Results for OncoGenex drug in early prostate cancer trial, Phase II now enrolling in Canada

11 September, 2005 - Clusterin is a protein found in tumor cells. Too much clusterin makes cancer cells lose the ability to do apoptosis (commit "cell suicide"), which damaged cells should do. Tumors overloaded with clusterin resist anticancer therapies.

OGX-011 is a targeted therapeutic designed to re-sensitize resistant tumors to conventional cancer therapeutics such as chemotherapy, hormone ablation therapy and radiation therapy.

Co-developed with Isis Pharmaceuticals, OGX-011 is in clinical trials in Canada and the USA to find out if it can enhance chemotherapy in solid tumours including prostate, non-small cell lung, ovarian, renal and breast malignancies.

A Phase I study found that OGX-011, targeted to clusterin, can be safely given to humans in therapeutic doses that inhibit clusterin expression in cancer tissues, resulting in increased cancer cell death. Primary and secondary objectives were achieved with statistical significance of OGX-011 in prostate cancer.

Targeted therapeutics have had to overcome challenges because early studies were not designed to establish if drugs achieved concentration in target tissue or if the drugs regulated their target. However, OncoGenex believes that this Phase I data proves that systematic administration of OGX-011 is well tolerated, achieves excellent drug concentration in target tissue and inhibits its target in prostate cancer cells and lymph nodes.

OGX-011 has been evaluated in 3 phase I studies involving 72 patients:

• OGX-011 inhibits clusterin in prostate cancer cells by greater than 90%
• OGX-011 inhibits clusterin expression in lymph nodes by greater than 95%
• OGX-011 is well tolerated; no dose limiting toxicity observed
• Safely established in combination with docetaxel, gemcitabine/cisplatin and neoadjuvant hormone therapy

Phase II trials of OGX-011 in prostate, breast and non-small cell lung cancer are ongoing since June 2005 or scheduled to be initiated later this year. These multi-center, open-label Phase 2 studies will enroll up to 70 patients who show evidence of metastatic or locally advanced disease, which is not amenable to treatment with curative intent.

Earlier this year, OncoGenex completed a Phase 1 study that examined the safety and tolerability of escalating doses of OGX-011 in combination with the standard dose of GEM/CIS in Non Small cell lung cancer (NSCLC) patients. This Phase 1 study, the results of which were presented earlier this year at the 11th World Conference on Lung Cancer, established that a 640 mg once-weekly dose of OGX-011 in combination with GEM/CIS was well tolerated by NSCLC patients. Patients in the current study will receive 2-hour intravenous infusions of 640 mg OGX-011 weekly on days 1, 8 and 15 of a 21-day cycle. GEM will be infused intravenously for 30 minutes on days 1 and 8 and CIS will be infused intravenously on day 1 of the 21-day cycle.

"We were initially pleased to have observed such exceptional results from preliminary phase I data presented at ASCO 2004," said Scott Cormack, president and CEO of OncoGenex, "and we are now thrilled to have achieved both primary and secondary endpoints of OGX-011 in the final data set."

"The data presents strong support for moving forward in phase II studies already underway. We are particularly excited to have confirmation from these findings that increasing doses of OGX-011 is associated with a statistically significant increase in cancer cell death."

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