Astrazeneca Plc · LSE:AZN
Astrazeneca — Investor Day (May 2015)
89 slides from Astrazeneca's investor day presentation, May 2015
Slide 1: AstraZeneca Mölndal
AstraZeneca Mölndal AstraZeneca Mölndal May 2015
Slide 2: Welcome & introduction
Welcome & introduction Thomas Kudsk Larsen Head of Investor Relations
Slide 3: Programme
Programme 10.00-10.30 Registration and coffee Introduction to AZ Sweden: 10.30-10.45 Jan-Olof Jacke (President, AZ Sweden) Innovative Medicines Biotech Unit: 10.45-11.15 Mene Pangalos (EVP, Innovative Medicines) Respiratory inhaled medicines early-stage pipeline: 11.15-11.45 Maarten Kraan (Head of R
Slide 4: The AstraZeneca IR Team
The AstraZeneca IR Team + two new colleagues in the US Feedback always welcome! 4
Slide 5: Introduction to AstraZeneca Sweden
Introduction to AstraZeneca Sweden Jan-Olof Jacke President, AstraZeneca Sweden
Slide 6: An important player
An important player Key numbers 39 mdr kr Export from Sweden Proportion of AZ’s total investment in 25% research & development 2 mdr kr Sales in Sweden (including parallel imports) 110,000 Number of registered Swedish shareholders 10% Percentage of Swedish ownership (of total shares) 6
Slide 7: Extensive research and manufacturing presence in Sweden
AstraZeneca has extensive research and manufacturing presence in Sweden Mölndal Södertälje 2,400 3,800 6,200 7
Slide 8: Mölndal
Mölndal 8
Slide 9: Mölndal: One of three strategic R&D centres
Mölndal One of three strategic R&D centres • Research in Mölndal is focused on: • Cardiovascular and Metabolic disease • Respiratory, Inflammation and Autoimmunity • The site has around 2,400 employees, including more than 300 scientists from 30 different countries • Our scientists work in close col
Slide 10: Södertälje
Södertälje Gärtuna Snäckviken 10
Slide 11: Södertälje: Our largest high-tech manufacturing and supply site
Södertälje Our largest high-tech manufacturing and supply site • Sweden Operations manufacture the active pharmaceutical substance and formulate & package the final products • Launch site for new medicines in form of tablets and capsules entering the global market • More than 35% of Product Sales va
Slide 12: Strengthening the life-science ecosystem in the Nordics
What are we doing to strengthen the life-science ecosystem in the Nordics? Ledarskap Tillbaka inom forskning till tillväxt • 300 lab & office seats Collaboration to nurture Nordic • Seven biotech companies and innovative ideas in life science more to come 12
Slide 13: Creating an environment where science thrives
Creating an environment where science thrives Mene Pangalos EVP Innovative Medicines
Slide 14: Strategic priorities
Strategic priorities Achieve 1 Return 2 Be a great 3 scientific to growth place to work leadership 14
Slide 15: Completing the first phase of the journey
Completing the first phase of the journey >$45bn in 2023 2012-2014 2015-2017 2018+ Building strong Delivering on return Sustainable delivery foundations to growth and growth 15
Slide 16: Remaining focused in our R&D approach
As we move forward, we will remain focused in our R&D approach… Respiratory/ Cardio- Oncology inflammation metabolism Infection & vaccines Neuroscience Main therapy areas Opportunity-driven Small Protein Biologics Immuno-therapies Devices molecules engineering Personalised healthcare capabilities 16
Slide 17: Evolving our business model to create value from R&D
…and continue to evolve our business model to create maximum value from strong R&D productivity Biotechs Out-license Development Internal Manufacturing Externalisation development Partner Commercialisation Value creation through internal development and externalisation 17
Slide 18: A strong, well balanced pipeline
We have a strong, well balanced pipeline RIA CVMD Oncology Infection Neuroscience Terminations in Q1 2015 AZD2115 (COPD) in P2, brodalumab (asthma) in P2, MEDI-559 (RSV prophylaxis) in P1 Divestitures in Q1 2015 AZD0914 (infection) in P2 † Includes significant fixed dose combination projects, and pa
Slide 19: Delivering late-stage pipeline well ahead of plan
…and are delivering late-stage pipeline well ahead of plan Pipeline events since 2014 Investor Day 13-15 • Lynparza approvals (US, EU) 13 • Moventig approval (EU) Phase III & Registration NME 11 • Duaklir approval (EU) pipeline volume (#) 9-10 • BACE (AZD3293) Phase II/III trial start 8 • Saxa/dapa
Slide 20: Our 5R framework
Our 5R framework has created an environment where science thrives 5Rs Framework Right target enables pushing the boundaries Right tissue of science Right safety Truth- Scientific seeking rigour Right patients behaviours Right commercial potential 20
Slide 21: Focus on high impact and high quality publications
We are strengthening our scientific reputation through a focus on high impact and high quality publications IMED peer-reviewed publications Other (lF = lt 5) High quality (IF = gt 5 & lt 15) High impact (IF = gt 15) Feedback suppression of PI3Kα signaling in PTEN negative tumors is relieved by selec
Slide 22: Attracting the best scientists
Which is enabling us to attract the best scientists A few examples of recent hires into the IMED Biotech Unit Jérémie Boucher, Donald Stanski Principal Scientist, Diabetes Early Clinical Development Previously Harvard Previously Stanford / Novartis / FDA 38 publications including Cell, Nature and 11
Slide 23: Scientific partnerships and alliances
Scientific partnerships and alliances…. …remain a driver of sustainable scientific innovation 23
Slide 24: Alliance with Lilly for BACE inhibitor AZD3293
Alliance with Lilly to accelerate development of our BACE inhibitor (AZD3293) • Familial AD linked to mutations in APP Highly promising approach to address unmet medical need in Alzheimer’s • Mutations in APP result in increased BACE activity and Aβ production • Inhibition of BACE1 should reduce pro
Slide 25: CRISPR/Cas9 won the 2015 Breakthrough Prize
CRISPR/Cas9 won the 2015 Breakthrough Prize in Life Sciences* AstraZeneca working collaboratively to embrace the gene-editing revolution Our IMED Genome Editing Team is unlocking the potential of CRISPR/Cas9 We are collaborating with pioneers and world experts in gene-editing Exciting technology wit
Slide 26: Open innovation uncovered potential new treatments
Our commitment to open innovation has uncovered potential new treatments for patients AZD0530 in trials for Alzheimer’s Disease Mouse model of Alzheimer’s disease - amyloid beta plaques (red) build up among neurons • AZD0530 - Fyn kinase inhibitor - developed to (green) in memory-related area of the
Slide 27: Enhanced collaboration is a key driver
Enhanced collaboration is a key driver behind our new UK facility at the Cambridge Biomedical Campus... 27
Slide 28: Connecting Cambridge & Gothenburg
…and by connecting Cambridge & Gothenburg we will create a scientific powerhouse in Europe AstraZeneca R&D Centre Examples of scientific collaborations Gothenburg Cambridge 28
Slide 29: Spotlight on Oncology
Spotlight on Oncology 29
Slide 30: AstraZeneca/MedImmune: Oncology pipeline
AstraZeneca/MedImmune: Oncology pipeline Four key areas under research development Tumor drivers and Resistance Armed Antibodies/ DNA Damage Response Immuno-Oncology Antibody Drug Conjugates Mechanisms • AZD9291 (EGFRm) • Olaparib (PARP) • MEDI4736 (PD-L1) • Moxetumomab (CD22) • Selumetinib (MEK) •
Slide 31: Two of our most exciting programmes: MEDI4736 and AZD9291
Two of our most exciting and talked-about programmes… MEDI4736: An engineered PD-L1 antibody AZD9291 • PD-L1 inhibits cancer immunity • Updated PFS for AZD9291 (NSCLC; AURA • Expressed on multiple tumours study) of 13.5 months in T790M, 80mg cohort, independent review • MEDI4736 binds to PD-L1 and a
Slide 32: Leading 'first-in-class' DDR portfolio
Leading ‘first-in-class’ DDR portfolio 32
Slide 33: Portfolio breadth allows combinations
Breadth of portfolio allows combinations with strong scientific rationale Breast AZD1775 combination with cancer Lynparza & AZD1775 in TNBC Lynparza in a TNBC PDX model Vehicle control Gastric 1500 Olaparib cancer Lynparza & AZD6738 in AZD1775 ATM-deficient GC Olaparib + AZD1775 1000 Tumour voume (m
Slide 34: Advancing inhalation science to change respiratory disease
Advancing inhalation science to change respiratory disease Maarten Kraan Head of RIA, Innovative Medicines
Slide 35: Four decades of leading innovation in respiratory disease
Four decades of leading innovation in respiratory disease 1970 1980 1990 2000 2004 2014 Bambec 35
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Slide 37: The inhaled portfolio remains the backbone of respiratory strategy
The inhaled portfolio remains the backbone of the respiratory strategy - but new treatments are needed 1 Continue to differentiate Symbicort and Pulmicort Unique inhaled 2 Win in triple therapy with the Pearl technology therapies 3 Leveraging our ‘two platform’ device strategy Innovative precision 4
Slide 38: Disease-modifying treatment changed rheumatoid arthritis
Disease-modifying treatment changed the lives of patients with rheumathoid arthritis 38
Slide 39: Immuno-modulatory medicine is required in respiratory disease
Immuno-modulatory medicine, effective in respiratory disease, is required 39
Slide 40: Revolutionary Inhaled Immuno-modulatory
Revolutionary Immuno- Inhaled modulatory 40
Slide 41: Most promising respiratory pipeline in the industry
Most promising respiratory pipeline in the industry LI Pre-clin Phase III/ HI LO Dev Phase I Phase IIa Phase IIb Registration AZD1419 AZD0548 PT003 GFF AZD9412 Abediterol Inhaled TLR9 Inhaled INF-beta LABA/LAMA LABA AZD7594 PT010 PT010 Lesinurad Inhaled SGRM Pearl Triple MDI Pearl Triple MDI URAT1 (
Slide 42: Progressing novel, game-changing therapies
Progressing novel, game-changing therapies Asthma COPD Biologics PT003 Inhaled TLR9 Inhaled p38 Inhaled IFNβ SGRM/MABA 42
Slide 43: PT003 demonstrates incremental benefit of combination therapy
PT003 demonstrates incremental benefit of combination therapy ~100mL FEV over monotherapy in Phase IIB 0.35 placebo in FEV1 AUC0-12 (L) 0.3 Adjusted difference from 0.25 0.2 0.15 0.1 0.05 0 GP MDI 18 µg FF MDI 9.6 µg GFF MDI 18/9.6 µg PT001 mono-therapy Treatment PT005 mono-therapy PT003 combination
Slide 44: Inhaled SGRM (AZD7594)
Inhaled SGRM (AZD7594) is a novel, inhaled, non-steroidal anti- inflammatory with potential for improved therapeutic ratio More potent than traditional inhaled steroids Zero cortisol suppression predicted Traditional AZD7594 Exploits water pocket beyond steroid-binding domain 44
Slide 45: Inhaled TLR9 (AZD1419) in healthy volunteers
Inhaled TLR9 (AZD1419) in healthy volunteers Flu-like symptoms Biomarker response* Dose group *Estimated fold change from baseline versus placebo 24 hr after first dose with 95% confidence interval (ANCOVA) Subjects reporting one or more incidence of influenza-like symptoms after 4 once-weekly dos
Slide 46: Inhaled IFNβ (AZD9412) may reduce exacerbations in asthma
Inhaled IFNβ (AZD9412) may reduce exacerbations on demand in asthma ‘Difficult-to-treat’ asthmatics benefit from 14 days of on-demand treatment with AZD9412 Lung Function Change in Morning PEFR 60 Placebo SNG001 Significant (56%) 40 reduction in Clinically moderate or (L/min) relevant 20 difference
Slide 47: Inhaled p38 inhibitor (AZD7624) in COPD
Inhaled p38 inhibitor (AZD7624) could change disease management for steroid-resistant patients with COPD Phospho p38+ alveolar Inflammatory cytokines in human Significant attenuation of macrophages in COPD lung alveolar macrophages LPS-induced TNF-α 40 TNF-α (pg/ml) 30.46 30 20 AZD7624 PLACEBO 10 4.
Slide 48: Unlocking new treatment possibilities with RORγ
Cutting-edge science with leading academics to unlock new treatment possibilities with RORγ RORγ drives important pathway in RORγ inhibitors have the potential to modulate and not just inflammatory responses suppress the inflammatory response RORγt Active inhibitor Inactive RORγt RORγt IL-22 IL-22 I
Slide 49: Collaborating with leading academic research groups
Collaborating with leading academic research groups to shape the future of inhaled, immuno-modulatory treatment GLAZgoDiscoveryCentre `www.GLAZgoDiscoveryCentre.co.uk 0131 330 6443 OpsManager@GLAZgoDiscoveryCentre.co.uk 49
Slide 50: Lab tours
Lab tours AstraZeneca @ What science can do
Slide 51: CVMD Pipeline Update
CVMD Pipeline Update Elisabeth Björk, VP, Head of Cardiovascular & Metabolic Disease GMD
Slide 52: CVMD strategy built on three pillars
CVMD strategy built on three pillars Reducing CV morbi-mortality and organ damage by addressing multiple CV risk factors Chronic Kidney Cardiovascular Metabolics Disease CHD/ Athero/ Heart Disease Symptomatic Diabetes NASH ACS Dyslip Failure progression treatment Regeneration Heart β- cell Kidney 52
Slide 53: Brilinta: PLATO results displayed unique clinical profile
Brilinta: PLATO results displayed unique clinical profile • Continuous benefit for one year • Mortality benefit • Potential unique benefit beyond P2Y12 inhibition driven by ENT1 K-M, Kaplan-Meier Wallentin L, et al. N Engl J Med. 2009;361:1045-1057 53
Slide 54: Beyond 12 months patients remain at risk
Beyond 12 months Patients remain at a significant risk APOLLO; late-breaking registry presentation at the 2014 European Society of Cardiology in Patients who are event free in first year after their index event will suffer a MI, stroke or death in the subsequent three years 54
Slide 55: PEGASUS-TIMI 54 meets primary endpoint
PEGASUS-TIMI 54 study of BRILINTA® / BRILIQUE™ meets primary endpoint in both 60mg and 90mg doses PEGASUS-TIMI 54 study PEGASUS-TIMI 54 study, epidemiology2 • Investigated 60mg and 90mg ticagrelor vs. placebo in Prior MI 13-36 months patients (low-dose aspirin) aged 50 and older with a history 4.5 m
Slide 56: Collaboration with TIMI Study Group; prepare to launch
Outstanding collaboration with TIMI Study Group Publication, regulatory, prepare to launch Study metrics Publication, regulatory Towards launch • 21,000 patients in 31 • FDA and EMA • Regulatory submission countries submissions complete • Pre-launch planning • >210,000 patient visits • Parallel pres
Slide 57: PARTHENON Programme: potential for four launches in four years
PARTHENON Programme Potential for four launches in four years 2015 2016 2017 2018 Patients OAP Billion Days of Enrolled Comparator Access Therapy (DoT) Key Facts PLATO Acute Coronary Syndrome 18,624 clopidogrel 10% - Launched 4 in 4 Number of launches in consecutive years PEGASUS Prior MI 21,162 pla
Slide 58: SOCRATES: next Brilinta study
SOCRATES - next Brilinta study, to read out in H1 2016 ...a complete Stratified blockage of a according to Ischemic Stroke cerebral artery, symptoms and Minor stroke (NIHSS≤5 = 53% leading to more disability at AIS population) eligible for AIS = Acute severe and presentation enrolment in SOCRATES pe
Slide 59: Roxadustat (CKD): potential first oral anaemia treatment
Roxadustat (CKD): Potential to be first oral erythropoietic anaemia treatment Hb correction in pre-dialysis CKD patients • Oral HIF-prolyl hydroxylase inhibitor 100 90 • Favourable efficacy and safety profile Hb increase >1g/dL at 4 weeks, % in Phase II 80 70 • >7,000 patient Phase III ALPINE 60 pro
Slide 60: Roxadustat: potential for reduced cardiovascular risk vs rEPO
Roxadustat (CKD): Potential for reduced cardiovascular risk vs. rEPO USRDS: Unadjusted 1-year mortality by • Higher doses of rEPO predict mortality epoetin dose & hematocrit regardless of hematocrit • Mechanism for increased CV risk with rEPO is uncertain, but may involve -supra-physiologic EPO leve
Slide 61: Roxadustat stimulates erythropoiesis like the body's response to hypoxia
Roxadustat (CKD): Stimulates erythropoiesis similar to the body’s normal co-ordinated response to hypoxia Median plasma EPO concentration at two oral doses of roxadustat postdialysis compared with reported EPO levels following IV administration of rhEPO [100 IU/kg]* • rEPO infusion produces supra- p
Slide 62: Diabetes: Strategy to transform patient care
Diabetes: Strategy to transform patient care Shift treatment paradigm to early combination therapy and accelerate achievement of treatment goals Develop a science-led life cycle management strategy Expand into new areas of unmet need, including expansion into Type 1 diabetes with Forxiga 62
Slide 63: Real world glycaemic control
The real world picture of glycaemic controls shows… … 50% of type 2 patients uncontrolled and above the 7% HbA1c goal, supporting the need for more effective treatment options and strategies Why ? • Disease progression • Modest doses of moderately effective oral agents cautiously added in sequence r
Slide 64: New guidelines more aggressive with earlier combinations
New guidelines more aggressive with earlier combinations Note: AACE guidelines were published March 2013, SGLT-2 recommendation was based on Ph3 data. 64
Slide 65: Helping patients along disease progression
Helping patients along disease progression Sequential treatment 7.5 -Illustration- HbA1c 7.0 6.5 6.0 65 Time
Slide 66: AstraZeneca's portfolio makes early combination possible
AstraZeneca’s portfolio: Makes early combination possible Current sequential paradigm Early combination future 3 2 saxa/dapa Insulin Potent A1C reduction, (weight gain and Low hypoglycaemia, hypoglycaemia) 2 no weight gain Sulfonilurea Sulfonilurea Metformin (weight gain and hypoglycaemia) (weight g
Slide 67: Potential of early combinations to slow disease progression
Potential of early combinations to slow disease progression Illustrative 67
Slide 68: Oral combinations: Saxa/dapa & saxa/dapa/metformin
Oral combinations: Saxa/dapa & saxa/dapa/metformin Portfolio well-positioned to enable early Significant reduction in HbA1c with low rates combination treatment of hypoglycemia Adjusted mean change from baseline in HbA1c at 24 weeks • Saxa/dapa added to metformin in poorly controlled T2DM – HbA1c re
Slide 69: Forxiga / Xigduo: insulin doses stable over two years
Add-on to Insulin, 90-006 Forxiga / Xigduo: Insulin doses remained stable over two years • Dapagliflozin showed sustained reductions in HbA1c in when used in combination with insulin • Patients on dapa +insulin lost weight -3kg vs insulin alone • Insulin doses remained stable over the study period F
Slide 70: Visualising diabetes impact via differentiated technology
Visualising diabetes impact via differentiated technology 70
Slide 71: Science-driven innovation into new areas of unmet need
Science-driven innovation into new areas of unmet need NASH / Fatty liver disease Type 1 Renal diabetes protection Heart failure Weight 71
Slide 72: Diabetes: R&D commitment
Diabetes: R&D commitment ~40,000 patients in clinical trials worldwide 72
Slide 73: Summary
Summary Strategy of reducing morbidity, mortality and organ damage Transform atherosclerosis through Brilinta PARTHENON trials Opportunity to change the lives of CKD patients Leveraging Diabetes portfolio - addressing unmet need through early combination therapy and expansion into new populations 73
Slide 74: What Science Can Do
What Science Can Do Marcus Schindler, PhD VP, Head of Cardiovascular & Metabolic Disease iMed
Slide 75: 3 strategic research areas in CVMD Innovative Medicines
3 strategic research areas in CVMD Innovative Medicines 1 Heart failure Diabetes 2 3 Chronic kidney disease 75
Slide 76: Redefining pharma/academia collaborations
Redefining pharma/academia collaborations • >40 global collaborations (excl CRO) • 70% of pipeline projects run in collaboration 76
Slide 77: Heart Failure Strategy
Heart Failure Strategy To identify and develop small or large molecules that enhance endogenous regenerative capacity of the heart for the treatment of post-MI cardiac dysfunction and heart failure by Activating resident stem cells in the heart: Epicardial progenitor cells or Cardiac stem cells EPDC
Slide 78: Our partnerships to deliver HF strategy
Our Partnerships to deliver HF strategy Access to human Access to modRNA stem cells & iPS Established Understanding heart expertise for local Access to novel derived cells for TV translational imaging failure patient tissue protein expertise in drug and phenotypic platform populations production tar
Slide 79: Exclusive agreement with Moderna on mRNA therapeutics
Exclusive agreement with Moderna to harness pioneering messenger RNA therapeutics technology VEGF expression • Entirely new modality for producing proteins 350 using modified mRNA 300 – Exclusivity in CVMD and selected targets VEGF (ng/ml) 250 in Oncology 200 Gen A • Five-year collaboration – flow o
Slide 80: Stopping diabetes from progressing remains an unmet need
Stopping diabetes from progressing remains an unmet medical need despite SoC 80
Slide 81: Route 1: Improving insulin sensitivity is key
Route 1: Improving insulin sensitivity is key Insulin sensitivity beyond normal levels after BPD Partitioning fatty acids into the right tissues: white Factors regulating differences in insulin sensitivity in and brown fat for storage and oxidation obese subjects pre-post bariatric surgery. Novel ta
Slide 82: Route 2: Improve functional β-cell mass
Route 2: Improve functional β-cell mass Growth Death Healthy Control T1D Subject Replication Trans-diffentiation Apoptosis Neogenesis De-differentiation Increasing β-cell mass : address multiple mechanisms β-cell mass imaging : “Imagine” to monitor decline with strong emphasis on human translation a
Slide 83: Partnerships to help deliver diabetes therapies
Partnerships to help deliver diabetes therapies Generation of insulin Preservation of Body weight White Brown and Insulin sensitizers producing cells in pancreatic β-cells reduction and insulin Beige fat the gut sensitisation by appetite control 83
Slide 84: Next generation human beta cell lines
Next generation human beta cell lines Cell. 2014;159:428-439 84
Slide 85: How this collaboration enables leading science
How this collaboration enables leading science Very limited supply of human islet cells from organ donors for HTV, hypothesis generation, etc No existing human (or rodent) cell models to study the role of α- and δ-cells in diabetes No existing models to study human (or rodent) β-cell dedifferentiati
Slide 86: Our vision: Treatment modalities for all targets
Our vision: “Treatment modalities for all targets” Messenger RNA Micro RNA Antisense oligonucleotides • Harnessing cutting edge mRNA • More than 500 microRNAs • Antisense oligonucleotides both technology to enable the body to identified in the human genome - knock down specific target mRNA produce i
Slide 87: What science can do
87 What science can do ll ©
Slide 88: Q&A
AstraZeneca @ What science can do Q&A
Slide 89: Confidentiality Notice
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