Cytel's Theradigm-HBV successfully stimulates a hepatitis B-specific immune response in Phase II patient trial.

SAN DIEGO--(BUSINESS WIRE)--March 14, 1996--Cytel Corporation (NASDAQ:CYTL) today announced that its novel therapeutic vaccine, Theradigm(TM)-HBV, in a Phase II trial safely stimulated a hepatitis B-specific immune response in chronically infected patients. The activation of such an immune response is thought to be therapeutically relevant.

Hepatitis B (HBV), a disease prevalent in approximately 350 million people worldwide, causes 2 million deaths annually. The only approved treatment in the U.S. is alpha interferon, which cures only a small percentage of patients and is often accompanied by undesirable side effects. Poor tolerance due to side effects associated with alpha interferon is believed to derive from stimulation of a general immune response that is not disease-specific.

The goal of Cytel's approach is to selectively stimulate a specific immune response, where initially only the white blood cells that target the HBV infection are stimulated, thereby providing a benefit to patients and causing fewer side effects. The Company believes that the data reported today provide the preliminary evidence that such an approach is feasible and will move forward with definitive efficacy studies. This is believed to be the first demonstration that a therapeutic vaccine can activate the white blood cells specific for HBV in infected patients.

Interim results from one of Cytel's two ongoing Phase II trials of Theradigm-HBV are being presented today at IBC's Second Annual Industry Congress on Hepatitis in Washington, D.C. by Robert W. Chesnut, Ph.D., Cytel's Vice President, Immune Stimulation Program. The objectives of the ongoing trials are to determine an effective dose and regimen for inducing CTLs (cytotoxic T lymphocytes, or killer T cells) in chronically infected patients, to establish the safety of inducing a CTL response in these patients and to see if activation of CTLs results in evidence of the desired clinical effect, manifested by a transient flare in alanine aminotransferase (ALT), normalization of ALT and reduction in HBV DNA.

The data being presented demonstrate that Theradigm-HBV caused a HBV-specific CTL immune response in chronically infected patients and that the vaccine was well tolerated. The data also show a correlation of CTL induction with biological responses that typically precede clearance of hepatitis infection in patients that mount an immune response. Data are based on a population of 27 chronically infected patients treated to date in an open-label, dose-escalation, non-comparator study of Theradigm-HBV administered as a single injection of 50, 500 or 5000 micrograms followed at six weeks by a single booster of the same dose. The trial will continue as a 4 dose study and will evaluate one or more higher doses.

"It is important to have observed that CTLs can be induced in chronically infected hepatitis patients," stated Virgil Thompson, President and Chief Executive Officer of Cytel. "Patients who clear this virus, either spontaneously or in response to interferon, typically display a flare in ALT followed by a reduction in viral DNA and this clearance can be correlated with activation of a CTL response. We are encouraged to see these effects in some of the patients in our trial and look forward to the data from patients who receive four injections or higher doses."

Interim Results

Data generated to date indicate that Theradigm-HBV can induce a CTL response in chronically infected patients. The ability to induce a CTL response is dose dependent, with 0 out of 5 subjects (0%) at the 50 microgram dose level showing induction of CTL activity, while induction of CTL activity was observed in 3 of 8 patients (37%) at the 500 microgram dose level and in 6 of 9 patients (67%) at the 5000 microgram dose level.

Flares in the ALT levels were observed in relationship to the dose of Theradigm-HBV administered. No ALT flares were observed prior to first injection or in the 50 microgram dose group. Out of 10 patients in the 500 microgram dose group, 2 flares were observed (20%) while 5 of the 12 patients (42%) in the 5000 microgram dose group exhibited flares in their ALT.

This observation is potentially significant because the majority of patients who ultimately clear chronic HBV infection as a result of interferon therapy produce a flare in their ALT prior to viral clearance. Another indication of a potential clinical effect is normalization of ALT. Normalization was achieved in 3 of 12 subjects (25%) in the 5000 microgram dose group, and in none of the patients in the 50 and 500 microgram dose groups.

A dose dependent drop in HBV DNA was also observed, despite the high viral burden of the patients in the study group. A drop in the level of HBV DNA at 2 or more time points during the study was defined as a potentially useful clinical effect. None of the 5 patients at the 50 microgram dose level had a 50% or greater drop in DNA, while 2 of 10 (20%) at the 500 microgram dose level and 3 of the 12 (25%) at the 5000 microgram dose level had decreases in HBV DNA greater than 50%. In addition, one patient in the 5000 microgram dose group showed total clearance of HBV DNA and HBeAg. Clearance of HBV DNA and HBeAg is a significant step toward complete elimination of the chronic infection.

Hepatitis B

Hepatitis B is the second most prevalent sexually transmitted disease worldwide with chronic carriers approximating 350 million. This disease kills up to two million people each year. All individuals chronically infected with HBV continue to be infectious and are at increased risk of suffering from fatal liver cancer. About one in four of these chronic carriers eventually develop a more aggressive form of the disease known as chronic active hepatitis that can lead to debilitation and death from liver damage called cirrhosis. While it is most prevalent in the Far East, it is estimated that there are as many as 1.25 million carriers in the U.S.

Cytel's Technology

Cytel's novel therapeutic vaccine, Theradigm-HBV, is designed to activate CTLs that can specifically recognize HBV infected liver cells and stop viral replication. CTLs represent an important effector arm of the immune system which plays a pivotal role in the control and elimination of many infectious diseases and cancers. Cytel is also pursuing Theradigm drugs engineered to induce CTL responses against other infectious diseases such as human immunodeficency virus (HIV), hepatitis C virus, as well as cancers such as malignant melanoma and cervical cancer.

Cytel Corporation, founded in 1987, is a leader in the discovery, design and development of immunotherapeutics, a new class of drugs which the Company believes will be more selective and have fewer side effects than drugs currently on the market. Utilizing Cytel's advanced understanding of the immune system's operation both in disease and in health, the Company is developing drug candidates under two distinct approaches: the immune suppression program targets inflammatory diseases and reperfusion injury through the use of cell adhesion blockers that prevent the excessive migration of white blood cells into surrounding tissue, and the immune stimulation program is directed to the development of therapeutic vaccines to treat infectious diseases and cancers by stimulating production of antigen-specific cytotoxic T-lymphocytes by the immune system.

Actual results may differ materially from the above forward- looking statements due to a number of important factors, including but not limited to the timing and cost of conducting human clinical trials and the possibility that further testing of Theradigm-HBV may not support the results of the interim data described above or may reveal undesirable and unintended side effects or other characteristics that may prevent or limit its commercial use. These factors are more fully discussed in the Company's most recent Form 10-K and Form 10-Qs.

CONTACT: Cytel Corporation

Karin Eastham

Vice President and Chief Financial Officer

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