- Data Presented at the American Association for Cancer Research -
PRINCETON, N.J., April 21 /PRNewswire-FirstCall/ -- Medarex, Inc. today announced preclinical efficacy and safety data from multiple programs, including antibodies to novel and potentially important cancer targets (CXCR4, fucosyl-GM1, glypican-3, mesothelin, CD70) and additional research in the area of antibody-drug conjugates. Data from the studies were presented at the Annual Meeting of the American Association for Cancer Research (AACR), April 18-22, 2009, in Colorado.
Characterization of MDX-1338, a human anti-CXCR4 antibody proposed for therapeutic application in AML and ALL (Abstract #LB-150)
CXCR4 is a seven-transmembrane, G-protein-coupled receptor in the CXC chemokine receptor family that is expressed on a variety of cancers including leukemias, lymphomas, breast, lung, colon, pancreatic, and ovarian cancer. In preclinical studies, MDX-1338, a fully human anti-CXCR4 antibody, effectively blocked the binding of CXCR4 to its ligand, CXCL12, thereby inhibiting chemotaxis and migration responses. In addition, MDX-1338 also reduced tumor growth in acute myelogenous leukemia and lymphoma xenograft models.
Efficacy of MDX-1110, an anti-Fucosyl-GM1 antibody in a SCLC tumor model (Abstract #838)
Fucosyl-GM1 is a ganglioside, a component of the cell plasma membrane, that is expressed on most small cell lung cancers (SCLC). In in vitro preclinical studies, a fully human, non-fucosylated anti-fucosyl-GM1 antibody, MDX-1110, demonstrated robust cytotoxic effector function (both antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity) for killing tumor cells. Additionally, MDX-1110 showed a favorable safety and toxicity profile. MDX-1110 also demonstrated potent anti-tumor activity as a monotherapy and enhanced efficacy and improved control of tumor cell growth in combination with standard of care chemotherapy in in vivo studies.
Development of anti-Glypican 3 therapeutic antibodies (Abstract #1233)
Glypican-3 is a protein that has been shown to be expressed in liver cancer. A panel of fully human anti-glypican-3 antibodies was generated from which a lead candidate, MDX-1414, was selected for its high affinity, specificity, effector function and internalization properties. MDX-1414 demonstrated anti-tumor efficacy leading to significant and durable suppression of established subcutaneous tumors in a liver cancer xenograft model with no evidence of toxicity. Targeting glypican-3 with antibodies enhanced for antibody-dependent cell-mediated cytotoxicity properties, as drug-conjugates or used in combination with existing therapies, may represent a potentially important new treatment for liver cancer.
Efficacy and Toxicity of anti-mesothelin antibody drug conjugate (Abstract #3235)
Mesothelin is a glycoprotein over-expressed on mesotheliomas and other cancers, including ovarian and lung cancer, and because of its limited expression in normal tissue, it is an attractive target for an antibody-drug conjugate. In xenograft models of ovarian and lung cancer, MDX-1204, a fully human anti-mesothelin antibody-drug conjugate, demonstrated significant anti-tumor activity at doses as low as 0.3 umole/kg. In addition, the antibody-drug conjugate was well-tolerated in cynomolgous monkeys and mouse models.
The critical role of cleavable linkers for minor groove binding alkylating agent (MGBA) based antibody-drug conjugates (Abstract #1722)
The effectiveness of a cleavable linker over a non-cleavable linker when used with MGBA-based antibody-drug conjugates was examined using fully human anti-CD70 antibody-drug conjugates. In renal cancer xenograft models, single dose treatment with conjugates using the cleavable linker demonstrated selective and antigen-dependent killing of tumor cells leading to the regression of established tumors. Antibody-drug conjugates comprising a non-cleavable linker had greatly reduced specificity and efficacy. In addition to demonstrating potent anti-tumor efficacy, conjugates using a cleavable linker also showed a more favorable toxicity and safety profile over conjugates using a non-cleavable linker.
Information about the AACR and its Annual Meeting may be found at www.aacr.org.
About Medarex
Medarex is a biopharmaceutical company focused on the discovery, development and potential commercialization of fully human antibody-based therapeutics to treat life-threatening and debilitating diseases, including cancer, inflammation, autoimmune disorders and infectious diseases. Medarex applies its UltiMAb(R) technology and product development and clinical manufacturing experience to generate, support and potentially commercialize a broad range of fully human antibody product candidates for itself and its partners. Over forty of these therapeutic product candidates derived from Medarex technology are in human clinical testing or have had INDs submitted for such trials, with the most advanced product candidates currently in Phase 3 clinical trials, the subject of regulatory applications for marketing authorization or approved in Canada and Europe. Medarex is committed to building value by developing a diverse pipeline of antibody products to address the world’s unmet healthcare needs. For more information about Medarex, visit its website at www.medarex.com.
Statement on Cautionary Factors
Except for the historical information presented herein, matters discussed herein may constitute forward-looking statements, as defined in the Private Securities Litigation Reform Act of 1995, that are subject to certain risks and uncertainties that could cause actual results to differ materially from any future results, performance or achievements expressed or implied by such statements. Statements that are not historical facts, including statements preceded by, followed by, or that include the words “potential”, “expect”, “believe”, or “may” or similar statements are forward-looking statements. Medarex disclaims, however, any intent or obligation to update these forward-looking statements. Risks and uncertainties include risks associated with product discovery and development, unforeseen safety issues from the administration of antibody products in humans, as well as risks and uncertainties detailed from time to time in Medarex’s public disclosure filings with the U.S. Securities and Exchange Commission (SEC), including its Annual Report on Form 10-K for the fiscal year ended December 31, 2008 and its quarterly reports on Form 10-Q. There can be no assurance that development efforts will succeed or that other developed products will receive required regulatory clearance or that, even if such regulatory clearance were received, such products would ultimately achieve commercial success. Copies of Medarex’s public disclosure filings are available from its investor relations department.
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