ImClone Systems Showcases Extensive Research and Development Program at the AACR Annual Meeting.Rich pipeline includes a broad array of IgG1 monoclonal antibodies that target emerging critical cancer pathways NEW YORK -- IgG1 monoclonal antibodies developed by ImClone Systems Incorporated (NASDAQ NASDAQ in full National Association of Securities Dealers Automated Quotations U.S. market for over-the-counter securities. Established in 1971 by the National Association of Securities Dealers (NASD), NASDAQ is an automated quotation system that reports on : IMCL IMCL International Making Cities Livable IMCL Inter Marine Container Lines IMCL International Management Consultants Ltd. IMCL Indraprastha Medical Corp Ltd (India) IMCL Imperial Majesty Cruise Line ) were the focus of 44 total presentations at the recently concluded 98th Annual Meeting of the American Association for Cancer Research Wikipedia is not the place for advertisement or self-advertising. The American Association for Cancer Research (AACR) is an organization based in Philadelphia, Pennsylvania, that focuses on all aspects of cancer research including basic, clinical and translational (AACR AACR American Association for Cancer Research AACR Anglo-American Cataloging Rules AACR Australasian Association of Cancer Registries AACR African Armed Conflicts Resolved ), including seven oral presentations and 37 posters. Important ERBITUX[R] (cetuximab) clinical data were the focus of two back-to-back oral presentations leading off the "Breakthroughs in Clinical Research" Plenary Session on April 16, 2007, which highlights the most important clinical studies presented at this prestigious meeting. The remaining presentations showcased ImClone's extensive research and development program with results from studies involving both ERBITUX, an IgG1 monoclonal antibody that targets the epidermal growth factor receptor This article is about a cell suface receptor. For estimated measure of kidney function (eGFR), see Glomerular filtration rate. The epidermal growth factor receptor (EGFR EGFR Epidermal Growth Factor Receptor (a kinase enzyme) EGFR Estimated Glomerular Filtration Rate ), and multiple investigational monoclonal antibodies in the ImClone pipeline that target other critical cancer pathways. Like ERBITUX, the monoclonal antibodies in the ImClone pipeline are all type 1 immunoglobulin G (IgG1) antibodies. In vitro, IgG1 antibodies elicit antibody-dependent cellular cytotoxicity (ADCC ADCC antibody-dependent cell-mediated cytotoxicity. ADCC antibody-dependent cell-mediated cytotoxicity. ), which can kill cancer cells and may contribute to their overall therapeutic effects. These novel fully human antibodies, many of which are in early phase clinical testing, target cell surface receptors in various signaling pathways known or believed to play important roles in the growth and proliferation of tumors or tumor vasculature vasculature /vas·cu·la·ture/ (vas´ku-lah-chur) 1. circulatory system. 2. any part of the circulatory system. vas·cu·la·ture n. . Specific targets include insulin-like growth factor-1 receptor (IGF-1R), vascular endothelial growth factor Vascular endothelial growth factor (VEGF) is an important signaling protein involved in both vasculogenesis (the de novo formation of the embryonic circulatory system) and angiogenesis (the growth of blood vessels from pre-existing vasculature). receptor-1 (VEGFR-1), VEGFR-2, VEGFR-3, platelet-derived growth factor receptor The platelet-derived growth factors PDGF-A and -B have for already more than 30 years been recognized as important factors regulating cell proliferation, cellular differentiation, cell growth, development and many diseases including cancer. alpha (PDGFR PDGFR Platelet Derived Growth Factor Receptor [eth]), FMS-like tyrosine kinase 3 receptor (FLT3), fibroblast growth factor receptor The fibroblast growth factor receptors are, as their name implies, receptors which bind to members of the fibroblast growth factor family of proteins. Structure The fibroblast growth factor receptors consist of an extracellular ligand domain comprised of three 3 (FGFR FGFR Fibroblast Growth Factor Receptor 3), among others. "Our pipeline consists of a robust collection of IgG1 monoclonal antibodies targeted against cellular pathways that are emerging as critical drivers of cancer growth, proliferation, and survival," said Eric Rowinsky, M.D., Chief Medical Officer and Senior Vice President of ImClone Systems. "With ERBITUX as our cornerstone, we are uniquely positioned to drive the science that will lead to new therapies of major clinical impact as well as define new combinatorial biologic therapies that may improve patient care." "We are extremely excited by the potential of ERBITUX and we are also increasingly enthusiastic about our pipeline of novel antibodies," said Alexander J. Denner, Ph.D., Chairman of ImClone System's Executive Committee. Among others, ERBITUX findings presented at the meeting included * In a large randomized ran·dom·ize tr.v. ran·dom·ized, ran·dom·iz·ing, ran·dom·iz·es To make random in arrangement, especially in order to control the variables in an experiment. phase III trial ERBITUX added to irinotecan significantly improved the secondary end points of progression free survival and tumor response compared to irinotecan alone in patients with metastatic colorectal cancer (mCRC) after failure of first-line therapy. Overall survival, the trial's primary end point, was similar between the treatment groups, plausibly due to the survival benefit of extensive post-study treatment with ERBITUX in patients in the irinotecan-alone arm. [#LB-2 in the "Breakthroughs in Clinical Research" Plenary Session, Sobrero et al. Randomized Phase III trial of cetuximab plus irinotecan versus irinotecan alone for metastatic colorectal cancer in 1298 patients who have failed prior oxaliplatin-based therapy: The EPIC trial.] * ERBITUX administered in patients with mCRC as a 500 mg/m2 dose administered every 2 weeks showed similar pharmacokinetics and efficacy, and no increased toxicity compared to the current standard weekly dosing regimen. [#LB-352, Cervantes et al: Optimal dose of cetuximab administered every 2 weeks (q2w): A phase I safety, pharmacokinetics (PK) and pharmacodynamics pharmacodynamics /phar·ma·co·dy·nam·ics/ (-di-nam´iks) the study of the biochemical and physiological effects of drugs and the mechanisms of their actions, including the correlation of their actions and effects with their chemical (PD) study of weekly (q1w) and q2w schedules in patients (pts) with metastatic colorectal cancer (mCRC).] * Different anti-EGFR agents, including other monoclonal antibodies, have different biological effects. [#336 Meira et al. Differences in activity between matuzumab and cetuximab in A431 cells may rely on MAPK MAPK Mitogen-Activated Protein Kinase MAPK Map Kinase cascade inhibition.] * Emerging biomarkers may serve as predictors of clinical response to ERBITUX. [#5670 Ford et al. Expression of epiregulin and amphiregulin and K-RAS mutation status may predict disease control in metastatic colorectal cancer patients treated with cetuximab (ERBITUX([R])); #5671 Lievre et al. K-RAS mutation in colorectal cancer is a predictive factor of response and progression free survival in patients treated with cetuximab.] * It is well established that the combination of ERBITUX and irinotecan can overcome irinotecan resistance in chemotherapy refractory patients with mCRC [Cunningham et al, N Engl J Med. 2004;351:337.] Results presented by Deevi et al. show that ERBITUX may also reverse oxaliplatin resistance. [#2329 Deevi et al. Mechanism for the benefits of cetuximab in combination with oxaliplatin, in oxaliplatin sensitive and resistant colon cancer cell lines.] * It is also well established that ERBITUX in combination with radiation therapy improves survival in patients with locally advanced head and neck cancer [Bonner et al, N Engl J Med. 2006;354:567.] In vitro studies presented show enhanced anticancer effects with ERBITUX in combination with radiation in non-small cell lung cancer Lung Cancer, Non-Small Cell Definition Non-small cell lung cancer (NSCLC) is a disease in which the cells of the lung tissues grow uncontrollably and form tumors. Description There are two kinds of lung cancers, primary and secondary. cells and in combination with HDAC or Src inhibition in colon cancer cells. [#3111 Brooks et al. Targeting EGFR signaling to enhance response of non-small cell lung cancer cells to radiation; #683 LaBonte et al. The effects of histone deacetylase inhibitors on epidermal growth factor receptor expression in colon cancer cell lines: implications for combination therapy; #4079 Kopetz et al. Synergistic activity of Src and EGFR inhibitors in colon cancer.] ImClone's broad portfolio of investigational fully human IgG1 monoclonal antibodies was featured in 14 AACR presentations. Much of the reported data provides scientific support for the continued evaluation of these antibodies in novel combinations of biologic therapies. * IMC-A12 (anti-IGF-1R MAb) [#425 Burtrum et al., Abrogation The destruction or annulling of a former law by an act of the legislative power, by constitutional authority, or by usage. It stands opposed to rogation; and is distinguished from derogation, which implies the taking away of only some part of a law; from Subrogation, of PTEN does not confer resistance to anti IGF-1R targeted therapy in IGF (Internet Governance Forum) An international organization of governments and U.N. agencies that was founded to discuss Internet issues such as security and spam. It was created at the United Nations Summit in 2005 after the U.S. responsive tumor cells ,#652 Prewett et al. IMC-A12 enhances the efficacy of cetuximab and gemcitabine therapy in human pancreatic carcinoma xenografts; #4396 Krystal et al. Selective inhibition of SCLC growth by the A12 anti-IGF-1R monoclonal antibody correlates with inhibition of Akt.] * IMC-18F1 (anti-VEGFR-1 MAb) [#4100 Wang et al. Expression of vascular endothelial growth factor receptor-1 in human tumor arrays.] * IMC-1121b (anti-VEGFR-2 MAb) [#4097 Corcoran et al. Comparison of combination anti-EGFR and anti-VEGFR2 therapy to MTD standard chemotherapeutic regimens.] * IMC-3G3 (anti-PDGFR[eth] MAb) and IMC 1121b (anti-VEGFR-2 MAb) [#4790 Shen et al. An antibody directed against platelet-derived growth factor platelet-derived growth factor n. A substance in platelets that is mitogenic for cells at the site of a wound, causing endothelial proliferation. [eth] receptor suppresses growth of human tumor xenografts and enhances antitumor activity of an anti-VEGFR2 antibody.] * IMC-EB10, NC7, and D4-3 (Anti-FLT3 MAb) [#4110 Williams et al. Elucidation of the antagonistic mechanisms of various anti-FLT3 antibodies via binding epitope dissection.] * IMC-D11 (anti-FGFR3 MAb) [#2080 DiRenzo et al. Neutralizing antibody against FGFR3 shows anti-tumor effects in multiple tumor models in vivo.] Additional details of the presentations can be found on the AACR website at http://www.aacr.org/. About ImClone Systems Incorporated ImClone Systems Incorporated is committed to advancing oncology care by developing and commercializing a portfolio of targeted biologic treatments designed to address the medical needs of patients with a variety of cancers. The Company's research and development programs include growth factor blockers and angiogenesis inhibitors. ImClone Systems' strategy is to become a fully integrated biopharmaceutical company, taking its development programs from the research stage to the market. ImClone Systems' headquarters and research operations are located in New York City New York City: see New York, city. New York City City (pop., 2000: 8,008,278), southeastern New York, at the mouth of the Hudson River. The largest city in the U.S. , with additional administration and manufacturing facilities in Branchburg, New Jersey. Certain matters discussed in this news release may constitute forward-looking statements within the meaning of the Private Securities Litigation Reform Act The Private Securities Litigation Reform Act of 1995 (PSLRA) implemented several significant substantive changes affecting certain cases brought under the federal securities laws, including changes related to pleading, discovery, liability, class representation and awards fees and of 1995 and the Federal securities laws. Although the company believes that the expectations reflected in such forward-looking statements are based upon reasonable assumptions it can give no assurance that its expectations will be achieved. Forward-looking information is subject to certain risks, trends and uncertainties that could cause actual results to differ materially from those projected. Many of these factors are beyond the company's ability to control or predict. Important factors that may cause actual results to differ materially and could impact the company and the statements contained in this news release can be found in the company's filings with the Securities and Exchange Commission including quarterly reports on Form 10-Q, current reports on Form 8-K and annual reports on Form 10-K. For forward-looking statements in this news release, the company claims the protection of the safe harbor for forward-looking statements contained in the Private Securities Litigation Reform Act of 1995. The company assumes no obligation to update or supplement any forward-looking statements whether as a result of new information, future events or otherwise. |
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