Clinical Investigators Report On Vical Cancer Therapy Results Support Ongoing Development of Gene-Based Immunotherapy for Kidney Cancer.

SAN DIEGO--(BW HealthWire)--Oct. 4, 1999--

In the October issue of the Journal of Clinical Oncology (JCO), investigators report encouraging Phase I/II clinical trial results for Leuvectin in patients with kidney cancer.

Leuvectin, an experimental gene therapy developed by Vical Incorporated (Nasdaq:VICL) of San Diego, uses a piece of DNA to attempt to make cancer cells produce interleukin-2 (IL-2). The IL-2 is then intended to stimulate the patient's immune system to attack and kill the cancer cells. Results indicate that the treatment was safe and well-tolerated by most kidney cancer patients in the trial. Some patients experienced tumor shrinkage lasting for more than a year after treatment.

In the JCO paper, lead author Eva Galanis, M.D., of the Mayo Clinic in Rochester, Minnesota, concluded, "If these responses are confirmed in the currently ongoing multi-center Phase II trial in patients with metastatic renal cell carcinoma (RCC), they would be comparable with results achieved after systemic IL-2 administration in RCC patients, but with minimal toxicity."

As reported in the JCO paper, in the Phase I/II trial with Leuvectin in kidney cancer, two of the 14 evaluable patients achieved clinical partial responses persisting for 16 to 19 months and continuing, and two achieved clinical stable disease persisting for 9 to 10 months and continuing. "We believe the results of these initial human trials validate the use of direct gene transfer as a means to deliver biologically active proteins," said Alain B. Schreiber, M.D., president and chief executive officer of Vical. "This novel treatment approach is significant not only for its potential application in patients with advanced kidney cancer, but also for its potential in delivering other therapeutic proteins to treat a wide variety of disease conditions."

Contributing authors included investigators from the Arizona Cancer Center in Tucson; the University of Colorado Cancer Center in Denver; Scott & White Clinic in Temple, Texas; Sidney Kimmel Cancer Agency in San Diego; Cedars-Sinai Comprehensive Cancer Center in Los Angeles; and the University of Michigan Medical Center in Ann Arbor. JCO is the official publication of the American Society of Clinical Oncology.

Leuvectin, a gene-based treatment that uses the body's own immune system to fight cancer, is now being tested in a Phase II trial for patients with metastatic renal cell carcinoma, the most common form of kidney cancer. The trial will enroll up to 80 patients who have had their primary tumor(s) removed, and for whom additional surgery would not be curative. Leuvectin is administered on an outpatient basis.

The multi-center Phase II efficacy trial is being conducted at the UCLA Jonsson Comprehensive Cancer Center under the direction of Robert Figlin, M.D., at the Mayo Clinic under the direction of Dr. Galanis at the University of Washington under the direction of John Thompson, M.D., and at the Cleveland Clinic Foundation under the direction of Ronald Bukowski, M.D. Patients enrolled in the trial receive two cycles of treatment with Leuvectin, each involving six weekly injections followed by a four-week observation period. Treatment with Leuvectin is intended to stimulate both a localized immune response against the injected tumor and a systemic immune response against any distant tumors.

Initial results from the Phase II trial were reported in May 1999 in conjunction with a presentation at the Annual Meeting of the American Society of Clinical Oncology (ASCO). Four of the 22 evaluable patients (18 percent) enrolled to date experienced significant (>25 percent) tumor reductions, including one patient who experienced 90 percent and 100 percent reductions in two non-injected tumors. Twelve additional patients (55 percent) had stabilization of the injected tumor for 6 to 28 weeks and continuing. Six of the 22 patients (27 percent) experienced clinical stable disease for 5 to 7 months and continuing. Side effects from the Leuvectin treatment were primarily mild, with the most common complaint being flu-like symptoms of chills, low-grade fever, body aches and fatigue. The only serious side effects reported were two incidents of severe pain at the injection site. Both were resolved with pain medication during brief hospital stays.

Background - Leuvectin

Leuvectin is a DNA-based product candidate currently being studied in kidney cancer and prostate cancer. The active ingredient in Leuvectin is a gene encoding IL-2, a naturally occurring protein that stimulates the immune system. Administration occurs by direct injection into a tumor, leading to uptake by the tumor cells and subsequent expression of the IL-2 protein. The company believes local expression of IL-2 by cancer cells may stimulate the patient's immune system to attack and destroy the tumor cells.

Recombinant IL-2 protein is an approved anti-cancer agent for the treatment of advanced kidney cancer and melanoma. When given systemically, it is frequently associated with serious side effects. Because Leuvectin delivers IL-2 locally within the tumor, it may provide similar benefits with fewer side effects than the systemic protein therapy.

As a result of initial Phase I/II clinical testing of Leuvectin in several cancer indications, Vical concluded that the product candidate appeared to be well-tolerated and successful in delivering the IL-2 gene in a majority of patients, and may have provided clinical benefit in certain patients. Leuvectin is currently being evaluated for efficacy in Phase II multi-center trials in patients with kidney cancer and prostate cancer.

Background - Renal Cell Carcinoma

Renal cell carcinoma, the most common type of kidney cancer, is more prevalent in males than females, predominantly in people over age 35. In the United States alone, 30,000 new cases of renal cell carcinoma and nearly 12,000 deaths are expected in 1999.

Kidney cancer frequently spreads to adjacent tissues and ultimately to other internal organs, most often the lungs, bone, brain, or liver. About 30 percent of patients have metastatic disease when first diagnosed. Treatment of regional metastatic kidney cancer involves surgical removal of the affected kidney and surrounding tissue, frequently combined with palliative radiation therapy to alleviate pain.

Immunotherapy with recombinant IL-2 protein, sometimes used in conjunction with lymphokine activated killer (LAK) cell infusions, has been effective but not well-tolerated at approved doses. Complications of high-dose IL-2 treatment can include moderate to severe flu-like symptoms of drowsiness, confusion and fever, decrease in clot-forming blood platelets, buildup of fluid in the lungs and severe breathing difficulties, liver failure, and heart attack. Alpha interferon has also been used with limited success. The five-year survival rate for metastatic disease where surgery cannot be curative is less than 10 percent with very few treatment alternatives.

Vical Inc. is focused on the development of pharmaceutical product candidates based on its patented naked DNA technology. A number of therapeutic and vaccine product candidates are currently under development for the prevention or treatment of cancer, infectious diseases and metabolic disorders by Vical and its collaborative partners, including Merck & Co., Pfizer Inc., Pasteur Merieux Connaught, Rhone-Poulenc Rorer, Centocor Inc., Merial, and Boston Scientific Corp. Allovectin-7, which uses a lipid-DNA complex to help the immune system recognize and attack cancer cells, is in Phase II and Phase III testing in certain patients with metastatic melanoma and in Phase II testing in patients with unresectable head and neck cancer. Leuvectin, which uses a lipid- DNA complex to stimulate an immune response against cancer cells, is in Phase II testing in patients with kidney cancer and prostate cancer. Vaxid, a naked DNA vaccine to prevent relapse of B-cell lymphoma, is in Phase I/II testing. In collaboration with the National Cancer Institute, a naked DNA vaccine to treat metastatic melanoma is in Phase I/II testing.

This press release contains forward-looking statements that are subject to risks and uncertainties that could cause actual results to differ materially from those set forth in the forward-looking statements, including whether Leuvectin or any other product candidates will be shown to be safe and efficacious in clinical trials, the timing of clinical trials, whether Vical will seek or gain approval to market any product candidates, and additional risks set forth in the company's filings with the Securities and Exchange Commission. Actual results may differ materially from those projected. These forward-looking statements represent the company's judgment as of the date of this release. The company disclaims, however, any intent or obligation to update these forward-looking statements.

For news releases and other information, visit the Vical Web site at http://www.vical.com.