Astrazeneca Plc · LSE:AZN
Astrazeneca — European Respiratory Society Investor science conference call 2016
39 slides from Astrazeneca's conference presentation, Sep 7, 2016
Slide 1: Investor science conference call European Respiratory Society
Investor science conference call European Respiratory Society 07 September 2016
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: Agenda
Agenda Unmet medical need Dr Colin Reisner Results from the Phase III Dr Mark FitzGerald SIROCCO and CALIMA trials Medical practice Dr Andrew Menzies-Gow Looking forward Tom Keith-Roach 3
Slide 4: Key late-stage medicines & lifecycle Phase III trials or under regulatory review
Key late-stage medicines & lifecycle Phase III trials or under regulatory review* Respiratory & Cardiovascular & Oncology Infection, Autoimmunity Metabolic Diseases Neuroscience (opportunistic) brodalumab* ZS-9* cediranib* AZD3293 (psoriasis) (hyperkalaemia) (ovarian cancer) (Alzheimer’s disease) be
Slide 5: Unmet medical need
Unmet medical need Dr Colin Reisner Chief Medical Officer, Pearl Therapeutics and Head of Clinical, Respiratory Global Medicines, AstraZeneca
Slide 6: 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 7: Eosinophils are a therapeutic target in severe asthma
Eosinophils are a therapeutic target in severe asthma Persistent eosinophilia despite standard treatment is a recognized severe asthma phenotype • Exacerbations are a constant risk for severe asthma Eosinophilia is patients despite current associated with treatments; exacerbations are the regulatory
Slide 8: GINA Guidelines
GINA Guidelines Step 5 Step 4 Step 3 Refer for add-on Step 1 Step 2 treatment, e.g. tiotropium*†, Preferred Low dose ICS Low dose Med/High omalizumab, controller ICS/LABA** ICS/LABA mepolizumab* choice Leukotriene receptor antagonist Med/High ICS Add tiotropium*† Consider low dose Other ICS (LTRA) L
Slide 9: Step-care for asthma
Step-care for asthma1 Approximately 40% of patients with severe asthma (step 4 or step 5 of GINA guidelines) remain uncontrolled on high-dose ICS + LABA2 GINA guidelines1: IL-5 therapy currently available3: Step 5 Mepolizumab Reslizumab Step 4 100mg SC, Q4W 3mg/kg IV Refer for add-on Administration
Slide 10: Benralizumab (Anti-IL-5R α)
Benralizumab (Anti-IL-5R α) A targeted, anti-eosinophil therapy under investigation for asthma • Anti-eosinophil monoclonal antibody that depletes eosinophils via antibody-dependent cell-mediated cytotoxicity (ADCC), the process by which natural killer cells are activated to target eosinophils • Ind
Slide 11: Only benralizumab directly targets the eosinophil
Only benralizumab directly targets the eosinophil Anti-cytokine modalities have an indirect effect on eosinophil function mepolizumab and reslizumab IL-5 IL-13 GM-CSF Eotaxins TSLP In-situ differentiation IL-3 Environmental pathogens IL-4 Epithelia damage IL-33 IL-4 IL-25 benralizumab Leptin 11
Slide 12: WINDWARD
WINDWARD Phase III benralizumab clinical programme in asthma • Largest known Phase III clinical trial programme of any respiratory biologic in asthma • Comprises six Phase III trials in 3,068 patients and 798 sites, across 26 countries SIROCCO1 and CALIMA2 - Efficacy and safety trials of benralizuma
Slide 13: Results from the Phase III SIROCCO and CALIMA trials in severe asthma
Results from the Phase III SIROCCO and CALIMA trials in severe asthma Dr Mark FitzGerald Director, Centre for Heart and Lung Health, Vancouver Coastal Health Research Institute, University of British Columbia, Canada
Slide 14: Results from the Phase III SIROCCO and CALIMA trials in severe asthma
Results from the Phase III SIROCCO and CALIMA trials in severe asthma J Mark FitzGerald Severe Asthma Clinic, VGH University of British Columbia
Slide 15: Conflicts of Interest
Conflicts of Interest • Research funding and/or honoraria from AstraZeneca, Boehringer-Ingelheim, Genentech, GlaxoSmithKline, Hoffmann-La Roche, MedImmune, Merck, Novartis • BC Ministry of Health • Member GINA Executive and of GINA Science Committee 15
Slide 16: Common study objectives: safety and efficacy of benralizumab
Common study objectives: To evaluate the safety and efficacy of benralizumab 30mg sc Q4W or Q8W in severe asthma PRIMARY ENDPOINT • Annual rate of asthma exacerbations KEY SECONDARY • FEV1 ENDPOINTS • Total asthma symptom score OTHER SECONDARY • ACQ-6 score ENDPOINTS • AQLQ(S)+12 score The primary a
Slide 17: Key inclusion criteria
Key inclusion criteria • Males and females, aged 12–75 years • Physician-diag. asthma requiring high-dosage ICS/LABA – Medium dose ICS/LABA cohort included in CALIMA • ≥2 asthma exacerbations in the previous 12 months • Symptomatic during run-in 17
Slide 18: SIROCCO (48 WK), CALIMA (56 WK): Common design
SIROCCO (48 WK), CALIMA (56 WK): Common design Planned 2:1 randomization ratio by eos (≥300/μL vs <300/μL) E Benralizumab 30mg Benralizumab 30mg N SC every 4 weeks SC every 4 weeks Primary R endpoint: O Run- Benralizumab 30mg Benralizumab 30mg AER in Rand L in 1:1:1 SC every 4 weeks SC every 8 weeks
Slide 19: Baseline disease state characteristics
Baseline disease state characteristics were consistent with an uncontrolled asthma population (full analysis set) SIROCCO CALIMAa Benra Q4W Benra Q8W Placebo Benra Q4W Benra Q8W Placebo N=399 N=398 N=407 N=425 N=441 N=440 Gender: female, n (%) 275 (68.9) 252 (63.3) 269 (66.1) 270 (63.5) 273 (61.9) 2
Slide 20: Benralizumab significantly reduced annual asthma exacerbation rate
Benralizumab significantly reduced annual asthma exacerbation rate, AER SIROCCO (48 wks) CALIMA (56 wks) -51%*** 1.60 - 45%*** 1.60 -28%* 1.40 1.40 -36%** 1.20 1.33 1.20 1.00 1.00 0.80 0.80 0.93 0.60 0.73 0.60 0.66 0.65 0.6 0.40 0.40 0.20 0.20 0.00 0.00 Placebo Benra Q4W Benra Q8W *p<0.05; **p<0.01;
Slide 21: SIROCCO and CALIMA: patients with ≥3 prior exacerbations
SIROCCO and CALIMA: patients with ≥3 prior exacerbations Benralizumab produced a similar magnitude of exacerbation reduction in higher risk patients SIROCCO (48 wks) CALIMA (56 wks) 2.5 -57% -46% -51% 2 1.96 -45% 1.5 1.58 1 1.06 0.84 0.86 0.78 0.5 N=118 N=102 N=103 N=97 N=102 N=95 0 SIROCCO CALIMA P
Slide 22: Prolonged time to first exacerbation
Prolonged time to first exacerbation SIROCCO (48 wks) CALIMA (56 wks) 70 70 Probability of experiencing an Probability of experiencing an 60 60 exacerbation (%) exacerbation (%) 50 50 40 40 30 30 20 20 10 10 0 0 0 4 8 12 16 20 24 28 32 36 40 44 48 0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 Time to fi
Slide 23: Benralizumab significantly improved lung function (FEV1)
Benralizumab significantly improved lung function (FEV1† ) SIROCCO (48 wks) CALIMA (56 wks) +159 mL* +116 mL* 0.5 0.5 LS mean difference compared with baseline LS mean difference compared with baseline +106 mL** +125 mL** 0.4 0.4 0.40 0.3 0.35 0.3 0.34 0.33 (L) (L) 0.2 0.24 0.2 0.22 0.1 0.1 0 0 Base
Slide 24: Improvement in FEV1 seen after the first dose
Improvement in FEV1 seen after the first dose of benralizumab; maintained throughout the treatment period SIROCCO (48 wks) CALIMA (56 wks) Benra Q4 Benra Q8 Placebo Benra Q4 Benra Q8 Placebo Mean at Baseline: Mean at Baseline: LS mean difference compared with baseline Benra Q4: 1.673L 0.50 Benra Q4:
Slide 25: Greater lung function improvement in higher risk patients
SIROCCO and CALIMA: patients with ≥3 prior exacerbations Benralizumab produced a greater magnitude of lung function improvement in higher risk patients SIROCCO (48 wks) CALIMAa (56 wks) 600 235 mL* 600 265mL*** 500 LS mean change in FEV1 (mL) LS mean change in FEV1 (mL) 108 mL** 486 500 400 486 400
Slide 26: Benralizumab Q8W improved total daily asthma symptom score
Benralizumab Q8W significantly improved total daily asthma symptom score compared to placebo SIROCCO (48 weeks) CALIMA (56 weeks) N= 267 275 267 N= 248 241 239 0 0 -0.2 -0.2 LS mean difference compared LS mean difference compared -0.4 -0.4 with baseline (L) with baseline (L) -0.6 -0.6 -0.8 -0.8 -1.0
Slide 27: Overall and serious adverse event frequencies similar to placebo
The overall and serious adverse event (AE) frequencies in both studies were similar for benralizumab and placebo in each study • The most common AEs (≥ 5%) were consistent with an uncontrolled asthma population • Imbalance in the frequency of DAEs: mostly single events with no trend in types of even
Slide 28: Conclusions: Benralizumab improved multiple measures of asthma control
Conclusions: Benralizumab 30mg sc significantly improved multiple measures of asthma control in two Phase 3 trials • In patients with severe eosinophilic asthma uncontrolled on standard-of-care ICS/LABA treatment, benralizumab: – Reduced annual asthma exacerbation rates (up to 51%) – Improved lung f
Slide 29: Medical practice
Medical practice Dr Andrew Menzies-Gow Consultant in Respiratory Medicine, and Director, Lung Division, Royal Brompton Hospital, London
Slide 30: How do you define a patient with 'severe asthma'?
How do you define a patient with ‘severe asthma’? How are they treated with todays’ standard of care? What are the greatest remaining unmet needs? 30
Slide 31: How important is exacerbation history?
How important is exacerbation history? What is the relationship between eosinophil levels and asthma severity? 31
Slide 32: How does benralizumab compare versus current therapies?
How does benralizumab compare versus current therapies? What’s your view? 32
Slide 33: What will it take for biologics to be a greater part of asthma care?
What will it take for biologics to be a greater part of asthma care? How do healthcare systems need to evolve? 33
Slide 34: Looking forward
Looking forward Tom Keith-Roach Head of Global Product & Portfolio Strategy, Respiratory, AstraZeneca
Slide 35: Benralizumab regulatory submission expected in H2 2016
Benralizumab regulatory submission expected in H2 2016 ~6,850 Key Patients in largest respiratory Regulatory submission biologic programme in asthma Asthma and COPD COPD GREGALE TERRANOVA ALIZE ZONDA GALATHEA ARIA CALIMA completed* BORA MELTEMI SIROCCO completed* BISE completed* 2016 2017 2018 2019
Slide 36: High economic burden and unmet need will 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 Markets1, 2 Asthma, rates1 2015 2025 103 Prevalence 315 315 69 55 Diagnosis 68% 38 5 2 Treatment 77% Global G12 markets Diagnosed Treated Maintenance Severe Uncontrolled Biologic 9%
Slide 37: Summary
Summary Positive Phase III data with Execution priorities Future milestones SIROCCO and CALIMA Efficacy across exacerbations, US and EU regulatory ZONDA presentation H1 2017 lung function and symptoms submissions H2 2016 Lung function improvements at 4- Full launch preparation underway VOYAGER data
Slide 38: Q&A
Q&A 38
Slide 39: Investor science conference call European Respiratory Society
Investor science conference call European Respiratory Society 07 September 2016
AstraZeneca — European Respiratory Society Investor science conference call 2016 on 6ix