AstraZenecaAstraZeneca and Merck & Co., Inc. will collaboration to research a novel combination anticancer regimen composed of two investigational compounds, MK-2206 from Merck and AZD6244 (ARRY-886*) from AstraZeneca. Preclinical evidence indicates that combined administration of these compounds could enhance their anticancer properties.

This is the first time that two large pharmaceutical companies have established a collaboration to evaluate the potential for combining candidate molecules at such an early stage of development. The collaboration will more quickly advance a potentially promising anticancer treatment. In general, such combinations would only be studied when one or both of the drugs has entered late-stage development or received marketing approval.

Under the terms of the agreement, AstraZeneca and Merck will work together to evaluate co-administration of the compounds in a Phase I clinical trial for the treatment of solid cancer tumors. All development costs will be shared jointly. Following the Phase I trial, the companies will consider opportunities for further clinical development.

Each candidate is designed to inhibit a protein known to be abnormally activated in human cancers. In preclinical studies, AZD6244 has been shown to affect MEK (Mitogen-activated protein kinase 1), an important signal that promotes cancer cell growth and survival. AZD6244 has completed Phase I evaluation, demonstrating proof of mechanism, and several Phase II monotherapy studies, which showed evidence of clinical activity. It is currently in Phase II clinical trials in a range of tumor types. Merck's MK-2206 has demonstrated an effect on AKT (a component of the phosphatidylinositol-3 kinase pathway), an important signal promoting cancer cell survival. Phase I clinical data on MK-2206 were presented this week at the American Society of Clinical Oncology annual meeting.

"There is strong scientific rationale to suggest that the potential benefit to cancer patients of this combination may far exceed the sum of the parts," said Gary Gilliland, senior vice president and franchise head Oncology, Merck Research Laboratories. "In order to harness the true potential of the combined administration of the compounds, AstraZeneca and Merck have established a pioneering, early stage collaboration based on our mutual determination to develop impactful therapies that improve patients' lives."

"This collaboration brings together two leading companies with a wealth of expertise in oncology," said Alan Barge, vice president and head of Oncology at AstraZeneca. "Through this agreement we are well positioned to implement a detailed and timely evaluation of the therapeutic potential of this novel combination, with the aim of bringing this potentially effective regimen to patients as rapidly as possible."

Exploring Two Anticancer Agents with Two Distinct Targets
Advances in cancer research have led to a new generation of drugs designed to precisely target features specific to cancer cells while minimizing the effect on healthy cells. Several of these drugs provide patient benefit as monotherapy, but increasingly the ability of cancer cells to adapt and develop resistance has become apparent. Research suggests that combination therapies that include drugs with different mechanisms of action impacting cancer cells in multiple ways may provide an improved anticancer benefit and decrease the risk of relapse.

Molecular profiling of human solid tumors has shown that both the MEK and AKT pathways are frequently abnormally activated. Preclinical studies have suggested that simultaneously inhibiting both of these pathways may have synergistic effects on tumor cell growth.

Usually, combinations of novel anticancer agents would only be studied in clinical trials when one component of the regimen is at a late stage of development or when one compound has received marketing approval. This agreement is pioneering in that two major pharmaceutical companies, each with one component of the combination regimen in its pipeline, are collaborating at an early stage in development, so that effective treatments may be brought to patients as rapidly as possible.

* AstraZeneca acquired exclusive worldwide rights to AZD6244 (ARRY-886) from Array Biopharma Inc. in December 2003.

About AstraZeneca
AstraZeneca is a major international healthcare business engaged in the research, development, manufacturing and marketing of meaningful prescription medicines and supplier for healthcare services. AstraZeneca is one of the world's leading pharmaceutical companies with healthcare sales of US$ 31.6 billion and is a leader in gastrointestinal, cardiovascular, neuroscience, respiratory, oncology and infectious disease medicines. For more information about AstraZeneca, please visit:

About Merck
Merck & Co., Inc. is a global research-driven pharmaceutical company dedicated to putting patients first. Established in 1891, Merck currently discovers, develops, manufactures and markets vaccines and medicines to address unmet medical needs. The company devotes extensive efforts to increase access to medicines through far-reaching programs that not only donate Merck medicines but help deliver them to the people who need them. Merck also publishes unbiased health information as a not-for-profit service. For more information, visit