12.11.2006

PharmaGap announces compelling proof of principle data for lead drug compound; expanded market indications

Ottawa, Ontario/December 11, 2006 – PharmaGap Inc. (TSX-V: GAP) (“PharmaGap” or “the Company”) announced today compelling proof of principle results for the Company’s lead cancer drug, PhGalpha1:

• Results demonstrate that intravenous administration of PhGalpha1 into normotensive Sprague-Dawley (“NSD”) rats causes a sustained and dose-dependent decrease in blood pressure, thereby establishing an in vivo mechanism of action for PhGalpha1 as an inhibitor of PKC alpha.
• Results demonstrate that PhGalpha1 is biologically active when administered intravenously, thereby confirming that the drug has the potential for clinical utility in treating cancer using intravenous administration.
• These results also suggest that PhGalpha1 may be a candidate for clinical development as a vasodepressor (blood pressure reducing) agent, which the Company will investigate as a potential expanded market indication for PhGalpha1, in addition to the cancer market for which it is being developed.

These results were produced by testing undertaken by Dr. Michael Adams, Professor of Pharmacology and Toxicology at Queen’s University in Kingston, Ontario. 

Dr. Adams observed that, “The results we have seen with the PKC alpha inhibitor PhGalpha1 are very impressive, and indicate a very marked inhibitory effect of the drug on vasoconstrictor pathways.  Its action as a rapid acting anti-hypertensive  agent may also open up an entirely new market application for the drug should PharmaGap wish to pursue further development in that regard, in addition to its design specifications as an anti-cancer drug. Its action in both single injection and continuous  administration, with a low toxicity profile, provides a compelling case for further development and testing of this drug leading to human clinical use.”                                                                              

Dr. David Barnes, Director of Clinical Development and Regulatory Affairs for PharmaGap, in reviewing these results, observed that “This is possibly the single most significant result for PhGalpha1 to date as an indication of the drug’s ability to proceed into clinical trials. The Company now has a drug that has demonstrated efficacy, exhibited low toxicity, and perhaps most importantly is acting as designed, as an inhibitor of PKC alpha. We are now in a position to accelerate the production of further data required to prepare and file submissions for human clinical trials in late 2007. The development risk associated with getting PhGalpha1 into human clinical trials has, with this result, been reduced significantly”

In these tests, the drug was administered to NSD rats implanted with catheters to allow for sustained drug delivery, and instrumented to record blood pressure and heart rate. PhGalpha1 was administered as both single dose and continuous infusion, using a range of doses for both. PKC alpha is directly implicated in the control of vascular tone and the development and maintenance of hypertension.  Specifically, the test model provided a direct method to assess if PhGalpha1 was acting as an inhibitor of PKC alpha, its design target.

In earlier in vitro (“test tube”) testing of PhGalpha1 carried out by the Company, the drug was shown to be a specific inhibitor of PKC alpha, and was efficacious in slowing the rate of growth of a range of human cancer cell lines, including lung, colon, breast and neuroblastoma. Significantly, PhGalpha1 was associated with reduction in resistance to anti-cancer drugs (multi drug resistance or “MDR”), a major problem in colon cancer, wherein the cancer cells develop the ability to expel chemotherapeutic agents from the targeted cancer cell, requiring ever-larger doses and extreme negative side effects associated with chemotherapy regimes, extending to complete treatment failure in many cases.

In an ongoing series of in vivo (animal) testing carried out at National Research Council of Canada (“NRC”) facilities by Company personnel over the past 12 months, PhGalpha1 has demonstrated efficacy in retarding the establishment and development of human colon cancer tumours grown in mice (“xenografts”), and as well has demonstrated mechanism of action on several critical cancer processes including action as a modulator of MDR in these in vivo tests. Most recently, PhGalpha1 was delivered by injection into the abdominal cavity of mice containing human colon cancer xenografts. The drug was shown to display sufficient stability to reach the tumour site, and to demonstrate a biological effect on the rate of growth of the tumour, with statistically significant results. Post mortem analyses of tumour samples taken from the mice treated with PhGalpha1 were shown to have levels of carcinoembryonic antigen (“CEA”) and vascular epithelial growth factor (“VEGF”) at levels associated with healthy cells compared to tumour samples taken from the untreated group, which displayed higher levels of CEA and VEGF known to be associated with malignant tumours. CEA and VEGF are both markers of malignancy used in the screening of cancer patients.

The test results announced today provides the “proof of principle” that PhGalpha1 is acting as designed when administered via intravenous injection, as an inhibitor of PKC alpha.

“When taken together, PharmaGap’s data make a compelling case for the efficacy and low toxicity profile of PhGalpha1 in the treatment of cancer, as well as potential secondary indications, and fully justify immediate further development efforts”, concluded Dr. Barnes.

Robert McInnis, President and C.E.O., observed that “The Company now intends to apply all of its resources to complete the remaining data production required in order to submit applications for human clinical trials by the fourth quarter of 2007, and to continue to pursue a licensing arrangement for PhGalpha1 for cancer. It is the Company’s intention to out-license PhGalpha1 prior to commencing human clinical trials.”

He went on to say, “In addition, the early indication of PhGalpha1’s effect as a potential anti-hypertensive agent will be further investigated with a view to expanding the market indication for PhGalpha1 and the licensing opportunities associated with that market. It is our intention to expand our use of third party experts under contract in order to maximize our effectiveness in producing the required data and independent validation of our program. In addition to the ongoing in vivo program underway internally, additional studies are in progress by Dr. Adams at Queen’s University in the areas of pharmacodynamics and pharmacokinetics, and PhGalpha1 is currently being tested by Dr. Gary Schwartz, Chief, Melanoma and Sarcoma Division, Memorial Sloan-Kettering Cancer Center in New York City in order to confirm and expand our earlier results. Other independent researchers and development laboratories in Canada and the United States will be used to augment the Company’s existing resources in order to generate the data required for the clinical trial submissions. The proof of principle for PhGalpha1 also provides evidence of the efficacy of our drug technology and the ability to design selective inhibitors of the remaining 11 isoforms of PKC, which form our future drug pipeline targeting the wide range of human diseases that are associated with the PKC family.”

About PharmaGap Inc.
PharmaGap Inc. (TSX-V: GAP), based in Ottawa, ON, is a biotechnology company with a core focus on developing novel therapeutic compounds for the treatment of cancer. PharmaGap's research platform targets cellular signalling pathways controlled by Protein Kinase C (PKC) isoforms. PharmaGap's lead drug compound, PhGalpha1, is in preclinical development and targets PKC alpha. The Company has a pipeline of compounds in the design stage which are selective inhibitors of other isoforms of PKC. The Company's strategy is to out-license drug compounds to larger life sciences companies at the preclinical stage. For more information on PharmaGap please visit the Company's website at www.pharmagap.com.

For information relating to this Release, please contact:
Robert McInnis, President & CEO
(613) 990-9551 bmcinnis@pharmagap.com

Note: The TSX-Venture Exchange does not accept responsibility for the adequacy or accuracy of this release.  No Securities Commission or other regulatory authority having jurisdiction over PharmaGap has approved or disapproved of the information contained herein.  This release contains forward looking statements that may not occur or may change materially.