Slide 1: Late-stage pipeline conference call
Late-stage pipeline conference call 2 December 2015
Slide 2: Introduction
Introduction Thomas Kudsk Larsen Head of Investor Relations
Slide 3: Forward-looking statements
Forward-looking statements In order, among other things, to utilise the 'safe harbour' provisions of the US Private Securities Litigation Reform Act 1995, we are providing the following cautionary statement: This document contains certain forward-looking statements with respect to the operations,
Slide 4: Meet the experts
Meet the experts 2015 review Sean Bohen Respiratory, Inflammation & Autoimmunity Bing Yao & David Chang Cardiovascular & Metabolic Disease Elisabeth Björk Oncology Mohammed Dar & Antoine Yver Closing Sean Bohen 4 - Introduction
Slide 5: 2015 review
2015 review Sean Bohen Executive Vice President, Global Medicines Development & Chief Medical Officer
Slide 6: 2015: Delivering the late-stage pipeline
2015: Delivering the late-stage pipeline cediranib Iressa lesinurad Tagrisso submission (EU) approval (US) positive Advisory approval (US) Committee (US) saxa/dapa lesinurad submission (EU) CAZ AVI saxa/dapa Brilinta submission submission (EU) Complete Response ACS, post-MI Letter (US) submission
Slide 7: 2015-2016: Delivering promises from Investor Day 2014
2015-2016: Delivering promises from Investor Day 2014 Building pipeline for long-term sustainability 14-16 12-16 • Focus on distinctive science in three therapy areas 8-10 • Shift toward more targeted 8 50% specialty-care programmes, often with NMEs 6 50% companion diagnostics NMEs 3 • High-q
Slide 8: Key late-stage new medicines and lifecycle programmes
Key late-stage new medicines and lifecycle programmes Respiratory, Inflammation Cardiovascular & Oncology Other & Autoimmunity Metabolic Disease Phase III Under review Phase III Under review Phase III Under review Under review PT010 PT003 roxadustat ZS-91 selumetinib cediranib CAZ AVI LAMA/LABA/IC
Slide 9: Highlights of today
Highlights of today Respiratory, Inflammation Cardiovascular & Oncology Other & Autoimmunity Metabolic Disease Phase III Under review Phase III Under review Phase III Under review Under review PT010 PT003 roxadustat ZS-91 selumetinib cediranib CAZ AVI LAMA/LABA/ICS LAMA/LABA HIF-PH Potassium binde
Slide 10: Respiratory, Inflammation & Autoimmunity
Respiratory, Inflammation & Autoimmunity Bing Yao, Senior Vice President, Head of Respiratory, Inflammation & Autoimmunity iMED, MedImmune David Chang, Vice President and Head, Inflammation, Autoimmunity & Neuroscience, Global Medicines Development
Slide 11: PT003: A novel co-suspension MDI
PT003: A novel co-suspension MDI Fixed-dose combination of LAMA/LABA • For long-term maintenance treatment of airflow obstruction in patients with moderate to severe COPD1 • Only LAMA/LABA2 combination developed in a pressurised Metered Dose Inhaler (pMDI) • First product using the Pearl co-susp
Slide 12: PT003: Phase III demonstrated superiority to monotherapy
PT003: Phase III demonstrated superiority to monotherapy Patients with moderate-to-severe COPD • Statistically-significant improvements in lung function • Symptomatic benefit observed based upon self-administered computerised TDI1 • Secondary endpoints generally supportive • Well-tolerated, wit
Slide 13: PT003: Key milestones
PT003: Key milestones Regulatory Regulatory approval submission* Launch (US) (US) (US) PDUFA Q2 2016 Q3 2015 Novel fixed-dose combination of LAMA/LABA in unique pMDI device Regulatory Regulatory submission* submission (EU) (JP, CN) H2 2016 2017 13 - Respiratory, Inflammation & Autoimmunity * Regul
Slide 14: COPD: Addresses all disease severities
COPD: Addresses all disease severities Near term e.g. benralizumab (IL-5R) LAMA/LABA: Duaklir & PT003 Symbicort + Eklira Biologics 2018 Medium term LAMA/LABA: Duaklir & PT003 Symbicort + Eklira FDC triple (PT010) Disease severity Mild Moderate-severe Very severe <1 exacerbation >2 exacerbations 14
Slide 15: Unique mechanism for eosinophilic inflammation
Unique mechanism for eosinophilic inflammation Benralizumab depletes eosinophils in a different way to anti-IL-5 ligand approaches • Binds to IL-5 receptor (IL-5Rα) on eosinophils and basophils • Leads to Antibody-Dependent Cell- mediated Cytotoxicity (ADCC) and death of eosinophils and basoph
Slide 16: Benralizumab: Targeting best-in-class efficacy
Benralizumab: Targeting best-in-class efficacy Differentiated profile Phase IIb: Exacerbation rate reduction • • Differentiated mode Differentiated MoA of action resulting in potent reduction of eosinophils reduction relative to placebo Annual exacerbation rate à Potent reduction in eosinophils •
Slide 17: Benralizumab: Comprehensive programme in severe asthma
Benralizumab: Comprehensive programme in severe asthma Key trials for regulatory submission CALIMA SIROCCO ZONDA BISE GREGALE BORA Adults with Adults/adolescents Adults with severe severe asthma, with severe asthma, Adults/adolescents with severe a sthma, asthma, inadequately inadequately inadequate
Slide 18: Anifrolumab: Targeting type-I interferon system in SLE
Anifrolumab: Targeting type-I interferon system in SLE • Central pathogenic mediator in SLE1,2 • Mixed trial results for sifalimumab3 and rontalizumab4 • All type-I IFN signalling is mediated by type-I IFN- α receptor (IFNAR)5 • Inhibiting IFNAR has potential to block the biological effects of a
Slide 19: Anifrolumab: Phase II trial conclusions
Anifrolumab: Phase II trial conclusions • Substantial benefit achieved across multiple global and organ-specific disease activity measures • Greater efficacy in patients with high IFN gene signatures supports the pathobiology of this treatment strategy • Safety and tolerability acceptable • Phase I
Slide 20: Anifrolumab: Potential differentiators in SLE
Anifrolumab: Potential differentiators in SLE First-in-class • Most-advanced molecule targeting IFNAR mechanism of action • Blocks all type-I interferons (not just IFN-α) Statistical significance achieved: • 26.0% treatment difference vs. placebo on SRI(4)1 response Potential at day 365 with a
Slide 21: Anifrolumab: Development status
Anifrolumab: Development status Phase III SLE programme initiated Lifecycle management programme • Final data available 2018 • Phase II lupus nephritis trial expected to • Regulatory submission 2019 start in due course • Phase I subcutaneous administration trial also expected to start in due course
Slide 22: Cardiovascular & Metabolic Disease
Cardiovascular & Metabolic Disease Elisabeth Björk Vice President, Cardiovascular & Metabolic Disease Head, Global Medicines Development
Slide 23: Cardiovascular & Metabolic Disease strategy
Cardiovascular & Metabolic Disease strategy Aim to reduce morbidity, mortality and organ damage by addressing multiple CV risk factors Chronic Kidney Cardiovascular Metabolic Disease (CKD) CHD1/ Athero/ Heart Disease Symptomatic Diabetes NASH3 ACS2 Dyslip Failure progression treatment Regeneration H
Slide 24: Brilinta/Brilique: PARTHENON programme potential to deliver four launches
Brilinta/Brilique: PARTHENON programme potential to deliver four launches in four years OAP1 access 2015 2016 2017 2018 Patients Comparator enrolled (cumulative) PLATO Acute Coronary Syndrome 18,624 clopidogrel 10% Launched 1.5 million Estimate of patients treated with PEGASUS Launched Prior Myocard
Slide 25: SOCRATES: Top-line data anticipated H1 2016
SOCRATES: Top-line data anticipated H1 2016 First large-scale prospective international trial in acute stroke and TIA “ It’s exciting to have an antiplatelet that can be used acutely. Anytime we have another option in our armamentarium, that’s always a good day.” Stroke key thought leader Brilinta
Slide 26: SOCRATES: Early treatment to address recurrent risk
SOCRATES: Early treatment to address recurrent risk Post-event risk of recurrent stroke relative to background risk 1,000x • Initiating treatment with Brilinta/Brilique greater risk within 24 hours of a stroke may reduce 100x the risk of recurrent events greater risk 10x • Approximately 3–15% of pa
Slide 27: EUCLID: PAD large and growing area of patient need
EUCLID: PAD large and growing area of patient need Clear precedent exists for superiority to clopidogrel PAD is almost half as prevalent as type-2 diabetes (T2D)1 PLATO trial;; PAD patients: 15% RRR (CVD/MI/stroke)2 PLATO trial;; PAD patients: 26% RRR (all-cause mortality)2 Brilinta/Brilique Relat
Slide 28: EUCLID: Trial design
EUCLID: Trial design 13,887 patients enrolled Patients (≥50 years) with established PAD PAD established as either: A. Prior lower-extremity (LE) Brilinta/Brilique Clopidogrel revascularisation (=57% trial) 90mg 2x/day 75mg 1x/day B. No prior LE revascularisation, but symptomatic PAD (IC1 or CLI2) w
Slide 29: Roxadustat: A potential first-in-class oral treatment
Roxadustat: A potential first-in-class oral treatment that mimics the body’s natural response at high altitude • Higher doses of rEPO1 predict mortality regardless of haematocrit Haematocrit-adjusted 1-year mortality by epoetin dose & hematocrit • Mechanism for increased CV risk with rEPO is 486
Slide 30: Roxadustat: Comprehensive development programme
Roxadustat: Comprehensive development programme roxadustat Phase III trials (Fibrogen, Astellas, AstraZeneca) Dialysis Non-dialysis vs. epoetin alfa vs. placebo Efficacy (powered for non- Efficacy (powered for s uperiority inferiority on Hb) on Hb) SIERRAS (N = 600) PYRENEES (N = 750) ANDES (N = 6
Slide 31: ZS-9: ~1,700 patients in clinical trial programme
ZS-9: ~1,700 patients in clinical trial programme Trial Published Trial type # Patients Duration Endpoint Phase II N = 90 ZS002 ∆ serum K+ level Double-blind Serum K 48 hours (completed) (3 doses) RCT 5.0–6.0 mEq/L Phase III N = 753 ZS003 ∆ serum K+ level Double-blind Serum K 14 days (completed)
Slide 32: ZS-9: Efficacy and safety
ZS-9: Efficacy and safety ZS005: Serum K+ over 52-weeks • 99% of patients achieved normokalaemia within 24-72hrs • Mean potassium levels were maintained throughout the 12-month period • Rates of edema and hypertension were consistent with the patient population over this time frame 32 - Cardiov
Slide 33: Oncology
Oncology Mohammed Dar, Vice President, Oncology Clinical Development, MedImmune Antoine Yver, Head of Oncology, Global Medicines Development
Slide 34: Immuno-Oncology (IO) strategy
Immuno-Oncology (IO) strategy Focus on combination & first-mover indications • Durvalumab in PD-L1 positive 3L+ NSCLC & 2L SCCHN Speed • Durva + treme in PD-L1 negative 2L SCCHN • Early-stage disease: Adjuvant and stage III, unresectable NSCLC • Durva + treme combo (chemo-free regimen) Differe
Slide 35: IO: Clinical activity in lung cancer
IO: Clinical activity in lung cancer Greatest unmet medical need is in PD-L1 negative tumours 60-70% of patients below IO combinations address major unmet medical need: 10% PD-L1 expression level PD-L1 negative tumours in lung cancer EGFR/ALK WT EGFRm ALKm SCLC 266k pts Mutation 48k pts 18k pts
Slide 36: Durvalumab: Promising activity in PD-L1 positive NSCLC
Durvalumab: Promising activity in PD-L1 positive NSCLC PD-L1 positive: Durvalumab monotherapy • Durvalumab monotherapy shows promising overall response rate (ORR) in PD-L1 positive NSCLC patients • Data emerging in additional indications (Study 1108) 36 - Oncology 30 June 2015 data cut for Study
Slide 37: Durva + treme: Promising activity in PD-L1 negative NSCLC
Durva + treme: Promising activity in PD-L1 negative NSCLC PD-L1 negative: Durva + treme combo therapy • Durvalumab works in tandem with tremelimumab to further break down the tumour defence and extends the benefit of immunotherapy to more patients (PD-L1 negative) 37 - Oncology 30 June 2015 data
Slide 38: IO: NSCLC top priority
IO: NSCLC top priority First in early stage and differentiated with durva + treme Unresectable Adjuvant 1st line 2nd line 3rd line stage III ATLANTIC MYSTIC (PFS) ADJUVANT PACIFIC PD-L1 pos.: durva + treme durvalumab v s. placebo durvalumab v s. placebo durvalumab s ingle-arm vs. durvalumab v s. S
Slide 39: IO: Additional tumour types
IO: Additional tumour types Leading with durva + treme and in early lines of treatment SCCHN SCCHN Bladder Gastric Liver Pancreatic 1st line 2nd line 1st line 2nd/3rd line 2nd line 2nd line PD-L1 pos. KESTREL HAWK DANUBE durva + treme durva + treme durva + treme durvalumab s ingle- durva + treme v
Slide 40: IO: Way to market
IO: Way to market Data availability from key ongoing trials Other tumour types DETERMINE PII 2L mesothelioma (randomised) Head & neck cancer HAWK CONDOR PII 2L PD-L1 positive (single arm) PIII 2L PD-L1 negative Lung cancer MYSTIC PIII 1L (PFS endpoint) ARCTIC B PIII 3L PD-L1 negative PACIFIC PIII
Slide 41: Lynparza: Strategy built on three pillars
Lynparza: Strategy built on three pillars BRCAm Other HRD Combinations Target disease with BRCA Expand to target other Combine to induce HRD, target mutations - germline and Homologous Recombination complimentary DNA Damage somatic Repair Deficiency (HRD) Repair (DDR) pathways or tumours potential
Slide 42: Lynparza: Backbone in ovarian cancer
Lynparza: Backbone in ovarian cancer Step four Displace c hemo in 1L with triple combos Step three Enhance efficacy across s egments Step two through double combos Expand beyond HRD with VEGFi combos Step one Displace c hemo in 2L Lynparza + durvalumab Establish Lynparza as + WEE1 standard of c are
Slide 43: Lynparza: 3rd line+ prostate cancer
Lynparza: 3rd line+ prostate cancer Trial published in NEJM informs lifecycle Responder DNA-repair defects No Yes RR% All-comer 33 16 33% Biomarker negative 31 2 <1% 88% RR1 and 9.8m PFS in biomarker- Biomarker positive 2 14 63% RECIST (BRCA/ATM;; 5/8) positive patients (N = 16) P-value P<0.001
Slide 44: Lynparza: Ongoing trials and expected newsflow
Lynparza: Ongoing trials and expected newsflow Pancreatic cancer POLO Phase III gBRCA Gastric cancer GOLD Phase III 2L Prostate cancer Phase II Metastatic castration- resistant Breast cancer OlympiAD OlympiA Phase III Phase III adjuvant metastatic BRCAm Ovarian cancer SOLO-1 Phase III 1L BRCAm mai
Slide 45: Tagrisso (osimertinib, formerly AZD9291)
Tagrisso (osimertinib, formerly AZD9291) 2 yrs 8 mths 59% ORR ~1.6m Clinical 12.4 mths Global lung development Duration of response time cancer deaths >80% <6 hrs Lung cancer is Time to first product NSCLC 10% shipment after a pproval Typical 5-year survival rate 45 - Oncology
Slide 46: Tagrisso: Innovative therapy with large potential
Tagrisso Innovative therapy with large potential Adjuvant • Record development speed, breakthrough United States: 3k EU5: 3k 14k designation Japan: 8k Patients treated • Crucial step to building 1st line leadership position in EGFRm NSCLC lung cancer market United States: 12k EU5: 9k 39k Japan: 18k
Slide 47: Tagrisso: Ongoing NSCLC trials and expected newsflow
Tagrisso: Ongoing NSCLC trials and expected newsflow Phase I Phase II Phase III AURA3 Phase III 2L EGFRm, T790Mm AURA AURA17 FLAURA CAURAL Phase I/II Phase II Phase III Phase III (combo with durvalumab) 2L EGFRm T790Mm 2L EGFRm T790Mm 1L EGFRm 2L EGFRm T790Mm AURA2 BLOOM TATTON ADAURA Phase II Phase
Slide 48: Tagrisso: CNS disease pre-clinical evidence
Tagrisso: CNS disease pre-clinical evidence Brain Brain to blood ratio AUC 0–90 min (corrected for radioactivity in cerebral blood) [11C]Tagrisso (N = 3) 2.6 ± 1.4 [11C]CO-1686 (N = 2) 0.025 [11C]gefitinib (N = 2) 0.28 [11C]Tagrisso cyno monkey 48 - Oncology
Slide 49: Tagrisso: CNS disease leptomeningeal metastasis
Tagrisso: CNS disease leptomeningeal metastasis Brain MRI at baseline Brain MRI at four months 160mg 1x/day Brain AACR NCI EORTC meeting Nov. 2015 49 - Oncology
Slide 50: Tagrisso: Reaching more patients through lifecycle
Tagrisso: Reaching more patients through lifecycle Transform Combos Survival o utcomes in all EGFRm NSCLC p atients as b ackbone o f combinations Patients benefit Adjuvant Expand Replace existing therapies in early EGFRm d isease 1st line Establish New standard o f care in ≥2L EGFRm NSCLC with T 790
Slide 51: Closing
Closing Sean Bohen Executive Vice President, Global Medicines Development & Chief Medical Officer
Slide 52: Key newsflow through 2016
Key newsflow through 2016 Regulatory approvals Key regulatory submissions Key Phase III readouts • lesinurad - gout (US) • brodalumab - psoriasis (US, EU) • durvalumab - lung cancer (PII) • ZS-91 - hyperkalaemia (EU) H1 2016 H1 2016 • benralizumab - severe asthma • PT003 - COPD (US) H1 2016 •
Slide 53: Disciplined execution of science-driven pipeline
Disciplined execution of science-driven pipeline 113 projects in 3 approvals clinical pipeline so far this year 16 new medicines1 in pivotal trials or under regulatory review 53 - Closing 1. Pending completion of ZS Pharma acquisition
Slide 54: Q&A
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Slide 55: Confidentiality Notice
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