Introgen reports significant increase in responses to combination therapy for Phase II lung cancer study

Introgen Therapeutics, Inc. (NASDAQ: INGN) today reported results of a Phase II lung cancer study and a Phase I ovarian cancer study in two separate presentations at the 37th Annual Meeting of the American Society for Clinical Oncology (ASCO) in San Francisco, CA.

The lung cancer study follows up on interim data presented at ASCO last year and was presented by Stephen Swisher, M.D., of The University of Texas M. D. Anderson Cancer Center Department of Thoracic and Cardiovascular Surgery. In the study, three intratumoral injections of INGN 201 were given in conjunction with conventional radiation therapy to 19 patients with localized non-small cell lung cancer who were not eligible for surgery or chemotherapy. Of the 19 patients, 12 or 63%, had complete or partial responses at the injected site measured 3 months after completing the treatment, and 4 patients could not be evaluated. These responses were pathologically confirmed by biopsies that were negative for cancer cells. Historically, the pathological response rate in locally advanced lung cancer following radiotherapy given alone is less than 18%. Compared to the historical analysis, the combination of INGN 201 and radiotherapy provided a three fold increase in pathologically confirmed response rates. Today�s presentation provided molecular evidence for the mechanism underlying these clinical results.

�This study was designed to efficiently determine how much additional benefit might be afforded to standard radiotherapy when a novel gene therapy was added,� said James A. Merritt, M.D., vice president of clinical affairs for Introgen. �We determined that the two treatments can be safely and effectively combined and clinical activity appears to be enhanced. Based on these results, and Introgen�s issued patent which covers combination therapy, this study is a precursor to a Phase III study in which we will further evaluate the effectiveness of this combination approach.�

�The high rate of pathologically confirmed local responses to this gene therapy drug candidate suggest that this therapy may offer a new treatment modality in our fight against cancer,� said Jack A. Roth, M.D., co-investigator of the study and Chair of the Department of Thoracic and Cardiovascular Surgery at M. D. Anderson Cancer Center.

Introgen controls a number of U.S. patents that relate to adenoviral p53 as well as adenoviral p53 combination therapy. Three patents cover gene therapy of cancer using a p53 tumor suppressor gene in combination with one or more chemotherapeutic drugs, radiation therapies, or other agents that have a damaging effect on the DNA of cancer cells. Two of these patents cover the clinical use of the p53 gene before, during or after treatment with chemotherapy or radiotherapy, and the third covers therapy using the p53 gene in combination with a class of chemotherapy agents called DNA repair inhibitors. An additional patent covers the treatment of cancer with adenoviral p53 to kill tumor cells and promote tumor regression.

Non-Small Cell Lung Cancer

Lung cancer is the most common cause of cancer-related death in the United States, with an estimated 164,000 new cases diagnosed annually. An estimated 157,000 deaths occurred in 2000, accounting for 28% of all cancer deaths. The five-year survival rate for patients diagnosed with lung cancer is 14%. Non-small cell, or NSC lung cancer, comprises approximately 80% of all lung cancer cases.

In a separate presentation today, Carolyn Muller, M.D., of The University of Texas Southwestern Medical Center presented results of a Phase I ovarian cancer study. Ten women with refractory ovarian cancer were treated monthly with three doses of INGN 201 delivered intraperitoneally, into the abdomen. This study was designed to evaluate safety and toxicity and transduction of tumor cells in the abdomen, which required treating patients with advanced disease. There was evidence that disease progression was slowed as some patients had a period of stable disease. The treatment appeared to be safe and well-tolerated. Treatment with INGN 201 resulted in up to a 17 fold increase in the percent of tumor cells expressing detectable p53 protein. This study is part of Introgen�s Cooperative Research and Development Agreement (CRADA) with the National Cancer Institute evaluating adenoviral p53 therapy in numerous cancer indications. Introgen�s agreement with the NCI has created the broadest clinical trial program for an adenoviral-p53 therapeutic in the world. These study results were invited to appear on the ASCO virtual meeting site.

�We were able to treat patients weekly in this study, and have not yet reached a maximum tolerated dose (MTD), suggesting that intraperitoneal administration of INGN 201 may be used as a repeat treatment with no additional toxicities,� said Dr. Muller.

Ovarian Cancer

There are an estimated 23,000 new cases of ovarian cancer diagnosed annually in the United States. It accounts for 4% of all cancers among women and ranks second among gynecological cancers. In approximately 80% of patients with advanced disease, the cancer remains localized within the peritoneal, or abdominal cavity. If diagnosed and treated early, the survival rates for this disease are high, however, only about 25% of all cases are detected at an early stage.

Introgen is a leader in the development and production of gene-based drugs for the treatment of cancer and other diseases. Introgen�s product candidates engage precise molecular targets to produce a highly specific therapeutic effect. Introgen specializes in combining appropriate gene delivery systems and therapeutic genes to make its gene-based drugs. Introgen�s lead product candidate, INGN 201, is currently in Phase III clinical trials for the treatment of head and neck cancer. INGN 201 has been used in numerous clinical trials worldwide either alone or in combination with conventional treatments such as chemotherapy and radiotherapy. Introgen is also conducting a Phase II clinical trial for INGN 201 in lung cancer and Phase I trials for INGN 201 in additional cancer indications including prostate, ovarian, bladder, brain, and breast cancer. In an announcement earlier this year, Introgen published results of preclinical studies which indicate a possible application of INGN 201 whereby the human immune system may be directed to attack tumor cells. Introgen�s second product candidate, INGN 241 (Adenoviral-mda7), for the treatment of solid tumors, is in Phase I clinical development. Introgen controls a broad intellectual property portfolio that includes more than 200 pending and issued patents for a variety of gene therapy technologies. Introgen has FDA inspected fully staffed validated Good Manufacturing Practices (cGMP) production facilities that are producing Phase III and commercial inventory of INGN 201. Introgen has received U.S. Patent No. 6,194,191 for the commercial scale production of adenovirus.

Certain statements in this press release that are not strictly historical may be �forward-looking� statements, which involve risks and uncertainties. Such forward-looking statements include, but are not limited to, those relating to safety and efficacy of drug product candidates, the efficacy of our drug product candidates in treating lung and ovarian cancer, and Introgen�s ability to complete its clinical trials or successfully commercialize INGN 201 or any other product candidates. There can be no assurance that Introgen will be able to commercially develop gene-based drugs, that necessary regulatory approvals will be obtained or that any clinical trials or studies undertaken will be successful or that the proposed treatments will prove to be safe and/or effective. The actual results may differ from those described in this press release due to risks and uncertainties that exist in Introgen�s operations and business environment, including, but without limitation, Introgen�s stage of product development and the limited experience in the development of gene-based drugs in general, its dependence upon proprietary technology and current competition, history of operating losses and accumulated deficits, Introgen�s reliance on collaborative relationships, and uncertainties related to clinical trials, safety, efficacy, the ability to obtain the appropriate regulatory approvals, 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 prospectus dated October 12, 2000 and the 10-Q filed on February 14, 2001. Introgen undertakes no obligation to publicly release the results of any revisions to any forward-looking statements that reflect events or circumstances arising from the date hereof.

Editor's Note: For more information on Introgen Therapeutics, or for a menu of archived press releases, please visit the Company Website at: www.introgen.com, or call Introgen�s toll-free Investor Relations hotline at 1-877-776-GENE (4363).