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AstraZeneca to Share Latest Data from an Industry-Leading Portfolio That Aims to Advance Clinical Understanding of Diabetes and CV Risk Management at ADA 2018

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Key data evaluating the efficacy and safety of dapagliflozin in
combination with other type 2 diabetes therapies head-to-head vs.
insulin or sulfonylurea

Latest data from the DEPICT clinical program evaluating
dapagliflozin to address an unmet need for oral therapy in adult
patients with type 1 diabetes

Debut of pre-clinical and clinical data for MEDI0382 in type 2
diabetes, a potential first-in-class oxyntomodulin-like peptide

AstraZeneca and its global biologics research and development arm,
MedImmune, will present 45 abstracts including seven late-breaking data
disclosures from the Company's Cardiovascular (CV), Renal and Metabolism
(CVRM) therapy area at the American Diabetes Association's (ADA) 78th
Scientific Sessions in Orlando, Florida, June 22-26, 2018.

This latest research will help to inform clinical practice with FARXIGA®
(dapagliflozin) and BYDUREON® (exenatide extended-release) in
type 2 diabetes (T2D), including data on their use alone and in
combination with other diabetes therapies. Highlights also include data
on the potential new use of dapagliflozin in type 1 diabetes (T1D) and
the debut of pre-clinical and clinical data for MEDI0382, an
oxyntomodulin-like peptide and potential new medicine. MEDI0382 has the
potential to be a first- in- class therapy and is the latest candidate
to advance in the Company's CVRM pipeline.

Commenting on AstraZeneca's scientific approach in CVRM, Ludovic
Helfgott, Vice President, Cardiovascular, Renal and Metabolism, said:
"At ADA this year, we are sharing data on novel approaches and potential
new medicines as we continue to advance treatments for patients with
diabetes. At AstraZeneca, we recognize the critical interconnectivity
between cardiovascular, renal and metabolic diseases, and aim to deliver
leading science that addresses patient needs across the global burden of
these conditions."

Clinical and real-world evidence data further evaluating
dapagliflozin in T2D

Highlights include several abstracts evaluating the effects of
dapagliflozin on glycemic control and additional endpoints, including
blood pressure and body weight, alone and in combination with other
diabetes treatments across a broad range of patients. Dapagliflozin is
not indicated for weight loss or for the treatment of hypertension.

Presentations assessing the combination of dapagliflozin and
saxagliptin, include 24-week results of dapagliflozin as add- on therapy
to saxagliptin, in addition to metformin compared with insulin in
patients with or without sulfonylurea therapy.

AstraZeneca will also present long-term data from the DURATION-8 trial
over 104 weeks (Late-breaking Poster 104-LB), which
evaluated the efficacy and safety of dapagliflozin once daily in
combination with weekly exenatide extended-release vs. each treatment
alone.

New analyses from the EXSCEL (Exenatide Study of Cardiovascular Event
Lowering) CV outcomes trial will be presented in a late breaking poster
which will evaluate the CV and renal effects in patients that received
SGLT-2 inhibitor (SGLT-2i) in the placebo group, and a moderated poster
will provide insights on the renal outcomes observed with exenatide
extended-release. Exenatide extended-release and dapagliflozin are not
indicated to reduce the risk of cardiovascular or renal outcomes.

A new analysis of the landmark CVD-REAL study presented as a
late-breaking poster, comparing the risk of all-cause mortality,
hospitalization for heart failure (hHF), myocardial infarction and
stroke in patients with T2D starting treatment with dapagliflozin vs.
any DPP-4 inhibitor, based on data from Canada, Israel, Japan and South
Korea. CVD-REAL provides real-world evidence of dapagliflozin on these
CV outcomes, while DECLARE (Dapagliflozin Effect on CardiovascuLAR
Events) will evaluate the CV efficacy and safety of dapagliflozin in the
largest SGLT-2i CV outcomes trial in a broad range of patients with T2D,
including those with multiple CV risk factors or established CV
disease. The trial is anticipated to read out in the second half of
2018. Dapagliflozin is not indicated to reduce the risk of death,
hospitalization for heart failure, or CV outcomes.

Data evaluating the potential of dapagliflozin to address an unmet
need in patients with T1D

Currently, there are no oral treatment options approved for adult
patients with T1D. The latest data from the DEPICT (Dapagliflozin
Evaluation in Patients with Inadequately Controlled Type 1 Diabetes)
clinical program will include results on the efficacy and safety of
dapagliflozin as add on to insulin over 52 weeks (from DEPICT-1) and 24
weeks (from DEPICT-2), as well as a pooled analyses of continuous
glucose monitoring (CGM) data from both trials. Dapagliflozin
is not approved for T1D.

First pre-clinical and clinical data for MEDI0382 in T2D

From the Company's promising CVRM pipeline, MedImmune will present
primary results from its MEDI0382 Phase 2a trial. MEDI0382 is an
oxyntomodulin-like peptide and potential new medicine designed to
simultaneously activate the glucagon-like peptide 1 (GLP-1) and glucagon
(GLU) receptors, with the goals of achieving glucose control, reduced
body weight and increased energy expenditure in patients with T2D.
Oxyntomodulin is a peptide hormone released from the gut that targets
the GLP-1 and glucagon receptors, both of which are critical to
controlling metabolic functions. In addition, two oral presentations
will feature data on the effects of MEDI0382 on hepatic (liver) fat in
patients with T2D, and its effects on pancreatic and incretin hormones,
respectively.

Details of the key abstracts from AstraZeneca/MedImmune are as follows:

       
Abstract title     Presentation details
Short-term and long-term data for dapagliflozin in
combination with other T2D therapies
Effect of Dapagliflozin Plus Saxagliptin vs. Insulin Glargine on A1C
in patients With Type-2 Diabetes Inadequately Controlled by
Metformin with or without Sulfonylurea
    Oral 260-OR, Monday, June 25, 09:30 - 09:45 EDT
Dapagliflozin Plus Saxagliptin Add-On vs. Glimepiride Add-On to
Metformin in Patients with Poorly Controlled Type-2 Diabetes
    Oral 261-OR, Monday, June 25, 09:45 - 10:00 EDT
Durability of Glycemic Control with Dapagliflozin vs Saxagliptin in
Patients with Inadequately Controlled Type-2 Diabetes
    Poster 1181-P, Sunday, June 24, 12:00 - 13:00 EDT
Triple vs. Dual Therapy with Low-Dose Dapagliflozin Plus Saxagliptin
vs. Each Monocomponent Added to Metformin in Uncontrolled Type-2
Diabetes
    Poster 1149-P, Sunday, June 24, 12:00 - 13:00 EDT
DURATION-8 Randomized Controlled Trial 104-Week Results: Once-Weekly
Exenatide (ExQW) Plus Once-Daily Dapagliflozin (DAPA) Versus ExQW or
DAPA Alone
    Late-breaking Poster 104-LB, Monday, June 25, 12:00 - 13:00 EDT
 
Analyses of renal and SGLT-2i outcomes in the EXSCEL trial
Impact of SGLT2 Inhibitors (SGLT2i) on Cardiovascular (CV) Risk and
Estimated Glomerular Filtration Rate (eGFR) in the EXSCEL Placebo
Group
    Late-breaking Poster 130-LB, Monday, June 25, 12:00 - 13:00 EDT
Renal Outcomes in the EXenatide Study of Cardiovascular Event
Lowering (EXSCEL)
    Poster 522-P, General Session, Saturday, June 23, 11:30 - 12:30 EDT
and Moderated Poster Session, Monday, June 25, 12:00 - 13:00 EDT
 
Real-world evidence evaluating CV outcomes with SGLT2i vs. DPP-4
Analysis of Risk of CV Events and Death Associated with Initiation
of SGLT-2 vs. DPP-4 Inhibitors from the CVD-REAL 2 Study
    Late-breaking Poster 124-LB, Monday, June 25, 12:00 - 13:00 EDT
 
Short-term and long-term data for dapagliflozin in T1D
Efficacy and Safety of Dapagliflozin in Patients with Inadequately
Controlled Type-1 Diabetes: DEPICT-2 Study
    Oral 213-OR, Sunday, June 24, 16:00 EDT
Long-Term Efficacy and Safety of Dapagliflozin in Patients with
Inadequately Controlled Type-1 Diabetes: The DEPICT-1 Study
    Late-breaking Poster 119-LB, Monday, June 25, 12:00 - 13:00 EDT
Glucose Variables in T1D Studies with Dapagliflozin: Pooled Analysis
of Continuous Glucose Monitoring Data from DEPICT-1 and 2
    Late-breaking Poster 125-LB, Monday, June 25, 12:00 - 13:00 EDT
 
Clinical and pre-clinical data for MEDI0382, a novel
oxyntomodulin-like (OXM) peptide
Effect of MEDI0382 on Hepatic Fat Content in Subjects with Type-2
Diabetes Mellitus
    Oral 78-OR, Saturday, June 23, 08:00 - 10:00 EDT
Effects of MEDI0382 on Insulin, Glucagon and Incretin Hormone
Profiles
    Oral 79-OR, Saturday, June 23, 08:00 - 10:00 EDT
Evaluation of Glucose Control and Weight Loss with MEDI0382, a
GLP-1/Glucagon Receptor Dual Agonist, in a 6-week Phase 2A Study of
T2DM Subjects
    Poster 1067-P, Sunday, June 24, 12:00 PM - 13:00 EDT
 
Latest analyses of the leading global diabetes registries
Vascular Events in Patients with Type-2 Diabetes in the Year
Following Initiation of Second-line Therapy: the DISCOVER Study
    Poster 1562-P, Sunday, June 24, 12:00-13:00 EDT
Composite Cardiovascular Risk Factor Target Achievement and its
Indicators in US Adults with Diabetes: The Diabetes Collaborative
Registry
    Poster 1487-P, Sunday, June 24, 12:00 - 13:00 EDT
 
CV outcomes and mortality in T2D with associated CV, renal and
metabolic co-morbidities
Cardiovascular Outcomes and Mortality in Type-2 Diabetes with
Associated Cardio-Renal-Metabolic Co-Morbidities
    Poster 1582-P, Sunday, June 24, 12:00 - 13:00 EDT
   

The full list of AstraZeneca/MedImmune scientific data can be accessed
on the ADA website here.
You can also follow us live during ADA 2018 on Twitter.

INDICATION AND LIMITATIONS OF USE FOR FARXIGA (dapagliflozin) tablets
5 mg and 10 mg

FARXIGA is indicated as an adjunct to diet and exercise to improve
glycemic control in adults with type 2 diabetes mellitus.

FARXIGA is not recommended for patients with type 1 diabetes mellitus or
for the treatment of diabetic ketoacidosis.

Please read US
Full Prescribing Information
 and Medication
Guide
 for FARXIGA.

IMPORTANT SAFETY INFORMATION FOR FARXIGA

Contraindications

  • Prior serious hypersensitivity reaction to FARXIGA
  • Severe renal impairment (eGFR <30 mL/min/1.73 m2),
    end-stage renal disease, or patients on dialysis

Warnings and Precautions

  • Hypotension: FARXIGA causes intravascular volume contraction,
    and symptomatic hypotension can occur. Assess and correct volume
    status before initiating FARXIGA in patients with impaired renal
    function, elderly patients, or patients on loop diuretics. Monitor for
    hypotension
  • Ketoacidosis has been reported in patients with type 1 and
    type 2 diabetes receiving FARXIGA. Some cases were fatal. Assess
    patients who present with signs and symptoms of metabolic acidosis for
    ketoacidosis, regardless of blood glucose level. If suspected,
    discontinue FARXIGA, evaluate and treat promptly. Before initiating
    FARXIGA, consider risk factors for ketoacidosis. Patients on FARXIGA
    may require monitoring and temporary discontinuation in situations
    known to predispose to ketoacidosis
  • Acute Kidney Injury and Impairment in Renal Function: FARXIGA
    causes intravascular volume contraction and renal impairment, with
    reports of acute kidney injury requiring hospitalization and dialysis.
    Consider temporarily discontinuing in settings of reduced oral intake
    or fluid losses. If acute kidney injury occurs, discontinue and
    promptly treat.
    FARXIGA increases serum creatinine and decreases
    eGFR. Elderly patients and patients with impaired renal function may
    be more susceptible to these changes. Before initiating FARXIGA,
    evaluate renal function and monitor periodically. FARXIGA is not
    recommended in patients with an eGFR persistently between 30 and <60
    mL/min/1.73 m2
  • Urosepsis and Pyelonephritis: SGLT2 inhibitors increase the
    risk for urinary tract infections [UTIs] and serious UTIs have been
    reported with FARXIGA. Evaluate for signs and symptoms of UTIs and
    treat promptly
  • Hypoglycemia: FARXIGA can increase the risk of hypoglycemia
    when coadministered with insulin and insulin secretagogues. Consider
    lowering the dose of these agents when coadministered with FARXIGA
  • Genital Mycotic Infections: FARXIGA increases the risk of
    genital mycotic infections, particularly in patients with prior
    genital mycotic infections. Monitor and treat appropriately
  • Increases in Low-Density Lipoprotein Cholesterol (LDL-C) occur
    with FARXIGA. Monitor LDL-C and treat per standard of care
  • Bladder cancer: An imbalance in bladder cancers was observed in
    clinical trials. There were too few cases to determine whether the
    emergence of these events is related to FARXIGA, and insufficient data
    to determine whether FARXIGA has an effect on pre-existing bladder
    tumors. FARXIGA should not be used in patients with active bladder
    cancer. Use with caution in patients with a history of bladder cancer
  • Macrovascular Outcomes: There have been no clinical studies
    establishing conclusive evidence of macrovascular risk reduction with
    FARXIGA

Adverse Reactions

In a pool of 12 placebo-controlled studies, the most common adverse
reactions (≥5%) associated with FARXIGA 5 mg, 10 mg, and placebo
respectively were female genital mycotic infections (8.4% vs 6.9% vs
1.5%), nasopharyngitis (6.6% vs 6.3% vs 6.2%), and urinary tract
infections (5.7% vs 4.3% vs 3.7%).

Use in Specific Populations

  • Pregnancy: Advise females of potential risk to a fetus
    especially during the second and third trimesters.
  • Lactation: FARXIGA is not recommended when breastfeeding

INDICATION AND LIMITATIONS OF USE FOR BYDUREON® (exenatide
extended-release) for injectable suspension 2mg

BYDUREON and BYDUREON BCise are both indicated as an adjunct to diet and
exercise to improve glycemic control in adults with type 2 diabetes
mellitus

  • Not recommended as first-line therapy for patients inadequately
    controlled on diet and exercise
  • Not a substitute for insulin. Should not be used to treat type 1
    diabetes or diabetic ketoacidosis
  • Not recommended for use with insulin
  • Do not coadminister with other exenatide-containing products
  • Not studied in patients with a history of pancreatitis. Consider other
    antidiabetic therapies in patients with a history of pancreatitis

IMPORTANT SAFETY INFORMATION ABOUT BYDUREON AND BYDUREON BCISE,
INCLUDING BOXED WARNING

WARNING: RISK OF THYROID C-CELL TUMORS

  • Exenatide extended-release causes an increased incidence in thyroid
    C-cell tumors at clinically relevant exposures in rats compared to
    controls. It is unknown whether BYDUREON or BYDUREON BCise cause
    thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in
    humans, as the human relevance of exenatide extended-release-induced
    rodent thyroid C-cell tumors has not been determined
  • BYDUREON and BYDUREON BCise are contraindicated in patients with a
    personal or family history of MTC or in patients with Multiple
    Endocrine Neoplasia syndrome type 2 (MEN 2). Counsel patients
    regarding the potential risk of MTC with the use of BYDUREON or
    BYDUREON BCise and inform them of symptoms of thyroid tumors (eg, mass
    in the neck, dysphagia, dyspnea, persistent hoarseness). Routine
    monitoring of serum calcitonin or using thyroid ultrasound is of
    uncertain value for detection of MTC in patients treated with BYDUREON
    or BYDUREON BCise

CONTRAINDICATIONS

  • Personal or family history of MTC, patients with MEN 2
  • Prior serious hypersensitivity reactions to exenatide or product
    components

WARNINGS AND PRECAUTIONS

  • Acute Pancreatitis including fatal and non-fatal
    hemorrhagic or necrotizing pancreatitis has been reported. After
    initiation, observe patients carefully for symptoms of pancreatitis.
    If suspected, discontinue promptly and do not restart if confirmed.
    Consider other antidiabetic therapies in patients with a history of
    pancreatitis
  • Hypoglycemia Risk of hypoglycemia is increased when
    exenatide is coadministered with insulin or insulin secretagogues.
    Consider lowering the dose of these agents when coadministered with
    BYDUREON or BYDUREON BCise
  • Acute Kidney Injury and Impairment of Renal Function Altered
    renal function, including increased serum creatinine, renal
    impairment, worsened chronic renal failure, and acute renal failure,
    sometimes requiring hemodialysis and kidney transplantation have been
    reported. Not recommended in patients with severe renal impairment or
    end-stage renal disease. Use caution in patients with renal
    transplantation or moderate renal impairment
  • Gastrointestinal Disease Because exenatide is commonly
    associated with gastrointestinal adverse reactions, not recommended in
    patients with severe gastrointestinal disease (eg, gastroparesis)
  • Immunogenicity Patients may develop antibodies to exenatide.
    Patients with higher titer antibodies may have an attenuated HbA1c
    response. In clinical trials, attenuated glycemic response was
    associated with BYDUREON- or BYDUREON BCise-treated patients. If
    worsening of or failure to achieve adequate glycemic control occurs,
    consider alternative antidiabetic therapy
  • Hypersensitivity Reports of serious hypersensitivity
    reactions (eg, anaphylaxis and angioedema). If this occurs, patients
    should discontinue BYDUREON or BYDUREON BCise and promptly seek
    medical advice
  • Injection-Site Reactions Serious reactions (eg, abscess,
    cellulitis, and necrosis), with or without subcutaneous nodules, have
    been reported
  • Macrovascular Outcomes No clinical studies establishing
    conclusive evidence of macrovascular risk reduction with exenatide

ADVERSE REACTIONS

  • Most common (≥5%) and occurring more frequently than comparator in
    BYDUREON clinical trials: nausea (16.9%), diarrhea (12.7%), headache
    (8.0%), vomiting (6.8%), constipation (5.9%), injection-site pruritus
    (5.9%), injection-site nodule (5.3%), dyspepsia (5.1%)
  • Most common (≥5%) in BYDUREON BCise clinical trials: injection-site
    nodule (10.5%), nausea (8.2%)

DRUG INTERACTIONS

  • Oral Medications BYDUREON and BYDUREON BCise slow gastric
    emptying and may reduce the rate of absorption of orally administered
    drugs
  • Warfarin Increased international normalized ratio (INR)
    sometimes associated with bleeding has been reported with concomitant
    use of exenatide with warfarin. Monitor INR frequently until stable
    upon initiation of BYDUREON or BYDUREON BCise

PREGNANCY

Use during pregnancy only if the potential benefit justifies the
potential risk to the fetus.

Please click
here
 for Prescribing Information and Medication Guide for
BYDUREON BCise.

Please click
here
 for Prescribing Information and Medication Guide for
BYDUREON.

INDICATIONS AND LIMITATIONS OF USE FOR ONGLYZA®
(saxagliptin) tablets 5mg

ONGLYZA is indicated as an adjunct to diet and exercise to improve
glycemic control in adults with type 2 diabetes mellitus.

ONGLYZA is not indicated for the treatment of type 1 diabetes mellitus
or diabetic ketoacidosis.

Important Safety Information for ONGLYZA

Contraindications

Prior serious hypersensitivity reaction to ONGLYZA

Pancreatitis: There have been postmarketing reports of acute
pancreatitis in patients taking ONGLYZA, and in the SAVOR cardiovascular
outcomes trial. Observe for pancreatitis. If pancreatitis is suspected,
discontinue ONGLYZA.

Heart Failure: In the SAVOR cardiovascular outcomes trial, more
patients treated with ONGLYZA were hospitalized for heart failure
compared to placebo. Patients with a prior history of heart failure or
renal impairment had a higher risk for hospitalization for heart
failure. Consider the risks and benefits of ONGLYZA in patients who have
known risk factors for heart failure. Monitor for signs and symptoms. If
heart failure develops, consider discontinuation of ONGLYZA.

Hypoglycemia: When ONGLYZA was used in combination with a
sulfonylurea or with insulin, the incidence of confirmed hypoglycemia
was increased over that of placebo. Consider lowering the dose of these
agents when coadministered with ONGLYZA.

Hypersensitivity Reactions: Serious reactions have been reported
in patients treated with ONGLYZA, including anaphylaxis, angioedema, and
exfoliative skin conditions. Onset of these reactions occurred within
the first 3 months after initiation of treatment with ONGLYZA, with some
reports occurring after the first dose. If a serious hypersensitivity
reaction is suspected, discontinue ONGLYZA. Use caution in patients with
a history of angioedema to another DPP-4 inhibitor.

Severe and Disabling Arthralgia has been reported in patients
taking DPP-4 inhibitors. The time to onset of symptoms following
initiation of drug therapy varied from one day to years. Patients
experienced relief of symptoms upon discontinuation. A subset of
patients experienced a recurrence of symptoms when restarting the same
drug or a different DPP-4 inhibitor. Consider discontinuing drug if
appropriate.

Bullous Pemphigoid: There have been postmarketing reports of
bullous pemphigoid requiring hospitalization in patients taking DPP-4
inhibitors. Tell patients to report development of blisters or erosions.
If suspected, discontinue ONGLYZA.

Macrovascular Outcomes: There have been no clinical studies
establishing conclusive evidence of macrovascular risk reduction with
ONGLYZA.

Most Common Adverse Reactions

Most common adverse reactions reported in ≥5% of patients treated with
ONGLYZA and more commonly than in patients treated with placebo were
upper respiratory tract infection (7.7%, 7.6%), urinary tract infection
(6.8%, 6.1%), and headache (6.5%, 5.9%).

Peripheral edema was reported more commonly in patients treated with the
combination of ONGLYZA 5 mg and a thiazolidinedione (TZD) than in
patients treated with the combination of placebo and TZD (8.1% vs 4.3%,
respectively).

Drug Interactions

Strong CYP3A4/5 inhibitors (eg, ketoconazole): Coadministration with
ONGLYZA significantly increases saxagliptin concentrations. Recommend
limiting ONGLYZA dosage to 2.5 mg once daily.

Use in Specific Populations

In patients with moderate or severe renal impairment, or end-stage renal
disease (eGFR <45 mL/min/1.73 m2), recommended dosage is
2.5 mg once daily regardless of meals. ONGLYZA should be administered
following hemodialysis. Assess renal function before starting ONGLYZA
and periodically thereafter.

Please see US Full Prescribing
Information
 and Medication
Guide
 for ONGLYZA.

NOTES TO EDITORS

About AstraZeneca in Cardiovascular, Renal & Metabolism (CVMD)

Cardiovascular, renal and metabolic diseases together form one of
AstraZeneca's main therapy areas and platforms for future growth. By
following the science to understand more clearly the underlying links
between the heart, kidney and pancreas, AstraZeneca is investing in a
portfolio of medicines to protect organs and improve outcomes by slowing
disease progression, reducing risks and tackling co-morbidities. Our
ambition is to modify or halt the natural course of CVMD diseases and
even regenerate organs and restore function, by continuing to deliver
transformative science that improves treatment practices and
cardiovascular health for millions of patients worldwide.

About MedImmune

MedImmune is the global biologics research and development arm of
AstraZeneca, a global, innovation-driven biopharmaceutical business that
focuses on the discovery, development and commercialization of small
molecule and biologic prescription medicines. MedImmune is pioneering
innovative research and exploring novel pathways across Oncology,
Respiratory, Cardiovascular, Renal and Metabolic Diseases, and Infection
and Vaccines. The MedImmune headquarters is located in Gaithersburg,
Md., one of AstraZeneca's three global R&D centers, with additional
sites in Cambridge, UK and South San Francisco, CA. For more
information, please visit www.medimmune.com.

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. 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 http://www.astrazeneca-us.com
and follow us on Twitter @AstraZenecaUS.

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