Cancer

We are pursuing the discovery and development of antisense drugs to treat cancers internally and through our partnerships with OncoGenex and Eli Lilly and Company. Cancer is one of our core therapeutic areas and an area where we are expanding our internal development activities. During 2009, our partners presented encouraging clinical data on a number of antisense drugs, including positive Phase 2 overall median survival data for OGX-011. We discovered or co-discovered these antisense drugs and licensed them to our partners to treat multiple types of cancer. We believe the favorable tolerability and early evidence of clinical benefit of these partnered drugs demonstrate how uniquely suited our technology is to create novel cancer therapeutics. Because of these observations, we have begun to build our internal cancer program, and, as a first step, we reacquired the rights to ISIS-EIF4E_Rx, an antisense drug we discovered and previously licensed to Eli Lilly and Company for the treatment of cancer. By reacquiring this important cancer program we can rapidly advance the program to Phase 2 studies in patients with multiple types of cancer. In addition to ISIS-EIF4E_Rx, our current portfolio consists of three antisense drugs that act upon biological targets associated with cancer progression and/or treatment resistance. We believe that our antisense drugs have pharmaceutical properties that make them attractive therapeutics for cancer, and we continue to expand our efforts in cancer to include new targets and new treatments.

• OGX-011 (Prostate, Lung, and Breast Cancer)
• LY2181308 (Prostate Cancer)
• ISIS-EIF4E_Rx (Cancer)
• OGX-427 (Cancer)

OGX-011

OGX-011, now under license to Teva Pharmaceutical Industries Ltd., 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. OGX-011 is designed to be used as an adjunct therapy to enhance the effectiveness of chemotherapy and has shown promising results when added to currently available chemotherapies in several tumor types. The FDA has granted OGX-011 two Fast Track Designations as a treatment in combination with first-line and second-line docetaxel for progressive metastatic prostate cancer. In December 2009, OncoGenex licensed OGX-011 to Teva as part of a global license and collaboration agreement to develop and commercialize OGX-011.

In May 2009, OncoGenex reported results of a randomized Phase 2 trial of OGX-011 in patients with advanced metastatic castrate resistant prostate cancer, or CRPC, at the American Society of Clinical Oncology. 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 OGX-011 continued to be well tolerated in combination with docetaxel.

OncoGenex has also evaluated OGX-011 in a Phase 1/2 combination study in patients with non-small cell lung cancer, or NSCLC. In February 2009, OncoGenex reported data showing that after two years, 30 percent of patients who had received OGX-011 with first-line chemotherapy were still alive. Previously, OncoGenex reported a mature median survival of 14.1 months and a one-year survival rate of 54 percent.

Teva and OncoGenex will collaborate on a global Phase 3 clinical program in patients with advanced prostate cancer and advanced NSCLC.

LY2181308

LY2181308 is an antisense drug that targets survivin, which plays a role in cancer cell death and is one of the most commonly over expressed proteins in cancers. We licensed our anti-cancer drug, LY2181308, to Eli Lilly and Company as part of the companies’ antisense drug discovery research collaboration in cancer. The researchers involved in this collaboration have shown that inhibiting the expression of survivin by LY2181308 inhibits the growth of cancer cells. Since normal cells in the body do not express survivin, we expect that this drug will have fewer side effects than traditional chemotherapy. Eli Lilly and Company completed its Phase 1 study of LY2181308 and presented first-in-human data from this study confirming that LY2181308 penetrates tumor tissue and reduces survivin messenger RNA, or mRNA, and protein levels in tumor cells.

Eli Lilly and Company is evaluating LY2181308 in two separate Phase 2 studies in patients with relapsed or refractory acute myeloid leukemia and as a combination therapy in patients with hormone refractory prostate cancer.

ISIS-EIF4E_Rx

ISIS-EIF4E_Rx is an antisense drug that targets eukaryotic initiation factor-4E, or eIF-4E, a protein involved in the translation of key growth and survival factors that contribute to tumor progression and the spread of cancer. eIF-4E is upregulated or overexpressed in a variety of cancers, including breast, head and neck, prostate, lung, bladder, colon, thyroid and non-Hodgkin’s lymphomas and is involved in the translation of key growth and survival factors that contribute to tumor progression and the spread of cancer. 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. In conjunction with scientists from Eli Lilly and Company and the Wood Hudson Cancer Research Laboratory, we published experimental data in The Journal of Clinical Investigation that suggests eIF-4E may act as a critical “switch” in cancer progression.

ISIS-EIF4E_Rx, formerly known as LY2275796, was discovered by us and licensed to Eli Lilly and Company for the treatment of cancer. In December 2009, we reacquired ISIS-EIF4E_Rx from Eli Lilly and Company. With the reacquisition of this asset, we will independently develop ISIS-EIF4E_Rx through Phase 2 proof-of-concept for the treatment of multiple types of cancer, potentially including, breast, lung, prostate, bladder and colon cancers. Eli Lilly and Company has the right to reacquire ISIS-EIF4E_Rx on predefined terms prior to the initiation of Phase 3 development.

Eli Lilly and Company completed a Phase 1 study of ISIS-EIF4E_Rx in patients with cancer that showed that the drug was well tolerated at doses up to 1200 mg per week.

OGX-427

OGX-427 is a second-generation antisense drug targeting heat shock protein 27, or Hsp27, which is a cell survival protein that is over-produced 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 May 2009, OncoGenex reported preliminary results from a Phase 1 study of OGX-427 in patients with a variety of cancers. In this study, treatment with OGX-427 was well tolerated as a monotherapy and demonstrated declines in circulating tumor cells at all doses evaluated as well as 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 August 2009, OncoGenex announced the initiation of another Phase 1 study of OGX-427 in patients with bladder cancer.

In early 2010, OncoGenex announced that a randomized, controlled Phase 2 clinical study evaluating OGX-427 as a monotherapy in patients with CRPC has received grant funding.