A Potential Treatment for non-Hodgkin’s Lymphoma

Pixantrone (pick-san-trone) (BBR 2778) is a new chemical compound for the treatment of non-Hodgkin’s lymphoma (NHL), and various other hematologic malignancies, solid tumors, and immunological disorders. It is being developed to improve the activity and safety in treating cancers usually treated with the anthracycline family of anti-cancer agents.

Anthracyclines have been shown to be very clinically active in a number of tumor types, such as lymphoma, leukemia, and breast cancer. For these diseases, anthracycline-containing chemotherapy regimens are effective in first-line treatment. Pixantrone is a novel DNA major groove binder with an aza-anthracenedione molecular structure, differentiating it from anthracycline chemotherapy agents.

Reducing Cardiac Toxicity

The cardiac toxicity of anthracyclines often prevents their repeat use in patients who relapse after first-line anthracycline treatment. As a result, chemotherapy regimens that do not include anthracyclines often are used for the second-line treatment of relapsed NHL. There are no drugs approved in the United States for second- or third-line treatment for patients with relapsed aggressive NHL.

Pixantrone has been designed to reduce the potential for these severe cardiotoxicities, as well as to potentially increase activity and simplify administration compared to the currently marketed anthracyclines. Pixantrone could allow repeat therapy in relapsed patients and combination therapy with a broader range of chemotherapies. Pixantrone also is easier to administer than anthracyclines. This is because it is less likely to cause tissue damage and can be administered through a peripheral vein, eliminating the need for a central line.

Potential Clinical Use

Pixantrone offers potential clinical use for treatment of:

• Patients with prior exposure to anthracyclines
• Patients with non-anthracycline-induced cardiac disorders
• Patients who might benefit from longer-term therapy than can be administered with currently approved agents in these classes

About NHL

Non-Hodgkin’s lymphoma (NHL) is the fifth most common cancer in the United States. It is caused by the abnormal proliferation of white blood cells. It normally spreads through the lymphatic system of vessels that drains fluid from the body. NHL can be broadly classified into to main forms: aggressive NHL, a rapidly spreading acute form of the disease, and indolent NHL, which progresses more slowly.

Pixantrone Clinical Research

Pixantrone has been studied in both indolent and aggressive NHL. The drug has demonstrated encouraging activity as a single agent in aggressive NHL, and recent clinical results suggest the compound also may be synergistic with other agents commonly used in combination therapy.

Pixantrone Regulatory Strategy

We are focusing resources on obtaining pixantrone approval based on the EXTEND (PIX301) phase III clinical trial of pixantrone for patients with relapsed aggressive NHL. Enrollment is complete in this trial, and in November 2008 we announced that this trial achieved the primary efficacy endpoint based on a preliminary intent to treat efficacy analysis. Further evaluation of additional details of the study will provide complete safety and progression-free survival information.