What science can do

What science can do
April 2015
Circulating tumour DNA
AstraZeneca has pioneered the use of circulating
tumour DNA (ctDNA) in the diagnosis of cancer.
Pieces of DNA break off from a tumour and
circulate in the bloodstream where they can
be analysed to give genetic information about
a patient’s tumour. This allows healthcare
professionals to determine the right treatment for
the patient using a non-invasive blood test.
A message
from
Pascal Soriot
At AstraZeneca, our purpose is to push the boundaries of science
to deliver life-changing medicines. We believe the best way we can
achieve this is to put science at the centre of everything we do. It
is this commitment that drives our ability to discover, develop and
deliver the advancements the world needs in complex and difficult
diseases like cancer, heart disease, diabetes, COPD and asthma.
For us, the discovery of medicines starts with our rare combination
of scientific capabilities in small molecules and biologics,
immunotherapies, protein engineering technologies, oligonucleotides
and devices. When combined with our strong focus on translational
science and personalised healthcare, we believe that we have a
unique and strong foundation for speeding novel, targeted therapies
from biologic concept to care.
We know that the best science doesn’t happen in isolation - it
happens through collaboration. That is why we seek to work so
extensively with scientific, academic and healthcare organisations
around the world - from the earliest discovery work in our research
labs, to our clinical trial programmes and to joint working with health
care providers to achieve optimal treatment outcomes.
We also take smart risks in developing and applying new
technologies which help us to explore new mechanisms of action
and create new types of treatments. It is when our scientists are
empowered to follow these transformative areas of science that we
see the most significant breakthroughs.
Minute pieces
of tumour DNA
circulating in the
bloodstream.
Every day and everywhere AstraZeneca employees work, we
endeavour to transform people’s lives through science. I hope you
see in all your interactions with us this commitment to unlocking the
power of what science can do.
Pascal Soriot
Chief Executive Officer
What science can do
Oncology combination therapies
AstraZeneca is investigating
combinations of biologic and small
molecule therapies for the treatment of
cancer. These combinations target the
tumour directly and some help boost
the body’s own immune system to
induce tumour cell death.
Antibody that blocks
inhibitory signals from
the tumour to cells of
the immune system,
resulting in enhanced
anti-tumour immunity.
Helping
more people
survive cancer
Our ambition is to transform the lives
of people with cancer and, through our
research and scientific partnerships,
we seek to eliminate cancer as a cause
of death.
AstraZeneca has a deep-rooted heritage in oncology.
Our vision is to help patients by redefining the way
in which cancer is diagnosed and treated, through
scientific innovation, accelerated clinical programmes
and collaboration. Our broad pipeline of medicines is
focused on four main disease areas: breast, ovarian,
lung and haematological cancers.
We believe that the challenge of beating cancer can
be met through the development of novel targeted
monotherapies (both small molecules and biologics)
and combinations that specifically address the
underlying mechanism of the disease or how it evades
effective immune response. Our goal is to understand
these mechanisms and develop treatment options that
significantly improve patient survival rates and quality
of life through a more complete tumour response,
suppression of tumour growth and delayed or reduced
tumour recurrence. Our industry-leading oncology
pipeline is broad and exciting, addressing multiple
disease pathways and allowing for combination
therapies to increase the benefit to patients.
1
AstraZeneca press release. Demonstrating our
oncology science at ASCO 2014, 30 May 2014.
http://www.astrazeneca.com/About-Us/Features/
Article/20140530--demonstrating-AstraZeneca-oncologyscience-ASCO-2014. Last accessed 23 February 2015.
AstraZeneca and the future of cancer care 1
Tumour drivers and resistance mechanisms
The inhibition of genetic disease drivers is a powerful way
to shrink tumours and improve progression-free survival
in many types of cancer. Tumours, however, eventually
develop resistance to therapy. Our research in this area
seeks to develop novel therapies that target both the
mutations that cause cancer cells to proliferate and the
mechanisms of resistance.
DNA damage repair
Our research programmes focus on identifying and
exploiting vulnerabilities that are unique to cancer
cells, so that new therapies can be developed that
selectively damage tumour cell DNA. We are exploring
tumour cell deficiencies such as enhanced sensitivity
to DNA damage or the potential to initiate programmed
cell death, to kill cancer cells while at the same time
minimising toxicity to the patient.
Antibody-drug conjugates
Antibody-drug conjugates offer a highly potent approach
that selectively targets cancer cells. We are seeking to
combine innovative antibody engineering capabilities
with cytotoxic drug ‘warheads’ to selectively attack and
kill the tumour while again keeping the toxic effects on
the patient to a minimum.
Immunotherapy
Our ambition is to be a scientific leader in immunotherapy,
a promising therapeutic approach that harnesses the
patient’s own immune system to help fight cancer.
We are working to understand how cancer evades the
immune system and to identify approaches that enhance
the immune system’s ability to fight cancer.
Making hearts
healthier
AstraZeneca is prioritising the treatment of cardiovascular and
metabolic diseases, focusing on bringing life-changing medicines
to patients with thrombosis, atherosclerosis, dyslipidaemia,
hypertension, heart failure and metabolic diseases, including
diabetes and related complications.
We invest both in the development of new treatments and in better
scientific understanding of our many existing medicines, in order
to increase our understanding of them and explore possible new
indications in areas of unmet medical need. We are also expanding
our capabilities and research programmes into new modalities and
regenerative medicine to provide new treatment paradigms for heart
failure, diabetes and chronic kidney disease.
2
Jha et al. Chronic kidney disease: global dimension and perspectives.
The Lancet 2013; 382:260-272.
3
https://www.clinicaltrials.gov/ct2/show/NCT02104817.
Last accessed February 2015.
We push the boundaries of science to create
innovative medicines that address multiple
cardiovascular risk factors and diseases,
offer individualised approaches for diabetes
patients, treat chronic kidney disease, and
ultimately save lives.
The future of Cardiovascular and Metabolic diseases
Cardiovascular disease
Our scientific area of focus is cardiac regeneration, where we
are investigating potential therapies by activating endogenous
stem cells in the heart to regenerate the lost muscle tissue in
patients with heart failure and cardiac dysfunction post-myocardial
infarction. If successful, such therapies could offer a potential
cure for heart disease.
Diabetes
We are investigating the underlying mechanisms of diabetes,
specifically looking beyond glucose control to studies that include
measurements of microvascular benefit and disease progression,
such as β-cell mass. Our researchers are also exploring avenues
with the potential to stop and reverse diabetes-related kidney
damage, as well as ways to address co-morbidities such as obesity
by targeting appetite control in the brain. In our early programmes
we are aiming to find routes that could stop, reverse or even cure
diabetes through innovative breakthrough science that targets insulin
resistance and increases the functional β-cell mass.
Chronic kidney disease (CKD)
CKD is a critical healthcare problem that affects several millions of
people worldwide.2 New treatments are required to help patients
manage their condition and AstraZeneca is accelerating potential
new therapies using a variety of approaches, including small
molecules, antibodies, peptides and proteins.
Lipid lowering
AstraZeneca is currently running the largest cardiovascular
outcomes trial of any prescription omega-3, STRENGTH, (STatin
Residual risk reduction with EpaNova in hiGh cardiovascular risk
paTients with Hypertriglycerideamia). STRENGTH will provide
important insight into the impact of lowering triglycerides with
EPANOVA (omega-3-carboxylic acids, the only free-fatty acid
prescription omega-3) in combination with statin therapy, in
patients with mixed dyslipidaemia who are at increased risk of
cardiovascular disease.3
Messenger RNA
being read by a
ribosome to produce
signalling proteins.
Helping people
breathe more easily
Through the introduction of new biologics
and more targeted therapies, we can help to
transform the way we treat asthma.
We are making significant progress in
respiratory disease with several projects
in late stage clinical development or
registration. Across both asthma and
COPD, AstraZeneca is progressing latestage clinical development of targeted
biological agents including highly selective
monoclonal antibodies that have the
potential to transform disease management.
In addition to asthma and COPD, our
research could lead to the availability of
the first biological treatment for idiopathic
pulmonary fibrosis, another disease with a
high unmet medical need.
Eosinophil just
before apoptosis.
Natural killer cell
recruited by biologic.
Understanding eosinophils
Our bold ambition is to transform the way
in which we treat asthma.
Eosinophils (a type of white blood cell)
have been shown to play a significant role
in the cause and severity of asthma, and to
be elevated during COPD exacerbations,
thus eosinophil depletion suggests the
potential for significant clinical benefit.
AstraZeneca is working on a unique
monoclonal antibody directed at the
interleukin-5 alpha (IL-5Rα) that depletes
eosinophils and basophils. This research
has the potential to bring a new therapeutic
option to patients with a clear unmet
medical need - the severe eosinophilic
asthma and COPD patients not benefiting
from current treatments.
Transforming inflammation and autoimmune disease
We are developing several promising
investigational agents for the treatment
of inflammation and autoimmune diseases,
including psoriasis, gout, systemic
lupus and rheumatoid arthritis. Our
development programmes are focused
on understanding the shared biological
pathways of these diseases and how their
related pathophysiology differs in
target populations.
We are building a pipeline across the
inflammation and autoimmune spectrum,
with the potential to launch numerous
novel first and best-in-class products in
the next decade.
CRISPR:
Technology
for genome
editing
Pioneering the next generation of drug discovery technology
In order to harness the latest technology and most advanced
scientific knowledge, one approach we are taking is to use what is
effectively a pair of molecular scissors to cut and edit the genome
at specific points. This technique, called CRISPR allows scientists
to make changes in individual genes far faster and in a much more
precise way than ever before. CRISPR will allow us to identify new
genes that are implicated in disease and test whether these genes
and their products could be targets for new medicines in models
that more closely resemble human disease.
We are collaborating with some of the world’s best CRISPR
scientists in line with our porous approach, including those at the
Wellcome Trust Sanger Institute (UK), The Innovative Genomics
Initiative (US), Thermo Fisher Scientific (US) and Whitehead Institute
(US). We will share cell lines and compounds with our partners and
work with them to publish findings of the application of CRISPR
technology, contributing to broader scientific progress in the field.
Source: AstraZeneca PLC. Fourth quarter and full year results 2014, 5 February 2015.
http://www.astrazeneca.com/Research/Our-pipeline-summary. Last accessed 23 February 2015.
AstraZeneca
at a glance
100
We operate in more than
countries worldwide
Third
fastest-growing top 10
multinational pharmaceutical
company in Emerging
Markets in 2014
850
More than
57,500
employees worldwide
Our three main therapy areas:
• Cardiovascular and
Metabolic diseases (CVMD)
• Oncology
• Respiratory, Inflammation
and Autoimmunity (RIA)
$26.1
billion
in worldwide sales in 2014
current collaborations
and partnerships globally
CRISPR gene
editing tool.
118
projects were in clinical
development in 2014
Thirteen
new molecular entities
(NMEs) in late stage clinical
development or under
regulatory review in 2014
We invested over
$4.9 billion
in the discovery and
development of lifechanging medicines
Our three strategic
R&D centres:
• Cambridge, UK Planned global R&D centre
and Corporate HQ
• Gaithersburg, Maryland US
• Mölndal, Sweden
Our
Products
Cardiovascular and Metabolic diseases
Respiratory, Inflammation and Autoimmunity
Trade mark
Generic name
Therapy area
Trade mark
Generic name
Therapy area
Atacand/Atacand HCT/Atacand Plus
candesartan cilexetil
Hypertension/heart failure
Accolate
zafirlukast
Asthma
Brilinta/Brilique
ticagrelor
Acute coronary syndromes
Bricanyl Turbuhaler
terbutaline in a dry powder inhaler
Asthma and COPD
Crestor
rosuvastatin calcium
Dyslipidaemia, hypercholesterolemia
aclidinium/formoterol
COPD
Plendil
felodipine
Hypertension, angina
Duaklir Genuair
(licensed to AZ by Almirall S.A.)
Seloken/Toprol-XL
metoprolol succinate
Hypertension, heart failure, angina
aclidinium
COPD
Tenormin
atenolol
Hypertension, angina pectoris
Eklira Genuair/Tudorza/Bretaris
(licensed to AZ by Almirall S.A.)
Zestril
lisinopril dihydrate
Hypertension
Oxis Turbuhaler
formoterol in a dry powder inhaler
Asthma and COPD
Byetta
exenatide injection
Type 2 diabetes mellitus
Pulmicort Turbuhaler/Pulmicort Flexhaler
budesonide in a dry powder inhaler
Asthma
Bydureon
exenatide extended-release
for injectable suspension
Type 2 diabetes mellitus
Pulmicort Respules
budesonide inhalation suspension
Asthma
Rhinocort
budesonide
Bydureon Pen
exenatide extended-release
for injectable suspension
Type 2 diabetes mellitus
Allergic rhinitis (hay fever),
perennial rhinitis and nasal polyps
Symbicort pMDI
Asthma and COPD
Forxiga/Farxiga
dapagliflozin
Type 2 diabetes mellitus
budesonide/formoterol in a
pressurised metered-dose inhaler
Kombiglyze XR
saxagliptin and metformin XR
Type 2 diabetes mellitus
Symbicort Turbuhaler
budesonide/formoterol in a
dry powder inhaler
Asthma and COPD
Komboglyze
saxagliptin and metformin HCl
Type 2 diabetes mellitus
Myalept
metreleptin for injection
Congenital/acquired
generalised lipodystrophy
Onglyza
saxagliptin
Type 2 diabetes mellitus
Symlin
pramlintide acetate
Type 1/Type 2 diabetes mellitus
Xigduo
dapagliflozin and metformin
hydrochloride
Type 2 diabetes mellitus
Xigduo XR
dapagliflozin and metformin
hydrochloride extended-release
Type 2 diabetes mellitus
Trade mark
Generic name
Therapy area
Arimidex
anastrozole
Breast cancer
Caprelsa
vandetanib
Medullary thyroid cancer
Casodex
bicalutamide
Prostate cancer
Faslodex
fulvestrant
Breast cancer
Iressa
gefitinib
Non-small cell lung cancer (NSCLC)
Nolvadex
tamoxifen citrate
Breast cancer
Lynparza
olaparib
Ovarian cancer
Zoladex
goserelin acetate implant
Prostate cancer, breast cancer
gynaecological disorders
Oncology
Atlas Approval ID: 687,023.011
Date of preparation February 2015
Date of expiry February 2016
AstraZeneca PLC
2 Kingdom Street
London
W2 6BD
T: +44 (0)20 7604 8000
www.astrazeneca.com