Phase 1 Clinical Trial Results

Phase 2 Clinical Trial Results

We have conducted five Phase 2 clinical trials to evaluate the ability of custirsen sodium (OGX-011), our lead product candidate, to enhance the effects of therapy in prostate, non-small cell lung and breast cancers. Interim data from these Phase 2 studies demonstrates the potential benefit of adding OGX-011, a second generation antisense molecule, to existing cancer therapies. Based on our Phase 2 results in 294 patients, we believe that registration trials for market approval of OGX-011 are warranted in Hormone Refractory Prostate Cancer (HRPC) and Nonsmall Cell Lung Cancer (NSCLC). Our initial registration trials will focus on the HRPC indication.

OGX-011 is designed to block production of clusterin, a cell survival protein that is over-produced in several cancer indications and in response to many cancer treatments, including hormone ablation therapy, chemotherapy and radiation therapy. Increased clusterin production is observed in many human cancers, including prostate, non-small cell lung, breast, ovarian, bladder, renal, pancreatic, anaplastic large cell lymphoma and colon cancers and melanoma. Increased clusterin production is linked to faster rates of cancer progression, treatment resistance and shorter survival duration. Clusterin levels may be further increased in response to standard cancer therapies, including hormone ablation therapy, chemotherapy and radiation therapy. Clusterin expression is linked to disease progression, treatment resistance, poor prognosis and survival in scientific publications. For example, increased expression of clusterin in prostate cancer is closely correlated with increasing Gleason score, which is a strong prognostic factor for poor survival of patients with prostate cancer.

A broad range of preclinical studies show that OGX-011 decreases clusterin levels and sensitizes tumor cells to standard chemotherapeutic drugs, resulting in increased rates of tumor cell death. Preclinical results also show that reducing clusterin production sensitizes prostate tumor cells to hormone ablation therapy and sensitizes prostate and non-small cell tumor cells to radiation therapy. The Clinical program for OGX-011 is summarized below.

Three Phase 1 clinical trials, involving a total of 75 patients, have been completed with OGX-011. In all of these clinical trials, OGX-011 was well tolerated by the patients.

In the first Phase 1 clinical trial, OGX-011 was intravenously administered once per week in combination with hormone ablation therapy to patients with localized prostate cancer in advance of surgery to remove the prostate gland. This clinical trial showed that once weekly administration of OGX-011 reduced clusterin mRNA levels by approximately 92 percent in prostate cancer tissue and approximately 98 percent in lymph node tissue, and more than doubled the rate of prostate tumor cell death compared to hormone ablation therapy alone.

In the second Phase 1 clinical trial, OGX-011 was intravenously administered once per week in combination with docetaxel chemotherapy to patients with solid tumors known to express clusterin. This clinical trial showed that serum clusterin levels dropped in patients while on treatment with 640 mg OGX-011 in combination with docetaxel.

In the third Phase 1 clinical trial, OGX-011 was intravenously administered once per week in combination with two commonly used chemotherapeutic agents to patients with advanced non-small cell lung cancer. The one-year survival rate for patients that received at least one dose of OGX-011 in combination with these chemotherapies was approximately 60 percent. This compares with results from prior published Phase 3 clinical trials which reported one-year survival rates of 33 to 43 percent for patients that received chemotherapy treatment alone.

OGX-011 is currently in five Phase 2 clinical trials investigating the potential to improve treatment outcomes for patients with prostate cancer, non-small cell lung cancer and breast cancer. We are conducting these clinical trials in parallel, rather than sequentially, to accelerate our evaluation of OGX-011 in several cancer indications and in combination with several treatment regimes, which will accelerate our assessment of these indications and combinations for further development.

OGX-011 is being developed to work in combination with therapies that are broadly used by clinicians and considered highly effective in the treatment of each cancer indication that we are targeting with the intent of delaying treatment resistance to those therapies. Since production of clusterin and the resulting treatment resistance occurs in an array of cancer indications and in response to a variety of cancer treatments, we believe that our development options for OGX-011 are numerous.