Astrazeneca Plc · LSE:AZN
Astrazeneca — ASCO 2015 investor science event
48 slides from Astrazeneca's conference presentation, Jun 1, 2015
Slide 1: ASCO 2015 investor science event
ASCO 2015 investor science event Chicago, IL, USA 01 June 2015
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: The preliminary announcement contains certain forward-looking statements with respect to the
Slide 3: Agenda
Agenda 1 AstraZeneca Oncology Mondher Mahjoubi Head of Oncology, Global Product & Portfolio Strategy 2 The power of combinations in IO 3 Clinical experience w/MEDI4736 + treme Mohammed M. Dar Scott Antonia VP, Oncology Clinical Development, MedImmune Moffitt Cancer Center, Tampa, FL, USA 4 Small-mol
Slide 4: AstraZeneca Oncology
AstraZeneca Oncology Mondher Mahjoubi Head of Oncology, Global Product & Portfolio Strategy
Slide 5: Oncology: Achieving scientific leadership
Oncology: Achieving scientific leadership ü Iressa Filing (US) ü MEDI4736 (PD-L1) Fast Track (US) cediranib (VEGFR) Filing ovarian cancer (EU) Illustrative ü AZD9291 Breakthrough ü Lynparza AZD9291 Iressa MEDI4736 (US) Approval (US, EU) Filing (US) Approval (US) Filing NSCLC 3L 2014 2015 2016 ü
Slide 6: Small molecules (SM): Growing momentum
Small molecules (SM): Growing momentum AZD9291 - Updated PFS of 13.5 months (AURA 2L study) (EGFR) - Encouraging data in EGFR-mutated 1L lung cancer - Combination with savolitinib to overcome resistance Genetic drivers savolitinib - Responses in MET-amplified gastric cancer (MET) and papillary renal
Slide 7: Immuno-Oncology (IO): Building leadership
Immuno-Oncology (IO): Building leadership 1. Create a diverse 2. Maximise value 3. Unlock the power portfolio across tumour types of combinations Optimising T-cell function Solid tumours and memory IO-IO combinations Inhibition by Haematology micro-environment Antigen presentation and IO-SM combinat
Slide 8: MEDI4736: Potential against haematological cancers
MEDI4736: Potential against haematological cancers Celgene joint development plan across wide range of uses DLBCL1 Lymphoma Relapsed / refractory settings FL2 Front line Multiple myeloma Relapsed / refractory Myelodysplastic syndrome Relapsed / refractory Further indications and combinations to be d
Slide 9: IO: Backbone with various combination partners targeting specific tumour biology
IO: Backbone with various combination partners targeting specific tumour biology - lung cancer example PD-L1 + Iressa Illustrative PD-L1 + AZD9291 Haematology Melanoma PD-L1 + small molecules Breast Lung PD-L1 + NKG2A Bladder PD-L1 mono Head & PD-L1 + OX40 Neck PD-L1 + CTLA-4 PD-1/PD-L1: Promise of
Slide 10: The power of combinations in IO
The power of combinations in IO Mohammed M. Dar Vice President, Oncology Clinical Development, MedImmune
Slide 11: Optimising anti-tumour immunity
Optimising anti-tumour immunity Portfolio addresses major escape mechanisms Key: New since ASCO 2014 Optimising T-cell function and memory PD-L1 CTLA-4 OX40 FP PD-1 NME-2015 OX40 hAb mOX40 combos with OX40 FP combo MEDI4736, treme, rituximab with MEDI4736 CART* (Juno) Antigen presentation Oncolytic
Slide 12: MEDI4736: Trend towards overall survival in NSCLC
MEDI4736: Trend towards overall survival in NSCLC Overall survival (OS) by PD-L1 (NSCLC 10 mg/kg Q2W) • Preliminary OS data from study 1108 are encouraging and suggest that patients with PD-L1 positive tumours may have improved OS compared to patients with PD-L1 negative tumours Unmet need remains i
Slide 13: The promise of combinations: stimulating innate and adaptive immunity
Brakes off Brakes off The promise of combinations NK activation T-cell activation Stimulating both innate and adaptive immunity + T NKG2A PD-L1 Anti-NKG2A Combination with MEDI4736 planned for H2 2015 • Like T-cells, NK cells are also capable of killing tumour cells • NKG2A is expressed both on NK a
Slide 14: The promise of combinations: PD-L1 + OX40 and CTLA-4 + OX40
Brakes off Gas on The promise of combinations T-cell activation T-cell activation PD-L1 + OX40 and CTLA-4 + OX40 T + T PD-L1 OX40 Pre-clinical1 data with PD-L1 2000 PD-L1 2000 OX40 2000 PD-L1 + OX40 T u m o r V o lu m e (m m ) T u m o r V o lu m e (m m ) T u m o r V o lu m e (m m ) 1500 1500 1500 3
Slide 15: Translation of IO strategy into the clinic: OX40 programme
Translation of IO strategy into the clinic: OX40 programme muOX40 + Advanced muOX40 treme or MEDI4736 malignancies MEDI6469 muOX40 + rituximab DLBCL Safety and huOX40FP biomarker huOX40FP Advanced malignancies learnings MEDI6383 huOX40FP + MEDI4736 huOX40mAb huOX40mAb Advanced MEDI0562 + combination
Slide 16: MEDI4736 + treme target two different escape pathways
MEDI4736 + treme target two different escape pathways Scientific rationale Activated T-cell attacks tumour Dendritic cells (DC) process Blocking of B7 binding to and is sustained in the tumour neoantigen CTLA-4 allows T-cell activation presence of PD-L1 blockade Tumour CD8 T-cell Tumour priming B7 C
Slide 17: Study 006: Dose selection for MEDI4736 + treme
Study 006: Dose selection for MEDI4736 + treme Design: Zone-based dose escalation and Phase Ib expansion phase Population: Stage III-IV NSCLC patients who have failed systemic therapy (no restrictions on # of prior therapies) Exploratory endpoints: 1st endpoint: 2nd endpoint: Peripheral Safety Effic
Slide 18: MEDI4736 + treme show efficacy regardless of PD-L1 status
MEDI4736 + treme show efficacy regardless of PD-L1 status Treme doses beyond 1 mg/kg do not increase efficacy M10-20 Q4/2W M10-20 Q4/2W M15 Q4W T1 mg/kg T3 mg/kg T10 mg/kg All cohorts All evaluable subjects1 (n) 27 24 9 632 ORR[2] - n (%) 9 (33%) 6 (25%) 2 (22%) 17 (27%) 95% CI (17% - 54%) (10% - 47
Slide 19: Responses with MEDI4736 + treme: Rapid and durable
Responses with MEDI4736 + treme: Rapid and durable Similar activity across PD-L1 positive and negative subsets PD-L1 positive PD-L1 negative M = MEDI4736; PD-L1 = programmed death-ligand 1; Q#W = every # weeks; SD = stable disease; T = tremelimumab 19
Slide 20: MEDI4736 + treme increases ORR over monotherapy
MEDI4736 + treme increases ORR over monotherapy Important improvement in PD-L1 negative patients Response rates at doses selected for pivotal studies 70% 60% 50% % of subjects 40% 38% 30% 33% 33% 27% 20% 10% 16% 5% 32/200 (9/27) 23/84 (3/9) (5/92) (5/13) 0% All PD-L1+ PD-L1- Mono Study 1108 Combo St
Slide 21: MEDI4736 + treme show promising activity
MEDI4736 + treme show promising activity Large unmet medical need in PD-L1 negative NSCLC patients PD-1/PD-L1 class Durable clinical benefit for a subset of patients monotherapy PD-1/PD-L1 + CTLA-4 MoA Strongest clinically-validated IO-IO combination to date combination Promising clinical activity i
Slide 22: Clinical experience with MEDI4736 + treme
Clinical experience with MEDI4736 + treme Scott Antonia Department Chair and Program Leader, Thoracic Oncology and Program Leader of the Immunology Program at Moffitt Cancer Center, Tampa, FL, USA
Slide 23: Study overview
Study overview Study design Key elements Ph Ib zone-based dose escalation design with ability to expand selected cohorts for safety/PD/efficacy Previously-treated patients with NSCLC Key eligibility criteria Key inclusion criteria Key exclusion criteria ECOG PS 0–1 Active or prior auto-immune diseas
Slide 24: MEDI4736 + tremelimumab: PK/PD summary
MEDI4736 + tremelimumab: PK/PD summary • PK exposure consistent with respective monotherapy studies; suggesting no PK interaction • Dose as low as 1 mg/kg of tremelimumab in combination demonstrated log fold greater peripheral pharmacodynamic activity (T-cell proliferation/activation) compared to ME
Slide 25: Treme 1 mg/kg Q4W well tolerated in combo with MEDI4736
Treme 1 mg/kg Q4W well tolerated in combo with MEDI4736 • Related grade 3/4 AEs and discontinuations due to related AEs were lowest in the 1 mg/kg Q4W tremelimumab cohorts • AEs did not appear related to dose or schedule of MEDI4736 M10-20 Q4/2W M10-20 Q4/2W M15 Q4W T1 mg/kg T3 mg/kg T10 mg/kg n=56
Slide 26: Related grade 3/4 events of special interest
Related grade 3/4 events of special interest Comparison to MEDI4736 monotherapy M10-20 Q4/2W Mono (study 1108) System organ class Event T1 mg/kg n=228 n=56 Any event 3% 13% Diarrhea <1% 5% Gastrointestinal Colitis 0% 2% Respiratory Pneumonitis 0% 0% Skin Rash (maculopapular) <1% 0% Hyperthyroidism <
Slide 27: Time to response and duration of response
Time to response and duration of response Patient continued to be treated after initial PD Time to and on-treatment response Off-treatment response Time to response D/C treatment Response ongoing Weeks since treatment initiation 27
Slide 28: MEDI4736 + treme combination: High activity and manageable safety
MEDI4736 + treme combination: High level of activity and manageable safety • MEDI4736 20 mg Q4W and tremelimumab 1 mg/kg Q4W (M20T1 Q4W) has been selected for Phase III development – Maximizes PD-L1 inhibition – Demonstrates manageable safety – Incorporates biologically-active dose of tremelimumab a
Slide 29: Small-molecule combinations
Small-molecule combinations Susan Galbraith Head of Oncology, Innovative Medicines Biotech Unit
Slide 30: Combination of targeted therapy and immune checkpoints
Combination of targeted therapy and immune checkpoints Targeted therapies: High response rate IO: High duration of response Example of AZD9291 + % Survival Targeted therapies + IO Immunotherapy Targeted therapy Chemotherapy Time Potential synergistic effect High RR and median PFS of targeted therapi
Slide 31: BRAFi + MEKi + MEDI4736
BRAFi + MEKi + MEDI4736 Unprecedented ORR (69%) and DCR (100%) Potential for well-tolerated, durable benefit Tumour size change from baseline: Cohort A in BRAFm melanoma Screening Cohort A (M+D+T) N- / n = 24 / 25 Change from baseline (%) 12 month treatment period BRAF MEDI4736 3 or 10 mg/kg Q2W Coh
Slide 32: Lynparza + MEDI4736
Lynparza + MEDI4736 DNA damage prone to immune response Rationale T-cell infiltrates in BC • BRCA-mutant breast and ovarian cancers associated with a CXCR3+ T-cell lymphocytic infiltrate: Immune response Sporadic BRCA-pathway deficient associated with DNA damage1,2 • High CXCL10, IDO, IFN gene expre
Slide 33: EGFRm+ NSCLC: SM-IO combination strategy
EGFRm+ NSCLC: SM-IO combination strategy 1L EGFRm+ 2L EGFRm+ T790M+ T790M- AZD9291 AZD9291 Other Targeted therapy combi- Iressa nations Improving response rates and prolonging duration of response AZD9291 + MEDI4736 Targeted therapy + IO Iressa + MEDI4736 TATTON study 33
Slide 34: AZD9291 + MEDI4736: TATTON study
AZD9291 + MEDI4736: TATTON study Potential for new SoC in EGFRm+ NSCLC Basket study in EGFRm+ NSCLC after Best percentage change from baseline in target progression on prior EGFRi lesion size AZD9291 + MEDI4736 arm 80% • Both drugs tolerated at full dose 60% 40% • One grade 3 AE at this dose (WBC de
Slide 35: Iressa + MEDI4736 in EGFRm TKI-naïve NSCLC
Iressa + MEDI4736 in EGFRm TKI-naïve NSCLC Providing evidence of good combinability for MEDI4736 Initial clinical data Tumour assessment: Expansion phase • Both drugs tolerated at full dose • Two expansion cohorts at full doses: – Arm 1 concomitant (n=6 evaluable) – Arm 2 four weeks monotherapy Ires
Slide 36: Additional small molecule + MEDI4736 combinations
Additional small molecule + MEDI4736 combinations Significant opportunities across multiple tumour types Mechanism Indication Study start IDO Solid tumours Dec 2014 BTK/ITK DLBCL, FL, solid tumours Mar 2015 STAT3 Solid tumours Q3 2015 CXCR2 Solid tumours Q3 2015 FGFR Bladder cancer Q3 2015 PI3Kβ/δ B
Slide 37: Small-molecule combinations: SM + MEDI4736 tested in >2,700 patients
Small-molecule combinations SM + MEDI4736 potential tested in >2,700 patients Tolerability MEDI4736 is tolerated in combination at full dose with multiple SMs Encouraging preliminary efficacy data. Update with larger patient Efficacy numbers and duration of follow-up later this year IO-targeted ther
Slide 38: IO: Maximising value across tumour types
IO: Maximising value across tumour types Robert Iannone Head of Immuno-Oncology, Global Medicines Development
Slide 39: IO strategy
IO strategy Focus on combination & first-mover indications • Mono MEDI4736 in PD-L1 positive NSCLC 3L+ / Head & Speed Neck (SCCHN) 2L • MEDI4736 + treme in PD-L1 negative SCCHN 2L • Early-stage disease e.g. Adjuvant and stage III Differentiation unresectable NSCLC • Chemo-free regimen e.g. MEDI4736
Slide 40: NSCLC: IO development programmes
NSCLC: IO development programmes Total now includes more than 5,600 patients Unresectable Adjuvant stage III 1st line 2nd line ≥3rd line ADJUVANT PACIFIC MYSTIC NEW ATLANTIC MEDI4736 vs. placebo MEDI4736 vs. placebo MEDI4736 + treme MEDI4736 PD-L1+ vs. MEDI4736 vs. SoC single arm MEDI4736 + treme NE
Slide 41: Additional tumour types: Exploring MEDI4736 + treme combination
Additional tumour types: Exploring the benefit of MEDI4736 + treme combination SCCHN Gastric Pancreas Bladder 2L 2/3L 2L 1L PD-L1+ Randomised Phase II Randomised Phase III HAWK Phase II MEDI4736 + treme vs. MEDI4736 + treme vs. MEDI4736 single-arm MEDI4736 + treme MEDI4736 vs. treme MEDI4736 vs. SoC
Slide 42: IO development summary
IO development summary Pivotal Phase II & Phase III studies in >8,300 patients # of Phase II studies # of Phase III studies Lung 1 8 Mesothelioma 1 - SCCHN 2 1 Gastric 1 - Pancreas 1 - Bladder - 1 Total 6 10 42
Slide 43: IO: Maximising value across tumour types
IO: Maximising value across tumour types Pioneer in IO combinations; registration studies well underway • Well-tolerated MEDI4736 + treme combination dose has been selected for Phase III and studies have been initiated • Comprehensive registration programme with MEDI4736 is underway across multiple
Slide 44: Closing and Q&A
Closing and Q&A Pascal Soriot Chief Executive Officer
Slide 45: AstraZeneca Immuno-Oncology: Pioneer in next-generation medicine
AstraZeneca Immuno-Oncology Pioneer in next-generation medicine Scientific leadership Future IO Combo therapy Now PD-L1 + CTLA-4 2011 IO Monotherapy PD-L1 + OX40 PD-L1 + NKG2A 1990s ipilimumab PD-1 / PD-L1 PD-L1 + small IL-2, IFN molecules / chemo Leadership Targeted small molecules, e.g. Iressa, Ly
Slide 46: Q&A
Q&A Please press *1 on your phone if you wish to ask a question Q&A • Pascal Soriot, moderator • Scott Antonia, Moffitt Cancer Center • Mondher Mahjoubi • Mohammed M. Dar • Susan Galbraith • Robert Iannone Q&A expected to end at 10pm 46
Slide 47: Thank you for joining today's ASCO investor science event
Thank you for joining today’s ASCO investor science event Please join for drinks in Continental Room C 47
Slide 48: ASCO 2015 investor science event
ASCO 2015 investor science event Chicago, IL, USA 01 June 2015