dual p38/Tie2 inhibitor, may be effective in the treatment of MDS, particularly in settings where
hypomethylating agents such as Vidaza and Dacogen have failed, by providing clinical benefit through
multi-lineage hematologic improvement (i.e. an increase in red blood cells, neutrophil cells and platelets),
thereby reducing the need for red blood cell and platelet transfusions.
tissues of the lung, usually in the cells lining air passages. The two main types of lung cancer are
non-small cell lung cancer (NSCLC), which represents about 85%, and small cell lung cancer (SCLC),
which represents about 15% of lung cancer. In 2012, the estimated new cases and deaths from all lung
cancer in the U.S. were 226,160 and 160,340, respectively. The overall five-year relative survival rate for
the period of 2002 to 2008 for patients with lung cancer was 15.9%. The five-year relative survival rate
varies markedly depending on the stage at diagnosis, from 52% to 25% to 4% for patients with local,
regional and metastatic disease, respectively.
control can be achieved with radiation therapy in a large number of patients with unresectable disease,
but a cure is seen only in a small number of patients. Patients with locally advanced, unresectable
disease may have long-term survival with radiation therapy combined with chemotherapy. Patients with
advanced metastatic disease may achieve improved survival and palliation of symptoms with
chemotherapy, however metastatic NSCLC remains a fatal disease.
$5.4 billion in 2020. Generic price erosion of key agents such as Alimta
chemotherapy has led to the investigation of targeted therapies. Mutations in the KRAS gene are
amongst the most common mutations in NSCLC, being found in 20% to 25% of patients. Typically, KRAS
mutations activate the RAS/RAF/MEK/ERK pathway, contributing to unregulated cell growth and
survival. Therapies that target this aberrant pathway, including MEK inhibitors, would therefore be
expected to have therapeutic activity in patients with mutated KRAS. Promising data from a double-blind,
randomized Phase 2 study comparing the efficacy of selumetinib, a MEK inhibitor we licensed to
AstraZeneca, in combination with docetaxel versus docetaxel alone in second-line patients with KRAS
mutation-positive locally advanced or metastatic NSCLC were presented at the 2012 ASCO Annual
Meeting. 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 overall
survival in favor of selumetinib in combination with docetaxel versus docetaxel alone.
increasing substantially over the past 30 years and at a rate which is among the fastest growing of any
human cancer. According to the American Cancer Society, the estimated new cases and deaths from
melanoma in the U.S. in 2012 are 76,250 and 9,180, respectively. Prognosis is heavily dependent upon
stage of the disease. The outlook for patients with metastatic disease is poor, with the five-year survival
rate of approximately 16%.
surgical excision is the treatment of choice with some of these patients receiving adjuvant therapy with
interferon alfa (IFNa). Surgical excision of limited distant metastatic disease can occasionally produce
durable benefit, but most patients with distant metastases require systemic therapy. Systemic therapies
include chemotherapy and immunotherapy, used either alone or in combination.
pharmaceutical markets forecasted to grow annually by 22% from $210 million in 2010 to $1.5 billion in
2020. This forecasted growth is driven largely by recent and anticipated launches of several novel,
high-priced therapies expected to capture substantial market share over time.
mutations in 40% to 60%, and NRAS mutations in 15-20% of melanoma patients, suggesting the
therapeutic potential for agents that target this pathway in melanoma. Following Roche's launch of the
BRAF inhibitor Zelboraf (vemurafenib) in 2011, several additional therapies that target this pathway are
under study. Included amongst these are several MEK inhibitors. As MEK inhibitors target the RAS/RAF/
MEK/ERK pathway which is activated with BRAF mutation, they may also have the potential for activity
not only in patients with BRAF-mutant melanoma, but also in patients with tumors that harbor mutations in
the NRAS gene, who currently have no adequate treatment option and poor prognosis. Promising data on
MEK162 in an ongoing Phase 2 trial of patients with BRAF and NRAS mutated advanced melanoma was
presented at the 2012 ASCO Annual Meeting. MEK162 showed clinical activity and good tolerability in
this patient population. This is the first targeted therapy to show activity in patients with NRAS mutated
and 1,780 deaths in 2012. The rapid increase in incidence rates is thought to be largely due to increased
and earlier detection. Thyroid cancer strikes relatively young patients, with most initial diagnoses
between ages 20 and 54, and occurs 2 to 3 times more often in women than in men, placing it as the fifth
most common malignancy diagnosed in women.
even when therapy is successful, the disease remains burdensome and potentially lethal: patients must
be tested routinely for the rest of their life, with as many as 35% of thyroid cancers recurring, one third of
which occur more than 10 years after initial treatment.
treatment, followed by radioiodine therapy, or RAI, to kill off residual cancer cells, and usually thyroid
hormone suppression therapy for maintenance to prevent recurrence. For metastatic disease, RAI is the
leading therapeutic option. However, a significant number of patients have disease not receptive to RAI
therapy, or RAI-refractory disease, and have few effective treatment alternatives. This remains a
significant unmet need, as distant metastases are the most frequent cause of death for patients with
papillary or follicular thyroid cancers which account for 90% of thyroid tumors, and decreased RAI
incorporation into metastatic sites has been shown to be associated with higher mortality.
as BRAF and NRAS mutations have a strong scientific underpinning for activity in this disease, with BRAF
mutations in approximately 39%, and NRAS mutations in approximately 7% of thyroid cancers. In a
recent pilot study, selumetinib has shown positive therapeutic activity in patients with RAI-refractory