Slide 1: AstraZeneca Clinical Programmes Summary
AstraZeneca Clinical Programmes Summary 3Q 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: Continued momentum in late stage pipeline
Continued momentum in late stage pipeline Regulatory milestones Compound Indication Milestone Lynparza (olaparib) PSR BRCAm ovarian cancer CHMP positive opinion Iressa ctDNA EGFRm NSCLC EU approval Xigduo XR Type 2 diabetes US approval Movantik OIC US approval Moventig OIC CHMP positive opinion Data
Slide 3: Movements since 2Q 2014 update
Movements since 2Q 2014 update New to Phase I New to Phase II New to Pivotal Study New to Registration NMEs (& significant combinations) NMEs NMEs Other movements AZD9291 + anti-PD-L1 or MEK or Lynparza (olaparib) tralokinumab asthma Movantik MET prostate cancer Approved US advanced EGFRm NSCLC Line
Slide 4: A growing and accelerating late stage pipeline
Oncology RIA CVMD Neuroscience Infection A growing and accelerating late stage pipeline Phase 1 (39 New Molecular Entities†) Phase 2 (24 New Molecular Entities†) Phase 3 / Registration (14 New Molecular Entities†)1 Small molecule Large molecule Small molecule Large molecule Small molecule Large mole
Slide 5: Continued strong newsflow anticipated
Continued strong newsflow anticipated Data readouts Compound Indication Milestone brodalumab psoriasis Ph III topline results sifalimumab SLE Ph IIb (ACR) mavrilimumab RA Ph IIb (ACR) BACE (AZD3293) Alzheimer’s disease Ph I (CTAD) Regulatory milestones Compound Indication Potential milestones Iressa
Slide 6: Potential NME & LE submissions 2014-16
Potential NME & LE submissions 2014-16 PD-L1 (MEDI4736) NSCLC CAZ AVI EU Tremelimumab US/EU/JP cephalosporin/BLI SBI mesothelioma Myalept EU PT003 EU lipodystrophy LABA/LAMA COPD NMEs PT003 US PT001 US/EU LABA/LAMA COPD LAMA COPD lesinurad AZD9291 US/EU/JP Benralizumab US/EU URAT1 gout EGFR T790M NS
Slide 7: AstraZeneca LE development programmes
AstraZeneca LE development programmes 3Q 2014 Results Update
Slide 8: 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 9: Forxiga/Farxiga Diabetes development programme
Forxiga/Farxiga (SGLT-2 inhibitor) Diabetes development programme Patient Phase # of Design Endpoint(s) Status Population Study patients Type 2 diabetes Phase III/IV N = 17150 • ARM 1: Forxiga 10 mg QD + • Time to first event included • FSI Q2 13 mellitus with DECLARE standard of care therapy QD in
Slide 10: Forxiga/Farxiga Diabetes development programme
Forxiga/Farxiga (SGLT-2 inhibitor) Diabetes development programme Patient Phase # of Design Endpoint(s) Status Population Study patients Asian Subjects Phase III N = 260 ARM 1: Forxiga 10 mg QD for 24 weeks • Change from • FSI Q1 14 With Type 2 + background Insulin baseline in HbA1c • LSI Q2 15 Diab
Slide 11: 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 = 444 • ARM 1: Onglyza 5 mg QD Primary: • FSI Q2 14 mellitus on • ARM 2: Placebo QD • The change from • LSI Q4 15 insulin treatment NCT0
Slide 12: 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 13: Bydureon Type 2 Diabetes development programme
Bydureon (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: Bydureon BiD SC (autoinjector) • Change in HbA1c • FSI Q1 13 DURATION- • ARM 2: Bydureon weekly suspension SC f
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 IV N = 14000 • ARM 1: Bydureon once weekly 2mg SC • Time to first • FSI Q2 10 EXSCEL • ARM 2: Placebo confirmed CV event •
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 = 162 • 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: Myalept • Glycaemic control • Ongoing Partnered • Triglycerides • Est. Completion date Q3 15 NIH /NIDDK Open label
Slide 17: Iressa EGFRm NSCLC development programme
Iressa (EGFR TKI) EGFRm NSCLC development programme Patient Phase # of Design Endpoint(s) Status Population Study patients NSCLC Phase I N = 47 Escalation phase • Safety • FSI Q2 14 (Escalation Standard 3+3 design with 28 days • Optimal biologic dose for the • LSI Q1 15 phase) NCT02088112 DLT period
Slide 18: Faslodex Breast cancer development programme
Faslodex (oestrogen receptor antagonist) Breast cancer development programme Patient Population Phase # of Design Endpoint(s) Status Study patients Postmenopausal Phase III N ~450 • ARM 1: Faslodex 500 mg monthly IM • Progression Free • FSI Q4 12 women with HR+ FALCON + an 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 600 • NI in Clinical Cure rate at the Test of • FSI Q2 12 complicated skin COVERS (801 mg q 8 hrs Cure (TOC) visit in b
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 Q4 14 children • ARM 2: Placebo • Safety and tolerability • LSI Q4 14 NCT02269475 • Est comple
Slide 23: Gastrointestinal Phase III development programmes
Gastrointestinal Phase III development programmes Compound 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
Slide 24: AstraZeneca Late stage development programmes
AstraZeneca Late stage development programmes 3Q 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 = 450-600 • ARM 1: Roxadustat • Haemoglobin • Sponsored by FibroGen Chronic Kidney Andes • ARM 2: Placebo response • FSI Q4 12 Disease Patients • Est completion
Slide 26: Lynparza Solid tumours development programmes
Lynparza (PARP inhibitor) Solid tumours development programmes Patient Phase # of Design Primary Status Population Study patients Endpoint PSR BRCAm Phase III N = 264 • ARM 1: Lynparza tablets 300 mg BiD as • Progression Free • FSI Q3 13 ovarian cancer SOLO-2 maintenance therapy until progression Su
Slide 27: Lynparza continued... Solid tumours development programmes
Lynparza (PARP inhibitor) continued... Solid tumours development programmes Patient Phase # of Design Primary Status Population Study patients Endpoint BRCAm Phase III N = 310 • ARM 1: Lynparza 300 mg BiD, continuous • Progression Free • FSI Q2 14 metastatic OlympiAD to progression Survival • LSI Q4
Slide 28: Selumetinib Solid tumours development programmes
Selumetinib (AZD6244, ARRY142886) (MEK-inhibitor) Solid tumours development programmes Patient Phase # of Design Endpoint(s) Status Population Study patients nd 2 Line KRAS Phase III N = 634 • ARM 1: Selumetinib 75mg BiD + docetaxel 75 • Progression Free • FSI Q3 13 M positive SELECT-1 mg/m2 IV on d
Slide 29: AZD9291 NSCLC development programme
AZD9291 (Highly selective, irreversible EGFR TKI) NSCLC development programme Patient Phase # of Design Endpoint(s) Status Population Study patients Advanced EGFRm Phase I/II N ~ 500 • Dose escalation study • Safety and • FSI Q1 13 NSCLC TKI failure AURA • Ph II Extension cohort 80mg QD tolerability
Slide 30: Anti-PD-L1 (MEDI4736) Solid tumours development programmes
Anti-PD-L1 (MEDI4736) Solid tumours development programmes Patient Population Phase # of Design Endpoint(s) Status Study patients Stage IIIB-IV Phase II N = 188 • ARM 1: MEDI4736 IV Q2W • Objective Response • FSI Q1 14 NSCLC patients Atlantic (EFGR/ALK WT) Rate • LSI Q1 15 • ARM 2: MEDI4736 IV Q2W •
Slide 31: Anti-PD-L1 (MEDI4736) continued…
Anti-PD-L1 (MEDI4736) continued… Solid tumours development programmes Patient Population Phase # of Design Endpoint(s) Status Study patients Stage IIIB-IV Phase II/III N = 400 5-Arm study based on biomarker expression • Progression Free • FSI Q2 14 NSCLC patients Lung Master (4736 arm • ARM 1: MEDI4
Slide 32: 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 Phase I N = 24 • Dose Escalation: 3 cohorts at Q2W and • Safety • FSI Q3 13 (all comers) 1 cohort at Q3W • Optimal biologic dose • LSI Q4 14 • Est
Slide 33: Anti-CTLA-4 (tremelimumab) Mesothelioma development 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 Q1 15 peritoneal malignant N
Slide 34: Moxetumomab Pasudotox Haematological malignancies programmes
Moxetumomab Pasudotox (anti-CD22) Haematological malignancies development programmes Patient Phase # of Design Endpoint(s) Status Population Study patients Adults with Phase I N = 49 • Open Label dose • MTD and efficacy • FSI Q2 07 relapsed escalation study • LSI Q1 14 NCT00586924 refractory HCL • E
Slide 35: Anti-IL-5R (benralizumab) Asthma development programme
Anti-IL-5R (benralizumab) Asthma development programme Patient Phase # of Design Endpoint(s) Status Population Study patients Severe asthma, Phase III N = 1026 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 • E
Slide 36: Anti-IL-5R (benralizumab) COPD development programme
Anti-IL-5R (benralizumab) COPD development programme Patient Phase # of Design Endpoint(s) Status Population 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 • Est completion d
Slide 37: Tralokinumab (anti-IL-13) Asthma development programme
Tralokinumab (anti-IL-13) Asthma development programme Patient Phase # of Design Endpoint(s) Status Population Study patients Adults with Phase III N = 1140 • Cohort 1: Primary Endpoint • FSI Q3 14 Uncontrolled STRATOS 1 • ARM 1: Tralokinumab dose regimen 1 • Annual asthma • Primary completion Q2 17
Slide 38: 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 BiD • Change from baseline • FSI Q2 13 Very Severe PINNAC
Slide 39: Anti-IL-17RA (brodalumab) Psoriasis & psoriatic arthritis programmes
Anti-IL-17RA (brodalumab) Psoriasis & psoriatic arthritis development programmes Patient Phase # of Design Endpoint(s) Status Population Study patients Moderate to Phase III N = 661 • ARM 1: 210 mg brodalumab SC • PASI at wk 12 • Primary data Q2 14 severe plaque AMAGINE-1 • ARM 2: 140 mg brodalumab
Slide 40: Lesinurad (SURI) Gout development programme
Lesinurad (SURI) 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 41: 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 42: 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 = 333 • ARM 1: CAZ-AVI 2000/500mg plus • Patients with clinical • FSI Q1 13 complicated urinary REPRISE Metronidazole IV cure at t
Slide 43: BACE (AZD3293) Alzheimer’s Disease development programme
BACE (AZD3293) Alzheimer’s Disease development programme Patient Phase # of Design Endpoint(s) Status Population Study Patients Healthy Phase I N = 56 • Active ARMS: • AEs, labs, vital signs, ECGs • Study completed. volunteers MAD Study • (Part 1) AZD3293 MAD starting • PK • Data from part 1 present
Slide 44: AstraZeneca Early development programmes
AstraZeneca Early development programmes 3Q 2014 Results Update
Slide 45: 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 46: 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 47: 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 48: WEE-1 (AZD1775) Solid tumours development 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 49: FGFR (AZD4547) Solid tumours development 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 Completed Q2 13 who have failed bd and od (c. 30 patients) Recommended dose f
Slide 50: FGFR (AZD4547) continued
FGFR (AZD4547) continued Solid tumours development programme Patient Phase # of Design Endpoint(s) Status population Study patients Advanced cancer Phase I N = 94 • Part A: Ascending oral doses of AZD4547 to define • Part A: MTD and Completed Q1 14 who have failed maximum tolerated dose (MTD) and /o
Slide 51: Volitinib (AZD6094) Phase I/II development 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 Q3 15 comers) NCT01773018 Conducted in Australia • Est
Slide 52: TORC 1/2 (AZD2014) Solid tumours development 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 53: AKT (AZD5363) Solid tumours development 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 54: PI3Kb/d (AZD8186) Solid tumours development programme
PI3Kb/d (AZD8186) Solid tumours development programme Patient Phase # of Design Endpoint(s) Status Population Study patients Advanced Phase I N = 96 • Part A: AZD8186 monotherapy in • Part A: PK, MTD and • FSI Q3 13 CRPC/SqNSCLC ascending intermittent doses in 2 Recommended dose and • Est completion
Slide 55: ISIS-AR (AZD5312) Solid tumours development 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 56: STAT3 (AZD9150) Haematological malignancies programme
STAT3 (AZD9150) Haematological malignancies development programme Patient Phase # of Design Endpoint(s) Status Population Study patients HCC Phase I N =64 • Dose-escalation and dose- • Safety and tolerability . • FSI Q2 13 expansion study • Recommended phase II • Est completion Q2 15 NCT01839604 • I
Slide 57: ATR (AZD6738) Solid tumours development programme
ATR (AZD6738) Solid tumours development programme Patient Phase # of Design Endpoint(s) Status Population Study patients Solid Phase I N = 119 • MAD • Safety and tolerability • FSI Q4 2014 tumours • Efficacy • Est completion Q4 2016 NCT02264678 North America – 1 site • Estimated external presentatio
Slide 58: LABA/LAMA/ICS (PT010) COPD & Asthma programme
LABA/LAMA/ICS (PT010) COPD & Asthma development programme Patient Phase # of Design Endpoint(s) Status Population Study patients (B/BD)= Budesonide, FF = Formoterol fumarate) Moderate to Phase II N = 160 • ARM 1: BFF MDI 320/9.6 μg BiD • Forced expiratory • FSI Q3 14 Severe COPD • ARM 2: BFF MDI 160
Slide 59: MABA (AZD2115) COPD clinical development 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 • Completed NCT01283984 • ARM 2: Placebo admini
Slide 60: p38 inhibitor (AZD7624) COPD development 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 61: URAT1 (RDEA3170) Gout development programme
URAT1 (RDEA3170) Gout development programme Patient Phase Study # of Design Primary endpoint Status Population patients Monotherapy Phase II N = 160 • Arm A: Placebo • Efficacy and Safety at • FSI Q3 13 study in Subjects • Arm B: RDEA3170 5 mg QD Week 12 • LSI Q4 13 with Gout NCT01927198 • Arm C: RD
Slide 62: 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 63: MPO (AZD3241) Parkinson’s Disease development 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 64: Histamine H3 receptor inverse agonist (AZD5213) Phase II programme
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 65: NMDA (AZD6423) Phase I clinical development 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 66: MedImmune Early development programmes
MedImmune Early development programmes 3Q 2014 Results Update
Slide 67: Cardiovascular biologics early development
Cardiovascular biologics early development Phase I clinical development programme Compound 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
Slide 68: 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 Phase II N = 180 • ARM 1: MEDI-551 IV (dose-level 1) and • ORR, including • FSI Q1 12 relapsed or Bendamustine Complete Response • Est completion
Slide 69: Immuno-oncology portfolio Monotherapy early development programme
Immuno-oncology portfolio Monotherapy early development programme Compound Patient Phase # of Design Endpoint(s) Status Population Study Patients PD-1 Solid tumours Phase Ia N = 72 • Dose Escalation (3+3) & • Safety and tolerability • FSI Q4 13 (MEDI0680) Expansion Study • LSI Q2 15 (escalation) NCT
Slide 70: 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 = 208 • Dose Escalation: minimum 5 cohorts • Safety • FSI Q4 13 (Immunotx naïve exploring various treme Q4W and MEDI4736 • Op
Slide 71: Anti-PD-L1 (MEDI4736) + dabrafenib/trametinib Melanoma programme
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 72: Anti-PD-L1 (MEDI4736) + Iressa (gefitinib) NSCLC programme
Anti-PD-L1 (MEDI4736) + Iressa (gefitinib) NSCLC development programme Patient Phase # of Design Endpoint(s) Status Population Study patients NSCLC Phase I N = 47 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 73: 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 74: Murine Anti-OX40 (MEDI6469) + combinations
Murine Anti-OX40 (MEDI6469) + combinations Advanced malignancies development programme Patient Phase # of Design Endpoint(s) Status Population Study Patients Advanced Phase I/II N = 212 Dose-escalation phase • Determination of MTD • FSI Q3 14 malignancies • MEDI6469 IV monotherapy • Safety • LSI Q2
Slide 75: OX40 agonist (MEDI6383) Advanced malignancies programme
OX40 agonist (MEDI6383) Advanced malignancies development programme Patient Phase # of Design Endpoint(s) Status Population Study Patients Advanced Phase I N = 116 Dose-escalation phase • Safety • FSI Q3 14 malignancies • MEDI6383 IV • Determination of MTD • LSI Q3 16 NCT02221960 • Est completion da
Slide 76: Oncology biologics early development Solid tumors programme
Oncology biologics early development Solid tumors development programme Compound Patient Phase # of Design Endpoint(s) Status Population Study patients Anti-Ang2 Solid tumors Phase I N = 16 • MEDI3617 + bevacizumab dose • Safety and • FSI Q4 2010 mAb and ovarian escalation, administered Q3W, IV tole
Slide 77: Oncology biologics early development Solid tumours programme
Oncology biologics early development Solid tumours development programme Compound 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 • FSI Q4 10 mAb gastrointestinal (GI) profile • Est compl
Slide 78: Tralokinumab (anti-IL-13) IPF development programme
Tralokinumab (anti-IL-13) IPF development programme Patient Phase # of Design Endpoint(s) Status Population Study patients Adults with Phase II N = 186 • ARM 1: Tralokinumab high dose IV • Change from baseline in • FSI Q4 12 Idiopathic • ARM 2: Tralokinumab low dose IV percent-predicted forced • Est
Slide 79: Anti-IL-17RA (brodalumab) Asthma development programme
Anti-IL-17RA (brodalumab) Asthma development programme Patient Phase # of Design Endpoint(s) Status Population 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 • ARM 2: placebo SC • Est completion date Q1 15 controlled
Slide 80: Anti-TSLP (MEDI9929) Asthma development programme
Anti-TSLP (MEDI9929) 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 Q4 13 inadequately PATHWAY • ARM 2: Low dose MEDI9929 SC asthma exacerbation rate • LSI Q
Slide 81: Mavrilimumab (anti-GMCSF) RA development 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 low dose SC • DAS28 • FSI Q3 12 inadequate response EARTH (final) • ARM 2: Mavrilimumab medium dose SC response at • LS
Slide 82: Sifalimumab (anti-interferon α) SLE development programme
Sifalimumab (anti-interferon α) SLE development programme Patient Phase Study # of Design Endpoint(s) Status Population patients Moderate- Phase ll N = 433 • ARM 1: 200 mg IV MEDI-545 Q2W for 4 wks then • Proportion of subjects • FSI Q1 11 severe SLE (final) Q4W for 44 wks achieving a response in •
Slide 83: Anifrolumab SLE development programme
Anifrolumab (anti-type I IFN receptor) SLE development programme Patient Phase # of Design Endpoint(s) Status Population Study patients Moderate- Phase ll N = 307 • ARM 1: 300 mg IV MEDI-546 Q4W for 48 weeks • Response in • FSI Q1 12 severe SLE (final) • ARM 2: 1000 mg IV MEDI-546 Q4W for 48 weeks S
Slide 84: Anti-B7RP-1 (MEDI5872) SLE development programme
Anti-B7RP-1 (MEDI5872) SLE development programme Patient Phase # of Design Endpoint(s) Status Population Study patients SLE and lupus Phase I N = 42 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 85: Infectious diseases biologics early development
Infectious diseases biologics early development Phase I/II clinical development programmes Compound Patient Phase # of Design Endpoint(s) Status Population Study patients Anti-Staph AT Healthy Phase II N = 462 • Placebo-controlled, • Efficacy and Safety • FSI October 2014 (MEDI4893) Adults single-do
Slide 86: Vaccines biologics early development
Vaccines biologics early development Phase I/II clinical development programmes Compound Patient Phase # of Design Endpoint(s) Status Population Study patients LAIV RSV Healthy 6-24 mo Phase I/IIa N = 116 • Randomized, Double- • Evaluate the Safety, • Completed Paediatric prevention of Blind, Placeb
Slide 87: Neuroscience biologics early development
Neuroscience biologics early development Phase I development programmes Compound 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 (MED
Slide 88: Gastrointestinal biologics early development
Gastrointestinal biologics early development Phase I/II development programmes Compound 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 • FSI Q4 12 Severe • ARM 2: MEDI7183 dose level 2, SC week 8 (
Slide 89: 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