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Oncothyreon Announces Presentation of PX-866 Clinical Data at American Association of Clinical Oncology Annual Meeting

Oncothyreon (NASDAQ: ONTY) announced Saturday that data from two clinical trials of PX-866, a pan-isoform phosphatidylinositol-3-kinase inhibitor, were presented today at the American Society of Clinical Oncology meeting in Chicago. Oncothyreon also provided an update on the status of its ongoing Phase 2 development program for PX-866.

Phase 1 Trial of PX-866 in Combination with Docetaxel
Data from the Phase 1 portion of the ongoing Phase 1/2 of PX-866 in combination with the chemotherapeutic agent docetaxel (Taxotere®) were presented by Antonio Jimeno, M.D., Ph.D., of the University of Colorado Cancer Center, Aurora, Colorado. The trial enrolled 43 patients with advanced cancer for whom docetaxel was considered standard of care. Patients were treated at three different dose levels of PX-866 administered daily in combination with the standard dose of docetaxel (75 mg/m2) administered once every three weeks. No dose-limiting toxicities were identified, and the recommended Phase 2 daily dose of PX-866 to be given in combination with docetaxel was determined to be the same as the single agent daily maximum tolerated dose of 8 mg.

The combination of PX-866 and docetaxel was generally well-tolerated, with most adverse events being mild to moderate in severity. The safety profile for combination treatment was consistent with that for either drug administered alone. Combination treatment had no impact on the pharmacokinetic profile of either drug.

Thirty-three patients were evaluable for response, defined as having undergone at least two cycles of therapy and a follow-up tumor assessment. In these patients, the disease control rate (partial response or stable disease) was 85 percent (28/33) after two cycles of therapy and 58 percent (19/33) after four cycles. Ten patients were on study for more than 200 days, five of whom remained on therapy at the time of the report. Nine patients with stable disease or better discontinued docetaxel after four or more cycles and continued on single agent PX-866, including all five remaining on therapy. No statistically significant differences in progression-free survival were identified for patients with PIK3CA mutations or PTEN deficiency.

Phase 2 Trial of PX-866 in Patients with Glioblastoma Multiforme
Interim data from an open-label single-arm Phase 2 trial of PX-866 in patients with glioblastoma multiforme, a type of brain cancer, were presented by Marshall W. Pitz, M.D., of CancerCare Manitoba, University of Manitoba, Winnipeg, Manitoba. The Phase 2 trial is being conducted at 7 Canadian centers by the NCIC Clinical Trials Group, Queen's University in Kingston, Canada, in patients whose brain tumor is in first relapse during or following primary therapy. The trial has a two-stage design, with progression to the second stage dependent upon achieving a pre-specified endpoint of response or lack of early progression.

Seventeen patients were enrolled in the first stage of the trial and were included in this presentation. PX-866 was well-tolerated in the study, with the most common adverse events being diarrhea and reversible liver enzyme elevation. All patients were evaluable for response, with one patient having a partial response and six patients with stable disease, three of whom remained on therapy at the time of the report. These efficacy data met the pre-specified endpoint, and the trial is currently enrolling a planned additional 15 patients in the second stage.

PX-866 Phase 2 Program Update
In addition to the above mentioned trial in patients with GBM, the NCIC CTG is also conducting a Phase 2 trial in up to 40 patients with metastatic or recurrent castration resistant prostate cancer who have not received prior chemotherapy. The primary endpoint of this single-arm screening trial is the proportion of patients with lack of disease progression at 12 weeks from the initiation of therapy with PX-866. The trial has a two-stage design, with progression to the second stage dependent upon achieving a pre-specified endpoint of lack of early progression. The trial has completed enrollment in the first stage of the study and the interim analysis is currently pending.

The Phase 1/2 trial of PX-866 in combination with docetaxel mentioned above has advanced to the Phase 2 portion, which is an open-label, randomized evaluation of the antitumor activity and safety of PX-866 administered at the recommended daily dose in combination with docetaxel, versus docetaxel alone, in two groups of patients. Group 1 is enrolling patients with non-small cell lung cancer receiving second or third line treatment. Group 2 is enrolling patients with locally advanced, recurrent or metastatic squamous cell carcinoma of the head and neck after failure of prior therapy. The two groups will be randomized and evaluated independently. Enrollment of a planned 88 patients in the NSCLC group is currently expected to be completed this month. Additional centers are being added to the SCCHN arm of the trial, with a goal to complete enrollment of 82 patients in the first half of 2013.

Oncothyreon has also advanced to the Phase 2 portion of a Phase 1/2 trial of PX-866 in combination with the chimeric monoclonal antibody cetuximab (Erbitux®), which is an open-label, randomized evaluation of the antitumor activity and safety of PX-866 administered at the recommended daily dose in combination with cetuximab, versus cetuximab alone, in two groups of patients. Group 1 is enrolling patients with metastatic colorectal cancer who have a history of progression or recurrence following prior treatment with irinotecan and oxaliplatin containing regimens or who are intolerant of irinotecan. Over 50 of a planned 80 patients are currently enrolled in this arm of the trial, with enrollment currently expected to be completed in the fourth quarter of 2012. Group 2 is currently enrolling patients with incurable progressive, recurrent or metastatic SCCHN. The two groups will be randomized and evaluated independently.

Oncothyreon also recently announced the initiation of a Phase 1/2 trial of PX-866 in combination with vemurafenib (Zelboraf®). The Phase 1 portion of this trial will evaluate the safety and tolerability of PX-866 in combination with twice daily oral administration of vemurafenib in up to 36 patients with any BRAF-mutant cancer. The Phase 2 portion of the trial will compare the anti-tumor activity and safety of PX-866 and vemurafenib at the doses recommended from Phase 1 with vemurafenib alone administered at the approved dose. This randomized Phase 2 trial is expected to enroll 110 patients with advanced BRAF-mutant melanoma and has a primary endpoint of progression-free survival. This Phase 1/2 trial is being conducted in collaboration with the Melanoma Research Foundation Breakthrough Consortium.

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