Preclinical	Phase I	Phase II	Phase III	Marketed
Pixantrone	In April 2009, we began a rolling submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for pixantrone to treat relapsed or refractory aggressive NHL. We will request priority review by FDA.

A Potential Treatment for non-Hodgkin’s Lymphoma

Pixantrone (pick-san-trone) (BBR 2778) is a novel DNA major groove binder with an aza-anthracenedione molecular structure that differentiates it from the anthracyclines and other related chemotherapy agents. Pixantrone is under development for the treatment of non-Hodgkin’s lymphoma (NHL) with the goal of demonstrating improved efficacy and better safety than other drugs in this class.

Pixantrone Target Profile

Anthracyclines are the cornerstone therapeutic for the treatment of lymphoma, leukemia, breast cancer, and other diseases. Although they are sufficiently effective to be used as first-line (initial) treatment, they cause cumulative heart damage that may result in congestive heart failure many years later. As a result, there is a lifetime limit of anthracycline doses and most patients who previously have been treated with an anthracycline are not able to receive further anthracycline treatment if their disease returns.

Pixantrone has been designed to reduce the potential for this severe heart damage without sacrificing anti-cancer activity.

It also can be administered through a peripheral vein rather than a central implanted catheter as required for other drugs in this class.

Potential Clinical Use

Pixantrone offers potential clinical use for treatment of:

• Patients with aggressive NHL in relapse and those with prior anthracycline therapy
• Other diseases for which anthracyclines or anthracenediones are currently used, including non-Hodgkin's and Hodgkin's lymphoma, acute leukemia, breast cancer, and multiple sclerosis

About Non-Hodgkin's Lymphoma

Non-Hodgkin’s lymphoma is the fifth most common cancer in the United States. It is caused by the abnormal growth of lymphocytes, cells key to the functioning of the immune system. It usually originates in lymph nodes and spreads through the lymphatic system. NHL can be broadly classified into two main forms — aggressive NHL, a rapidly growing form of the disease that is lethal without effective therapy, and indolent NHL, which progresses more slowly.

There currently is no effective therapy for patients with aggressive NHL who relapse after or are refractory to second-line treatment.

Pixantrone Clinical Research

The pivotal phase III EXTEND (PIX301) clinical trial explored the role of single-agent pixantrone treatment in patients with relapsed or refractory aggressive non-Hodgkin's lymphoma who failed at least two other combination chemotherapy regimens.

The phase II RAPID (PIX203) trial investigated whether the substitution of pixantrone for the anthracycline doxorubicin in the first-line treatment of patients with advanced aggressive NHL can provide a comparable major response rate while reducing known doxorubicin-related toxicities.

Pixantrone has been studied in both indolent and aggressive NHL.

Pixantrone Regulatory Strategy

We are focusing 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 we have announced that it achieved the primary efficacy endpoint based on a preliminary intent-to-treat efficacy analysis.

In April 2009, we began a rolling submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for pixantrone to treat relapsed or refractory aggressive NHL. We will request priority review by FDA.

The FDA has granted fast track designation for pixantrone in third-line (or more) treatment of relapsed or refractory aggressive NHL.