Slide 1: Clinical Trials Appendix Q4 2014 Results Update
Clinical Trials Appendix Q4 2014 Results Update The following information about ongoing AstraZeneca clinical studies in Phases I-IV has been created with selected information from clinicaltrials.gov to facilitate understanding of key aspects of our clinical programmes and is correct to the best of o
Slide 2: Movement since Q3 2014 update
Movement since Q3 2014 update New to Phase I New to Phase II New to Pivotal Study New to Registration NMEs NMEs NMEs AZD3759 AZD0548¥ lesinurad EGFR TK EGFRm lung cancer LABA asthma/COPD SURI gout AZD8108 AZD0914 NMDA suicidal ideation GyrAR serious bacterial infection AZD8835 AZD3293 PI3Kα solid tu
Slide 3: Q4 2014 NME Pipeline
Q4 2014 NME† Pipeline Phase 1 (38 New Molecular Entities†) Phase 2 (28 New Molecular Entities†) Phase 3 / Registration (13 New Molecular Entities†)1 Small molecule Large molecule Small molecule Large molecule Small molecule Large molecule AZD3759 MEDI0639 AZD1775 MEDI-551 AZD9291ψ MEDI4736 EGFR EGFR
Slide 4: 2015-2016: 14-16 NME & LE submissions
2015-2016: 14-16 NME & LE submissions MEDI4736 + tremelimumab 2L SCCHN Faslodex MEDI4736 1L metastatic breast 2L SCCHN cancer Lynparza LE submission Brilinta BRCAm metastatic opportunities stroke breast cancer Lynparza saxa/dapa FDC brodalumab* BRCAm PSR type 2 diabetes psoriatic arthritis ovarian c
Slide 5: Clinical trials – Approved medicines
AstraZeneca Clinical trials – Approved medicines Q4 2014 Results Update
Slide 6: Symbicort (ICS/LABA)
Symbicort (ICS/LABA) Mild asthma development programme Patient Population Phase # of Design Endpoint(s) Status Study patients Patients in need of GINA Phase III N = 3750 • ARM 1: Symbicort Turbuhaler 160/4.5 μg • Well controlled asthma weeks • FSI: Q3 14 step 2 treatment SYGMA1 'as needed' + Placebo
Slide 7: Epanova (prescription grade Omega-3 free fatty acid EPA+DHA)
Epanova (prescription grade Omega-3 free fatty acid EPA+DHA) Hypertriglyceridaemia development programme Patient Population Phase # of Design Endpoint(s) Status Study patients Severe hyper- Phase III N = 162 • ARM 1: Epanova 2g QD • Change in serum triglycerides over 12 weeks • FSI: Q4 13 triglyceri
Slide 8: Epanova (prescription grade Omega-3 free fatty acid EPA+DHA)
Epanova (prescription grade Omega-3 free fatty acid EPA+DHA) Hypertriglyceridaemia development programme Patient Population Phase # of Design Endpoint(s) Status Study patients Type 2 DiM Phase II N = 100 • ARM 1: Epanova 4g QD • Reduction in liver fat content (%) at the end • FSI: Q1 15 Liver fat >5
Slide 9: Onglyza (DPP-IV inhibitor)
Onglyza (DPP-IV inhibitor) Type 2 Diabetes development programme Patient Population Phase # of Design Endpoint(s) Status Study patients Type 2 Diabetes Phase III N = 444 • ARM 1: Onglyza 5 mg QD +insulin or Primary: • FSI: Q2 14 Mellitus Onglyza 5 mg QD+ insulin + Met • Change from baseline in HbA1C
Slide 10: Forxiga/Farxiga (SGLT-2 inhibitor)
Forxiga/Farxiga (SGLT-2 inhibitor) Diabetes development programme Patient Population Phase # of Design Endpoint(s) Status Study patients Type 2 diabetes Phase III/IV N = 17150 • ARM 1: Forxiga 10 mg QD + standard of • Time to first event included in the composite • FSI: Q2 13 mellitus with high DECL
Slide 11: Forxiga/Farxiga (SGLT-2 inhibitor)
Forxiga/Farxiga (SGLT-2 inhibitor) Diabetes development programme Patient Population Phase # of Design Endpoint(s) Status Study patients Asian Subjects With Phase III N = 260 ARM 1: Forxiga 10 mg QD for 24 weeks + • Change from baseline in HbA1c at • FSI: Q1 14 Type 2 Diabetes Who background Insulin
Slide 12: Saxagliptin/dapagliflozin (DPP-4/SGLT-2 inhibitors)
Saxagliptin/dapagliflozin (DPP-4/SGLT-2 inhibitors) FDC Type 2 Diabetes development programme Patient Population Phase # of Design Endpoint(s) Status* Study patients Type 2 Diabetes Phase III N = 280 • ARM 1: Saxa 5mg + Dapa 10 mg + Met Primary: • FSI: Q2 12 Mellitus IR • Mean change from baseline i
Slide 13: Bydureon (GLP-1 receptor antagonist)
Bydureon (GLP-1 receptor antagonist) Type 2 Diabetes development programme Patient Population Phase # of Design Endpoint(s) Status Study Patients Type 2 Diabetes Phase III N = 375 • ARM 1: Bydureon BiD SC (autoinjector) • Change in HbA1c from baseline at 28 • FSI: Q1 13 DURATION-NEO 1 • ARM 2: Bydur
Slide 14: Bydureon/exenatide (GLP-1 receptor antagonist)
Bydureon/exenatide (GLP-1 receptor antagonist) Type 2 Diabetes development programme Patient Population Phase # of Design Endpoint(s) Status Study patients Type 2 Diabetes Phase IV N = 14000 • ARM 1: Bydureon once weekly 2mg SC • Time to first confirmed CV • FSI: Q2 10 EXSCEL • ARM 2: Placebo event
Slide 15: Brilinta/Brilique (ADP receptor antagonist)
Brilinta/Brilique (ADP receptor antagonist) PARTHENON development programme Patient Population Phase # of Design Endpoint(s) Status Study patients Patients with prior MI Phase III N = 21000 • ARM 1: Ticagrelor 90 mg BiD • Composite of CV death, non-fatal MI and • FSI: Q4 10 PEGASUS • ARM 2: Ticagrel
Slide 16: Faslodex (oestrogen receptor antagonist)
Faslodex (oestrogen receptor antagonist) Breast cancer development programme Patient Population Phase # of Design Endpoint(s) Status Study patients Postmenopausal women Phase III N ~450 • ARM 1: Faslodex 500 mg monthly IM + an • Progression Free Survival (PFS) • FSI: Q4 12 with HR+ locally FALCON ad
Slide 17: Caprelsa
Caprelsa Thyroid cancer development programme Patient Population Phase # of Design Endpoint(s) Status Study patients Differentiated thyroid Phase III N = 227 • ARM 1: Vandetanib 300 mg oral dose QD • Progression Free Survival • FSI: Q3 13 cancer refractory or • LSI: Q4 14 unsuitable for NCT01876784
Slide 18: Lynparza (PARP inhibitor)
Lynparza (PARP inhibitor) Solid tumours development programmes Patient Population Phase # of Design Primary Status Study patients Endpoint PSR BRCAm ovarian Phase III N = 264 • ARM 1: Lynparza tablets 300 mg BiD as maintenance • Progression Free Survival • FSI: Q3 13 cancer SOLO-2 therapy until prog
Slide 19: Lynparza (PARP inhibitor) continued...
Lynparza (PARP inhibitor) continued... Solid tumours development programmes Patient Population Phase # of Design Primary Status Study patients Endpoint BRCAm metastatic Phase III N = 310 • ARM 1: Lynparza 300 mg BiD, continuous to • Progression Free Survival • FSI: Q2 14 breast cancer OlympiAD progr
Slide 20: Zinforo
Zinforo Serious infections development programme Patient Population Phase # of Design Endpoint(s) Status Study patients Patients with Phase III N = 765 • ARM 1: Ceftaroline fosamil 600 mg q 8 hrs • NI in Clinical Cure rate at the Test of Cure (TOC) • FSI: Q2 12 complicated skin and COVERS (801 actua
Slide 21: FluMist Quadrivalent
FluMist Quadrivalent Vaccine development programme Patient Population Phase # of Design Endpoint(s) Status Study patients Healthy children Phase llI N = 1008 • ARM 1: One or two doses of MEDI3250 • Efficacy • FSI: Q4 14 Age 7-18 years • ARM 2: Placebo • Safety and tolerability • LSI: Q4 14 NCT022694
Slide 22: Gastrointestinal
Gastrointestinal Phase III development programmes Compound Patient Population Phase # of Design Endpoint(s) Status Study Patients Nexium Refractory RE Phase III N = 280 • ARM 1: Nexium 20 mg BiD • Healing of refractory RE • FSI: Q3 12 ROSE • ARM 2: Nexium 20 mg QD • LSI: Q1 14 • Completion date: Q2
Slide 23: Late stage development programmes
AstraZeneca Late stage development programmes Q4 2014 Results Update
Slide 24: Lesinurad (SURI)
Lesinurad (SURI) Gout development programme Patient Population Phase # of Design Primary endpoint Status Study patients Gout with Inadequate Phase III N = 600 • ARM 1: Placebo • Proportion of subjects with an sUA level that • FSI: Q1 12 Hypouricemic Response CLEAR 1 • ARM 2: lesinurad 200 mg QD is <
Slide 25: Anti-IL-17RA (brodalumab)
Anti-IL-17RA (brodalumab) Psoriasis & psoriatic arthritis development programmes Patient Population Phase # of Design Endpoint(s) Status Study patients Moderate to severe Phase III N = 661 • ARM 1: 210 mg brodalumab SC • PASI at wk 12 • Completed plaque psoriasis AMAGINE-1 • ARM 2: 140 mg brodalumab
Slide 26: LABA/LAMA (PT003) & LAMA (PT001)
LABA/LAMA (PT003) & LAMA (PT001) COPD development program Patient Population Phase # of Design Endpoint(s) Status Study patients G = Glycopyrronium, F = Formoterol fumarate Moderate to Very Severe Phase III N = 2054 Treatment (24-week Treatment Period) • Change from baseline in • FSI: Q2 13 COPD PIN
Slide 27: LABA/LAMA (PT003) & LAMA (PT001)
LABA/LAMA (PT003) & LAMA (PT001) COPD development program continued Patient Population Phase # of Design Endpoint(s) Status Study patients G = Glycopyrronium, F = Formoterol fumarate Moderate to Severe Phase IIIb 125 Treatment ( 5- to 6- week Treatment Period) Percentage of devices where number of •
Slide 28: LABA/LAMA (PT003) & LAMA (PT001)
LABA/LAMA (PT003) & LAMA (PT001) COPD development program continued Patient Population Phase # of Design Endpoint(s) Status Study patients G = Glycopyrronium, F = Formoterol fumarate moderate to severe Phase IIIb N=40 Treatments ( 8-week Treatment Period) FEV1 AUC0-24 on Day 29 • FSI: Q1 15 COPD • G
Slide 29: Anti-IL-5Rα (benralizumab)
Anti-IL-5Rα (benralizumab) Asthma development programme Patient Population Phase # of Design Endpoint(s) Status Study patients Severe asthma, Phase III N = 1026 HD + • ARM 1: 30 mg Q8w SC • Annual asthma exacerbation rate • FSI: Q4 13 inadequately controlled CALIMA up to 250 MD • ARM 2: 30 mg Q4w SC
Slide 30: Anti-IL-5Rα (benralizumab)
Anti-IL-5Rα (benralizumab) Asthma development programme (continued) Patient Population Phase # of Design Endpoint(s) Status Study patients Asthmatic with FEV1 (50- Phase III N = 200 • ARM 1: 30 mg Q4w SC • Pulmonary function (FEV1) • FSI: Q1 15 90% predicted) on low to • ARM 3: Placebo SC • Est comp
Slide 31: Anti-IL-5Rα (benralizumab)
Anti-IL-5Rα (benralizumab) COPD development programme Patient Population Phase # of Design Endpoint(s) Status Study patients Moderate to Very Severe Phase III N = 2324 • ARM 1: 10 mg Q8w SC • Rate of COPD • FSI: Q3 14 Chronic Obstructive TERRANOVA • ARM 2: 30 mg Q4w SC exacerbation Pulmonary Disease
Slide 32: Tralokinumab (anti-IL-13)
Tralokinumab (anti-IL-13) Asthma development programme Patient Population Phase # of Design Endpoint(s) Status Study patients Adults with Uncontrolled Phase III N = 1140 Cohort 1: Primary endpoint: • FSI: Q3 14 Severe Asthma STRATOS 1 • ARM 1: Tralokinumab dose regimen 1, SC • Annual asthma exacerba
Slide 33: Roxadustat (HIF-PHI)
Roxadustat (HIF-PHI) Phase III CKD programme Patient Population Phase # of Design Endpoint(s) Status Study patients Anaemia in Chronic Phase III ANDES N = 450-600 • ARM 1: Roxadustat • Haemoglobin response • Sponsored by FibroGen Kidney Disease Patients • ARM 2: Placebo • FSI: Q4 12 Not Receiving NC
Slide 34: AZD9291 (Highly selective, irreversible EGFR TKI)
AZD9291 (Highly selective, irreversible EGFR TKI) NSCLC development programme Patient Population Phase # of Design Endpoint(s) Status Study patients Advanced EGFRm NSCLC Phase I/II N ~ 500 • Dose escalation study • Safety and tolerability • FSI: Q1 13 TKI failure + /- primary AURA • Ph II Extension
Slide 35: Selumetinib (MEK-inhibitor)
Selumetinib (AZD6244, ARRY142886) (MEK-inhibitor) Solid tumours development programmes Patient Population Phase # of Design Endpoint(s) Status Study patients 2nd Line KRASm Phase III N = 634 • ARM 1: Selumetinib 75mg BiD + docetaxel 75 mg/m2 IV on day 1 • Progression Free Survival • FSI: Q3 13 posit
Slide 36: Selumetinib (MEK-inhibitor)
Selumetinib (AZD6244, ARRY142886) (MEK-inhibitor) Solid tumours development programmes Patient Population Phase # of Design Endpoint(s) Status Study patients 2nd Line KRASm Phase II N = 265 • ARM 1: Selumetinib 75mg BiD + docetaxel 75 mg/m2 IV on day 1 • Progression Free Survival • FSI: Q1 13 negati
Slide 37: Anti-PD-L1 (MEDI4736)
Anti-PD-L1 (MEDI4736) Solid tumours development programmes Patient Population Phase # of Design Endpoint(s) Status Study patients Stage IIIB-IV NSCLC Phase II N = 188 • Cohort 1: MEDI4736 IV Q2W (EFGR/ALK WT) • Objective Response Rate • FSI: Q1 14 patients ATLANTIC • Cohort 2: MEDI4736 IV Q2W (EFGR/
Slide 38: Anti-PD-L1 (MEDI4736) continued…
Anti-PD-L1 (MEDI4736) continued… Solid tumours development programmes Patient Population Phase # of patients Design Endpoint(s) Status Study Stage IV Squamous Phase II/III Lung N = 400 (4736 Umbrella study with 5 substudies based on biomarker • Progression Free Survival (PFS) • FSI: Q3 14 NSCLC pati
Slide 39: Anti-PD-L1 (MEDI4736) continued…
Anti-PD-L1 (MEDI4736) continued… Solid tumours development programmes Patient Population Phase # of Design Endpoint(s) Status Study patients Solid Tumors (Treme Phase 1 N=22 • Tremelimumab + MEDI4736 • Safety • FSI: Q2 14 Phase I) combination in • Dose Escalation study • Optimal biologic dose • LSI:
Slide 40: Anti-PD-L1 (MEDI4736) continued…
Anti-PD-L1 (MEDI4736) continued… Solid tumours development programmes Patient Population Phase # of Design Endpoint(s) Status Study patients Solid tumours Phase I Partnered N= 108 • Dose Escalation: N=36, 3 cohorts receiving • Safety and Tolerability • FSI: Q4 14 with KHK Treatment A (mogamulizumab+
Slide 41: Anti-CTLA-4 (tremelimumab)
Anti-CTLA-4 (tremelimumab) Mesothelioma development programme Patient Population Phase # of Design Endpoint(s) Status Study Patients Patients with Phase II N = 564 • ARM 1: Tremelimumab IV • Overall survival (OS) • FSI: Q2 13 unresectable pleural or • ARM 2: Placebo • LSI: Q4 14 peritoneal malignant
Slide 42: Moxetumomab Pasudotox (anti-CD22)
Moxetumomab Pasudotox (anti-CD22) Haematological malignancies development Patient programmes Population Phase # of Design Endpoint(s) Status Study patients Adults with relapsed Phase I N = 49 • Open Label dose escalation study • MTD and efficacy • FSI: Q2 07 refractory HCL • LSI: Q1 14 NCT00586924 •
Slide 43: CAZ AVI (BLI/cephalosporin SBI)
CAZ AVI (BLI/cephalosporin SBI) Serious infections development programme Patient Population Phase # of Design Endpoint(s) Status Study patients Hospitalised patients Phase III N = 493 • ARM 1: CAZ-AVI 2000/500mg plus Metronidazole IV Co primary of: • FSI: Q1 12 with complicated intra- RECLAIM-1 • AR
Slide 44: CAZ AVI (BLI/cephalosporin SBI)
CAZ AVI (BLI/cephalosporin SBI) Serious infections development programme Patient Population Phase # of Design Endpoint(s) Status Study patients Patients with Phase III N = 333 • ARM 1: CAZ-AVI 2000/500mg plus • Patients with clinical cure at the Test of • FSI: Q1 13 complicated urinary tract REPRISE
Slide 45: BACE (AZD3293)
BACE (AZD3293) Alzheimer’s Disease development programme Patient Population Phase # of Design Endpoint(s) Status Study Patients Alzheimer’s Disease Phase II/III N=1551 • ARM 1: AZD3293 20 mg once daily • Change in Clinical Dementia Rating Sum of • FSI: Q3 14 Patients AMARANTH • ARM 2: AZD3293 50 mg
Slide 46: Early development programmes
AstraZeneca Early development programmes Q4 2014 Results Update
Slide 47: LABA/LAMA/ICS (PT010)
LABA/LAMA/ICS (PT010) COPD & Asthma development program Patient Population Phase # of Design Endpoint(s) Status Study patients (B/BD)= Budesonide, FF = Formoterol fumarate) Moderate to Severe Phase II N = 160 • ARM 1: BFF MDI 320/9.6 μg BiD • Forced expiratory volume in 1 • FSI: Q2 14 COPD • ARM 2:
Slide 48: LABA/LAMA/ICS (PT010)
LABA/LAMA/ICS (PT010) COPD & Asthma development program continued Patient Population Phase # of Design Endpoint(s) Status Study patients (B/BD)= Budesonide, FF = Formoterol fumarate) Japanese Healthy Phase I N = 20 Treatment (2-week Treatment Period) • Overall safety • FSI: Q3 14 Volunteers • ARM 1:
Slide 49: LABA/LAMA/ICS (PT010)
LABA/LAMA/ICS (PT010) COPD & Asthma development program continued Patient Population Phase # of Design Endpoint(s) Status Study patients (B/BD)= Budesonide, FF = Formoterol fumarate) Moderate to Very Severe Phase III N = 1800 Treatments ( 24-week Treatment Period) Co-Primary Endpoints (EU): • FSI: Q
Slide 50: LABA/LAMA/ICS (PT010)
LABA/LAMA/ICS (PT010) COPD & Asthma development program continued Patient Population Phase # of Design Endpoint(s) Status Study patients (B/BD)= Budesonide, FF = Formoterol fumarate) Moderate to Very Severe Phase III N = TBD Treatments ( 52-week Treatment Period) Bone Mineral Density Sub-study Endpo
Slide 51: MABA (AZD2115)
MABA (AZD2115) COPD clinical development program Patient Population Phase # of Design Endpoint(s) Status Study Patients Healthy subjects Phase I N = 72 • ARM 1: SAD AZD2115 as nebulised solution • Safety and tolerability following • FSI: Q1 11 • ARM 2: Placebo inhaled administration with single • Co
Slide 52: p38 inhibitor (AZD7624)
p38 inhibitor (AZD7624) COPD development programme Patient Population Phase # of Design Endpoint(s) Status Study patients Healthy subjects Phase I N = 40 SAD • Safety and tolerability following • FSI: Q1 13 • Five different dose levels investigated vs placebo inhaled administration with • Completed
Slide 53: DPP1 inhibitor (AZD7986)
DPP1 inhibitor (AZD7986) COPD development programme Patient Population Phase # of Design Endpoint(s) Status Study patients Healthy subjects and Phase I N= up to 152 Part 1 (SAD) • Safety and tolerability and PK • FSI: Q4 14 COPD • Five different dose levels investigated vs placebo following oral adm
Slide 54: URAT1 (RDEA3170)
URAT1 (RDEA3170) Gout development programme Patient Population Phase Study # of patients Design Primary endpoint Status Monotherapy study in Phase II N = 160 • Arm A: Placebo • Efficacy and Safety at Week 24 • FSI: Q3 13 Subjects with Gout • Arm B: RDEA3170 5 mg QD • LSI: Q4 13 NCT01927198 • Arm C:
Slide 55: Tenapanor/AZD1722 (NHE3 inhibitor)
Tenapanor/AZD1722 (NHE3 inhibitor) Phase II development programme Patient Population Phase # of Design Endpoint(s) Status Study patients End Stage Renal Disease Phase IIb N = 150 • ARM 1: AZD1722,1 mg BiD • Change in serum phosphate levels • FSI: Q1 14 (ESRD) patients on • ARM 2: AZD1722, 3 mg BiD •
Slide 56: WEE-1 (AZD1775)
WEE-1 (AZD1775) Solid tumours development programme Patient Population Phase # of Design Endpoint(s) Status Study patients p53 mutant PSR ovarian Phase II N = 120 • ARM 1: carbo/paclitaxel + AZD1775 225mg • Progression Free Survival • FSI: Q4 12 cancer • ARM 2: carbo/paclitaxel + placebo • LSI: Q3 1
Slide 57: TORC 1/2 (AZD2014)
TORC 1/2 (AZD2014) Solid tumours development programme Patient Population Phase # of Design Endpoint(s) Status Study patients nd 2 line ER+ Metastatic Phase II N = 300 • ARM 1: Fulvestrant • Progression Free Survival • FSI: Q2 14 Breast Cancer MANTA • ARM 2: Fulvestrant + AZD2014 50mg BD continuous
Slide 58: FGFR (AZD4547)
FGFR (AZD4547) Solid tumours development programme Patient Population Phase # of patients Design Endpoint(s) Status Study Advanced cancer who Phase I N = 33 • Part A: AZD4547 in ascending multiple doses given bd and • Part A: MTD and Recommended • Completed: Q2 13 have failed standard od (c. 30 pati
Slide 59: FGFR (AZD4547) continued
FGFR (AZD4547) continued Solid tumours development programme Patient Population Phase # of patients Design Endpoint(s) Status Study Advanced cancer who Phase I N = 94 • Part A: Ascending oral doses of AZD4547 to define maximum • Part A: MTD and Recommended dose • Completed: Q1 14 have failed standar
Slide 60: ISIS-AR (AZD5312)
ISIS-AR (AZD5312) Solid tumours development programme Patient Population Phase # of patients Design Endpoint(s) Status Study Advanced solid tumours Phase I N = 90 Part A: Dose escalation • Part A: MTD and Recommended • FSI: Q2 14 with androgen receptor • AZD5312 in ascending multiple doses given iv
Slide 61: AKT (AZD5363)
AKT (AZD5363) Solid tumours development programme Patient Population Phase # of Design Endpoint(s) Status Study patients Breast and Phase I N = 20 per arm Monotherapy AZD5363 480mg BD 4 days on 3 days off • Safety and tolerability • FSI: Q3 13 Gynaecological cancers • Part C arm 1: Breast with PIK3C
Slide 62: PI3Kα/δ inhibitor (AZD8835)
PI3Kα/δ inhibitor (AZD8835) Solid tumours development programme Patient Population Phase # of Design Endpoint(s) Status Study patients Women With Estrogen Phase I N = 100 Part A: AZD8835 single agent dose escalation • MTD and recommended Phase II dose of oral • FSI: Q4 14 Receptor Positive HER-2 AZD
Slide 63: MET (Savolitinib/AZD6094)
MET (Savolitinib/AZD6094 ) Phase I/II development programme Patient Population Phase # of Design Endpoint(s) Status Study patients Advanced Cancer (All Phase I N = 50 • Dose escalation study • Safety and tolerability • FSI: Q1 12 comers) • LSI: Q3 15 NCT01773018 Conducted in Australia • Est completi
Slide 64: ATR (AZD6738)
ATR (AZD6738) Solid tumours development programme Patient Population Phase # of Design Endpoint(s) Status Study patients Solid tumours Phase I N = 119 • MAD • Safety and tolerability • FSI: Q4 14 • Efficacy • Est completion: Q4 2016 NCT02264678 North America – 1 site • Est external presentation: 201
Slide 65: PI3Kb/d (AZD8186)
PI3Kb/d (AZD8186) Solid tumours development programme Patient Population Phase # of Design Endpoint(s) Status Study patients Advanced Phase I N = 96 • Part A: AZD8186 monotherapy in ascending intermittent • Part A: PK, MTD and • FSI: Q2 13 CRPC/SqNSCLC/TNBC doses in 2 schedules Recommended dose and
Slide 66: STAT3 (AZD9150)
STAT3 (AZD9150) Haematological malignancies development Patient programme Population Phase # of Design Endpoint(s) Status Study patients HCC Phase I N =64 • Dose-escalation and dose-expansion study • Safety and tolerability . • FSI: Q2 13 • IV • Recommended phase II dose and schedule • Est completio
Slide 67: EGFRM BBB (AZD3759)
EGFRM BBB (AZD3759) Lung cancer with LM and/or brain metastases Patient Population Phase # of Design Endpoint(s) Status Study patients EGFRm+ NSCLC Phase I N = 47 • MAD • Safety and tolerability • FSI: Q4 14 • Expansion in LM patients at RP2D with AZD3759 • Preliminary anti-tumour activity • Est com
Slide 68: Infection early development
Infection early development Serious infections development programme Compound Patient Phase # of Design Endpoint(s) Status Population Study Patients ATM-AVI Healthy Phase I • Randomised, double-blind, 3-part study in healthy young and • Safety/tolerability • FSI: Q4 12 (Aztreonam- volunteers elderly
Slide 69: MPO (AZD3241)
MPO (AZD3241) Parkinson’s Disease development programme Patient Population Phase # of Design Endpoint(s) Status Study patients Healthy Subjects Phase I N = 46 • Active ARMS: SAD • AEs, labs, vital signs, ECGs • Study completed • Comparator ARM: placebo • PK NCT00729443 1 site in Sweden Healthy Subje
Slide 70: Histamine H3 receptor inverse agonist (AZD5213)
Histamine H3 receptor inverse agonist (AZD5213) Phase II clinical development programme Patient Population Phase # of Design Endpoint(s) Status Study patients Tourette’s Disorder Phase IIa N = 18 • Part 1: • Improvement in Total Tic Severity • FSI: Q4 13 Single blind to determine tolerability and PK
Slide 71: NMDA (AZD8108)
NMDA (AZD8108) Phase I clinical development programme Patient Population Phase # of Design Endpoint(s) Status Study patients Healthy Volunteers Phase I N = 56 • Randomized, double-blind, placebo-controlled • Safety and tolerability • FSI Q4 14 Part 1 SAD 3 dosage-level cohorts Additional endpoints:
Slide 72: NK3 Receptor Antagonist (AZD4901)
NK3 Receptor Antagonist (AZD4901) Phase II clinical development programme Patient Population Phase # of Design Endpoint(s) Status Study patients Polycystic Ovary Phase IIa N = 56 • ARM 1: AZD4901 20 mg QD • Change from baseline at day 7 in Luteinizing • Completed: Q4 14 Syndrome patients with • ARM
Slide 73: MedImmune Early development programmes
MedImmune Early development programmes Q4 2014 Results Update
Slide 74: Anti-IL-17RA (brodalumab)
Anti-IL-17RA (brodalumab) Asthma development programme Patient Population Phase # of Design Endpoint(s) Status Study patients Moderate to severe Phase II N = 566 • ARM 1: 210 mg brodalumab SC • Change in ACQ at wk 24 • FSI: Q2 13 inadequately controlled • ARM 2: placebo SC • Est completion date: Q1
Slide 75: Tralokinumab (anti-IL-13)
Tralokinumab (anti-IL-13) IPF development programme Patient Population Phase # of Design Endpoint(s) Status Study patients Adults with Idiopathic Phase II N = 186 • ARM 1: Tralokinumab high dose IV • Change from baseline in percent-predicted forced • FSI: Q4 12 Pulmonary Fibrosis • ARM 2: Tralokinum
Slide 76: Tralokinumab (anti-IL-13)
Tralokinumab (anti-IL-13) Atopic Dermatitis development programme Patient Population Phase # of Design Endpoint(s) Status Study patients Adults with Atopic Phase II N = 186 • ARM 1: Tralokinumab dose 1 SC • Change from baseline in EASI at week 12 • FSI: Q1 15 Dermatitis • ARM 2: Tralokinumab dose 2
Slide 77: Anti-TSLP (MEDI9929)
Anti-TSLP (MEDI9929) Asthma development programme Patient Population Phase Study # of patients Design Endpoint(s) Status Adult subjects with Phase II N = 552 • ARM 1: Placebo • Reduction in the annualized asthma • FSI: Q2 13 inadequately controlled, PATHWAY • ARM 2: Low dose MEDI9929 SC exacerbation
Slide 78: Sifalimumab (anti-interferon α)
Sifalimumab (anti-interferon α) SLE development programme Patient Population Phase Study # of patients Design Endpoint(s) Status Moderate-severe SLE Phase ll N = 433 (final) • ARM 1: 200 mg IV MEDI-545 Q2W for 4 wks then Q4W • Proportion of subjects achieving a • FSI: Q1 11 patients for 44 wks respo
Slide 79: Anifrolumab (anti-type I IFN receptor)
Anifrolumab (anti-type I IFN receptor) SLE development programme Patient Population Phase # of patients Design Endpoint(s) Status Study Moderate-severe SLE Phase ll N = 307 (final) • ARM 1: 300 mg IV MEDI-546 Q4W for 48 weeks • Response in SLE responder • FSI: Q1 12 patients • ARM 2: 1000 mg IV MEDI
Slide 80: Anti-B7RP-1 (MEDI5872)
Anti-B7RP-1 (MEDI5872) SLE development programme Patient Population Phase # of Design Endpoint(s) Status Study patients SLE and lupus related Phase I N = 40 Dose escalation study: • Safety and tolerability • FSI: Q2 12 inflammatory arthritis • ARM 1: MEDI5872 SC • Est completion date: Q2 16 NCT01683
Slide 81: Mavrilimumab (anti-GMCSF)
Mavrilimumab (anti-GMCSF) RA development programme Patient Population Phase study # of patients Design Endpoint(s) Status RA patients with an Phase II N = 326 • ARM 1: Mavrilimumab low dose SC • DAS28 response at wk12 • FSI: Q3 12 inadequate response to EARTH (final) • ARM 2: Mavrilimumab medium dos
Slide 82: Autoimmunity biologics early development
Autoimmunity biologics early development Phase I/II clinical development programmes Compound Patient population Phase study # of patients Design Endpoint(s) Status Anti-CD19 mAb Adults with Phase II/III N = 212 • ARM 1: MEDI-551 IV • Primary: Time to attack • FSI: Q1 15 (MEDI-551) Neuromyelitis • AR
Slide 83: Cardiovascular biologics early development
Cardiovascular biologics early development Phase I clinical development programme Compound Patient Population Phase # of Design Endpoint(s) Status Study patients rhLCAT (MEDI6012) Adults with stable Phase I N = 16 • SAD IV • Safety • Completed by Alphacore Coronary Artery • Changes in total HDL Dise
Slide 84: Immuno-oncology portfolio
Immuno-oncology portfolio Monotherapy early development programme Compound Patient Population Phase # of Design Endpoint(s) Status Study Patients PD-1 Solid tumours Phase Ia N = 72 • Dose Escalation (3+3) & Expansion Study • Safety and tolerability • FSI: Q4 13 (MEDI0680) • Study amended to explore
Slide 85: Anti-PD-L1 (MEDI4736) + Iressa (gefitinib)
Anti-PD-L1 (MEDI4736) + Iressa (gefitinib) NSCLC development programme Patient Population Phase # of Design Endpoint(s) Status Study patients NSCLC Phase I N = 47 Escalation phase • Safety • FSI: Q2 14 (Escalation phase) Standard 3+3 design with 28 days DLT period • Optimal biologic dose for the com
Slide 86: Anti-PD-L1 (MEDI4736) + dabrafenib/trametinib (GSK)
Anti-PD-L1 (MEDI4736) + dabrafenib/trametinib (GSK) Melanoma development programme Patient Population Phase # of Design Endpoint(s) Status Study patients Metastatic or Phase I/II N = 69 Dose Escalation: • Safety • FSI: Q1 14 unresectable melanoma • Cohort A • Optimal biologic dose for the combinatio
Slide 87: Anti-PD-L1 (MEDI4736) + Anti-CTLA-4 (tremelimumab)
Anti-PD-L1 (MEDI4736) + Anti-CTLA-4 (tremelimumab) Solid tumours development programme Patient Population Phase # of Design Endpoint(s) Status Study patients NSCLC Phase Ib N = 301 • Dose Escalation: minimum 5 cohorts exploring various • Safety • FSI: Q4 13 (Immunotx naïve and treme Q4W and MEDI4736
Slide 88: Anti-PD-L1 (MEDI4736) + Anti-PD-1 (MEDI0680)
Anti-PD-L1 (MEDI4736) + Anti-PD-1 (MEDI0680) Advanced malignancies development programme Patient Population Phase # of Design Endpoint(s) Status Study Patients Advanced malignancies Phase I N = 150 Dose-escalation phase • Safety • FSI: Q2 14 • MEDI4736 IV + MEDI0680 IV • Determination of MTD • LSI:
Slide 89: Murine Anti-OX40 (MEDI6469) + combinations
Murine Anti-OX40 (MEDI6469) + combinations Advanced malignancies development programme Patient Population Phase # of Design Endpoint(s) Status Study Patients Advanced malignancies Phase I/II N = 212 Dose-escalation phase • Determination of MTD • FSI: Q3 14 • MEDI6469 IV monotherapy • Safety • LSI: Q
Slide 90: OX40 agonist (MEDI6383)
OX40 agonist (MEDI6383) Advanced malignancies development programme Patient Population Phase # of Design Endpoint(s) Status Study Patients Advanced malignancies Phase I N = 116 Dose-escalation phase • Safety • FSI: Q3 14 • MEDI6383 IV • Determination of MTD • LSI: Q3 16 NCT02221960 • Est completion
Slide 91: OX40 agonist (MEDI0562)
OX40 agonist (MEDI0562) Advanced malignancies development programme Patient Population Phase # of Design Endpoint(s) Status Study Patients Advanced malignancies Phase I N = 50 Dose-escalation phase • Safety • FSI: Planned Q1 15 • MEDI0562 IV • Determination of MTD • LSI: Q3 16 NCT02318394 • Est comp
Slide 92: Anti-CD19 (MEDI-551)
Anti-CD19 (MEDI-551) Haematological malignancies development programme Patient Population Phase Study # of patients Design Endpoint(s) Status Adults with relapsed or Phase II N = 180 • ARM 1: MEDI-551 IV (dose-level 1) and Bendamustine • ORR, including Complete • FSI: Q1 12 refractory B-cell chronic
Slide 93: Oncology biologics early development
Oncology biologics early development Solid tumours development programme Compound Patient Population Phase # of Design Endpoint(s) Status Study patients Anti-Ang2 mAb Solid tumours and Phase I N = 16 • MEDI3617 + bevacizumab dose escalation, • Safety and tolerability • FSI: Q4 10 (MEDI3617) ovarian
Slide 94: Oncology biologics early development
Oncology biologics early development Solid tumours development programme Compound Patient Population Phase Study # of patients Design Endpoint(s) Status Anti-CEA BiTE mAb Adults with Phase I N = 51 max • Dose-escalation (3+3), IV • MTD and safety profile • FSI: Q1 11 (MEDI-565) gastrointestinal (GI)
Slide 95: Infectious diseases biologics early development
Infectious diseases biologics early development Phase I/II clinical development programmes Compound Patient Population Phase # of Design Endpoint(s) Status Study patients Anti-Staph AT Intubated ICU Phase II N = 462 • Placebo-controlled, single- • Efficacy and Safety • FSI: Q4 14 (MEDI4893) dose, do
Slide 96: Infectious diseases biologics early development
Infectious diseases biologics early development Phase I/II clinical development programmes Compound Patient Population Phase # of Design Endpoint(s) Status Study patients Anti- Healthy Adults Phase I N = 56 • Randomized, Double-blind, • Evaluate the Safety, Tolerability, and • FSI: Q3 14 Pseudomonas
Slide 97: Vaccines biologics early development
Vaccines biologics early development Phase I/II clinical development programmes Compound Patient Population Phase # of Design Endpoint(s) Status Study patients LAIV RSV Healthy 6-24 mo Phase I/IIa N = 116 • Randomized, Double-Blind, Placebo- • Evaluate the Safety, Tolerability, • Completed Paediatri
Slide 98: Neuroscience biologics early development
Neuroscience biologics early development Phase I development programmes Compound Patient Population Phase # of Design Endpoint(s) Status Study patients Anti-amyloid beta Alzheimers Disease & Phase I N = 121 • SAD & MAD • Safety, tolerability • FSI: Q2 14 mAb Healthy Elderly • Up to 10 iv cohorts are
Slide 99: Gastrointestinal biologics early development
Gastrointestinal biologics early development Phase I/II development programmes Compound Patient Population Phase Study # of patients Design Endpoint(s) Status Moderate to Severe Phase II N = 360 • ARM 1: MEDI7183 dose level 1, SC • Remission at week 8 • FSI: Q4 12 Ulcerative Colitis • ARM 2: MEDI718
Slide 100: AstraZeneca Clinical Programmes Summary – List of abbreviations
AstraZeneca Clinical Programmes Summary List of abbreviations TOC Test of Cure SC Sub-cutaneous LAMA Long Acting Muscarinic Agonist MITT Modified Intent-To-Treat population IV Intra-venous MTX Methotrexate cMITT Clinical Modified Intent-To-Treat population IM Intra-muscular ASA Acetylsalicylic Acid