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Data from Pre-Clinical Studies Presented at the 2011 ASCO Annual Meeting Show Potential Combinability of Custirsen with MDV3100 and Hsp90 Inhibitors to Enhance Anti-Tumor Activity in Prostate Cancer
BOTHELL, WA and VANCOUVER, BC - June 6, 2011 - OncoGenex Pharmaceuticals, Inc. (NASDAQ: OGXI) announced new data showing how the company's lead investigational compound, custirsen (OGX-011/TV-1011), may work with innovative therapies MDV3100 and heat-shock protein 90 (Hsp90) inhibitors to suppress prostate cancer cell survival and improve treatment outcomes. These pre-clinical data were presented at the 47th Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago, June 3-7, 2011.
Cancer cells can develop resistance to treatment over time, leading to treatment failure and disease progression. Custirsen is the only compound in development designed to inhibit the production of the protein clusterin, commonly overproduced in cancer cells and a cause of treatment resistance. In pre-clinical models custirsen has enhanced the activity of hormone ablation therapy, radiation therapy and chemotherapy.
"As new treatments are becoming available for castrate-resistant prostate cancer, these types of data can help clinicians understand when and in what combinations to use them," says Dr. Martin Gleave, Director of The Vancouver Prostate Centre at The University of British Columbia. "It's important to support academic partnerships that will help us understand the best way to optimize treatment and minimize drug resistance in patients with late-stage prostate cancer."
Data evaluating custirsen in combination with second generation anti-androgen therapy MDV3100 in a castrate-resistant prostate cancer model was presented as part of an oral session, "Translational Science Advancing AR Targeting in Prostate Cancer" on Saturday, June 4 [Abstract #4502]. The study found that combining custirsen with MDV3100 more potently suppressed prostate cancer cell growth rates than either drug alone. The combination showed a synergistic effect in combining custirsen and MDV3100, down-regulating androgen receptor (AR) level and activity and suppressing androgen-sensitive prostate cancer cell growth in vitro and in vivo. In castrated male athymic mice, the combination significantly delayed castrate resistant tumor growth progression compared to control (scramble antisense oligonucleotide + MDV3100) at 12 weeks.
In another pre-clinical study presented on June 5 [Abstract #4573], custirsen was shown to work synergistically with Hsp90 inhibitors PF-04928473, 17-AAG, and PF-04929113 to inhibit tumor growth. While several small molecule Hsp90 inhibitors are showing efficacy in CRPC and other cancers, most also trigger the elevation of compensatory survival mechanisms that result in the production of clusterin, leading to cancer cell survival and treatment resistance. In vitro, custirsen enhanced the activity of both PF-04928473 and 17-AAG on cancer cell growth and cell death. In vivo, custirsen combined with both PF-04929113 and 17-AAG significantly inhibited tumor growth by 80% and prolonged survival in a CRPC model compared with each agent alone.
These preclinical data further support the ongoing, Phase 3 custirsen development program in prostate cancer:
- The Prostate Cancer SATURN trial, evaluating a durable pain palliation benefit for custirsen in combination with docetaxel retreatment as second-line chemotherapy in approximately 300 patients with CRPC
- The SYNERGY trial, evaluating a survival benefit for custirsen in combination with first-line docetaxel treatment in approximately 800 patients with CRPC
Custirsen is the only compound currently in development designed to inhibit the production of clusterin, a protein commonly over-produced in cancer cells, and one cause of treatment resistance. In Phase 2 trials of patients with metastatic castrate-resistant prostate cancer (mCRPC), custirsen combined with docetaxel showed a 6.9 month improvement in overall survival over docetaxel alone. Additionally, 50 percent of patients experienced durable pain palliation for a duration of 12 weeks or longer. Unlike opioids or agents that target the androgen receptor, custirsen is mechanistically unique in its ability to impact pain responses via the regulation of NF-kB (nuclear factor kappa-light-chain-enhancer of activated B cells) activity. This is a potential attribute that could contribute to custirsen's clinical benefit in combination with numerous anti-cancer treatments.
Custirsen has received Fast Track designation from the U.S. Food and Drug Administration (FDA).
More information is available at www.OncoGenex.com and www.tevapharm.com/research.
About OncoGenex Pharmaceuticals
OncoGenex is a biopharmaceutical company committed to the development and commercialization of new cancer therapies that address treatment resistance in cancer patients. OncoGenex has a diverse oncology pipeline, with each product candidate having a distinct mechanism of action and representing a unique opportunity for cancer drug development. OncoGenexandTeva Pharmaceutical Industries Ltd. have entered a global collaboration and license agreement to develop and commercialize OncoGenex' lead drug candidate, custirsen. Custirsen is currently in Phase 3 clinical development as a treatment in men with metastatic castrate-resistant prostate cancer. The companies plan to begin Phase 3 development of custirsen in first-line treatment of advanced, unresectable non-small cell lung cancer in 2011. OGX-427 is in Phase 2 clinical development; and CSP-9222 and OGX-225 are currently in pre-clinical development.
OncoGenex' Forward Looking Statements:
This press release contains forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995, including, but not limited to, statements concerning the potential benefits of our product candidates and statements regarding our anticipated product development activities. All statements other than statements of historical fact are statements that could be deemed forward-looking statements. These statements are based on management's current expectations and beliefs and are subject to a number of risks, uncertainties and assumptions that could cause actual results to differ materially from those described in the forward-looking statements. Such forward-looking statements are subject to risks and uncertainties, including, among others, the risk that we are unable to complete our product development activities as planned, if at all, the risk that our product development activities are not successful and that our product candidates do not obtain the requisite regulatory approvals for commercialization, and the risk factors set forth in the Company's filings with the Securities and Exchange Commission, including the Company's Quarterly Report on Form 10-Q for the quarter ended March 31, 2011. The Company undertakes no obligation to update the forward-looking statements contained herein or to reflect events or circumstances occurring after the date hereof, other than as may be required by applicable law.
SOURCE OncoGenex Pharmaceuticals, Inc.