Selumetinib Granted US Breakthrough Therapy Designation in Neurofibromatosis Type 1

AstraZeneca and Merck & Co., Inc., Kenilworth, NJ, US (known as MSD
outside the US and Canada) today announced that the US Food and Drug
Administration (FDA) has granted Breakthrough Therapy Designation (BTD)
for the investigational MEK 1/2 inhibitor and potential new medicine
selumetinib.

This designation is for the treatment of pediatric patients aged three
years and older with neurofibromatosis type 1 (NF1) symptomatic and/or
progressive, inoperable plexiform neurofibromas (PN), a rare, incurable
genetic condition.

José Baselga, Executive Vice President, Research and Development,
Oncology, said: “Selumetinib shows promise in the treatment of
NF1-related plexiform neurofibromas, a rare and debilitating disease
with no approved medications to date. The Breakthrough Therapy
Designation acknowledges the significant unmet need of these patients
and the potential benefit of selumetinib in this setting.”

Roy Baynes, Senior Vice President and Head of Global Clinical
Development, Chief Medical Officer, at Merck Research Laboratories,
said: “This new designation validates our ongoing development of
selumetinib. As a result of this, selumetinib has the potential to
receive expedited regulatory review and we hope to bring this medicine
to patients as soon as possible.”

The BTD is based on Phase II data from the SPRINT trial, testing
selumetinib as an oral monotherapy in pediatric patients, aged three
years or older with inoperable NF1-related PN.The results of
the trial were presented by the National Cancer Institute (NCI) at the
2018 American Society of Clinical Oncology Annual Meeting.

This is the ninth BTD that AstraZeneca has received from the FDA since
2014. A BTD is designed to expedite the development and regulatory
review of medicines that are intended to treat a serious condition and
that have shown encouraging early clinical results, which may
demonstrate substantial improvement on a clinically-significant endpoint
over available medicines.

Selumetinib was granted Orphan Drug Designation for the treatment of NF1
by the US FDA in February 2018 and the European Medicines Agency in
August 2018.

About selumetinib

Selumetinib is a MEK 1/2 inhibitor and potential new medicine licensed
by AstraZeneca from Array BioPharma Inc. in 2003. AstraZeneca and Merck
& Co., Inc., Kenilworth, NJ, entered a co-development and
co-commercialization agreement for selumetinib in 2017.

The NF1 gene provides instructions for making a protein called
neurofibromin, which negatively regulates the RAS/MAPK pathway, helping
to control cell growth, differentiation and survival. Mutations in the NF1
gene may result in dysregulations in RAS/RAF/MEK/ERK signaling, which
can cause cells to grow, divide and copy themselves in an uncontrolled
manner, and may result in tumor growth. Selumetinib inhibits the MEK
enzyme in this pathway, potentially leading to inhibition of tumor
growth.

Selumetinib is being assessed as a monotherapy and in combination with
other treatments in ongoing clinical trials.

About SPRINT

The SPRINT trial is a US Cancer Therapy Evaluation Program (CTEP)
NCI-sponsored Phase I/II trial. The Phase I trial was designed to
identify the optimal Phase II dosing regimen, and the results were
published in the New England Journal of Medicine.

About NF1

Neurofibromatosis type 1 (NF1) is an incurable genetic condition that
affects one in 3,000 to 4,000 individuals in the U.S.It is
caused by a spontaneous or inherited mutation in the NF1 gene and
is associated with many symptoms, including soft lumps on and under the
skin (cutaneous neurofibromas), skin pigmentation (so-called ‘cafe au
lait’ spots) and, in 20-50% of patients, tumors develop on the nerve
sheaths (plexiform neurofibromas).These plexiform neurofibromas can
cause clinical complications such as pain, motor dysfunction, airway
dysfunction, bowel/bladder dysfunction and disfigurement as well as
having the potential to transform into malignant peripheral nerve sheath
tumors (MPNST).

People with NF1 may experience a number of complications such as
learning difficulties, visual impairment, twisting and curvature of the
spine, high blood pressure, and epilepsy. NF1 also increases a person’s
risk of developing other cancers, including malignant brain tumors,
MPNST and leukemia. Symptoms begin during early childhood, with varying
degrees of severity, and can reduce life expectancy by up to 15 years.

About the AstraZeneca and the Merck Oncology Collaboration

In July 2017, AstraZeneca and Merck & Co., Inc., Kenilworth, NJ, US,
known as MSD outside the United States and Canada, announced a global
strategic oncology collaboration to co-develop and co-commercialize
LYNPARZA (olaparib), the world’s first PARP inhibitor and potential new
medicine selumetinib, a MEK inhibitor, for multiple cancer types.
Working together, the companies will develop LYNPARZA and
selumetinib in combination with other potential new medicines and as
monotherapies. Independently, the companies will develop LYNPARZA and
selumetinib in combination with their respective PD-L1 and PD-1
medicines.

About AstraZeneca in Oncology

AstraZeneca has a deep-rooted heritage in Oncology and offers a
quickly-growing portfolio of new medicines that has the potential to
transform patients’ lives and the Company’s future. With at least six
new medicines to be launched between 2014 and 2020, and a broad pipeline
of small molecules and biologics in development, we are committed to
advance New Oncology as one of AstraZeneca’s five Growth Platforms
focused on lung, ovarian, breast and blood cancers. In addition to our
core capabilities, we actively pursue innovative partnerships and
investments that accelerate the delivery of our strategy, as illustrated
by our investment in Acerta Pharma in hematology.

By harnessing the power of four scientific platforms – Immuno-Oncology,
Tumor Drivers and Resistance, DNA Damage Response and Antibody Drug
Conjugates – and by championing the development of personalized
combinations, AstraZeneca has the vision to redefine cancer treatment
and one day eliminate cancer as a cause of death.

About AstraZeneca

AstraZeneca is a global, science-led biopharmaceutical company that
focuses on the discovery, development and commercialization of
prescription medicines, primarily for the treatment of diseases in three
therapy areas - Oncology, Cardiovascular, Renal & Metabolism and
Respiratory. AstraZeneca operates in over 100 countries and its
innovative medicines are used by millions of patients worldwide. For
more information, please visit www.astrazeneca-us.com and
follow us on Twitter @AstraZenecaUS.

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