BZL Biologics LLC announced that its development partner, Millennium Pharmaceuticals Inc has initiated a phase I clinical trial of MLN2704 (formerly known as MLN591 DM1) in patients with metastatic androgen-independent prostate cancer. MLN2704 employs a novel approach designed to deliver chemotherapy directly to prostate tumor cells while minimizing harm to healthy cells. The primary objectives of the open-label, dose-escalation study are to determine the dose-limiting toxicity, the maximum tolerated dose, and pharmacokinetic properties of MLN2704.

The agent combines the cytotoxic agent DM1 with a monoclonal antibody, MLN591, which binds to a specific protein on the surface of prostate cancer cells called prostate-specific membrane antigen (PMSA). Known as a "Tumor- targeted Monoclonal Antibody Vehicle" or T-MAV, MLN591 was discovered by a team headed by Dr. Neil H. Bander, the Bernard and Josephine Chaus Professor of Urological Oncology at Cornell University Medical Center.

"We are very pleased with the continued clinical progress of the MLN591 antibody vehicle," said Dr. Bander. "We are particularly excited to begin this new stage of clinical research which will combine the tumor-specific targeting of MLN591, already demonstrated in patients, with the known potencyof a drug such as DM1."

To be eligible for the study, patients must have androgen-independent prostate cancer (cancer that is resistant to hormone manipulation therapy) with progressive measurable or evaluable disease, defined as having progressive tumor lesions (changes in the size of lymph nodes or parenchymal masses on physical examination or x-ray), progressive bone metastasis (presence of new lesion(s) on a bone scan), and/or progressive prostate specific antigen (PSA) levels.

Prior to the license and development agreement with Millennium, BZL had completed the de-immunization process for MLN591 and created a highly productive cell line and commercial-scale GMP manufacturing of the antibody. Phase I studies with radiolabeled MLN591 antibody, conducted at New York-Presbyterian Hospital/Cornell and Memorial Sloan-Kettering Cancer Center and sponsored by BZL, demonstrated specific targeting of both prostate and solid tumors.

To date, more than 125 patients have received the de-immunized version of MLN591 in seven different BZL-sponsored trials at two different institutions. These studies include patients with prostate cancer as well as other types of solid tumors. MLN591 has been extremely well tolerated and non-immunogenic and appears to target sites of cancer anywhere in the body in virtually all patients regardless of whether they have prostate cancer or other types of solid tumors.