Slide 1: Delivering in Respiratory ATS Analyst Briefing
Delivering in Respiratory ATS Analyst Briefing James Ward-Lilley, VP of RIA Therapy Area AstraZeneca Bing Yao, SVP & Head RIA iMED MedImmune 20 May 2014 San Diego
Slide 2: Cautionary statement regarding forward-looking statements
2 Cautionary statement regarding 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 presentation contains certain forward-looking statemen
Slide 3: Respiratory panel
3 Respiratory panel James Ward-Lilley Bing Yao VP of RIA Therapy Area Head of MedImmune AstraZeneca RIA iMED Maarten Kraan Bill Mezzanotte Chuck Bramlage Head of RIA Head of RIA President, CEO Small Molecules Global Medicines Pearl Therapeutics R&D iMED Development AstraZeneca AstraZeneca
Slide 4: Respiratory Strategy
Respiratory Strategy James Ward-Lilley, VP of RIA Therapy Area AstraZeneca
Slide 5: Our vision is to become an industry leader in innovative inhaled and targeted therapies
Our vision is to become an industry leader in innovative inhaled and targeted therapies for Asthma, COPD, and Idiopathic Pulmonary Fibrosis (IPF)
Slide 6: Significant unmet medical need remains in asthma and COPD
6 Significant unmet medical need remains in asthma and COPD Asthma COPD Number of active patients Number of GOLD-defined patients 70 Inc. 1.7M severe, Inc. 1.8M severe, inadequately inadequately 60 59 controlled despite controlled despite • Significant unmet compliance 54 compliance need remains in
Slide 7: Our Respiratory Strategy
7 Our Respiratory Strategy 1 Unique inhaled therapies 2 Innovation-driven targeted therapies 3 Transform disease management Symbicort® differentiation Introduce novel Evolve treatment paradigms PHC-driven therapies Build differentiated Understand biology and inhaled range Expand therapeutic modaliti
Slide 8: AZ unique inhaled portfolio potential: Clear positioning across the continuum of care
8 AZ unique inhaled portfolio potential: Clear positioning across the continuum of care Asthma: GINA steps and treatment COPD: GOLD patient segments and treatment C D PT010 LABA/LAMA/I PT010 GINA GOLD 4 CS triple ICS/ ≥2 or 1 hospitalisation LAMA 5 + PT001 LAMA Exacerbations per year 4 GOLD 3 Budeso
Slide 9: AstraZeneca's Respiratory Pipeline
9 AstraZeneca’s Respiratory Pipeline Phase l 4 New Products Phase ll 6 New Products Phase lll 3 New Products Small molecule Small molecule Biologic Small molecule Biologic Inhaled TLR7 agonist CXCR2 antagonist benralizumab PT003 benralizumab AZD8848 AZD5069 IL-5R LABA/LAMA IL-5R asthma asthma COPD C
Slide 10: Scientific Leadership in Asthma and COPD
Scientific Leadership in Asthma and COPD Bing Yao, SVP & Head RIA iMED MedImmune
Slide 11: Benralizumab in asthma: Potent anti-IL-5R antibody
11 Benralizumab in asthma: Potent anti-IL-5R antibody Mechanism of Action: anti-IL-5Rα Benralizumab ~40-60% of severe asthmatics have eosinophilia* Eosinophil count associated with exacerbation Binds with high affinity to IL-5Rα and depletes eosinophils through Antibody- Dependent Cell-Mediated Cyto
Slide 12: Benralizumab in eosinophilic asthma: Potential for best-in-disease profile
12 Benralizumab in eosinophilic asthma: Potential for best-in-disease profile 1 Unique MoA 2 Efficacy 3 Dosing The only IL-5 receptor Reduction in asthma Q4W/Q8W targeting antibody exacerbations Potent depletion of Improvement in FEV1 target cells Improvement in ACQ-6 score FEV1 – forced expiratory
Slide 13: Benralizumab: Eosinophil count reduction
13 Benralizumab: Eosinophil count reduction Blood eosinophil count over time in eosinophilic subjects (mITT population) weeks Final dose Primary Dose administered administered analysis All doses of benralizumab decreased blood eosinophil counts to very low levels after first dose. mITT – modified in
Slide 14: Benralizumab: Reduction in Asthma Exacerbation Rates (AER)
14 Benralizumab: Reduction in Asthma Exacerbation Rates (AER) AER by eosinophil group (mITT population) 36% 41% 22% Eosinophilic Non - eosinophilic Met primary endpoint: In the eosinophilic group benralizumab 100 mg had a statistically significant reduction in AER compared with placebo * P<0.169 vs.
Slide 15: Benralizumab: Reduction in Asthma Exacerbation Rates (AER)
15 Benralizumab: Reduction in Asthma Exacerbation Rates (AER) AER by baseline eosinophil cut-off point (mITT population) 24% 30% 43% 57% 57% 70% ≥ 200 cells/μL ≥ 300 cells/μL ≥ 400 cells/μL In the pre-specified subgroup analysis, benralizumab produced greater improvements as baseline blood eosinophi
Slide 16: Benralizumab: Improvement in lung function
16 Benralizumab: Improvement in lung function FEV1 (L) change from baseline (mITT population) FEV1 (L) change from baseline ≥ 200 cells/μL ≥ 300 cells/μL ≥ 400 cells/μL In subjects with blood eosinophil counts ≥200, ≥300 and ≥400 cells/μL, benralizumab resulted in significant improvement from baseli
Slide 17: Benralizumab: Improvement in asthma control in patients with elevated eosinophils
17 Benralizumab: Improvement in asthma control in patients with elevated eosinophils ACQ-6 for baseline eosinophil (mITT population) <300 cells/μL ≥300 cells/μL –0.76 (1.20) –1.00 (1.14) p=0.156 –1.14 (1.19) p=0.079 –1.26 (1.28) p=0.015 Significant improvements from baseline to Week 52 in mean ACQ-6
Slide 18: Benralizumab Phase III asthma development plan
18 Benralizumab Phase lll asthma development plan Two pivotal studies: • Severe asthma uncontrolled on ICS/LABA therapies • A range of blood eosinophil levels to fully characterize which Phase III ongoing patients may respond best to therapy and on track to complete by • Primary endpoint: Reduction
Slide 19: Benralizumab in COPD: Potent anti-IL-5R antibody
19 Benralizumab in COPD: Potent anti-IL-5R antibody Mechanism of Action: anti-IL-5Rα ~30% of severe COPD patients have elevated blood eosinophils* Elevated eosinophil count may be associated with increased exacerbations in this population Binds with high affinity to IL-5Rα and depletes eosinophils t
Slide 20: Benralizumab in COPD: Potential for best-in-class profile
20 Benralizumab in COPD: Potential for best-in-class profile 1 1 Unique MoA 2 2 Efficacy 3 3 Dosing Significant improvement of The only IL-5 receptor FEV1 Q4W/Q8W targeting antibody Did not meet primary end in reduction of COPD Potent depletion of target exacerbations, however cells trend toward red
Slide 21: Benralizumab phase 2a COPD results: Acute exacerbation rate
21 Benralizumab phase 2a COPD results Acute exacerbation rate AECOPD rate for all-comers and by eosinophil group Primary Endpoint not met in overall population; however, reduction in AECOPD* rate for benralizumab with elevated eosinophils *AECOPD = acute exacerbations of COPD
Slide 22: Benralizumab in COPD: Improvement in lung function
22 Benralizumab in COPD: Improvement in lung function Mean change from baseline in FEV1 over time (PP population) P = 0.014 weeks Dose administered Final dose administered Improvement occurred after first dose and sustained PP – per protocol, FEV1 – forced expiratory volume in 1 second
Slide 23: Benralizumab in COPD: Improvement in lung function
23 Benralizumab in COPD: Improvement in lung function Change from baseline to Week 56 in FEV1 by baseline blood eosinophil count (PP population) Significant improvements in FEV1 through to Week 52 and improvement up to 32 weeks post last dose * Statistically significant PP – per protocol, FEV1 – for
Slide 24: Benralizumab in COPD: Improvement in SGRQ-C score
24 Benralizumab in COPD: Improvement in SGRQ-C score Change from baseline to Week 56 in SGRQ-C total and symptom scores by baseline blood eosinophil count (PP population) Greatest improvements in SGRQ-C total or symptom scores seen in patients with blood eos ≥200 and ≥300 cells/μL PP – per protocol,
Slide 25: Benralizumab Phase III COPD development plan
25 Benralizumab Phase III COPD development plan Two pivotal studies: • Moderate to severe COPD patients with high exacerbation risk while receiving appropriate ICS/LABA/LAMA, ICS/LABA or LABA/LAMA therapies Phase III start • Trial includes patients with a range of blood eosinophil levels to planned
Slide 26: Tralokinumab (anti-IL-13) for severe uncontrolled asthma
26 Tralokinumab (anti-IL-13) for severe uncontrolled asthma Mechanism of Action: anti-IL-13 Human antibody blocking IL-13 – a central mediator of asthma Potential biomarkers to target treatment and optimise measures of asthma control Asthma Phase lll start expected 3Q2014 IPF Phase ll ongoing DPP-4
Slide 27: Hypothesis that tralokinumab has enhanced activity with elevated IL-13 pathway activation
27 Hypothesis that tralokinumab has enhanced activity with elevated IL-13 pathway activation DPP-4 and periostin expression levels in lung epithelial cells after IL-13 stimulation IL-13 stimulation increases periostin and DPP-4 expression in lung epithelial cells, with potential as surrogate biomark
Slide 28: Tralokinumab: Effect on Asthma Exacerbation Rates (AER)
28 Tralokinumab: Effect on Asthma Exacerbation Rates (AER) Percentage AER reduction (95% CI) for tralokinumab 300 mg Q2W vs placebo at Week 52 (subgroup analyses) Trends towards greater AER reduction vs placebo in periostin-high and DPP-4-high subgroups, and subjects responsive to bronchodilators an
Slide 29: Tralokinumab: Effect on Asthma Exacerbation Rates (AER)
29 Tralokinumab: Effect on Asthma Exacerbation Rates (AER) AER for tralokinumab 300 mg Q2W vs placebo at Week 52 40% 32% (273, -53) 20% 7% 0% (886, -88) -20% -40% (22, -74) -44% (30, -86) -60% (-2, -89) -57% -67% -80% All (33) Periostin high Periostin low DPP-4 high DPP-4 low (18) (15) (24) (8) Enha
Slide 30: Tralokinumab: Improvement in lung function in periostin-high patients
30 Tralokinumab: Improvement in lung function in periostin-high patients* FEV1 % change from baseline (net of placebo) 25 20.3% 20 (1.2, 39.5) 0.038 14.7% 15 12% (-0.2, 29.5) p=0.054 (1.5, 22.5) 10 0.025 8% (-7.0, 23.0) 5 p=0.294 -0.9% (-15.4, 13.5) 0.897 0 -5 All (33) Periostin high Periostin low D
Slide 31: Tralokinumab Phase IIb asthma results: Secondary endpoints
31 Tralokinumab Phase IIb asthma results Secondary endpoints Tralokinumab 300 mg (Q2W reversible without OCS use) Periostin- Periostin- Secondary endpoints difference All high low DPP-4-high DPP-4-low from placebo (n=33) (n=18) (n=15) (n=24) (n=8) ACQ-6 change from -0.55 -0.68 -0.23 -0.89 -0.43 base
Slide 32: Tralokinumab in asthma
32 Tralokinumab in asthma 1 Novel biomarker 2 Efficacy 3 Target Population Periostin and DPP-4: Improvements across a Phase III will confirm promising IL-13 range of asthma control the population that will surrogate biomarkers measures observed in optimally benefit from for PHC approach Phase llb su
Slide 33: Tralokinumab Phase III asthma development plan
33 Tralokinumab Phase III asthma development plan Two pivotal studies: • Phase III design and patient population builds on learning from the Phase II program Phase III start • Focus will be on the 300mg Q2W dosing schedule and confirming planned for patient biomarker selection criteria 3Q 2014 • Pri
Slide 34: Anti-TSLP (MEDI9929/AMG 157)
34 Anti-TSLP* (MEDI9929/AMG 157) Mechanism of Action: anti-TSLP Strong allergen challenge data (Phase Ib) Decreased EAR & LAR MEDI9929 Decreased blood and sputum eosinophils Reduced FENO * Co-developed with Amgen; EAR - Early asthmatic response; LAR - Late asthmatic response; FENO - Fractional exhal
Slide 35: Anti-TSLP (MEDI9929/AMG 157) data published in NEJM today
35 Anti-TSLP* (MEDI9929/AMG 157) data published in NEJM today Phase II Study in Severe Asthma is Recruiting *Co-developed with Amgen
Slide 36: Severe asthma: Potential to transform disease management by targeting distinct patient subsets
36 Severe asthma: Potential to transform disease management by targeting distinct patient subsets Asthma: Highly heterogeneous disease EOS TH2 Neutro IgE • Developing understanding of underlying cause Neutrophil - CXCR2 Tralokinumab high • Studying patient sub-types TH2 - Driven • Developing diagnos
Slide 37: Q&A
37 Q&A James Ward-Lilley Bing Yao VP of RIA Therapy Area Head of MedImmune AstraZeneca RIA iMED Maarten Kraan Bill Mezzanotte Chuck Bramlage Head of RIA Head of RIA President, CEO Small Molecules Global Medicines Pearl Therapeutics R&D iMED Development AstraZeneca AstraZeneca
Slide 38: Delivering in Respiratory ATS Analyst Briefing
Delivering in Respiratory ATS Analyst Briefing 20 May 2014 San Diego