OncoGenex Technologies Inc and Isis Pharmaceuticals Inc have established a drug development collaboration to co-develop and commercialize OGX-011, an anti-cancer antisense drug candidate. OGX-011 combines OncoGenex's proprietary antisense position in inhibitors to the target, clusterin, with Isis' proprietary second-generation antisense chemistry.
OGX-011 is designed to inhibit the secretory protein clusterin, which acts as a cell-survival protein that is over-expressed in response to tumor killing strategies, such as chemotherapy, hormone ablation and radiation therapy. Based on analysis of human tumor tissue, clusterin is over-expressed in several cancers, including prostate, renal, bladder, lung, ovarian and urothelial. Inhibiting clusterin is intended to enhance the effects of drug therapies in the treatment of the disease.
In preclinical animal studies, scientists from both OncoGenex and Isis demonstrated OGX-011 improved the potency of traditional chemotherapies more than 10-fold in prostate cancer without compromising safety. OGX-011 has also been shown to reduce levels of clusterin, as well as significantly delay disease progression in prostate and renal tumor models in animals. These findings support the continued development of OGX-011 in combination with chemotherapeutic and other agents.
"We believe the combined experience of OncoGenex in cancer biology and clinical trials together with Isis' development experience and advances in second-generation antisense chemistry will contribute tremendously to the potential of this promising new cancer compound," said Scott D. Cormack, OncoGenex's President and CEO.
Initially, Isis will conduct preclinical toxicology and pharmacokinetic studies of OGX-011. Isis will also manufacture OGX-011 for preclinical and Phase I/II studies. OncoGenex will perform Phase I/II clinical trials to assess the safety and efficacy of OGX-011 as a single agent and in combination with docetaxel (Taxotere) in men with localized and hormone refractory prostate cancer. As part of its ongoing commitment to elevating the standard of care in prostate cancer, Aventis Pharma Inc. will provide financial support as well as supply the neo-adjuvant hormone therapy for the study protocol. Specific financial terms of the deal between Isis and OncoGenex were not disclosed.
OGX-011 will be the first antisense drug based on Isis' proprietary second-generation chemistry, called 2'-O-methoxyethyl, to enter the clinic for the treatment of cancer. Second-generation antisense drugs offer greater potency, enhanced tolerability via subcutaneous injection, and improved dosing convenience compared to first-generation antisense drugs.
"The agreement will allow Isis to further develop and capitalize on the benefits of our proprietary second-generation chemistry through an established relationship with OncoGenex that builds on previous work, which produced intriguing antisense data on clusterin," said Stanley T. Crooke, Isis' Chairman and Chief Executive Officer. "This strategic partnership is in alignment with our overall business plan to expand the reach and potential of antisense therapeutics, specifically in cancer.
According to the Prostate Cancer Research Institute, 180,000 men are diagnosed with prostate cancer every year in the United States. It is the second leading cause of cancer death in both American and Canadian men. The National Cancer Institute of Canada estimates that 17,800 Canadian men will be diagnosed with prostate cancer in 2001, making prostate cancer the leading cancer diagnosed in Canadian men.