Bellicum Pharmaceuticals, Inc.

Bellicum's first product, BP-GMAX-CD1, is a genetically-modified autologous cell-based vaccine that is in late stage preclinical development and is scheduled to enter phase 1/2 clinical trials in early 2008, pending FDA authorization.

BP-GMAX-CD1, is a novel cancer vaccine produced by genetically modifiying autologous dendritic cells (DCs) to express an inducible costimulatory CD40 (iCD40) receptor. These genetically modified dendritic cells (gmDCs), after antigen loading, are "activated" in a spatially and temporally specific fashion by administration of AP1903, a dimerizer agent, 24 hours after vaccination, when these gmDCs have had time to travel to draining lymph nodes (LNs). Thus, BP-GMAX-CD1 is the first cancer vaccine that can be precisely "activated" at an optimal time and location in the body. Preclinical studies have demonstrated dramatic and complete eradication of established murine tumors, including very aggressive B16 melanomas, coupled with potent antigen-specific immune responses. Vaccinated animals also display a heightened resistance to the formation of new tumors when the animals are re-challenged with tumor cells. These results are far superior to those observed with control DCs matured in a standard fashion, which model earlier dendritic cell approaches that have advanced into late stage clinical trials. The limited successes and favorable toxicity profile demonstrated in those clinical studies has provided proof-in-principle for the concept of employing autologous DCs cells pulsed with a tumor specific antigens for the treatment of advanced prostate cancer. Our approach is novel, building on these early modest successes by correcting key deficiencies thought to be limiting the efficacy in these previous vaccine protocols.

BP-GMAX-CD1 is pulsed with a prostate cancer antigen, and is intended for the treatment of patients with androgen-independent prostate cancer, with the possibility of expansion into earlier stages of the disease. Beyond this first target indication, versions of BP-GMAX-CD1 pulsed with antigens for other tumor types may be developed for treating other cancers (e.g. breast, colon, and lung cancer).

References:

Re-engineered CD40 receptor enables potent pharmacological activation of dendritic-cell cancer vaccines in vivo. Hanks BA, Jiang J, Singh RA, Song W, Barry M, Huls MH, Slawin KM, Spencer DM. Nature Medicine 11(2):130-137, January, 2005.

Lapteva N, Seethammagari MR, Hanks BA, Jiang J, Levitt JM, Slawin KM, Spencer DM: Enhancement of immunostimulatory functions of human dendritic cells by inducible CD40 and TLR4 ligation. Cancer Research 2007, in press.

Prostate Cancer: Prostate cancer is the most common solid tumor in the United States and the second leading cause of cancer mortality in U.S. men, leading to the death of 30,350 men in 2005. While great strides have been made in the detection and cure of early stage, clinically localized prostate cancer, once cancer progression, as evidenced by a rising PSA blood test, occurs indicating failure of local therapy, only palliative, but not curative, treatment options are available for these patients. The standard initial systemic therapy for progressive prostate cancer is androgen deprivation therapy (ADT), and while response rates are as long as 7 to 11 years for patients treated prior to the development of clinical metastases, the long-term consequences of ADT, which can lead to diabetes, hyperlipidemia, and osteoporosis, are increasingly recognized as major sources of morbidity for patients treated with ADT. In men who already have clinical metastases prior to the initiation of ADT, response to ADT may only lasts 14 to 30 months, before progression to androgen-independent prostate cancer (AIPC), the lethal form of prostate cancer, occurs. The options for treatment of AIPC are much more limited, with short-term efficacy offset by significant side effects. FDA-approved docetaxel chemotherapy yields a modest 2 month increase in median survival at the expense of fatigue, infections, hair loss and neuropathy.