Cancer

We are discovering and developing antisense drugs, both internally and through our partners, to treat cancers. Cancer is an area of significant unmet medical need and an area in which our antisense technology provides us with unique advantages in discovering new drugs. Cancer is an extremely complex disease that involves a large number of targets. With our technology we can evaluate a very broad and diverse range of targets and identify their involvement in different types of cancers. Using the information we gain early in research on each of these targets, we can quickly identify the most promising targets for an anti-cancer drug. We select anti-cancer targets that provide a multi-faceted approach to treating cancer. We develop drugs to targets that are directly involved in cancer growth, migration or survival, such as our STAT3 drug.

Our cancer pipeline consists of anti-cancer antisense drugs that act upon biological targets associated with cancer progression and/or treatment resistance. Over the past couple of years, our partners presented encouraging clinical data on a number of our antisense drugs, including positive Phase 2 overall median survival data for OGX-011 in prostate cancer and positive clinical data on OGX-427 in both prostate and bladder cancers. We co-discovered these antisense drugs and licensed them to OncoGenex to treat multiple types of cancer.

We believe the favorable tolerability and early evidence of clinical benefit of the anti-cancer drugs in our pipeline demonstrate how uniquely suited our technology is to create novel cancer therapeutics. Because of the early evidence of clinical benefit, cancer is one of our core therapeutic areas and an area in which we are expanding our efforts to include new targets and new treatments.

• OGX-011 (Prostate and Lung Cancer)
• ISIS-EIF4E_Rx (Cancer)
• OGX-427 (Cancer)
• ISIS-STAT3_Rx (Cancer)

OGX-011 (Custirsen)

OGX-011, now under license to Teva Pharmaceutical Industries Ltd., or Teva, is a second-generation antisense drug that targets clusterin, a secreted protein that acts as a cell-survival protein and is over-expressed in response to anti-cancer agents. We and OncoGenex jointly discovered and conducted the initial development of OGX-011. In December 2009, OncoGenex licensed OGX-011 to Teva as part of a global license and collaboration agreement to develop and commercialize OGX-011. Teva is studying OGX-011 for use as an adjunct therapy to enhance the effectiveness of chemotherapy. OGX-011 has shown promising results in combination with currently available chemotherapies in several tumor types. The FDA granted OGX-011 two Fast Track Designations as a treatment in combination with first-line and second-line docetaxel for progressive metastatic prostate cancer.

OncoGenex evaluated OGX-011 in five Phase 2 studies in combination with various cancer therapies for prostate cancer, non-small cell lung cancer, or NSCLC, and breast cancer. OncoGenex reported results from a randomized Phase 2 study of OGX-011 in patients with advanced metastatic castrate resistant prostate cancer, or CRPC. In this study, OncoGenex reported a median overall survival of 23.8 months in patients treated with OGX-011 plus docetaxel compared to 16.9 months for patients treated with docetaxel alone. In addition, OncoGenex reported that the unadjusted hazard ratio, a measure used to determine the difference in survival between treatment groups, was 0.61, representing a 39 percent reduction in the rate of death for patients treated with OGX-011. OncoGenex also reported that patients treated with OGX-011 in combination with docetaxel tolerated OGX-011 well.

OncoGenex has also evaluated OGX-011 in a Phase 1/2 combination study in patients with NSCLC. In January 2012, OncoGenex reported that one- and two-year survival rates were 54 percent and 30 percent, respectively, and 12 percent of patients were still alive at a median follow-up of 41 months. The median overall survival was 14.1 months and progression-free survival was 4.3 months.

Teva and OncoGenex are collaborating on a global Phase 3 clinical program in patients with advanced prostate cancer and advanced NSCLC. OncoGenex and Teva are evaluating OGX-011 in a Phase 3 clinical study for first-line chemotherapy in patients with metastatic CRPC. OncoGenex and Teva announced that they intend to start a second Phase 3 study for OGX-011 in 2012 for second-line chemotherapy in patients with prostate cancer. OncoGenex also announced that, together with Teva, it intends to initiate an additional Phase 3 study of OGX-011 as first-line treatment in patients with advanced, inoperable NSCLC.

ISIS-EIF4E_Rx

ISIS-EIF4E_Rx targets the gene that is responsible for producing the protein eukaryotic initiation factor-4e, or eIF-4E, which cells over-express in a variety of cancers, including prostate, lung, ovarian, liver, breast, head and neck, bladder, colon, thyroid and lymphoma. eIF-4E facilitates the synthesis of factors in the body that support the development, growth, progression and survival of cancer. In preclinical studies, we and collaborators demonstrated marked anti-cancer activity in a broad range of animal models of cancer and provided the first in vivo evidence that tumor growth may be more susceptible to eIF-4E inhibition than growth of normal tissue. Targeting eIF-4E has been of great interest to the pharmaceutical industry and the oncology community. However the pharmaceutical industry considers eIF-4E a difficult protein to target with traditional pharmaceutical approaches.

Eli Lilly and Company completed a Phase 1 study of ISIS-EIF4E_Rx in patients with cancer that showed that the subjects tolerated the drug well at doses up to 1,200 mg per week. Eli Lilly and Company has rights to license ISIS-EIF4E_Rx from us on predefined terms.

In 2010, we initiated a Phase 2 program of ISIS-EIF4E_Rx in patients with NSCLC and prostate cancer. The endpoints for both studies include progression-free survival, overall survival, response rates, time to progression and the reduction of a variety of biomarkers. We plan to expand our Phase 2 program over time to evaluate ISIS-EIF4E_Rx in other cancers that over-express eIF-4E.

OGX-427

OGX-427 is a second-generation antisense drug targeting heat shock protein 27, or Hsp27, which is a cell survival protein that cells over produce in response to many cancer treatments, including hormone ablation therapy, chemotherapy and radiation therapy. Studies have shown that increased Hsp27 production is prevalent in many human cancers, including prostate, NSCLC, breast, ovarian, bladder, renal, pancreatic, multiple myeloma and liver cancers. Studies have also linked increased Hsp27 production to faster rates of cancer progression, treatment resistance and shorter survival duration.

OncoGenex is evaluating OGX-427 in patients with cancer. In June 2010, OncoGenex reported results from a Phase 1 study of OGX-427 in patients with a variety of cancers. In this study, patients treated with OGX-427 as a monotherapy and in combination with docetaxel tolerated the drug well. In addition, OGX-427, when used as a single agent, demonstrated declines in circulating tumor cells at all doses and in all types of cancer OncoGenex evaluated. OGX-427 also demonstrated evidence of reduction in tumor markers defined as declines of prostate-specific antigen, or PSA, levels in prostate cancer and cancer-antigen-125 levels in ovarian cancer.

In February 2012, OncoGenex reported preliminary results from a Phase 1 study in patients with superficial bladder cancer. In this study, OncoGenex reported that treatment with OGX-427 resulted in a trend towards decreased levels of Hsp27 and increased tumor cell death rates.

OncoGenex is also evaluating OGX-427 in two Phase 2 studies, one in men with metastatic CRPC and one as a first-line treatment for metastatic bladder cancer. In February 2012, OncoGenex reported preliminary results from a Phase 2 study in patients with CRPC. In this study, OncoGenex reported that treatment with OGX-427 in combination with prednisone resulted in a higher number of patients without disease progression at 12 weeks and greater declines in prostate-specific antigen, or PSA, and circulating tumor cells compared to patients treated with prednisone alone.

OncoGenex plans to initiate a Phase 2 study of OGX-427 in combination with abiraterone in men with CRPC.

ISIS-STAT3_Rx

ISIS-STAT3_Rx is designed to treat cancer by inhibiting the production of a gene critical for tumor cell growth and survival. Signal transducer and activator of transcription 3, or STAT3, is over-active in a variety of cancers, including brain, lung, breast, bone, liver and multiple myeloma and promotes tumor cell growth and prevents cell death.

In preclinical studies, ISIS-STAT3_Rx demonstrated antitumor activity in animal models of human cancer with an attractive safety profile. We plan to evaluate ISIS-STAT3_Rx in a variety of cancers in which scientists believe STAT3 plays a key role, such as liver cancers and multiple myeloma. We are currently evaluating ISIS-STAT3_Rx in a phase 1 study in patients with cancer.