Vical Begins Allovectin-7 Registration Trials; Supportive Efficacy Results Presented At ASCO Meeting.

LOS ANGELES--(BW HealthWire)--May 18, 1998--Vical Incorporated (NASDAQ:VICL) announced today the initiation of registration-supportive expanded Phase II and Phase III multi-center clinical trials with Allovectin-7, the company's lead oncology product candidate, in certain patients with metastatic melanoma.

Either or both of the pivotal trials could support initial product registration if endpoints are achieved. The U.S. Food and Drug Administration (FDA) has reviewed data from previous studies and has confirmed acceptability of the designs, endpoints and analysis plans for both new trials. Allovectin-7 is also being tested in certain patients with unresectable head and neck cancer. Results from previous trials in both indications are being presented at the annual meeting of the American Society of Clinical Oncology (ASCO).

Alain B. Schreiber, M.D., Vical's president and chief executive officer, said, "Our development and testing of Allovectin-7 has yielded consistent safety and efficacy data in numerous advanced melanoma patients at multiple clinical centers over a period of several years. We believe the results provide evidence that Allovectin-7 can offer durable clinical benefits with no serious side effects for certain patients with advanced melanoma."

Allovectin-7 Registration Trials in Melanoma Patients

Vical is initiating two separate pivotal clinical trials in certain advanced metastatic melanoma patients, either or both of which could lead to registration for their respective patient populations if endpoints are achieved. Data for both trials will be evaluated by independent safety and efficacy committees to determine response rates and durations and to assess disease progression.

In the Phase III study, when data are available on the first 70 patients, the independent committee will analyze interim results. For both the interim analysis and final review, the committee will review objective data without knowing whether patients were in the experimental group or the control group.

Expanded Phase II Clinical Trial 

The open-label, multi-center Phase II trial is designed to confirm the efficacy of Allovectin-7 in the defined patient population which appeared to benefit most in earlier Phase II trials. Enrollment will be open to patients with metastatic (spread beyond the initial site), refractory (unresponsive to standard therapy), Stage III or IV disease that has not yet spread to multiple internal organs. Up to 70 advanced melanoma patients will be enrolled at approximately 15 leading cancer treatment centers throughout North America. The objective is a clinical partial or complete response in at least 15 percent of the evaluable patients, persisting with a median duration of at least four months. Earlier Phase II trials testing Allovectin-7 in this patient population would have exceeded this objective (see details below).

A clinical partial response is defined by the World Health Organization (WHO) as a reduction of 50 percent or more in a patient's total tumor burden lasting for at least four weeks, with no new tumors and no growth of 25 percent or more in any tumor. A clinical complete response is defined as elimination of all detectable tumors lasting for at least four weeks. Stable disease is defined as a reduction of less than 50 percent in a patient's total tumor burden lasting for at least four weeks with no new tumors and no growth of 25 percent or more in any tumor.

Treatments will be administered by six weekly intratumoral injections of 10 ug per dose. If the disease is stable or regressing after a 4-week observation period, another series of six weekly injections may be administered.

Phase III Clinical Trial 

The open-label, multi-center, randomized, controlled Phase III trial is designed to determine the efficacy of Allovectin-7 when combined with standard chemotherapy in patients with unresectable, metastatic melanoma not previously treated with chemotherapy. In prior trials, Allovectin-7 was used only after standard therapies had failed.

In the new trial, patients may be enrolled upon diagnosis or upon progression to Stage III or Stage IV disease when surgery or radiation therapy are usually no longer curative. Because Allovectin-7 is intended to trigger an immune response against tumor cells, the company believes the treatment may be more effective in patients whose immune systems have not been compromised.

Approximately 140 patients per group, randomized by sex, age, and extent of disease spread, will be enrolled into a chemotherapy-plus-Allovectin-7 experimental group or a chemotherapy-only control group. The objective is a greater relative clinical benefit for the experimental group than for the control group. Acceptable endpoints are either an improvement of at least two months in the median time to disease progression with no decrease in the rate of objective clinical responses, or an improvement of at least 15 percent in the rate of objective clinical responses with no decrease in the median time to disease progression.

The chemotherapy agent dacarbazine (DTIC) will be administered intravenously over one hour at a dose of 800 mg/sq m in three cycles at four-week intervals. For the experimental group, Allovectin-7 will be administered by two weekly intratumoral injections of 10 ug per dose during each of the three DTIC treatment cycles.

Background -- Allovectin-7

Allovectin-7 is a novel, gene-based product candidate being studied in melanoma and head and neck cancer. The active ingredient in Allovectin-7 is a gene encoding HLA-B7, an antigen responsible for strong immune responses such as organ transplant rejection. To improve delivery, the gene is complexed with a proprietary lipid and suspended in a water-based solution. Administration occurs by direct injection into a tumor, leading to uptake by the tumor cells and subsequent expression of the HLA-B7 antigen. The company believes that expression of HLA-B7 by cancer cells may trigger the patient's immune system to recognize these cells as "foreign" and selectively destroy the tumor.

As a result of Phase I/II clinical testing of Allovectin-7 in several cancer indications, completed in 1995, Vical concluded that the product candidate appeared to be safe and well-tolerated, successful in delivering the HLA-B7 gene in a majority of patients, and effective in inducing tumor shrinkage in some patients. Multi-center Phase II trials began in September 1995 studying Allovectin-7 in patients with melanoma and other cancer indications. In October 1996, Vical initiated a multi-center Phase II trial in which approximately 50 patients with advanced metastatic melanoma were treated.

Allovectin-7 in Melanoma

Vical's Allovectin-7 melanoma trials to date have been conducted predominantly in patients with Stage IV, metastatic, refractory disease. In independent Phase I/II trials conducted at the Arizona Cancer Center, the University of Michigan, and the British Columbia Cancer Agency, seven of 36 evaluable patients attained clinical responses lasting from 8 to 45 months, with one of the seven attaining a clinical complete response and remaining tumor-free for 45 months until death from an unrelated cause.

The overall clinical experience to date was presented at the ASCO annual meeting by Evan Hersh, M.D., of the Arizona Cancer Center, and an investigator on several of the trials. Phase II trials were conducted at the Arizona Cancer Center, British Columbia Cancer Agency, City of Hope, Mayo Clinic, Scott & White Clinic, University of Michigan, Northern California Medical Center, University of Colorado and University of Washington.

The company believes certain results from the first Phase II melanoma trial indicated the potential efficacy of Allovectin-7 in treating melanoma patients, and suggested a correlation between disease spread and such potential efficacy. Among 11 evaluable melanoma patients with refractory metastatic disease that had not yet spread to multiple internal organs, two patients achieved clinical partial responses lasting 6 to 16 months and continuing. Three additional patients in this group achieved stable disease lasting 2 to 11 months and continuing, yielding a total of five out of 11 evaluable patients (45 percent) deriving clinical benefit from treatment. Of the 14 evaluable patients with widespread advanced disease affecting multiple internal organs, none achieved a clinical response, while three patients achieved stable disease lasting 2 to 11 months and continuing.

The company believes results from the second Phase II melanoma trial appeared to confirm the correlation between disease spread and potential efficacy. Among 12 evaluable patients with refractory metastatic disease that had not yet spread to multiple internal organs, two patients achieved clinical partial responses lasting 2 to 16 months and continuing. Three additional patients in this group achieved stable disease lasting 4 to 6 months and continuing, yielding a total of five out of 12 evaluable patients (42 percent) deriving clinical benefit from treatment. Of the 36 evaluable patients with widespread advanced disease affecting multiple internal organs, two patients achieved a clinical response lasting 2 to 12 months and continuing, while seven patients achieved stable disease lasting 4 to 9 months and continuing.

Combined results from the two Phase II trials in patients meeting eligibility criteria for the expanded Phase II trial totaled four of 23 evaluable patients (17 percent) achieving clinical partial responses with a median duration of 11 months. Among the total of 73 evaluable patients in the Phase II trials, 22 patients (30 percent) derived clinical benefit from treatment. Results from the three Phase I/II trials, which included patients meeting eligibility criteria for the expanded Phase II trial and patients with widespread metastases, totaled seven out of 36 evaluable patients (19 percent) achieving clinical partial or complete responses with a duration of at least 8 months. These results compare favorably with available clinical data on other FDA-approved biological agents such as alpha interferon and interleukin-2.

"Our experience with Allovectin-7 in advanced melanoma patients strongly suggests that we have established achievable endpoints for our expanded Phase II registration trial," said Schreiber. "We believe we have designed a trial that provides a potentially beneficial treatment to the most appropriate patients, and offers a good chance of success for Vical."

Schreiber added: "While we are extending our application of Allovectin-7 into a new segment of the melanoma population with our Phase III trial, we are excited by the opportunity to treat patients whose immune systems may be more fully functional. We hope these patients will respond at least as well as the refractory patients in our prior studies."

Allovectin-7 in Head and Neck Cancer

Allovectin-7 is also being evaluated in patients with refractory, unresectable or recurrent post-surgical squamous-cell cancers of the head and neck. Of the 11 patients treated in an investigator-sponsored Phase I/II clinical trial conducted at the University of Cincinnati, one achieved a clinical complete response lasting 29 months and continuing, and three achieved clinical partial responses lasting at least 5 months.

Preliminary results for 23 evaluable patients in a company-sponsored multi-center Phase II trial yielded one clinical complete response lasting 4 months and continuing, and 10 patients with stable disease after 2 to 4 months and continuing. The Phase II trial was conducted at the University of Cincinnati, the University of Arkansas, the University of California at Los Angeles, the University of Michigan, the University of Minnesota VA and the University of Washington.

"Allovectin-7 can result in disease regression or stabilization of even large, previously treated head and neck cancer," concluded Lyon L. Gleich, M.D., Department of Otolaryngology at the University of Cincinnati and an investigator in both studies. He further stated, "Responses seen in these advanced cases (where standard therapy alternatives have been exhausted) suggest Allovectin-7 will be active in earlier disease."

"We are very encouraged by the high number of patients deriving clinical benefit at this early evaluation point," said Schreiber, "and we look forward to collecting more complete long-term data."

Background -- Melanoma

Melanoma is a skin cancer found predominantly in Caucasians, most often in fair-skinned people susceptible to sunburn. Exposure to sunlight, particularly UVB rays, is considered the primary cause. The incidence of melanoma is doubling every 6 to 10 years among affected populations, with 41,600 new cases and 7,300 deaths estimated for 1998 in the U.S.

Melanoma frequently spreads to tissues beneath the skin and to internal organs, most often the lymph nodes, lungs, brain, or liver. If the disease progresses to Stage III, defined as limited regional metastases, treatment may involve surgical removal of the tumors and any affected lymph nodes, followed by systemic or local chemotherapy with single or multiple agents. The five-year survival rate for treated Stage III patients is about 60 percent, and quality of life is often compromised by both the disease and the treatment.

If the disease progresses to Stage IV, defined as advanced regional or any distant metastases, treatment may include surgical removal of tumors and affected lymph nodes, systemic or local chemotherapy, radiation therapy, and immunotherapy. The prognosis is poor, with a five-year survival rate for treated Stage IV patients of about 15 percent and a severely impaired quality of life. The spontaneous remission rate in metastatic melanoma patients is less than one percent.

Background -- Head and Neck Cancer

Head and neck cancer describes any of several localized tumors affecting the oral cavity, the pharynx or larynx, or the esophagus. Head and neck cancers are found more frequently in men than in women, and most often in men over age 40. Risk factors vary with the particular location, but can include use of tobacco and excessive consumption of alcohol. New diagnoses in the U.S. for the various head and neck cancers total more than 53,000 new cases and more than 24,000 deaths are estimated for 1998.

In advanced head and neck cancer, radical surgery and/or radiation therapy may be preceded by systemic chemotherapy to improve treatability, or followed by systemic chemotherapy to address remaining cancer cells, most often with a combination of agents. The five-year survival rate for head and neck cancer patients with widespread, unresectable malignancies is less than 5 percent.

Vical Inc. is focused on the development of gene-based pharmaceutical product candidates for the prevention or treatment of cancer, infectious diseases and metabolic disorders. A number of therapeutic and vaccine product candidates are currently under development by Vical and its collaborative partners, including Merck, Pasteur Merieux Connaught, Rhone-Poulenc Rorer, Centocor and Genzyme.

Allovectin-7, which uses a lipid-DNA complex to help the immune system recognize and attack cancer cells, is in Phase II testing in patients with melanoma and head and neck cancer. Leuvectin, which uses a lipid-DNA complex to stimulate an immune response against cancer cells, is in Phase I/II testing in patients with melanoma, kidney cancer, sarcoma, and prostate cancer. Vaxid, a naked DNA vaccine to prevent relapse of B-cell lymphoma, 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 any 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.

CONTACT: Vical Inc.

Alan R. Engbring, 619/646-1127