Slide 1: AstraZeneca Clinical Programmes Summary
AstraZeneca Clinical Programmes Summary 2Q 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 t
Slide 2: 2Q 2014: 4 new NME pivotal study starts
2Q 2014: 4 new NME pivotal study starts contributing to growing late stage pipeline Pivotal study starts in 2Q 2014 Number of NMEs in pivotal studies 14 roxadustat (HIF) CKD & ESRD tremelimumab (CTLA-4) mesothelioma 11 NMEs AZD9291 (EGFR) 2L NSCLC 9-10 PD-L1 (MEDI4736) NSCLC 8 8 6 benralizumab (IL-5
Slide 3: 2014: Continued strong momentum in late stage pipeline
2014: Continued strong momentum in late stage pipeline BACE (AZD3293) Alzheimer’s disease tenapanor (NHE3) ESRD anifrolumab (IFN-αR) SLE roxadustat (HIF) sifalimumab (IFN-α) CKD & ESRD SLE NMEs tremelimumab (CTLA-4) mavrilimumab (GM-CSF) mesothelioma RA AZD9291 (EGFR) cediranib (VEGF) 2L NSCLC ovari
Slide 4: Movements since Q1 2014 update
Movements since Q1 2014 update New to Phase I New to Phase II New to Pivotal Study New to Registration NMEs NMEs NMEs MCH (AZD1979) IFNβ (AZD9412) (SNG001)¥ AZD9291 obesity asthma, COPD EGFR T790M+ NSCLC Androgen (AZD5312) TSLP (MEDI9929) PD-L1 (MEDI4736) prostate cancer asthma Stage III NSCLC CD19
Slide 5: A growing and accelerating late stage pipeline
A growing and accelerating late stage pipeline Phase 1 Phase 2 Phase 3 / Registration 35 New Molecular Entities 24 New Molecular Entities 14 New Molecular Entities Small molecule Large molecule Small molecule Large molecule Small molecule Large molecule PIM (AZD1208) DLL-4 (MEDI0639) WEE-1 (AZD1775)
Slide 6: 2H 2014: Key data readouts
2H 2014: Key data readouts Compound Indication Milestone lesinurad gout Ph III topline results CAZ AVI cIAI Ph III topline results brodalumab psoriasis Ph III topline results sifalimumab SLE Ph IIb (ACR) mavrilimumab RA Ph IIb (ACR) MEDI4736 solid tumours Ph I (ESMO) MEDI4736 + tremelimumab NSCLC Ph
Slide 7: 2H 2014: Key regulatory milestones
2H 2014: Key regulatory milestones Compound Indication Potential milestones Iressa EGFRm NSCLC US filing Movantik OIC US approval (PDUFA 16 Sep 2014) Movantik OIC EU approval Brilinta ACS JP approval olaparib PSR BRCAm ovarian cancer US approval (PDUFA 3 Jan 2015) Xigduo XR type 2 diabetes US approv
Slide 8: Potential NME & LE submissions 2014-16
Potential NME & LE submissions 2014-16 Myalept EU lipodystrophy PT003 LABA/LAMA COPD PT001 LAMA COPD CAZ AVI EU brodalumab* PD-L1 (MEDI4736) cephalosporin/BLI SBI IL-17R psoriasis NSCLC lesinurad AZD9291 US/EU/JP benralizumab NMEs URAT1 gout EGFR T790M NSCLC IL-5R asthma olaparib US selumetinib roxa
Slide 9: AstraZeneca LE development programmes
AstraZeneca LE development programmes 2Q 2014 Results Update
Slide 10: Brilinta/Brilique PARTHENON development programme
Brilinta/Brilique (ADP receptor antagonist) PARTHENON development programme Patient Phase # of Design Endpoint(s) Status Population Study patients Patients with Phase III N = 21000 • ARM 1: Ticagrelor 90 mg BiD • Composite of CV death, • FSI Q4 10 prior MI PEGASUS • ARM 2: Ticagrelor 60 mg BiD non-f
Slide 11: Forxiga/Farxiga Type 2 Diabetes development programme
Forxiga/Farxiga (SGLT-2 inhibitor) Type 2 Diabetes development programme Patient Phase # of Design Endpoint(s) Status Population Study patients Typ 2 diabetes Phase III/IV N = 17150 • ARM 1: Dapagliflozin 10 mg QD + standard • Time to first • FSI Q2 13 mellitus with DECLARE of care therapy QD event
Slide 12: Onglyza Type 2 Diabetes development programme
Onglyza (DPP-IV inhibitor) Type 2 Diabetes development programme Patient Phase # of Design Endpoint(s) Status Population Study patients Type 2 diabetes Phase III N = 740 • ARM 1: Saxagliptin 5 mg QD Primary: • FSI Q2 14 mellitus on • ARM 2: Placebo QD • Mean change from • LSI Q4 15 insulin treatment
Slide 13: Saxagliptin/dapagliflozin FDC Type 2 Diabetes programme
Saxagliptin/dapagliflozin (DPP-4/SGLT-2 inhibitors) FDC Type 2 Diabetes development programme Patient Phase # of Design Endpoint(s) Status* Population Study patients Type 2 Phase III N = 516 • ARM 1: Saxa 5 mg + Met XR QD Primary: • FSI Q3 12 Diabetes • ARM 2: Dapa 10 mg + Met XR QD • Mean change fr
Slide 14: Bydureon/exenatide Type 2 Diabetes development programme
Bydureon/exenatide (GLP-1 receptor antagonist) Type 2 Diabetes development programme Patient Phase # of Design Endpoint(s) Status Population Study patients Type 2 Diabetes Phase III N = 375 • ARM 1: Exenatide BiD SC (autoinjector) • Change in HbA1c • FSI Q1 13 DURATION- • ARM 2: Exenatide weekly sus
Slide 15: Epanova Hypertriglyceridaemia development programme
Epanova (prescription grade Omega-3 free fatty acid EPA+DHA) Hypertriglyceridaemia development programme Patient Phase # of Design Endpoint(s) Status Population Study patients Severe hyper- Phase III N = 104 • ARM 1: Epanova 2g QD • Change in serum • FSI Q4 13 triglyceridaemia EVOLVE II • ARM 2: Pla
Slide 16: Myalept Lipodystrophy development programme
Myalept (recombinant leptin analogue) Lipodystrophy development programme Patient Phase # of Design Endpoint(s) Status Population Study patients Lipodystrophy Phase III N = 72* • ARM 1: Metreleptin • Glycaemic control • Ongoing Partnered • Triglycerides • Est. Completion date Q3 15 NIH /NIDDK Open l
Slide 17: Iressa EGFR M+ NSCLC development programme
Iressa (EGFR TKI) EGFR M+ NSCLC development programme Patient Phase # of Design Endpoint(s) Status Population Study patients EGFR M+ Phase III N = 250 • ARM 1: Gefitinib 250 mg QD + max 6 • Progression Free Survival • FSI Q1 12 NSCLC who IMPRESS cycles of cisplatin and pemetrexed • LSI Q4 13 have •
Slide 18: Faslodex Breast cancer development programme
Faslodex (oestrogen receptor antagonist) Breast cancer development programme Patient Phase # of Design Endpoint(s) Status Population Study patients Postmenopausal Phase III N ~450 • ARM 1: Faslodex 500 mg monthly IM + an • Progression Free • FSI Q4 12 women with HR+ FALCON additional dose on d14 (+
Slide 19: Caprelsa Thyroid cancer development programme
Caprelsa Thyroid cancer development programme Patient Phase # of Design Endpoint(s) Status Population Study patients Differentiated Phase III N = 227 • ARM 1: Vandetanib 300 mg oral dose QD • Progression Free • FSI Q3 13 thyroid cancer • ARM 2: Placebo Survival • LSI Q4 14 NCT01876784 refractory or
Slide 20: Symbicort Mild asthma development programme
Symbicort (ICS/LABA) Mild asthma development programme Patient Phase # of Design Endpoint(s) Status Population Study patients Asthma Phase III N = 3750 • ARM 1: Symbicort Turbuhaler 160/4.5 μg 'as • Well controlled asthma • FSI Q3 14 patients SYGMA1 needed' + Placebo Pulmicort Turbuhaler 200 μg week
Slide 21: Zinforo Serious infections development programme
Zinforo Serious infections development programme Patient Phase # of Design Endpoint(s) Status Population Study patients Patients with Phase III N = 765 • Arm 1: Ceftaroline fosamil • NI in Clinical Cure rate at the Test • FSI Q2 12 complicated skin COVERS 600 mg q 8 hrs of Cure (TOC) visit in both t
Slide 22: FluMist Quadrivalent Phase III development programme
FluMist Quadrivalent Phase III development programme Patient Phase Study # of Design Endpoint(s) Status Population patients Healthy Phase llI N = 1008 • ARM 1: One or two doses of MEDI3250 • Efficacy • FSI Q3 14 children • ARM 2: Placebo • Safety and tolerability • Est completion Q2 15 To be posted
Slide 23: Gastrointestinal Phase III development programme
Gastrointestinal Phase III development programme Patient Phase # of Design Endpoint(s) Status Population Study patients Nexium Refractory RE Phase III N = 280 • ARM 1: Nexium 20 mg BiD • Healing of • FSI Q3 2012 Rose • ARM 2: Nexium 20 mg QD refractory RE • LSI Q1 2014 • Completion date Q2 2014 NCT0
Slide 24: AstraZeneca Late stage development programmes
AstraZeneca Late stage development programmes 2Q 2014 Results Update
Slide 25: Roxadustat Phase III CKD programme
Roxadustat (HIF-PHI) Phase III CKD programme Patient Phase # of Design Endpoint(s) Status Population Study patients Anaemia in Phase III N = 450 • ARM 1: Roxadustat • Haemoglobin • Sponsored by FibroGen Chronic Kidney Andes • ARM 2: Placebo response • FSI Q4 12 Disease • Est completion Q1 16 Patient
Slide 26: Olaparib Solid tumours development programme
Olaparib (PARP inhibitor) Solid tumours development programme Patient Phase # of Design Primary Status Population Study patients Endpoint PSR BRCAm Phase III N = 264 • ARM 1: olaparib tablets 300 mg BiD as • Progression Free • FSI Q3 13 ovarian cancer SOLO-2 maintenance therapy until progression Sur
Slide 27: Olaparib continued...
Olaparib (PARP inhibitor) continued... Solid tumours development programme Patient Phase # of Design Primary Status Population Study patients Endpoint BRCAm Phase III N = 1320 • Arm 1: Olaparib 300 mg BiD • IDFS • FSI Q2 14 adjuvant OlympiA 12 month duration • Secondary Endpoint • LSI Q1 18 breast c
Slide 28: Selumetinib Solid tumours development programme
Selumetinib (AZD6244, ARRY142886) (MEK-inhibitor) Solid tumours development programme Patient Phase # of Design Endpoint(s) Status Population Study patients nd 2 Line KRAS M Phase III N = 634 • ARM 1: Selumetinib 75mg BiD + docetaxel 75 • Progression Free • FSI Q3 13 positive NSCLC SELECT-1 mg/m2 IV
Slide 29: AZD9291 NSCLC development programme
AZD9291 (3rd Generation EGFR TKI) NSCLC development programme Patient Population Phase # of Design Endpoint(s) Status Study patients Advanced EGFR Phase I/II N ~ 500 • Dose escalation study • Safety and tolerability • FSI Q1 13 m+ NSCLC TKI AURA • Ph II Extension cohort 80mg QD • ORR • Est completio
Slide 30: Anti-PD-L1 (MEDI4736) Solid tumours development programme
Anti-PD-L1 (MEDI4736) Solid tumours development programme Patient Population Phase # of Design Endpoint(s) Status Study patients Stage IIIB-IV Phase II N = 188 • ARM 1: MEDI4736 IV Q2W (EFGR/ALK • Objective Response • FSI Q1 14 NSCLC patients Atlantic WT) Rate • LSI Q2 15 • ARM 2: MEDI4736 IV Q2W (E
Slide 31: Anti-PD-L1 (MEDI4736) continued…
Anti-PD-L1 (MEDI4736) continued… Solid tumours development programme Patient Population Phase # of Design Endpoint(s) Status Study patients Stage IIIB-IV NSCLC Phase II/III N = 400 5-Arm study based on biomarker • Progression Free • Planned: FSI Q3 14 patients Lung Master (4736 arm expression Surviv
Slide 32: Anti-CTLA-4 (tremelimumab) Mesothelioma programme
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 • FSI Q2 13 unresectable pleural or • ARM 2: Placebo (OS) • LSI Q2 15 peritoneal malignant N
Slide 33: Moxetumomab Pasudotox Haematological malignancies programme
Moxetumomab Pasudotox (anti-CD22) Haematological malignancies development programme Patient Phase # of Design Endpoint(s) Status Population Study patients Adults with Phase I N = 75 • Open Label dose escalation • MTD and efficacy • FSI Q2 07 relapsed study • LSI Q1 14 NCT00586924 refractory HCL • Es
Slide 34: Anti-IL-5Rα (benralizumab) Asthma programme
Anti-IL-5Rα (benralizumab) Asthma development programme Patient Phase # of Design Endpoint(s) Status Population Study patients Severe asthma, Phase III N = 102 6 HD • ARM 1: 30 mg Q8w SC • Annual Asthma • FSI Q4 13 inadequately controlled CALIMA + up to 250 • ARM 2: 30 mg Q4w SC Exacerbation Rate •
Slide 35: Anti-IL-5Rα (benralizumab) COPD programme
Anti-IL-5Rα (benralizumab) COPD development programme Patient Phase # of Design Endpoint(s) Status Population Study patients Subjects with moderate- Phase IIa N = 101 • ARM 1: 100mg Q8w SC • Rate of Exacerbations • Completed Q3 13 to-severe COPD who • ARM 2: Placebo SC • Est external presentation Q2
Slide 36: LABA/LAMA (PT003) & LAMA (PT001) COPD programme
LABA/LAMA (PT003) & LAMA (PT001) COPD development programme Patient Phase # of Design Endpoint(s) Status Population Study patients G = Glycopyrronium, F = Formoterol fumarate Moderate to Phase III N = 2054 • ARM 1: GFF MDI (PT003) 14.4/9.6 μg • Change from baseline • FSI Q2 13 Very Severe PINNACLE 1
Slide 37: Anti-IL-17RA (brodalumab) Inflammatory diseases programme
Anti-IL-17RA (brodalumab) Inflammatory diseases development programme Patient Phase # of Design Endpoint(s) Status Population Study patients Moderate to severe Phase III N = 661 • ARM 1: 210 mg brodalumab SC • PASI at wk 12 • Primary data Q2 14 plaque psoriasis AMAGINE-1 • ARM 2: 140 mg brodalumab S
Slide 38: Lesinurad Gout development programme
Lesinurad (URAT1) Gout development programme Patient Population Phase # of Design Primary endpoint Status Study patients Gout with Phase III N = 600 • Arm 1: Placebo • Proportion of subjects with an • FSI Q1 12 Inadequate CLEAR 1 • Arm 2: lesinurad 200 mg QD sUA level that is < 6.0 mg/dL • LSI Q3 13
Slide 39: CAZ-AVI Serious infections development programme
CAZ-AVI (BLI/cephalosporin SBI) Serious infections development programme Patient Phase # of Design Endpoint(s) Status Population Study patients Hospitalised Phase III N = 490 • ARM 1: CAZ-AVI 2000/500mg plus • Co primary of: • FSI Q1 12 patients with RECLAIM-1 Metronidazole IV (i) clinical response
Slide 40: CAZ-AVI Serious infections development programme
CAZ-AVI (BLI/cephalosporin SBI) Serious infections development programme Patient Phase # of Design Endpoint(s) Status Population Study patients Patients with Phase III N = 400 • ARM 1: CAZ-AVI 2000/500mg plus • Patients with clinical • FSI Q1 13 complicated urinary REPRISE Metronidazole IV cure at t
Slide 41: AstraZeneca Early development programmes
AstraZeneca Early development programmes 2Q 2014 Results Update
Slide 42: Tenapanor/AZD1722 Phase II development programme
Tenapanor/AZD1722 (NHE3 inhibitor) Phase II development programme Patient Phase # of Design Endpoint(s) Status Population Study patients End Stage Renal Phase IIb N = 150 • ARM 1: AZD1722,1 mg BiD • Change in serum phosphate • FSI Q1 14 Disease (ESRD) • ARM 2: AZD1722, 3 mg BiD levels • LSI Q3 14 pa
Slide 43: Hormone Modulator (AZD4901) Phase II programme
Hormone Modulator (AZD4901) Phase II clinical development programme Patient Phase # of Design Endpoint(s) Status Population Study patients Polycystic Phase IIa N = 56 • ARM 1: AZD4901 20 mg QD • Change from baseline at day • FSI Q2 13 Ovary • ARM 2: AZD4901 20 mg BiD 7 in Luteinizing Hormone • LSI Q
Slide 44: MCH (AZD1979) Phase I programme
MCH (AZD1979) Phase I clinical development programme Patient Phase # of Design Primary Status Population Study Patients Endpoint Healthy Phase I N = 56 • Single Ascending Dose study – single- • Safety and tolerability • FSI Q2 2014. subjects planned (72 center, single-blind, randomized and • Study s
Slide 45: WEE-1 (AZD1775) Solid tumours programme
WEE-1 (AZD1775) Solid tumours development programme Patient Phase # of Design Endpoint(s) Status Population Study patients p53 mutant PSR Phase II N = 120 • ARM 1: carbo/paclitaxel + AZD1775 225mg • Progression Free • FSI Q4 11 ovarian cancer • ARM 2: carbo/paclitaxel + placebo Survival • LSI Q3 14
Slide 46: FGFR (AZD4547) Solid tumours programme
FGFR (AZD4547) Solid tumours development programme Patient Phase # of Design Endpoint(s) Status population Study patients Advanced cancer Phase I N = 33 • Part A: AZD4547 in ascending multiple doses given • Part A: MTD and Recruited Q1 13 who have failed bd and od (c. 30 patients) Recommended dose f
Slide 47: Volitinib (AZD6094) Phase I/II programme
Volitinib (AZD6094) (HMPL-504) (cMET) Phase I/II development programme Patient Phase # of Design Endpoint(s) Status Population Study patients Advanced Phase I N = 50 • Dose escalation study • Safety and tolerability • FSI Q1 12 Cancer (All • LSI Q4 14 comers) NCT01773018 Conducted in Australia • Est
Slide 48: TORC 1/2 (AZD2014) Solid tumours programme
TORC 1/2 (AZD2014) Solid tumours development programme Patient Phase # of Design Endpoint(s) Status Population Study patients nd 2 line ER+ Phase II N = 300 • ARM 1: Fulvestrant • Progression Free • FSI Q2 14 Metastatic MANTA • ARM 2: Fulvestrant + AZD2014 50mg BD Survival • LSI Q4 15 Breast Cancer
Slide 49: AKT (AZD5363) Solid tumours programme
AKT (AZD5363) Solid tumours development programme Patient Phase # of Design Endpoint(s) Status Population Study patients Breast and Phase I N = 20 Monotherapy AZD5363 480mg BD 4 days on 3 days off • Safety and • FSI Q3 13 Gynaecological per arm • Part C arm 1: Breast with PIK3CA mutation tolerabilit
Slide 50: PI3Kb/d (AZD8186) Solid tumours programme
PI3Kb/d (AZD8186) Solid tumours development programme Patient Phase # of Design Endpoint(s) Status Population Study patients Advanced Phase I N = 48 • Part A: AZD8186 monotherapy in • Part A: PK, MTD and • FSI Q3 13 CRPC/SqNSCLC ascending intermittent doses Recommended dose for • Est completion Q2 1
Slide 51: ISIS-AR (AZD5312) Solid tumours programme
ISIS-AR (AZD5312) Solid tumours development programme Patient Phase # of Design Endpoint(s) Status population Study patients Advanced solid Phase I N = 90 Part A: Dose escalation • Part A: MTD and • FSI Q2 14 tumours with • AZD5312 in ascending multiple doses given iv (c. 30 Recommended dose for • E
Slide 52: Oncology Haematological malignancies programme
Oncology Haematological malignancies development programme Patient Phase # of Design Endpoint(s) Status Population Study patients HCC Phase I N = 80 • Dose-escalation and dose- • Safety and tolerability • FSI Q2 13 expansion study . • Est completion Q1 15 NCT01839604 • IV • Recommended phase • Est e
Slide 53: LABA/LAMA/ICS (PT010) COPD programme
LABA/LAMA/ICS (PT010) COPD development programme Patient Phase # of Design Endpoint(s) Status Population Study patients (B= Budesonide, G = Glycopyrronium, F = Formoterol fumarate) Healthy Phase I N = 84 • ARM 1: BGF MDI 320/14.4/9.6 μg • Overall safety • FSI Q4 13 volunteers • ARM 2: BGF MDI 160/14
Slide 54: MABA (AZD2115) COPD programme
MABA (AZD2115) COPD clinical development programme Patient Phase # of Design Endpoint(s) Status Population Study Patients Healthy Phase I N = 72 • ARM 1: SAD AZD2115 as nebulised • Safety and tolerability • FSI Q1 11 subjects solution following inhaled • Est external presentation NCT01283984 • ARM 2
Slide 55: p38 inhibitor (AZD7624) COPD programme
p38 inhibitor (AZD7624) COPD development programme Patient Phase # of Design Endpoint(s) Status Population Study patients Healthy Phase I N = 40 SAD • Safety and tolerability • FSI: Q1 2013 subjects • Five different dose levels investigated vs following inhaled • Completed NCT01754844 placebo admini
Slide 56: TLR7 agonist (AZD8848) Phase I programme
TLR7 agonist (AZD8848) Phase I clinical development programme Patient Phase # of Design Endpoint(s) Status Population Study Patients Healthy Phase I N = 4 active SAD • Safety and tolerability of • Est completion Q3 14 subjects + 2 placebo ascending doses of AZD8848 NCT01560234 per cohort in healthy
Slide 57: URAT1 (RDEA3170) Gout programme
URAT1 (RDEA3170) Gout development programme Patient Phase Study # of Design Primary endpoint Status Population patients Subjects with Phase II N = 160 • Arm A: Placebo • Efficacy and Safety at • FSI Q3 13 Gout • Arm B: RDEA3170 5 mg QD Week 24 • LSI Q4 13 NCT01927198 • Arm C: RDEA3170 10 mg QD • Est
Slide 58: Infection early development Serious infections programme
Infection early development Serious infections development programme Patient Phase # of Design Endpoint(s) Status Population Study patients ATM-AVI Healthy Phase I • Randomised, double-blind, 3-part study in • Safety/tolerability • FSI Q4 12 (Aztreonam- volunteers healthy young and elderly volunteer
Slide 59: BACE (AZD3293) Alzheimer's Disease programme
BACE (AZD3293) Alzheimer’s Disease development programme Patient Phase # of Design Endpoint(s) Status Population Study Patients Healthy Phase I N =72 • Active ARMS: AZD3293 single doses, • AEs, labs, vital • Study completed. Volunteers SAD Study ascending doses ranging from 1mg to a signs, ECGs • Po
Slide 60: MPO (AZD3241) Parkinson's Disease programme
MPO (AZD3241) Parkinson’s Disease development programme Patient Phase # of Design Endpoint(s) Status Population Study patients Healthy Phase I N = 46 • Active ARMS: SAD • AEs, labs, vital signs, • Study completed Subjects • Comparator ARM: placebo ECGs NCT00729443 • PK 1 site in Sweden Healthy Phase
Slide 61: Histamine H3 receptor inverse agonist (AZD5213) Phase II
Histamine H3 receptor inverse agonist (AZD5213) Phase II clinical development programme Patient Phase # of Design Endpoint(s) Status Population Study patients Tourette’s Phase IIa N = 18 • Part 1: Single blind to determine tolerability • Improvement in Total • FSI Q4 13 Disorder and PK in adolescent
Slide 62: NMDA (AZD6423) Phase I programme
NMDA (AZD6423) Phase I clinical development programme Patient Phase # of Design Endpoint(s) Status Population Study patients Healthy Phase I N = 64 • SAD/MAD: Ascending dose cohorts of n=8 • Safety and • FSI Q3 13 Volunteers (6 active drug, 2 placebo); IV administration tolerability • LSI Q1 14 NCT0
Slide 63: MedImmune Early development programmes
MedImmune Early development programmes 2Q 2014 Results Update
Slide 64: Cardiovascular biologics early development
Cardiovascular biologics early development Phase I clinical development programme Patient Phase # of Design Endpoint(s) Status Population Study patients rhLCAT Adults with Phase I N = 16 • SAD IV • Safety • Completed by Alphacore (MEDI6012) stable • Changes in total HDL Coronary NCT01554800 • Change
Slide 65: Anti-CD19 (MEDI-551) Haematological malignancies programme
Anti-CD19 (MEDI-551) Haematological malignancies development programme Patient Phase # of Design Endpoint(s) Status Population Study patients Adults with relapsed Phase II N = 180 • ARM 1: MEDI-551 IV (dose-level 1) and • ORR, including Complete • FSI Q1 12 or refractory B-cell Bendamustine Response
Slide 66: Immuno-oncology portfolio Monotherapy early development
Immuno-oncology portfolio Monotherapy early development programme Patient Phase # of Design Endpoint(s) Status Population Study Patients PD-1 Solid tumours Phase Ia N = 72 • Dose Escalation (3+3) & Expansion • Safety and • FSI Q4 13 (MEDI0680) Study tolerability • LSI Q4 14 (escalation) NCT02013804
Slide 67: Anti-PD-L1 (MEDI4736) + Anti-CTLA-4 (tremelimumab)
Anti-PD-L1 (MEDI4736) + Anti-CTLA-4 (tremelimumab) Solid tumours development programme Patient Phase # of Design Endpoint(s) Status Population Study patients NSCLC Phase Ib N = 204 • Dose Escalation: minimum 5 cohorts • Safety • FSI Q4 13 (Immunotx naïve exploring various treme Q4w and • Optimal bio
Slide 68: Anti-PD-L1 (MEDI4736) + dabrafenib/trametinib Melanoma
Anti-PD-L1 (MEDI4736) + dabrafenib/trametinib (GSK) Melanoma development programme Patient Phase # of Design Endpoint(s) Status Population Study patients Metastatic or Phase I/II N = 69 Dose Escalation: • Safety • FSI Q4 13 unresectable • Cohort A – dabrafenib 150mg BiD/ • Optimal biologic dose for
Slide 69: Anti-PD-L1 (MEDI4736) + Iressa (gefitinib) NSCLC
Anti-PD-L1 (MEDI4736) + Iressa (gefitinib) NSCLC development programme Patient Phase # of Design Endpoint(s) Status Population Study patients NSCLC Phase I N = 29 Escalation phase • Safety • FSI Q1 14 (Escalation Standard 3+3 design with 28 days DLT • Optimal biologic dose for the • LSI Q1 15 phase)
Slide 70: Anti-PD-L1 (MEDI4736) + Anti-PD-1 (MEDI0680)
Anti-PD-L1 (MEDI4736) + Anti-PD-1 (MEDI0680) Advanced malignancies development programme Patient Phase # of Design Endpoint(s) Status Population Study Patients Advanced Phase I N = 130 Dose-escalation phase • Safety • FSI Q2 14 malignancies • MEDI4736 IV + MEDI0680 IV • Determination of MTD • LSI Q3
Slide 71: Anti-CTLA-4 (tremelimumab) + Iressa (gefitinib) NSCLC
Anti-CTLA-4 (tremelimumab) + Iressa (gefitinib) NSCLC development programme Patient Phase # of Design Endpoint(s) Status Population Study patients EGFRm+ NSCLC Phase I N = 24 Cohort 1: Tremelimumab IV 3 mg/kg q4w plus • Safety and • FSI Q1 14 Gefitinib 250 mg QD, 6 patients (+ 6 patients if 3 tolera
Slide 72: Oncology biologics early development Solid tumors
Oncology biologics early development Solid tumors development programme Patient Population Phase # of Design Endpoint(s) Status Study patients Anti-Ang2 Solid tumors and Phase I • Safety and tolerability • Recruitment Complete mAb ovarian cancer (MEDI3617) NCT01248949 N = 15-24 • MEDI3617 + bevacizu
Slide 73: Oncology biologics early development Solid tumours
Oncology biologics early development Solid tumours development programme Patient Phase # of patients Design Endpoint(s) Status Population Study Anti-CEA BiTE Adults with Phase I N = 51 max • Dose-escalation (3+3), IV • MTD and safety profile • FSI Q4 10 mAb gastrointestinal (GI) • Est completion Q3
Slide 74: Tralokinumab (anti-IL-13) Asthma & IPF programme
Tralokinumab (anti-IL-13) Asthma & IPF development programme Patient Phase # of Design Endpoint(s) Status Population Study patients Adults with Phase III N = 1140 • Cohort 1: Primary Endpoint • Planned FSI Q3 14 Uncontrolled • ARM 1: Tralokinumab dose regimen 1 • Annual asthma • Primary completion Q
Slide 75: Tralokinumab (anti-IL-13) continued…
Tralokinumab (anti-IL-13) continued… Asthma & IPF development programme Patient Phase # of Design Endpoint(s) Status Population Study patients Adults with Phase II N = 186 • ARM 1: Tralokinumab high dose • Change from baseline in • FSI Q4 12 Idiopathic • ARM 2: Tralokinumab low dose percent-predicte
Slide 76: Anti-TSLP (MEDI9929/AMG 157) Asthma programme
Anti-TSLP (MEDI9929/AMG 157) Asthma development programme Patient Phase # of Design Endpoint(s) Status Population Study patients Adult subjects with Phase II N = 552 • ARM 1: Placebo • Reduction in the annualized • FSI Q2 14 inadequately PATHWAY • ARM 2: Low dose MEDI9929 SC asthma exacerbation rate
Slide 77: Mavrilimumab (anti-GMCSF) RA programme
Mavrilimumab (anti-GMCSF) RA development programme Patient Phase # of Design Endpoint(s) Status Population Study patients RA patients with an Phase II N = 326 • ARM 1: Mavrilimumab 30 mg SC • DAS28 response at • FSI Q3 12 inadequate response EARTH (final) • ARM 2: Mavrilimumab 100 mg SC wk12 • LSI Q
Slide 78: Sifalimumab (anti-interferon α) SLE programme
Sifalimumab (anti-interferon α) SLE development programme Patient Phase Study # of Design Endpoint(s) Status Population patients Moderate- Phase ll N = 431 • Arm 1: 200 mg IV MEDI-545 q2w for 4 wks then • Proportion of subjects • FSI Q2 11 severe SLE q4wk for 44 wks achieving a response in • Est com
Slide 79: Anifrolumab (anti-type I IFN receptor) SLE programme
Anifrolumab (anti-type I IFN receptor) SLE development programme Patient Phase # of Design Endpoint(s) Status Population Study patients Moderate- Phase ll N = 300 • ARM 1: 300 mg IV MEDI-546 q4w for 48 weeks • Response in SLE • FSI Q1 12 severe SLE • ARM 2: 1000 mg IV MEDI-546 q4w for 48 weeks respo
Slide 80: Anti-B7RP-1 (MEDI5872) SLE programme
Anti-B7RP-1 (MEDI5872) SLE development programme Patient Phase # of Design Endpoint(s) Status Population Study patients SLE and lupus Phase I N = 40 Dose escalation study: • Safety and tolerability • FSI Q2 12 related • ARM 1: MEDI5872 SC • LSI Q2 15 NCT01683695 inflammatory • AMR 2: placebo SC • Lu
Slide 81: Anti-Staph AT (MEDI4893) Phase I programme
Anti-Staph AT (MEDI4893) Phase I clinical development programme Patient Phase # of Design Endpoint(s) Status Population Study patients Healthy Adults Phase I N = 33 • Randomized, Double-blind, • Evaluate the Safety, Tolerability, • Dosing completed Placebo-Controlled, Dose- and Pharmacokinetics of N
Slide 82: LAIV RSV Paediatric Vaccine (MEDI-559) Phase I/IIa
LAIV RSV Paediatric Vaccine (MEDI-559) Phase I/IIa clinical development programme Patient Phase # of Design Endpoint(s) Status Population Study patients Healthy 6-24 mo Phase I/IIa N = 116 • Randomized, Double-Blind, • Evaluate the Safety, Tolerability, • Completed prevention of RSV Placebo-Controll
Slide 83: Pandemic flu library (MEDI-550) Phase I programme
Pandemic flu library (MEDI-550) Phase I clinical development programme Patient Phase # of Design Endpoint(s) Status Population Study patients Healthy adults Phase I Varies • Administration of live • Safety and Immunogenicity • Study Starts: 2005-2012 attenuated influenza virus • Primary Completion D
Slide 84: RSV sF+GLA-SE (MEDI7510) Phase I programme
RSV sF+GLA-SE (MEDI7510) Phase I development programme Patient Phase # of Design Endpoint(s) Status Population Study patients Adults ≥ 60 yrs Phase I N = 144 • ARM 1: MEDI7510 IM • Safety and tolerability • FSI Q2 14 • ARM 2: RSV sF IM • Humoral and cell-mediated • Est completion Q3 14 NCT02115815 •
Slide 85: Anti-RSV mAb-YTE (MEDI8897) Phase I programme
Anti-RSV mAb-YTE (MEDI8897) Phase I clinical development programme Patient Phase # of Design Endpoint(s) Status Population Study patients Healthy Adults Phase Ia N = 136 • ARM 1: MEDI8897 IV & IM • Evaluate Safety, Tolerability, • FSI Q2 14 • ARM 2: Placebo PK and ADA • Est completion Q4 14 NCT02114
Slide 86: Neuroscience biologics early development Phase I programmes
Neuroscience biologics early development Phase I development programmes Patient Phase # of Design Endpoint(s) Status Population Study patients Anti-amyloid Alzheimers Phase I N = 121 • SAD & MAD • Safety, tolerability • FSI Q2 14 beta mAb Disease & • Up to 10 iv cohorts are • LSI Q2 16 (MEDI1814) He
Slide 87: Gastrointestinal biologics early development UC & CD
Gastrointestinal biologics early development UC & CD development programme Patient Phase # of Design Endpoint(s) Status Population Study patients Moderate to Phase II N = 360 • ARM 1: MEDI7183 dose level 1, SC • Remission at week 8 • FSI Q4 12 Severe • ARM 2: MEDI7183 dose level 2, SC (Mayo Score) •
Slide 88: List of abbreviations
AstraZeneca Clinical Programmes Summary List of abbreviations TOC Test of Cure MTD Maximum Tolerated Dose MITT Modified Intent-To-Treat population PFS Progression Free Survival cMITT Clinical Modified Intent-To-Treat population ORR Objective Response Rate mMITT Microbiological Modified Intent-To-Tre