Delivering the next wave of scientific innovation - Innovative Medicines and Early Development Biotech Unit 2017 - A year in review - AstraZeneca
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Delivering the next wave of scientific innovation Innovative Medicines and Early Development Biotech Unit 2017 – A year in review
New modalities
Introduction
In our aspiration to transform disease,
we recognise the need to target the
By 2017, the IMED portfolio was
enhanced by collaborative work on
Contents
novel biology we uncover, and as our seven modalities as well as small
understanding of molecular mechanisms molecules: modified mRNA, antisense
advances, our modalities are also oligonucleotides (ASOs), oligonucleotide
becoming more diverse. We are opening conjugates, bicyclic peptides, proteolysis
up a new world of therapeutics beyond targeting chimeras (PROTACs),
small molecules, focussed on the therapeutic proteins and Anticalin®
molecular machinery of cells. molecules. This ever-growing diversity Introduction
is helping AstraZeneca to pioneer new 02 The next wave of scientific innovation:
Modified mRNA therapy, depicted in the approaches to drug discovery. An introduction from Mene Pangalos
image, is an example of an exciting new
modality which enables tissue specific 04 IMED Biotech Unit 2017 in numbers
Therapy area progress
production of a target protein from a 06 Case Study: 5R Framework
clinical grade mRNA transcript.
Therapy area progress
08 IMED Oncology
18 IMED Respiratory, Inflammation and Autoimmunity
28 IMED Cardiovascular, Renal and Metabolism
38 IMED Neuroscience
IMED functions
IMED functions
46 Case Study: Artificial Intelligence and machine learning
50 Discovery Sciences
58 Drug Safety and Metabolism
66 Early Clinical Development
78 Pharmaceutical Sciences
88 Precision Medicine and Genomics
Collaborating for science innovation
98 Case Study: Expanding our science and platforms beyond small molecules
102 Achieving scientific leadership through entrepreneurial partnerships
science innovation
Collaborating for
106 Innovation without boundaries
108 Open Innovation
112 Case Study: New joint venture promotes innovation in medical science
An environment where science thrives
114 Inspiring great scientists
116 Our thriving science centres and biohubs
120 A milestone year for our Cambridge site
122 Our reputation for scientific leadership
126 High impact publications in 2017
where science thrives
An environment
130 Preparing for the future with our IMED Futures teams
132 IMED Events 2017
mRNA being read by
a ribsome to produce
signalling proteins
Delivering the next wave of scientific innovation 01
Introduction
Introduction
The next wave of
scientific innovation: I am immensely proud of our
An introduction from
scientific leadership and our
ability to follow the science.”
Mene Pangalos
Therapy area progress
Mene Pangalos
Executive Vice President
IMED Biotech Unit and Global
Business Development
As I reflect on the We published our second 5R framework such as modified RNA and antisense Our biotech-style operating model gives Genomics and renamed the function as
publication in Nature Reviews Drug oligonucleotides are already in clinical us access to the best science, both a consequence. Our focus and emphasis
transformation we have
Discovery in January 2018, detailing development. In partnership with Moderna, internal and external, and we are open on precision medicine means that 2017 was a defining year
made in the IMED Biotech how we have achieved greater than five‑fold we were granted the Phase IIa clinical trial to exploring new and different kinds of approximately 90 per cent of our clinical
Unit over the past seven increase in our success rates since 2012 application for AZD8601, a modified RNA collaborations. In 2017, we entered into pipeline follows a precision medicine for AstraZeneca. It was a
years, 2017 was an inflection from pre-clinical development to Phase for vascular endothelial growth factor A key partnerships with Imperial College, the approach, a 10 per cent increase from year in which our IMED
III completion – from four per cent to (VEGF-A) to explore cardiac regeneration Crick Institute, and the Medical Research 2016. Our in-house Centre for Genomics Biotech Unit flourished and
point for me. The end of one 19 per cent against an industry average in patients undergoing coronary artery Council – Laboratory of Molecular Biology Research has now analysed over 200,000
IMED functions
chapter and the beginning that remains around four to five per cent. bypass graft surgery with moderately (MRC-LMB), to further our understanding genomes, representing 10 per cent of our continued to drive research and
of another. We are now in This has been achieved by embedding
impaired systolic function. In immuno- of the underlying biology of disease, with two million target by 2026, and shows development productivity.
oncology, and in partnership with Ionis the intent to publish all output in journals our commitment to bringing innovative
the best position we have the 5R framework into everything we
Therapeutics, AZD9150, our antisense of the highest impact. Specifically with targeted medicines to the patients most
The diversity of our early
do, and at the same time establishing pipeline is pushing the
ever been to enable the oligonucleotide signal transducer and Imperial College, one collaboration likely to benefit.
an open, collaborative, ‘truth seeking’
translation of innovative culture with scientific rigor at its heart.
activator of transcription 3 (STAT3) moved consists of supporting a Joint Research
I am immensely proud of our scientific boundaries of science,
into Phase IIb clinical trials, and is being Fellowship programme and the second
science into medicines. We focussed investment across our
evaluated for anti-tumour activity in creates a joint Respiratory Hub where
leadership and our ability to follow the delivering the next wave of
core therapeutic areas. This has brought science. In 2017, we continued to publish
combination with our PD-L1 inhibitor, our scientists will work side-by-side with innovation beyond small
several new medicines to patients such high quality science from our laboratories
following completion of Phase Ib. Also Imperial scientists. With the MRC-LMB molecules, and strengthening
as osimertinib, olaparib, acalabrutinib, and partnerships. We published 44 high
in 2017, we forged new partnerships Blue Sky programme, we have funded
ticagrelor, lokelma and avibactam with
with APT Therapeutics, accessing their 22 research projects. One breakthrough
impact and 344 high quality publications, our position as a thought
several potential new medicines in Phase and a total of 625 publications overall.
III or under registration. At the same time
therapeutic protein platform; with Pieris to project, published in Science Advances
This demonstrates the quality and
leader in precision medicine
develop novel inhaled drugs that leverage has applied cutting-edge cryo-electron
science innovation
Collaborating for
we have broadened our drug modalities, depth of our science and the strength and genomics. Our continued
Pieris’ Anticalin® platform, and with Bicycle microscopy to uncover novel structures
so we could follow the biology. Our work of the scientific partnerships we have success and growth is
Therapeutics in support of respiratory of ataxia-telangiectasia mutated, a key
goes beyond small molecules, with about established around the world. This puts
30 per cent of our programmes now using
and cardiovascular diseases to develop protein in DNA damage response for
us as one of the leading industrial R&D driven by our agile and
a new class of therapeutics based on IMED Oncology.
new modalities, a testament to our trying
its proprietary bicyclic peptide product
centres for published scientific research entrepreneurial culture, our
to make every target druggable. Modalities In 2017, IMED continued to pioneer relative to our peers. We are starting to network of partnerships and
platforms.
new approaches to open innovation, turn science fiction into science fact.
Looking more broadly at our clinical enabling our scientists to share their ideas the extraordinary people who
Whilst it is impossible to capture all of the
progress, in 2017 eight new molecular more freely and collaborate on projects
achievements from across our teams in the
make up our workforce, all
entities (NME) transitioned from across with external scientists. The IMED of whom are committed to
past year, I hope the IMED Annual Review
our therapy areas and a further eight Open Innovation portal allows external
2017 gives you a feel for the outstanding delivering our science
non-NMEs transitioned in oncology, researchers to access the full range of
calibre of our science and our scientists,
expanding the number of novel open innovation programmes. By the end
and how we strive to push the boundaries to patients.”
combination studies ongoing. We of 2017, our teams had reviewed more
of science to deliver life-changing Pascal Soriot, CEO AstraZeneca
where science thrives
An environment
continued to fuel our pre-clinical and than 500 proposals for new drug projects.
medicines for patients around the world.
Phase I pipeline with exciting new Of these, 26 have progressed as far as
molecules against targets notoriously clinical trials, while more than 150 are in
difficult to drug, such as MCL1 and the pre-clinical stage.
KRAS in oncology. Our aim is to be able
To reflect the broad range of cutting-
to design a chemical lead for any novel
edge technologies used in IMED,
biological target.
including molecular diagnostics, tissue Mene Pangalos
diagnostics, next generation sequencing Executive Vice President
and point of care diagnostics, we took IMED Biotech Unit and Global
Cells under a microscope the decision to move from Personalised Business Development
Healthcare to Precision Medicine and
02 IMED Annual Review 2017 Delivering the next wave of scientific innovation 03
Introduction
Introduction
IMED Biotech Unit
2017 in numbers
~90%
of projects with
a precision medicine
120
Therapy area progress
approach
post docs 2,400
people in
IMED
61 74
16 new
IMED functions
clinical Open Innovation
combination projects projects
Phase I
19
in oncology
and II NME
starts
diagnostics
launched
625 1,165
35
science innovation
Collaborating for
current
3
peer reviewed
collaborations
publications NME clinical
44
high impact
Phase III
investment
projects
decisions
433
publications
~30%
where science thrives
An environment
new hires
of our pipeline
is new modality
Cardiac regenerating muscle cells
04 IMED Annual Review 2017 Delivering the next wave of scientific innovation 05
Introduction
Case Study
5R framework:
Right Target
By implementing a stronger focus on biological rationale and
understanding of the target, we have markedly reduced the number of
A four-fold increase in research projects in our discovery portfolio. We have expanded the classes of drug
targets that we are investigating and doubled our ‘hit to lead’ success rate
and development productivity
from 23 per cent to 48 per cent. Our expansion into new modalities beyond
small molecules has enabled us to work on more novel drug targets, many
of which were previously considered undruggable (e.g. KRAS).
over five years Right Tissue
Therapy area progress
We are increasingly using biomarkers to confirm that our compounds
are engaging with desired targets and are active in the right tissues. This
is because evidence of target engagement or proof of mechanism is
Following a major review of our research and development strategy in 2010, key to improving the probability of project success. We are carrying out
we created a 5R framework to guide how we discover and develop new drug research to clearly demonstrate that a candidate drug is engaging the
target at a predefined and quantitative level, with a functional effect. By
candidates. Looking at our productivity and success rates over the past five years
improving our pre-clinical models for measuring the pharmacokinetics,
we can now see a transformation in our productivity – enabling us to increase our pharmacodynamics, absorption, distribution, metabolism and excretion of
chances of turning science into medicine. our molecules, we are enhancing candidate selection and have improved
dose-setting and exposure predictions in the clinic by 18 per cent.
Right Safety
Through changes to the way we assess safety, we can now identify
A recent analysis, published in Nature Reviews Drug Discovery In a high risk industry with
IMED functions
early pre-clinical safety signals and integrate in vitro and in vivo data for
explains how our 5R framework (right target, right patient, right quantitative risk assessment of future human use. This includes exploring
tissue, right safety, right commercial potential) has helped
a well documented decline
the physiological role of a target in health and disease, and performing
guide successful, efficient drug discovery and development. in productivity, I am proud in silico and in vitro safety assays on molecules with potential for lead
In five years, we have achieved a four-fold improvement in the to see the impact of our 5R generation to understand their possible impact on key organs. Additional
proportion of pipeline molecules advancing from pre-clinical in vitro and in vivo assays across species are carried out as projects move
investigation to completion of Phase III clinical trials – from four framework on the pipeline.
closer to candidate selection, including microtissue and human organoid
per cent to 19 per cent. This improvement moves AstraZeneca There is still much room tests, in order to gain clearer insights into potential toxicity than previously
well above the average success rates of six per cent for small for improvement but we possible. Following the introduction of our right safety focus, there was a
molecules in the 2013-2015 timeframe (Data sourced from greater than four-fold decrease in our pre-clinical safety attrition rate.
CMR International’s 2016 Global Research and Development expect that our continued
Performance Metrics Programme). focus on scientific rigour Right Patient
The 5R framework has become embedded into the way we work in and collaboration, precision At inception of a drug discovery project, we work on defining ways of
the IMED Biotech Unit, and its success is based on improvements stratifying patients to identify those most likely to benefit from treatment.
medicine and other emerging
science innovation
Collaborating for
across our research and development operation. At the heart Across our pipeline, projects with a strong focus on patient selection
of this transformation has been our change in culture. We have technologies will further were more likely to move into the next phase in development — 62 per
established a collaborative ‘truth seeking’ culture where science enhance our capability for cent for those with patient versus 44 per cent with no selection strategy.
thrives. A stimulating culture, where we ask the ‘killer questions’ This facilitates timely development of biomarkers to identify the ‘right
translating science into patient’ for treatment and, where appropriate, development of
and rigorously test our hypotheses. A culture, which has enabled
us to improve the quality of the drug candidates we take forward innovative medicines for the companion diagnostics.
into pre-clinical studies and into clinical trials. patients who need them.” Right Commercial potential
Mene Pangalos, Executive Vice In research and early development, teams need to understand the
President, IMED Biotech Unit and key questions that will position this programme competitively from
Project success rates Global Business Development the perspective of differentiation relative to future standard of care.
100 Experiments in the laboratory and the clinic need to set efficacy and
tolerability benchmarks using appropriate comparators. By the time
88 a project reaches a Phase III investment decision, we are committed
where science thrives
An environment
to ensuring that a thorough commercial assessment has been
72
71 71 70 made, with clarity around the patient population, the unmet medical
66 66
59 60 2005-10 (industry) need, differentiation versus standard of care, payer criteria for global
59
Percentage
51 reimbursement, competitive environment and sales projections.
2005-10 (AZ)
46
43
2003-15 (industry)
2012-16 (AZ)
22
18 19
15
6 4 4
0 Pre-clinical Phase I Phase II Phase III Overall
06 IMED Annual Review 2017 Delivering the next wave of scientific innovation 07
Therapy area progress
“2017 was a pivotal year for Oncology, with with durvalumab. In addition, we moved our
Introduction
important data readouts for osimertinib, cell death portfolio into the clinic. Translational
Oncology olaparib, durvalumab and acalabrutinib. We
made exciting progress with combinations:
science has been critical to these developments
and is helping to ensure we treat patients who
olaparib with other agents from our DNA are most likely to benefit from our innovative
damage response (DDR) portfolio, savolitinib approaches.”
with osimertinib, and AZD9150, our antisense Susan Galbraith, Vice President, Head of IMED Oncology
oligonucleotide (ASO) signal transducer and
activator of transcription 3 (STAT3) inhibitor,
Aurora B nanoparticle
Therapy area progress
IMED functions
science innovation
Collaborating for
where science thrives
An environment
08 IMED Annual Review 2017 Delivering the next wave of scientific innovation 09
Therapy area progress
Introduction
Oncology
Therapy area progress
During 2017, IMED Oncology made substantial advances, People spotlight Andrew Pape, Vice President
Strategy Oncology
Ultan McDermott, Chief Scientist
Ultan McDermott joined
Wenlin Shao, Project leader
Wenlin Shao is a director and global
delivering six investigational new drugs (INDs) and
Andrew Pape joined AstraZeneca AstraZeneca in December 2017 as project leader in IMED Oncology.
in 2017. His oncology expertise Chief Scientist in IMED Oncology. Prior to joining AstraZeneca
and wealth of experience in the Ultan is a clinician scientist, with a in 2016, Wenlin was a project
providing wide ranging translational support for clinical pharmaceutical industry are a great
contribution to IMED Oncology.
Andrew is a member of the IMED
lifelong interest in understanding
how cancer genomes influence
response to therapy in the clinic, and
and group leader at Novartis
Oncology having led multiple drug
discovery programmes from pre-
programmes. We delivered combination data including Oncology Leadership Team and
plays a key role in the direction of
more recently in the mechanisms
of drug resistance. Much of his
clinical research to early clinical
development. Wenlin is currently
savolitinib with osimertinib, and AZD9150 with durvalumab.
oncology strategy at an enterprise recent focus has been on the use of leading several oncology projects
level and within IMED. Andrew genome-wide Clustered Regularly including in 2017 the successful
also leads the Strategy Group, Interspaced Short Palindromic delivery of candidate drug
a team of scientific experts with Repeats (CRISPR) and chemical AZD4573 (CDK9) for its first time
responsibility for collaborations, mutagenesis screens to define the in man study. In addition, Wenlin
alliances and partnerships. drug resistance landscape for a is one of the key drivers of the cell
The group engages with leading number of therapeutic agents. death portfolio and is integrally
IMED functions
scientific institutions and clinical He has also published extensively involved in shaping and developing
centres across the globe, in in the area of cancer genomics, and the Haematology Franchise through
addition to the biotech community. has been a senior author on papers the collaboration with Acerta.
With Andrew’s lead, the team foster in Nature, Cell and Cell Reports.
and establish relationships which Ultan joined the Sanger Institute in
are essential to our continued 2009 as a clinical research fellow
immersion in innovative science and was appointed to the faculty as
and the delivery of novel medicines a Group Leader in 2010 following
to cancer patients. the award of a Cancer Research UK
Andrew trained as a chemist Clinician Scientist Fellowship. He
and has a PhD from University of has also worked as a postdoctoral
Cambridge. He was previously a fellow with Jeff Settleman on
team leader in medicinal chemistry high-throughput cancer cell line
at Alderley Park, before moving drug screens at Massachusetts
to Basel in 2009. He has re- General Hospital Cancer Center. He
joined AstraZeneca from Novartis is a Fellow of the Royal College of
With acalabrutinib, a Bruton’s tyrosine In 2017, our other DDR agents targeting In 2017, IMED scientists Ray Finlay, Physicians and continues to practice
science innovation
Collaborating for
where he was Global Head of
kinase (BTK) inhibitor, we have the WEE1, ataxia telangiectasia and Rad3 Richard Ward and Darren Cross Strategy in the Novartis Institutes as an oncologist at Addenbrooke’s
potential of a backbone therapy for B-cell -related protein (ATR) and ataxia received the Malcolm Campbell Award for BioMedical Research (NIBR) Hospital in Cambridge. He holds
driven cancers with which to combine telangiectasia mutated kinase (ATM) for ‘excellence in medicinal chemistry’ Oncology Disease Area. an Honorary Faculty position at the
Sanger Institute.
our cell death portfolio agents and with progressed in the clinic, and systematic relating to the pioneering research that
the aim of establishing a strong franchise research has been carried out to improve led to the discovery of osimertinib. The
in haematology. We are evaluating understanding of the mechanism of prestigious award is awarded biennially Oncology tumour drivers – cell surface and lipid bilayer with receptor
new compounds in patients with blood resistance to poly ADP-ribose polymerase by the Royal Society of Chemistry to
cancers, with three new projects entering (PARP) inhibition in different cancer researchers who have contributed
the clinic in 2017-18 – AZD5991, inhibitor types with a focus on PDX models. seminal research in the area of chemical
of myeloid cell leukemia 1 (MCL1), Furthermore, our partnership with Merck science and drug discovery.
AZD4573, a cyclin dependant kinase aimed to deepen, broaden and extend
As we move forward with development
(CDK9) inhibitor and AZD0466, a B-cell responses to olaparib in new patient
of our new modalities, including
lymphoma 2/extra large (BCL2/xL) populations, and to develop a better
oligonucleotides and nanoparticles,
nanoparticle – targeting complementary understanding of resistance in the clinic.
we will target novel mechanisms, such
where science thrives
An environment
aspects of cell death mechanisms.
Our immunotherapy portfolio has as tumour microenvironment and
In women’s cancers, we continue to expanded, with developments in three resistance. There will also be further
focus on the role of the estrogen receptor clinical programmes and extended pre- investment in protein degradation and the
(ER) in breast cancer and the multiple clinical capabilities and new targets. We development of a therapeutic proteolysis
ways it can be degraded, advancing are using a broad biomarker platform to targeting chimera (PROTAC) platform to
our mechanistic understanding with predict sensitivity to agents targeting the further increase the number of patients
enhanced patient derived xenograft (PDX) immune myeloid cells in tumours and to with cancer who can benefit from our
model capabilities, and supporting label explore further combinations from our therapies in the future.
extensions for our selective ER degrader DDR and immunotherapy portfolios.
(SERD) fulvestrant.
10 IMED Annual Review 2017 Delivering the next wave of scientific innovation 11
Therapy area progress
Introduction
Oncology
Highlights
We set out to We delivered We set out to We delivered
Deliver the most effective anti- AstraZeneca continued to develop our industry leading portfolio of endocrine therapies with the aim
Progress savolitinib, our potent We progressed evaluation of savolitinib in collaboration with our Global Medicines Development
to treat patients with hormone receptor positive (HR+) breast cancer. The development of our next (GMD) colleagues, by continued enrolment in a clinical study in c-MET-driven EGFR mutation
hormonal therapies for patients generation oral SERD, AZD9496, has had the first patients evaluated in a ‘window of opportunity’, and highly selective small molecule positive non-small cell lung cancer (NSCLC), combining savolitinib with osimertinib in the TATTON
pre-surgical clinical trial. This innovative trial is comparing head-to-head the degree of ER
with hormone receptor positive degradation induced by AZD9496 and fulvestrant. This is testing the hypothesis that the improved inhibitor of the c-Met receptor trial and completing enrolment with gefitinib in a trial in China. Initiation of these studies was based
on strong science highlighting the co-dependence on both c-MET and EGFR in some cancers and
breast cancer pharmacokinetic cover potentially afforded by an orally bioavailable SERD will translate into more
tyrosine kinase in combination the potential for combining inhibitors targeting both of these receptor tyrosine kinases in a subset
complete target engagement. We pioneered this approach during the development of fulvestrant,
Therapy area progress
of patients with lung cancer. Clinical data were presented at the World Congress on Lung Cancer
where the increase in dose from 250 mg to 500 mg resulted in more ER degradation. with osimertinib in Japan in 2017. A Phase III investment decision was made in 2016 for c-MET-driven papillary
In pre-clinical research, we are building a panel of HR+ breast cancer patient derived xenografts renal cell cancer (PRCC). Initiation of the Phase III trial in PRCC occurred in 2017, with enrolment
(PDX), utilising models developed within AstraZeneca and with academic collaborators and contract ongoing. Savolitinib monotherapy continues to be explored in Phase I/II studies in other cancers,
research organisations. We are partnering with Champions to develop new PDX models from including stomach, kidney and lung, and in combination with durvalumab, a programmed death-
patients progressing on current standard of care therapies. We are also investigating alternative ligand 1 (PD-L1) antibody, in kidney cancer.
modes of action to cause ER degradation as potential future therapeutic options.
Complement and broaden our Together with our colleagues in IMED Scientific Partnering and Alliances, we successfully
Accelerate progress in key strategic We accelerated development of key DDR assets in the clinic, with the addition of DDR-DDR
industry leading oncology portfolio
partnered and licensed innovative opportunities that are key to the industry leading portfolio we
have today. The programmes below are all in clinical trials to evaluate their potential:
combinations to multiple basket trials. Significant progress has been made in defining robust doses
DDR areas and maximise the for combinations of AZD1775 (WEE1 inhibitor), and olaparib, and our blood brain barrier penetrating
as a partner of choice AZD9150: a first-in-class, ASO inhibitor of STAT3, was licensed from Ionis Pharmaceuticals, and is
AZD1390 (ATM inhibitor) which was dosed in the first healthy volunteer. Through tumour profiling,
potential of our agents in the clinic evidence of DDR associated immunogenicity in the clinic led to the development of novel DDR/
evaluated for anti-tumour activity in combination with durvalumab.
Savolitinib: a highly selective small molecule inhibitor of c-MET, partnered with Hutchison Pharma,
immuno-oncology (IO) combinations, with promising early data from clinical trials.
is being evaluated in c-MET-driven cancers. It is currently in a confirmatory Phase III trial in PRCC,
We established teams dedicated to building our pre-clinical capability, to increase mechanistic is also being evaluated in a Phase II trial in patients with a certain type of lung cancer.
understanding of our DDR agents, and, with investment in technology to measure replication
IMED functions
AZD1775: a novel small molecule inhibitor of WEE1 kinase was licensed from Merck and is
dynamics, to facilitate better understanding of replication stress in cancer and the targeting of the
currently being evaluated in Phase II trials as part of our industry leading DDR pipeline.
replication stress response. Development of syngeneic models has enabled pre-clinical assessment
of DDR/IO combinations, and we are building a panel of PDX models with DDR mutations for pre- We are also creating opportunities to assess the full potential of our oncology portfolio through
clinical and co-clinical trial studies. Emerging data from external collaborations, using PDX models new external partnerships. Dizal Pharmaceuticals was recently established through a joint venture
will guide differentiation of DDR inhibitor combinations. between AstraZeneca and the China State Development and Investment Corporation (SDIC).
Through this venture we are able to leverage the capabilities of AstraZeneca’s Innovation Centre
The accelerated programme with AZD6738 (ATR inhibitor), and olaparib resulted in important
China (ICC) unit to create value from existing and new portfolio projects across disease areas.
insights of dose and schedule, with Phase II trials initiated in both gastric and breast cancer.
IMED Oncology contributed AZD4205 (Janus kinase 1 (JAK1) inhibitor), to the joint venture and we
The VIOLETTE multi-centre clinical study, designed to investigate AZD6738 versus AZD1775 in expect the initiation of clinical trials in patients with lung cancer during 2018.
combination with olaparib in breast cancer, was initiated in 2017, with tolerability data expected
in 2018. In addition to providing proof of concept regarding the potential of DDR inhibitors in
combination with olaparib, the study, which includes patients with homologous recombination repair
(HRR) mutations including BRCAm, as well as HRR proficient cancers, is expected to deliver key Expand and progress our We progressed three clinical programmes, AZD9150 (STAT3 inhibitor), AZD5069 (chemokine receptor
2 (CXCR2) antagonist), and AZD4635, (adenosine A2a receptor (A2AR) antagonist). The study of
data on patient selection strategies for these two DDR-DDR combinations.
portfolio of small molecule AZD9150 and durvalumab in metastatic head and neck cancer has enrolled the target patient
Our global strategic collaboration agreement with Merck to co-develop and co-commercialise cohort and interim data were presented at the annual congress of the European Society for Medical
olaparib, provides an opportunity to evaluate the potential for olaparib combinations across immuno-oncology agents and Oncology (ESMO) in 2017. We have initiated a Phase II study to evaluate AZD5069 in combination
multiple tumour types. We have already had productive discussions on trial design and translational
increase our ability to model with durvalumab in metastatic pancreatic cancer, and Phase II monotherapy and combination studies
science innovation
Collaborating for
endpoints and aim to accelerate development of olaparib and selumetinib. with durvalumab. In addition, we successfully transitioned multiple pre-clinical projects through
tumour immunobiology key investment decisions and we added several additional new targets for potential therapies for
lymphoid and myeloid cancers to our early discovery portfolio.
We developed a suite of in vitro and in vivo models that enable the impact of specific molecules on
key drivers of the immune system to be assessed. This includes investigating innovative ways of
generating mouse genetic models of cancer and exploring the interaction between DNA damage
and the immune system, via paired biopsies from the AZD9150 programme, with changes in
tumour microenvironment. This is giving us fresh insights related to the STAT3 combination with
durvalumab. Furthermore, as part of a Cancer Research UK Grand Challenge team to map tumours
in unprecedented detail, which we hope will improve our understanding of cancer, allowing us to
identify new and better ways to diagnose and treat the disease.
where science thrives
An environment
Antibody that blocks inhibitory signals from the tumour to cells of the
immune system resulting in enhanced anti-tumour immunity
12 IMED Annual Review 2017 Delivering the next wave of scientific innovation 13
Therapy area progress
Introduction
Oncology
Redefining treatment of haematological malignancies with a new class of medicines Targeting STAT3 to boost the immune response against cancer
Recent advances in understanding of Another study is exploring the dosing haematological disease. This is based on The field of immuno-oncology (IO) is AZD9150 is an ASO that targets STAT3
the pathogenomic signalling pathways of acalabrutinib with AZD6738 (ATR extensive cell panel screening and the contributing to the evolving treatment mRNA, leading to the depletion of
of haematological malignancies are inhibitor), which has previously shown activity seen in pre-clinical combination possibilities for patients with later stage STAT3 protein and a reduction in signals
transforming the way we are addressing potential in tumours that are deficient for studies with various agents, including cancer. The FDA has issued a number of through the STAT3 pathway. In 2013-
these challenging diseases, which ATM function. acalabrutinib. approvals in recent years for the class of 2014, we performed a translational
currently account for more than 10 per agents known as PD-1/PD-L1 checkpoint science analysis of tumour tissues
A class of drug targets that is of particular The breadth of our haematology pipeline
cent of all cancer deaths. blocking antibodies. This new class collected from patients with late stage
interest in haematology is the ‘cell death’ presents a unique opportunity to use
of drugs, which includes durvalumab, lymphoma from a monotherapy study with Oncology pipeline
Therapy area progress
We are prioritising development of group. We are designing compounds master protocols to rapidly evaluate the
engages the immune system to induce AZD9150. Those analyses revealed that
combinations of this BTK inhibitor with which are intended to antagonise these numerous monotherapy and combination
durable tumour responses, in a subset of AZD9150 targeted STAT3 in several cell Pre-clinical
promising compounds from our exciting pro-survival proteins (BCL2 family) which opportunities in key diseases such as
patients. However, approximately 75 per types of the tumour microenvironment,
oncology pipeline. These combinations tumours up-regulate to avoid apoptosis. DLBCL, acute myelogenous leukaemia AZD0346 / ERK
cent of patients with responsive types including immune cells. In addition,
provide the opportunity to strengthen The class has been validated clinically (AML), MCL and follicular lymphoma AZD0466 / Bcl2-xl
of disease do not derive durable benefit gene expression profiling showed that
responses in diseases where some through the approval of venetoclax (BCL2 (FL). ‘PRISM’ is such a study, evaluating
from PD-1/PD-L1 blocking antibodies, in patients treated with AZD9150, the AZD7648 / DPKB
other BTK inhibitors have already been inhibitor) in CLL and AstraZeneca is three to five treatment arms per annum
and there is a continuing unmet need tumour microenvironment was altered in AZD3458 / PI3Kg
approved, such as chronic lymphocytic evaluating a BCL2/xL dual inhibitor which in a highly characterised population of
for treatment. a way that may make it likely to respond
leukaemia (CLL), and establish their has the potential to follow suit. MCL1 is DLBCL patients. Investigator interest
to PD-1/PD-L1 drugs. In parallel, clinical Phase I
potential role in settings, such as another member of this family of proteins has been very strong and the study
biomarker studies showed the effects of
diffuse large B cell lymphoma (DLBCL) that tumours use to avoid cell death, and design should allow more rapid and
STAT3 blockade, in combination with PD- AZD4573 / CDK9
where monotherapy data have been is being targeted directly by AZD5991 efficient evaluation of combinations in
L1 blockade in several disease models. AZD2811 / AURN
less impressive. which disturbs the protein-protein this difficult disease where high quality
These clinical and pre-clinical mechanistic AZD0156 / ATM
interaction between MCL1 and pro-death genetic information is going to be critical
In 2017, we initiated a study in DLBCL studies, led us to hypothesise that treating
IMED functions
effectors. A complementary approach is in identifying responder populations. AZD4785 / KRAS
combining acalabrutinib with vistusertib patients with anti-PD-1/PD-L1 drugs,
being developed with AZD4573 (CDK9 AZD5153 / BRD4
(dual TORC1/C2 inhibitor) based on the in combination with AZD9150 could
inhibitor), which provides an indirect
promising pre-clinical data, and will overcome immune suppression in the AZD5991 / MCL1
method of inhibiting both MCL1 and MYC.
evaluate the initial clinical benefit in a tumours and potentially lead to improved AZD1390 / ATM-BBB
These three ‘cell death’ agents are being
DLBCL all-comer population exploring Immune response to cancer – white blood patient outcomes. AZD9496 / SERD
evaluated clinically with a strong focus on
both continuous and intermittent dosing. cells attacking a cancerous cell
In 2014, we initiated a Phase II study
(named SCORES) investigating the Phase II
combination of AZD9150 and durvalumab
AZD1775 / WEE1
inute pieces of circulating tumour
M in patients with metastatic head and neck
DNA in the bloodstream
cancer who may or may not have received AZD6738 / ATR
prior immunotherapy. These proof of AZD9150 / STAT3
concept data were presented at the AZD5069 / CXCR2
Tumours are complex tissues that have
ESMO congress in 2017 and generated a
microenvironments comprised of multiple AZD8186 / PI3Kβ
science innovation
Collaborating for
lot of positive interest. The programme is
cell types besides malignant tumour AZD4635 / A2aR
expanding quickly to other disease types
cells. A tumour may be infiltrated by AZD5363 / AKT
to more broadly evaluate the concept
immune cells recruited by malignant cells.
of blocking multiple checkpoints to AZD4547 / FGFR
The tumour takes on the normal immune
overcome immune suppression from the vistusertib / TORC1/2
function of these cells to counteract the
tumour microenvironment.
patient’s ability to mount an immune
response. In some cases, this prevents Phase III / LCM
IO drugs, from benefiting the patient.
savolitinib / MET
STAT3 is a transcriptional factor that olaparib / PARP
is crucial to the function of several osimertinib / EGFR
types of immune cells, and aberrant
acalabrutinib / BTK
signalling has been shown to lead to
immunosuppression in several cancers. selumetinib / MEK
where science thrives
An environment
fulvestrant / ER antagonist
Pipeline correct as of Q4 2017, not
including MedImmune programmes.
14 IMED Annual Review 2017 Delivering the next wave of scientific innovation 15
Therapy area progress Key publications in 2017
Introduction
Oncology
Publication Title Author
A selection of key collaborations in 2017 Journal of Clinical Oncology Osimertinib as first-line treatment of EGFR Ramalingam SS, Yang JC, Lee CK, Kurata T, Kim
DW, John T, Nogami N, Ohe Y, Mann H, Rukazenkov
mutation-positive advanced non-small-cell lung
cancer Y, Ghiorghiu S, Stetson D, Markovets A, Barrett JC,
Thress KS, Jänne PA
1. 4. 8.
University of Cambridge, UK University of Oxford, UK Institute for Cancer Research, UK
We are working with Steven Jackson on in vitro We are collaborating with Anderson Ryan Christopher Lord is using combination CRISPR Nature Medicine HRDetect is a predictor of BRCA1 and BRCA2 Davies H, Glodzik D, Morganella, S, Yates LR, Staaf
J, Zou X, Ramakrishna M, Martin S, Boyault S,
screens to investigate resistance to DDR to evaluate the biological responses of screens to identify novel genetic determinants deficiency based on mutational signatures
inhibitors in order to identify genetic components combinations of DDR inhibitors. The of tumour response to DDR inhibitors. This work Sieuwerts AM, Simpson PT, King TA, Raine K, Eyfjord
in ATM-deficient cells that drive the sensitivity collaboration focusses on fractionated may identify patient selection hypotheses and JE, Kong G, Borg A, Birney E, Stunnenberg HG, van
and resistance. Depending on the resistance radiotherapy to both the tumour and surrounding insights into mechanisms of action. de Vijver MJ, Borresen-Dale AL, Martens JWM, Span
profile to the different inhibitors observed, normal tissue in a novel autochthonous PN, Lakhani SR, Vincent-Salomon A, Sotiriou C, Tutt
9. A Thompson AM, Van Laere S, Richardson AL, Viari
rational combinations may be tested to provide syngeneic mouse model of lung cancer.
Therapy area progress
synergistic effects or to overcome resistance. University of Cambridge, UK A, Campbell PJ, Stratton MR, Nik-Zainal S
5. The Carlos Caldas collaboration investigates
2. MD Anderson Cancer Center, USA the use of patient derived breast tumour models
Vanderbilt University School of Medicine, USA With John Heymach, we are evaluating DDR to understand the pathways and biomarkers Journal of Clinical Oncology AKT inhibition in solid tumors with AKT1 mutations Hyman DM, Smyth L. Donoghue MTA, Westin SN,
Bedard PL, Dean EJ, Bando H, El-Khoueiry AB,
Dr. Cortez’s laboratory uses the iPOND technique inhibitors and IO agents in pre-clinical models of involved in the response to novel therapies. A
Perez-Fidalgo J, Mita A, Schellens JHM, Chang
they developed that provides mass spectrometry KRAS-mutant lung, head and neck cancer. The number of novel, large scale analysis techniques
MT, Reichel JB, Bouvier N, Selcuklu SD, Soumerai
characterisation of protein changes at DNA effect of DDR-IO combinations on tumour cell have been used for these studies, including RNA
TE, Torrisi J, Erinerji JP, Ambrose H, Barrett JC,
replication forks. This is achieved by treating death, growth and metastasis, and on the tumour sequencing and mass cytometry (cytometry by
Dougherty B, Foxley A, Lindermann JPO, McEwen
cancer cell lines with DDR inhibitors such as immune microenvironment will be assessed. Time of Flight, CyTOF).
R, Pass M, Schiavon G, Berger MF, Chandarlapaty
ATR, WEE1 and olaparib, and observing the level
6. 10. S, Solit DB, Banerji U, Baselga J, Taylor BS
of replication stress following treatment. The
goal is to gain insights into the use of different Beatson Institute, UK Samsung Medical Centre, South Korea
combinations of DDR agents and identify the Together with Owen Sansom, we are studying Jeeyun Lee and Keunchil Park are Principal
genetic backgrounds where these approaches the impact of novel therapeutics on the tumour Investigators of the Phase II VIKTORY and Journal of Clinical Oncology Biomarker-based Phase II trial of savolitinib in Choueiri TK, Plimack E, Arkenau HT, Jonasch
E, Heng DYC, Powles T, Frigault MM, Clark EA,
patients with advanced papillary renal cell cancer
are most impactful. microenvironment in genetically engineered SUKSES umbrella clinical studies in gastric Handzel AA, Gardner H, Morgan S, Albiges L,
models of colorectal and pancreatic cancer. cancer and small cell lung cancer, designed to Pal SK
3. As part of the collaboration, immune checkpoint enable signal seeking in molecularly-selected
IMED functions
University of Pittsburgh, USA inhibitors are combined with the novel agents to patients. Emerging clinical and translational
Chris Bakkenist is working to establish the look for increased activity. Multiple manuscripts science data is facilitating better definition of Science Translational Targeting KRAS-dependent tumors with AZD4785, Ross SJ, Revnko AS, Hanson LL, Ellston R,
Staniszewska A, Whalley N, Pandey S, Revill M,
optimal combination and dose of DDR inhibitors have resulted from this collaboration. molecular subtypes, mechanisms of resistance a high-affinity therapeutic antisense oligonucleotide
and radiation to treat ATM-proficient and ATM-
7.
and exploration of specific responder/non- Medicine inhibitor of KRAS Rooney C, Buckett LK, Klein S, Hudson K, Monia
deficient xenografts of human lung cancer grown responder patients. BP, Zinda M, Blakey D, Lyne PD, Macleod AR
in immunocompromised mice. The goal is to Dana-Farber Cancer Institute, USA
David Weinstock is carrying out pre-clinical work 11.
outline mechanisms that connect DNA damage
signalling and immune checkpoints, and to to evaluate modulators of cell death pathways Merck & Company, Inc., USA
determine whether DDR inhibitors suppress in T-cell lymphoma and other haematological We combine resources and work collaboratively Nature Communications An industry perspective on organic synthesis for Blakemore D, Castro L, Churcher I, Rees D,
Thomas A, Wilson D, Wood A
drug discovery
immune checkpoint expression after radiation. cancer types being used to identify new with Merck, with the aim of producing new clinical
indications and molecular markers for our novel trial proposals. The partnership enables the
agents. efficient production of studies which would not
otherwise be as readily feasible, by capitalising on
Journal of the American Effect of selumetinib plus docetaxel compared Jänne P, van den Heuvel M, Barlesi F, Cobo M,
Mazieres J, Crinò L, Orlov S, Blackhall F, Wolf J,
with docetaxel alone on progression-free survival
the skills and expertise of both AstraZeneca and Medical Association in patients with KRAS-mutant advanced non-small Garrido P, Poltoratskiy A, Mariani G, Ghiorghiu
Merck. In 2017, we set a shared goal to deepen, cell lung cancer: the SELECT-1 randomized clinical D, Kilgour E, Smith P, Kohlmann A, Carlile D,
broaden and extend responses to olaparib in trial Lawrence D, Bowen K, Vansteenkiste J
new patient populations, and to develop a better
understanding of resistance in the clinic.
science innovation
Collaborating for
Molecular Cell PTEN regulates PI(3,4)P2 signalling downstream of Malek M, Kielkowska A, Chessa T, Anderson KE,
Barneda D, Pir P, Nakanishi H, Eguchi S, Koizum
Class I PI3K
Ai, Sasaki J, Juvin V, Kiselev VY, Niewczas I, Gray
A, Valayer A, Spensberger D, Imbert M, Felisbino
S, Habuchi T, Beinke S, Cosulich S, Le Novère N,
Sasaki T, Clark J, Hawkins PT, Stephens LR
9 8
4 1 6
The Lancet Oncology Olaparib in combination with paclitaxel in patients Bang Y-J, Xu R-H, Chin K, Lee K-W, Park SH, Rha
SY, Shen L, Qin S, Xu N, Im S-A, Locker G, Rowe P,
with advanced gastric cancer who have progressed
following first-line therapy (GOLD): a double-blind, Shi X, Hodgson D, Liu Y-Z, Boku N
5 randomised, placebo-controlled, Phase III trial
7 3 2 10
11 Journal of Clinical Oncology Gefitinib plus chemotherapy vs chemotherapy in Mok TSK, Kim SW, Wu YL, Nakagawa K, Yang JJ,
Ahn MJ, Wang J, Yang JC, Lu Y, Atagi S, Ponce S,
epidermal growth factor receptor mutation-positive
non-small-cell lung cancer resistant to first-line Shi X, Rukazenkov Y, Haddad V, Thress KS,
gefitinib (IMPRESS): Overall survival and biomarker Soria JC
where science thrives
An environment
analyses
Gut Fibroblast drug scavenging increases gemcitabine Hessmann E, Patzak M, Klein L, Chen N, Kari
V, Ramu I, Bapiro TE, Frese KK, Gopinathan A,
accumulation in murine pancreas cancer
Richards FM, Jodrell DI, Verbeke C, Li X, Heuchel
R, Löhr JM, Johnsen SA, Gress TM, Ellenrieder V,
Neesse A
16 IMED Annual Review 2017 Delivering the next wave of scientific innovation 17Therapy area progress
“2017 was a year of significant change small molecules to new modalities, we are
Introduction
for IMED Respiratory Inflammation establishing IMED RIA as a recognised
Respiratory, Inflammation and Autoimmunity (RIA) as we built an
organisation fit to deliver on our ambition
scientific leader in the field of respiratory
research.”
and Autoimmunity of transformative therapies aiming for disease
modification and cure in respiratory disease.
Maria Belvisi, Vice President and Head of IMED
Respiratory, Inflammation and Autoimmunity
With our research moving beyond traditional
ntibody that binds upstream epithelial cytokines to
A
prevent a range of inflammatory responses
Therapy area progress
IMED functions
science innovation
Collaborating for
where science thrives
An environment
18 IMED Annual Review 2017 Delivering the next wave of scientific innovation 19People spotlight
Therapy area progress
Introduction
Respiratory, Inflammation
and Autoimmunity
Therapy area progress
In 2017, we restructured our IMED RIA organisation to focus our efforts on three Werngard Czechtizky
Head of Medicinal Chemistry
Christina Keen
Senior Project Leader
Holger Schluter
Senior Research Scientist
Zala Rojnik
Senior Research Scientist,
scientific pillars: lung epithelium, lung immunity and lung regeneration to tackle Werngard Czechtizky joined Clinical insight is invaluable for Bioscience Regeneration Bioscience Epithelium
IMED RIA in 2017, with significant what we do in IMED RIA, which Holger Schluter is a key player in Zala’s ability to initiate and drive
the underlying causes of chronic lung diseases. This new direction builds on our experience in the field of new is why Christina Keen was a key working towards the IMED RIA lung innovative research projects which
modality chemistry. She gained recruitment in 2017. She brings regeneration objectives. Our central result in high impact publications,
strong portfolio and experiences in respiratory medicine, including most recently a PhD from the Swiss Federal experience as Senior Medical hypothesis relies on identifying make her a leading young scientist
benralizumab (IL-5R mAb), tezepelumab (TSLP mAb) and PT010 (LABA/LAMA/ICS). Institute of Technology in Zürich
and did her postdoctoral work
Lead from Global Medicines
Development, where she recently
and quantifying differential patient
biology, and for that we must
in the lung epithelium community.
Her technical expertise is pivotal
at Harvard University on natural led a large Phase III programme in provide cells with their contextual for her capacity to identify and
product total synthesis. In 2002, mild asthma (SYGMA programme). binding partners. Holger is at the propose new target ideas. Together
Our respiratory strategy
she joined Aventis in Frankfurt, Christina started her career forefront of work to determine with IMED colleagues, Zala has
To realise our ambition of disease modification and cure in respiratory disease, we focus on three core themes: lung epithelium, lung immunity and lung
focussing on target based lead at AstraZeneca within patient how the disease matrix influences developed an exciting story to
regeneration. This continued scientific focus aims to achieve breakthrough innovation and establish world-class capabilities in respiratory disease to
generation approaches on safety and brings with her an human lung fibroblast phenotype describe the identification of a
enable IMED RIA as scientific leaders in this field.
G-protein-coupled receptors and excellent network of internal and function. His expertise in novel molecular phenotype in
ion channels. She joined Sanofi and external experts within the microscopy is central to observing asthma, underpinned by lung
in 2005, becoming the Head of cell changes within 3D spheroid epithelium IL-6 trans-signaling. This
IMED functions
field of respiratory research and
Medicinal Chemistry in 2014. drug development. Christina is culture systems. Furthermore, has been achieved by phenotyping
Working across several therapeutic a Medical Director and has over Holger’s experience in isolating, the differential gene expression
areas, she was responsible for 15 years of clinical experience as culturing and manipulating stem profiles of asthmatic patients. The
exploring new modalities, and allergologist/respiratory physician cell populations from skin will work provides a ground-breaking
expanding the focus from small and pediatrician. She has a PhD help us explore lung regenerative opportunity for AstraZeneca to
molecules and natural products from Gothenburg University where biology, what has been perturbed target this specific subset of poorly
to peptides, macrocycles she studied small airway disease in disease and how we might controlled asthmatic patients. Zala
and conjugates. Werngard is in asthma and cystic fibrosis. She rejuvenate stem populations into introduced the IL-6 phenotype at
an experienced conference is now responsible for several functional, healthy tissue. the Asthma Keystone Symposia,
speaker, author and co-author projects in IMED RIA and continues demonstrating our industry leading
of approximately 60 patents and position in this area.
Lung epithelium Lung immunity Lung regeneration to contribute with her knowledge
publications. in clinical drug development within
Disruption of the lung epithelium is a key Building on our established expertise By understanding the key drivers of the organisation.
driver of lung diseases and autoimmunity. in immunology and inflammation we pathogenesis in the lung we aim to
Our goal is to identify therapies that can aim to alter disease course by resetting establish hypotheses for driving lung
restore normal tissue architecture and immunological dysfunction in respiratory regeneration. We are investing in novel
science innovation
Collaborating for
lung epithelial integrity thereby improving disease. We aim to identify molecules pre-clinical models and new technologies
patient outcome. which modify disease by normalising that will enable us to explore new
immune homeostasis in target systems. biological pathways with the aim of
understanding how we can restore or
regenerate lung tissue to prevent, reverse Progressing our first inhaled Anticalin® protein, AZD1402, in collaboration
and one day cure respiratory disease. with Pieris Pharmaceuticals Inc.
For the estimated 300 million people IL-4Ra is a validated target based on with a range of respiratory diseases.
worldwide who have asthma, there is a clinical Phase III data for subcutaneously
Lung epithelium was once considered Lung immunity continues to represent As we improve our understanding of In 2017, it was agreed to move
continuing need for advances in therapy, dosed dupilumab. We believe that
a mere physical barrier to the lung. a strong competence area in IMED RIA the key drivers of lung disease, we are forward with AZD1402 as a candidate
especially for those whose symptoms AZD1402 may bring similar benefit
However, the disruption of lung epithelium as we prioritise discovery of disease- generating hypotheses for stimulating drug, less than two months after the
cannot be controlled by today’s medicines. to patients, with the convenience of
is now recognised as a key driver in modifying therapies to reverse the regeneration of lung tissue. We are completion of the agreement with
inhalation rather than injection.
respiratory disease. Our goal is to restore immunological imbalances that we making major investments in novel AZD1402 is a first in class, inhaled Pieris Pharmaceuticals. The Phase
lung tissue architecture and epithelial know occur in the lungs of patients pre-clinical models and emerging Anticalin® protein developed for patients AZD1402 is the first of five inhaled I programme sponsored by Pieris
where science thrives
An environment
integrity in patients with respiratory with respiratory diseases. In 2017, technologies that will improve our with inadequately controlled, moderate Anticalin® proteins whose development Pharmaceuticals was initiated and the
disease. Following 2016’s first time in we have nominated AZD1402, our understanding of the underlying biology to severe asthma. It is designed with has been made possible by our recently project achieved first dose in man in
man studies with AZD5634, our inhaled first in class inhaled interleukin - 4 of regeneration and enable us to explore the aim to offer improved efficacy and completed agreement with Pieris 2017 with the aim of establishing proof
epithelial sodium channel (ENaC) inhibitor, alpha receptor (IL-4Rɑ) antagonist, biological pathways which can provide tolerability compared to injectable Pharmaceuticals Inc. The Anticalin® of mechanism in a cohort of patients.
we have initiated a proof of mechanism for further development as part of our novel targets for regenerative therapies. biologics by using convenient and proteins are bioengineered by Pieris
The partnership between AstraZeneca
study in patients with cystic fibrosis Pieris Anticalin® collaboration, and The overall aims of our strategy remain familiar inhaled delivery. AZD1402 is to interact with antibody-like precision
and Pieris for inhaled Anticalin® proteins
(CF). ENaC play an important role in successfully achieving first dose in man. unchanged – in addition to treatment we directed against the alpha subunit of and potency at drug targets that would
in respiratory diseases was nominated
maintaining surface liquid in the airways We are also moving rapidly forward aim to prevent, reverse and one day hope the human IL-4 and IL-13 receptors and normally be intractable to traditional small
for ‘Best Partnership Alliance’ in the 2017
and hyperactivity in patients with CF leads with a Phase IIa study of AZD1419, our to cure respiratory disease. thereby blocks signaling of both IL-4 molecule research. This collaboration
Scrip Awards.
to impaired mucus clearance, recurrent inhaled oligonucleotide toll-like receptor and IL-13, two of the signature cytokines extends our ability to potentially deliver
infection and chronic lung disease. 9 (TLR9) agonist. driving inflammation in asthma. unique, new inhaled medicines to people
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