In recent tests in PharmaGap's development labs, PharmaGap has shown the effectiveness of GAP-107B8 in limiting growth of three human bladder cancer cell lines representative of transitional cell carcinomas of varying degrees of malignancy (e.g. grade I, II, and III tumours).This is the first instance whereby testing of GAP-107B8 in bladder cancer has been explored. Estimates for 2010 report 77,630 new cases of bladder cancer and 16,530 deaths (U.S. National Cancer Institute and Canadian Cancer Society figures). Current therapeutic options in bladder cancer are limited.
Bladder cancer is an attractive initial cancer target for GAP-107B8 using intravesical route of administration. Intravesical administration represents a non-systemic route of delivery, which permits more direct targeting of bladder cancer tumours within the bladder, compared with systemic delivery which is less well targeted and has higher possibility of unwanted toxicity at the required dose levels. As a result, dosing levels can be better refined in order to mitigate any sensitivity issues.
The initial phase of work at Queens is designed to enable investigators to design and deliver a subsequent in vivo study to determine the Maximum Tolerated Dose (MTD) and efficacy of GAP-107B8 in a murine bladder cancer model using intravesical infusion. Intravesical infusion is a recognized, clinically-acceptable method of drug administration for bladder cancer which entails the direct injection and retention of the drug for a period of time directly in the bladder for uptake by the affected membrane.
Test programs are currently underway at Queen's (bladder cancer), Ottawa Hospital Research Institute ("OHRI") (ovarian cancer), Memorial Sloan-Kettering Cancer Center of New York, NY. (" MSKCC") (melanomas and sarcomas), and internally at PharmaGap in conjunction with a number of external contract research organizations. These programs are designed to provide the Company with the basis for selection of the optimal cancer target and route of administration for human clinical trials. The selection of cancer target is based on numerous factors including efficacy of the drug, identification of the best route of administration to deliver the drug to the target within safe dose limits, final formulation of the drug and any excipients to aid in safe and effective delivery, and current best standard of care in clinical use for the selected cancer target.
All studies are directed by Dr. Ken Sokoll, Vice President Clinical Development and Chief Operating Officer for PharmaGap. Principal Investigators are Drs. Charles Graham and Robert Siemens at Queen's, Dr. Barbara Vanderhyden at OHRI and Dr. Gary Schwartz at MSKCC.
In commenting on the program, Dr. Sokoll observed "We are pleased that Dr. Charles Graham and Dr. Rob Siemens of Queens University will be assisting our efforts to develop GAP-107B8 for the treatment of bladder cancer. We anticipate that positive results from this collaboration will facilitate the selection of the preferred cancer target and route of administration for clinical development of GAP-107B8 and enable discussions directed towards licensing with pharmaceutical companies."