Oncothyreon Inc., a biotechnology company and Array BioPharma Inc. will be collaborating to develop and commercialise ARRY-380, an orally active, reversible and selective small-molecule HER2 inhibitor. HER2, also known as ErbB2, is a receptor tyrosine kinase that is over-expressed in breast cancer and other cancers such as gastric and ovarian cancer.

Array previously completed a phase I clinical trial of ARRY-380 in patients with heavily pre-treated metastatic breast cancer which demonstrated that the compound was well tolerated and had anti-tumour activity.

Oncothyreon has agreed to pay Array an upfront fee of $10 million upon initiation of the collaboration. Under the agreement, Oncothyreon will fund and conduct the clinical development of ARRY-380 through a defined set of combination proof-of-concept trials in patients with metastatic breast cancer, including patients with brain metastases. ARRY-380 has demonstrated superior activity, based on overall survival, compared to Tykerb (lapatinib) and to the investigational drug, neratinib, in an intracranial HER2+ breast cancer xenograft model. This provides a strong rationale to explore whether ARRY-380 can provide benefit to patients with brain metastases, which occur in approximately one-third of women with metastatic HER2+ breast cancer.

Oncothyreon and Array intend to jointly conduct phase III development supported by the proof-of-concept studies, with each party retaining the right to opt out of further development and commercialisation in exchange for a significant royalty. Array is responsible for worldwide commercialisation of the product. Oncothyreon has a co-promotion right in the US, and the two companies will share the cost of US commercialisation, including any profit, equally. Outside of the US, Oncothyreon will receive a double-digit royalty on net sales intended to approximate a 50 per cent profit share, and the two companies will share equally the proceeds from any sublicense of marketing rights.

"We are pleased to expand our pipeline of oncology products in development through this collaboration with Array," said Robert L Kirkman, MD, president and chief executive officer of Oncothyreon. "As the only selective small-molecule inhibitor of HER2 in clinical development, we believe ARRY-380 has the potential to significantly enhance the care of women with metastatic breast cancer."

"We believe ARRY-380 has the potential to be a very important long-term treatment option for patients living with breast cancer," said Ron Squarer, CEO, Array BioPharma. "We are pleased to have a partner in Oncothyreon to advance the drug through these important proof-of-concept studies and beyond."

ARRY-380 is an orally active, reversible and selective HER2 inhibitor. In multiple preclinical tumour models, ARRY-380 was well tolerated and demonstrated significant dose-related tumor growth inhibition that was superior to Herceptin (trastuzumab) and Tykerb. Additionally, in these models, ARRY-380 demonstrated synergistic or additive tumor growth inhibition when dosed in combination with the standard-of-care therapeutics Herceptin or Taxotere (docetaxel).

A phase I trial of ARRY-380, with both dose-escalation and expansion components, has been completed in 50 patients, 43 of whom had HER2+ metastatic breast cancer. All HER2+ breast cancer patients had progressed on a trastuzumab-containing regimen. In addition, over 80 per cent had been treated with lapatinib, with many having progressed on therapy. In this study, ARRY-380 demonstrated an acceptable safety profile; treatment-related adverse events were primarily Grade 1. Because ARRY-380 is selective for HER2 and does not inhibit EGFR, there was a low incidence and severity of treatment-related diarrhea, rash and fatigue. Additionally, there were no treatment-related cardiac events or Grade 4 treatment-related adverse events reported. The maximum tolerated dose of ARRY-380 established in this phase I trial was 600 mg twice daily (BID). Twenty-two HER2+ breast cancer patients with measurable disease were treated with ARRY-380 at doses = 600 mg BID. In this heavily pretreated patient population, there was a clinical benefit rate (partial response [n = 3] plus stable disease for at least 6 months [n = 3]) of 27%. Notably, two of the patients with partial responses during treatment with ARRY-380 had confirmed progressions while on prior lapatinib- and trastuzumab-containing regimens.

Oncothyreon is specializing in the development of innovative therapeutic products for the treatment of cancer.

Array BioPharma Inc. is focused on the discovery, development and commercialization of targeted small-molecule drugs to treat patients afflicted with cancer.