these diseases, that is, consolidation therapy with a BiTE antibody (MT103) after initial treatment with a chemotherapeutic regimen."

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 tumor 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, which 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 MT103 (MEDI-538)

MT103, which is being co-developed with MedImmune as MEDI-538, is a BiTE(R) antibody being developed with the intent to treat patients with certain types of B-cell lymphomas. MT103 received orphan drug designation from the EMEA for the treatment of mantle cell lymphoma and chronic lymphocytic leukemia. In February 2006, the U.S. Food and Drug Administration (FDA) also approved an orphan drug designation for MT103 for the treatment of certain indolent B-cell lymphomas. MT103 specifically targets the CD19 antigen, which is present on B-cells and B cell-derived tumors but not on other types of blood cells or healthy tissues.

About Micromet, Inc. (http://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 using the BiTE (R)technology platform to be clinically validated in Micromet's product pipeline, is being evaluated 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 to eliminate cancer cells. Micromet is developing MT103 in collaboration with AstraZeneca plc's subsidiary MedImmune, Inc. 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.

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.

Micromet, Inc.
http://www.micromet-inc.com

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