The First DeCIDe™ Vaccine

BPX-101 is designed to elicit a greater and earlier clinical response than has been observed with other vaccine strategies, by pairing DeCIDe™ technology (for maximal immune response activation) with a form of the PSMA antigen, in an autologous format.

Enhanced Immune Response Drives Clinical Response

Recent late stage trials of cancer vaccines for prostate cancer have demonstrated modest median overall survival benefit, in the absence of near term evidence of efficacy (i.e. no reduction in PSA, no shrinkage of tumors on scans, no improvement in progression free survival, etc). These trials have also consistently failed to show a survival benefit during the first year of treatment, suggesting that patients with poor prognosis (<18 months projected survival) are unlikely to benefit. However, in one of these trials, patients with a measurably stronger immune response experienced the greatest overall survival benefit. This observation suggests that induction of a more potent immune response may translate to more meaningful improvements in progression free survival (PFS) and overall survival (OS), and may lead to measurable near term responses, potentially opening the benefits of vaccine therapy to patients with more advanced, aggressive disease. These hypotheses may be supported by interim clinical data from the ongoing BP-PC-001 trial.

PSMA Antigen

An antigen is a molecule recognized by the immune system. In the context of a cancer vaccine, the antigen should be selected based on its ability to target the immune response against cancer cells and not normal cells. In 2009, a National Cancer Institute pilot project to prioritize cancer antigens ranked PSMA highest among prostate cancer antigens, based on nine weighted criteria: therapeutic function, immunogenicity, role of the antigen in oncogenicity, specificity, expression level and percent of antigen-positive cells, stem cell expression, number of patients with antigen-positive cancers, number of antigenic epitopes, and cellular location of antigen expression.

PSMA is a type II membrane protein with neuropeptidase and folate hydrolase activities, but the true function of PSMA is currently unclear. Expression is largely, but not exclusively, prostate-specific and is maintained in advanced and hormone refractory disease, and up-regulated following androgen deprivation therapy (ADT). Ectopic expression of PSMA has been observed in tumor vascular endothelium of not only prostate, but also most other solid tumors. PSMA is not found in the vascular endothelial cells of corresponding benign tissue. Although one early histological study of metastatic prostate disease suggested that only ~ 50% (8 of 18) of bone metastases (with 7 of 8 lymph node metastases) expressed PSMA, the more sensitive reagent, 177Lu-radiolabeled MoAb J591, targeted to the ectodomain of PSMA, could target all known sites of bone and soft tissue metastasis in 30 of 30 patients, suggesting near universal expression in advanced prostate cancer.

Autologous Format

Bellicum's ultimate goal for the DeCIDe™ vaccine program is to deliver the DeCIDe™ gene and antigen to dendritic cells in situ, obviating the need for cell collection and external cell processing. While the core technology is already suitable for such an off the shelf embodiment, the technology needed to deliver the DeCIDe™ genetic material to DCs in vivo is not yet ready for clinical evaluation. Moreover, for proof of principle purposes, autologous processing eliminates significant variables and unknowns, allowing tight control and confirmation of successful dendritic cell processing and function.