Pharmacotherapy
p53-based Targets as Novel Cancer Treatment Strategies
By Introgen Therapeutics, Inc.
Jun 3, 2005 - 10:22:00 AM

ADVEXIN(R) and INGN 225, investigational cancer therapies currently being evaluated in Phase 3 and Phase 2 trials, respectively, by Introgen Therapeutics, Inc. , were highlighted today in a special session, titled "The Clinical Trial Data on Ad-p53 Gene Therapy of Cancer" at the American Society of Gene Therapy 8th Annual Meeting (ASGT).

Introgen's collaborators, Jack A. Roth, M.D., Chairman and Professor of the Department of Thoracic and Cardiovascular Surgery at The University of Texas M. D. Anderson Cancer Center, and Dmitry Gabrilovich, M.D., Associate Professor of Oncology at the H. Lee Moffitt Cancer Center reviewed the data generated to date with these investigational therapies.

The special session titled "The Clinical Trial Data on Ad-p53 Gene Therapy of Cancer" was co-chaired by Drs. James S. Norris, Medical University of South Carolina, and Helen E. Heslop, . Joining Drs. Roth and Gabrilovich was Dr. Yongsong Guan of Sichuan University.

"The presented data emphasize the broad potential application of ADVEXIN as a monotherapy and in combination with other treatments in the therapy of numerous cancers in a wide range of clinical settings," said Robert E. Sobol, M.D., senior vice president, Medical and Scientific Affairs at Introgen. "This special session at ASGT also underscores the ongoing interest in the p53 tumor suppressor gene as a novel cancer therapy. With ADVEXIN now in Phase 3 trials, we are closer than ever to realizing the potential of this key tumor suppressor gene in the treatment of cancer. Additionally, our clinical data with INGN 225, a therapeutic cancer vaccine utilizing ADVEXIN-treated immune cells, further demonstrates the broad utility of p53-based targets combined with standard therapies in the development of novel cancer treatment strategies."

Dr. Roth presented data from several ADVEXIN clinical studies including head and neck, lung, breast and new data in esophageal cancer.

ADVEXIN Provides Symptomatic Improvement in Esophageal Cancer Patients

The results of a Phase I/II trial of ADVEXIN in esophageal cancer refractory to chemotherapy and radiation were reported for the first time at ASGT by Dr. Roth. The trial was performed by Drs. Takenori Ochiai, Hideaki Shimada and colleagues from Chiba University in Japan. In this study, 30 percent of the patients (3/10) had significant symptomatic improvement in swallowing after ADVEXIN therapy. In addition, the median survival of the ADVEXIN treated patients was approximately 12 months which compared favorably to historical controls from that institution in which survival of less than 10 months was observed for patients who did not respond to these standard treatments. Six patients (60 percent) were still alive 1 year after beginning therapy.

ADVEXIN Trials in Head and Neck, Breast and Lung Cancers

In addition to these new findings regarding ADVEXIN in esophageal cancer, previously reported results of ADVEXIN as monotherapy in recurrent head and neck cancer and as part of initial therapy in combination with chemotherapy or radiation for breast and lung cancer were also presented.

The results of multi-national, multi-site Phase 2 clinical trials of ADVEXIN therapy in 217 patients with recurrent squamous cell cancer of the head and neck were reviewed. Patients treated with higher doses of ADVEXIN had a statistically significant increase in median survival compared to patients treated with lower doses (243 vs. 119 days). A subpopulation of patients participating in these trials had certain defining prognostic, medical and biological characteristics that represent refined targeting of ADVEXIN therapy. Analysis of the data from this patient subpopulation showed that the objective response rate (complete responses and partial responses with greater than 50% tumor reduction) was over 15%. Patients achieving disease control also showed clinical benefit reflected by either lack of progression and/or improvement in disease related morbidity.

In the breast cancer study of 12 women with very large tumors, the combination of ADVEXIN and chemotherapy resulted in objective clinical responses with greater than 50 percent tumor reduction in all patients and the ability to completely remove all of the tumors surgically. These data are better than the expected results with chemotherapy alone. Similarly, in 19 non-small cell lung cancer patients, combined ADVEXIN and radiation treatment resulted in 63 percent biopsy-proven complete responses at 3 months that is approximately 4 times the expected rate with radiotherapy alone.

INGN 225 in Patients with Advanced Small Cell Lung Cancer

Dr. Gabrilovich presented data from the ongoing Phase 2 trial of INGN 225 in patients with advanced small cell lung cancer previously treated with chemotherapy. These findings were presented in May 2005 at the American Society of Clinical Oncology Annual Meeting. These data show that the vaccine was well tolerated, with no appreciable INGN 225 related toxicity in any of the treated patients. After vaccine therapy, eighteen patients with progressive disease were treated with second-line chemotherapy. To date, 12 patients (66.7 percent) had objective responses or tumor reduction greater than 50 percent. Historically the expected objective response rate in these patients is between 20 and 30 percent. There was a statistically significant correlation between the development of a p53 immunological response to vaccination and objective responses to second line chemotherapy.

About ADVEXIN

ADVEXIN supplies the tumor suppressor p53 protein in very high concentrations in cancer tissue to selectively kill cancer cells. p53 is a normal constituent of cells and is known as a tumor suppressor because it inhibits the growth of tumor cells. One of the major roles of this protein is to eliminate cancerous cells by recognizing when DNA has been damaged by mutations or therapy and stopping cell growth. If the cell is damaged beyond repair, p53 activates programmed cell death pathways (apoptosis) to prevent the growth and propagation of cells with DNA damage.

There are two Phase 3 trials of ADVEXIN therapy currently underway in recurrent squamous cell cancer of the head and neck (SCCHN). Introgen has received FDA Fast Track designation for ADVEXIN therapy and ADVEXIN has been designated as an Orphan Drug for the treatment of head and neck cancer under the Orphan Drug Act.

About INGN 225

INGN 225 is a personalized therapeutic vaccine consisting of a cancer patient's dendritic cells, a type of immune cell, treated with an adenovector carrying the human p53 gene (Ad-p53). As a personalized vaccine, a small blood sample is obtained from a cancer patient and used as a source of dendritic cells, a type of cell that play a critical role in activating T- cells to attack cancerous or virally infected cells. An adenoviral vector is then used to deliver the p53 gene to the purified dendritic cells. When these modified dendritic cells are returned to the patient's body, they activate the patient's T-cells to seek out and destroy cancer cells that express p53.

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