Market Overview

LYNPARZA® (olaparib) Significantly Delays Disease Progression in Phase III 1st-Line SOLO-1 Trial for Ovarian Cancer

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LYNPARZA met primary endpoint of progression-free survival in
women with BRCA-mutated advanced ovarian cancer and showed a safety
profile consistent with previous trials

AstraZeneca and Merck's LYNPARZA is the only PARP inhibitor to
demonstrate significant activity in the 1st-line maintenance setting

AstraZeneca and Merck & Co., Inc., Kenilworth, N.J., US (Merck: known as
MSD outside the US and Canada) today announced positive results from the
randomized, double-blinded, placebo-controlled, Phase III SOLO-1 trial
of LYNPARZA® (olaparib) tablets (300 mg twice daily).

Women with BRCA-mutated (BRCAm) advanced ovarian cancer treated
1st-line with LYNPARZA maintenance therapy had a
statistically-significant and clinically-meaningful improvement in
progression-free survival compared to placebo. The safety and
tolerability profile of LYNPARZA was consistent with previous trials.
Based upon these data, AstraZeneca and Merck plan to initiate
discussions with health authorities regarding regulatory submissions.

Sean Bohen, Executive Vice President, Global Medicines Development and
Chief Medical Officer at AstraZeneca, said: "For the first time, we see
a significant and clinically-impactful improvement in progression-free
survival in the 1st-line maintenance setting for women with BRCA-mutated
ovarian cancer treated with a PARP inhibitor. The SOLO-1 data reinforce
the importance of knowing BRCA status at diagnosis, as this may
enable women with BRCA-mutated ovarian cancer to receive LYNPARZA
earlier. We would like to thank the investigators, hospitals and
most of all, the patients who took part in this trial, without whom
medical advancements would not be possible."

Roy Baynes, Senior Vice President and Head of Global Clinical
Development, Chief Medical Officer, Merck Research Laboratories, said:
"Building on the strong data we've seen with LYNPARZA to date, the
data from SOLO-1 reinforces LYNPARZA's ability to provide meaningful
disease control with a well-characterized safety and tolerability
profile. We look forward to presenting the full data set for SOLO-1 at a
future medical meeting and working with regulatory authorities to bring
LYNPARZA to women with ovarian cancer in the 1st-line
maintenance setting as quickly as possible."

LYNPARZA is not currently FDA-approved for 1st-line ovarian maintenance
treatment. LYNPARZA is indicated for the maintenance treatment of
recurrent ovarian cancer in response to platinum-based chemotherapy
regardless of BRCA mutation status, and for the treatment of
advanced ovarian cancer patients with a germline BRCA-mutation
previously treated with three or more lines of chemotherapy. Physicians
should select advanced ovarian cancer patients for therapy based on a
FDA-approved companion diagnostic. Please see complete indications below.

Additionally, the ongoing GINECO/ENGOTov25 Phase III trial, PAOLA-1,
sponsored by ENGOT/GCIG, is testing the effect of LYNPARZA in
combination with bevacizumab as a 1st-line maintenance treatment in
women with newly-diagnosed advanced ovarian cancer, regardless of their BRCA
status. Results are expected in 2019.

LYNPARZA is a first-in-class PARP inhibitor approved in the US for
certain patients with recurrent ovarian and metastatic breast cancer and
has treated nearly 5,500 patients since 2014. LYNPARZA has a broad
clinical-development program and AstraZeneca and Merck are working
together to deliver LYNPARZA as quickly as possible to more patients
across multiple cancer types, including prostate and pancreatic cancers.

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

There are no contraindications for LYNPARZA.

WARNINGS AND PRECAUTIONS

Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML): Occurred
in <1.5% of patients exposed to LYNPARZA monotherapy, and the majority
of events had a fatal outcome. The duration of therapy in patients who
developed secondary MDS/AML varied from <6 months to >2 years. All of
these patients had previous chemotherapy with platinum agents and/or
other DNA-damaging agents, including radiotherapy, and some also had a
history of more than one primary malignancy or of bone marrow dysplasia.

Do not start LYNPARZA until patients have recovered from hematological
toxicity caused by previous chemotherapy (≤Grade 1). Monitor complete
blood count for cytopenia at baseline and monthly thereafter for
clinically significant changes during treatment. For prolonged
hematological toxicities, interrupt LYNPARZA and monitor blood count
weekly until recovery.

If the levels have not recovered to Grade 1 or less after 4 weeks, refer
the patient to a hematologist for further investigations, including bone
marrow analysis and blood sample for cytogenetics. Discontinue LYNPARZA
if MDS/AML is confirmed.

Pneumonitis: Occurred in <1% of patients exposed to LYNPARZA, and
some cases were fatal. If patients present with new or worsening
respiratory symptoms such as dyspnea, cough, and fever, or a
radiological abnormality occurs, interrupt LYNPARZA treatment and
initiate prompt investigation. Discontinue LYNPARZA if pneumonitis is
confirmed and treat patient appropriately.

Embryo-Fetal Toxicity: Based on its mechanism of action and
findings in animals, LYNPARZA can cause fetal harm. A pregnancy test is
recommended for females of reproductive potential prior to initiating
treatment.

Females

Advise females of reproductive potential of the potential risk to a
fetus and to use effective contraception during treatment and for 6
months following the last dose.

Males

Advise male patients with female partners of reproductive potential or
who are pregnant to use effective contraception during treatment and for
3 months following the last dose of LYNPARZA and to not donate sperm
during this time.

ADVERSE REACTIONS—Maintenance Setting

Most common adverse reactions (Grades 1-4) in ≥20% of patients in
clinical trials of LYNPARZA in the maintenance setting for SOLO-2:
nausea (76%), fatigue (including asthenia) (66%), anemia (44%), vomiting
(37%), nasopharyngitis/upper respiratory tract infection (URI)/influenza
(36%), diarrhea (33%), arthralgia/myalgia (30%), dysgeusia (27%),
headache (26%), decreased appetite (22%), and stomatitis (20%).

Study 19: nausea (71%), fatigue (including asthenia) (63%),
vomiting (35%), diarrhea (28%), anemia (23%), respiratory tract
infection (22%), constipation (22%), headache (21%), and decreased
appetite (21%).

Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients in
clinical trials of LYNPARZA in the maintenance setting (SOLO-2/Study
19
) were: increase in mean corpuscular volume (89%/82%), decrease in
hemoglobin (83%/82%), decrease in leukocytes (69%/58%), decrease in
lymphocytes (67%/52%), decrease in absolute neutrophil count (51%/47%),
increase in serum creatinine (44%/45%), and decrease in platelets
(42%/36%).

ADVERSE REACTIONS—Advanced gBRCAm ovarian cancer

Most common adverse reactions (Grades 1-4) in ≥20% of patients in
clinical trials of LYNPARZA for advanced gBRCAm ovarian cancer
after 3 or more lines of chemotherapy
(pooled from 6 studies) were:
fatigue (including asthenia) (66%), nausea (64%), vomiting (43%), anemia
(34%), diarrhea (31%), nasopharyngitis/upper respiratory tract infection
(URI) (26%), dyspepsia (25%), myalgia (22%), decreased appetite (22%),
and arthralgia/musculoskeletal pain (21%).

Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients in
clinical trials of LYNPARZA for advanced gBRCAm ovarian cancer (pooled
from 6 studies) were: decrease in hemoglobin (90%), increase in mean
corpuscular volume (57%), decrease in lymphocytes (56%), increase in
serum creatinine (30%), decrease in platelets (30%), and decrease in
absolute neutrophil count (25%).

ADVERSE REACTIONS—gBRCAm, HER2-negative breast cancer

Most common adverse reactions (Grades 1-4) in ≥20% of patients in OlympiAD
were: nausea (58%), anemia (40%), fatigue (including asthenia) (37%),
vomiting (30%), neutropenia (27%), respiratory tract infection (27%),
leukopenia (25%), diarrhea (21%), and headache (20%).

Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients in OlympiAD
were: decrease in hemoglobin (82%), decrease in lymphocytes (73%),
decrease in leukocytes (71%), increase in mean corpuscular volume (71%),
decrease in absolute neutrophil count (46%), and decrease in platelets
(33%).

DRUG INTERACTIONS

Anticancer Agents: Clinical studies of LYNPARZA in combination
with other myelosuppressive anticancer agents, including DNA-damaging
agents, indicate a potentiation and prolongation of myelosuppressive
toxicity.

CYP3A Inhibitors: Avoid concomitant use of strong or moderate
CYP3A inhibitors. If a strong or moderate CYP3A inhibitor must be
co-administered, reduce the dose of LYNPARZA. Advise patients to avoid
grapefruit, grapefruit juice, Seville oranges, and Seville orange juice
during LYNPARZA treatment.

CYP3A Inducers: Avoid concomitant use of strong or moderate CYP3A
inducers when using LYNPARZA. If a moderate inducer cannot be avoided,
there is a potential for decreased efficacy of LYNPARZA.

USE IN SPECIFIC POPULATIONS

Lactation: No data are available regarding the presence of
olaparib in human milk, its effects on the breastfed infant or on milk
production. Because of the potential for serious adverse reactions in
the breastfed infant, advise a lactating woman not to breastfeed during
treatment with LYNPARZA and for 1 month after receiving the final dose.

Pediatric Use: The safety and efficacy of LYNPARZA have not been
established in pediatric patients.

Hepatic Impairment: No adjustment to the starting dose is
required in patients with mild hepatic impairment (Child-Pugh
classification A). There are no data in patients with moderate or severe
hepatic impairment.

Renal Impairment: No adjustment to the starting dose is necessary
in patients with mild renal impairment (CLcr=51-80 mL/min). In patients
with moderate renal impairment (CLcr=31-50 mL/min), reduce the dose to
200 mg twice daily. There are no data in patients with severe renal
impairment or end-stage renal disease (CLcr ≤30 mL/min).

INDICATIONS

LYNPARZA is a poly (ADP-ribose) polymerase (PARP) inhibitor indicated:

For the maintenance treatment of adult patients with recurrent
epithelial ovarian, fallopian tube, or primary peritoneal cancer, who
are in complete or partial response to platinum-based chemotherapy.

For the treatment of adult patients with deleterious or suspected
deleterious germline BRCA-mutated (gBRCAm) advanced
ovarian cancer who have been treated with 3 or more prior lines of
chemotherapy. Select patients for therapy based on an FDA-approved
companion diagnostic for LYNPARZA.

In patients with deleterious or suspected deleterious gBRCAm, human
epidermal growth factor receptor 2 (HER2)-negative metastatic breast
cancer who have been treated with chemotherapy in the neoadjuvant,
adjuvant or metastatic setting. Patients with hormone receptor
(HR)-positive breast cancer should have been treated with a prior
endocrine therapy or be considered inappropriate for endocrine therapy.
Select patients for therapy based on an FDA-approved companion
diagnostic for LYNPARZA.

Please see complete Prescribing
Information
, including Patient Information (Medication Guide).

NOTES TO EDITORS

About SOLO-1

SOLO-1 is a Phase III randomized, double-blinded, placebo-controlled
multi-center trial to evaluate the efficacy and safety of LYNPARZA tablets
as 1st-line maintenance monotherapy compared with placebo, in patients
with BRCAm advanced ovarian cancer. The trial randomized 391
patients with a deleterious or suspected deleterious BRCA1 or BRCA2
mutation who were in clinical complete or partial response following
platinum-based chemotherapy. Eligible patients were randomized (2:1) to
receive LYNPARZA 300 mg tablets twice daily or placebo tablets
twice daily. The primary endpoint was progression free survival and
secondary key endpoints include time to second disease progression or
death and overall survival.

About Ovarian Cancer

Approximately 20,000 women in the United States are diagnosed with
ovarian cancer (including ovarian, fallopian tube and primary peritoneal
cancers) each year. Among women in the United States, it is the ninth
most common cancer and the fifth leading cause of cancer death.

The risk of developing ovarian cancer is increased in women with
specific inherited genetic abnormalities, including BRCA
mutations.

For newly diagnosed advanced ovarian cancer, the primary aim of
treatment is to delay progression of the disease for as long as possible
and maintain the patient's quality of life with the intent of achieving
complete remission or cure.

About BRCA Mutations

BRCA1 and BRCA2 are human genes that produce proteins
responsible for repairing damaged DNA and play an important role in
maintaining the genetic stability of cells. When either of these genes
is mutated, or altered, such that its protein product either is not made
or does not function correctly, DNA damage may not be repaired properly
and cells become unstable. As a result, cells are more likely to develop
additional genetic alterations that can lead to cancer.

About LYNPARZA® (olaparib)

LYNPARZA was the first in class PARP inhibitor and the first
targeted treatment to potentially exploit DNA damage response (DDR)
pathway deficiencies, such as BRCA mutations, to
preferentially kill cancer cells. Specifically, in vitro studies
have shown that LYNPARZA-induced cytotoxicity may involve inhibition of
PARP enzymatic activity and increased formation of PARP-DNA complexes,
resulting in DNA damage and cancer cell death.

LYNPARZA is being tested in a range of DDR-deficient tumor types and is
the foundation of AstraZeneca's industry-leading portfolio of compounds
targeting DDR mechanisms in cancer cells.

LYNPARZA, which is being jointly developed and commercialized by
AstraZeneca and Merck, has a broad and advanced clinical trial
development program, and AstraZeneca and Merck are working together to
deliver it as quickly as possible to more patients across multiple
cancer types.

About the AstraZeneca and Merck Strategic 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
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 olaparib and selumetinib in
combination with other potential new medicines and as monotherapies.
Independently, the companies will develop olaparib 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 Oncology as one of AstraZeneca's Four 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, DDR 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
main therapy areas - Oncology, Cardiovascular, Renal & Metabolism and
Respiratory. The Company also is selectively active in the areas of
autoimmunity, neuroscience and infection. 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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