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 to the best of our knowledge as at 30 June 2014.
It includes estimated timelines with regards to study completion and first external presentations of primary data. These estimates are subject to change as programmes recruit faster or slower than anticipated.
Project postings on clinicaltrials.gov are updated on a continuous basis as projects progress. For the most up to date information on our clinical programmes please visit clinicaltrials.gov.
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) 8 NSCLC 8 6 benralizumab (IL-5R) COPD LEs olaparib (PARP) adjuvant BRCAm BC
HY 2013 FY 2013 HY 2014
Oncology RIA CVMD 2 2 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 ovarian PD-L1 (MEDI4736) tralokinumab (IL-13) CD19 (MEDI-551) NSCLC severe asthma CLL
benralizumab (IL-5R) Forxiga (SGLT-2) PD-L1 (MEDI4736) COPD Type 1 diabetes additional tumours brodalumab (IL-17R) Symbicort (ICS/LABA) PD-L1 combinations psoriatic arthritis mild asthma additional tumours olaparib (PARP) AZD9291 (EGFR) AZD9291 combinations adjuvant BRCAm BC 1L NSCLC EGFRM+ NSCLC LEs olaparib (PARP) PD-L1 +/- tremelimumab metastatic BRCAm BC SCCHN selumetinib (MEK) PD-L1 + tremelimumab metastatic uveal melanoma NSCLC
Pivotal study starts Pivotal study decision Pivotal study decision 1H 2014 made 1H 2014 pending 2H 2014 3 Oncology RIA CVMD Neuroscience 3 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 (MEDI-551) + rituximab LABA/LAMA/ICS (PT010) Roxadustat (HIF) haems COPD anaemia in CKD/ESRD Amyloidβ (MEDI1814) Volitinib (MET) Tremelimumab (CTLA-4) Alzheimer’s solid tumours mesothelioma PD-L1 (MEDI4736) + Iressa EGFR M+ NSCLC Additional indications PD-L1 (MEDI4736) + PD-1 Benralizumab (IL-5R) (MEDI0680) solid tumours COPD CD40L (MEDI4920) PD-L1 (MEDI4736) Primary Sjögren’s syndrome 3L NSCLC RSV sF+GLA –SE (MEDI7510) olaparib RSV prophylaxis PARP adjuvant breast cancer RSV Mab YTE (MEDI8897) RSV prophylaxis Tremelimumab (CTLA-4) + Iressa EGFR M+ NSCLC
Added back to pipeline SGRM (AZD7594) asthma, COPD
Removed from Phase I Removed from Phase II Removed from Phase III Removed from Registration
NMEs NMEs Epanova (US)* CXCR2 (AZD4721) CXCR2 (AZD5069) hypertriglyceridaemia COPD asthma HtN9 vaccine (MEDI9287) IL-1R (MEDI8968) avian flu COPD, HS
Additional indications Tenapanor (NHE3) fluid retention ¥ New business development; *Approved Q2 2014
4 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) CD19 (MEDI-551) AZD9291 (EGFRm+ t790m+) PD-L1 (MEDI4736) haems solid tumours ovarian, 1L NSCLC CLL, DLBCL NSCLC NSCLC
Androgen (AZD5312) PD-1 (MEDI0680) TORC ½ (AZD2014) IGF (MEDI-573) olaparib (PARP) Moxetumomab (CD22) prostate solid tumours solid tumours metastatic breast cancer BRCA ovarian, gastric, breast HCL
ATR (AZD6738) CEA BiTE (MEDI-565) FGFR (AZD4547) anifrolumab selumetinib (MEK) tremelimumab (CTLA-4) CLL, H&N GI tumours solid tumours IFNaR SLE 2L KRAS+ve NSCLC, uveal melanoma, DTC mesothelioma
PI3Kβδ (AZD8186) ANG-2 (MEDI3617) AKT (AZD5363) AZD9412 (Inhaled βIFN) lesinurad (URAT1) brodalumab (IL-17R) solid tumours solid tumours breast cancer asthma, COPD gout psoriasis, psoriatic arthritis
STAT3 (AZD9150) mOX40 (MEDI6469) volitinib (MET) mavrilimumab (GM-CSFR) LABA/LAMA (PT003) benralizumab (IL-5R) haems + solids solid tumours solid tumours rheumatoid arthritis COPD severe asthma, COPD
TLR9 (AZD1419) CD40L (MEDI4920) MABA (AZD2115) IL-23 (MEDI2070) LAMA (PT001) asthma Primary Sjögren’s Syndrome COPD Crohn’s COPD
SGRM (AZD7594) B7RP1 (MEDI5872) LABA/LAMA/ICS (PT010) α4β7 (MEDI7183) roxadustat (HIF) asthma, COPD SLE COPD Crohn’s, ulcerative colitis anaemia CKD/ESRD
p38 inhibitor (AZD7624) LCAT (MEDI6012) URAT1 (RDEA3170) TSLP (MEDI9929) Movantik (PAMORA) COPD ACS gout asthma opioid induced constipation
TLR7 agonist (AZD8848) Rh-Factor II (MEDI8111) Hormone mod. (AZD4901) sifalimumab (IFNa) CAZ AVI (BLI/cephalosporin) asthma rauma/bleeding PCOS SLE SBI
MCH (AZD1979) Amyloidβ (MEDI1814) tenapanor (AZD1722) IL-13 (tralokinumab) obesity Alzheimer’s NHE3 inhibitor ESRD-Pi/CKD asthma, IPF
BACE (AZD3293) MEDI-550 MPO (AZD3241) Alzheimer's pandemic influenza virus vaccine Multiple System Atrophy New approvals 1 New Molecular Entity NMDA (AZD6423) staph alpha tox. (MEDI4893) H3R (AZD5213) suicidal ideation SSI Tourette’s, neuropathic pain Small molecule Large molecule ATM AVI MEDI7510 Oxazolidinone (AZD5847) Epanova BL/BLI SBI RSV sF+GLA-SE RSV prevention TB hypertriglyceridaemia
GyrAr (AZD0914) MEDI8897 BLI/cephalosporin (CXL) serious infection RSV Mab YTE passive RSV prophylaxis MRSA
PRVV (MEDI-559) Paediatric RSV vaccine
Oncology combinations PD-L1 + dabrafenib + trametinib PD-L1 + PD-1 melanoma solid tumours Oncology RIA CVMD Neuroscience Infection
PD-L1 + Iressa CD-19 + rituximab Terminations in Q2 2014 EGFR M+ NSCLC haems AZD5069 (asthma) in Phase 2, MEDI8968 (COPD, HS) in Phase 2, AZD4721 (COPD) in Phase 1, MEDI9287 (avian flu) in Phase 1 (AZD5069 and AZD4721 termination decisions made in July 2014) PD-L1 + tremelimumab tremelimumab + Iressa solid5 tumours| NSCLC Pipeline table as of 30th June 2014 5 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 I (ESMO)
AZD9291 NSCLC Ph I (ESMO)
AZD3293 Alzheimer’s disease Ph I (CTAD)
6 6 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 approval (PDUFA 29 Oct 2014)
saxagliptin/dapagliflozin FDC type 2 diabetes US filing
lesinurad gout EU, US filing
CAZ AVI cIAI EU filing
7 7 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 roxadustat (FG-4592) CH PARP PSR BRCAm ovarian MEK uveal melanoma HIF anaemia CKD/ESRD
2014 2015 2016
Bydureon Dual Chamber Pen JP Brilinta PEGASUS US/EU/JP Brilinta EUCLID US/EU GLP-1 T2D ADP receptor antagonist ADP receptor antagonist Onglyza SAVOR US/EU Bydureon Autoinjector US/EU Brilinta SOCRATES US/EU/JP DPP-4 T2D GLP-1 T2D ADP receptor antagonist saxa-dapa FDC US/EU Iressa IMPRESS EU/JP/CH Caprelsa US/EU/JP DPP-4/SGLT-2 T2D EGFRm+ NSCLC differentiated thyroid cancer Iressa US Faslodex US/EU/JP/CH EGFRm+ NSCLC ER antagonist olaparib SOLO-2 US/EU/JP/CH LEs PSR BRCAm ovarian cancer olaparib OlympiAD US/EU/JP New since 1Q 14 results update PARP metastatic breast cancer lesinurad FDC US/EU SURI/XOI gout 8 * Filing is the responsibility of partner Oncology RIA CVMD Neuroscience Infection 8 AstraZeneca LE development programmes
2Q 2014 Results Update 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-fatal MI and non-fatal • LSI Q2 13 • ARM 3: Placebo BiD stroke • Est. completion date Q1 15 NCT01225562 on a background of ASA • Est. external presentation Q3 15 (ESC) Global study – 31 countries Patients with Phase III N = 13500 • ARM 1: Ticagrelor 90 mg BiD • Composite of CV death, • FSI Q3 12 PAD EUCLID • ARM 2: Clopidogrel 75 mg QD non-fatal MI and ischemic • LSI Q1 14 monotherapy trial stroke • Est. completion date Q1 16 NCT01732822 • Est. external presentation 2016 Global study – 28 countries
Patients with Phase III N = 9600 • ARM 1: Ticagrelor 90 mg BiD • Composite of non-fatal • FSI Q1 14 Stroke or TIA SOCRATES • ARM 2: ASA 100mg/day stroke, non-fatal MI and all • Est. completion date Q4 15 monotherapy trial cause death • Est. external presentation 2016 NCT01994720
Global study – approx. 32 countries Patients with Phase III N = 17000 • ARM 1: Ticagrelor 90 mg BiD • Composite of CV death, • FSI Q1 14 Type 2 Diabetes THEMIS • ARM 2: Placebo BiD non-fatal MI and non-fatal • Est. completion date Q1 17 and Coronary on a background of ASA if not contra stroke • Est. external presentation beyond Artery Disease NCT01991795 indicated or not tolerated planning horizon without a previous history Global study – approx. 40 countries of MI or Stroke
10 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 included in • LSI Q2 16 high risk for CV • ARM 2: Placebo + standard of care therapy the composite • Est. completion date Q2 19 event NCT01730534 for Type 2 Diabetes endpoint of CV • Est. external presentation 2020 death, MI or Global study – 33 countries ischemic stroke
11 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 NCT02104804 baseline in HbA1C • Est. Primary completion date Q2 16 Study in China at 24 week • Est. Study completion date Q2 16
Secondary: • The change from baseline at 24 week in 120-minute postprandial plasma glucose (PPG) in response to a meal tolerance
12 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 from baseline in • LSI Q2 13 Mellitus NCT01606007 • ARM 3: Saxa 5 mg + Dapa 10 mg + HbA1C at 24 week • Primary completion date Q1 14 Met XR QD • Targeted as Late Breaking abstract Secondary: Q2 14 (ADA) Global study – 12 countries • Mean change from baseline in 2h MTT at 24 week Type 2 Phase III N = 280 • ARM 1: Saxa 5mg + Dapa 10 mg + Primary: • FSI Q2 12 Diabetes Met IR • Mean change from baseline in • Est. Primary completion date Q2 14 Mellitus NCT01619059 • ARM 2: Placebo + Dapa 10 mg + HbA1C at 24 week • Est. Study completion date Q1 15 Met IR • Est. external presentation 2015 Secondary: Global study – 9 countries • Mean change from baseline in 2h MTT at 24 week Type 2 Phase III N = 280 • ARM 1: Dapa 10 mg + Saxa 5 mg + Primary: • FSI Q3 12 Diabetes Met IR • Mean change from baseline in • Est. Primary completion date Q3 14 Mellitus NCT01646320 • ARM 2: Placebo + Saxa 5 mg + Met HbA1C at 24 week • Est. Study completion date Q1 15 IR • Est. external presentation 2015 Secondary: Global study – 8 countries • Mean change from baseline in FPG at 24 week
*studies performed by BMS 13 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 suspension SC from baseline at 28 • Est. completion date Q3 14 NEO 1 (autoinjector) weeks • Est. external presentation Q3 14 Partnered On a background of diet & exercise alone or NCT01652716 with stable regimen of oral antidiabetes
US only Type 2 Diabetes Phase III N = 360 • ARM 1: Sitagliptin • Change in HbA1c • FSI Q1 13 DURATION- • ARM 2: Exenatide weekly suspension SC from baseline at 28 • Est. completion date Q2 14 NEO 2 (autoinjector) weeks • Est. external presentation Q3 14 Partnered • ARM 3: Placebo
NCT01652729 On a background of diet & exercise alone or with stable regimen of oral antidiabetes
US only 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 • Est completion date Q2 18 Partnered in the primary • Estimated External Presentation On a background of standard of care composite CV Beyond Planning Horizon NCT01144338 medication, different degree of CV risk endpoint (CV death, non-fatal MI, non- Global study fatal stroke)
14 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: Placebo (olive oil) triglycerides over 12 • LSI Q4 14 weeks • Est completion date Q4 15 NCT02009865 Global study – 7 countries
Patient with Phase III 13,000 • ARM 1: Epanova 4g QD + statin • Composite of MACE • FSI planned to H2 14 hypertri- STRENGTH • ARM 2: Placebo (corn oil) + statin • Est completion date Q2 19 glyceridaemia and high CVD NCT02104817 Global study – 18 countries risk
15 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 label treatment protocol • Various sub- NIH sponsored protocols ISS Patients from multiple countries
NCT01778556 Lipodystrophy Phase III N = 28* • ARM 1: Metreleptin • Glycaemic control • Ongoing with associated FHA101 • Triglycerides • Est. Completion date Q4 14 diabetes and/or Partnered Open label treatment protocol hyper- BMS triglyceridaemia NCT00677313 * Relates to data-cut for BLA submission: studies are ongoing
16 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 • ARM 2: Placebo + max 6 cycles of • Overall Survival is a • Est completion date Q2 14 progressed on NCT01544179 cisplatin and pemetrexed secondary endpoint • Est. external presentationpresentation:: Q3 st 1 line IRESSA 14 Global study – 11 countries NSCLC Phase I N = 47 Escalation phase • Safety • FSI Q2 14 (Escalation Standard 3+3 design with 28 days DLT • Optimal biologic dose for the • LSI Q1 15 phase) NCT02088112 period combination • Est completion date Q4 17 • Gefitinib (QD) + MEDI4736 IV • Estimated external EGFR M+ • Secondary endpoints include presentation beyond planning NSCLC naïve to Expansion phase tumour response, Objective horizon EGFR-TKI • Gefitinib (QD) + MEDI4736 IV response rate, disease control therapy recommended dose rate, progression-free survival, (Expansion immunogenicity, phase) Study to be conducted in US and Korea pharmacokinetics, pharmacodynamics
17 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 (+ oral placebo) Survival (PFS) • LSI Q4 14 locally advanced • ARM 2: Arimidex 1 mg (+ placebo injection) • Est primary completion date Q2 16 or metastatic NCT01602380 • Overall Survival is a • Est. external presentation 2016 breast cancer, Global study – 21 countries secondary endpoint who have not previously been treated with any hormonal therapy st (1 -line) Chinese, Phase III N = 221 • ARM 1: Faslodex 500 mg monthly IM + an • Progression Free • FSI Q1 11 postmenopausal additional dose on day 14 Survival • LSI Q4 13 women with HR+ • ARM 2: Faslodex 250 mg monthly IM • Est primary Completion Date Q1 14 advanced breast NCT01300351 • Est. external presentation Q4 14 cancer, China study San Antonio Breast Cancer progressing or Symposium relapsing after previous endocrine therapy nd (2 -line )
18 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 refractory or NCT01876784 • Est completion date Q2 17 unsuitable for Global study – 12 countries • Est external presentation Q4 17 radioiodine therapy
Unresectable Phase I/II N = 10 • ARM 1: Vandetanib 300mg oral dose QD • Frequency and • FSI Q4 12 locally severity of adverse • LSI Q2 13 advanced or NCT01661179 Japanese patients events • Est completion date Q3 14 metastatic • Secondary end point medullary objective response thyroid rate carcinoma
19 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 weeks • LSI Q3 15 GINA 2 bid • Time to first severe • Est. completion date Q4 16 NCT02149199 • ARM 2: Pulmicort 200 μg Turbuhaler bid + asthma exacerbation • Est. external presentation terbutaline 0.4 mg Turbuhaler 'as needed' • Time to first moderate or beyond planning horizon • ARM 3: terbutaline Turbuhaler 0.4 mg 'as severe asthma needed' + placebo Pulmicort 200 μg Turbuhaler exacerbation bid • Average change from baseline in pre-dose FEV1 Global study – 19 countries
20 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 the • LSI Q2 14 and soft tissue • Arm 2: Vancomycin plus modified Intent-To-Treat (IIT) and • Est completion date Q2 14 infections NCT01499277 aztreonam the Clinically Evaluable (CE) (cSSTI) analysis sets
• Secondary endpoints include clinical response at End of Treatment (EOT) visit and microbiological response at TOC and EOT Patients with Phase III N = 692 • Arm 1: Ceftaroline fosamil 600 mg • NI in Clinical Cure rate at the Test • FSI Q4 11 Community- CAP q 12 hrs of Cure (TOC) visit in Clinically • LSI Q2 13 Acquired • Arm 2: Ceftriaxone 2 g q 24 hrs Evaluable (CE) population • Est completion date Q2 13 Pneumonia NCT01371838 • Est external presentation Q2 14 (CAP) in Asia • Secondary endpoints include clinical response at End of Treatment (EOT) visit and microbiological response at EOT
21 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 shortly Nasal administration
Japan only
Healthy Phase III N =100 • ARM 1: One or two doses of MEDI3250 • Safety and tolerability • FSI Q3 14 children • Est completion Q4 14 To be posted shortly Nasal administration
Japan only
22 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 NCT01669811 Japan-only study • Targeted as late breaking abstract at ACG Oct 2014 or DDW May 2015
Nexium Seriously ill Phase III N=300 • ARM 1: Nexium 30 min intermittent • Proportion of • FSI Q3 14 patients infusions given for max.14 patients with • LSI Q3 16 (Stress Ulcer NCT02157376 days upper GI bleeding • Est completion date Q3 16
Prophylaxis, • ARM 2: Cimetidine(Tagamet) 30 min • Est external presentation 18 SUP) bolus infusion + continuous infusion for max. 14 days
China-only study
Entocort Crohn’s Phase III N = 110 • ARM 1: Entocort 9 mg QD • Remission • FSI Q1 12 disease (mild • ARM 2: Mesalazine 1 g TD defined by a CDAI • LSI Q2 14 to moderate) NCT01514240 score of ≤150 • Est completion Q4 14 Japan-only study • Est external presentation 16
Linaclotide IBS-C Phase III N = 800 • ARM 1: Linaclotide 290μg QD • 12-week • FSI Q3 13 • ARM 2: placebo abdominal • LSI Q3 14 NCT01880424 pain/abdominal • Est completion date Q4 14
Participating countries China, Australia, discomfort • Est external presentation 16 New Zealand response
• 12-week IBS degree of relief response
23 AstraZeneca Late stage development programmes
2Q 2014 Results Update 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 Patients Not NCT01750190 Global study – 14 countries Receiving Dialysis Phase III N = 600 • ARM 1: Roxadustat • Haemoglobin • Sponsored by Astellas Alps • ARM 2: Placebo response • FSI Q2 13 • Est completion Q2 16 NCT01887600 Global study – 14 countries
Phase III N = 570 • ARM 1: Roxadustat • Haemoglobin • Sponsored by Astellas Dolomites • ARM 2: Darbepoetin alfa response • FSI Q1 14 • Est completion Q3 17 NCT02021318 Global study – 8 countries
Phase III N = 5200 • ARM 1: Roxadustat • MACE • Sponsored by AstraZeneca Olympus enrolled, 2600 • ARM 2: Placebo • FSI Q2 14 randomized • Est completion Q1 17 NCT02174627 Global study – 4 countries
Anaemia in Phase III N = 2850 • ARM 1: Roxadustat • MACE • Sponsored by AstraZeneca CKD in Patients Rockies enrolled, 1425 • ARM 2: Epoetin alfa • FSI Q2 14 Receiving randomized • Est completion Q1 17 Dialysis NCT02174731 Global study – 5 countries
Anaemia in Phase III N = 750 • ARM 1: Roxadustat • Haemoglobin • Sponsored by FibroGen Newly Initiated Himalayas • ARM 2: Epoetin alfa response • FSI Q4 13 Dialysis • Est completion Q2 16 Patients NCT02052310 Global study – 3 countries 25 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 Survival • LSI Q1 15 • ARM 2: placebo tablets BiD • Primary analysis planned Q3 15 NCT01874353 • Overall Survival is a • Primary presentation Q2 16 Global study – 16 countries secondary endpoint. st 1 line Phase III N = 344 • ARM 1: olaparib tablets 300 mg BiD • Progression Free • FSI Q3 13 maintenance SOLO-1 maintenance therapy for 2 years or until Survival • LSI Q1 15 BRCAm ovarian disease progression • Primary analysis planned Q3 16 cancer NCT01844986 • ARM 2: placebo • Overall Survival is a • Primary presentation Q2 17 secondary endpoint. Global study – 15 countries nd 2 line gastric Phase III N = 500 • ARM 1: paclitaxel + olaparib until progression • Overall Survival • FSI Q3 13 cancer (all GOLD • ARM 2: paclitaxel + placebo • LSI Q3 15 patients with a • Est completion date Q3 16 co-primary sub NCT01924533 olaparib dose 100mg BiD throughout paclitaxel • Est external presentation Q3 17 population) dose cycle & 300 mg BiD post cycle
The study will be conducted in Korea, China, Taiwan and Japan
BRCAm Phase III N = 310 • Arm 1: Olaparib 300 mg BiD, continuous to • Progression Free • FSI Q2 14 metastatic OlympiAD progression Survival • LSI Q4 15 breast cancer • Arm 2: Physician’s choice: • Overall Survival is a • Est completion date Q2 16 NCT02000622 Capecitabine 2500 mg/m2 x 14 q 21 secondary endpoint • External Presentation Q2 17 Vinorelbine 30 mg/m2 d 1, 8 q 21 Eribulin 1.4 mg/m2 d 1, 8 q 21 to progression Metastatic Phase II N = 170 • ARM 1: Olaparib 200 or 300mg BiD + • Radiologic • FSI Q2 14 Castration Abiraterone Progression Free • LSI Q3 2017 Resistant NCT01972217 • ARM 2: Placebo + Abiraterone Survival • Est completion date Q316 26 Prostate CA Global study 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 cancer • Arm 2: Placebo 12 month duration DFS and OS • Est primary analysis Q1 20 NCT02032823 Global study partnership with BIG and NCI/NRG
Pancreas Phase III N = 145 • Arm 1: olaparib tablets 300 mg twice daily • Primary Endpoint • FSI Q3 2014 gBRCA POLO as maintenance therapy until progression. PFS • LSI: Q4 2015 • Arm 2: placebo tablets BiD • OS secondary • Results : Q1 2016 NCT02184195 endpoint • Presentation: Q2 2016 • Global Study approx 10 countries
27 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 on day 1 of each 21 day cycle Survival • LSI Q1 16 • ARM 2: Placebo BiD + docetaxel 75 mg/m2 IV • Est completion date Q1 17 NCT01933932 on day 1 of each 21 day cycle • Overall Survival is a • Estimated external presentation secondary beyond planning horizon Global study – 26 countries endpoint. nd 2 Line KRAS M Phase II N = 265 • ARM 1: Selumetinib 75mg BiD + docetaxel 75 • Progression Free • FSI Q4 12 negative NSCLC SELECT-2 mg/m2 IV on day 1 of each 21 day cycle Survival • LSI Q4 14 • ARM 2: Selumetinib 75mg BiD + docetaxel 60 • Est completion date Q3 15 NCT01750281 mg/m2 IV on day 1 of each 21 day cycle • Overall Survival is a • Est external presentation 2015 • ARM 3: Placebo BiD + docetaxel 75 mg/m2 IV on secondary day 1 of each 21 day cycle endpoint.
Global study – 7 countries Metastatic Uveal Phase III N = 128 • ARM 1: Selumetinib 75 mg BiD + dacarbazine • Progression Free • FSI Q2 14 2 Melanoma SUMIT 1000 mg/m day 1 of every 21 day cycle Survival • LSI Q1 15 2 • ARM 2: Placebo BiD + dacarbazine 1000 mg/m • Est completion date Q2 15 NCT01974752 day 1 of every 21 day cycle • Est external presentation 2015
3:1 Randomisation Global study – 10 countries • ARM 1: Selumetinib 75mg BiD 5 weeks duration • FSI Q3 13 Differentiated Phase III N = 304 a • Complete remission Thyroid Cancer ASTRA + RAI 100mCi (CR) rate at 18 • LSI Q4 14 • ARM 2: Placebo BiD 5 weeks duration + RAI months post-RAI • Est completion date Q216 100mCia NCT01843062 • Estimated external presentation
beyond planning horizon Global study – 8 countries • Clinical remission
a 131 rate at 18 m post Single dose of 100mCi I administered following RAI (per SoC) 28 4 weeks of selumetinib (or placebo). 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 completion Q2 15 failure + /- primary • PFS and OS • Next external presentation Q3 14 resistance mutation NCT01802632 secondary endpoints (ESMO) T790M • Est external presentation final data Q2 15 (ASCO)
Advanced EGFR Phase II N = 175 • ARM 1: AZD9291 80 mg QD • ORR • FSI Q2 14 m+ NSCLC TKI AURA2 • Est completion Q3 15 failure and primary Global study – 8 countries • PFS and OS • Est external presentation: TBD resistance mutation NCT02094261 secondary endpoints T790M
Advanced EGFR Phase III N= 610 • ARM 1: AZD9291 80mg QD • PFS • FSI Q3 14 m+ NSCLC TKI AURA 3 • ARM2: pemetrexed 500mg/m2 + • OS and QoL as • Est completion Q2 16 failure and primary carboplatin AUC5 or pemetrexed secondary endpoints • Est external presentation: TBD resistance mutation NCT02151981 500mg/m2 + cisplatin 75mg/m2 (2:1 T790M randomization)
Advanced EGFRm+ Phase Ib N ~ 90 • AZD9291 in combination with MEDI4736 • Safety, Tolerability, • FSI Q3 14 NSCLC TKI failure TATTON • AZD9291 in combination with AZD6094 Pharmacokinetics • Est completion Q3 15 • AZD9291 in combination with selumetinib and Preliminary Anti- • Est external presentation: TBD NCT02143466 tumour Activity
29 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 (EFGR/ALK • Est completion date Q2 15 PD-L1+ve Patients NCT02087423 M+) • Secondary endpoints • Est external presentation: 2016 include duration of Global study – 18 countries response, progression free survival and overall survival
Unresectable Stage Phase III N = 702 • ARM 1: MEDI4736 IV Q2W • Progression Free • FSI Q2 14 III NSCLC patients Pacific • ARM 2: placebo Survival (PFS) • LSI Q2 16 following platinum- • Overall Survival (OS) • Est completion date Q2 17 NCT02125461 based concurrent Global study • Est external presentation beyond chemo-radiation planning horizon therapy Stage IIIB-IV NSCLC Phase III N = 484 • ARM 1: MEDI4736 IV Q2W (PD-L1+ • Progression Free Monotherapy arm patients who have Arctic patients) Survival (PFS) • Planned: FSI Q3 14 not be tested vs • Overall Survival (OS) • LSI 4Q15 positive for Not yet posted • ARM 2: Standard of Care • Est completion date 1Q17 (PFS) EGFR/Alk mutation • ARM 3: MEDI4736+tremelimumab Combination therapy IV Q4W (PD-L1 –ve patients) • Planned: FSI Q3 14 vs • LSI 2Q15 • ARM 4: Standard of Care • Est completion date 3Q16 (PFS)
• Est external presentation beyond planning horizon
30 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 Survival (PFS) • LSI (Phase II Q1 15) Protocol only) • ARM 1: MEDI4736Unmatched biomarker • Overall Survival (OS) • Est completion date Q4 16 Biomarker-Targeted IVQ2W • Estexternal presentation Second-Line Therapy Partnered • ARM 2: AZD4547 (FGFR inhibitor) beyond planning horizon with NCI and • ARM 3: CDK4/6 inhibitor SWOG • ARM 4: PI3K Inhibitor • ARM 5: HGFR Inhibitor NCT02154490 Stage IIIB-IV Phase I/II N = 72 • ARM 1: Iressa initially then switch to • Complete Response • Planned: FSI Q3 14 NSCLC patients Sequencing MEDI4736 IVQ2W Rate • LSI Q2 15 Study • ARM 2: AZD9291 then switch to • Est completion date Q2 16 MEDI4736 • ORR, Disease Control • Est external presentation: NCT02179671 • ARM 3: Selumetinib + Docetaxel then Rate 2016 switch to MEDI4736 • ARM 4: tremelimumab then switch to MEDI4736 NSCLC, SCCHN Phase I N = 220 • Dose Escalation: 5 cohorts at Q2W and • Safety • FSI Q3 12 HCC, pancreas, 1 cohort at Q3W • Optimal biologic dose • LSI Q4 14 triple-negative BC, NCT01693562 • Est completion Q2 15 gastroesophageal, • Dose Expansion: At least 8 tumor type • Secondary endpoints • Est external presentations Q2 uveal melanoma, cohorts at the Q2W MTD defined during include PK, 14 of both dose escalation and cutaneous dose escalation immunogenicity and dose expansion (ASCO) melanoma antitumor activity • Further potential update Q3 14 Global study – 5 countries (ESMO) 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 NCT01938612 • Est completion Q2 16 This study is being conducted in Japan
31 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 NCT01843374 • External presentation Q2 14 mesothelioma (ASCO)
32 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 • Est. completion Q1 15
Adults with Phase III N = 77 • Multicenter, Single-Arm, • Duration of response (CR and PR) • FSI Q1 13 relapsed or Open label study • ORR, PFS, TTF • Est completion Q3 16 refractory HCL NCT01829711 • Safety and tolerability • Clinical activity of CAT-8015
Children, Phase I N = 55 • Multicenter, Dose Escalation • To estimate MTCD • FSI Q3 08 Adolescents Study • To characterize tolerability and safety • LSI Q2 14 and Young NCT00659425 profile • Est. Completion Q3 14 Adults with • To study clinical PK refractory ALL • To observe anti-tumor activity or NHL Pediatrics with Phase II N = 76 • Multicenter, Single-arm, • Evaluate efficacy by MRD negative CRc • FSI Q3 14 relapsed or Open label study rate, ORR (CR, CRi, PR), DCOR, DOR, • LSI Q2 16 refractory pALL To be posted PFS and OS • Est Completion Q4 17 or • Safety and tolerability lymphoblastic • Evaluate PK lymphoma of B- cell origin
33 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 • Est completion date Q1 16 despite background MD • ARM 3: Placebo SC • Assess pulmonary function, controller medication, NCT01914757 asthma symptoms, other MD & HD ICS + LABA ± asthma control metrics, 56-week study chronic OCS ER/ED hospitalization visits, Age 12 – 75yrs Global study – 11 countries PK, and IM Severe asthma, Phase III N = 1134 • ARM 1: 30 mg Q8w SC • Annual Asthma • FSI Q4 13 inadequately controlled SIROCCO • ARM 2: 30 mg Q4w SC Exacerbation Rate • Est completion date Q1 16 despite background • ARM 3: Placebo SC • Assess pulmonary function, controller medication HD NCT01928771 asthma symptoms, other ICS + LABA ± chronic asthma control metrics, 48-week study OCS ER/ED hospitalization visits, Age 12 – 75 yrs Global study – 17 countries PK, and IM Severe asthma, Phase III N = 120 • ARM 1: 30 mg Q8w SC • Reduction of Oral • FSI Q3 14 inadequately controlled ZONDA • ARM 2: 30 mg Q4w SC Corticosteroid dose • Est completion date Q1 16 on high dose inhaled • ARM 3: Placebo SC corticosteroid plus long- NCT02075255 acting β2 agonist and chronic oral 46-week study corticosteroid therapy Global study – 7 countries Age 18 – 75 yrs
34 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 14 exhibit eosinophilia (≥ NCT01227278 (ATS) 3.0% sputum eosinophilia) 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 date Q4 17 Pulmonary Disease • ARM 3: 100 mg Q8w SC (COPD) with NCT02155660 • ARM 4: Placebo SC Exacerbation History
48-week study Global study – 17 countries Moderate to Very Severe Phase III N = 1743 • ARM 1: 30 mg Q4w SC • Rate of COPD • FSI Q3 14 Chronic Obstructive GALATHEA • ARM 2: 100 mg Q8w SC Exacerbation • Est completion date Q4 17 Pulmonary Disease • ARM 3: Placebo SC (COPD) with NCT02138916
Exacerbation History 48-week study Global study – 15 countries
35 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 • ARM 2: GP MDI (PT001) 14.4 μg in morning pre-dose • LSI Sept 14 • Results Q2 15* COPD • ARM 3: FF MDI (PT005) 9.6 μg trough FEV1 NCT01854645 • ARM 4: Open-label tiotropium bromide inhalation powder • ARM 5: Placebo MDI
24 week study US, Australia, New Zealand Moderate to Phase III N = 1614 • ARM 1: GFF MDI (PT003) 14.4/9.6 μg • Change from baseline • FSI Q3 13 Very Severe PINNACLE 2 • ARM 2: GP MDI (PT001) 14.4 μg in morning pre-dose • LSI Sept 14 • Results Q2 15* COPD • ARM 3: FF MDI (PT005) 9.6 μg trough FEV1 NCT01854658 • ARM 4: Placebo MDI
24 week study US, Australia, New Zealand Moderate to Phase III N = 850 • ARM 1: GFF MDI (PT003) 14.4/9.6 μg • Overall safety, • FSI Q4 13 Very Severe PINNACLE 3 • ARM 2: GP MDI (PT001) 14.4 μg tolerability and efficacy • LSI Sept14 • Results Q2 15 COPD • ARM 3: FF MDI (PT005) 9.6 μg NCT01970878 • ARM 4: Open-label tiotropium bromide inhalation powder
28 week extension US, Australia, New Zealand
36
*Results for Phase III efficacy studies to remain blinded until completion of PINNACLE 3 safety extension. Overall summary of Phase III data available in Jan 2015 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 SC • Static physician’s global • ARM 3: placebo SC assessment (sPGA) at wk 12 NCT01708590
Moderate to severe Phase III N = 1800 • ARM 1: 210 mg brodalumab SC • PASI at wk 12 • FSI Q3 12 plaque psoriasis AMAGINE-2 • ARM 2: 140 mg brodalumab SC • Static physician’s global • Est completion date H2 14 • ARM 3: 45 or 90 mg ustekinumab SC assessment (sPGA) at wk 12 • Est external presentation Q1 15 NCT01708603 • ARM 4: placeboSC
Moderate to severe Phase III N = 1881 • ARM 1: 210 mg brodalumab SC • PASI at wk 12 • FSI Q3 12 plaque psoriasis AMAGINE-3 • ARM 2: 140 mg brodalumab SC • Static physician’s global • Est completion date H2 14 • ARM 3: 45 or 90 mg ustekinumab SC assessment (sPGA) at wk 12 • Est external presentation Q1 15 NCT01708629 • ARM 4: placeboSC
Moderate to severe Phase II N = 156 • ARM 1: 280 mg brodalumab SC • ACR20 response at wk 12 • Primary data Q4 12 Psoriatic Arthritis • ARM 2: 210 mg brodalumab SC • OLE ongoing, FSI Q1 14 NCT01516957 • ARM 3: 140 mg brodalumab SC • External presentation 12w data • ARM 4: placebo SC EULAR 2013, 24w data ACR 2013
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 high NCT01902290 reversibility asthma Adult subjects with Phase III N = 630 • ARM 1: 210mg brodalumab SC Primary: • FSI March 2014 Psoriatic Arthritis AMVISION-1 • ARM 2: 140 mg brodalumab SC • ACR20 response at wk 16 • Recruitment Ongoing • ARM 3: placebo SC • Est primary completion Q1 16 NCT02029495 Secondary • Radiographic assessment of joints • PASI 75, HAQ-DI and PSI
Adult subjects with Phase III N = 495 • ARM 1: 210mg brodalumab SC • ACR20 response at wk 16 • FSI March 2014 Psoriatic Arthritis AMVISION-2 • ARM 2: 140 mg brodalumab SC • Recruitment Ongoing • ARM 3: placebo SC • Est primary completion Q1 16 37 NCT02024646 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 Hypouricemic • Arm 3: lesinurad 400 mg QD by Month 6 • Est completion date Q3 14 Response to NCT01510158 All arms: SOC allopurinol QD • Est external present Q4 14 (ACR) Allopurinol Gout with Phase III N = 600 • Arm 1: Placebo • Proportion of subjects with an • FSI Q4 11 Inadequate CLEAR 2 • Arm 2: lesinurad 200 mg QD sUA level that is < 6.0 mg/dL • LSI Q2 13 Hypouricemic • Arm 3: lesinurad 400 mg QD by Month 6 • Est completion date Q3 14 Response to NCT01493531 All arms: SOC allopurinol QD • Est external present Q4 14 (ACR) Allopurinol Tophaceous Gout Phase III N = 315 • Arm 1: Placebo • Proportion of subjects with an • FSI Q1 12 CRYSTAL • Arm 2: lesinurad 200 mg QD sUA level that is < 5.0 mg/dL • LSI Q2 13 • Arm 3: lesinurad 400 mg QD by Month 6 • Est completion date Q3 14 NCT01510769 All arms: febuxostat 80 mg QD • Est external present Q4 14 (ACR)
Gout with Phase III N = 200 • Arm 1: Placebo • Proportion of subjects with an • FSI Q1 12 Intolerance or LIGHT • Arm 2: lesinurad 400 mg QD sUA level that is < 6.0 mg/dL • LSI Q2 13 Contraindication at Month 6 • Study complete, press release to a Xanthine NCT01508702 issued Oxidase Inhibitor • Est external present Q4 14 (ACR) Gout previously Phase III N = 143 All arms: open-label lesinurad • Assess the long-term efficacy • FSI Q4 12 enrolled LIGHT LIGHT Ext 400 mg QD and safety of lesinurad • LSI 1Q 14 study monotherapy. • Study complete NCT01650246 • Est external present Q4 14 (ACR) Gout previously Phase III N ≤ 200 • Arm 1: lesinurad 200 mg QD • Assess the long-term efficacy • FSI Q1 13 enrolled in studies CLEAR Ext • Arm 2: lesinurad 400 mg QD and safety of lesinurad in • Recruitment ongoing CLEAR 1 & 2 NCT01808131 All arms: SOC allopurinol QD combination with allopurinol. Gout previously Phase III N ≤ 315 • Arm 1: lesinurad 200 mg QD • Assess the long-term efficacy • FSI Q1 13 enrolled in CRYSTAL • Arm 2: lesinurad 400 mg QD and safety of lesinurad in • Recruitment ongoing 38 CRYSTAL study Ext All arms: febuxostat 80 mg QD combination with febuxostat. NCT01808144 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 at • LSI Q2 14 complicated • ARM 2: Meropenem IV TOC (MITT) • Est completion date Q3 14 intra- NCT01499290 (ii) clinical response at • Est external presentation abdominal Global study – 20 countries TOC (i.e. clinically Q2 15 infections evaluable) Hospitalised Phase III N = 576 • ARM 1: CAZ-AVI 2000/500mg plus • Co primary of: • FSI Q2 12 patients with RECLAIM-2 Metronidazole IV (i) clinical response at • LSI Q2 14 complicated • ARM 2: Meropenem IV TOC (MITT) • Est completion date Q3 14 intra- NCT01500239 (ii) clinical response at • Est external presentation abdominal Global study – 21 countries TOC (i.e. clinically Q2 15 infections evaluable) Hospitalised Phase III N = 520 • ARM 1: CAZ-AVI 2000/500mg IV plus either • Per patient microbiological • FSI Q4 12 Adults With RECAPTURE-1 500 mg of oral ciprofloxacin or 800 mg/160 response at TOC in • LSI Q3 14 complicated mg of oral sulfamethoxazole/trimethoprim patients with a cUTI and a • Est completion date Q4 14 urinary tract NCT01595438 • ARM 2: Doripenem 500 mg IV plus either 500 Gram-negative pathogen • Est external presentation Infections mg of oral ciprofloxacin or 800 mg/160 mg of (i.e. mMITT) Q3 15 oral sulfamethoxazole/trimethoprim
Global study – 26 countries Hospitalised Phase III N = 511 • ARM 1: CAZ-AVI 2000/500mg IV plus either • Per patient microbiological • FSI Q4 12 patients with RECAPTURE-2 500 mg of oral ciprofloxacin or 800 mg/160 response at TOC in • LSI Q3 14 complicated mg of oral sulfamethoxazole/trimethoprim patients with a cUTI and a • Est completion date Q4 14 urinary tract NCT01599806 • ARM 2: Doripenem 500 mg IV plus either 500 Gram-negative pathogen • Est external presentation infections mg of oral ciprofloxacin or 800 mg/160 mg of (i.e. mMITT) Q3 15 oral sulfamethoxazole/trimethoprim
Global study – 25 countries
39 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 the Test of • LSI Q1 15 tract infections and • ARM 2: Best available therapy Cure visit in the • Est completion date Q2 15 complicated intra- NCT01644643 microbiological intent • Est external presentation 2015 abdominal infections Global study – 30 countries to treat analysis set Hospitalised patients Phase III N = 404 • ARM 1: CAZ-AVI 2000/500mg plus • Clinical Cure at the • FSI Q1 13 with complicated RECLAIM-3 Metronidazole IV TOC visit in the MITT • LSI Q4 14 intra-abdominal • ARM 2: Meropenem IV analysis set • Est completion date Q1 15 infections NCT01726023 • Est external presentation 2015 Asia-focused study – 3 countries (China, Vietnam & Korea) Hospitalised patients Phase III N =1660 • ARM 1: CAZ-AVI 2000/500mg IV • Proportion of patients • FSI Q2 13 with nosocomial REPROVE • ARM 2: Meropenem IV with clinical cure at • LSI Q2 16 pneumonia infections, the TOC visit in the • Est completion date Q3 16 including hospital NCT01808092 Global study – 24 countries cMITT and CE • Est external presentation beyond acquired pneumonia analysis sets (co- planning horizon (HAP) and ventilator primary analyses). associated pneumonia (VAP)
40 AstraZeneca Early development programmes
2Q 2014 Results Update 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 patients on NCT02081534 • ARM 3: AZD1722, 10 mg BiD • Dose response relationship of • Completion date Q4 14 hemodialysis (HD) • ARM 4: AZD1722, 30 mg BiD AZD1722 on serum phosphate • Est external presentation with • ARM 5: AZD1722, 3 mg OD levels Q4 15 Hyperphosphatemia • ARM 6: AZD1722, 30 mg OD • Number of patients reaching serum • ARM 7: Placebo phosphate goal levels vs placebo
Conducted in the US, UK, Slovakia, Poland Patients with ESRD Phase IIa N = 86 • ARM 1: AZD1722, starting dose 45 mg • Reduction in mean weekly • FSI Q1 13 on HD BiD, down titration based on tolerability interdialytic weight gain (IDWG) • LSI Q413 NCT01764854 • ARM 2: Placebo • Effect of AZD1722 on IDWG after • Completion date Q4 13 weekly intervals of treatment • Est external presentation Conducted in the US Q4 15 Patients with Phase IIa N = 140 • ARM 1: AZD1722, starting dose 15 mg • Changes in Urine Albumin to • FSI Q2 13 Chronic Kidney BiD, dose escalation based on Creatinine Ratio (UACR) • LSI Q4 14 Disease (CKD), Type NCT01847092 tolerability (max 60 mg BiD) • Effects on UACR, eGFR, blood • Completion date Q4 14 2 Diabetes and • ARM 2: Placebo pressure, p-NT-proBNP, s-cardiac • Est external presentation Albuminuria troponin, u-aldosterone, p-renin Q4 15 Conducted in the US, Germany activity, and bioimpedence. Patients with Phase IIb N = 360 • ARM 1: AZD1722, 5 mg BiD • Percent Complete Spontaneous • FSI Q3 13 constipation • ARM 2: AZD1722, 20 mg BiD Bowel Movement (CSBM) • LSI Q2 14 predominant NCT01923428 • ARM 3: AZD1722, 50 mg BiD responders • Completion date Q4 14 Irritable Bowel • ARM 4: Placebo • Percent abdominal pain responders • Est external presentation Syndrome (IBS-C) • Percent overall responder for both Q4 15 Conducted in the US • CSBM and abdominal pain
42 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 Q2 14 Syndrome NCT01872078 • ARM 3: AZD4901 40 mg BiD AUC(0-8) • Est completion Q3 14 patients with • ARM 4: placebo • External presentation Q2 15 amenorrhea or Secondary endpoints: (ENDO or ESHRE) oligomenorrhea 28 day dosing period • Change from baseline in free and total testosterone at Study sites in US, UK, Germany day 7 & day 28
43 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 stopping criteria met at NCT02072993 maximum) placebo-controlled. dose level 4 (dosing June 17- • 7 planned cohorts/dose levels 18).
44 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 NCT01357161 • Est completion Q1 15 Global study 9 countries • Overall Survival is a • Est external presentation Q2 16 secondary endpoint. (ASCO) Previously Phase II N = 130 • ARM 1: carboplatin + pemetrexed + • Progression Free • FSI Q1 14 Untreated Stage AZD1775 225 mg BiD Survival • LSI Q2 15 IV Non- NCT02087241 • ARM 2: carboplatin + pemetrexed + placebo • Est completion Q4 15 Squamous • Overall Survival is a • Est external presentation Q2 17 NSCLC with 6 patients safety lead in secondary endpoint. (ASCO) TP53 mutations Conducted in US
Previously Phase II N = 135 • ARM 1: docetaxel + AZD1775 225 mg BiD • Progression Free • FSI Q1 14 Treated NSCLC • ARM 2: docetaxel+ placebo Survival • LSI Q2 15 with TP53 NCT02087176 • Est completion Q4 15 mutations 20-25 patient run in for safety and efficacy • Overall Survival is a • Est external presentation Q2 17 Conducted in US secondary endpoint. (ASCO)
45 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 for standard therapy NCT01213160 • Part B: AZD4547 in patients whose tumours have Parts B and C • Est external or for whom no FGFR amplification (c. 8 patients) • Part B: Safety and presentation beyond standard therapy tolerability and preliminary planning horizon exists Conducted in Japan anti-tumour activity Female ER+ Phase II N = 900 • Part A: AZD4547 in ascending multiple doses in • Part A: MTD of AZD4547 Recruitment closed Q2 Breast cancer GLOW combination with 25mg exemestane in combination with 25mg 14 patients whose • Part B: exemestane in three disease has NCT01202591 • ARM 1: AZD4547 (dose from part A) + fulvestrant schedules of AZD4547 • Est external progressed • ARM 2: placebo + fulvestrant • Part B Interim analysis: presentation beyond following Tumour size analysis on planning horizon treatment with Patients with FGFR1 polysomy (30 patients) or FGFR1 30 FGFR amplified one prior amplification (60 patients) patients endocrine • Part B Final analysis: therapy Progression Free Survival Advanced gastro- Phase II N = 71 • Stratum A (FGFR2 polysomy): AZD4547 vs paclitaxel • Progression Free Survival Recruitment closed after oesophageal SHINE randomised 1:1 (30 to 80 patients) an interim analysis Q2 13 cancer • Stratum B (FGFR 2 low gene amplification: AZD4547 • Key Secondary: Overall NCT01457846 vs paclitaxel randomised 3:2 (25 to 80 patients) survival/Tumour size • Est external • Stratum C (FGFR2 high gene amplification: AZD4547 presentation Q4 14 vs paclitaxel randomised 3:2 (25 to 80 patients) Stage IIIB-IV Phase N = 400 5-Arm study based on biomarker expression • Progression Free • Planned: FSI Q3 14 NSCLC patients II/III Lung (4736 • ARM 1: MEDI4736Unmatched biomarker IVQ2W Survival (PFS) • LSI (Phase II Q1 15) Master arm • ARM 2: AZD4547 (FGFR inhibitor) • Overall Survival (OS) • Est completion date Q4 Biomarker-Targeted Protocol only) • ARM 3: CDK4/6 inhibitor 16 Second-Line Therapy • ARM 4: PI3K Inhibitor • Estexternal presentation Partnered • ARM 5: HGFR Inhibitor beyond planning horizon with NCI and SWOG
46 NCT02154490 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 completion Q4 14 • Est external presentation Q2 15 (AACR & ASCO) Advanced Phase I N =70 • Dose escalation study • Safety and tolerability • FSI Q2 13 Cancer (All • LSI Q3 15 comers) NCT01985555 Conducted in China • Est completion Q4 14 Papillary Renal Phase II N =75 • Single arm study: AZD6094 600mg QD • Overall Response • FSI Q2 14 Cell Cancer Rate • LSI Q3 15 NCT02127710 Conducted in UK, US • Est completion Q4 14
47 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 Partnered* continuous dosing • Est completion Q2 17 • ARM 3: Fulvestrant + AZD2014 125mg BD • Overall Survival is a • Est external presentation Q4 17 Not yet posted two days on, 5 off secondary endpoint • ARM 4: Fulvestrant + everolimus
The study will be conducted in Europe Advanced Solid Phase I N = ~163 • SAD and MAD with dose expansion. • Safety and tolerability of • FSI Q4 09 Malignancies Continuous and intermittent dosing. AZD2014 • LSI Q2 14 NCT01026402 • Est completion Q3 14 Sites in UK • External presentation Q2 12 (ASCO)
ER+ Advanced Phase I N = ~70 • SAD and MAD. Continuous and intermittent • Safety and tolerability of • FSI Q2 12 Metastatic dosing schedules in combination with AZD2014 in combination • LSI Q4 14 Breast Cancer NCT01597388 fulvestrant with fulvestrant • Est completion Q4 14 • Determination of steady • Est external presentation Q4 14 Sites in US state PK profile of AZD2014 in combination with fulvestrant
*Collaborative study. Peter Schmid PI. Sponsor QMUL
48 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 tolerability • Est completion Q3 15 cancers with PIK NCT01226316 • Part C arm 2: Gynaecological with PIK3CA pathway • mutation • Response mutation • Part D arm 1: Breast with AKT-1 mutation Rate (ORR) • Part D arm 2: Gynaecological with AKT-1 mutation • Part D arm 3: other tumours with AKT-1 mutation
Possible expansion up to 120 patients per arm ER+ breast Phase IIb N =100 • ARM 1: AZD5363 + paclitaxel • Progression • Est completion Q4 16 cancer receiving • ARM 2: Paclitaxel alone Free survival • Est external presentation of st 1 treatment NCT01625286 (PFS) Part A dose escalation Q4 14 with paclitaxel in Two strata: PIK3CA mutation positive vs Mutation not (SABCS) the advanced detected • Response rate setting (ORR) & overall survival are secondary endpoints All-comers solid Phase I N = min • Comparison of PK between new tablet and original • PK • FSI Q1 14 tumours 12-24 capsule formulation and preliminary assessment of food • Est completion Q4 14 NCT01895946 effect on tablet PK • AZD5363 monotherapy 480mg bd 4 days on 3 days off • 12 pts for each of formulation switch and food effect
49 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 16 /TNBC and NCT01884285 Part B • Est external presentation Q2 15 patients with • Part B: AZD8186 monotherapy at (AACR or ASCO) known PTEN- recommended dose from Part A in PTEN • Part B: Safety and deficient deficient patients with advanced cancer tolerability and preliminary tumours assessment of antitumor Study conducted in Canada, US & UK activity (POM)
50 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 • Est completion Q2 16 androgen NCT02144051 patients) Parts B. Safety and • Est external receptor pathway Part B: Dose expansion tolerability and preliminary presentation beyond as a potential • AZD5312 at recommended dose from Part A, given iv anti-tumour activity planning horizon factor • Arm 1: Prostate cancer patients who have received a • Part B (prostate patients) second generation antihormonal therapy (eg. Response rate, blood abiraterone, enzalutamide) but have not responded PSA, circulating tumour (n=20). AZD5312 at RP2D cell enumeration, disease • Arm 2: Prostate cancer patients who have initially progression responded to a second generation anti-hormonal therapy, but later relapsed (n=20). • Arm 3: Non-mCRPC patient population (eg. breast, bladder, ovarian) expansion, where AR pathway may be a potential factor (n=20).
51 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 external presentation Q4 14 Study conducted in Japan, Korea, II dose and schedule STAT3 Taiwan and Hong Kong (AZD9150) DLBLC Phase I/II* N = 80 • Dose-escalation and dose- • Safety and tolerability • FSI Q1 12 Partnered expansion study . • Est completion Q2 15 ISIS • IV • Recommended phase • Est external presentation Q4 14 NCT01563302 Study conducted in US II dose and schedule AML Phase I N = 74 • SAD • Safety and tolerability • FSI Q2 12 relapsed/ • Dose finding/MTD • LSI Q2 14 refractory NCT01489722 North America – 4 sites • PK • Estimated completion Q4 14* • Estimated external presentation Q4 PIM 14 (ASH) (AZD1208) Solids and Phase I N = 40 • SAD • Safety and tolerability • FSI Q3 12 Lymphoma • Dose finding/MTD • LSI Q2 14 NCT01588548 Europe and Asia – 2 sites • PK • Estimated completion Q4 14* • Estimated external presentation Q2 15 nd ATR 2 Line Phase I N = 56 • Dose Escalation (Part A): • Part A: Safety and • Study completed (AZD6738) B-cell AZD6738 20 mg BD starting tolerability, MTD lymphomas NCT01955668 dose; All comers B-cell lymphomas • Part B: Safety, • Dose Expansion (Part B): tolerability, PK and AZD6738 MTD; 11q del or ATM biological activity deficient CLL
US study 52
* clinicaltrials.gov being updated 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 160/14.4/9.6 μg • PK parameters • LSI Q4 13 NCT01980615 • ARM 3: BGF MDI 80/14.4/9.6 μg AUC0-12 and Cmax • Completed • ARM 4: GF MDI 14.4/9.6 μg • Est external presentation Q3 14 • ARM 5: Symbicort MDI 320/9 μg (ERS) • ARM 6: Symbicort MDI 160/9 μg
Randomized, double-blind within device, four- period, six- treatment, cross-over
Single centre Phase 1 unit
53 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: Placebo administration with Q3 14 single ascending dose Healthy Phase I N = 36 • ARM 1: SAD and MAD AZD2115 as • Safety and tolerability • FSI Q4 11 subjects nebulised solution following administration • Est external presentation NCT01445782 • ARM 2: Placebo of multiple ascending Q3 14 inhaled doses Conducted in UK COPD patients Phase IIa N = 39 • ARM 1: AZD2115 25 μg (iNeb) • Peak and trough FEV1 • FSI Q1 12 MISTRAL • ARM 2: AZD2115 80 μg (iNeb) • LSI Q2 13 • ARM 3: AZD2115 240 μg (iNeb) • Est external presentation NCT01498081 • ARM 4: indacaterol 150 μg 2016 • ARM 5: indacaterol 150 μg + tiotropium 18 μg • ARM 6: placebo
Conducted in Sweden and Poland COPD patients Phase IIa N = 30 • ARM 1: AZD2115 Dose 1 BiD (pMDI) • FEV1 AUC(0-12) relative • FSI (planned) Q2 14 • ARM 2: AZD2115 Dose 2 BiD (pMDI) to baseline following • LSI Q2 14 NCT02109406 • ARM 3: placebo chronic dosing on • Est external presentation Day 15 2016 Multiple dose, 3 way cross over
Conducted in US.
54 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 administration with • Estimated publication: 2015 • Inhaled (nebulised) administration single ascending dose
Study conducted in the UK
Healthy Phase I N = 44 MAD • Safety and tolerability • FSI: Q3 13 subjects and • Different dose levels investigated vs in healthy subjects and • LSI: Q3 14 COPD patients NCT01817855 placebo in healthy volunteers and patients with COPD • Estimated completion: Q3 14 patients with COPD following administration • Estimated publication: 2015 • Inhaled (nebulised) administration of multiple ascending inhaled doses Study conducted in the UK
Healthy Phase Ib N = 60 • 2-way cross-over RCT • Effect on neutrophils in • FSI: Q4 13 subjects LPS • Single administration of 1200μg of induced sputum after • Completed AZD7624 or placebo at 0.5 hours prior oral inhalation of LPS, • Estimated publication: 2015 NCT01937338 to lipopolysaccharide (LPS) challenge. compared to placebo • Inhaled (nebulised) administration
Study conducted in the UK
55 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 subjects
• Secondary endpoints include PoM marker CXCL10
Healthy Phase I N = 6 active MAD • Safety and tolerability of • FSI Q1 14 subjects + 2 placebo • 2-3 cohorts investigated ascending doses of AZD8848 • Est completion Q3 14 NCT01818869 per cohort in healthy subjects
• Secondary endpoints include PoM marker CXCL10
56 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 • Estimated completion Q3 14 • Arm D: RDEA3170 12.5 mg QD
Japanese Phase II N = 200 • Arm A: Placebo • To compare the efficacy of • FSI: Q1 14 Patients with • Arm B: RDEA3170 5 mg QD RDEA3170 monotherapy at • LSI: Q3 14 Gout or NCT02078219 • Arm C: RDEA3170 10 mg QD Week 16 with placebo and • Estimated completion: Q1 15 Asymptomatic • Arm D: RDEA3170 12.5 mg QD Allopurinol. Hyperuricemia • Arm E: Open-label Allo 100mg BiD
57 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 volunteers given • Pharmacokinetics • LSI Q1 15 Avibactam) NCT01689207 Aztreonam and Avibactam alone and in (secondary) • Est completion date Q2 15 combination • Est presentation Q3 15 (ICAAC) N = 12 • Part A: single 1 hour IV infusions
N = 56 • Part B: single IV infusion on Days 1 and 11 and multiple (every 6 hr) IV infusions on Days 2-10. Various dose regimens of Aztreonam-Avibactam are being tested.
N = 35 • Part C: multiple (every 6 hr) IV infusions Days 1-10 in healthy young and elderly volunteers
Single centre in UK GyrAR Healthy Phase I N = 70 • Arm 1: SAD • Safety and • FSI Q3 13 (AZD0914) Volunteers • Arm 2 Single doses food effect. Subjects to tolerability • Study completed Q1 14 NCT01929629 receive 2 single oral doses, one fed and • Estimated presentation Q3 14 one fasted Secondary (ICAAC) • Pharmacokinetics • Single center in US • Effect of food on PK
Rib50s Extended Phase IIa N = 75 • ARM 1: AZD5847 500mg QD • Rate of change in • LSI Q4 13 (AZD5847) Early • ARM 2: AZD5847 500mg BiD sputum colony • Est completion date Q4 13 Bactericidal NCT01516203 • ARM 3: AZD5847 1200mg QD forming unit (CFU) • Est. external presentation Q4 Effect • ARM 4: AZD5847 800mg BiD counts during 14 14 (EBA)* • ARM 5: Placebo (Rifafour, weight based) days of study drug administration (EBA 58 Study conducted in Cape Town, South Africa 0-14) * Study sponsored by the National Institutes for Allergy and Infectious Disease (NIAID) 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 • Poster presentation Clinical Trial in maximum of 1000mg • PK Alzheimer’s Disease Conference NCT01739647 • Comparator ARM: placebo • PD (Aβ 40 and 42 November 2013. plasma) • Full data presented Springfield 1 site in US Alzheimer’s Conference March 2014
Healthy Phase I N = 56 • Active ARMS: • AEs, labs, vital • Study completed. volunteers and MAD Study • (Part 1) AZD3293 MAD starting with signs, ECGs • Data from part 1 presented in Clinical Alzheimer’s 5 mg • PK Trial in Alzheimer’s Disease Disease NCT01795339 • (Part 2) Multiple doses (12 days) of • PD (Aβ40 and 42 Conference November 2013. Patients AZD3293 one to up to 3 dosage plasma and CSF) • 2 more presentations of data in March levels and July 2014 • Comparator ARM: Placebo • AD patient data to be presented at Clinical Trial in Alzheimer’s Disease 1 site in US Conference November 2014 Healthy Phase I N = 40 • Active ARMS: Ascending AZD3293 • AEs, labs, vital • Study in reporting phase Volunteers JSMAD Study SAD (15, 50, 150 mg planned) and MAD signs, ECGs • FSI Q4 13 (15, 50 mg doses planned) • PK • LSI Q3 14 NCT02005211 • Comparator ARM: placebo • PD (Aβ 40 and 42 plasma) 1 site in Japan
59 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 I N = 18 • Active ARMS: MAD • AEs, labs, vital signs, • Study completed Subjects • Comparator ARM: placebo ECGs NCT01457807 • PK 1 site in UK
Healthy Phase I N = 59 • Active ARMS: MAD • AEs, labs, vital signs, • Study completed Subjects • Comparator ARM: placebo ECGs NCT00914303 • PK 1 site in Sweden
Parkinson’s Phase II N = 24 • ARM 1: AZD3241 600 mg BID for 8 weeks • Microglia activation • Study completed Disease • ARM 2: Placebo represented by • Poster presented at Movement Patients NCT01527695 [11C]PBR28 binding Disorders Society meeting June Randomization 3:1 active to placebo. 2014 Secondary endpoints: 3 sites in Sweden and Finland • PD symptoms measured by UPDRS • Plasma MPO activity Parkinson’s Phase II N = 51 • ARM 1: AZD3241 300 mg BID for 12 weeks • AEs, labs, vital signs, • Study completed Disease • ARM 2: AZD3241 600 mg BID for 12 weeks ECGs • Poster presented at Movement Patients NCT01603069 • ARM 3: Placebo Disorders Society meeting June Secondary endpoints: 2014 Randomization 1:1:1 across arms • PD symptoms measured by UPDRS 13 sites in US • Plasma MPO activity
60 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 age group (age ≥12 to Tic Severity Score • LSI Q2 14 NCT01904773 <18). (TTS) on the Yale • Est completion Q4 14 • Part 2: Randomized, double-blind, six- Global Tic Severity • Est external presentation 2015 period, three-treatment, cross-over Scale (YGTSS) at the • ARM 1: AZD5213 low dose last day of receiving • ARM 2: AZD5213 high dose treatment. • ARM 3: Placebo
US only study, 9 sites Painful Diabetic Phase IIa N = 32 • Part 1: Training to improve reliability to • Significant change on • FSI Q4 13 Neuropathy assess pain. average severity of • LSI Q2 14 NCT01928381 • Part 2: Randomized, double-blind, three- pain (BPI-DPN). • Est completion Q2 14 period, three-treatment, cross-over • Est external presentation 2015 • ARM 1: AZD5213 + Pregabalin • ARM 2: Pregabalin • ARM 3: Placebo
US only study, 4 sites
61 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 NCT01926366 • 8 dose cohorts planned (5 SAD, 3 MAD) Additional endpoints: • Study completed • Pharmacokinetics • Est. external presentation 2015 • Pharmacodynamic biomarker (qEEG)
62 MedImmune Early development programmes
2Q 2014 Results Update 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 in Cholestryl Ester Artery Disease and low HDL rh-Factor II Healthy male Phase I N = 62 • SAD IV administration • Safety profile in terms of • FSI Q4 13 (MEDI8111) subjects adverse events (AE), vital • LSI Q3 14 NCT01958645 UK study site signs, ECG, telemetry, lab • Est completion Q4 14 variables, immunogenicity and physical examination
64 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 (CR) or Partial • Est completion Q4 14 chronic lymphocytic NCT01466153 • ARM 2: MEDI-551 IV (dose-level 2) and Response (PR) • Est external leukemia (CLL) Bendamustine presentation Q2 15 • ARM 3: Rituxan and Bendamustine
Open label study Adults with relapsed Phase II N = 170 • ARM 1: MEDI-551 dose level 1 and ICE/DHAP • ORR, including Complete • FSI Q3 11 or refractory B-cell • ARM 2: MEDI-551 dose level 2 and ICE/DHAP Response (CR) or Partial • Restart Q2 12 diffuse large B-cell NCT01453205 • ARM 2: Rituxan + ICE/DHAP Response (PR) • Est completion Q3 16 lymphoma (DLBCL) Open label study Adults with relapsed Phase I/II N = 91 • Dose-escalation study IV • MTD and efficacy • FSI Q2 10 or refractory B-cell • Est completion Q1 18 malignancies NCT00983619 Open label study Adults with relapsed Phase I N = 18 • Dose-escalation study IV • MTD and efficacy • FSI Q2 11 or refractory B-cell • Est completion Q4 14 malignancies NCT01957579 Conducted in Japan Adults with Newly Phase I N = 15 • Lenalidomide, Dexamethasone and MEDI-551 IV • Effect of Lenalidomide, • FSI Q2 14 Diagnosed multiple dexamethasone and MEDI- • Est completion Q3 15 myeloma NCT01861340 551 on multiple myeloma cancer stem cells
Adults with relapsed Phase I/II N = 193 • Arm A: MEDI-551 IV dose escalation study and • MTD and efficacy • FSI Q2 14 or refractory B-cell expansion (FL/CLL/DLBCL/MM) • Safety and tolerability • Est completion Q1 18 malignancies NCT00983619 • Arm B: MedI-551 IV dose escalation and • Clinical activity of MEDI- expansion (CLL) 551 • Arm C: MEDI-551 IV dose escalation and 65 expansion with Rituximab (DLBCL) • Arm D: MEDI-551 IV (CD20 refractory DLBCL) 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 • Study amended to explore q2w • LSI Q3 15 (expansion) schedule and doses > 10mg/kg • Est. completion date Q3 15 PD-L1 Myelodysplastic Phase I N = 70 Dose-escalation and dose-expansion • Safety and • FSI Q2 14 (MEDI4736) syndrome study tolerability • LSI Q1 15 (40 pts) NCT02117219 • ARM 1: MEDI4736 IV • LSI Q2 15 (70 pts) • Secondary • Est completion date Q4 15 endpoints include duration of response, progression free survival and overall survival
66 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 biologic dose for the • LSI Q3 15 and Immunotx NCT02000947 MEDI4736 IV Q4w dose combinations, combination • Est completion Q1 17 pretreated patient higher dose levels and alternate q2 • Abstract accepted for cohorts) schedule added with amendment • Secondary endpoints include publication only Q2 14 Antitumour activity, PK and (ASCO) • Dose Expansion: MTD for the immunogenicity • Est external presentation Q3 combination in escalation to be explored 14 in expansion
North American study centers, exploration of 1-2 ex-US countries for expansion
67 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 the • LSI Q4 15 melanoma NCT02027961 trametinib 2mg QD/ MEDI4736 IV combination • Est completion Q1 17 • Cohort B – trametinib 2mg QD/ BRAF mutation+ MEDI4736 IV • Secondary endpoints include (Cohort A) • Cohort C – trametinib 2mg QD/ Objective Response and Disease MEDI4736 IV Control, Duration of Response, BRAF Wild Type Progression-free Survival and (Cohorts B&C) • Dose Expansion: Each cohort will be Overall Survival, Pharmacokinetics expanded at the MTD to enroll a total of and immunogenicity 20 subjects per cohort
Global study – 2 countries
68 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) NCT02088112 period combination • Est completion date Q4 17 • Gefitinib (QD) + MEDI4736 IV EGFR M+ NSCLC • Secondary endpoints include naïve to EGFR- Expansion phase tumour response (CR, PR, SD, TKI therapy • Gefitinib (QD) + MEDI4736 IV PD), Objective response rate, (Expansion recommended dose disease control rate, progression- phase) free survival, immunogenicity, Study to be conducted in US and pharmacokinetics, Korea pharmacodynamics
69 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 15 NCT02118337 • Est completion date Q1 17 Dose-expansion phase at selected • Secondary endpoints include dose from dose-escalation phase tumour response such as • MEDI4736 IV + MEDI0680 IV objective response rate, disease recommended dose control rate, progression-free survival, duration of response, overall survival, immunogenicity, pharmacokinetics, pharmacodynamics
70 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 tolerability • Est completion date Q2 15 NCT02040064 mg/kg is the MTD) • Secondary Cohort 2: Tremelimumab IV 6 mg/kg q4w plus endpoints include Gefitinib 250 mg QD, 6 patients (+ 6 patients if 6 tumour response; mg/kg is the MTD) RECIST, disease Cohort 3: Tremelimumab IV 10 mg/kg q4w plus control rate, PFS Gefitinib 250 mg QD, 6 patients (+ 6 patients if 10 mg/kg is the MTD)
71 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 + bevacizumab dose escalation, administered Q3w, IV (US only) N = 9-12 • MEDI3617 + paclitaxel dose escalation, IV (US only) N = 9-12 • MEDI3617 + carboplatin + paclitaxel dose escalation, IV (US only) N = 15-24 • MEDI3617 + bevacizumab dose escalation, administered Q2w , IV (US only) N = 25 • MEDI3617 single-agent expansion • Safety and tolerability • FSI Q4 12 in ovarian cancer patients, IV (US • > 20% efficacy signal • LSI Q4 14 only) • Est completion date Q3 15 • External presentation Q2 14 (ASCO) Anti-IGF Patients with HR+ Phase I/II N = 176 • ARM 1: MEDI-573 IV and • Progression Free Survival • FSI Q2 11 st ligand mAb HER2-, 1 line, Aromatase Inhibitor • LSI Q2 13 (MEDI-573) metastatic breast NCT01446159 • ARM 2: Aromatase Inhibitor alone • Retrospective evaluation • Est study completion cancer taking of predictive biomarker Q4 15 aromatase Open label study +ve subgroups • Est external inhibitors presentation 2015
72 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 17 (MEDI-565) adenocarcinoma NCT01284231 with no available standard or Partnered curative treatments.
Refractory N = 60 max, • Dose expansion study, IV pancreatic, 20 in each colorectal and cohort gastro-esophageal cancers Anti-DLL4 Adults with Phase I N = up to 28 • Dose-escalation study • MTD and safety profile • FSI Q2 12 mAb advanced solid N = up to 32 (3+3); IV • LSI Q4 15 (MEDI0639) tumors including NCT01577745 • Est completion Q4 16 SCLC • Combination dose- • MTD and safety profile in • Est external escalation and expansion combination presentation 2015 study; IV
73 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 Q2 17 Severe Asthma NCT02161757 SC exacerbation rate • ARM 2: Placebo SC • Cohort 2 : Key Secondary Endpoints: • ARM 1: Tralokinumab dose regimen 2 • Effect of tralokinumab on SC measures of pulmonary • ARM 2: Placebo SC function (FEV1), asthma symptoms (Asthma Daily • 2:1 randomisation in both cohorts Diary), asthma control (ACQ-6) and asthma Global study – 4 countries related QoL (AQLQ (S) +12)
Adults with Phase III N = 770 • ARM 1: Tralokinumab SC Primary Endpoint • Planned FSI Q4 14 Uncontrolled • ARM 2: Placebo SC • Annual asthma • Primary completion Q3 17 Severe Asthma NCT02194699 • 1:1 randomisation exacerbation rate
Global study – 11 countries including Key Secondary Endpoints: Japan • Effect of tralokinumab on measures of pulmonary function (FEV1), asthma symptoms (Asthma Daily Diary), asthma control (ACQ-6) and asthma related QoL (AQLQ (S) +12)
74 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-predicted forced • Est primary completion Q1 17 Pulmonary NCT01629667 • ARM 3: Placebo vital capacity at week 72 Fibrosis High dose: low dose: placebo (1:1:1) Key Secondary Endpoints: Global study – 6 countries • No. of patients with disease progression • Safety and tolerability • Tralokinumab serum concentration Japanese Phase II N = 20 Cohort 1: • Safety and tolerability • FSI Q1 14 Adults with • ARM 1: Tralokinumab high dose • Est completion Q4 15 Idiopathic NCT02036580 • ARM 2: Placebo Key Secondary Endpoints: Pulmonary • Tralokinumab serum Fibrosis Cohort 2 : concentration • ARM 1: Tralokinumab low dose • Immunogenicity • ARM 2: Placebo
8:2 randomisation in both cohorts Japan only study
75 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 • LSI Q3 15 controlled, severe • ARM 3: Medium dose MEDI9929 SC (AER) measured at Week 52 • Est completion Q4 16 asthma NCT02054130 • ARM 4: High dose MEDI9929 SC
Partnered Healthy adult male Phase I N = 24 • ARM 1: SAD MEDI9929 SC • Safety and tolerability of single • Completed Japanese subjects • ARM 2: Placebo ascending subcutaneous doses • Final report Q2 14 NCT01913028
Partnered
76 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 Q2 13 to DMARDs Explorer 1 • ARM 3: Mavrilimumab 150 mg SC • ACR 20 at wk 24 • Completed Q1 14 • ARM 4: Placebo • Est external presentation NCT01706926 planned Q4 14 Global study (ex-US) on MTX background RA patients who Phase II N = 135 • ARM 1: Mavrilimumab 100 mg SC q2w • ACR 20/50/70 at wk • FSI Q1 13 have failed 1 or 2 EARTH (final) • ARM 2: golimumab 24 • LSI Q2 14 anti-TNF for efficacy, Explorer 2 • DAS28 remission • Est completion Q1 15 intolerance or Global study (ex-US) on MTX background • Function (HAQ-DI) • Est external presentation safety, OR NCT01715896 beyond planning horizon an inadequate response to DMARDs Eligible RA patients Phase II N = 400 • ARM 1: Mavrilimumab 100 mg SC q2w • Sustained disease • FSI Q1 13 from Explorer 1 & 2 EARTH projected improvement & • OLE, ongoing until regulatory Explorer X Open label extension of Explorer 1 & 2 safety filing • Est external presentation NCT01712399 Global study (ex-US) on MTX background beyond planning horizon
77 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 completion Q2 14 patients NCT01283139 • Arm 2: 600 mg IV MEDI-545 q2w for 4 wks then an SLE responder index • Est external presentation q4wk for 44 wks at 12 months Q4 14 (ACR) • Arm 3: 1200 mg IV MEDI-545 q2w for 4 wks then q4wk for 44 wks • Arm 4: placebo IV q2w for 4 wks then q4wk for 44 wks SLE, DM or Phase II N = 260 • 600 mg IV Medi-545 • Evaluate long-term • FSI Q3 10 PM patients safety and tolerability of • Est completion Q1 15 NCT00979654 Open label study multiple IV doses of MEDI-545
78 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 responder index at 6 • Est completion Q2 15 patients NCT01438489 • ARM 3: placebo IV q4w for 48 weeks months • Estimated external presentation beyond planning horizon Moderate- Phase II N = 240 • ARM 1: MEDI-546, IV q4w for 104 weeks • Open-label • FSI Q1 13 severe SLE extension to • Est completion Q3 17 patients NCT01753193 evaluate long-term safety and tolerability Japanese Phase II N = 17 • ARM 1: • Safety profile of • FSI Q1 12 SLE patients • Stage I: 100mg IV MEDI-546, single dose and multiple MEDI-546: adverse • Est completion Q3 14 NCT01559090 doses q4w for 48 wks. events, vital signs,
• Stage II: 300mgIV, multiple doses q4w for 104 wks clinical laboratory • ARM 2: assessments and • Stage I: 300mg IV MEDI-546, single dose and multiple ECGs doses q4w for 48 wks. • Stage II: 300mgIV, multiple doses q4w for 104 wks • ARM 3: • Stage I: 1000mg IV MEDI-546, single dose and multiple doses q4w for 48 wks. • Stage II: 1000mgIV, multiple doses q4w for 104 wks
79 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 • Lupus Arthritis Response Rate • Est. Completion Q2 16 arthritis Partnered Global study – 8 countries
80 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 NCT01769417 Escalation Study • Route of administration: intravenous
81 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-Controlled Study Immunogenicity and Viral disease in infants NCT00767416 • Route of administration: Shedding • MEDI-559 was found to be intranasal biologically active and immunogenic in the 6-24month seronegative pediatric population. An imbalance in MA- LRIs was observed and warrants expanded safety studies
82 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 Dates: NCT01175122 NCT00922259 vaccine for the following 2005-2012 NCT00516035 strains: H2N2, H2N3, H5N1, NCT00853255 H6N1, H7N3, H7N7, H9N2 NCT01674205 NCT00110279 (separate studies for each NCT01443663 strain) NCT00347672 NCT00488046 NCT01534468 Nasal administraion NCT00722774 NCT00734175 NCT00380237 US only
Partnered
83 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 • ARM 3: Placebo IM immune responses
84 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 NCT02114268
85 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) Healthy Elderly NCT02036645 planned vs placebo • Est. Completion date Q4 16
• 2 SC cohorts are planned • Est. external presentation vs placebo beyond planning horizon
US only Anti-CD19 Multiple Phase I N = 28 • SAD (IV/SC) • Safety, PK • Study is recruiting mAb sclerosis • Est. completion date Q1 15 (MEDI-551) NCT01585766 Global study • Estimated external presentation beyond planning horizon Anti-CD40L Healthy Adults Phase I N = 56 • Dose-escalation study, • Safety, tolerability, and • FSI Q2 14 (MEDI4920) single IV dose pharmacokinetics, anti-drug • Est completion Q2 15 NCT02151110 antibody, inhibition of T-cell dependent antibody response
86 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) • Enrollment suspended due to Ulcerative NCT01694485 • ARM 3: MEDI7183 dose level 3, SC logistical issues re-started Q4 Colitis • ARM 4: MEDI7183 dose level 4, SC 13 Partnered • ARM 5: Matching Placebo, SC • LSI Q4 14 • Est completion Q1 15 Global study - 19 countries • Est external presentation 2016 Moderate to Phase II N = 252 • ARM 1: MEDI7183 low dose, SC • Remission at week 8 • FSI Q4 12 Severe Crohn’s • ARM 2: MEDI7183 medium dose, SC (CDAI < 150) • Enrollment suspended due to Anti-α4β7 Disease NCT01696396 • ARM 3: MEDI7183 high dose, SC logistical issues re-started Q4 mAb • ARM 4: Matching Placebo, SC 13 (MEDI7183) Partnered • LSI Q4 14 Global study - 12 countries • Est completion Q2 15 • Est external presentation 2016 Japanese Phase II N = 48 • ARM 1: MEDI7183 low dose, SC • Remission at week 8 • FSI Q4 13 subjects with • ARM 2: MEDI7183 medium dose, SC (Mayo Score) • LSI Q2 14 moderate to NCT01959165 • ARM 3: MEDI7183 high dose, SC • Est completion Q1 15 severe • ARM 4: Matching Placebo, SC Ulcerative Partnered Colitis Anti-IL-23 Patients with Phase II N = 120 • ARM 1: MEDI2070, IV (SC for OLE) • CDAI response at • FSI Q1 13 mAb Moderate to • ARM 2: Placebo, IV Week 8 defined by • LSI Q1 14 MEDI2070 Severe Crohn’s NCT01714726 either a CDAI score • Est completion Q2 14 Disease Global study - 9 countries of < 150 or a CDAI • Est external presentation Q4 Partnered reduction from 14 baseline of at least 100 points 87 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-Treat population OS Overall Survival CE Clinically Evaluable FEV Forced Expiratory Volume SAD Single Ascending Dose Study DLT Dose Limiting Toxicity MAD Multiple Ascending Dose Study AEs Adverse Events QD Once Daily FSI First Subject In BiD Twice Daily LSI Last Subject In TiD Three Times a Day OLE Open Long Term Extension Q2W Every Other Week MDI Metered Dose Inhaler Q3W Every Three Weeks ICS Inhaled Corticosteroid Q4W Every Four Weeks LABA Long Acting Beta Agonist Q8W Every Eight Weeks LAMA Long Acting Muscarinic Agonist XR Extended Release MTX Methotrexate IR Immediate Release ASA Acetylsalicylic Acid SC Sub-cutaneous PARP Poly ADP ribose polymerase IV Intra-venous HIF-PHI Hypoxia-inducible factor prolyl hydroxylase IM Intra-muscular
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