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Anti-MUC1 AR20.5

Products Under Development * Anti-MUC1 AR20.5

BrevaRex MAb-AR20.5 is a novel immunotherapeutic drug for investigational use in the treatment of patients with malignancies expressing the tumor-associated antigen known as MUC1.

The active component is the murine monoclonal antibody (MAb) AR20.5,which binds with high affinity to MUC1, recognizing the tandem repeat peptide sequence DTRPAP of the high molecular weight MUC1 glycoprotein. MUC1 is expressed on many adenocarcinomas including breast, lung, colon and prostate as well as in multiple myeloma and this epitope uniquely exposed in malignant cells.

Preclinical studies with MAb AR20.5 has found to be active in pancreatic cancer models and augmented the therapeutic response obtained with gemcitabine in that model. The antibody has already been evaluated in a phase I clinical trial that evaluated patients with MUC1-expressing cancer. Immune stimulatory dose levels of 1, 2 and 4 mg doses were studied and no dose limiting toxicity was encountered. Both humoral and cellular immune responses were detected in this heavily pretreated population. The dose level of 2 mg was associated with the most prominent immune responses. Treatment-emergent MUC1-specific T-cell responses were detected in five of 10 evaluable patients treated with MAb-AR20.5.

Ongoing Clinical Development Plan

OncoQuest is planning to initiate a proof-of-concept clinical trial to establish the utility of BrevaRex MAb-AR20.5 in combination with chemotherapy (and with other active immunoadjuvants leveraging the experience obtained from the oregovomab program) in pancreatic cancer. The protocol will involve a homogenous population of resectable patients who will receive 2 cycles of neodjuvant treatment, scheduled surgery, and 4 cycles of adjuvant therapy. Point estimates of PFS and OS will be calculated using Kaplan Meier analysis and a lower 95% confidence interval established relative to the performance of the combination of gemcitabine and Abraxane in the same population being currently studied in a phase III clinical trial in the US. The ability of the immunization to induce MUC1 specific T cell immunity will be established as a primary bioactivity endpoint of interest. This program is funded by a $5.3M National Cancer Institute (SPORE) grant to Dr. Tony Hollingsworth at University of Nebraska Medical Center.