Maxim Pharmaceuticals announced that it has completed enrollment for the confirmatory Phase 3 trial of its lead drug candidate Ceplene (histamine dihydrochloride) in combination with Interleukin-2 (IL-2) for the treatment of advanced malignant melanoma patients with liver metastases. The M0104 trial includes 225 patients with advanced malignant melanoma, the most life-threatening form of skin cancer, with liver metastases. The multinational, controlled, and randomized Phase 3 trial is designed to compare patient survival of the combination treatment of Ceplene and IL-2 versus IL-2 alone. The Phase 3 trial is expected to conclude in the second half of 2004.

"With the enrollment of this trial complete, we have achieved another major 2003 corporate objective and moved closer to bringing Ceplene to market," said Larry G. Stambaugh, Maxim's Chairman and Chief Executive Officer. "Data from this confirmatory trial will supplement the results of the first Phase 3 trial (M01) reported in 2000 and will be added to our existing New Drug Application (NDA) to seek U.S. approval. We are also proceeding with our plans to file an application for market authorization in Europe in November 2003. We will file under the central procedure to seek approval in the European Union to market Ceplene for the treatment of advanced malignant melanoma based on the results from the M01 Phase 3 trial combined with the results of our recently completed M0103 Phase 2 trial."

The M0104 trial studies the treatment of patients with advanced malignant melanoma who have liver metastases, a patient population with expected survival duration of less than five months. Ceplene demonstrated the strongest statistically significant survival benefit in liver metastases patients in the completed M01 Phase 3 trial, despite the poor prognosis for this patient population. The primary endpoint of the M0104 Phase 3 study is survival, with secondary endpoints including tumor response rate, progression-free survival, and duration of response. The study protocol has been reviewed and accepted under the Food and Drug Administration's (FDA) "Special Protocol Assessment" procedures.

"This is the third clinical trial of Ceplene in which I have participated over the last six years, and my personal observation is that the combination of Ceplene and IL-2 appears to be safe and well-tolerated by patients," said Dr. Sanjiv S. Agarwala, a principal investigator in the trial and Associate Professor at the University of Pittsburgh Cancer Institute. "Previous studies strongly suggest that there is a meaningful survival benefit associated with Ceplene therapy with no trade-off in terms of adversely effecting the patient's quality of life. I look forward to the results of the confirming Phase 3 clinical study."

"Available treatments for advanced malignant melanoma, such as higher doses of IL-2, often require in-patient hospitalization due to the severity of toxic side effects," said Professor Ulrich Keilholz, a principal investigator in the trial and Professor at the Benjamin Franklin University Clinic in Berlin, Germany. "By contrast, in clinical trials completed or ongoing to date Ceplene has been shown to be well-tolerated and safe to administer at home, an important consideration for critically ill patients and their caregivers."

After 36 months of follow-up, the Ceplene/IL-2 combination demonstrated a statistically significant (p=0.039, Log-Rank test) increase in survival in the overall intent-to-treat population compared to treatment with the same dose regimen of IL-2 alone. The increase in survival duration for patients treated with the Ceplene/IL-2 combination in the liver metastases subpopulation was also statistically significant after 36 months of follow up (0.0062, adjusted for multiple hypotheses). Generally, melanoma patients with liver metastases have a very poor prognosis for survival, with a median survival of two to four months and with less than three percent of patients surviving for two years. In the M01 trial, two-year survival rates for patients with liver metastases were 18.2 percent for the group treated with the Ceplene/IL-2 combination versus 2.7 percent for the group treated with IL-2 alone. The 12 and 24-month follow-up results were published the Journal of Clinical Oncology (JCO) Classic Papers in Melanoma published in September 2002.

Melanoma is one of the fastest-growing cancers in the developed world, with an estimated prevalence in 2002 of 230,000 in the United States and 150,000 in Europe. The incidence of melanoma more than tripled among Caucasians between 1980 and 2002. Today, there is no accepted standard for care of these patients and there is a critical need for effective therapies for this rapidly growing and deadly cancer.

Natural Killer (NK) cells and cytotoxic T cells possess an ability to kill and support the killing of cancer cells and virally infected cells. Much of the current practice of immunotherapy is based on treatment with cytokines such as IL-2 or interferon, proteins that stimulate NK and T cells. However, research has shown that oxygen free radicals released by certain immune cells can suppress NK and T cells and damage normal tissue, a process commonly referred to as oxidative stress. Oxidative stress, implicated in numerous diseases, is most pronounced in the liver.

Ceplene, based on the naturally occurring molecule histamine, has been shown to reduce oxidative stress. Accordingly, treatment with Ceplene may prevent the production and release of oxygen free radicals, thereby protecting NK cells and T cells and facilitating their activation by cytokines such as IL-2, interferon or other immunomodulators and protecting other critical cells and tissues, including the liver. Research regarding histamine, the active agent underlying Ceplene, and related clinical results has been the subject of more than 80 presentations at major scientific and clinical meetings, and have been published in more than 300 scientific and clinical articles. A three-minute animation of Ceplene's mechanism of action can be viewed on the Company's website.

Ongoing or completed Phase 3 combination studies of Ceplene have been conducted in Stage IV malignant melanoma and acute myeloid leukemia. Ceplene has also been tested in Phase 2 trials in hepatitis C and advanced renal cell carcinoma. Over 2,000 patients have participated in the Company's 17 completed and ongoing clinical trials in 20 countries for cancer and hepatitis C. Ceplene is an investigational drug and has not been approved by the FDA or any international regulatory agency.

Maxim Pharmaceuticals is a global biopharmaceutical company focused on developing and commercializing therapeutic products for life-threatening cancers and chronic liver diseases. Maxim's research and development programs are designed to deliver safe and effective drugs that possess the potential to extend survival while maintaining quality of life. Currently, the Company is conducting a confirmatory Phase 3 clinical trial in advanced malignant melanoma and a Phase 2 trial in hepatitis C. In addition to Ceplene, Maxim is developing small-molecule inhibitors and activators of programmed cell death, also known as apoptosis, which may serve as drug candidates for cancer, cardiovascular disease and other degenerative diseases. The Company's third technology platform, the MX8899 topical gel, is being tested in an attempt to help patients who suffer from oral mucositis and radiation dermatitis, both of which are debilitating side effects of certain cancer therapies.