OncoGenex Presents Additional Phase 3 SYNERGY Analyses Showing Custirsen Significantly Reduced Serum Clusterin Levels in Metastatic Prostate Cancer Patients; Low Levels Correlate with Improved Survival in Those at Increased Risk for Poor Outcomes

BOTHELL, Wash. and VANCOUVER, British Columbia, Sept. 28, 2015 -- OncoGenex Pharmaceuticals, Inc. (NASDAQ:OGXI - News) announced today results from additional exploratory analyses of the Phase 3 SYNERGY trial demonstrating that custirsen treatment significantly lowered serum clusterin (sCLU) levels from baseline in men with metastatic castrate-resistant prostate cancer (mCRPC). In addition, these data presented at the 2015 European Cancer Congress (ECC 2015) in Vienna showed that sCLU reductions after custirsen treatment resulted in higher two-year survival rates in patients who were at increased risk for poor outcomes. Of those patients with lower sCLU levels, the data also showed a correlation to an overall survival benefit for custirsen-treated patients who were at increased risk for poor outcomes.

"These data support that custirsen is inhibiting the production of clusterin in men with metastatic CRPC and a correlation between treatment-induced reductions in sCLU and clinical benefit in those patients at risk for poor outcomes," said Scott Cormack, President and CEO of OncoGenex. "We look forward to top line results in metastatic CRPC patients at risk for poor outcomes later this year in our Phase 3 AFFINITY trial."

Production of the protein clusterin is a fundamental cellular repair mechanism that tumor cells exploit to evade destruction by anti-cancer therapies. Overproduction of clusterin, which occurs in response to a variety of cancer treatments, is associated with faster rates of cancer progression and shorter survival. Custirsen is a highly specific clusterin inhibitor designed to improve survival in patients with advanced cancer.

A previous retrospective analysis from the SYNERGY trial showed a benefit with custirsen therapy in men with metastatic CRPC who had at least two of five common risk factors for poor prognosis. For those men, a 27 percent lower risk of death occurred when custirsen was used in combination with first-line docetaxel compared to docetaxel alone. 

About the Study Results
(Abstract: 2560 - Baseline serum clusterin level in patients with poor prognostic features was associated with response to custirsen treatment: Results from the phase 3 SYNERGY trial of docetaxel +/- custirsen, Monday, September 28, 2015, 16:45 - 18:45 CEST, Hall C)

The analysis presented at ECC 2015 further demonstrates the impact of custirsen treatment on mCRPC patients at increased risk for poor outcomes, including a reduced risk of death among poor prognostic patients who achieved lower sCLU levels (Day 140 Area Under Curve (AUC)) during treatment. Patients in the poor prognostic subgroup who were treated with custirsen and had reduced Day 140 AUC sCLU levels showed a trend for higher two-year survival status. A landmark analysis also showed that overall survival benefit for the custirsen arm appeared greater in the poor prognostic patients who achieved lower Day 140 AUC sCLU levels.

In patients with lower sCLU at baseline, a trend for greater effect of custirsen treatment on survival was also observed, especially in patients at increased risk for poor outcomes. Patients at risk for poor outcomes with low baseline sCLU treated with custirsen (n=176) experienced a median survival of 18.4 months, compared to 14.4 months for patients on the control arm (n=170) [HR=0.689 (95% CI: 0.483-0.983); the median baseline sCLU was 55.30 ug/mL for patients at risk for poor outcomes. In the subpopulation of patients with a good prognosis, patients with low baseline sCLU treated with custirsen (n=171) experienced a median survival of 31.2 months in comparison to 27.2 months for patients on the control arm (n=186) [HR = 0.823 (95% CI: 0.505-1.34); the median baseline sCLU was 53.2 ug/mL for patients with a good prognosis.

Apatorsen Update
(Abstract: 2637 - Baseline circulating tumor cells (CTC) and serum heat shock protein 27 (Hsp27) levels are increased in advanced bladder cancer (BC) patients with poor prognostic factors: Results from the randomized phase 2 Borealis-1^TM trial of first-line gemcitabine/cisplatin plus apatorsen or placebo, Monday, September 28, 2015, 16:45 - 18:45 CEST, Hall C)

Results from the company's other lead product candidate, apatorsen, presented at ECC 2015 confirmed that patients with advanced bladder cancer at increased risk for poor outcomes had increased baseline levels of circulating tumor cells (CTC) and of serum heat shock protein 27 (Hsp27). The study showed that baseline Hsp27 and CTC  levels were independent risk factors for survival outcomes.

"Apatorsen is designed to inhibit the production of Hsp27 and thereby to disable cancer cells' defenses and overcome treatment resistance that is common in this disease," said Cindy Jacobs, PhD, MD, Chief Medical Officer and Executive Vice President of OncoGenex. "Patients in the Borealis-1^TM trial with advanced disease who had specific poor prognostic risk factors experienced a clinical benefit with apatorsen. We are continuing to work closely with investigators and regulatory agencies to determine next steps as we collect more evidence regarding apatorsen's activity in this disease." 

Data from the Borealis-1 trial previously reported at the American Society of Clinical Oncology Annual Meeting earlier this year showed that metastatic bladder cancer patients with poor prognostic features (low performance status, liver involvement, low hemoglobin and high alkaline phosphatase) showed a potential survival benefit with apatorsen 600mg added to first-line chemotherapy (HR = 0.72) compared to chemotherapy alone. Patients in the trial with a Karnofsky Performance Status of 80 percent or less, a common indicator of poor prognosis, experienced a 50 percent reduction in risk of death with the addition of apatorsen therapy (HR = 0.50).

Completion of enrollment in the Phase 2 Borealis-2™ bladder cancer trial is expected to occur by the end of 2015 and will evaluate apatorsen in combination with docetaxel in patients with advanced or metastatic bladder cancer who have disease progression following first-line platinum-based chemotherapy.

About Clusterin

A major barrier to extending survival in patients with advanced cancer is treatment failure due to the ability of tumor cells to exploit fundamental cellular mechanisms that allow them to evade destruction by anti-cancer therapies. The production of the protein clusterin is a fundamental cellular repair mechanism that tumor cells exploit to evade destruction by anti-cancer therapies. Increased clusterin production has been linked to faster rates of cancer progression, treatment resistance and shorter survival duration in patients.

About Custirsen

Custirsen is a highly specific clusterin inhibitor designed to improve survival in patients with advanced cancer by disabling a fundamental cellular repair mechanism used by tumor cells. Custirsen binds to clusterin mRNA to block the production of clusterin protein and has enhanced the tumor cell destructive effects of multiple anti-cancer therapies across a variety of tumor models. By inhibiting clusterin, custirsen is designed to alter tumor dynamics by slowing tumor growth and inhibiting tumor resistance to partner treatments, so that the benefits of therapy, including survival, may be extended.

Custirsen has Fast Track designation by the U.S. Food and Drug Administration for metastatic CRPC and non-small cell lung cancer.

About Apatorsen and ORCA™
Apatorsen (OGX-427) is designed to inhibit production of heat shock protein 27 (Hsp27), disable cancer cells' defenses and overcome treatment resistance. Hsp27 is an intracellular protein that protects cancer cells by helping them survive, leading to resistance and more aggressive cancer phenotypes. Both the potential single-agent activity and synergistic activity of apatorsen with cancer treatments may increase the overall benefit of existing therapies and augment the durability of treatment outcomes, which could lead to increased patient survival.

The ORCA (Ongoing Studies Evaluating Treatment Resistance in CAncer) program encompasses clinical trials of apatorsen. Phase 2 clinical trials are underway in bladder, lung, pancreatic and prostate cancers. For more information on apatorsen and ORCA, please visit www.OncoGenex.com or www.orcatrials.com.

About OncoGenex
OncoGenex is a biopharmaceutical company committed to the development and commercialization of new 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. Custirsen is currently in Phase 3 clinical development as a treatment in men with metastatic castrate-resistant prostate cancer and in patients with advanced, unresectable non-small cell lung cancer. Apatorsen is in Phase 2 clinical development and OGX-225 is currently in pre-clinical development. More information is available at www.OncoGenex.com and at the company's Twitter account:  https://twitter.com/OncoGenex_IR.

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 regarding the potential benefits and potential development of our product candidates. 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, including, among others, the risk that our product candidates do not demonstrate the hypothesized or expected benefits, the risk of delays in our expected clinical trials, the risk that new developments in the rapidly evolving cancer therapy landscape require changes in our clinical trial plans or limit the potential benefits of our product and the other factors described in our risk factors set forth in our filings with the Securities and Exchange Commission from time to time, including the Company's Annual Report on Form 10-K and Quarterly Reports on Form 10-Q. 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.

Borealis-1™, Borealis-2™ and ORCA™ are registered trademarks of OncoGenex Pharmaceuticals, Inc.

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SOURCE OncoGenex Pharmaceuticals, Inc.