WASHINGTON, April 3 /PRNewswire-FirstCall/ -- Introgen Therapeutics, Inc. reported data from preclinical studies evaluating MDA-7, the active component of INGN 241, in combination with Avastin(R) (bevacizumab) in models of lung cancer. Study results demonstrate that INGN 241 and Avastin each inhibit tumor angiogenesis through distinct mechanisms, and that their combination significantly increases anti-tumor activity compared with either agent used separately. Researchers at Introgen and The University of Texas M. D. Anderson Cancer Center conducted the study. Dr. Rajagopal Ramesh, Associate Professor, Department of Thoracic and Cardiovascular Medicine at M. D. Anderson Cancer Center was principal investigator of the study. The data were presented yesterday in a poster session at the American Association of Cancer Research 97th Annual Meeting (AACR), held in Washington, D.C.
“These results are very encouraging because they suggest that the anti- cancer activity of targeted, anti-angiogenic agents can be enhanced without increasing toxicity,” said Sunil Chada, Ph.D., associate vice president, Clinical Research and Development, at Introgen. “The approval of Avastin validated angiogenesis inhibition as a therapeutic approach to treating cancer. The data presented yesterday, and our robust body of clinical data demonstrating the favorable safety and tolerability profiles of INGN 241 suggests that this investigational cancer therapy may be combined with Avastin to make VEGF inhibition a more potent weapon in the fight against cancer.”
Tumor angiogenesis -- the formation of new blood vessels within a tumor -- is essential to support the growth of tumors beyond a minimum size. Avastin is a therapeutic antibody designed to inhibit angiogenesis by binding to and inhibiting the activity of vascular endothelial growth factor (VEGF), a key mediator of angiogenesis. Although inhibiting VEGF activity with Avastin reduces tumor angiogenesis and growth, it does not eradicate tumors. MDA-7 also has been shown to have potent anti-angiogenic activity, and works via a different mechanism than Avastin. The reported study was designed to evaluate the combination of INGN 241 and Avastin on tumor angiogenesis, growth and survival.
Study results, presented in Abstract #251, show that MDA-7 inhibits VEGF activity by decreasing expression of the VEGF gene. When used as single agents in cultured lung cancer cells, both INGN 241 and Avastin inhibited VEGF activity with no effect on tumor cell growth. However, treatment with both agents resulted in enhanced VEGF inhibition and significant inhibition of cell proliferation. In animal models of transplanted human lung tumors, approximately 70 percent of animals treated with INGN 241 and Avastin showed complete tumor regression, which resulted in significantly improved survival. These effects were not observed in animals treated with either agent alone or in controls. These results suggest that combining INGN 241 and Avastin may provide a novel and effective strategy for treating lung cancer.
Dr. Chada continued, “INGN 241 functions to block angiogenesis by inhibiting expression of VEGF -- a critical protein in tumor angiogenesis. In contrast, Avastin blocks binding of VEGF to its receptor. Thus combining these two agents with distinct anti-angiogenic mechanisms provides enhanced anti-tumor effects and completely eradicates tumors in mice, resulting in dramatic improvement in survival.”
Another abstract presented yesterday, and two abstracts presented today, provide additional preclinical data on the molecular mechanisms of INGN 241- mediated cell killing in a variety of cancer cell types. Abstracts #722 and #2207 identify cell survival pathways that are activated in response to INGN 241. Although INGN 241 results in potent cancer cell killing even when these pathways are activated, the study results suggest that strategies to block activation of these pathways may further increase its robust anti-cancer activity. Abstract #2456 reports that adenoviral vectors can be engineered to target MDA-7 protein expression to specific parts of a cell. The data show that targeting MDA-7 results in increased tumor cell killing compared with untargeted protein and provides novel insights into the mechanism of action of this unique molecule.
About INGN 241
In a Phase 1 trial of INGN 241 clinical activity was observed in patients with advanced melanoma. Based on the encouraging findings of INGN 241 treatment in the Phase 1 clinical trial, later stage trials have been initiated. A Phase 2 trial in patients with metastatic melanoma and a Phase 3 trial for solid tumors in combination with radiation therapy are ongoing. The mda-7 gene was discovered by the laboratory of Dr. Paul B. Fisher, professor of clinical pathology at Columbia University. Introgen holds an exclusive worldwide license for all gene therapy applications from the Corixa Corporation.
About Introgen
Introgen Therapeutics, Inc. is a biopharmaceutical company focused on the discovery, development and commercialization of targeted molecular therapies for the treatment of cancer and other diseases. Introgen is developing molecular therapeutics, immunotherapies, vaccines and nano-particle tumor suppressor therapies to treat a wide range of cancers using tumor suppressors, cytokines and genes. Introgen maintains integrated research, development, manufacturing, clinical and regulatory departments and operates multiple manufacturing facilities including a commercial scale cGMP manufacturing facility.
Introgen holds a licensing agreement with M. D. Anderson Cancer Center to commercialize products based on licensed technologies, and has the option to license future technologies under sponsored research agreements. The University of Texas Board of Regents owns stock in Introgen. These arrangements are managed in accordance with M. D. Anderson’s conflict of interest policies.
Statements in this release that are not strictly historical may be “forward-looking” statements, including those relating to Introgen’s future success with its INGN 241 clinical development program in combination for treatment of cancer. The actual results may differ from those described in this release due to risks and uncertainties that exist in Introgen’s operations and business environment, including Introgen’s stage of product development and the limited experience in the development of gene-based drugs in general, dependence upon proprietary technology and the current competitive environment, history of operating losses and accumulated deficits, reliance on collaborative relationships, and uncertainties related to clinical trials, the safety and efficacy of Introgen’s product candidates, the ability to obtain the appropriate regulatory approvals, Introgen’s patent protection and market acceptance, as well as other risks detailed from time to time in Introgen’s filings with the Securities and Exchange Commission including its filings on Form 10-K and Form 10-Q. Introgen undertakes no obligation to publicly release the results of any revisions to any forward-looking statements that reflect events or circumstances arising after the date hereof.
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Contact: Introgen Therapeutics, Inc. C. Channing Burke (512) 708 9310 Ext. 322 Email: c.burke@introgen.com
Introgen Therapeutics, Inc.
CONTACT: C. Channing Burke of Introgen Therapeutics, Inc., +1-512-708-9310Ext. 322, or c.burke@introgen.com
