With the second phase III failure of antisense oligonucleotide custirsen in castrate-resistant prostate cancer (CRPC), Oncogenex Pharmaceuticals Inc. investors have turned their eyes to non-small-cell lung cancer (NSCLC), where the clusterin inhibitor is undergoing late-stage tests in combination with docetaxel.

CEO Scott Cormack acknowledged the NSCLC field is crowded, but pointed out during a brief conference call on the latest data – a call that fielded just one question – that "unfortunately those therapies don't provide cures. We see that the landscape certainly can have room for something like this."

Shares of Oncogenex (NASDAQ:OGXI) closed Tuesday at 53 cents, down 36 cents, or 40 percent, not far from its 52-week low of 45 cents. The company, which last month reported $39.7 million in cash and equivalents – enough to last until the third quarter of 2017 – said it has engaged MTS Health Partners LP as its advisor to help explore strategic alternatives.

In the most recent setback, the firm's AFFINITY phase III trial, testing custirsen in metastatic CRPC patients whose disease has progressed after treatment with docetaxel, missed the primary endpoint of statistically significant improvement in overall survival. Patients treated with custirsen in combination with cabazitaxel, a form of chemotherapy, plus the steroid prednisone, were compared to those given cabazitaxel/prednisone alone.

The AFFINITY news follows the late-stage blowup in newly diagnosed CRPC called SYNERGY. Data were disclosed in April 2014, which is about when Oncogenex's stock began to slide seriously. Yet to report outcomes is the NSCLC phase III trial known ENSPIRIT with custirsen, a compound once partnered with Petah Tikva, Israel-based Teva Pharmaceutical Industries Ltd., in a deal that ended in April 2015. After losing Teva, Oncogenex revised (with the FDA's blessing) AFFINITY's protocol, inspiring hope in some company watchers. (See BioWorld Today, April 29, 2014.)

The ongoing ENSPIRIT trial is testing custirsen with second-line docetaxel.

"Obviously the plan that we have is to advance to an early analysis of ENSPIRIT," CEO Cormack said during the conference call. "Since the trial has fast track designation, our hope is that a meeting will occur in a timely manner in order to obtain the FDA's feedback" and, "depending on the outcome of our discussions with the agency, we expect that final survival results could be available early in the fourth quarter of this year."

"While we are [blinded] to the ENSPIRIT results, we remain encouraged by the two rigorous futility analyses that have already been performed in which the futility boundaries were not crossed," Cormack said. "We believe our proposed plan for an expedited analysis of the ENSPIRIT data will conserve capital that otherwise would be required to continue this phase III trial to completion and will extend our cash runway. Our plan to accelerate the timeline will also allow us to gain a better understanding of custirsen's value in NSCLC and act on this knowledge faster."

hsp27 candidate still kicking

Meanwhile, Oncogenex settled this month the lawsuit filed by Ionis Pharmaceuticals Inc., of Carlsbad, Calif. In the action filed in January of this year, Ionis claimed that Oncogenex was in breach of an amended and restated license agreement between the pair that dated back to 2008. The deal granted Ionis a share of certain forms of non-royalty revenue received by Oncogenex, but no share of revenue collected for R&D reimbursement. Ionis wanted 30 percent of the $23.2 million breakup fee Oncogenex gained from Teva, money that was described as an advance reimbursement for continuing R&D related to custirsen and other antisense clusterin inhibitors. Oncogenex filed a motion to dismiss the lawsuit in March. The settlement puts Ionis in line for a $1.4 million payment followed by more if custirsen meets with success.

Also ahead, probably in the fourth quarter of this year, are data from phase II BOREALIS-2, which is testing Oncogenex's apatorsen in combo with docetaxel in bladder cancer. RBC Capital Markets analyst Douglas Miehm noted in a research report that the company has met with the FDA to discuss an IND submission for a phase I/II study evaluating apatorsen for intravesical administration in combination with the current standard of care, Bacillus Calmette-Guerin, in non-muscle invasive bladder cancer. "Management anticipates that it will complete an IND," he wrote, "but gave no timeline on when it intends to submit this IND to the FDA."

Designed to inhibit heat-shock protein 27, which is linked to treatment resistance and more aggressive cancer phenotypes, apatorsen (formerly OGX-427) has been the subject of multiple trials. It chalked up a phase II failure in pancreatic cancer in the effort called RANIER last year. In January, Oncogenex said the phase II SPRUCE trial testing apatorsen as a combo therapy in NSCLC fell short of statistically significant improvement in progression-free survival. (See BioWorld Today, Sept. 24, 2015, and BioWorld Insight, Jan. 26, 2016.)

Also underway is the phase II PACIFIC experiment, an investigator-sponsored, randomized study evaluating apatorsen in metastatic CRPC who are experiencing rising prostate-specific antigen levels while on Zytiga (abiraterone acetate, Janssen Biotech Inc.). PACIFIC aims to discover the potential benefit of adding apatorsen to Zytiga plus prednisone for patients with metastatic CRPC by measuring the treatments' ability to extend time without disease progression. The trial is backed by the Hoosier Cancer Research Network in Indianapolis.

But the attention Tuesday landed on custirsen, and interest still percolates around clusterin (the protein is also known as alipoprotein J), which is implicated not only in cancer but in Alzheimer's disease and infectious diseases such as hepatitis C. A study in the current issue of Allergy and Asthma Proceedings suggests that serum levels of clusterin may turn out to be a biomarker for children atopic dermatitis, too.