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Development Status: Array is continuing a randomized, double-blind, six week, 180 patient, Phase 2
trial in persistent asthma. Array expects top-line results from this trial during the second quarter of
calendar 2013 and intends to seek a partner for further development of ARRY-502 in this large market
disease.
Partnered Development Programs
Below are summaries of our most advanced, ongoing partnered development programs. Any information
we report about the development plans or the progress or results of clinical trials or other development
activities of our partners is based on information that has been reported to us or is otherwise publicly
disclosed by our collaboration partners.
1.
AstraZeneca -- Selumetinib and AZD8330 -- MEK Program
In December 2003, we entered into an out-licensing and collaboration agreement with AstraZeneca to
develop our MEK program. Under the agreement, AstraZeneca acquired exclusive worldwide rights to
our clinical development candidate, selumetinib (previously known as AZD6244, or ARRY-142886),
together with two other compounds for oncology indications, including AZD8330, which we invented
during the collaboration. We retained the rights to all therapeutic indications for MEK compounds not
selected by AstraZeneca for development, subject to the parties' agreement to work exclusively together.
In April 2009, the exclusivity of the parties' relationship ended, and both companies are now free to
independently research, develop and commercialize small molecule MEK inhibitors in the field of
oncology. To date, we have earned $21.5 million in up-front and milestone payments. The agreement
also provided for research funding, which is now complete, and provides potential additional development
milestone payments of approximately $75 million and royalties on product sales.
Under this collaboration, we were responsible for Phase 1 clinical testing, which we completed in 2004,
and AstraZeneca is responsible for all future development and commercialization of the compounds
under the collaboration.
MEK is a key protein kinase in the RAS/RAF/MEK/ERK pathway, which signals cancer cell proliferation
and survival. MEK has been shown to be frequently activated in cancer, in particular in tumors that have
mutations, including BRAF and NRAS, in the RAS and RAF pathways. Selumetinib is a small molecule
MEK inhibitor that targets a key position in this pathway.
Development Status: Selumentinib is currently in Phase 2 development in a range of solid tumors.
There were two presentations of significant data for selumetinib during fiscal 2012, which are summarized
below.
Phase 2 trial in patients with KRAS non-small cell lung cancer (NSCLC) Data was presented in June
2012 at the American Society of Clinical Oncology (ASCO) Annual Meeting from a double-blind,
randomized Phase 2 study conducted by AstraZeneca comparing the efficacy of selumetinib in
combination with docetaxel versus docetaxel alone in second-line therapy in 87 patients with
KRAS-mutation positive locally advanced or metastatic NSCLC (Stage IIIB -- IV). This study showed
statistically significant improvement in progression-free survival, objective response rate, and alive and
progression-free at six months as well as a trend for improvement in median overall survival in favor of
selumetinib in combination with docetaxel versus docetaxel alone (9.4 mo vs 5.2 mo; 56 events, median
follow-up 219 days) but did not reach statistical significance. Hazards were non-proportional (HR 0.80;
80% CI 0.56, 1.14; 1-sided p=0.2069). All secondary endpoints, including response rate (selumetinib/
docetaxel 37%, docetaxel 0%; p<0.0001) and progression free survival (selumetinib/docetaxel 5.3 mo,
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docetaxel 2.1 mo; 71 events; HR = 0.58; 80% CI 0.42, 0.79; 1-sided p=0.0138), were significantly
improved for selumetinib in combination with docetaxel versus docetaxel alone.
The tolerability profile of selumetinib in combination with docetaxel was consistent with previously
conducted studies. There was an increased incidence of Grade 3 or 4 neutropenia and febrile
neutropenia and of Grade 1 or 2 diarrhea in patients receiving the selumetinib combination versus
docetaxel alone.
This study was the first completed randomized combination trial with a MEK inhibitor in KRAS mutant
advanced NSCLC and Array believes was the first prospective study to demonstrate clinical benefit as
defined by response rate and progression free survival of a targeted therapy for patients with KRAS
mutant cancer of any type. Approximately 20 to 25 percent of the NSCLC patient population has the
KRAS mutation which amounts to approximately 160,000 patients globally. Currently, patients with KRAS
NSCLC have a poor prognosis with limited treatment options. Targeting MEK dependent tumors with
selumetinib demonstrates the potential of a personalized approach to medicine in the treatment of cancer
and suggests that further clinical evaluation of selumetinib in KRAS mutation positive NSCLC patients is
warranted.
Phase 2 trial in patients with recurrent low-grade serous ovarian or peritoneal cancer In April 2012, the
Gynecologic Oncology Group presented results of a Phase 2 trial with selumetinib in women with
recurrent low-grade serous ovarian or peritoneal cancer at the American Association for Cancer
Research Annual Meeting. This trial was funded by the National Cancer Institute and run by the
Gynecologic Oncology Group.
In the reported trial, 52 women each received 100-mg doses of selumetinib orally twice daily in four-week
cycles until disease progression or toxicity. The median number of cycles received was 4.5; 33% received
12 or more cycles. Prior to the trial, 58% of the patients in the trial had received three or more rounds of
chemotherapy. The disease control rate, defined as either complete or partial response or
progression-free survival or progression-free survival of greater than 6 months, was 81% of patients.
Eight patients had complete (1) or partial (7) responses, and 34 (63%) had progression-free survival of
greater than 6 months. The median survival rate without cancer progression was 11 months. Only three
patients experienced grade 4 adverse events.
There are 38 on-going trials with selumetinib, including trials in NSCLC, thyroid cancer, melanoma, ocular
melanoma, hepatocellular cancer, rectal cancer, colorectal cancer, pancreatic cancer and breast cancer.
2.
Novartis -- MEK162 and MEK300 -- MEK Inhibitor Program
In April 2010, we granted Novartis, under a License Agreement, the exclusive worldwide right to develop
and commercialize MEK162. Under the agreement, we are responsible for completing the on-going
single agent Phase 1 clinical trial of MEK162 and may conduct further development of MEK162 in a
specific cancer indication. Novartis is responsible for all other development activities. Novartis is also
responsible for the commercialization of products under the agreement, subject to our option to co-detail
approved drugs in the U.S.
In connection with signing the agreement, Novartis paid us $45 million, comprising an up-front fee and an
initial milestone payment. In April 2011, we received a $10 million clinical research milestone from
Novartis after Novartis had its first patient visit in a Phase 2 clinical trial. We are also eligible under the
agreement to receive up to approximately $412 million in aggregate milestone payments if all clinical,
regulatory and commercial milestones specified in the agreement are achieved for MEK162 and
additional commercial milestone payments for MEK300 and other MEK inhibitors Novartis elects to
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