Astrazeneca Plc · LSE:AZN
Astrazeneca — Non-Deal Roadshow (November 2013)
48 slides from Astrazeneca's roadshow presentation, Nov 7, 2013
Slide 1: MedImmune R&D Roadshow
MedImmune R&D Roadshow November 7, 2013 Gaithersburg, Maryland
Slide 2: Cautionary Statement Regarding Forward-Looking Statements
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 statements
Slide 3: Agenda
Agenda Presentations: Dr. Bahija Jallal, Executive Vice President, AstraZeneca Head of MedImmune Dr. Bing Yao, Head of Respiratory, Inflammation & Autoimmune iMed Dr. Ed Bradley, Head of MedImmune Oncology iMed Q&A Reception 3
Slide 4: MedImmune, the global biologics R&D arm of AstraZeneca
MedImmune, the global biologics R&D arm of AstraZeneca Dr. Bahija Jallal Executive Vice President, AstraZeneca Head of MedImmune
Slide 5: Today's Discussion
Today’s Discussion Enterprise Strategy MedImmune’s Roadmap 5
Slide 6: Our Strategic Priorities
Our Strategic Priorities 1 2 3 Achieve Return Be a great scientific to growth place to work leadership 6
Slide 7: Achieve Scientific Leadership
Achieve Scientific Leadership 1 FOCUS on distinctive science in 3 core TAs Achieve PRIORITISE & ACCELERATE our pipeline scientific leadership TRANSFORM our innovation culture & model 7
Slide 8: Our core focus
FOCUS on distinctive science Our core focus in 3 core TAs Cardio- Respiratory/ Metabolism Oncology inflammation Infection & Vaccines Neuroscience Core TAs Opportunity-Driven Small Protein Biologics Molecules Immuno-therapies engineering 8
Slide 9: Growing late-stage pipeline
PRIORITISE & ACCELERATE Growing late-stage pipeline our pipeline Phase 1 - 25 NMEs Phase 2 - 23 NMEs Phase 3 / Reg - 8 NMEs Small molecule Biologics Small molecule Biologics Small molecule Biologics AZD5363* MEDI0639* selumetinib* MEDI-551* lesinurad moxetumomab* AKT solid tumours DLL-4 solid tumour
Slide 10: Bringing It Together
TRANSFORM our innovation Bringing It Together culture & model “Biotech Organizations” “Large Pharma” Research To POC Late Stage Development Innovative Medicines Small Molecules Global Medicines Development Combination Projects Scientific Collaboration Small Molecules & Biologics MedImmune Biologics
Slide 11: Co-locate around three strategic sites
TRANSFORM our innovation Co-locate around three culture & model strategic sites Gaithersburg Cambridge Mölndal Co-locate around Co-locate R&D in world-class Leverage historical strength biologics/specialty care science cluster Respiratory and CV/Met Proximity to NIH, New site in Cambridge with close
Slide 12: Today's Discussion
Today’s Discussion Enterprise Strategy MedImmune’s Roadmap 12
Slide 13: Building on a deep heritage of innovation
Building on a deep heritage of innovation During the past 25 years, MedImmune has played a role in the following… RSV Inflammatory Diseases HPV Vaccine RespiGam 1996 2002 2009 CMV Flu Vaccine SLE 1998 2003 2011 RSV HPV Vaccine Flu Vaccine 1998 2006 2012 13
Slide 14: Distinctive MedImmune strength in immunology is a foundation across TAs
Distinctive MedImmune strength in immunology is a foundation across TAs CVMD RIA Oncology ID / Vaccines NS Type 2 Respiratory & Immune Adjuvants & Neuro- Diabetes Autoimmune Mediated Chronic Inflammatory Disease Cancer Tx Infection Tx Deep understanding of immunology biology 14
Slide 15: MedImmune Antibody Technologies
MedImmune Antibody Technologies Competitive antibody design and protein engineering toolkit lets us tackle multiple targets Single-chain Bispecific Ab-drug Ab NK conjugate immunotoxin T cell mAb Ab (+YTE) mimetic BiTE Antibody* Internalized Ab Agonist/ ADCC antagonist mAb Blocks Induction Release of
Slide 16: Personalized healthcare and diagnostics
Personalized healthcare and diagnostics 80% of our pipeline has a personalized healthcare approach Meaningful questions being asked by our Personalized Healthcare colleagues: • What is the right indication to pursue in the clinic? • What are the patient populations most likely to respond? • What is
Slide 17: Characteristics of biologics seem to lead to greater likelihood of success
Characteristics of biologics seem to lead to greater likelihood of success NME Success By Molecule Size 2007–2011 Industry Portrait Preclinical Phase 1 Phase 2 Phase 3 Registration NME Entries To 1.2 1.2 Achieve 1 Approval 2.0 1.9 Small 4.3 Large Small 7.6 9.9 Large 10.3 24.7 Success Rate For 61% 42
Slide 18: Biologics Pipeline
Biologics Pipeline Pre-Clinical Submission/ Discovery Phase 1 Phase 2 Phase 3 Development Approved Oncology Oncology Anti-DLL-4 MAb Moxetumomab Anti-IGF Mab Anti-CD19 MAb Moxetumomab Q-LAIV Flu Solid Tumor Pasudotox MBC CLL Pasudotox Vaccine Leukemia/Lympho Hairy Cell Leukemia Influenza Oncology Ant
Slide 19: Programs in Phase 3 in 2013
Programs in Phase 3 in 2013 Benralizumab Brodalumab Moxetumomab IL-5R IL-17RA CD22 Asthma Psoriasis (PsO) Hairy Cell Leukemia (HCL) • Phase 3 started in October • Phase 3 started Aug 2012 • Phase 3 started in May • Estimated biologics license • Estimated biologics license application filing 2015 app
Slide 20: MedImmune's Roadmap
MedImmune’s Roadmap 2013-2014 2015-2016 2016+ Immediate priorities Mid-term goals Long-term aspiration • Deliver mid-stage cohort • Deliver next • Steady state delivery of of assets to Ph3 biologics license important medicines to application patients • Focus on immune- mediated therapies for cancer
Slide 21: Helping Patients with Respiratory, Inflammation & Autoimmune Diseases
Helping Patients with Respiratory, Inflammation & Autoimmune Diseases Dr. Bing Yao, Senior Vice President and Head of RIA iMed, MedImmune
Slide 22: Vision is to be industry leader in innovative inhaled and targeted therapies
Vision is to be industry leader in innovative inhaled and targeted therapies for people with asthma, COPD, and IPF Innovation-driven targeted Unique inhaled therapies therapies • Understand patient phenotypes • Symbicort® (clinical and molecular) (budesonide/formoterol fumarate dihydrate) Inhalation
Slide 23: Significant unmet needs and opportunity for growth in asthma and COPD
Significant unmet needs and opportunity for growth in both asthma and COPD Asthma1 - $19 billion, growing 6.5% COPD1 - $15 billion, growing 8.8% Number of active patients (G7 markets, M)1 Number of active patients (G7 markets, M)2 53 86 2.0M severe, 39 inadequately controlled despite 34 compliance 2
Slide 24: Unmet need and shared biology presents a significant opportunity in autoimmune diseases
Unmet need and shared biology presents a significant opportunity in autoimmune diseases Pursue potential therapeutic spanning Explore shared biology and pathway multiple indications Cytokines e.g., IFNa, IL17, IL23 MS T-Cell Co-stimulators PsA e.g., B7RP RA Effector Macrophages e.g., GM-CSF Lupus T
Slide 25: A robust respiratory and autoimmune disease portfolio
A robust respiratory and autoimmune disease portfolio Phase 1 Phase 2a Phase 2b Phase 3 MEDI9929 Benralizumab Brodalumab Brodalumab Dx TSLP Asthma * IL5R, COPD IL17R, PsA * IL17R, PsO * Dx MEDI5872 MEDI8968 Tralokinumab Benralizumab B7RP1, SLE * IL1R, COPD IL13, Asthma IL5R, Asthma MEDI-551 CD19, MS
Slide 26: Personalized healthcare approach: targeting different segments of severe asthma
Personalized healthcare approach: targeting different segments of the severe asthma Asthma is a highly heterogeneous MEDI9929 disease (TSLP) tralokinumab Neutrophil- AZD5069 Developing (IL-13) high (CXCR2) understanding of TH2- underlying cause driven Studying patient sub- brodalumab types (IL-1
Slide 27: Benralizumab (MEDI-563): asthma (Ph3) targeted therapy for severe eosinophilic asthma
1) Benralizumab (MEDI-563): asthma (Ph3) targeted therapy for severe eosinophilic asthma Mechanism of Action: anti-IL-5Rα Eosinophilic asthma Asthmatics with eosinophilia represent ~40-60% of severe asthmatics Eosinophil count associated with exacerbation Binding with high affinity to IL-5Rα d
Slide 28: Benralizumab potently depletes eosinophils
Benralizumab potently depletes eosinophils Eosinophil depletion in periphery Eosinophil depletion in lung 0.4 Dose (mg/kg) 0.0003 (n=5) 0.3 Pre-Dose Blood EOS (x10-3) 0.003 (n=6) 0.03 (n=6) 0.3 0.1 (n=6) 0.3 (n=6) 0.0 1 (n=9) 3 (n=6 Post-Dose -0.1 -20 -5 10 25 40 55 70 85 Study day 28 Note: Study co
Slide 29: Phase 2a showed reduced exacerbations and hospitalizations
Phase 2a showed reduced exacerbations and hospitalizations in a high risk patient population Decreased rate of exacerbations Decreased rate of ICU/hospital admissions/ED visits 60 Placebo 50 0.3 mg/kg Exacerbations 1.0 mg/kg -50% 40 30 20 10 0 0 30 60 90 120 150 180 Study day 29 Molfino et al, ATS 2
Slide 30: Benralizumab with novel mechanism of action enters Ph3
Benralizumab with novel mechanism of action enters Ph3 for eosinophilic patients Differentiation Development plan Receptor vs. ligand approach Phase 3 start asthma Announced the Phase III Windward program Q4/8W subcutaneous dosing on 30 October Complete eosinophil depletion with potential Ph
Slide 31: Tralokinumab (CAT-354): asthma Ph2b targeted against a cytokine central to asthma
2) Tralokinumab (CAT-354): asthma Ph2b targeted against a cytokine central to asthma Mechanism of Action: Anti-IL-13 Target severe, inadequately controlled asthma Tralokinumab a fully human antibody targeting IL-13 Key cytokine involved in many aspects of asthma Validated target from pre- cl
Slide 32: Tralokinumab has demonstrated clinical response
Tralokinumab has demonstrated clinical response Change in baseline in lung function Development plan Placebo (n=42) Phase IIB asthma Follow-Up Period Tralokinumab • Assesses exacerbation reduction Combined (n=144) vs. placebo in severe uncontrolled asthma • Evaluating spectrum of blood and serum bio
Slide 33: Brodalumab: high unmet needs remain for psoriasis
3) Brodalumab: high unmet needs remain for psoriasis and IL-17 family of cytokines are drivers of the diseases IL-1 ~12M diagnosed PsO patients in the 7 major markets* Plaques that can cover >10% of the body Severe disease significantly impacts quality of life due to location of plaques, pain,
Slide 34: Brodalumab Ph1/2 Results
BrodalumabPercentage (Ph3)Improvement Ph1/2 inResults PASI Scores over Time. Percentage Improvement in PASI Scores over Time. Figure 1. Percentage Improvement in PASI Scores over Time. The P value for the comparison of the 70-mg dose of brodalumab with placebo (P<0.001) is for all the time points ex
Slide 35: Brodalumab: Psoriatic Arthritis Phase 2 Study Summary
Brodalumab: Psoriatic Arthritis Phase 2 Study Summary Phase 2 study of brodalumab demonstrated efficacy in PsA with acceptable safety profile Primary endpoint of study was met with both doses of brodalumab (140 mg Q2W and 280 mg QW) demonstrating superiority to placebo for ACR 20 responses No
Slide 36: Additional Phase I and II Investigational Programs
Additional Phase I and II Investigational Programs Disease Disease area Asset Mechanism Phase area Asset Mechanism Phase COPD benralizumab IL-5Rα II Crohn’s MEDI2070 IL-23 II Disease MEDI8968 IL1-R II MEDI7183 α4β7 II SLE MEDI5872 B7RP1 I Asthma tralokinumab IL-13 II sifalimumab IFNα II brodalumab a
Slide 37: MedImmune's Competitive Advantage in RIA
MedImmune’s Competitive Advantage in RIA Robust Broad spectrum of respiratory and autoimmune pipeline diseases Transformative To evolve treatment paradigm from “failure-based therapies approach” to personalized Accelerated Multiple programs with potential to move into Phase delivery III by the end o
Slide 38: Exploring New Approaches in Oncology
Exploring New Approaches in Oncology Dr. Ed Bradley, Senior Vice President and Head of the Oncology iMed, MedImmune
Slide 39: MedImmune Oncology Biologics Strategy
MedImmune Oncology Biologics Strategy Specific Immune Targeting Specific Tumor Targeting Immune Mediated Generating potent Armed antibodies Therapy (IMT) immunologic response via T cell Precise tumor targeting modulation and other to cause cell death with immune cell range of technologies, mechanism
Slide 40: Empowering the Immune System to Fight Cancer
Empowering the Immune System to Fight Cancer The biologics IMEDs “If we are ever going to use the word ‘cure’, the immune system is going to come into play.” Stephen Hodi, M.D., Dana-Farber, WSJ 6/14/11 40
Slide 41: Critical Checkpoints Hijacked by Cancer
Critical Checkpoints Hijacked by Cancer Putting the Gas Putting the Brakes on the immune on the immune system system (+) (-) Tremelimumab Activating Inhibitory Receptors Receptors MEDI6469 AMP-514 Oncology iMED Cell PD-L1 MIC-A MEDI4736 CD40 B7-H3 Adapted from Mellman, I. Nature 480: 480-489, 2011 4
Slide 42: Spotlight: MEDI4736 or Anti-PD-L1 mAb
Spotlight: MEDI4736 or Anti-PD-L1 mAb 42
Slide 43: How This Works
43 How This Works The biologics Oncology IMEDs iMED
Slide 44: IMT-C and IMT-C Combinations Are Now Clinically Validated
IMT-C and IMT-C Combinations Are Now Clinically Validated ASCO 2011 Approval of first anti-CTLA4 with impressive prolonged OS, in melanoma ASCO 2012 Next IMT pathway validated: PD-1 extends activity to lung ASCO 2013 Synergy of PD-1 and CTLA-4 dramatically validated pre- clinical models 44
Slide 45: Immune Therapy Portfolio Enables Novel Combinations
Immune Therapy Portfolio Enables Novel Combinations Tremelimumab MEDI4736 AMP-514 MEDI6469 Anti-CTLA-4 mAb Anti-PD-L1 mAb Anti-PD-1 mAb mOX40 agonist mAb Phase 2 in solid tumours Phase 1 in solid Humanized, anti-PD-1 Murine mAb in Phase tumours IgG4 1 in solid tumours Validated pathway V
Slide 46: MEDI4736 – Early Phase 1 Clinical Activity Observed
MEDI4736 – Early Phase 1 Clinical Activity Observed Phase I Highlights Documented Clinical Evidence • Encouraging level of clinical activity in Phase 1 dose escalation with responses observed at lowest dose tested • Early tumor shrinkage was observed across a range of doses • Manageable safety profi
Slide 47: IMT-C Development Plan Focused on Novel, Proprietary Combination Opportunities
IMT-C Development Plan Focused on Novel, Proprietary Combination Opportunities 2013 2014 2015 H2 H1 H2 H1 H2 Monotherapy in new indications with favourable immune signature Novel IMT-C combinations: • MEDI4736 (PD-L1) + Tremelimumab • CTLA-4 + mOX40 Registration enabling Other proprietary IMT-C tria
Slide 48: The Power of a Combined Portfolio
The Power of a Combined Portfolio AZ and MedImmune are uniquely positioned to combine agents within and between key scientific mechanisms Target key Enhance immune Tip cancer cells response to Potent + Durable tumor drivers into cell death improve overall Response and resistance survival Selected Pr