Maxim Announces Additional Ceplene Clinical Trial Results Demonstrating Survival Benefit for Skin Cancer Patients.

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SAN DIEGO--(BW HealthWire)--May 20, 2002

Trial Results Presented at American Society of

Clinical Oncology Meeting

Maxim Pharmaceuticals Inc. (Nasdaq:MAXM)(SSE:MAXM) announced at the 38th meeting of the American Society of Clinical Oncology (ASCO), the results of clinical studies of its lead drug candidate, Ceplene(TM), in combination with interleukin-2 (IL-2) for the treatment of advanced metastatic melanoma, the most deadly form of skin cancer.

These results included additional analyses of Maxim's controlled 305-patient Phase 3 clinical trial (M01) of the Ceplene/IL-2 combination in the treatment of advanced metastatic melanoma. These analyses suggested that the Ceplene/IL-2 combination in the study provided a statistically significant survival benefit for the most critically ill patients, those that are categorized as "M1c" under a new American Joint Committee on Cancer (AJCC) definition. After 24 months of follow-up, 17 percent of the patients receiving Ceplene and IL-2 were alive compared to eight percent of patients receiving IL-2 alone.

In January 2002, clinical investigators commenced treating patients in a second Phase 3 trial of Ceplene and IL-2 in advanced metastatic melanoma with liver metastases. The current Phase 3 trial (M104) is designed to form the basis, in combination with the M01 Phase 3 study completed in 2000, for approval in the United States and other countries. Malignant melanoma is one of the fastest-growing cancers in the developed world, particularly among younger patients. There are more than 100,000 new cases and 15,000 deaths from melanoma each year in the United States, Europe and Australia combined.

Researchers also presented at the ASCO conference, the results of a Phase 2 study in melanoma suggesting that the combination of Ceplene and IL-2 may restore key immunologic function of patients and decrease apoptosis (programmed cell death) of natural-killer (NK) and cytotoxic T cells, both of which are critical immune cells. The two melanoma studies were among the five studies of Ceplene presented by researchers this week or accepted as abstracts at the ASCO meeting.

Dr. Eric Whitman of the Melanoma Center of St. Louis presented the results of additional analyses of Maxim's controlled 305-patient Phase 3 clinical trial (M01) of the Ceplene/IL-2 combination in the treatment of advanced metastatic melanoma. The results suggested that the Ceplene/IL-2 combination in the study provided a statistically significant survival benefit for those patients that are categorized as "M1c" under the new American Joint Committee on Cancer (AJCC) staging definition. Results previously reported for the Phase 3 study suggested that the most substantial survival benefit achieved with the Ceplene/IL-2 combination was for those patients who had metastases of their cancer to the liver (Agarwala SS et al., Journal of Clinical Oncology, January 2002).

The AJCC recently revised the staging for melanoma patients and has subdivided patients with distant metastases (stage IV) into 3 groups (M1a, M1b and M1c). M1c includes all patients with visceral metastases or any patient with an elevated serum LDH above the upper limit of normal regardless of disease site, and represents a patient group with poor prognosis. Researchers conducted an analysis of the Phase 3 trial, including all patients with M1c melanoma, to determine if the treatment benefit observed in patients with liver metastases extended to the larger M1c population. An analysis at 24 months of follow-up showed a statistically significant increase in overall survival (p=0.0189, log-rank test) for patients receiving Ceplene and IL-2 (n=105), with 17 percent of those patients treated with the Ceplene/IL-2 combination alive after 24 months compared to eight percent of those patients receiving IL-2 alone (n=106).

The researchers concluded that the results suggest that the previously reported statistically significant survival benefit of combination treatment with Ceplene/IL-2 for patients with advanced metastatic melanoma with liver metastases extends to those patients with stage M1c under the new AJCC staging system.

"We are pleased that over the last few months, additional study results have further supported the potential longer-term benefit of Ceplene in melanoma," said Dr. Kurt R. Gehlsen, Maxim's senior vice president, research and chief scientific officer. "Data continues to emerge that highlights the potential contributions that Ceplene provides as an important adjunct to immunotherapy. It is becoming clearer in cancer and other diseases that immune suppression due to oxidative stress can have a significant negative impact on treatment efficacy. Ceplene acts to reverse this suppression, and the data continue to support Ceplene as a potentially significant addition to immunotherapy."

Ceplene and IL-2 Effect on Immune System

Research has shown that oxygen free radicals released by certain immune cells such as monocytes can suppress the immune system and damage normal tissue, a process commonly referred to as oxidative stress. Ceplene, based on the naturally occurring molecule histamine, has been shown in preclinical work to prevent the production and release of oxygen free radicals, thereby reducing oxidative stress. In the case of cancer and hepatitis, oxygen free radicals may induce apoptosis (programmed cell death) in NK cells and T cells, both of which have the ability to kill cancerous or virally infected cells. By preventing the production and release of oxygen free radicals, Ceplene may protect NK and T cells. For the treatment of cancer and hepatitis, Ceplene is administered in combination with cytokines such as IL-2 and interferon-alpha, proteins that stimulate these same immune cells.

In recent years, much interest in cancer research has been focused on an indicator marker of white blood cells, CD-3 zeta. This molecule, which transduces activating signals to NK cells and T cells, is deficient in many cancer patients. The deficiency of CD-3 zeta may explain why NK cells and T cells are frequently non-functional and cannot exert their protective effects in cancer patients.

As reported by Dr. Theresa Whiteside, University of Pittsburgh Cancer Institute, Pittsburgh, and colleagues, a multi-center Phase 2 clinical study was conducted to evaluate the effect of Ceplene and IL-2 on the expression of immune markers for oxidative stress (CD-3 zeta and caspase-3 activity in T and NK cells) and for activated monocytes (superoxide generation, IL-6 production and serum neopterin levels). Important findings reported by the research team included the following:

-- Statistically significant increases in CD-3 zeta expression in NK and T cells were noted within each cycle of therapy and longitudinally between the first and second cycle of treatment.

-- Both spontaneous and stimulated IL-6 secretion by monocytes was significantly decreased post-therapy.

The researchers concluded that the combination of Ceplene and IL-2 may restore key immunologic function and decrease apoptosis (programmed cell death) of natural-killer (NK) and cytotoxic T cells.

Ceplene is currently being tested in Phase 3 cancer clinical trials for advanced metastatic melanoma and acute myelogenous leukemia. Phase 2 trials of Ceplene are also underway for the treatment of hepatitis C and advanced renal cell carcinoma. More than 1,300 patients have participated in the company's completed and ongoing clinical trials. Ceplene is an investigational drug and has not been approved by the U.S. Food and Drug Administration or any international regulatory agency.

Maxim Overview

Maxim Pharmaceuticals is a global biopharmaceutical company with a diverse pipeline of therapeutic candidates for life-threatening cancers and liver diseases. Maxim's research and development programs are designed to offer hope to patients by developing safe and effective therapeutic candidates that have the potential to extend survival while maintaining quality of life. Maxim has attracted an experienced international management group and a team of employees dedicated to commercializing life-enhancing product candidates. Joining this motivated team in its mission are world-leading scientific and clinical investigators and major pharmaceutical development partners.

In addition to Ceplene, Maxim is also developing small-molecule inhibitors and activators of programmed cell death, also known as apoptosis, that may serve as drug candidates for cancer, cardiovascular disease and other degenerative diseases. The company is also developing MaxDerm(TM), a technology platform designed for the treatment of medical conditions for which topical therapy is appropriate such as oral mucositis, herpes, decubitus ulcers, shingles, burns and related conditions.

This news release contains certain forward-looking statements that involve risks and uncertainties. Such forward-looking statements include statements regarding the efficacy and intended utilization of Ceplene, the apoptosis modulator technology and MaxDerm, and regarding the company's clinical trials. Such statements are only predictions and the company's actual results may differ materially from those anticipated in these forward-looking statements. Factors that may cause such differences include the risk that products that appeared promising in early research and clinical trials do not demonstrate safety or efficacy in larger-scale clinical trials, the risk that the company will not obtain approval to market its products, and the risk that clinical trials may not commence when planned. These factors and others are more fully discussed in the company's periodic reports and other filings with the Securities and Exchange Commission.

Note: Ceplene(TM), MaxDerm(TM) and the Maxim logo are trademarks of the company.

Editor's Note: This release is also available on the Internet at http://www.maxim.com.