PharmaGap Inc. has announced that it has successfully completed the design, development, manufacture and testing of a liposome formulation of both basic and enhanced versions of its lead cancer drug GAP-107B8, and will proceed to in vivo testing of both formulations in bladder and ovarian cancer models in order to select one formulation and cancer target for first human clinical trials.
This in vivo testing will be undertaken between now and the end of 2011, with a final selection based on the results seen in these tests.
This development program has involved the production of a number of prototype designs, each at a range of drug concentrations within the liposome carrier.
These prototypes were tested for potency across a 3 human bladder cancer and 3 human ovarian cancer cell lines, and compared head to head with the GAP-107B8 peptides alone (basic and enhanced versions), and with the empty liposome carriers.
This testing was carried out at PharmaGap labs over the past 6 months. The liposome formulations and the enhanced version of GAP-107B8 represent novel and material new intellectual property for PharmaGap, and is the subject of a patent filing for the Company.
Dr. Ken Sokoll, Vice President of Clinical Development and Chief Operating Office for PharmaGap, stated "I am very pleased that we have achieved our objective of successfully identifying a liposomal formulation of both versions of our lead cancer drug, in the time frame established when we embarked on this program in the first quarter of the year. We now are presented with the prospect of a widened therapeutic window, and are seeing in vitro effectiveness at dose ranges suitable to proceed to human clinical trials. This has been a very labour intensive effort both internally by our staff as well as at our contractor sites, and I want to thank each of them for a high degree of effort and diligence in arriving at this key point in our program."
The successful development of the liposomal formulations of basic and enhanced GAP-107B8 has significantly widened the GAP-107B8 Therapeutic Window (the range of doses between the lowest effective dose and the highest dose where unacceptable toxicity become evident), which is a key consideration for effective clinical trial design and ultimate success of the drug in the marketplace.
Liposomal delivery systems are an accepted, proven, and commercially viable strategy for the formulation of pharmaceuticals for clinical use. These delivery systems are employed to improve tumour targeting, modulate the pharmacokinetics of the active agent and enhance its stability following administration.
Therapeutic activity may be improved by modulating drug exposure and accumulation (controlled release) in the region where the target cells are located.
The two formulated GAP-107B8 compounds will now both proceed through in vivo pharmacokinetic and pharmacodynamic testing (to assess physical characteristic of the drug in a live system), as well as the determination of Maximum Tolerated Dose, in order to determine the optimum dose ranges for use in the in vivo efficacy testing of both formulations in bladder cancer (using intravesical administration) and ovarian cancer (using intraperitoneal administration) in the 4th quarter of this year.