Slide 1: Investor science webcast: ERS 2017
Investor science webcast: ERS 2017 Conference call and webcast for investors and analysts, Milan, Italy 13 September 2017
Slide 2: 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, pe
Slide 3: Presenters
Presenters Dr Colin Reisner Dr Andrew Menzies-Gow Chief Executive Officer, Pearl Therapeutics Consultant in Respiratory Medicine and and Head of Clinical, Respiratory, Global Director, Lung Division, Royal Brompton Medicines Development, AstraZeneca Hospital, London, UK Dr Jonathan Corren Tom Keith-
Slide 4: Agenda
Agenda Introduction Unmet medical need Characterising responders to benralizumab Tezepelumab Phase IIb PATHWAY Commercial opportunity 4
Slide 5: Late-stage pipeline overview
Late-stage pipeline overview Significant opportunities from lifecycle and potential new medicines Cardiovascular & Oncology Respiratory Metabolic Diseases Lynparza1, 2 ZS-92 benralizumab1, 2 multiple cancers hyperkalaemia severe, uncontrolled asthma / COPD Tagrisso1, 2 roxadustat2 tralokinumab lung
Slide 6: Agenda
Agenda Introduction Unmet medical need Characterising responders to benralizumab Tezepelumab Phase IIb PATHWAY Commercial opportunity 6
Slide 7: Asthma inadequately controlled by high-dose ICS-based therapy represents a significant healthcare burden
Asthma that is inadequately controlled by high-dose ICS-based therapy represents a significant healthcare burden Asthma varies in disease Linked to poor outcomes and Severe asthma accounts for severity1,2,3 medical emergencies4,5 majority of asthma costs6 Share (%) of total direct cost of In patient
Slide 8: Glucocorticoid-associated side effects increased in severe asthma with high OCS use
Glucocorticoids-associated side effects increased in severe asthma with high OCS use Cross-section of OPCRD database and BTS difficult asthma registry Severe asthma (GINA 5 ≥ 4 OCS burst) vs. mild/moderate asthma Cataracts Gastrointestinal OR 1.89, p<0.001 OR 3.99, p<0.001 Osteoporosis Diabetes OR 5
Slide 9: A biologics portfolio that follows the science
A biologics portfolio that follows the science Benralizumab is an anti- Tralokinumab is an anti- Tezepelumab is a eosinophil monoclonal IL-13 monoclonal potential first in class antibody that targets the IL- antibody that blocks monoclonal antibody that 5 receptor, thereby inducing binding and signa
Slide 10: Agenda
Agenda Introduction Unmet medical need Characterising responders to benralizumab Tezepelumab Phase IIb PATHWAY Commercial opportunity 10
Slide 11: Benralizumab for uncontrolled, severe asthma (ZONDA, SIROCCO and CALIMA)
Benralizumab for uncontrolled, severe asthma (ZONDA, SIROCCO and CALIMA)
Slide 12: ZONDA: OCS sparing trial in adult OCS-dependent asthma patients
ZONDA: OCS sparing trial in adult OCS-dependent asthma patients Benralizumab 30mg SC Benralizumab 30mg SC Q4W Q4W Primary OCS optimisation and Benralizumab 30mg SC Benralizumab 30mg endpoint run-in Q4W SC alternating with placebo Q8W % reduction in final OCS Placebo SC Placebo SC dose every 4 weeks
Slide 13: ZONDA: Benralizumab significantly reduced final OCS doses at week 28
ZONDA: Benralizumab significantly reduced final OCS doses at week 28 while maintaining asthma control vs. placebo (full analysis set) Primary Analysis Categorical Analysis Reduction in Benralizumab Benralizumab 0 Final OCS Dose, Placebo 30mg 30mg N=75 -10 n (%) Q4W, N=72 Q8W, N=73 -20 -25 ≥90% 9 (12
Slide 14: ZONDA: Benralizumab significantly reduced annualised asthma exacerbation rate
ZONDA: Benralizumab significantly reduced annualised asthma exacerbation rate, while reducing OCS doses at Week 28 2.5 -70% (p< 0.001) -55% (p=0.003) Placebo Exacerbation definition (at least 1)2 2.0 • A temporary bolus/burst of Annual AER (rate ratio) (1.33-2.50) Benralizumab Q4W 1.83 Benralizumab
Slide 15: Characterising responders to benralizumab for severe asthma: pooled SIROCCO and CALIMA analysis
OA2902 Characterising responders (enhanced efficacy) to benralizumab for severe asthma: pooled analysis of the SIROCCO and CALIMA studies J. Mark FitzGerald1, Eugene R. Bleecker2, Andrew Menzies-Gow3, James G. Zangrilli4, Paul Metcalfe5, Ian Hirsch4, Paul Newbold6, Mitchell Goldman4 1Centre for Hear
Slide 16: Objectives and methods
Objectives To determine the relationship between benralizumab’s clinical efficacy versus baseline blood eosinophil counts and exacerbation history To identify other intrinsic and/or extrinsic factors that might influence benralizumab’s efficacy Methods • Post hoc analysis of pooled results for SIROC
Slide 17: Subgroup analysis of benralizumab Q8W AER and FEV1 response
Subgroup analysis of benralizumab Q8W treatment AER and FEV1 response (baseline blood eosinophils ≥300 cells/µL; full analysis set, pooled) Larger AER reductions and FEV1 improvements were associated with characteristic features of an 17 eosinophilic phenotype including, exacerbation history, OCS us
Slide 18: Annual asthma exacerbation rate reduction with benralizumab Q8W by eosinophil ranges
Annual asthma exacerbation rate reduction with benralizumab Q8W by eosinophil ranges (full analysis set, pooled) 1.8 Placebo Benralizumab 1.6 −36% −37% −43% −50% 1.4 Annual exacerbation rate (1.06–1.47) 1.2 (1.05–1.28) estimate (95% CI) (1.02–1.28) (1.00–1.29) 1.25 1.0 1.16 1.14 1.14 0.8 (0.66–0.84)
Slide 19: Prebronchodilator FEV1 increase with benralizumab Q8W by eosinophil ranges
Prebronchodilator FEV1 increase with benralizumab Q8W by eosinophil ranges (full analysis set, pooled) Placebo Benralizumab 500 Prebronchodilator FEV1 change from 99 120 146 239 450 mL mL mL mL baseline to EOT, LS mean (mL) 400 448 350 370 300 250 311 284 200 224 150 191 209 185 100 50 n=752 n=741 n
Slide 20: Greater improvement in symptoms and quality of life with increasing baseline eosinophils
Greater improvement in symptoms and asthma-related quality of life with benralizumab Q8W with increasing baseline blood eosinophil counts Total asthma symptom score ACQ-6 AQLQ(S)+12 ≥0 ≥150 ≥300 ≥450 ≥0 ≥150 ≥300 ≥450 ≥0 ≥150 ≥300 ≥450 cells/µL cells/µL cells/µL cells/µL cells/µL cells/µL cells/µL c
Slide 21: Greater benralizumab Q8W efficacy with more frequent exacerbation history
Greater benralizumab Q8W efficacy for patients with more frequent exacerbation history Blood eosinophil counts Exacerbations in previous year ≥300 cells/µL 2 ≥3 Annual exacerbation ratea n=308 n=198 Rate ratio vs. placebo 0.73 (0.55 to 0.95) 0.45 (0.34 to 0.60) P-value vs. placebo 0.019 <0.001 Prebr
Slide 22: Conclusions
Conclusions • In combination with high-dosage ICS/LABA, benralizumab provides additional benefit for patients with severe, uncontrolled asthma across the spectrum of baseline blood eosinophil counts • Improvements were greater for patients with increased baseline blood eosinophil counts • Enhanced e
Slide 23: Agenda
Agenda Introduction Unmet medical need Characterising responders to benralizumab Tezepelumab Phase IIb PATHWAY Commercial opportunity 23
Slide 24: Efficacy and safety of tezepelumab in adults with severe asthma: A randomised Phase II Study
OA3189 Efficacy and safety of tezepelumab in adults with severe asthma: A randomised Phase II Study Jonathan Corren, M.D.,1 Jane R. Parnes, M.D.,2 Liangwei Wang, Ph.D.,3 May Mo, M.S.,2 Stephanie L. Roseti, A.P.N., M.S.N.,3 Janet M. Griffiths, Ph.D.,3 René van der Merwe, M.B.Ch.B.4 ERS 2017, 9–13 1Da
Slide 25: Functions of TSLP
Functions of TSLP • TSLP is an epithelial-derived cytokine central to the regulation of type 2 immunity1–4 • TSLP expression is increased in the airways of patients with asthma, and correlates with Th2 cytokine and chemokine expression, and disease severity5–7 • Tezepelumab (AMG 157/MEDI9929) is an
Slide 26: PATHWAY Phase 2b placebo-controlled trial design
PATHWAY Phase 2b placebo-controlled trial design (NCT02054130) Tezepelumab 70mg (low dose) SC Q4W (N=145) Tezepelumab 210mg (medium dose) SC Q4W (N=145) Screening Randomisation 1:1:1:1 Tezepelumab 280mg (high dose) SC Q2W (N=146) Placebo SC Q2W (N=148) Screening/run-in period Treatment period (ICS +
Slide 27: Baseline patient characteristics
Baseline patient characteristics Baseline demographics were similar between Placebo Low dose Medium dose High dose treatment groups (ITT population) (70 mg Q4W) (210 mg Q4W) (280 mg Q2W) (N=148) (N=145) (N=145) (N=146) Age, years Mean (SD) 52.2 (11.5) 50.6 (12.4) 52.6 (12.5) 50.1 (12.2) Male n (%) 4
Slide 28: Tezepelumab reduced the annualised AER vs. placebo at Week 52
Tezepelumab treatment reduced the annualised AER vs. placebo at Week 52 Significant reduction in annualised AER for all tezepelumab treatment groups compared with placebo; P<0.001 Asthma exacerbation rate (per patient-year) 0.6 0.67 61%*** 71%*** 66%*** 0.4 Percentage AER reduction vs placebo 0.2 0.
Slide 29: Tezepelumab reduced annualised AER irrespective of baseline biomarker status
Tezepelumab treatment reduced annualised AER vs. placebo at Week 52 irrespective of baseline biomarker status 1.0 Asthma exacerbation rate 0.8 *** 72% (per patient-year) *** *** 77% 0.6 62% *** *** 65% *** 78% ** 65% *** 82% 59% *** 51% *** 73% *** ** 79% ** 63% 63% 0.4 56% *** 71% 43% ** 62% 46% 0.
Slide 30: Tezepelumab increased pre-BD FEV1 vs. placebo at Week 52
Tezepelumab treatment increased pre-BD FEV1 vs. placebo at Week 52 *** ** ** 0.2 ** ** *** *** ** ** *** ** *** *** ** ** *** *** *** *** ** *** Difference in change Least squares mean change from baseline at 0.1 Week 52 (P value) in FEV1 (L)* 0.12 (0.014) 0.0 0.11 (0.022) –0.1 0.15 (0.002) –0.2 Bas
Slide 31: Tezepelumab treatment reduced blood eosinophils
Tezepelumab treatment reduced blood eosinophils 50 Mean change in eosinophil counts 0 –50 (cell/µL)* –100 –150 –200 –250 –300 Baseline 4 12 20 28 40 52 Weeks Placebo (N=148) Tezepelumab 210mg Q4W (medium dose) (N=145) Tezepelumab 70mg Q4W (low dose) (N=145) Tezepelumab 280mg Q2W (high dose) (N=146)
Slide 32: Tezepelumab treatment reduced FENO
Tezepelumab treatment reduced FENO 5 0 Mean change in FENO (ppb)* –5 –10 –15 –20 Baseline 4 8 12 20 28 40 52 Weeks Placebo (N=148) Tezepelumab 210mg Q4W (medium dose) (N=145) Tezepelumab 70mg Q4W (low dose) (N=145) Tezepelumab 280mg Q2W (high dose) (N=146) 32 *Mean and SE of the observed data were p
Slide 33: Tezepelumab treatment reduced total serum IgE
Tezepelumab treatment reduced total serum IgE 100 Mean change in total IgE (IU/mL) 0 –100 –200 Baseline 4 12 20 28 40 52 Weeks Placebo (N=148) Tezepelumab 210mg Q4W (medium dose) (N=145) Tezepelumab 70mg Q4W (low dose) (N=145) Tezepelumab 280mg Q2W (high dose) (N=146) 33 *Mean and SE of the observed
Slide 34: Safety summary
Safety summary Low dose Medium dose High dose Placebo (70 mg Q4W) (210 mg Q4W) (280 mg Q2W) Patients* with (N=148) (N=145) (N=145) (N=146) At least one AE, % 62.2 66.2 64.8 61.6 At least one AE of ≥Grade 18.9 17.9 20.0 14.4 3–5 severity, %† Death (Grade 5 severity†), n 0 1 0 0 At least one serious‡
Slide 35: Conclusions
Conclusions • Tezepelumab treatment reduced blood eosinophil, FENO and total IgE counts, indicating that tezepelumab has important effects on IL-4, IL-5 and IL-13 pathways – Inhibition of TSLP appears to have broader physiological effects than the targeting of individual Th2 cytokines • These data p
Slide 36: Agenda
Agenda Introduction Unmet medical need Characterising responders to benralizumab Tezepelumab Phase IIb PATHWAY Commercial opportunity 36
Slide 37: How does benralizumab compare to currently-approved biologics and those in late-stage development?
How does benralizumab compare to currently-approved biologics and those in late- stage development? 37
Slide 38: How do you see tezepelumab fitting into or potentially changing the treatment paradigm?
How do you see tezepelumab fitting into or potentially changing the treatment paradigm? 38
Slide 39: What factors will enable more asthma patients to benefit from biologic medicines in the future?
What factors will enable more asthma patients to benefit from biologic medicines in the future? 39
Slide 40: Respiratory - strategy: therapy area with potential for biologics leadership
Respiratory - strategy Therapy area with potential for biologics leadership Drivers of market growth Strength in inhaled Leading biologics Disease portfolio modification Biologics Backbone of care Early intervention Transforming outcomes Inhaled +8% Established medicines Benralizumab Epithelium Symb
Slide 41: High economic burden and a clear unmet need will continue to drive the severe asthma and COPD market
High economic burden and a clear unmet need will continue to drive the severe asthma and COPD market Asthma, 2015, G12 Countries1, 2 Asthma, rates1 2015 2017 2025 111 Prevalence 350 360 350 71 55 Diagnosis 64% 65% 40 5 2 Treatment 77% 78% Global G12 markets Diagnosed Treated Maintenance Severe Uncon
Slide 42: Benralizumab: Potential precision medicine for eosinophilic asthma
Benralizumab: Potential precision medicine for eosinophilic asthma Clear patient phenotype Strong Phase III clinical profile Next steps in clinical practice • Annual exacerbation rate (AERR) • Blood eosinophils ≥ 300 cells/μL • Awaiting regulatory decision US (H2 reduction up to 51% 2017), EU and Ja
Slide 43: Tezepelumab: First-in-class/first-in-disease treatment that blocks TSLP
Tezepelumab: First-in-class/first-in-disease treatment that blocks TSLP - an upstream driver of inflammation in asthma Broadest potential role Best-in-disease Phase II efficacy Next steps in clinical practice • Reduced exacerbation rates 61% - 71% • Best in disease T2 profile • Evaluating Phase III
Slide 44: A biologics portfolio that follows the science
A biologics portfolio that follows the science Benralizumab is an anti- Tralokinumab is an anti- Tezepelumab is a eosinophil monoclonal IL-13 monoclonal potential first in class antibody that targets the antibody that blocks monoclonal antibody that IL-5 receptor, thereby binding and signalling of s
Slide 45: Q&A
Q&A 45
Slide 46: Use of AstraZeneca webcast, conference call and presentation slides
Use of AstraZeneca webcast, conference call and presentation slides The AstraZeneca webcast, conference call and presentation slides (together the ‘AstraZeneca Materials’) are for your personal, non- commercial use only. You may not copy, reproduce, republish, post, broadcast, transmit, make availab
Slide 47: Investor science webcast: ERS 2017
Investor science webcast: ERS 2017 Conference call and webcast for investors and analysts, Milan, Italy 13 September 2017