February 22nd, 2006
Micromet Deciphers Key Mode of BiTE™ Action
Results published in Molecular Immunology explain the potency and specificity of BiTE™ molecules
February 22, 2006, Munich, Germany -- Micromet AG reports new findings on the mode of action of its proprietary class of antibody derivatives called BiTE™. Previous studies have shown that minute doses of BiTE™ molecules can activate cytotoxic T cells against cancer cells resulting in efficient and precise cancer cell destruction without the need for co-stimulation of T cells.
Results published in the recent issue of Molecular Immunology (1) suggest that BiTE™'s potency and independence of co-stimuli may come from the highly effective induction of cytolytic synapses between T cells and target cells. Such cytolytic immunological synapses represent key subcellular structures for specific T cell function and activation, which are normally induced by the interaction of a specific T cell receptor (TCR) on T cells with a corresponding peptide/MHC class I complex on target cells. Intriguingly, BiTE™ molecules are capable of triggering formation of cytolytic synapses independent of TCR specificity and the expression of MHC class I molecules on target cells. In cancer patients, a BiTE™ may therefore be able to circumvent major immune evasion strategies frequently employed by tumor cells to escape T cell attack.
Confocal microscopy showed that BiTE™-induced synapses are indistinguishable in terms of size, composition and subdomain arrangement from regular cytolytic synapses. In addition, an effective displacement of the negative T cell regulator CD45 was observed within BiTE™-induced synapses, which may provide an explanation as to why BiTE™ molecules potently activate T cells without the need for co-stimulation.
"The present study deciphered a key mechanism of BiTE™ action and shows that BiTE™ molecules employ a regular subcellular structure of cytotoxic T cells for tumor cell lysis," Patrick Baeuerle, Micromet's CSO, comments. "The ability of BiTE™ molecules to engage essentially all cytotoxic T cells in the body and to overcome major immune evasion strategies of tumor cells, differentiates BiTE™ from today's most prevalent therapeutic approaches, such as vaccination and adoptive T cell transfer, which are trying to activate tumor-specific T cells."
In January 2006, Micromet announced a definitive agreement to merge with CancerVax Corporation (NASDAQ: CNVX) to create a transatlantic, NASDAQ-listed company with a highly differentiated drug development pipeline focused on oncology, autoimmune and inflammatory diseases, and a proprietary technology base for the development of antibody-based product candidates. The merger is subject to a number of conditions and is expected to close in the second quarter of 2006. Upon closing of the transaction, the Company's shares are expected to continue to trade on the NASDAQ National Market. CancerVax will be renamed "Micromet", Inc., and application will be made to NASDAQ to change the ticker symbol to "MITI". On February 13, 2006, CancerVax filed a registration statement on Form S-4 in connection with the transaction that contains a proxy statement/prospectus with the U.S. Securities and Exchange Commission. ###
Reference
(1) Offner S, Hofmeister R, Romaniuk A, Kufer P, Baeuerle PA. Induction of regular cytolytic T cell synapses by bispecific single-chain antibody constructs on MHC class I-negative tumor cells. Mol Immunol, 2006; 43: 763-771.
The full article with colored images can be obtained as reprint from Micromet or online at sciencedirect.com
Contact
Media: Evelyn Wolf, Phone: +49 89 895277-220, Email: evelyn.wolf@micromet.de
Investors: Ines-Regina Buth, Phone: +49 89 895277-221, Email: ines-regina.buth@micromet.de
About Micromet
Micromet AG is a private Munich, Germany-based biotechnology company with a focus on the development of novel, proprietary antibody-based products for cancer and inflammatory and autoimmune diseases. Two product candidates are currently in clinical trials. MT201, a recombinant human monoclonal antibody is being evaluated in Phase 2 clinical trials for the treatment of certain solid tumors. MT103 is being studied in a Phase 1 clinical trial. The Company has established a powerful drug development platform based on its BiTE™ technology, a unique drug format that leverages the cytotoxic potential of T cells, the most powerful 'killer cells' of the human immune system. Micromet has integrated infrastructure and expertise in all disciplines of drug design and development. The Company has attracted both top-tier life science investors and collaborators, such as MedImmune, Inc. and Serono.
In January 2006, Micromet announced an agreement to merge with CancerVax Corporation (NASDAQ: CNVX) to create a transatlantic, NASDAQ-listed company with a highly differentiated drug development pipeline focused on oncology, autoimmune and inflammatory diseases, and a proprietary technology base for the development of antibody-based product candidates. The merger is subject to a number of conditions and expected to close in the second quarter of 2006.
For further information, please visit the Company's website at www.micromet.de.
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. Such forward-looking statements include statements regarding the proposed transaction, the efficacy, safety, and intended utilization of the companies' respective product candidates including BiTE™ molecules, the conduct and results of future clinical trials, and plans regarding regulatory filings, future research and clinical trials and plans regarding partnering activities. Factors that may cause actual results to differ materially include the risk that CancerVax and Micromet may not be able to complete the proposed transaction, the risk that product candidates that appeared promising in early research and clinical trials do not demonstrate safety and/or efficacy in larger-scale or later clinical trials, the risk that CancerVax and Micromet will not obtain approval to market their respective products, the risks associated with reliance on outside financing to meet capital requirements, and the risks associated with reliance on collaborative partners for further clinical trials, development and commercialization of product candidates. You are urged to consider statements that include the words "may," "will," "would," "could," "should," "believes," "estimates," "projects," "potential," "expects," "plans," "anticipates," "intends," "continues," "forecast," "designed," "goal," or the negative of those words or other comparable words to be uncertain and forward-looking. The transaction with CancerVax is subject to customary closing conditions, including approval of CancerVax's stockholders. These factors and others are more fully discussed in CancerVax's registration statement on Form S-4 filed with the SEC on February 13, 2006, in CancerVax's 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. Neither Micromet nor CancerVax undertake any obligation to publicly update any forward-looking statements, whether as a result of new information, future events or otherwise. |
