Clinical trials appendix H1 2020 results update Movement since Q1 2020 update
New to Phase I New to Phase II New to Pivotal trial New to registration
Additional indication NME Lifecycle management brazikumab AZD1222# Enhertu#¶ DESTINY-Gastric01 [JP] 1 IL23 ulcerative colitis SARS-CoV-2 COVID vaccine HER2 targeting antibody drug conjugate HER2- overexpressing advanced gastric or gastroesophageal MEDI3506 brazikumab¶ junction adenocarcinoma patients who have progressed on IL33 mAb asthma IL23 crohn’s disease two prior treatment regimens
MEDI3506 Additional indication # IL33 mAb COVID-19 capivasertib + fulvestrant CAPItello-291 AKT inhibitor + fulvestrant locally advanced Lifecycle management (inoperable) or metastatic breast cancer Calquence CALAVI-US & CALAVI-RoW Lynparza# + Imfinzi# DUO-E BTK inhibitor COVID-19 PARP inhibitor + PD-L1 mAb 1st-line endometrial cancer
Lifecycle management Fasenra NATRON IL-5R mAb hypereosinophilic syndrome
Removed from Phase Removed from Phase II Removed from Phase III Removed from registration I
NME NME Lifecycle management Lifecycle management MEDI5083 Imfinzi# + AZD5069 or Imfinzi# + danvatirsen# Brilinta/Brilique4 HESTIA Brilinta/Brilique4 THEMIS [US] 2 CD40 ligand fusion protein PD-L1 mAb + CXCR2 antagonist or PD-L1 mAb + P2Y12 receptor antagonist prevention of vaso- P2Y12 receptor antagonist cardiovascular outcomes trial in solid tumours STAT3 inhibitor HNSCC, bladder and NSCLC occlusive crises in paediatric patients with sickle cell patients with coronary artery disease and type-2 diabetes disease without a previous history of myocardial infarction or stroke MEDI7219 Lynparza# + adavosertib# anti diabetic type-2 diabetes PARP inhibitor + Wee1 inhibitor solid tumours Farxiga/Forxiga3 Dapa-HF [US] 2 SGLT-2 inhibitor worsening heart failure or cardiovascular Lifecycle management death in patients with chronic heart failure (HFrEF) Lynparza# + cediranib CONCERTO PARP inhibitor + VEGF inhibitor recurrent platinum- Lynparza# PROFOUND [US] 2 resistant ovarian cancer PARP inhibitor prostate cancer
2 ¶ Registrational Phase II/III trial # Partnered and/or in collaboration 1 Submission accepted 2 Approved 3 Farxiga in the US; Forxiga in ROW 4 Brilinta in the US, China, Russia and Japan; Brilique in ROW Q2 2020 new molecular entity (NME)1 pipeline
Phase I Phase II Phase III Under Review 19 New Molecular Entities 24 New Molecular Entities 9 New Molecular Entities 0 New Molecular Entities
capivasertib#+fulvestrant CAPItello-291 Imfinzi#+RT (platform) CLOVER adavosertib# Imfinzi#+oleclumab AZD0466 AKT+fulvestrant locally-advanced BCL2/xL haematological and solid PD-L1+RT HNSCC NSCLC SCLC Wee1 ovarian cancer, solid tumours PD-L1+CD73 solid tumours (inoperable) or metastatic breast
AZD2811 nanoparticle capivasertib+chemotherapy CAPItello- AZD1390 Imfinzi Imfinzi#+tremelimumab #+tremelimumab Aurora solid tumours, haematological 290 glioblastoma PD-L1+CTLA-4 solid tumours PD-L1+CTLA-4 gastric cancer malignancies AKT+chemotherapy mTNBC 1L
Imfinzi#+tremelimumab+chemo Imfinzi#+/-tremelimumab+chemo AZD4573 AZD4635 Imfinzi#+tremelimumab PD-L1+CTLA-4 1L PDAC oesophageal POSEIDON CDK9 haematological malignancies A2aR inhibitor prostate cancer PD-L1+CTLA-4 biliary tract oesophageal SCLC PD-L1+/-CTLA-4+SoC 1L NSCLC
AZD5153 Imfinzi+selumetinib# AZD9833 Imfinzi+Lynparza# BAYOU Imfinzi#+/-tremelimumab+CRT ADRIATIC BRD4 haematological and solid tumours PD-L1+MEK solid tumours SERD ER+ breast PD-L1+PARP bladder PD-L1+/-CTLA-4+CRT LS-SCLC
AZD5991 IPH5201# capivasertib# Lynparza#+AZD6738 VIOLETTE Imfinzi#+tremelimumab HIMALAYA MCL1 haematological malignancies CD39 solid tumours AKT prostate PARP+ATR breast PD-L1+CTLA-4 1L HCC
Imfinzi (platform) HUDSON Lynparza#+Imfinzi MEDIOLA AZD7648# MEDI1191 Imfinzi#+tremelimumab KESTREL PD-L1+multiple novel ONC therapies post PARP+PD-L1 ovarian breast gastric DNAPK solid and haematological tumours IL12 mRNA solid tumours PD-L1+CTLA-4 1L HNSCC IO NSCLC SCLC
Imfinzi# (platform) COAST AZD9496 MEDI2228 MEDI5752 Imfinzi#+tremelimumab+SoC NILE PD-L1+multiple novel ONC therapies SERD ER+ breast BCMA ADC multiple myeloma PD-1/CTLA-4 solid tumours PD-L1+CTLA-4+SoC 1L urothelial cancer NSCLC
Imfinzi# (platform) NeoCOAST Calquence+ceralasertib MEDI5395 oleclumab+AZD4635 Lynparza#+Imfinzi# DUO-E PD-L1++multiple novel ONC therapies BTK+ATR haematological tumours rNDV GMCSF solid tumours CD73+A2aR prostate cancer PARP+PD-L1 1L endometrial cancer NSCLC
Calquence+danvatirsen oleclumab+chemo or Lynparza#+Imfinzi#+bevacizumab oleclumab+Tagrisso Imfinzi#+AZD4635 BTK+STAT3 haematological Imfinzi#+oleclumab+chemo DUO-O CD73+EGFR EGFRm NSCLC PD-L1+A2aR prostate cancer malignancies CD73+chemo or PD-L1+CD73+chemo PARP+PD-L1+VEGF 1L ovarian
Post-1L Tagrisso (platform) ORCHARD Imfinzi#+adavosertib# Imfinzi#+Lynparza# ORION EGFR+multiple novel ONC therapies PD-L1+Wee1 solid tumours PD-L1+PARP 1L mNSCLC EGFRm NSCLC
Imfinzi#+MEDI0457# Tagrisso combo# TATTON PD-L1+DNA HPV vaccine HNSCC EGFR+PD-L1/MEK/MET NSCLC
Imfinzi#+monalizumab# Tagrisso+savolitinib# SAVANNAH PD-L1+NKG2a solid tumours EGFR+MET advanced EGFRm NSCLC 1 Includes novel combinations and additional indications for assets where the lead is not yet launched 3 # Partnered and/or in collaboration; ¶ Registrational Phase II/III trial Oncology Precision medicine approach being explored Q2 2020 new molecular entity (NME)1 pipeline
Phase I Phase II Phase III Under Review 16 New Molecular Entities 21 New Molecular Entities 6 New Molecular Entities 0 New Molecular Entities
AZD0284 AZD8154 abediterol# MEDI3506 anifrolumab# TULIP RORg psoriasis / respiratory Inhaled PI3Kgd asthma LABA asthma / COPD Diabetic kidney disease Type I IFN receptor SLE
AZD0449 AZD8233 anifrolumab# MEDI3506 AZD1222# Inhaled JAK inhibitor asthma hypercholesterolemia cardiovascular Type I IFN receptor SLE SC IL33 AD / COPD / asthma / COVID-19 SARS-CoV-2 COVID vaccine
AZD1402# AZD9977 anifrolumab# MEDI5884# brazikumab¶ inhaled IL-4Ra asthma MCR cardiovascular Type I IFN receptor lupus nephritis cholesterol modulation cardiovascular IL23 crohns disease
MEDI0618# nirsevimab# AZD2373 AZD4831 MEDI6012 PAR2 antagonist mAb osteooarthritis RSV mAb-YTE passive RSV Podocyte health nephropathy MPO HFpEF LCAT cardiovascular pain immunisation
MEDI7352 AZD2693 MEDI1341# AZD5718 PT027 NGF/TNF OA pain / painful diabetic nonalcoholic steatohepatitis alpha synuclein parkinson's disease FLAP coronary artery disease ICS/SABA asthma neuropathy
AZD4041# MEDI1814# AZD7986# navafenterol (AZD8871)# tezepelumab# NAVIGATOR SOURCE orexin 1 receptor antagonist opioid use amyloidβ alzheimer's disease DPP1 COPD MABA COPD TSLP severe uncontrolled asthma disorder
AZD5634 MEDI5117# China AZD8601# suvratoxumab inhaled ENaC cystic fibrosis IL6 YTE rheumatoid arthritis VEGF-A cardiovascular α-Toxin Staphylococcus pneumonia
AZD6615 MEDI6570 AZD9567 tezepelumab# hypercholesterolemia CV disease LOX-1 CV disease SGRM RA / respiratory TSLP atopic dermatitis
brazikumab tezepelumab# IL23 ulcerative colitis TSLP COPD
cotadutide velsecorat (AZD7594) GLP-1/glucagon type-2 diabetes / Inhaled SGRM asthma / COPD obesity / NASH
verinurad URAT-1 chronic kidney disease
1 Includes novel combinations and additional indications for assets where the lead is not yet launched Precision medicine approach being explored 4 # Partnered and/or in collaboration; ¶ Registrational Phase II/III trial BioPharmaceuticals Q2 2020 lifecycle management (LCM)1 pipeline
Phase I Phase II Phase III Under Review 1 Project 8 Projects 23 Projects 1 Project
Imfinzi#+azacitidine# Calquence CALAVI-US & CALAVI-RoW Calquence# Imfinzi# post-SBRT PACIFIC-4 Imfinzi#+VEGF+TACE EMERALD-1 Enhertu¶# DESTINY-Gastric01 PD-L1+azacitidine MDS BTK inhibitor COVID-19 BTK inhibitor 1st line MCL PD-L1 post-SBRT stage I/II NSCLC PD-L1+VEGF+TACE locoregional HCC ADC gastric
Enhertu# DESTINY-CRC-01 Calquence# Imfinzi# POTOMAC Lynparza# OlympiA ADC colorectal cancer BTK inhibitor r/r CLL, high risk PD-L1 non muscle invasive bladder cancer PARP gBRCA adjuvant breast
Enhertu# DESTINY-Gastric02 Calquence#+venetoclax+obinutuzumab Imfinzi#+CRT PACIFIC-2 Lynparza# SOLO-3 ADC gastric BTK+BCL-2+anti-CD20 1st line CLL PD-L1+CRT NSCLC PARP BRCAm PSR ovarian
Enhertu# U204 Enhertu# DESTINY-Breast02 Imfinzi#+CRT PACIFIC-5 (China) Lynparza+abiraterone# PROpel ADC NSCLC ADC breast PD-L1+CRT locally-advanced stage III PARP+NHA prostate cancer
Imfinzi# (platform) BEGONIA Enhertu# DESTINY-Breast03 Imfinzi#+CTx neoadjuvant AEGEAN Tagrisso ADAURA PD-L1 1L mTNBC ADC breast PD-L1+CTx locally-advanced stage I-III EGFR adj. EGFRm NSCLC
Imfinzi#+CTx NIAGARA Tagrisso LAURA Enhertu# DESTINY-Breast04 Imfinzi# (platform) MAGELLAN PD-L1+CTx muscle invasive bladder EGFRm locally-advanced unresectable PD-L1 1L mNSCLC ADC breast cancer NSCLC
Imfinzi+FOLFOX+bevacizumab (platform) Imfinzi# CALLA Imfinzi#+CTx TOPAZ-1 Tagrisso+chemo FLAURA2 COLUMBIA1 PD-L1+ chemo + VEGF + PD-L1 adj. locally-advanced cervical PD-L1+CTx 1L biliary tract cancer EGFR+chemo 1L adv EGFRm NSCLC multiple novel ONC therapies 1L MSS-CRC cancer
Lynparza# (basket) MK-7339-002/LYNK002 Imfinzi# PEARL Imfinzi#+VEGF EMERALD-2 PARP HRRm cancer PD-L1 1L metastatic NSCLC PD-L1+VEGF adjuvant HCC
1 Includes significant LCM projects and parallel indications for assets beyond Phase III 5 # Partnered and/or in collaboration; ¶ Registrational Phase II/III trial Oncology Precision medicine approach being explored Q2 2020 lifecycle management (LCM)1 pipeline
Phase I Phase II Phase III Under Review 0 Projects 2 Projects 9 Projects 3 Projects
Breztri Farxiga/Forxiga Dapa-CKD Brilinta/Brilique THALES LABA/LAMA/ICS asthma SGLT2 CKD P2Y12 stroke
roxadustat# Farxiga/Forxiga DELIVER Nexium (CN only) HIF-PH inhibitor chemo induced anaemia SGLT2 HFpEF stress ulcer prophylaxis
Farxiga/Forxiga DETERMINE-Preserved Symbicort SYGMA SGLT2 HFpEF as needed in mild asthma
Farxiga/Forxiga DETERMINE-Reduced SGLT2 HFrEF
Fasenra NATRON IL-5R hypereosinophilic syndrome
Fasenra MANDARA IL-5R EGPA
Fasenra# OSTRO, ORCHID IL-5R nasal polyposis
Fasenra# RESOLUTE IL-5R COPD
roxadustat# HIFPH anaemia MDS
1 Includes significant LCM projects and parallel indications for assets beyond Phase III 6 # Partnered and/or in collaboration; ¶ Registrational Phase II/III trial BioPharmaceuticals Precision medicine approach being explored Estimated key regulatory submission acceptances
capivasertib + fulvestrant locally advanced or Fasenra mBC CAPItello-291 severe asthma (China) anifrolumab SLE capivasertb + CTx 1L mTNBC nirsevimab TULIP CAPItello-290 passive RSV immunisation tezepelumab asthma Imfinzi + tremelimumab + SoC urothelial Lynparza +Imfinzi + bevacizumab ovarian AZD1222 (ChAdOx1) SARS-CoV-2 PT027 asthma NAVIGATOR NILE DUO-O
NME Imfinzi + tremelimumab HCC Imfinzi + tremelimumab + CRT LDS-SCLC Lynparza + Imfinzi endometrial cancer Imfinzi + tremelimumab HNSCC KESTREL Imfinzi +/- tremelimumab NSCLC POSEIDON HIMALAYA ADRIATIC DUO-E H2 2020 H1 2021 H2 2021 2021+ Lynparza ovarian Lynparza prostate Calquence r/r CLL, high risk Calquence + venetoclax + Imfinzi cervical SOLO-3 PROFOUND (China) ELEVATE-RR obinutuzumab 1L CLL AMPLIFY CALLA Tagrisso EGFrm NSCLC Imfinzi + CRT NSCLC Enhertu Calquence 1L MCL Imfinzi non muscle invasive bladder ADAURA PACIFIC-2 DESTINY-Breast03 ECHO POTOMAC LCM Brilinta stroke Fasenra nasal polyposis Imfinzi NSCLC Enhertu Tagrisso locally adv. unresectable NSCLC THALES (China) OSTRO PEARL DESTINY-Breast02 LAURA Farxiga CKD Lynparza breast Enhertu Tagrisso + CTx EGFRm NSCLC DAPA-CKD OLYMPIA DESTINY-Breast04 FLAURA2 Symbicort mild astha (EU) Lynparza + abiraterone prostate Imfinzi adjuvant NSCLC roxadustat anemia in MDS SYGMA PROPEL BR.31 Imfinzi + VEGF + TACE locoregional HCC Imfinzi neoadjuvant NSCLC Bydureon Bcise EMERALD-1 AEGEAN type-2 diabetes (China) Imfinzi + chemo Xigduo XR/Xigduo Duaklir Genuair COPD (China) muscle invasive bladder NIAGARA type-2 diabetes (China) Farxiga HF (HFpEF) Imfinzi + CTx biliary tract Fasenra COPD DELIVER TOPAZ-1 RESOLUTE Imfinzi + VEGF adjuvant HCC Fasenra EGPA EMERALD-2 MANDARA Imfinzi + CRT NSCLC Fasenra HES PACIFIC-5 (China) NATRON Imfinzi post-SBRT NSCLC Fasenra nasal polyposis PACIFIC-4 ORCHID (China / Japan)
7 Note. NME section includes novel combinations and additional indications for assets where the lead is not yet launched Oncology BioPharmaceuticals Designations 5 15 12 30 29 Accelerated approvals Breakthrough / PRIME1 / Sakigake2 Fast Track Priority Review / RTOR3 Orphan
Lynparza ovarian cancer SOLO-2 (US) Tagrisso EGFRm T790M NSCLC (US) MEDI3902 Psl-PcrV pneumo Px (US) Tagrisso EGFRm T790M NSCLC (JP) Lynparza ovarian cancer SOLO-2 (US) Tagrisso EGFRm T790M NSCLC (US) Lynparza prostate cancer PROFOUND (US) savratoxumab Staph HAP (US) Tagrisso EGFRm T790M NSCLC (US) Lumoxiti HCL PLAIT (US) Imfinzi bladder cancer (US) Imfinzi bladder cancer 1L (US) Imfinzi NSCLC (US) Imfinzi bladder cancer 2L (US) Lumoxiti HCL PLAIT (EU) Calquence MCL (US) Calquence MCL (US) nirsevimab (MEDI8897) RSV mAB (US) Tagrisso NSCLC AURA3 (US) Crestor paediatric (US) Enhertu unresectable or HER2+ MBC 3L (DESTINY-Breast01) (US) Imfinzi stage III NSCLC 1L PACIFIC (US) Imfinzi HNSCC HAWK (US) Calquence MCL (US) cediranib VEGFR tki (US) Tagrisso NSCLC 1L FLAURA (US) anifrolumab SLE (US) Lynparza breast cancer OLYMPIAD (US) Iressa EGFRm NSCLC (US) tezepelumab asthma (US) Lynparza ovarian cancer SOLO-2 (US) roxadustat CKD (CN) Tagrisso EGFRm T790M NSCLC (US) nirsevimab (MEDI8897) RSV mAB (US) Tagrisso EGFRm T790M NSCLC (CN) Tagrisso NSCLC FLAURA (US) AZD3241 MPO (EU) nirsevimab (MEDI8897) RSV mAB (EU)1 Farxiga HFrEF (US) Imfinzi stage III NSCLC PACIFIC (EU) Calquence CLL 1L (US) selumetinib NFI type 1 SPRINT (US) Farxiga chronic kidney disease (US) Imfinzi stage III NSCLC PACIFIC (JP) Calquence MCL (US) Enhertu DESINTY-BREAST01 (US) cotadutide non-alcoholic steatohepatitis (US) Lynparza tablet (US) Calquence WM (US) Calquence CLL (US) Farxiga MI RRCT DAPA-MI (US) Lynparza tablet (CN) Calquence WM (EU) Enhertu gastric cancer (JP)2 Lynparza breast cancer OLYMPIAD (JP) Calquence CLL 1L (EU) Enhertu HER2+/HER2low gastric 3L DESTINY-Gastric01 (US) Tagrisso NSCLC 1L FLAURA (JP) Calquence MCL 1L (EU) Enhertu HER2mut NSCLC 2L+ DESTINY-Lung01 (US) Lumoxiti HCL PLAIT (US) selumetinib thyroid cancer ASTRA (US) Lynparza ovarian SOLO-1 (US) Lynparza breast cancer OLYMPIAD (JP) Lynparza ovarian SOLO-1 (CN) Lynparza ovarian cancer SOLO-2 (JP) Breztri Aerosphere (PT010) COPD (CN) Koselugo/ selumetinib NFI type 1 SPRINT (US) ACCELERATED APPROVAL, these regulations allowed medicines for serious conditions that addressed an unmet medical need to be approved based on a Tagrisso NSCLC 1L FLAURA (CN) Koselugo/ selumetinib NFI type 1 SPRINT (EU) surrogate endpoint. Breztri Aerosphere (PT010) (CN) Lynparza pancreatic cancer POLO (US)
BREAKTHROUGH DESIGNATION is a process designed to expedite the development and review of medicines which may demonstrate substantial Lokelma hyperkalaemia (CN) Fasenra EGPA (US) improvement over available therapy. 1PRIME is a scheme launched by the EMA to enhance support for the development of medicines that target an unmet Lynparza pancreatic 1L (US) Fasenra HES (US) medical need. 2SAKIGAKE is aimed at early introduction of innovative medicines, medical devices, etc. that are initially developed in Japan. Enhertu DESINTY-BREAST01 (US) saracatinib IPF (US) Farxiga HF DAPA-HF (US) Imfinzi +/-treme+SOC SCLC 1L CASPIAN (US) FAST TRACK is a process designed to facilitate the development, and expedite the review of medicines to treat serious conditions and fill an unmet medical need. 3REAL-TIME ONCOLOGY REVIEW (RTOR) and Project Orbis is an initiative of the FDA Oncology Centre of Excellence (OCE) providing a Imfinzi +/-treme+SOC SCLC 1L CASPIAN (US) Fasenra EoE (US) framework for concurrent submission and review of oncology products among international partners. Lynparza prostate PROfound (US) Imfinzi +treme HCC 1L HIMALAYA (US) PRIORITY REVIEW DESIGNATION is the US FDA’s goal to take action on an application within 6 months. Lynparza +Avastin ovarian 1L PAOLA-1 (US) Lynparza pancreatic cancer POLO (JP)
ORPHAN DRUG DESIGNATION, intended for treatment, diagnosis or prevention of rare diseases/disorders that affect fewer than 200,000 patients in the Koselugo/ selumetinib NFI type 1 SPRINT (US) Enhertu HER2+/HER2low gastric 3L DESTINY-Gastric01 (US) US, or that affect more than 200,000 patients but are not expected to recover the costs of developing and marketing a treatment drug. Calquence CLL ELEVATE-TN, ASCEND3 (US) Koselugo /selumetinib NFI type 1 SPRINT (JP) Brilinta stroke THALES (US)
8 Oncology BioPharmaceuticals Oncology - approved medicines and late-stage pipeline Approved medicines Late-stage development Tagrisso (highly-selective, irreversible EGFRi) Early development NSCLC Oncology
Trial Population Patients Design Endpoints Status
Phase III Adjuvant EGFRm NSCLC 682 • Arm 1: Tagrisso QD following complete tumour resection, with • Primary endpoint: DFS • FPCD: Q4 2015 ADAURA or without chemo • Secondary endpoints: DFS Rate, OS, OS • LPCD: Q1 2019 • Arm 2: placebo Rate, QoL • Data readout: Q1 2020
NCT02511106 • Trial unblinded due to efficacy CVRM Global trial - 25 countries
Phase III Maintenance therapy in 200 • Arm 1: Tagrisso • Primary endpoint: PFS (BICR) • FPCD: Q4 2018 LAURA patients with • Arm 2: placebo • Secondary endpoints: CNS PFS, OS, • Data anticipated: 2021+ locally advanced, DoR, ORR, DCR NCT03521154 Global trial - 11 countries unresectable EGFRm Stage III NSCLC whose disease has not progressed following
platinum-based R&I chemoradiation therapy Phase III Real world setting in adult 3,020 Single-arm trial - Tagrisso • Primary endpoints: OS and safety • FPCD: Q3 2015 ASTRIS patients with advanced or • Secondary endpoint: PFS • LPCD: Q4 2017 metastatic, EGFRm T790M+ Global trial - 16 countries NCT02474355 NSCLC
Phase II EGFR TKI treatment-naïve 150 Single arm trial - Tagrisso • Primary Endpoint: proportion of patients • FPCD: Q2 2018 ELIOS patients with locally-advanced with a given tumour genetic and or metastatic EGFRm NSCLC Global trial - five countries proteomic marker at the point of disease NCT03239340 progression as defined by the investigator Other • Secondary endpoint: PFS, ORR, DoR
Phase I Patients with EGFRm NSCLC 8 Single-arm trial - Tagrisso • Primary Endpoints: assessments of brain • FPCD: Q4 2018 ODIN-BM with brain metastases standard uptake value (SUV) and • LPCD: Q2 2020 pharmacokinetics (PK) • Data anticipated: H2 2021 NCT03463525 • Secondary endpoints: PK
10 Approved medicines Late-stage development Tagrisso (highly-selective, irreversible EGFRi) Early development NSCLC, combinations Oncology
Trial Population Patients Design Endpoints Status
Phase III Neoadjuvant EGFRm NSCLC 351 Arm 1: placebo plus plus Pemetrexed/Carboplatin or • Primary endpoint: mPR • FPCD Q2 2020 NeoADAURA Pemetrexed/Cisplatin • Secondary endpoints cPR, EFS, DFS, • Data anticipated: 2021+ Arm 2: Tagrisso plus Pemetrexed/Carboplatin or OS
NCT04351555 Pemetrexed/Cisplatin CVRM Arm 3: Tagrisso
Global trial – 12+ countries
Phase III 1st-line EGFRm NSCLC 586 Arm 1: Tagrisso plus Pemetrexed/Carboplatin or • Primary endpoint: PFS • FPCD: Q4 2019 FLAURA2 Pemetrexed/Cisplatin • Secondary endpoints: OS, LOS, ORR • Data anticipated: 2021+ Arm 2: Tagrisso DoR, Depth of response, PFS2. QoL, PK NCT04035486
Global trial – 5+ countries R&I
Phase II Advanced EGFRm NSCLC 150 Modular design platform trial: • Primary endpoint: ORR • FPCD: Q3 2019 ORCHARD patients who have progressed • Module 1: Tagrisso + savolitinib • Secondary endpoints: PFS, DoR, OS, • Data anticipated: 2021+ on first line Tagrisso treatment • Module 2: Tagrisso + gefitinib safety and tolerability NCT03944772 • Module 3: Tagrisso + necitumumab • Module 4: carboplatin + pemetrexed + Imfinzi • No intervention: observational cohort –
Global trial - 8 countries Other
Phase II EGFRm / MET+, locally 172 • Single arm trial: Tagrisso + savolitinib • Primary endpoint: ORR • FPCD Q1 2019 SAVANNAH advanced or metastatic • Secondary endpoints include PFS, DoR • Data anticipated: 2021+ NSCLC who have progressed Global trial and OS NCT03778229 following treatment with Tagrisso Phase Ib Advanced EGFRm NSCLC 344 • Arm 1: Tagrisso + Imfinzi • Safety, tolerability, pharmacokinetics and • FPCD: Q3 2014 TATTON TKI failure • Arm 2: Tagrisso + savolitinib preliminary anti-tumour activity • Data anticipated: H2 2020 • Arm 3: Tagrisso + selumetinib NCT02143466 Enrolment to Tagrisso + Imfinzi arm will not restart
Global trial
11 Approved medicines Late-stage development Imfinzi (PD-L1 mAb) Early development NSCLC, early disease Oncology
Trial Population Patients Design Endpoints Status
Phase III Completely resected 332 • Arm 1: Imfinzi + SoCd chemo Primary endpoint: • Initiating MERMAID-1 Stage II and III NSCLC • Arm 2: placebo + SoC chemo • DFS • Data anticipated: 2021+ Secondary endpoint
NCT04385368 • DFS, OS, CVRM
Phase III Neoadjuvant NSCLC patients 800 • Arm 1: Imfinzi + platinum-based chemo Primary endpoint: • FPCD: Q1 2019 AEGEAN Stage II and III resected • Arm 2: placebo + platinum-based chemo • mPR, EFS • Data anticipated: 2021+ NSCLC Secondary endpoint NCT03800134 (incl. EGFR/ALK positive) • pCR
Phase III Adjuvant NSCLC patients 1,360 • Arm 1: Imfinzi mg/kg i.v. Q4W x 12m Primary endpoint: • FPCD: Q1 2015 R&I ADJUVANT BR.31 Ib (≥4cm) – stage IIIa resected • Arm 2: placebo • DFS • LPCD Q1 2020 NSCLC • Data anticipated: 2021+ NCT02273375 (incl. EGFR/ALK positive) Global trial Secondary endpoint: Partnered • OS
Phase III Unresected, locally-advanced 300 • Arm 1: Imfinzi i.v. Q4W + chemo/RT Primary endpoint: • FPCD: Q2 2018 PACIFIC-2 NSCLC • Arm 2: placebo + chemo/RT • PFS • LPCD: Q3 2019 • ORR • Data anticipated: H2 2020 NCT03519971 ex US global trial Secondary endpoint:
• OS Other Phase III Imfinzi with SBRT in 630 • Arm 1: Imfinzi i.v. Q4W with definitive SBRT Primary endpoint: •FPCD: Q2 2019 PACIFIC-4 unresected, Stage I/II NSCLC • Arm 2: placebo with definitive SBRT • PFS •Data anticipated: 2021+ Secondary endpoint: NCT03833154 • OS
Phase III Unresected, locally-advanced 360 • Arm 1: Imfinzi i.v. Q4W following chemo/RT Primary endpoint: • FPCD: Q1 2019 PACIFIC-5 NSCLC • Arm 2: placebo following chemo/RT • PFS • Data anticipated: 2021+ Secondary endpoint: NCT03706690 ex US global trial, China focus • OS
Phase II/III Lung Master Stage IV squamous NSCLC 140 • Subtrial A: Imfinzi (non-match for other biomarker driven Primary endpoints: • FPCD: Q2 2014 Protocol patients subtrials) i.v. Q2W single arm Imfinzi Phase II only • ORR • Data anticipated: 2021+ • Subtrial B: PI3K inhibitor vs. docetaxel • PFS NCT02154490 Biomarker-targeted • Subtrial C: CDK4/6 inhibitor vs, docetaxel • OS 2L therapy • Subtrial D: AZD4547 (FGFR inhibitor) vs. docetaxel Partnered • Subtrial E: C-MET/HGFR Inhibitor + erlotinib vs. erlotinib 12 Approved medicines Late-stage development Imfinzi (PD-L1 mAb) +/- treme (CTLA-4 mAb) Early development Lung cancer, advanced disease Oncology
Trial Population Patients Design Endpoints Status
Phase III NSCLC 1L 650 • Arm 1: Imfinzi Q4W Primary endpoint: • FPCD: Q1 2017 PEARL • Arm 2: chemotherapy • OS • LPCD: Q1 2019 • Data anticipated: H1 2021 NCT03003962 Asia trial CVRM
Phase III NSCLC 1L 1,000 • Arm 1: Imfinzi + chemo Primary endpoint: • FPCD: Q2 2017 POSEIDON • Arm 2: Imfinzi + tremelimumab + chemo • OS • LPCD: Q4 2018 • Arm 3: SoC • PFS • Data readout: Q4 2019 NCT03164616 • PFS primary endpoint met • OS data anticipated: H2 2021
Phase II NSCLC 1L 200 • Arm A1: Imfinzi Primary endpoint: • FPCD: Q1 2019 MAGELLAN • Arm A2: Imfinzi + danvatirsen • Safety & tolerability • Data anticipated: H2 2020
• Arm A3: Imfinzi + oleclumab Secondary endpoint: R&I NCT03819465 • Arm B1: Imfinzi + Investigator's choice of chemo • ORR, DoR, PFS, OS, PK, ADA • Arm B2: Imfinzi + danvatirsen + Investigator's choice of chemo • Arm B3: Imfinzi + oleclumab + Investigator's choice of chemo
Phase III Limited stage SCLC 1L 600 • Arm 1: Imfinzi + tremelimumab (4 doses) Primary endpoints: • FPCD: Q4 2018 ADRIATIC following platinum-based • Arm 2: Imfinzi • PFS • Data anticipated: 2021+ concurrent chemoradiation • Arm 3: placebo • OS NCT03703297 therapy
Phase III Extensive stage SCLC 1L 795 • Arm 1: Imfinzi + tremelimumab + EP (carboplatin or cisplatin + Primary endpoint: • FPCD: Q1 2017 Other CASPIAN etoposide) • OS • LPCD: Q2 2018 • Arm 2: Imfinzi + EP (carboplatin or cisplatin + etoposide) • Data readout: Q2 2019 NCT03043872 • Arm 3: EP (carboplatin or cisplatin + etoposide) • OS Primary endpoint met for Imfinzi monotherapy • OS primary endpoint not met for Imfinzi + tremelimumab
Phase II SCLC 80 • Arm A: Imfinzi + tremelimumab Q4W • Primary endpoint: ORR • FPCD: Q4 2016 BALTIC • Arm B: adavosertib and carboplatin BID • Data anticipated: H1 2021 • Arm C: AZD6738 and Lynparza NCT02937818
13 Approved medicines Late-stage development Imfinzi (PD-L1 mAb) Early development Other cancers, early disease Oncology
Trial Population Patients Design Endpoints Status
Phase III Non-muscle invasive bladder 975 • Arm 1: BCG (Induction + maintenance) Primary endpoints: • FPCD: Q2 2018 POTOMAC cancer • Arm 2: Imfinzi + BCG (Induction only) • DFS • Data anticipated: 2021+ • Arm 3: Imfinzi + BCG (Induction + maintenance)
NCT03528694 CVRM
Phase III Muscle-invasive bladder 960 • Arm 1: Imfinzi in combination with gemcitabine + cisplatin, Coprimary endpoints: • FPCD: Q4 2018 NIAGARA cancer Imfinzi maintenance • pCR • Data anticipated: H2 2021 • Arm 2: gemcitabine + cisplatin • EFS NCT03732677
Phase III Locoregional HCC 600 • Arm A: TACE in combination with Imfinzi Primary endpoint • FPCD: Q1 2019 EMERALD-1 • Arm B: TACE in combination with Imfinzi + bevacizumab PFS for Arm A vs Arm C • Data anticipated: H2 2021 • Arm C: TACE in combination with placebo
NCT03778957 Secondary endpoint R&I PFS for Arm B vs Arm C , OS
Phase III Adjuvant therapy in HCC 888 • Arm 1: Imfinzi + bevacizumab Primary endpoint: • FPCD: Q2 2019 EMERALD-2 • Arm 2: Imfinzi + placebo • RFS for Arm 2 vs Arm 3 • Data anticipated: 2021+ • Arm 3: placebo + placebo NCT03847428 Secondary endpoint: • RFS Arm 1 vs Arm 3, OS, RFS at 24
mos Other
14 Approved medicines Late-stage development Imfinzi (PD-L1 mAb) +/- treme (CTLA-4 mAb) Early development Other cancers, advanced disease Oncology
Trial Population Patients Design Endpoints Status
Phase III Cis-eligible and ineligible 1,005 • Arm 1: Imfinzi + tremelimumab Primary endpoints: • FPCD: Q4 2015 DANUBE bladder cancer 1L • Arm 2: Imfinzi • OS • LPCD: Q1 2017 • Arm 3: SoC • Data readout: Q1 2020
NCT02516241 • Primary endpoints not met CVRM
Phase III Bladder cancer 1L 885 • Arm 1: Imfinzi + tremelimumab + SoC Primary endpoints: • FPCD: Q4 2018 NILE • Arm 2: Imfinzi + SoC • PFS • Data anticipated: 2021+ • Arm 3: SoC • OS NCT03682068
Phase III HNSCC 1L 823 • Arm 1: Imfinzi Primary endpoints: • FPCD: Q4 2015 KESTREL • Arm 2: Imfinzi + tremelimumab • OS • LPCD Q1 2017 • Arm 3: SoC Secondary endpoint: • Data anticipated: H1 2021
NCT02551159 R&I • PFS, ORR, DoR, safety, biomarkers
Phase III HCC 1L 1,310 • Arm 1: Imfinzi + tremelimumab Primary endpoint: • FPCD: Q4 2017 HIMALAYA • Arm 2: Imfinzi • OS • LPCD: Q4 2019 • Arm 3: sorafenib Secondary endpoint: • Data anticipated: H2 2020 NCT03298451 • PFS, TTP, ORR
Phase II Urothelial bladder cancer 76 • Arm 1 tremelimumab (urothelial bladder cancer) Primary endpoint: • FPCD: Q4 2015 triple-negative breast cancer • Arm 2 tremelimumab (triple-negative breast cancer) • ORR • Data readout: Q4 2018 pancreatic ductal- • Arm 3 tremelimumab (pancreatic ductal-adenocarcinoma)
NCT02527434 adenocarcinoma Secondary endpoints: Other • Safety, DoR
Phase III BTC 1L 474 • Treatment Arm 1 Imfinzi + gemcitabine + cisplatin Primary endpoint: • FPCD Q2 2019 TOPAZ-1 • Treatment Arm 2 placebo + gemcitabine + cisplatin • OS • Data anticipated: H2 2021
NCT03875235 Global trial Secondary endpoint: • PFS, ORR, DoR
Phase III Locally advanced cervical 714 • Arm 1 Imfinzi + EBRT + brachytherapy with platinum Primary • FPCD: Q1 2019 CALLA cancer • Arm 2 placebo + EBRT + brachytherapy with platinum • PFS • Data anticipated: 2021+ Secondary NCT03830866 Global trial • OS, CR rate, DoR, ORR, safety/tolerability
15 Approved medicines Late-stage development Imfinzi (PD-L1 mAb) +/- treme (CTLA-4 mAb) Early development Other cancers, advanced disease Oncology
Trial Population Patients Design Endpoints Status
Phase III Advanced solid malignancies 1,200 • Arm 1: Imfinzi • Primary endpoint: Safety • FPCD: Q2 2017 STRONG • Arm 2: Imfinzi + tremelimumab • Data anticipated: 2021+
NCT03084471 CVRM
Phase I Combination in Solid tumours 80 • Arm 2 SCLC: Imfinzi + tremelimumab + carboplatin + etoposide • Safety • FPCD: Q1 2016 Advanced Solid Tumours • Arm 3 TNBC: Imfinzi + tremelimumab + chemo • LPCD: Q1 2019 • Arm 4 TNBC: Imfinzi + tremelimumab + chemo • Data anticipated: 2021+ NCT02658214 • Arm 5 GEJ: Imfinzi + tremelimumab + oxaliplatin + 5-FU + leucovorin • Arm 6 PDAC: Imfinzi + tremelimumab + chemo • Arm 7 ESSC: Imfinzi + tremelimumab + chemo
Phase I Immunotherapy in HNSCC, NSCLC, SCLC 300 • HNSCC Arm 1 • Safety • FPCD: Q2 2018 R&I Combination With • NSCLC Arm 1 • Data anticipated: 2021+ Chemoradiation in Patients • NSCLC Arm 2 With Advanced Solid • NSCLC Arm 3 Tumours • SCLC Arm 2 • SCLC Arm 3 CLOVER • SCLC Arm 4
NCT03509012
Phase II mTNBC 1L 110 • Arm 1 Imfinzi + paclitaxel Primary endpoint: • FPCD: Q1 2019
BEGONIA • Arm 2 Imfinzi + paclitaxel + capivasertib • Safety and tolerability • Data anticipated: 2021 Other • Arm 4 Imfinzi + paclitaxel + danvatirsen NCT03742102 • Arm 5 Imfinzi + paclitaxel + oleclumab Secondary endpoint: • ORR, PFS, DoR, OS, PK, ADA Global trial
16 Approved medicines Late-stage development Lynparza (PARP inhibitor) Early development Other cancers Oncology
Trial Population Patients Design Endpoints Status
Phase III BRCAm adjuvant breast 1,836 • Arm 1: Lynparza BiD 12 month duration • Primary endpoint: invasive disease-free • FPCD: Q2 2014 OlympiA cancer • Arm 2: placebo 12-month duration survival (IDFS) • LPCD: Q2 2019 • Secondary endpoint: distant disease-free • Data anticipated: H1 2021
NCT02032823 Global trial partnership with BIG and NCI/NRG survival and OS CVRM
Partnered
Phase III gBRCAm pancreatic cancer 154 • Arm 1: Lynparza tablets 300mg twice daily as maintenance • Primary endpoint: PFS • FPCD: Q1 2015 POLO therapy until progression • Secondary endpoint: OS • LPCD: Q1 2019 • Arm 2: placebo tablets BID • Data readout: Q1 2019 NCT02184195 • Primary endpoint met Global trial
Phase III Metastatic castration-resistant 387 • Arm 1: Lynparza BID • Primary endpoint: radiologic PFS • FPCD: Q2 2017 R&I PROfound prostate cancer • Arm 2: physician’s choice: • Secondary endpoints: ORR, Time to Pain • LPCD: Q4 2018 HRRm, 2L+ enzalutamide 160mg once daily or abiraterone acetate Progression, OS • Data readout : Q3 2019 NCT02987543 1,000mg once daily • Primary endpoint met
Global trial Other
17 Approved medicines Late-stage development Lynparza (PARP inhibitor) Early development Imfinzi combinations Oncology
Trial Population Patients Design Endpoints Status
Phase III Advanced ovarian cancer 1L 1,256 Non tBRCAm (tumour BRCA) patients Primary endpoint: • FPCD: Q1 2019 DuO-O • Arm 1: bevacizumab • PFS • Data anticipated: 2021+ • Arm 2: bevacizumab + Imfinzi
NCT03737643 • Arm 3: bevacizumab + Imfinzi + Lynparza Secondary endpoints: CVRM • OS, PFS2 tBRCAm patients • bevacizumab (optional) + Imfinzi + Lynparza
Global trial
Phase III Advanced and recurrent endometrial 699 • Arm 1: Chemo + Imfinzi placebo followed by Imfinzi placebo Primary endpoint • FPCD: Q2 2020 DUO-E cancer 1L and Lynparza placebo • PFS • Data anticipated: 2021+ • Arm 2: Chemo + Imfinzi followed by Imfinzi + Lynparza
NCT04269200 placebo Secondary endpoints: R&I • Arm 3: Chemo + Imfinzi followed by Imfinzi + Lynparza • OS, PFS2, ORR, DoR
Global Trial
Phase II Stage IV NSCLC whose disease has 250 • Arm 1: Imfinzi + Lynparza Primary endpoint: • FPCD Q1 2019 ORION not progressed following SoC chemo • Arm 2: Imfinzi + placebo • PFS • Data anticipated: 2021 + Imfinzi Maintenance therapy 1L NCT03775486 Global trial Secondary enpoints: • OS, ORR, DoR, PFS in HRRm, PK, ADA
Phase II Platinum-Ineligible unresectable 154 • Arm 1: Imfinzi + Lynparza • Primary endpoint: PFS • FPCD: Q2 2018 Other BAYOU Stage IV urothelial cancer • Arm 2: Imfinzi + placebo • Data anticipated : H2 2020 • Secondary endpoints: OS, DoR, ORR, NCT03459846 Global trial PFS in HRRm, PFS6, PK, ADA, PRO
Phase I / II gBRCAm ovarian cancer 2L+ 148 • Arm 1: Lynparza + Imfinzi Primary endpoints: • FPCD: Q2 2016 MEDIOLA gBRCAm HER2-negative breast • Dose until progression • DCR at 12 weeks • LPCD: Q2 2017 cancer 1-3L • Safety and tolerability NCT02734004 SCLC 2L+ Global trial Gastric cancer 2L+
Phase I / II gBRCAm ovarian cancer 2L+ 140 • Arm 1: Lynparza + Imfinzi Primary endpoints: • FPCD: Q2 2018 MEDIOLA Non-gBRCAm ovarian cancer 2L+ • Arm 2: Lynparza + Imfinzi • DCR at 12 weeks (Ovarian expansion) Non-gBRCAm ovarian cancer 2L+ • Arm 3: Lynparza + Imfinzi + bevacizumab • ORR • Dose until progression • Safety and tolerability NCT02734004 Global trial
18 Approved medicines Late-stage development Lynparza (PARP inhibitor) Early development Other combinations Oncology
Trial Population Patients Design Endpoints Status
Phase III Advanced ovarian cancer 1L 806 • Arm 1: Lynparza maintenance therapy for two years or until Primary endpoint: • FPCD: Q2 2015 PAOLA-1 maintenance disease progression • PFS • LPCD: Q2 2018 • Arm 2: placebo for two years or until disease progression • Data readout: Q3 2019
NCT02477644 Secondary endpoints: • Primary endpoint met CVRM Externally sponsored Global trial • OS, PFS2
Phase III Metastatic castration-resistant 720 • Arm 1: Lynparza + abiraterone Primary Endpoint: • FPCD: Q4 2018 PROpel prostate cancer 1L • Arm 2: placebo + abiraterone • rPFS • Data anticipated: H2 2021 Global trial NCT03732820 Secondary endpoints: • TFST, TTPP, OS
Phase II TNBC 450 • Arm 1: AZD6738 + Lynparza • PFS • FPCD: Q2 2018 R&I • Arm 2: Lynparza • ORR / OS • Data anticipated: H2 2021 VIOLETTE Trial conducted in 15 countries: North America, Europe and Asia • Safety and tolerability NCT03330847
Phase II/III Recurrent platinum 680 • Arm 1: chemo Primary endpoints: • FPCD: Q2 2016 GY005 resistant/refractory ovarian • Arm 2: cediranib + Lynparza • PFS, OS • Data anticipated: 2021+ cancer • Arm 3: cediranib NCT02502266 • Arm 4: Lynparza Secondary endpoints: Externally sponsored • ORR, QoL, safety
• US/Canada sites Other Phase II HRRm or HRD-positive 370 • Arm 1: Lynparza Primary endpoints: • FPCD: Q1 2019 LYNK-002 advanced cancer • ORR Trial conducted in 15 countries worldwide NCT03742895 Secondary endpoints: Partnered • DOR, OS, PFS, AE, Prog by CA-125
Phase III Advanced colorectal cancer 525 • Arm 1: bevacizumab + 5-FU maintenance Primary endpoints: • Initiating LYNK-003 1L • Arm 2: bevacizumab + Lynparza maintenance • PFS • Data anticipated: 2021+ • Arm 3: Lynparza maintenance NCT04456699 Secondary endpoints: Partnered Trial conducted in 15 countries worldwide • OS, ORR, DoR, AEs
19 Approved medicines Late-stage development Enhertu (trastuzumab deruxtecan, HER2 ADC) Early development Breast cancer Oncology
Trial Population Patients Design Endpoints Status
Phase II HER2-positive, unresectable and/or 230 Randomised, open label, sequential assignment Primary endpoint ORR • FPCD: Q4 2017 DESTINY-Breast01 metastatic breast cancer patients • Enhertu • LPCD: Q4 2018 previously treated with trastuzumab Secondary end points DoR, CBR, CBR, • Data readout: Q2 2019
NCT03248492 emtansine PFS, OS • Primary objective met CVRM Partnered
Phase III HER2-positive, unresectable and/or 600 Randomised open label parallel assignment Primacy endpoint PFS • FPCD: Q4 2018 DESTINY-Breast02 metastatic breast cancer pretreated with • Enhertu • Data anticipated H2 2021 prior standard of care HER2 therapies, Physicians choice of Secondary endpoints OS, ORR, DoR, CBR NCT03523585 including trastuzumab emtansine • Lapatinib + capecitabine
Partnered • Trastuzumab + capecitabine R&I Phase III HER2-positive, unresectable and/or 500 Randomised open label parallel assignment Primary endpoint PFS • FPCD: Q4 2018 DESTINY-Breast03 metastatic breast cancer patients • Enhertu • Data anticipated H2 2021 previously treated with trastuzumab and • Ado-trastuzumab emtansine Secondary endpoints OS, ORR, DoR, CBR NCT03529110 taxane Partnered
Phase III HER2-low, unresectable and/or 540 Randomised open label parallel assignment Primary end point PFS • FPCD: Q4 2018 DESTINY-Breast04 metastatic breast cancer patients • Enhertu • Data anticipated H2 2021 • Physicians choice of SoC chemo (choice of capecitabine, Secondary end points OS, DoR, ORR NCT03734029 eribulin, gemcitabine, paclitaxel or nab-paclitaxel) Other Partnered
20 Approved medicines Late-stage development Enhertu (trastuzumab deruxtecan, HER2 ADC) Early development Gastric cancer Oncology
Trial Population Patients Design Endpoints Status
Phase II HER2-overexpressing advanced gastric 220 Randomised open label parallel assignment Primary end point ORR • FPCD: Q4 2017 DESTINY-Gastric01 or gastroesophageal junction • Enhertu • LPCD: Q2 2019
adenocarcinoma patients who have • SoC chemo Secondary end points PFS, OS, DoR, • Data readout Q1 2020 CVRM NCT03329690 progressed on two prior treatment DCR, TTF, range of PK endpoints • Primary endpoint met Partnered regimens Asian trial 2 countries
Phase II HER2-positive gastric cancer that cannot 72 Open label single group assignment Primary endpoint ORR • FPCD: Q4 2019 DESTINY-Gastric02 be surgically removed or has spread • Enhertu Secondary endpoints PFS, ORR, OS, DoR NCT04014075 Global trial 5 countries
Partnered R&I Phase Ib/II HER2-overexpressing gastric or gastro- 220 • Open label parallel assignment Part 1 • FPCD Q2 2020 DESTINY-Gastric03 oesophageal junction cancer patients • Part 1: To determine recommended Phase 2 dose Primary endpoint safety • 5 Arms combine Enhertu with standard of care chemotherapies NCT04379596 (5-FU, capecitabine, oxaliplatin) and / or durvalumab Part 2 Primary endpoint ORR
• Part 2: To assess efficacy of the selected combinations Secondary end points • Arm 2A Standard chemotherapy (control) DoR, DCR, PFS, OS, range of PK • Arm 2B Enhertu monotherapy endpoints, ADAs • Arm 2C Enhertu with chemotherapy
• Arm 2D Enhertu with chemotherapy and durvalumab Other
Global trial 8 countries
21 Approved medicines Late-stage development Enhertu (trastuzumab deruxtecan, HER2 ADC) Early development Other cancers Oncology
Trial Population Patients Design Endpoints Status
Phase II HER2 expressing tumours 280 Non randomised single group assignment Primary endpoint: ORR • Initiating DPT02 • Enhertu Secondary endpoints: DoR, DCR, PFS, OS
NCT04482309 CVRM
Phase II HER2-expressing advanced colorectal 90 Non randomised single group assignment Primary endpoint ORR • FPCD Q1 2018 DESTINY-CRC01 cancer • Enhertu • LPCD Q2 2019 Secondary endpoints PFS, OS, DoR, • Data readout: Q2 2020 NCT03384940 range of PK endpoints • Primary endpoint met
Partnered R&I
Phase II HER2-over-expressing or mutated, 130 Non randomised parallel group assignment Primary endpoint ORR • FPCD Q2 2018 DESTINY-Lung01 unresectable and/or metastatic NSCLC • Enhertu • Data anticipated H2 2021 Secondary en points DoR, PFS, OS NCT03505710
Partnered
Phase I Advanced solid malignant tumours 278 Non randomised single group assignment Primary end points number of subjects with • FPCD Q3 2015 J101 • Enhertu AEs, tumour response • Data read out Q3 2018
NCT02564900 Secondary endpoints PK Other
Partnered
Phase I Locally Advanced/Metastatic Breast or 115 • Non randomised parallel group assignment Primary end points DLT, ORR • FPCD Q1 2020 Non-Small Cell Lung Cancer • Enhertu NCT04042701 • Pembrolizumab Secondary endpoints DoR, DCR, PFS, TTR, OS Partnered Global trial 2 countries
Phase I HER2-expressing breast and urothelial 99 • Non randomised sequential assignment Primary end points DLT, ORR, TEAEs • FPCD Q2 2018 cancer • Enhertu NCT03523572 • Nivolumab Secondary endpoints DoR, DCR, PFS, TTR, OS, ORR (investigator) Partnered Global trial 7 countries
22 Approved medicines Late-stage development Calquence (BTK inhibitor) Early development Blood cancers Oncology
Trial Population Patients Design Endpoint(s) Status
Phase III Previously untreated CLL 535 • Arm A: chlorambucil + obinutuzumab • Primary endpoint: PFS (Arm A vs. Arm B) • FPCD: Q2 2015 ACE-CL-007 (ELEVATE-TN) • Arm B: Calquence + obinutuzumab • Secondary endpoints: IRC (independent • Data readout: Q2 2019 • Arm C: Calquence review committee) assessed ORR, OS • Primary endpoint met
NCT02475681 (Arm A vs. Arm B vs. Arm C) CVRM
Phase III Previously untreated CLL 780 • Arm A; Calquence + venetoclax • Primary – IRC assessed PFS (arm A vs • FPCD: Q1 2019 fit • Arm B: Calquence + venetoclax + obinutuzumab arm C) • Data anticipated: 2021+ ACE-CL-311 • Arm C: FCR or BR • Secondary - IRC assessed PFS (arm B NCT03836261 vs arm C); INV assessed PFS (arm A vs
arm C; arm B vs arm C) R&I
Phase III Relapsed/refractory CLL 306 • Arm A: Calquence • Primary endpoint: IRC assessed PFS • FPCD Q3 2016 ACE-CL-309 (ASCEND) • Arm B: rituximab + idelalisib or bendamustine (investigator’s (arm A vs. Arm B) • Data readout: Q2 2019 NCT02970318 choice) • Secondary endpoints: INV-assessed • Primary endpoint met ORR, OS, DoR, PROs
Phase III Relapsed/refractory high risk 533 • Arm A: Calquence • Primary endpoint: PFS • FPCD: Q2 2015 ACE-CL-006 (ELEVATE-RR) CLL • Arm B: ibrutinib • Secondary endpoints: comparison of • Data anticipated: H2 2021 incidence of infections, RTs (Richter’s
NCT02477696 Transformation) and atrial fibrillation, OS Other Phase III Previously untreated MCL 546 • Arm A: Calquence + bendamustine + rituximab • Primary endpoint: PFS by Lugano • FPCD: Q1 2017 ACE-LY-308 • Arm B: bendamustine + rituximab Classification for NHL • Data anticipated: 2021+ • Secondary endpoints: IA, PFS, ORR; NCT02972840 IRC-assessed ORR, DoR, time to response, OS
Phase II Relapsed/ refractory CLL, 60 Calquence monotherapy • ORR at 36 cycles • FPCD: Q1 2016 ACE-CL-208 intolerant to ibrutinib • Data anticipated: H1 2020
NCT02717611
Phase II Relapsed/refractory and 48 Calquence monotherapy • ORR • FPCD: Q4 2014 15-H-0016 treatment naïve/del17p • Arm A: lymph node biopsy • Data anticipated: 2021+ CLL/SLL • Arm B: bone marrow biopsy NCT02337829
Phase I/II CLL/SLL/Richter's 306 Calquence monotherapy • Safety, PK, PD • FPCD: Q1 2014 ACE-CL-001 transformation Dose escalation and expansion • Data anticipated: 2021 23 NCT02029443 Approved medicines Late-stage development Calquence (BTK inhibitor) Early development Blood cancers Oncology
Trial Population Patients Design Endpoint(s) Status
Phase I/II B-cell malignancies 40 Dose escalation and expansion trial of the combination of • Safety • FPCD: Q1 2015 ACE-LY-001 Calquence and ACP-319 (Pi3K inhibitor) • ORR • Data anticipated: H1 2020
NCT02328014 CVRM
Phase I/II Haematological malignancies 161 Calquence + pembrolizumab • Safety • FPCD: Q1 2015 ACE-LY-005 • Secondary endpoints: ORR, DoR, PFS, • Data anticipated: 2021 OS, TTNT (time to next therapy) NCT02362035
Phase I/II Waldenstrom 106 Calquence monotherapy • ORR • FPCD: Q3 2014 ACE-WM-001 microglobulinaemia • Data readout: Q4 2019
NCT02180724 R&I Phase Ib Relapsed/refractory de novo 21 Calquence monotherapy • Safety • FPCD: Q3 2014 ACE-LY-002 activated B-cell DLBCL • Data anticipated: H2 2019
NCT02112526
Phase Ib MCL 70 Calquence in combination with bendamustine and rituxumab • Safety • FPCD: Q1 2016 ACE-LY-106 • Arm A: treatment naive • Data anticipated: 2021+ • Arm B: relapsed/refractory NCT02717624 • Arm C: treatment naïve: Calquence + venetoclax + rituxumab
• Safety • FPCD: Q1 2015
Phase Ib Relapsed/refractory MM 28 • Arm A: Calquence Other ACE-MY-001 • Arm B: Calquence + dexamethasone • Data readout: Q2 2019
NCT02211014
Phase I Relapsed/refractory follicular 80 • Arm A: Calquence • Safety • FPCD: Q1 2015 ACE-LY-003 lymphoma • Arm B: Calquence + rituximab • Data anticipated: 2021+ • Arm C: Calquence + rituximab + lenolidomide NCT02180711
Phase I Relapsed/refractory CLL/ SLL 12 Calquence in combination with ACP-319 • Safety, PK, PD • FPCD: Q3 2014 ACE-CL-002 dose escalation • Data anticipated: H2 2020
NCT02157324
Phase I CLL/SLL/PLL 69 Calquence + obinutuzumab • Safety, ORR • FPCD: Q4 2014 ACE-CL-003 • Arm A: relapsed/refractory • Secondary endpoints: PD, PFS, TTNT, • Data anticipated: 2021+ • Arm B: treatment naïve OS NCT02296918 Calquence + venetoclax + rituxumab • Arm C: relapsed/refractory 24 • Arm D: treatment naïve Approved medicines Late-stage development Calquence (BTK inhibitor) Early development Blood and other cancers Oncology
Trial Population Patients Design Endpoint(s) Status
Phase I Japanese adults with 34 • Calquence monotherapy • Safety • FPCD: Q2 2017 advanced B-cell malignancies • Dose confirmation and expansion • PK • Data anticipated: 2021+ • Calquence + obinutuzumab
NCT03198650 CVRM
Phase I/II CLL r/r 62 • Arm A: ceralasertib (AZD6738) monotherapy • Identify dose of ceralasertib and safety FPCD: Q1 2018 CL-110 • Arm B: Calquence + ceralasertib (AZD6738) of co-administration of Calquence + Data anticipated: H1 2020 ceralasertib NCT03328273
Phase I/II B-cell malignancies r/r 25 • Part 1: Calquence daily + vistusertib daily • MTD and optimal dosing schedule FPCD: Q3 2017 LY-110 • Part 2: Calquence daily + vistusertib 5 days on/2 days off • Safety Data anticipated: H2 2020
NCT03205046 R&I
Phase III CLL TN and r/r 600 • Arm A: treatment naïve • Safety Data anticipated: 2021+ CL-312 • Arm B: relapsed/refractory • Arm C: prior BTKi therapy NCT04008706 • Arm D: concomitant vitamin K antagonists
Phase Ib/II Relapsed/refractory 88 • Arm 1: Calquence + danvatirsen • Primary outcome; safety & tolerability FPCD: Q2 2018 PRISM aggressive NHL • Arm 2: Calquence + AZD6738 • Secondary outcomes; ORR, DOR, PFS, Data anticipated: 2021 • Arm 3: Calquence + Hu5F9G4 + Rituxan OS
NCT03527147 • Arm 4: Calquence + AZD5153 Other An open-label platform trial with trial centres in US and UK
Phase Ib/II ≥ 2L glioblastoma multiforme 52 • Arm A: Calquence 200mg BID • Safety, ORR • FPCD: Q1 2016 ACE-ST-209 • Arm B: Calquence 400mg QD • Data anticipated: H2 2019
NCT02586857
25 26 Paediatric neurofibromatosistumours1, solid type Koselugo PartneredLeadtrial) (Merck NCT03745989 inhibitor) Koselugo Phase Partnered NCT01362803 SPRINT II Phase Trial Ib + MK - 8353(ERK Advanced solid solid tumours Advanced NF1Paediatric Population ( selumetinib 80 (dose escalation 80 (Stratum 2)25 (stratum 50 1) Patients trial) , MEK inhibitor) • Design Phase Single Koselugo • • Stratum enrolmentPN at morbidity relatedStratum nopresent 2: morbidity relatedenrolmentStratum PN at 1: present Ib arm: arm: open in participants with advanced solid solid participants in tumours advancedwith Koselugo - label trial MK of label 25mg/m - 8353 in combination combination within 8353 2 BID BID strata: with2 • • • • • Endpoints Trial drug discontinuations due to an AE an to Trialdue discontinuations drug AEs DLTs outcomes/QoL functional andresponse Durationof volumetric ratebymeasured MRI Complete partial and complete responsecomplete partialand ; • • • • • Status Earlydevelopment Late Approved medicines FPCD: Q1 2019 Primary met endpoint Q1 2019 Datareadout: LPCD:Q4 2016 FPCD: Q3 2015 - stage development
Other R&I CVRM Oncology Approved medicines Late-stage development Lumoxiti (moxetumomab pasudotox,CD22 mAb) Early development Blood cancer Oncology
Trial Population Patients Design Endpoints Status
Phase III Adults with relapsed or 80 • Multicentre, single-arm, open-label Phase III trial • Primary endpoint: rate of durable CR • FPCD: Q2 2013 PLAIT refractory HCL • Lumoxiti i.v. at the recommended dose (complete response): CR maintained for • Data readout: Q3 2017 > 180 days • Primary endpoint met
NCT01829711 • Secondary endpoints CVRM • Efficacy: CR rate, ORR, Duration of Partnered CR and ORR, TTR, PFS • Safety and tolerability
• PK and immunogenicity
R&I Other
27 Approved medicines Late-stage development Savolitinib (MET inhibitor) Early development NSCLC and other cancers Oncology
Trial Population Patients Design Endpoints Status
Phase I Advanced NSCLC 85 • Dose escalation trial • Primary endpoint: safety and tolerability • FPCD: Q2 2013 (all comers) • Secondary endpoint: PK profile • Data anticipated: H2 2020
NCT01985555 Conducted in China CVRM Partnered
Phase II Lung PSC and other NSCLC 65 • Single arm trial: savolitinib QD • Primary endpoint: ORR • FPCD: Q1 2017 • Secondary endpoint: PFS, safety • Data anticipated: H1 2020 NCT02897479 Conducted in China parameters
Partnered
R&I Other
28 Approved medicines Late-stage development Capivasertib (AKT inhibitor) Early development Breast cancer, prostate cancer Oncology
Trial Population Patients Design Endpoints Status
Phase III Locally advanced or 800 Double-blind randomised comparative trial • PFS • FPCD Q3 2019 CAPItello-290 metastatic TNBC • Arm 1: capivasertib + paclitaxel • OS • Data anticipated: 2021+ • Arm 2: placebo + paclitaxel
NCT03997123 CVRM
Phase III Locally advanced (Inoperable) 834 Double-blind randomised comparative trial • PFS • FPCD Q2 2020 CAPItello-291 or metastatic HR+/HER2− • Arm 1: capivasertib + Faslodex • Data anticipated: 2021+ breast cancer • Arm 2: placebo +Faslodex
NCT04305496 R&I
Phase II (ESR) Metastatic castration resistant 150 Randomised comparative • PFS • FPCD Q1 2014 PROCAID prostate cancer eligible for • Arm 1: docetaxel + prednisolone + capivasertib • Data anticipated: Q2 2020 treatment with docetaxel • Arm 2: docetaxel + prednisolone + placebo
NCT02121639 chemotherapy Other
29 Oncology - early-stage development Approved medicines Late-stage development Imfinzi (PD-L1 mAb) Early development Cancer Oncology
Trial Compound Population Patients Design Endpoints Status
Phase I/II Imfinzi Solid tumours 1,022 • Dose escalation: 5 cohorts at Q2W and 1 cohort at Q3W • Safety • FPCD: Q3 2012 STUDY 1108 • Dose expansion: 16 tumour type cohorts at the Q2W MTD • Optimal biologic dose • LPCD: Q4 2016 defined during dose escalation • Secondary endpoints include PK, • Data readout: Q2 2020
NCT01693562 • Dose exploration: cohort at 20mg Q4W immunogenicity and antitumour activity CVRM
Global trial - nine countries
Phase I Imfinzi, azacitidine Myelodysplastic 79 Dose escalation and dose expansion trial • Safety and tolerability of monotherapy • FPCD: Q2 2014 syndrome • Part 1: Imfinzi and combination • Data anticipated: H2 2020 NCT02117219 • Part 2 Arm 1: Imfinzi and tremelimumab • Secondary endpoints include duration of • Part 2 Arm 2: Imfinzi, tremelimumab and azacitidine response, PFS and OS, PK and immunogenicity Global trial - four countries
Phase I MEDI9090 Solid tumours 42 Multi-centre, open-label, single-arm trial for adult subjects • Safety, PK, number of subjects reporting • FPCD: Q3 2016 R&I infusion related reaction • Data readout: Q2 2020 NCT02900157 US and Japan trial centers
Phase II Imfinzi NSCLC 320 5 modules encompassing 13 cohorts • Primary outcome; ORR • FPCD: Q1 2018 HUDSON Lynparza • Module 1; Imfinzi and Lynparza • Secondary outcomes; efficacy including • Data anticipated: 2021+ vistusertib • Module 2; Imfinzi and danvatirsen OS, PFS, DCR, and safety and NCT03334617 ceralasertib • Module 3; Imfinzi and ceralasertib (AZD6738) tolerability, DoR (AZD6738) • Module 4; Imfinzi and vistusertib danvatirsen • Module 5; Imfinzi and oleclumab oleclumab • Module 6; Imfinzi and Enhertu
Enhertu • Module 7; Imfinzi and cedirinib Other cediranib Open-label, biomarker-directed, multi-centre Phase II umbrella trial in patients with NSCLC, who progressed on an anti-PD-1/PD- L1 containing therapy
Phase II Imfinzi Stage III NSCLC 300 • Arm A: Imfinzi Primary • FPCD: Q4 2018 COAST unresectable • Arm B: Imfinzi + oleclumab • OR per RECIST v1.1 • Data anticipated: H2 2020 • Arm C: Imfinzi + monalizumab NCT03822351
Phase II Imfinzi Resectable, early 160 • Arm A: Imfinzi Primary • FPCD: Q1 2019 NeoCOAST stage NSCLC • Arm B: Imfinzi + oleclumab • Major pathological response rate • Data anticipated: H2 2020 • Arm C: Imfinzi + monalizumab NCT03794544 • Arm D: Imfinzi + danvatirsen
31 Approved medicines Late-stage development Imfinzi (PD-L1 mAb) Early development Cancer Oncology
Trial Compound Population Patients Design Endpoints Status
Phase Ib/II Imfinzi 1L metastatic MSS- 112 • Part 1 S1 FOLFOX + bevacizumab + Imfinzi + oleclumab Primary • FPCD: Q3 2019 COLUMBIA 1 CRC • Part 2 Control 1 FOLFOX + bevacizumab • Part 1: Safety • Data anticipated: H2 2020 • Part 2 E1 FOLFOX + bevacizumab + Imfinzi + oleclumab • Part 2: Efficacy - OR
NCT04068610 Secondary CVRM • Part 1: Efficacy – OR, BOR, DoR, PFS • Part 2: Safety and Efficacy ( BOR,
DoR, DC, PFS, OS)
R&I Other
32 Approved medicines Late-stage development Imfinzi (PD-L1 mAb) + Early development tremelimumab (CTLA-4 mAb) Oncology Cancer
Trial Population Patients Design Endpoints Status CVRM Phase Ib/II Hepatocellular carcinoma 545 • Arm A: Imfinzi + tremelimumab • Primary endpoints: Safety & tolerability, • FPCD: Q4 2015 STUDY 22 • Arm B: Imfinzi 2L DLTs • Data anticipated: H2 2020 • Arm C: tremelimumab 2L • Secondary endpoints: ORR, DoR, OS NCT02519348 • Arm D: Imfinzi + tremelimumab • Arm E: Imfinzi in combination with bevacizumab
Phase Ib NSCLC 459 • Dose escalation: minimum 5 cohorts exploring various treme Primary endpoints: • FPCD: Q4 2013 STUDY 006 (Immunotx naïve and Q4W and Imfinzi i.v. Q4W dose combinations, higher dose • Safety • LPCD: Q4 2016 Immunotx pretreated patient levels and alternate Q2 schedule added with amendment • Optimal biologic dose for the combination • Data anticipated: H1 2020
NCT02000947 cohorts) • Dose expansion: MTD for the combination in escalation to be • OR R&I explored in expansion • Secondary endpoints include antitumour activity, PK and immunogenicity North American, EU and ROW trial centres
Phase I Solid tumours (basket trial) 380 • Dose expansion: MTD for the combination in escalation to be Primary endpoints: • FPCD: Q4 2014 STUDY 10 explored in expansion cohorts specific for each of 7 tumour • Safety • LPCD: Q2 2017 types • Optimal biologic dose for the combination • Data anticipated: Q2 2020 NCT02261220 • Dose exploration: 2 cohorts exploring various Q4W treme and • Secondary endpoints include Imfinzi dose combinations and 2 cohorts exploring various Q2W anti-tumour activity, PK/PD and treme and Imfinzi dose combinations immunogenicity
North American, EU and ROW trial centres Other
33 Approved medicines Late-stage development Imfinzi (PD-L1 mAb) + Early development monalizumab (NKG2a mAb) Oncology Cancer
Trial Population Patients Design Endpoints Status CVRM Phase I/II Advanced solid tumours 381 Escalation phase Primary endpoints: • FPCD: Q2 2016 • monalizumab + Imfinzi i.v. • Safety • Data anticipated: 2021+ NCT02671435 • Exploration Phase: Objective Response Expansion phase per RECIST • monalizumab + Imfinzi i.v. recommended dose • Secondary endpoints include tumour Exploration phase response (OR, DC, DoR, PFS and OS), • monalizumab + Imfinzi i.v. recommended dose + SoC systemic immunogenicity, pharmacokinetics, therapy with or without biologic agent and monalizumab in pharmacodynamics
combination with a biologic agent in adult subjects with CRC R&I
Global trial Other
34 Approved medicines Late-stage development Imfinzi (PD-L1 mAb) + Early development MEDI0457 (DNA HPV Vaccine) Oncology Head and neck squamous cell carcinoma (HNSCC)
Trial Population Patients Design Endpoints Status CVRM Phase Ib/IIa HPV associated 50 Multi-centre, open label trial to evaluate the safety and efficacy of Primary endpoints: • FPCD: Q3 2017 recurrent/metastatic head and combination treatment with MEDI0457 and Imfinzi Safety & Tolerability, ORR • Data anticipated: H2 2020 NCT03162224 neck cancer Secondary endpoints:
PK, ADA, DCR, OS, PFS
R&I Other
35 Approved medicines Late-stage development AZD0466 (Bcl2/xL inhibitor) Early development Cancer Oncology
Trial Population Patients Design Endpoints Status
Phase I Advanced hematologic 102 Monotherapy dose escalation, consisting of two arms: • Primary: safety • FPCD: Q4 2019 malignancies or solid tumours • Arm A: Patients with low risk for tumour lysis syndrome (solid • Secondary: PK, anti-tumour activity • Data anticipated: 2021+ NCT04214093 tumours, lymphomas, myelomas)
• Arm B: Patients with high risk for tumour lysis syndrome CVRM
(relapsed/refractory haem malignancies)
R&I Other
36 Approved medicines Late-stage development MEDI1191 (IL12 modRNA) Early development Cancer Oncology
Trial Population Patients Design Endpoints Status
Phase I Advanced solid tumours 87 First-time-in-human Phase I, open-label, dose-escalation and • Primary endpoint: safety and tolerability • FPCD: Q2 2019 expansion trial of MEDI1191 administered intratumourally as • Data anticipated: 2021+ NCT03946800 monotherapy and in combination with Imfinzi • Secondary endpoints: PK,
immunogenicity and efficacy
CVRM
R&I Other
37 Approved medicines Late-stage development AZD1390 (ATM inhibitor) Early development Cancer Oncology
Trial Population Subjects Design Endpoints Status
Phase I Recurrent glioblastoma 132 • Primary: investigate the safety, • FPCD Q2 2018 eligible for re-irradiation, brain • Designed to evaluate the safety, tolerability and PK of tolerability, and MTD of AZD1390 • Data anticipated: H2 2021 NCT03423628 metastases and AZD1390 in combination with radiation therapy in patients with administered in combination with radiation
leptomeningeal disease, GBM and brain metastases from solid tumours therapy in brain malignancies CVRM newly-diagnosed glioblastoma patients • Dose and schedule of AZD1390 administration will be adjusted during assessment of safety and tolerability during this Phase I trial
Conducted across seven sites in USA and UK
R&I Other
38 Approved medicines Late-stage development Adavosertib (AZD1775, WEE-1 inhibitor) Early development
Ovarian cancer, solid tumours Oncology
Trial Population Patients Design Endpoints Status
Phase II Platinum-resistant (PR) 95 • Arm B: paclitaxel + adavosertib • Primary endpoint: ORR • FPCD: Q1 2015 ovarian cancer • Arm C: carboplatin + adavosertib • LPCD: Q2 2018 D6010C00004 • Secondary endpoints: DoR, PFS, OS, • Data readout: Q3 2019
Global trial DCR, safety and tolerability CVRM NCT02272790
Phase I Advanced solid tumours 128 • Dose escalation trial to determine MTD (adavosertib + • Safety and tolerability • FPCD: Q3 2015 Lynparza) followed by an expansions in SCLC • Secondary endpoints: ORR, DCR, DoR, • LPCD: Q4 2018 D6010C00005 PFS • Data readout Q4 2019 Conducted in US, Canada NCT02511795
Phase I Advanced solid tumours 56 • Dose escalation trial to determine MTD (adavosertib + Imfinzi) • Safety and tolerability • FPCD: Q4 2015 • LPCD: Q4 2018 D6015C00002 Conducted in US • Data readout Q4 2019 R&I
NCT02617277
Phase I Advanced solid tumours 33 Part A: caffeine (200mg), omeprazole (20mg) and midazolam • Primary endpoints: • FPCD: Q4 2017 (1mL of 2mg/mL syrup) followed 7-14 days later by adavosertib • Part A: Plasma AUC, AUC0-t and CMAX • LPCD: Q4 2018 D6014C00006 225mg bid for 2.5 days plus caffeine (200mg), omeprazole for cocktail parent compounds • Data readout Q4 2019 (20mg) and midazolam (1mL of 2mg/mL syrup) on day 3. (midazolam, omeprazole and caffeine) NCT03333824 Part B: 7-14 days after end of Part A, adavosertib 225mg BID for • Part B: dECG (differentiated ECG) 2.5 days. intervals (QTcF) for absolute values and time-matched change from baseline
Conducted in US Other
Phase I Advanced solid tumours 48 adavosertib monotherapy once daily. • Safety and tolerability • FPCD: Q4 2017 • LPCD: Q1 2019 D6014C00007 Conducted in US and Europe • Data readout Q4 2019
NCT03313557
39 Approved medicines Late-stage development MEDI2228 (BCMA antibody drug conjugate) Early development Cancer Oncology
Trial Population Patients Design Endpoints Status
Phase I Relapsed/refractory multiple 129 First-time-in-human Phase I, multi-centre, open-label, single-arm, Primary endpoints: • FPCD: Q2 2018 myeloma dose-escalation, and dose-expansion trial for adult subjects • Safety • Data anticipated: 2021+
NCT03489525 • Determination of MTD CVRM • Secondary endpoints: pPK, immunogenicity, ORR, DCR, DoR, PFS,
OS
R&I Other
40 Approved medicines Late-stage development AZD2811NP (AURN) Early development Cancer Oncology
Trial Population Patients Design Endpoints Status
Phase I Solid tumours 72 • Arm 1: AZD2811NP dose escalation • Safety and tolerability • FPCD: Q4 2015 • Arm 2: AZD2811NP dose expansion SCLC • PK and efficacy • Data anticipated: H2 2020
NCT02579226 CVRM
Phase I AML/high-risk MDS 130 • Part A: AZD2811NP monotherapy / azacitidine combination / • Safety and tolerability • FPCD: Q3 2017 venetoclax combination dose escalation cohorts • PK and efficacy • Data anticipated: 2021+ NCT03217838 • Part B: AZD2811NP monotherapy / azacitidine combination / venetoclax combination dose expansions to further explore the
tolerability, PK and clinical activity
R&I Other
41 Approved medicines Late-stage development AZD4573 (CDK9 inhibitor) Early development Cancer Oncology
Trial Population Patients Design Endpoints Status
Phase I Relapsed/refractory 45 Dose escalation in relapsed/refractory haematological Primary: • FPCD: Q4 2017 haematologic malignancies malignancies • safety/PK; • Data anticipated: H2 2020 NCT03263637 Secondary:
AZD4573 will be administered in 2 parallel arms (1-6 cohorts of • efficacy CVRM
dose escalations) based on the haematological malignancy
R&I Other
42 Approved medicines Late-stage development AZD4635 (A2AR inhibitor) Early development Cancer Oncology
Trial Population Patients Design Endpoints Status
Phase I Phase Ia: patients with 3067 Phase Ia – solid tumours or mCPRC: Primary outcome measure: • FPCD: Q2 2016 advanced solid tumours • AZD4635 monotherapy • Safety and tolerability NCT02740985 • AZD4635 + Imfinzi • AZD4635 + abiraterone Phase Ib: Secondary outcome measures: CVRM Post-immunotherapy NSCLC • AZD4635 + enzalutamide • Preliminary assessment of anti-tumour Other post-immunotherapy • AZD4635 + Imfinzi + oleclumab activity • AZD4635 + docetaxel. solid tumours Phase Ib: AZD4635 monotherapy or AZD4635 + Imfinzi dose Immune checkpoint-naïve expansions in NSCLC, mCRPC, CRC and other post- mCRPC Immune checkpoint- immunotherapy and immune checkpoint-naïve solid tumours naïve CRC Other immune checkpoint- Conducted at sites in the US
naïve solid tumours R&I Phase I Healthy male volunteers 21 • Part A 2-period randomised crossover trial of single doses of Primary outcome measures: • FPCD: Q4 2018 AZD4635, nanosuspension or solid oral formulation in fasted • Cmax and exposure (AUC) of AZD4635 • LPCD: Q2 2019 NCT03710434 state solid oral formulation and nano- • Part B, 4-period, open-label, randomised, crossover trial of suspension single doses of AZD4635 in the same subjects from Part A to assess food effect, pH effect and formulation variants Both parts conducted at a site in the UK
Phase II Prostate cancer 60 ARM 1: AZD4635 + Imfinzi • Primary outcome measure: Efficacy; • FPCD: Q3 2019 Other ARM 2: AZD4635 + oleclumab (ORR and PSA response) NCT04089553 Conducted at sites in the US • Secondary outcome measure: Efficacy, PK, safety and tolerability
Phase I Japanese patients with 12 AZD4635 dose escalation Primary outcome measure: • FPCD: Q3 2019 advanced solid malignancies • Safety and tolerability NCT03980821 Conducted at sites in Japan Secondary outcome measure: • PK and preliminary anti-tumour activity
43 Approved medicines Late-stage development AZD5153 (BRD4 inhibitor) Early development Cancer Oncology
Trial Population Patients Design Endpoints Status
Phase I/Ib Relapsed/refractory solid 60 Monotherapy dose escalation in advanced solid tumours and • Primary: safety • FPCD: Q2 2017 tumours, lymphomas lymphomas • Secondary: efficacy, PK • Data anticipated: H2 2020 NCT03205176
Dose escalation of AZD5153 in combination with Lynparza in CVRM
platinum resistant/refractory HGS patients.
R&I Other
44 Approved medicines Late-stage development MEDI5395 (rNDV GMCSF) Early development Cancer Oncology
Trial Population Patients Design Endpoints Status
Phase I Select advanced solid 164 First-time-in-human Phase I, open-label, dose-escalation and • Primary endpoint: safety and tolerability • FPCD: Q4 2019 tumours expansion arm of MEDI5395 in combination with Imfinzi • Data anticipated: 2021+ NCT03889275 • Secondary endpoints: PK, PD,
immunogenicity and efficacy
CVRM
R&I Other
45 Approved medicines Late-stage development MEDI5752 (PD-1/CTLA-4 bispecific mAb) Early development Cancer Oncology
Trial Population Patients Design Endpoints Status
Phase I Advanced solid tumours 272 Open-label, dose-escalation and dose-expansion: Primary endpoints: • FPCD: Q2 2018 • dose-escalation: safety & determination • Data anticipated: 2021+ NCT03530397 • Dose-escalation: MEDI5752 i.v. of MTD
• dose-expansion: assessment of CVRM • Dose-expansion arm: MEDI5752 i.v. in combination with antitumour activity based on OR chemotherapy Secondary endpoints: • PK, ADA, tumoural baseline PD-L1, assessment of antitumour activity
based on OR, DoR, DC, PFS, OS
R&I Other
46 Approved medicines Late-stage development AZD5991 (MCL1 inhibitor) Early development Cancer Oncology
Trial Population Patients Design Endpoints Status
Phase I/Ib/IIa Relapsed/refractory 177 • Arm1: monotherapy dose escalation & expansions in • Primary: safety • FPCD: Q3 2017 haematologic malignancies relapsed/refractory haematological malignancies • Secondary: PK, efficacy • Data anticipated: H2 2021 NCT03218683 • Arm2: combination dose escalation (AZD5991+venetoclax) in
relapsed/refractory AML/MDS;. CVRM • i.v. route of administration
• US only
R&I Other
47 Approved medicines Late-stage development Ceralasertib (AZD6738, ATR inhibitor) Early development Cancer Oncology
Trial Population Patients Design Endpoints Status
Phase I Solid tumours 250 • Arm 1: ceralasertib + carboplatin • Safety and tolerability • FPCD: Q4 2014 • Arm 2: ceralasertib dose escalation, ceralasertib + Lynparza • PK and efficacy • Data anticipated: 2021+
NCT02264678 • Arm 3: ceralasertib + Imfinzi CVRM Trial conducted in North America, Europe and South Korea
Phase I HNSCC 44 Window of opportunity • Biomarker change • FPCD: Q4 2017 • Arm 1: ceralasertib • Data anticipated: H2 2020 NCT03022409 • Arm 2: Lynparza
Trial conducted in US, France, Taiwan and the UK
R&I Other
48 Approved medicines Late-stage development AZD7648 (selective DNA-PK inhibitor) Early development Advanced solid tumours Oncology
Trial Population Patients Design Endpoints Status
Phase I Advanced Malignancies 234 • This is a modular Phase I/IIa, open-label, multi-centre, trial of • Primary outcome measures: safety and • Initiating AZD7648 administered orally, either as a monotherapy, or in tolerability NCT03907969 combination with either cytotoxic chemotherapies or novel • Secondary outcome measures: Cmax, anti-cancer agents in participants with advanced
AUC, Cytochromes P450, ORR CVRM malignancies. The modular design allows for an escalation of the dose of AZD7648 alone or in combination with either cytotoxic chemotherapies or novel anti-cancer agents, with intensive safety monitoring to ensure the safety of the
participants.
R&I Other
49 Approved medicines Late-stage development Danvatirsen (AZD9150, STAT3 inhibitor) Early development Cancer Oncology
Trial Population Patients Design Endpoints Status
Phase Ib/II HNSCC 339 Dose escalation advanced solid and blood cancers • Safety/efficacy trial • FPCD: Q3 2015 • Arm A1: AZD9150/Imfinzi • LPCD: Q2 2019 NCT02499328 • Arm A2 : AZD5069/Imfinzi • Data anticipated: H2 2021
• Arm A4: AZD9150/Imfinzi/treme CVRM • Arm A5: AZD5069/Imfinzi/treme Dose expansion 2L HNSCC: • Arm B1: AZD9150 • Arm B2: AZD5069 • Arm B3: AZD9150/Imfinzi • Arm B4: AZD5069/Imfinzi • Arm B5: AZD9150 mono • Arm B6: AZD5069 mono • Arm B7: AZD9150/Imfinzi (1L HNSCC)
• Arm B8: AZD9150 Q2W/Imfinzi (1L HNSCC) R&I
Phase Ib/II NSCLC, advanced solid 76 Dose escalation advanced solid and blood cancers • Safety/efficacy trial • FPCD: Q1 2018 tumours • Arm A1: AZD9150 alternate week/Imfinzi • Data anticipated: H2 2021 NCT03421353 • Arm A2-A5 : AZD9150/Imfinzi + SoC chemo
Dose expansion 1L HNSCC: • Arm D1/D2/D3: AZD9150 i.v. vs s.c. formulations/Imfinzi
(advanced solid tumours) Other
50 Approved medicines Late-stage development Oleclumab (MEDI9447, CD73 mAb) Early development Cancer Oncology
Trial Population Patients Design Endpoints Status
Phase I Advanced malignancies 348 Dose escalation phase Primary endpoints: • FPCD: Q3 2015 • oleclumab i.v. • Safety • Data anticipated: 2021+
NCT02503774 • oleclumab i.v. + Imfinzi i.v. • Determination of MTD CVRM • Secondary endpoints include preliminary Dose expansion phase anti-tumour activity, PK, PD, • oleclumab i.v. recommended dose + Imfinzi i.v. immunogenicity and biomarker activity
US, South Korean and Australian trial centres
Phase Ib/II Pancreatic 339 • Arm A1: gemcitabine and nab paclitaxel i.v. Primary endpoints: • FPCD: Q2 2018 1L and 2L with prior • Arm A2: gemcitabine and nab paclitaxel i.v. + oleclumab i.v. • Safety and anti-tumour activity • Data anticipated: H2 2021 NCT03611556 gemcitabine-based • Arm A3: gemcitabine and nab paclitaxel i.v. + oleclumab i.v. +
chemotherapy Imfinzi i.v. • Secondary endpoints include PFS, PK, R&I • Arm B1: mFOLFOX (oxaliplatin, leucovorin, 5-FU) i.v. immunogenicity, safety and anti-tumour • Arm B2: mFOLFOX (oxaliplatin, leucovorin, 5-FU) i.v. + activity oleclumab i.v. • Arm B3: mFOLFOX (oxaliplatin, leucovorin, 5-FU) i.v. + oleclumab i.v. + Imfinzi i.v.
US, Norway, Spain and Australian trial centres Phase Ib/II NSCLC 98 • Arm A: oleclumab i.v. + Tagrisso Primary endpoints: • FPCD: Q2 2018 • Safety • Data anticipated: 2021+ NCT03381274 US, South Korean and Taiwan trial centres • ORR Secondary endpoints: Other • DoR, DCR, PFS, OS, PK and immunogenicity
51 Approved medicines Late-stage development AZD9496 (SERD, oral) Early development Breast cancer Oncology
Trial Population Patients Design Endpoints Status
Phase I ER+ breast cancer c. 50 • This is an open label randomised multicentre pre-surgical • Primary outcome measures: PD changes • FPCD: Q4 2017 pharmacodynamics trial to compare and assess the biological to ER expression following treatment with • Data readout: Q1 2020 NCT03236974 effects of AZD9496 and Faslodex in postmenopausal women AZD9496 or Faslodex
with ER+, HER2- primary breast cancer. Patients will receive • Secondary outcome measures: CVRM pharmacodynamics changes to Ki67 and AZD9496 or Faslodex and will have a pre-dose and an on- PgR expression following treatment with treatment core biopsy after 5-14 days of commencing AZD9496 or Faslodex
treatment. • Safety, tolerability + pharmacokinetics
R&I Other
52 Approved medicines Late-stage development AZD9833 (SERD, oral) Early development Breast cancer Oncology
Trial Population Patients Design Endpoints Status
Phase I ER+ breast cancer 240 • This is a Phase I open label multicentre trial of AZD9833 • Primary outcome measures: safety and • FPCD: Q4 2018 administered orally in patients with advanced ER+ HER2 tolerability NCT03616587 negative breast cancer. The trial design allows an escalation • Secondary outcome measures: multiple of dose with intensive safety monitoring to ensure the safety
dose PK of AZD9833 alone and in CVRM of patients. The trial will determine the maximum tolerated combination with palbociclib dose of AZD9833 as monotherapy and in combination with antitumour activity palbociclib. In addition, randomised expansion cohort(s) at potential therapeutic dose(s) in patients will be enrolled to further determine the safety, tolerability, pharmacokinetics and biological activity of AZD9833 alone and in combination with palbociclib
Phase II ER+ breast cancer 288 • This is a Phase II randomised, open-label, parallel-group, • Primary outcome measure: mPFS • Initiating
multicentre trial aimed to compare the efficacy and safety of R&I NCT04214288 oral AZD9833 versus intramuscular (IM) Faslodex in women
with advanced breast cancer. Other
53 Approved medicines Late-stage development IPH5201 (CD39 mAb) Early development Solid Tumour Oncology
Trial Population Patients Design Endpoints Status Phase I Advanced Solid tumours 204 • First time in human Phase I, open-label, dose- Primary endpoints: • FPCD: Q1 2020 escalation trial to determine MTD of IPH5201 as AE, SAE, DLT • Data anticipated: 2021+ NCT04261075 monotherapy, or in combination with Imfinzi +/- Partnered oleclumab. Secondary endpoints: CVRM OR, DC, PK, ADA • Part 1: IPH5201 monotherapy dose escalation to MTD • Part 2: IPH5201 + Imfinzi dose escalation to MTD • Part 3: IPH5201 + Imfinzi + Oleclumab dose escalation to MTD • Route of Administration: IV
• Geographical Regions: 4 countries - US and 3 in EU.
R&I Other
54 BioPharmaceuticals - approved medicines and late-stage pipeline Approved medicines Late-stage development Farxiga (SGLT2 inhibitor) Early development Heart failure and chronic kidney disease Oncology
Trial Population Patients Design Endpoints Status
Phase III CHF patients with HFrEF 4,744 • Arm 1: Farxiga 10mg or 5 mg QD + SoC therapy • Primary endpoint: time to the first • FPCD: Q1 2017 Dapa-HF • Arm 2: placebo + SoC therapy occurrence of any of the components of • LPCD Q4 2018 the composite: CV death or • Data readout: Q3 2019 • Global trial - 20 countries • Primary endpoint met
NCT03036124 hospitalisation for HF or an urgent HF CVRM visit
Phase III Patients With CKD 4,000 • Arm 1: Farxiga 10mg or 5 mg QD • Primary endpoint: time to the first • FPCD: Q1 2017 Dapa-CKD • Arm 2: placebo occurrence of any of the components of • LPCD: Q2 2020 the composite: ≥50% sustained decline • Data readout: Q1 2020 NCT03036150 Global trial - 21 countries in eGFR or reaching ESRD or CV death • Trial stopped early based on IDMC or renal death recommendation
Phase III CHF patients with HFpEF 6,100 • Arm 1: Farxiga 10mg QD • Primary endpoint: time to the first • FPCD: Q4 2018 R&I DELIVER • Arm 2: placebo occurrence of any of the components of • Data anticipated: H2 2021 the composite: CV death or NCT03619213 • Global trial - 21 countries hospitalisation for HF or an urgent HF visit
Phase III CHF patients with HFpEF 500 • Arm 1: Farxiga 10mg QD Family of primary endpoints: • FPCD: Q2 2019 DETERMINE-preserved • Arm 2: placebo • Change from baseline in the KCCQ- • LPCD: Q3 2020 TSS at Week 16. • Data anticipated: H2 2020 • Global trial - 12 countries NCT03877224 • Change from baseline in the KCCQ-
PLS at Week 16. Other • Change from baseline in 6 min walking distance at Week 16
Phase III CHF patients with HFrEF 300 • Arm 1: Farxiga 10mg QD Family of primary endpoints: • FPCD: Q2 2019 DETERMINE-reduced • Arm 2: placebo • Change from baseline in the KCCQ- • LPCD Q1 2020 TSS at Week 16. • Data anticipated: H2 2020 • Global trial - 9 countries NCT03877237 • Change from baseline in the KCCQ- PLS at Week 16. • Change from baseline in 6 min walking distance at Week 16
56 Approved medicines Late-stage development Brilinta (P2Y12 receptor antagonist) Early development Cardiovascular risk reduction Oncology
Trial Population Patients Design Endpoints (primary) Status
Phase III Patients with type-2 diabetes 19,000 • Arm 1: Brilinta 60mg BiD • Primary endpoint: composite of CV • FPCD: Q1 2014 THEMIS and coronary artery disease • Arm 2: placebo BID death, non-fatal MI and non-fatal stroke • LPCD: Q2 2016 without a previous history of on a background of acetylsalicylic acid if not contra-indicated or • Data readout: Q1 2019 NCT01991795 MI or stroke not tolerated • Primary endpoint met
Secondary endpoints: CVRM • Prevention of CV death Global trial – 42 countries • Prevention of MI • Prevention of ischaemic stroke • Prevention of all-cause death
Phase III Patients with acute ischaemic 11,000 • Arm 1: Brilinta 90mg BiD Primary endpoint: • FPCD: Q1 2018 THALES stroke or transient ischaemic • Arm 2: placebo BiD • Prevention of the composite of • LPCD: Q4 2019 attack on a background of acetylsalicylic acid if not contra-indicated or subsequent stroke and death at 30 days • Data readout: Q1 2020 NCT03354429 not tolerated • Primary endpoint met
Secondary endpoints include: R&I Global trial – 28 countries • Prevention of subsequent ischaemic stroke at 30 days • Reduction of overall disability at 30 days
Phase III Paediatric patients (2-18 years 182 • Arm 1: Brilinta 15, 30 or 45mg (dose based on subject weight) • Primary endpoint: the number of vaso- • FPCD: Q3 2018 HESTIA3 old) with sickle cell disease • Arm 2: placebo occlusive crisis which is the composite • Data anticipated: H2 2020 of painful crisis and/or acute chest pain
NCT03615924 Global trial – 18 countries Other
57 Approved medicines Late-stage development Lokelma (sodium zirconium cyclosilicate) Early development Hyperkalaemia Oncology
Trial Population Patients Design Endpoints Status Phase II Patients with chronic heart 182 • Arm 1: Lokelma 5g QD for 12 weeks. Option to uptitrate to 10 • Primary endpoint: difference between • FPCD: Q3 2018 PRIORITIZE HF failure and hyperkalaemia or and 15g QD or downtitrate to 5g QOD Lokelma and placebo in RAAS (renin– • Data readout: H2 2020 at high risk of developing • Arm 2: placebo QD for 12 weeks angiotensin–aldosterone system)
NCT03532009 hyperkalaemia blockade treatment. CVRM
Global trial – nine countries
R&I Other
58 Approved medicines Late-stage development Roxadustat (HIF-PH inhibitor) Early development Anaemia Oncology
Trial Population Patients Design Endpoints Status
Phase III Anaemia in CKD in patients 922 • Arm 1: roxadustat • Primary endpoint: Haemoglobin response • FPCD: Q4 2012 ANDES not receiving dialysis • Arm 2: placebo • LPCD: Q3 2018 • Data readout: Q4 2018 NCT01750190 Global trial
• Primary endpoint met CVRM Partnered Sponsored by FibroGen
Phase III 597 • Arm 1: roxadustat • Primary endpoint: Haemoglobin response • FPCD: Q2 2013 ALPS • Arm 2: placebo • LPCD: Q4 2017 • Data readout: Q3 2018 NCT01887600 Global trial • Primary endpoint met Partnered Sponsored by Astellas
Phase III 616 • Arm 1: roxadustat • Primary endpoint: Haemoglobin response • FPCD: Q1 2014
DOLOMITES • Arm 2: darbepoetin alfa • LPCD: Q4 2019 R&I • Data readout: Q1 2020 NCT02021318 Global trial • Primary endpoint met Partnered Sponsored by Astellas
Phase III 2,781 • Arm 1: roxadustat • Primary efficacy endpoint: Haemoglobin • FPCD: Q3 2014 OLYMPUS • Arm 2: placebo response • LPCD: Q4 2018 • Data readout: Q4 2018 NCT02174627 Global trial • Primary safety objective: Contribute CV • Primary endpoint met safety data to pooled safety Sponsored by AstraZeneca
• analyses across the Phase III program Other Phase III Anaemia in CKD in patients 2,133 • Arm 1: roxadustat • Primary efficacy endpoint: Haemoglobin • FPCD: Q3 2014 ROCKIES receiving dialysis • Arm 2: epoetin alfa response • LPCD: Q3 2018 • Data readout: Q4 2018 NCT02174731 Global trial • Primary safety objective:Contribute CV • Primary endpoint met safety data to pooled safety Sponsored by AstraZeneca • analyses across the Phase III program
Phase III 741 • Arm 1: roxadustat • Primary endpoint: Haemoglobin response • FPCD: Q4 2014 SIERRAS • Arm 2: epoetin alfa • LPCD: Q3 2018 • Data readout: Q4 2018 NCT02273726 Global trial • Primary endpoint met Partnered Sponsored by FibroGen
Phase III 838 • Arm 1: roxadustat • Primary endpoint: Haemoglobin response • FPCD: Q4 2014 PYRENEES • Arm 2: epoetin alfa or darbepoetin alfa • LPCD: Q3 2018 • Data readout: Q3 2018 NCT02278341 Global trial • Primary endpoint met Partnered Sponsored by Astellas 59 Approved medicines Late-stage development Roxadustat (HIF-PH inhibitor) Early development Anaemia Oncology
Trial Population Patients Design Endpoints Status
Phase III Anaemia in newly initiated 1,043 • Arm 1: roxadustat • Primary endpoint: Haemoglobin response • FPCD: Q4 2013 HIMALAYAS dialysis patients • Arm 2: epoetin alfa • LPCD: Q3 2018 • Data readout: Q4 2018 NCT02052310 Global trial • Primary endpoint met Partnered Sponsored by FibroGen CVRM
Phase III Anaemia in lower risk MDS 184 Open label roxadustat lead-in • Primary endpoint: Proportion of patients • FPCD: Q3 2017 patients Arm 1: roxadustat achieving transfusion independence • Data anticipated: 2021 NCT03263091 Arm 2: placebo Sponsored by FibroGen Partnered US/global trial
Phase II/III Anaemia in lower risk MDS 175 Open label roxadustat lead-in • Primary endpoint: Haemoglobin
patients Arm 1: roxadustat response • FPCD: Q2 2018 R&I NCT03303066 Arm 2: placebo • Data anticipated: 2020 Partnered Sponsored by FibroGen China
Phase II Anemia in patients receiving 100 US • Primary endpoint: Maximum change in • FPCD: Q3 2019 chemotherapy treatment for hemoglobin within 16 weeks from • LPCD: Q3 2020 NCT04076943 non-myeloid malignancies baseline without RBC transfusion • Data anticipated: H2 2020
Partnered Sponsored by FibroGen Other
60 Approved medicines Late-stage development Eklira/Tudorza (LAMA, DPI) Early development COPD Oncology
Trial Population Number of patients Design Endpoints Status
Phase I Healthy Chinese 18 Open-label, 2-period ascending dose incomplete block, cross-over • To investigate the PK of aclidinium • Initiating volunteers trial bromide and its metabolites after single • Data anticipated: H2 2021 NCT03276052 and multiple doses (BID) of aclidinium • Arm 1: aclidinium bromide 200 μg DPI bromide 200 μg, 400 μg and 800 μg • Arm 2: aclidinium bromide 400 μg DPI • To evaluate the safety, and tolerability CVRM • Arm 3: aclidinium bromide 800 μg DPI of aclidinium bromide 200 μg, 400 μg and 800 μg after single and multiple dose administration (BID)
Global trial – one Country
R&I Other
61 Approved medicines Late-stage development Duaklir Genuair (LAMA/LABA, DPI) Early development COPD Oncology
Trial Population Patients Design Endpoints Status
Phase III Patients with stable COPD 1,060 • Arm 1: Duaklir Genuair 400/12 μg DPI Primary endpoints: • FPCD: Q1 2017 AVANT • Arm 2: aclidinium bromide 400 μg DPI • Change from baseline in one hour • Data anticipated: H2 2021 • Arm 3: formoterol fumarate 12 μg DPI morning post-dose dose FEV1 Duaklir NCT03022097 • Arm 4: tiotropium 18 μg DPI Genuair 400/12 μg compared to CVRM Aclidinium bromide at Week 24 • Change from baseline in morning pre- Global trial – five countries dose (trough) FEV1 of Duaklir Genuair 400/12 μg compared to Formoterol fumarate at Week 24 • Change from baseline in trough FEV1 of Aclidinium bromide 400 µg compared to
placebo at Week 24
R&I Other
62 Approved medicines Late-stage development Breztri (PT010, LAMA/LABA/ICS, pMDI) Early development COPD Oncology
Trial Population Patients Design Endpoints Status
Phase III Moderate to very severe 500 Treatments (52-week treatment period) Primary endpoints: • FPCD: Q3 2015 COPD • BGF (budesonide, glycopyrronium, and formoterol fumarate) • Bone mineral density sub-trial endpoint. • LPCD: Q3 2016 MDI 320/14.4/9.6µg BID pMDI change from baseline in BMD of the • Data readout: Q1 2018
NCT02536508 • GFF (glycopyrronium and formoterol fumarate) MDI 14.4/9.6µg lumbar spine measured using DXA (dual • Primary endpoints met CVRM BID pMDI energy X-ray absorptiometry) scans of • BFF (budesonide and formoterol fumarate) MDI 320/9.6µg BID L1-L4 at week 52 pMDI • Ocular sub-trial safety endpoint change Randomised, double-blind, chronic-dosing, multi-centre from baseline in LOCS III at week 52
Country – US
Phase III Moderate to very severe 8,588 Treatments (1-year treatment period) • Primary endpoint: rate of moderate or • FPCD: Q3 2015 ETHOS COPD • BGF MDI 320/14.4/9.6µg BID pMDI severe COPD exacerbations • LPCD: Q3 2018
• BGF MDI 160/14.4/9.6µg BID pMDI • Data readout: Q3 2019 R&I NCT02465567 • BFF MDI 320/9.6µg BID pMDI • Secondary endpoint: time to first • Primary endpoint met • GFF MDI 14.4/9.6µg BID pMDI moderate or severe COPD exacerbation
Randomised, double-blind, multi-centre and parallel-group
Multi-country
Phase III Moderate to very severe 1,800 Treatments (24-week treatment period) Primary Endpoints: • FPCD: Q3 2015 KRONOS COPD • BGF MDI 320/14.4/9.6µg BID pMDI • FEV1 area under curve from 0 to 4 hours • LPCD: Q2 2017 • GFF MDI 14.4/9.6µg BID pMDI (AUC0-4) over 24 weeks (BGF MDI vs. • Data readout: Q1 2018 NCT02497001 • BFF MDI 320/9.6µg BID pMDI BFF MDI and BGF MDI vs. Symbicort • 8/9 Primary endpoints met
• Symbicort Turbuhaler 400/12µg BID DPI Turbuhaler) Other • Change from baseline in morning pre- Randomised, double-blind, parallel-group, and chronic dosing and dose trough FEV1 over 24 weeks (BGF multi-centre MDI vs. GFF MDI) • TDI focal score over 24 weeks (BGF MDI vs. BFF MDI and BGF MDI vs. GFF Multi-country MDI)
Phase III Moderate to very severe 324 Treatments (28-week treatment period) Primary outcome measures: • FPCD Q3 2016 COPD • BGF MDI 320/14.4/9.6µg BID pMDI • Long-term safety and tolerability (52 • LPCD Q4 2017 NCT03262012 • GFF MDI 14.4/9.6µg BID pMDI weeks): adverse events, 12-lead ECG, • Data readout: Q3 2018 • BFF MDI 320/9.6µg BID pMDI laboratory tests, vital signs • Primary safety endpoint met • Symbicort Turbuhaler 400/12µg BID DPI
Randomised, double-blind, parallel-group, chronic dosing, multicenter
Country: Japan 63 Approved medicines Late-stage development Daliresp/Daxas (PDE4 inhibitor, oral) Early development COPD Oncology
Trial Population Patients Design Endpoints Status
Post Launch COPD 124,080 • This is a retrospective cohort trial comparing COPD patients • Primary endpoint: all-cause mortality (up • Data anticipated: 2021+ PASS aged 40 years and older with new exposure to roflumilast with to five years) up to 5 unexposed (i.e., not roflumilast-exposed) COPD NCT03381573
controls matched by propensity score (PS), age, sex, and year CVRM of cohort entry. The trial is using electronic healthcare databases in the US (Military Health System database), Germany (German Pharmacoepidemiological Research Database), and Sweden (national databases including
healthcare, death, and demographics data).
R&I Other
64 Approved medicines Late-stage development Fasenra (IL5R mAb) Early development Severe, uncontrolled asthma Oncology
Trial Population Patients Design Endpoints Status
Phase III A multi-centre, open-label, 447 • Arm 1: Fasenra 30mg Q4W s.c. • Primary endpoint: safety and tolerability • FPCD: Q2 2016 MELTEMI safety extension trial with • Arm 2: Fasenra 30mg Q8W s.c. • LPCD: Q3 2019 Fasenra for asthmatic adults • Data anticipated: H2 2020
NCT02808819 on ICS plus LABA2 Agonist Global trial - 15 countries CVRM Age 18-75 years
Phase IIIb Severe eosinophilic 598 Arm 1: Fasenra 30mg Q8W s.c. • Primary endpoint: reduction of oral • FPCD: Q3 2018 PONENTE asthmatics receiving HD ICS corticosteroid dose • LPCD: Q3 2019 + LABA and chronic OCS with 38-week trial • Data anticipated: H2 2020 NCT03557307 or without additional asthma Global trial – 16 countries controller(s). Age 18 Years and older
D3250C00036 China Severe, uncontrolled asthma, 666 • Arm 1: Fasenra 30mg Q8W s.c. • Primary endpoint: annual asthma • FPCD: Q4 2017 ICS/LABA Trial (MIRACLE) despite background controller • Arm 2: placebo s.c. exacerbation rate • Data readout: 2021+ R&I medication, MD & HD ICS + • Secondary endpoints: assess pulmonary NCT03186209 LABA ± chronic OCS 56-week trial function, asthma symptoms, other
Age 12-75 years Global trial – 4 countries asthma control metrics Other
65 Approved medicines Late-stage development Fasenra (IL5R mAb) Early development Severe, uncontrolled asthma Oncology
Trial Population Patients Design Endpoints Status
Phase III Severe asthma, inadequately 2,133 • Arm 1: Fasenra 30mg Q4W s.c. • Primary endpoint: safety and tolerability • FPCD: Q4 2014 BORA controlled despite background • Arm 2: Fasenra 30mg Q8W s.c.* • Data readout: Q3 2018 controller medication, MD & • Primary endpoint met
NCT02258542 HD ICS + LABA ± chronic • placebo administered at select interim visits to CVRM OCS maintain blind between treatment arms Age 12-75 years 56-week (adults) 108-week (adolescents) Global trial – 24 countries
Phase III Severe asthma, inadequately 162 • Arm 1: Fasenra 30mg Q4W s.c. • Primary endpoint: functionality, reliability, • FPCD: Q2 2015 GREGALE controlled despite background and performance of a pre-filled syringe • Data readout: Q2 2016
controller medication, MD & 28-week (adults) with Fasenra administered at home • Primary endpoint met R&I NCT02417961 HD ICS + LABA ± chronic Global trial – two countries OCS Age 18-75 years
Phase lll A double-blind, randomised, 46 • Arm 1 : Fasenra 30mg Q4W s.c. • Primary endpoint: safety and tolerability • FPCD Q4 2016 ARIA parallel group, placebo- • Arm 2: placebo s.c. • Data anticipated: H2 2020 controlled multi-centre trial to • Primary endpoint: the effect of Fasenra NCT02821416 evaluate the effect of Fasenra 37-week trial on allergen induced eosinophil changes on allergen-induced in sputum and allergen-induced late inflammation in Mild, atopic asthmatic response asthmatic Other Age 18-65 years
Phase lll A multi-centre, randomised, 103 • Arm 1: Fasenra 30mg Q4W s.c. with one dose of seasonal Primary endpoints: • FPCD: Q3 2016 ALIZE double-blind, parallel group, influenza virus vaccine IM at week eight • Post-dose strain-specific HAI) antibody • Data readout: Q3 2017 placebo-controlled, Phase IIIb • Arm 2: placebo Q4W s.c. with one dose of seasonal influenza GMFRs • Primary endpoint met NCT02814643 trial to evaluate the potential virus vaccine intra muscular at week • Post-dose strain-specific serum HAI effect of Fasenra on the antibody GMTs humoral immune response to 12-week trial • Proportion of patients who experience a the seasonal influenza strain-specific post-dose antibody vaccination in adolescent and response with antibody response defined young adult patients with as a ≥4-fold rise in HAI antibody titer severe asthma Ages 12-21 years
66 Approved medicines Late-stage development Fasenra (IL5R mAb) Early development Severe, uncontrolled asthma Oncology
Trial Population Patients Design Endpoints Status
Phase III Severe asthma on ICS-LABA 121 Open label Fasenra 30mg Q4w • Primary endpoint: percentage of patients/ • FPCD: Q4 2016 GRECO Age 18-75 years caregivers who successfully self • Data readout: Q4 2017 28-week trial administer at home • Primary endpoint met
NCT02918071 Global trial - two countries CVRM
Phase lllb A multi-centre, randomised, 659 • Arm 1: Fasenra 30mg Q8W s.c. • Primary endpoint: rate of asthma • FPCD: Q3 2017 ANDHI double-blind, parallel group, • Arm 2: placebo s.c. exacerbations • LPCD: Q1 2019
placebo controlled, Phase IIIb • Secondary outcome measures: Saint • Data readout: Q4 2019 R&I NCT03170271 trial to evaluate the safety and 24-week trial George Respiratory Questionnaire • Primary endpoint met efficacy of Fasenra 30 mg s.c. Global trial – 15 countries (SGRQ) in patients with severe asthma uncontrolled on SoC treatment. Age 18-75
Phase I Healthy volunteers 180 Open label trial to compare 30 mg Fasenra PK administered by • Primary endpoint: PK comparability • FPCD: Q1 2017
AMES age 18-55 years APFS or AI device • Data readout: Q3 2017 Other NCT02968914 8-week trial Global trial – two countries
67 Approved medicines Late-stage development Fasenra (IL5R mAb) Early development Nasal polyposis and other eosinophilic diseases Oncology
Trial Population Patients Design Endpoints Status
Phase III Patients with severe bilateral 413 • Arm 1: Fasenra 30mg Q8W s.c. • Primary endpoint: effect of Fasenra on • FPCD: Q1 2018 OSTRO nasal polyposis who are still • Arm 2: placebo s.c. nasal polyp burden and on patient • LPCD: Q2 2019 symptomatic despite standard reported nasal blockage • Data anticipated: H2 2020
NCT03401229 of care therapy 56-week trial CVRM Global trial- 8 countries Age 18-75 years
Phase III Patients with eosinophilic 148 Arm 1: Fasenra 30mg Q8W s.c. • Primary endpoint: Change in endoscopic • FPCD: Q4 2019 ORCHID chronic rhinosinusitis with Arm 2: placebo Q8W s.c. total nasal polyp score and Change in • Data anticipated: 2021+ severe nasal polyposis mean nasal blockage score NCT04157335 56-week trial Age 18-75 years
Asian countries (4 countries) R&I
Phase III Patients with relapsing or 140 • Arm 1: Fasenra 30mg Q4W s.c. • Primary endpoint: Proportion of patients • FPCD: Q4 2019 MANDARA refractory EGPA on • Arm 2: mepolizumab 300mg Q4W s.c. achieving remission (BVAS=0 and OCS • Data anticipated: 2021+ corticosteroid therapy with or dose ≤ 4mg/day) at both weeks 36 and NCT04157348 without stable 52-week trial with a minimum 1 year open label extension 48. immunosuppressive therapy Global trial- 9 countries
Age 18 years and older Phase III Patients with HES (history of 120 • Arm 1: Fasenra 30mg Q4W s.c. • Primary endpoint: Time to first HES • FPCD Q3 2020
NATRON persistent eosinophilia >1500 • Arm 2: placebo Q4W s.c. worsening/flare. • Data anticipated: 2021+ Other cells/μL with evidence of NCT04191304 end organ manifestations 24-week trial with a minimum 1 year open label extension attributable to eosinophilia) Global trial- 9-12 countries and signs or symptoms of HES worsening/flare at Visit 1
Age 12 years and older Phase III Documented diagnosis of EoE 170 • Arm 1: Fasenra 30mg Q4W s.c. • Primary endpoints: • Initiating Age 12 to 65 years • Arm 2: placebo Q4W s.c. Histologic response at week 24 • Data anticipated: 2021+ MESSINA 24-week double blind treatment period and open label period(s) Change from baseline in DSQ score at week 24
68 Approved medicines Late-stage development Fasenra (IL5R mAb) Early development COPD Oncology
Trial Population Patients Design Endpoints Status
Phase III Patients with moderate to very 1216 • Double-blind, placebo controlled, single dose (100mg q8w) • Primary endpoint: annualized rate of • FPCD Q4 2019 RESOLUTE severe COPD with a history of • 56-week treatment moderate or severe exacerbations over • Data anticipated: 2021+ frequent exacerbations on a • Global trial 56 weeks
NCT04053634 background triple therapy CVRM (ICS/LABA/LAMA)
Age 40-85 years
R&I Other
69 Approved medicines Late-stage development Tezepelumab (TSLP mAb) Early development Severe, uncontrolled asthma Oncology
Trial Population Patients Design Endpoints Status
Phase III Severe asthma 1,061 • Arm 1: tezepelumab s.c. • Primary endpoint: Annual asthma • FPCD: Q1 2018 NAVIGATOR Age 12-80 years • Arm 2: placebo s.c. exacerbation rate • LPCD: Q3 2019 • Secondary endpoints: Change from • Data anticipated: H2 2020
NCT03347279 52 week trial baseline in pre-BD FEV1, asthma related CVRM QoL (AQLQ(S)+12), asthma control Partnered Global trial – 18 countries (ACQ-6)
Phase III Severe asthma 150 • Arm 1: tezepelumab s.c. • Primary endpoint: Reduction from • FPCD: Q2 2018 SOURCE Age 18-80 years • Arm 2: placebo s.c. baseline in daily OCS dose while not • LPCD: Q4 2019 losing asthma control • Data anticipated: H2 2020 NCT03406078 48 week trial • Secondary endpoint: Annual asthma exacerbation rate
Partnered Global trial – seven countries R&I
Phase III Severe asthma ~975 • Arm 1: tezepelumab s.c. • Primary endpoint: Exposure adjusted • FPCD: Q1 2019 DESTINATION Age 12-80 years • Arm 2: placebo s.c. rates of AEs/SAEs Secondary endpoints: • Data anticipated: 2021+ Annual asthma exacerbation rate NCT03706079 Extension trial to NAVIGATOR and SOURCE. 52 week trial (subjects from NAVIGATOR); 56 week trial (subjects from Partnered SOURCE)
Global trial – ~ 20 countries Other Phase III Severe asthma 216 • Arm 1: tezepelumab s.c. via autoinjector (AI) Primary endpoint: Proportion of health care • FPCD: Q2 2019 PATH-HOME Age 12-80 years • Arm 2: tezepelumab s.c. via accessorized pre-filled syringe professionals and • LPCD: Q3 2019 (APFS) patients /caregivers who successfully • Data anticipated: H2 2020 NCT03968978 administrated tezepelumab in clinic and 24 week trial Partnered Global trial – 4 countries at home with an APFS or an AI, respectively
70 Approved medicines Late-stage development Tezepelumab (TSLP mAb) Early development Severe, uncontrolled asthma Oncology
Trial Population Patients Design Endpoints Status
Phase II Severe asthma 116 • Arm 1: tezepelumab s.c. • Primary endpoint: number of airway • FPCD: Q4 2018 CASCADE Age 18-75 years • Arm 2: placebo s.c. submucosal inflammatory cells/mm2 of • LPCD: Q4 2019 28 week trial bronchoscopic biopsies CVRM NCT03688074 Global trial – five countries Partnered Phase III Severe asthma 396 • Arm 1: tezepelumab s.c. • Primary endpoint: Annual asthma • FPCD: Q3 2019 DIRECTION Age 18-80 years • Arm 2: placebo s.c. exacerbation rate • Secondary endpoints: Change from NCT03927157 52 week trial baseline in pre-BD FEV1, asthma related QoL (AQLQ(S)+12), asthma control
Partnered Regional Asia trial – three countries (ACQ-6) R&I
Phase III Severe asthma 66 Arm 1: tezepelumab s.c. • Primary endpoint: Number of patients • FPCD: Q2 2019 NOZOMI 12-80 years 52 week trial with adverse events • LPCD: Q4 2019 Local trial - Japan NCT04048343
Partnered
Phase IIa Moderate to very severe 282 • Arm 1: tezepelumab s.c. • Primary endpoint: Rate of moderate or • FPCD Q3 2019 COURSE COPD • Arm 2: placebo s.c. severe COPD exacerbations • Data anticipated: 2021+ Age 40-80 Other NCT04039113 52 week trial
Partnered Global trial – 10 countries
71 Approved medicines Late-stage development PT027 (SABA/ICS, pMDI) Early development Asthma Oncology
Trial Population Patients Design Endpoints Status
Phase III Moderate to severe asthma 3,100 Treatments (minimum 24-week treatment period) Primary endpoint: • FPCD: Q4 2018 MANDALA • BDA (budesonide albuterol) MDI 80/180 μg prn • Time to first severe asthma exacerbation • Data anticipated: H2 2021 • BDA MDI 160/180 μg prn NCT03769090 • AS (albuterol sulphate) MDI 180 μg prn Secondary endpoints: CVRM • Severe exacerbation rate (annualised) Managed by Avillion Randomised, double-blind, multi-centre, parallel group • Total corticosteroid exposure over the treatment period Multi-country • Asthma Control Questionnaire -5 change from baseline and responder analysis at Week 24 • Asthma quality of life questionnaire for 12 years and older/paediatric asthma quality of life questionnaire change from baseline R&I and responder analysis at week 24
Phase III Mild to moderate asthma 600 Treatments (12 week treatment period) Dual primary endpoints: • FPCD: Q2 2019 DENALI • BDA MDI 80/180 μg QID • Change from baseline in FEV1 AUC0-6 • Data anticipated: H2 2021 • BDA MDI 160/180 μg QID hours over 12 weeks NCT03847896 • BD MDI 160 μg QID • Change from baseline in trough FEV1 at • AS MDI 180 μg QID week 12 Managed by Avillion • placebo MDI QID
Randomised, double-blind, multi-centre and parallel-group Other
Multi-country
Phase III Asthma with exercise induced 60 Treatments (single dose) Primary endpoint: • FPCD Q1 2019 TYREE bronchoconstriction • BDA MDI 160/180 μg • The maximum percentage fall from • FPCD: Q1 2020 • placebo MDI QID post-dose, pre-exercise baseline in • Data anticipated: H2 2020 NCT04234464 forced expiratory volume in 1 second Randomised, double-blind, multi-centre crossover (FEV1) observed up to 60 minutes post- Managed by Avillion exercise challenge Country: US
72 Approved medicines Late-stage development Anifrolumab (type I interferon receptor mAb) Early development Lupus (SLE / LN) Oncology
Trial Population Patients Design Endpoints Status
Phase III Moderate to severe SLE 450 • Arm 1: 300mg i.v. anifrolumab Q4W for 48 weeks • Primary endpoint: response in SLE • FPCD: Q4 2015 TULIP SLE 1 • Arm 2: 150mg i.v. anifrolumab Q4W for 48 weeks responder index at week 52 • LPCD: Q4 2017 • Arm 3: placebo i.v. Q4W for 48 weeks • Data readout: Q3 2018 • Primary endpoint not met
NCT02446912 CVRM
Phase III Moderate to severe SLE 360 • Arm 1: 300mg i.v. anifrolumab Q4W for 48 weeks • Primary endpoint: response in SLE • FPCD: Q4 2015 TULIP SLE 2 • Arm 2: placebo i.v. Q4W for 48 weeks responder index at week 52 • LPCD: Q4 2017 BICLA at week 52 • Data readout: Q3 2019 NCT02446899 • Primary endpoint met
Phase III Moderate to severe SLE 630 • Arm 1: 300mg i.v. anifrolumab Q4W for 152 weeks • Primary endpoint: extension to evaluate • FPCD: Q2 2016 TULIP LTE • Arm 2: placebo i.v. Q4W for 152 weeks long-term safety and tolerability • LPCD: Q4 2018 • Data anticipated: 2021+ NCT02794285 R&I
Phase ll Moderate to severe SLE 307 • Arm 1: 300mg i.v. anifrolumab Q4W for 48 weeks • Primary endpoint: response in SLE • FPCD: Q1 2012 patients • Arm 2: 1000mg i.v. anifrolumab Q4W for 48 weeks responder index at 6 months • LPCD: Q1 2015 NCT01438489 • Arm 3: placebo i.v. Q4W for 48 weeks • Data readout: Q3 2014
Phase II Moderate to severe SLE 218 • Arm 1: anifrolumab, i.v. Q4W for 104 weeks • Primary endpoint: open-label extension • FPCD: Q1 2013 patients to evaluate long-term safety and • Data readout: Q4 2018 NCT01753193 tolerability
Phase II Moderate to severe SLE 32 • Arm 1: 150mg s.c. every other week • PK/PD, safety, tolerability, primary • FPCD: Q1 2017
patients • Arm 2: 300mg s.c. every other week analysis at week 12, secondary analysis • LPCD: Q4 2017 Other NCT02962960 • Arm 3: placebo s.c. every other week at week 52 • Data readout: Q1 2018
Phase II Active Proliferative LN 150 • Arm 1: 900 mg i.v. Q4W for 12 weeks then 300mg i.v. • Response in proteinuria at week 52 • FPCD: Q4 2015 TULIP-LN1 anifrolumab Q4W for 36 weeks • LPCD: Q4 2018 • Arm 2: 300 mg i.v. anifrolumab Q4W for 48 weeks • Data anticipated: H1 2021 NCT02547922 • Arm 3: placebo i.v. Q4W for 48 weeks
73 Approved medicines Late-stage development Brazikumab (IL-23 inhibitor) Early development Inflammatory Bowel Disease (Crohn’s Disease, Ulcerative Colitis) Oncology
Trial Population Patients Design Endpoints Status
Phase IIb / III Crohn’s Disease 1,140 • Arm 1: brazikumab 1440 mg IV induction + 240 mg SC Primary • FPCD: Q4 2018 INTREPID maintenance every 4 weeks • Endoscopic response and clinical • Data anticipated: 2021+ • Arm 2: brazikumab 720 mg IV induction + 240 mg SC remission at week 12 NCT03759288 maintenance every 4 weeks Secondary CVRM • Arm 3: adalimumab 160 mg SC on day 1 and 40 mg • Endoscope response and clinical maintenance every 2 weeks remission at both weeks 12 and 52 • Arm 4: placebo • Endoscopic remission and clinical remission at week 52
Phase III Crohn’s Disease 1,000 • Open label extension • Safety of long-term treatment with • FPCD: Q1 2020 brazikumab • Data anticipated: 2021+
NCT03961815 R&I Phase II Ulcerative Colitis 375 • Arm 1: brazikumab 2100 mg IV on days 1, 15, 43 + 210 or 105 Primary • FPCD: Q3 2018 EXPEDITION mg SC maintenance every 4 weeks • Clinical remission at week 10 • Data anticipated: 2021+ • Arm 2: brazikumab 1440 mg IV on days 1, 15, 43 + 210 or 105 Secondary NCT03616821 mg SC maintenance every 4 weeks • Sustained clinical remission at week 54 • Arm 3: brazikumab 720 mg IV on days 1, 15, 43 + 210 or 105 mg SC maintenance every 4 weeks • Arm 4: vedolizumab 300 mg IV on days 1, 15, 43, 99 and every 9 weeksmaintenance every 2 weeks • Arm 5: placebo
Phase II Ulcerative Colitis 300 • Open label extension • Clinically significant adverse events • FPCD: Q1 2020 • Data anticipated: 2021+ Other NCT04277546
74 Approved medicines Late-stage development Nirsevimab (MEDI8897, Respiratory syncytial virus mAb-YTE ) Early development Infection Oncology
Trial Population Patients Design Endpoints Status
Phase IIb 29-35 WK GA (Gestational 1,453 • Randomised, double-blind, placebo-controlled trial • Safety and efficacy • FPCD: Q4 2016 age) infants • Route of administration: intramuscular • LPCD: Q4 2017 NCT02878330 • Data readout: Q4 2018
• Primary endpoint met CVRM
Phase II/III High risk preterm (born 35 1,500 • Randomized, Double-blind, Palivizumab-controlled • Primary: Safety and tolerability • FPCD: Q3 2019 weeks 0 day or less GA), CHD • Route of administration: intramuscular • Secondary: PK, ADA and descriptive • Data readout: 2021+ MEDLEY and CLD infants eligible to • Global trial – 32 countries efficacy receive palivizumab NCT03959488
Phase III Healthy infants (born 35 3,000 • Randomized, Double-blind, Placebo-controlled • Primary: Efficacy • FPCD: Q3 2019 weeks 0 days or greater GA) • Route of administration: intramuscular • Secondary: Safety, PK, ADA • Data readout: 2021+
MELODY • Global trial – 31 countries R&I
NCT03979313 Other
75 Approved medicines Late-stage development AZD1222 (SARS-CoV-02) Early development Prevention of COVID-19 Oncology
Trial Population Patients Design Endpoints Status
Phase I/II Healthy adults 1,077 Single-blinded, randomised, controlled, multi-centre trial • Primary endpoint: efficacy and safety • FPCD: Q2 2020 COV001 (UK) Age 18-55 years • AZD1222 • Secondary endpoints: safety, • LPCD: Q2 2020 • Control vaccine: MenACWY tolerability, reactogenicity, and CVRM UK immunogenicity NCT04324606
Partnered
Phase I/II Healthy adults 2,200 Adaptive, double-blinded, randomised placebo-controlled trial • Primary endpoint: efficacy, safety, and • FPCD: Q2 2020 Age 18-65 years • AZD1222 immunogenicity NCT04444674 • Placebo
HIV+ subgroup R&I Partnered South Africa
Phase II/III Main efficacy trial: healthy 10,260 Single-blinded, randomised, controlled, multi-centre trial with • Primary endpoint: efficacy and safety • FPCD: Q2 2020 COV002 (UK) adults aged ≥18 years sequential age escalation/de-escalation immunogenicity sub- • Secondary endpoints: safety, studies that include prime boost tolerability, reactogenicity, and NCT04400838 Sub-studies: • AZD1222 immunogenicity Healthy adults 56 - <70 years • Control vaccine: MenACWY Partnered Healthy adults 70 years Healthy children 5 – 12 years UK
Phase III Healthy adults 30,000 Adaptive, double-blinded, randomised placebo-controlled trial • Initiating • Initiating D8110C00001 (US) Age 18-65 years • AZD1222 Other • Placebo
Phase III Health professionals and 5,000 Single-blinded, randomised, controlled multi-centre trial • Primary endpoint: efficacy • FPCD: Q2 2020
COV003 adults with high potential for • AZD1222 • Secondary endpoints: safety, 19 - exposure to SARS-CoV-2 • Control vaccine: MenACWY tolerability, reactogenicity, and NCT# pending Age 18-55 years immunogenicity Brazil
Partnered COVID
76 Approved medicines Late-stage development COVID-19 trials Early development Prevention of COVID-19 Oncology
Trial Compound Population Patients Design Endpoints Status
Phase IIb Calquence COVID-19 60 • Arm 1: Calquence + best supportive care • Primary outcomes: safety, subject alive • FPCD: Q2 2020 CALAVI- US • Arm 2: best supportive care alone and free of respiratory failure at Day 28 • Data anticipated: H2 2020
NCT04380688 CVRM
Phase IIb Calquence COVID-19 140 • Arm 1: Calquence + best supportive care • Primary outcome: subject alive and free • FPCD: Pending CALAVI- RoW • Arm 2: best supportive care alone of respiratory failure at Day 14 • Data anticipated: H2 2020
NCT04346199
Phase II Farxiga COVID-19 900 • Current SoC or current SoC + Farxiga • Primary outcome measures: time to first • Data anticipated H2 2020 DARE-19 occurrence of either death from any cause or new/worsened organ
NCT04350593 dysfunction through 30 days of follow up R&I
Phase II Farxiga COVID-19 1,407 • Current SoC or current SoC + Farxiga + ambrisentan • Primary Outcome Measures: time to • Data anticipated H2 2020 TACTIC-E incidence of the composite endpoint of: death, mechanical ventilation, NCT04393246 extracorporeal membrane oxygenation, cardiovascular organ support, or renal failure
Phase IiIa Pulmicort COVID-19 300 • Current SoC or SoC + Pulmicort • Primary outcome measures: proportion • Data anticipated H2 2020 TACTIC-COVID of patients in both arms fulfilling the criteria for treatment failure NCT04355637 Other
Phase IIIa Pulmicort COVID-19 478 • Current SoC or SoC + Pulmicort • Primary Outcome Measures: emergency • Data anticipated H2 2020 STOIC department attendance of hospitalisation related to COVID-19 NCT04416399
Phase IIIa Symbicort COVID-19 436 • Current SoC or SoC + Symbicort • Primary Outcome Measures: time (in • Data anticipated H2 2020 19 INHASCO days) to clinical improvement within 30 - days after randomisation NCT04331054
Phase II MEDI3506 COVID-19 180 • Current SoC or current SoC + MEDI3506 • Primary endpoints: time to a 2-point • Data anticipated H2 2020 ACCORD improvement on a 9-point category COVID ordinal scale, discharge from hospital, or considered fit for discharge whichever comes first by Day 29
Phase I AZD7442 COVID-19 48 • Placebo or MEDI7442 • Primary endpoints: Safety, tolerability of • Data anticipated 2021 AZD7442 77 BioPharmaceuticals - early-stage development Approved medicines Late-stage development Cotadutide (MEDI0382, GLP-1-glucagon agonist) Early development Diabetes/obesity Oncology
Trial Population Patients Design Endpoints Status
Phase II Adults with type-2 65 • Arm1: cotadutide s.c. or placebo • Primary: efficacy MMT glucose AUC, body weight loss • FPCD: Q3 2017 diabetes • Arm2: cotadutide s.c. or placebo • Secondary: efficacy HbA1c, fasting plasma glucose • LPCD: Q4 2017 NCT03244800 • Germany • Secondary: safety profile in terms of adverse events, heart rate, blood • Data readout: Q1 2018
pressure, vital signs, ECG, lab variables CVRM
Phase II Overweight and 834 • Arm1: cotadutide low dose s.c. + metformin • Primary: efficacy HbA1c, body weight loss • FPCD: Q3 2017 Obese patients with • Arm2: cotadutide mid dose s.c. + metformin • Secondary: percentage of patients achieving weight loss of ≥5% and • LPCD: Q1 2018 NCT03235050 type-2 diabetes • Arm3: cotadutide high dose s.c. + metformin ≥10% • Data readout Q3 2019 • Arm4: placebo s.c. + metformin • Secondary: proportion of patients rescued or discontinued for lack of • Arm5: liraglutide s.c. + metformin glycaemic control • Secondary: PK and immunogenicity US, Canada, Bulgaria, Czech Rep, Germany,
Mexico, Russia, Slovakia R&I
Phase II Overweight/obese 49 • Arm1: cotadutide + dapagliflozin • Primary: efficacy MMT glucose AUC • FPCD: Q3 2018 NCT03444584 patients with type-2 • Arm2: placebo + dapagliflozin • Secondary: safety • LPCD: Q4 2018 diabetes • Germany, Hungary • Secondary: PK • Data readout: Q1 2019 • Secondary: immunogenicity
Phase II Adults with type-2 41 • Cotadutide or placebo s.c. • Primary: efficacy MMT glucose AUC • FPCD Q2 2018
NCT03550378 diabetes and renal • Germany, UK • Secondary: safety • LPCD; Q4 2018 Other impairment • Secondary: tolerability • Data readout: Q1 2019 • Secondary: PK • Secondary: immunogenicity
Phase II Adults with type-2 44 • Part A: cotadutide or placebo s.c. • Primary: change in hepatic glycogen concentration postprandially, • FPCD: Q2 2018 NCT03555994 diabetes • Part B: cotadutide s.c. or placebo s.c. or adjusted by liver volume • Part A LPCD: Q4 2018 liraglutide s.c. • Secondary: safety • Data readout: Q1 2019 • Sweden • Secondary: tolerability • Part B FPCD: Q1 2020 • Secondary: immunogenicity • LPCD: H2 2020
79 Approved medicines Late-stage development Cotadutide (MEDI0382, GLP-1-glucagon agonist) Early development Diabetes/obesity, NASH Oncology
Trial Population Patients Design Endpoints Status
Phase II Overweight and 27 • Cotadutide or placebo s.c. • Primary: efficacy body weight loss • FPCD: Q4 2018 NCT03596177 obese patients with • UK • Secondary: change in total energy intake • LPCD: Q4 2019 type-2 diabetes • Secondary: change in total energy expenditure, active energy • Data anticipated: H2 2020
expenditure, resting energy expenditure CVRM • Secondary: safety
Phase I Non-diabetic obese 51 • Cotadutide or placebo s.c. with 7 week, 10 • Primary: safety, tolerability • FPCD: Q3 2018 NCT03625778 patients week or 16 week titration period • Secondary: PK • LPCD: Q2 2019 • Secondary: immunogenicity • Data readout Q3 2019 • US
Phase II Overweight and 20 • Cotadutide or placebo s.c. • Primary: safety, tolerability • FPCD: Q1 2019 NCT03745937 obese patients with • Germany • Secondary: PK • LPCD: Q2 2019
type-2 diabetes • Secondary: immunogenicity • Data readout: Q3 2019 R&I • Secondary: glucose control
Phase II Japanese preobese 61 • MAD s.c. administration • Primary: safety, glucose AUC, body weight • FPCD: Q3 2018 NCT03645421 or obese patients with • Japan • Secondary: HbA1c, FPG, fructosamine • LPCD: Q3 2018 type-2 diabetes • Secondary: glucose control • Data readout: Q2 2019 • Secondary: PK, immunogenicity
Phase II Obese patients with 72 • Arm1: cotadutide high dose s.c. • Primary: safety and tolerability • FPCD: Q4 2019 NCT04019561 non-alcoholic fatty • Arm2: placebo high dose s.c. • Secondary: change in hepatic fat fraction, • LPCD: H2 2020 liver disease • Arm3: cotadutide low dose s.c. • Secondary: change in liver fat volume
(NAFLD)/non- • Arm4: placebo low dose s.c. • Secondary: change in visceral adipose tissue Other alcoholic • US steatohepatitis (NASH)
Phase I Healthy adult patients 36 • Primary: to evaluate exposure following a single s.c of cotadutide at • FPCD: Q4 2019 NCT04091373 each of 3 different sites of injection • LPCD: Q1 2020 • Secondary: immunogenicity • Data readout: H2 2020 • Secondary: safety and tolerability
80 Approved medicines Late-stage development Verinurad (RDEA3170, URAT1 inhibitor) Early development CKD Oncology
Trial Population Patients Design Endpoints Status
Phase II CKD patients with 60 • Arm A: verinurad 9 mg and febuxostat 80 mg To assess the effects of intensive uric acid • FPCD: Q2 2017 hyperuricaemia, • Arm B: placebo lowering therapy with RDEA3170 and • LPCD: Q3 2018 NCT03118739 albuminuria, and Type 2 The trial is a multi-centre trial conducted in the US febuxostat on UACR • Data readout: Q4 2018
diabetes CVRM
Phase II Asymptomatic hyperuricaemic 36 • Arm A: 9 mg verinurad + 80 mg febuxostat + 10 mg Primary: Peak uric acid excretion during • FPCD: Q4 2017 patients (sUA (serum uric acid dapagliflozin the first 8 hours) on Day 7 of treatment • LPCD: Q3 2018 levels) > 6.0 mg/dL) • Arm B: 9 mg verinurad + 80 mg febuxostat + placebo Secondary: serum uric acid levels after 7 • Data readout: Q4 2019 NCT03316131 The trial is a two-centre trial conducted in the US days of treatment.
Phase II Healthy volunteers 25 • Verinurad ER8 capsule formulation (fasted) Relative bioavailability (AUC, Cmax) • FPCD: Q3 2019 • Verinurad capsule A formulation (fasted) between the ER8 capsule formulation given • LPCD: Q3 2019 NCT04024501 • Verinurad capsule A formulation (fed) under fasted conditions and 2 new capsule • Data readout: Q4 2019 R&I • Verinurad capsule B formulation (fasted) formulation of verinurad (A-capsule and B- • Verinurad capsule B formulation (fed) capsule) given under fed or fasted This trial is a single centre trial conducted in Germany conditions Phase II Healthy volunteers of Asian 23 • Arm A: verinurad 24 mg + allopurinol 300 mg Safety analyses (AEs, ECG abnormalities, • FPCD: Q1 2019 descent • Arm B; verinurad 12 mg + allopurinol 300 mg vital sign abnormalities, laboratory • LPCD: Q2 2019 NCT03836599 • Arm C: Placebo abnormalities) • Data readout: Q4 2019 This trial is a single centre trial conducted in the US PK outcomes (AUC, Cmax, tmax)
Phase II 725 • FPCD: Q3 2019
Patients with: • Arm A; Verinurad 12 mg + allopurinol 300 mg Ratio of urinary albumin to urinary Other • sUA ≥6.0 mg/dL • Arm B Verinurad 7.5 mg + allopurinol 300 mg creatinine • Data anticipated: H2 2021 NCT03990363 • eGFR ≥25 mL/min/1.73 • Arm C; Verinurad 3 mg + allopurinol 300 mg Changes in eGFR, Cystatin C, and uric acid m2 Chronic Kidney • Arm D; Verinurad placebo + allopurinol 300 mg Disease Epidemiology • Arm E; Verinurad placebo + allopurinol placebo Collaboration (CKD-EPI formula) This trial is multi-centre trial conducted in USA, China, Czech • Mean UACR between 30 Republic, France, Hungary, Israel, Italy, Mexico, Poland, mg/g and 5000 mg/g Romania, Slovakia, South Africa, Spain
Phase I Healthy volunteers 24 • Treatment A: Verinurad 24 mg ER8 formulation + 300 mg To assess the effect of a single dose of • FPCD: Q3 2020 • allopurinol verinurad given as either a 24 mg • Data readout: H2 2020 NCT03118739 • Treatment B: Verinurad 40 mg IR formulation + 300 mg extended-release (ER8) formulation • allopurinol (therapeutic exposure) or a 40 mg • Treatment C: Matched placebos for both verinurad and immediate-release (IR) formulation (supra- allopurinol therapeutic exposure), both in combination The trial is a single-centre, randomised, placebo-controlled, with allopurinol 300 mg, on the QT interval double-blind, 3-period, cross-over trial conducted in Germany corrected for heart rate using Fridericia’s 81 formula (QTcF) compared to placebo Approved medicines Late-stage development Verinurad (RDEA3170, URAT1 inhibitor) Early development HFpEF Oncology
Trial Population Patients Design Endpoints Status
Phase II Patients with heart failure with 435 • Arm A: verinurad 12 mg + allopurinol 300 mg Peak V02 Change from baseline at Week • FPCD: Q3 2020 preserved ejection fraction • Arm B: verinurad placebo + allopurinol 300 mg 28 in exercise capacity • Data readout: 2021+ NCT04327024 • Arm C: verinurad placebo + allopurinol placebo Change from baseline at Week 28 in The trial is a multi-centre trial conducted in Argentina, Australia, Kansas-City Cardiomyopathy CVRM Austria, Bulgaria, Canada, Germany, Mexico, Poland, Russia, Questionnaire-Total Symptom Score Slovakia South Korea, USA
(KCCQ-TSS)
R&I Other
82 Approved medicines Late-stage development AZD2373 Early development Chronic Kidney Disease Oncology
Trial Population Patients Design Endpoints Status
Phase I Healthy volunteers 48 SAD Primary: • FPCD: Q1 2020 • Safety and tolerability NCT04269031 Dose escalation in 6 cohorts with 6 volunteers receiving
AZD2373 and 2 volunteers receiving placebo in each cohort Secondary; CVRM • PK parameters
Trial conducted in the US
R&I Other
83 Approved medicines Late-stage development AZD2693 (resolution of NASH) Early development NASH Oncology
Trial Population Patients Design Endpoints Status
Phase I Healthy volunteers 48 SAD Primary: • FPCD: Q4 2019 • Safety and tolerability • Data anticipated: H2 2020 NCT04142424 6 cohorts with 6 volunteers receiving AZD2693 and 2 volunteers
receiving placebo in each cohort Secondary; CVRM • PK Route of administration: subcutaneous injections
Trial conducted in the US.
R&I Other
84 Approved medicines Late-stage development MEDI3506 (IL33 ligand mAb) Early development Diabetic Kidney Disease (DKD) Oncology
Trial Population Patients Design Endpoints Status
Phase II Adult patients with diabetic 168 Randomized, double-blind, placebo-controlled, multicenter trial to • Efficacy and safety • FPCD: Q4 2019 kidney disease evaluate the efficacy, safety, PK, and immunogenicity of
NCT04170543 MEDI3506 in adult patients with diabetic kidney disease
CVRM
R&I Other
85 Approved medicines Late-stage development AZD4831 (MPO inhibitor) Early development Cardiovascular disease Oncology
Trial Population Patients Design Endpoints Status
Phase I Healthy patients c. 96 SAD trial (one trial site in Germany) • Safety and tolerability • FPCD: Q3 2016 • Planned to investigate 6 different dose levels vs. placebo but • PK parameters • LPCD: Q4 2016
NCT02712372 up to 10 cohort may be used • Data readout Q2 2017 CVRM
Phase I Healthy patients c. 40 MAD (one trial site in USA) • Safety and tolerability • FPCD: Q2 2017 • The planned number of cohorts is four but up to five cohorts • PK parameters • LPCD: Q4 2017 NCT03136991 may be included • Data readout: Q1 2018
Phase IIa HFpEF 96 Arm 1: AZD4831 • Primary endpoint: The change from • FPCD: Q4 2018 Arm 2: placebo baseline in MPO activity in % after • Data readout: H2 2020 NCT03756285 AZD4831 treatment R&I Global trial – five countries
Phase I Healthy patients 40 SAD trial in Japanese and Chinese patients • Safety and tolerability • FPCD Q1 2020
NCT04232345 Other
86 Approved medicines Late-stage development AZD5718 (FLAP inhibitor) Early development Cardiovascular disease Oncology
Trial Population Patients Design Endpoints Status
Phase IIa CAD 129 • Arm 1: AZD5718 Dose A • Primary endpoint: PD effect of AZD5718 • FPCD: Q4 2017 • Arm 2: AZD5718 Dose B by assessment of u-LTE4 • LPCD: Q4 2019
NCT03317002 • Arm 3: placebo CVRM Global trial – three countries in Europe
Phase I Healthy patients 6 hADME trial (one trial site in UK) • Mass balance, with routes and rates of • FPCD: Q2 2019 • Oral administration elimination of [14C]AZD5718. • LPCD: Q2 2019 NCT03948451 Open-label trial to characterize the absorption, distribution, • Metabolite profiling and structural metabolism and excretion following a single oral dose of identification [14C]AZD5718 in healthy male volunteers • PK and total radioactivity
Phase I Healthy patients 14 BA trial (one trial site in UK) • To evaluate the pharmacokinetics and • FPCD: Q4 2019 R&I An open-label, randomized, 3-period, 3-treatment, crossover trial exposure of 3 different doses • LPCD: Q4 2019 NCT04087187 to assess the drug absorption into the blood after administration of AZD5718 of 3 doses of AZD5718 • Safety and tolerability
Phase I Healthy patients 12 BA trial (one trial site in UK) To evaluate: • FPCD: Q1 2020 NCT04210388 The trial is a randomized, single-dose, open-label, combined 2x2 • The relative bioavailability of different • LPCD: Q1 2020 dose and 3x3 dose crossover design in fixed sequence. formulations
• Safety and tolerability Other
87 Approved medicines Late-stage development AZD6615 (anti-hypercholesterolemia) Early development Hypercholesterolemia Oncology
Trial Population Patients Design Endpoints Status
Phase I Healthy volunteers 40 SAD Primary: • FPCD: Q3 2019 • Safety and tolerability NCT04055168 3 cohorts of non-Asian subjects (Part 1) and 2 cohorts of
Japanese subjects (Part 2). 6 subjects receiving AZD6615 and Secondary; CVRM 2 subjects receiving placebo in each cohort. • PK and PD parameters
Trial conducted in the US.
R&I Other
88 Approved medicines Late-stage development AZD8233 (anti-hypercholesterolemia) Early development Hypercholesterolemia Oncology
Trial Population Patients Design Endpoints Status
Phase I Healthy subjects 72 SAD Primary: • FPCD: Q3 2018 • Safety and tolerability NCT03593785 7 cohorts with 6 subjects receiving AZD8233 and 2 subjects
receiving placebo in each cohort Secondary; CVRM • PK and PD parameters Trial conducted in the US.
Phase I Dyslipidemia 33 MAD Primary: • FPCD Q1 2020 • Safety and tolerability NCT04155645 Up to 3 cohorts with 8 subjects receiving AZD8233 and 3 subjects receiving placebo in each cohort Secondary; • PK and PD parameters
Trial conducted in the US
R&I Other
89 Approved medicines Late-stage development AZD8601 (VEGF-A modified RNA) Early development Cardiovascular disease Oncology
Trial Population Patients Design Endpoints Status
Phase I Type 2 diabetic patients c. 60 SAD trial (one trial site in Germany) • Safety and tolerability • FPCD: Q1 2017 • Planned to investigate 3 different dose levels vs. placebo but • LPCD: Q3 2017
NCT02935712 up to 5 cohort may be used • Data readout: Q1 2018 CVRM
Phase IIa HF Up to 33 Phase IIa trial (two trial sites in Finland) • Safety and tolerability • FPCD: Q1 2018 • Arm 1: AZD8601 Dose A NCTT03370887 • Arm 2: AZD 8601 Dose B
• Arm 3: placebo
R&I Other
90 Approved medicines Late-stage development AZD9977 Early development Heart failure Oncology
Trial Population Patients Design Endpoints Status
Phase I Healthy volunteers 27 MAD Primary: • FPCD: Q1 2018 • Safety and tolerability • LPCD: Q2 2018 NCT03435276 Dose escalation in 3 cohorts with 6 subjects receiving AZD9977 • Data readout: Q3 2018
and 3 volunteers receiving placebo in each cohort Secondary; CVRM • PK parameters Trial conducted in the UK.
Phase I Healthy volunteers 12 Bioavailability trial Primary: • FPCD: Q2 2018 • relative bioavailability vs. oral suspension • LPCD: Q2 2018 NCT03450759 Investigation of four different oral formulations of AZD9977 and (reference) • Data readout: Q3 2018 influence of food. • PK parameters
Trial conducted in the UK.
Phase I HF 60 Proof of differentiation Primary: • FPCD Q4 2018 R&I • serum potassium • LPCD Q1 2019 NCT03682497 To compare the effect of AZD9977 with spironolactone on serum potassium
Phase I Healthy volunteers 14 DDI Primary: • FPCD: Q1 2019 • PK parameters • LPCD: Q1 2019 NCT03843060 To assess the effect of itraconazole on the pharmacokinetics of • Data readout: Q3 2019 AZD9977 Secondary; • Safety and tolerability
Trial conducted in the US Other Phase I Healthy volunteers 45 JSMAD Primary: • FPCD: Q1 2019 • Safety and tolerability • LPCD: Q2 2019 NCT03801967 Single and multiple-ascending dose administration in Japanese • Data readout: Q3 2019 healthy volunteers. Secondary; • PK parameters Trial conducted in the UK
Phase I Healthy volunteers 12 Bioavailability trial Primary: • FPCD: Q1 2019 • relative bioavailability vs. capsule • LPCD: Q2 2019 NCT03804645 Investigation of four different oral formulations of AZD9977 and formulation (reference) • Data readout: Q3 2019 influence of food. • PK parameters
Trial conducted in the UK
91 Approved medicines Late-stage development Biologics Early development Cardiovascular & metabolic diseases Oncology
Trial Compound Population Patients Design Endpoints Status
Phase IIb MEDI6012 Subjects 30-80 540 • Cohort A: 2-dose regimen Primary endpoints: Infarct size as a percentage of left ventricle • FPCD: Q2 18 rhLCAT years of age 300 mg of MEDI6012 or placebo on day 1 (LV) mass at 10-12 weeks post-MI (myocardial infarction) • Data anticipated: 2021+ EudraCT 2017- inclusive, (loading dose) prior to pPCI followed by a compared to placebo 004521-32 presenting with second inpatient dose Secondary endpoints: CVRM acute STEMI of 150 mg or placebo on Day 3 by i.v. • Ejection Fraction at 10-12 weeks post-MI compared to placebo. push. • Change in NCPV in the coronary arteries from at10-12 • Cohort B: 6-dose regimen weeks post-MI compared with placebo 300 mg of MEDI6012 or placebo on day 1 • Myocardial mass and LV volumes at end-systole and end- prior to pPCI followed by a second diastole inpatient dose of 150 mg or placebo on day • Incidence of TEAEs and treatment-emergent SAEs. 3 and outpatient maintenance doses of 100 • LCAT mass and ADAs mg or placebo on days 10, 17, 24, and 31 by i.v. push. R&I
Phase IIa MEDI5884 Adults with stable 133 • MEDI5884 (5 dose cohorts) vs. placebo in • Safety profile in terms of AEs, vital signs, ECG, lab variables • FPCD Q4 2017 cholesterol CHD stable CHD patients • Changes in HDL-C over time • Data readout: Q4 2018 NCT03351738 modulation • PK, immunogenicity, and Apolipoprotein B
Phase I MEDI6570 Atherosclerotic 88 • SAD followed by multi ascending dose • Primary endpoints: Safety and tolerability • FPCD: Q4 2018 cardiovascular with 3 monthly doses in T2DM subjects • Data anticipated: 2021
NCT03654313 disease Other
92 Approved medicines Late-stage development AZD0449 (inhaled JAK-1 inhibitor) Early development Asthma Oncology
Trial Population Patients Design Endpoints Status
Phase I Healthy subjects and patients 156 SAD/MAD/Bridge trial (UK) Primary endpoint: • FPCD: Q4 2018 with mild asthma Part 1 SAD • Safety and tolerability NCT03766399 • Dose escalation in 6 cohorts with 6 subjects receiving
AZD0449 and 2 subjects receiving placebo in each cohort Secondary endpoint: CVRM • i.v. cohort with 8 subjects • PK parameters • FENO Part 2 MAD: • 2 cohorts of (6, 6,) mild asthmatics receiving two different doses of AZD0449 and (3,3) patients receiving placebo in each cohort • 1 cohort of 6 patients receiving 1 dose of AZD0449 and 2 patients receiving placebo
Part 3 bridge R&I • 1 cohort of 6 patients receiving 1 dose of AZD0449 (DPI formulation) and 2 patients receiving placebo. • Up to 18 mild asthmatic patients will receive AZD0449 (DPI) and 18 patients receiving placebo. Interim analysis planned after 9 +9 patients.
Trial conducted in the UK Other
93 Approved medicines Late-stage development AZD1402 (IL4 receptor antagonist) Early development Asthma Oncology
Trial Population Patients Design Endpoints Status
Phase Ib Patients with mild asthma 75 PoM. Primary endpoint: • FPCD: Q3 2018 A dose-escalating, single blind trial to assess the • Safety and tolerability NCT03574805 safety, tolerability, and pharmacokinetics of multiple
doses of PRS-060 administered by oral Inhalation In Secondary endpoint: CVRM Partnered subjects with mild asthma • PK parameters • Potential immunogenicity • Change in FENO
Australia
R&I Other
94 Approved medicines Late-stage development MEDI3506 (IL33 ligand mAb) Early development COPD, atopic dermatitis Oncology
Trial Population Patients Design Endpoints Status
Phase I (Combined SAD / SAD: healthy subjects with SAD: 56 SAD: • Safety and tolerability • FPCD: Q2 2017 MAD) mild atopy • 7 sequential placebo-controlled single dose cohorts by either • LPCD: Q2 2019 SC or IV route (active N=6 / placebo N = 2 within each • Data anticipated: H2 2020
NCT03096795 cohort) CVRM
J-SD: healthy Japanese J-SD: 8 subjects J-SD: • single placebo-controlled single dose cohort by IV route (active N=6 / placebo N = 2 within cohort) MAD: GOLD I-II COPD MAD: 24 MAD: • 3 sequential placebo-controlled multiple dosing cohorts by SC
route (active N=6 / placebo N = 2 within each cohort) R&I
Conducted in UK
Phase II Adult subjects with atopic 152 Randomised, blinded, placebo-controlled trial to determine the • Primary: change from baseline at week • FPCD: Q4 2019 dermatitis efficacy and safety of different strengths of MEDI3506 by SC 16 in Eczema Area and Severity Index NCT04212169 route (EASI) score • Secondary: safety and other efficacy measures
Conducted in US, Australia, Germany, Poland & UK Other
95 Approved medicines Late-stage development Velsecorat (AZD7594, SGRM, inhaled) Early development Asthma Oncology
Trial Population Patients Design Endpoints Status
Phase I Adolescent asthma patients 24 An open-label, multi-centre, Phase I trial to assess the PK, PD Primary endpoint: • FPCD: Q3 2019 and safety of 2-week treatment with inhaled velsecorat in • PK, safety and tolerability following 2 • Data readout: H2 2020
NCT03976869 adolescents (12 to 17 years) with asthma weeks treatment with velsecorat CVRM Secondary endpoints • Changes from baseline in lung function, asthma control and plasma cortisol on
day 15
R&I Other
96 Approved medicines Late-stage development AZD7986 (DPP1) Early development COPD Oncology
Trial Population Patients Design Endpoints Status
Phase I Healthy volunteers 15 This is a phase I, non-randomised, fixed sequence, 3-period, • Safety and tolerability • FPCD: Q1 2016 drug-drug interaction trial to assess the PK of AZD7986 in healthy • PK/PD and DDI • Data readout: Q2 2016 NCT02653872 subjects when administered alone and in combination with
multiple doses of verapamil and itraconazole or diltiazem CVRM
• Arm 1: AZD7986 (alone) treatment period 1 • Arm 2: verapamil (with AZD7986) treatment period 2 • Arm 3: itraconazole (with AZD7986) treatment Period 3 • Arm 4: diltiazem (with AZD7986) treatment period 3
Phase I Healthy volunteers 89 A phase I, randomised, single-blind, placebo-controlled, 2-part • Safety and tolerability • FPCD: Q4 2014 R&I trial to assess the safety, tolerability, PK and food effect of single • PK/PD • Data readout: Q3 2016 NCT02303574 and multiple oral doses of AZD7986 in healthy volunteers. • Bioavailability
• Arm 1: AZD7986, single and multiple oral doses
• Arm 2: placebo, single and multiple doses Other
97 Approved medicines Late-stage development AZD8154 (PI3Kδ inhibitor) Early development Asthma Oncology
Trial Population Patients Design Endpoints Status
Phase I Healthy subjects 78 SAD/MAD Primary endpoint: • FPCD: Q3 2018 A Phase I trial to assess the safety, tolerability and PK of • Safety and tolerability • LPCD: Q3 2019 NCT03436316 AZD8154 following single dose administration and multiple dose • Data readout: Q4 2019
administration in healthy subjects Secondary endpoint: CVRM
• PK parameters
R&I Other
98 Approved medicines Late-stage development AZD8871 (MABA, inhaled) Early development Respiratory Oncology
Trial Population Patients Design Endpoints Status
Phase IIa Patients with COPD 73 Randomised, double-blind, placebo and active-controlled Primary endpoint: • FPCD: Q4 2018 crossover trial. Eligible patients will be randomised in 1:1:1:1:1:1 • Change from baseline in trough FEV1 on • LPCD: Q2 2019 NCT03645434 ratio to 1 of 6 treatment sequences and will receive 1 of the day 15 • Data anticipated: Q3 2019
following 3 treatments sequence in the form of dry powder Secondary endpoints: CVRM • To characterize the pharmacokinetics of inhalation: AZD8871 following multiple inhaled • AZD8871 600 µg once daily doses • Anoro® Ellipta® (55 µg umeclidinium [UMEC]/ 22 µg • To assess safety and tolerability of vilanterol [VI]) once daily AZD8871
• Placebo
R&I Other
99 Approved medicines Late-stage development AZD9567 (SGRM, oral) Early development Respiratory Oncology
Trial Population Patients Design Endpoints Status
Phase I Healthy subjects 71 MAD trial with a total of 6 dose levels of AZD9567: 10 mg, 20mg, Primary endpoint: • FPCD: Q2 2016 40mg, 80mg and 125 mg as well as with 3 dose levels of • To assess the safety and tolerability of • Data readout: Q2 2018 NCT02760316 prednisolone: 5 mg, 20 mg and 40 mg AZD9567 following multiple oral
ascending doses in subjects with BMI CVRM between 28 and 38 kg/m2 and with a positive glucose tolerance test (7,8 to 11,0 mmol/L) Secondary endpoints: • To characterise the pharmacokinetics of AZD9567 following multiple oral administration of ascending doses • To characterise the pharmacodynamics of AZD9567 assessed as effect on
glucose homeostasis through OGTT (oral R&I glucose tolerance test) in comparison with prednisolone
Phase IIa Patients with active RA 21 A randomised, double-blind, parallel trial to assess the efficacy, Primary endpoint: • FPCD: Q1 2018 NCT03368235 safety and tolerability of AZD9567 compared to prednisolone 20 To assess the efficacy of AZD9567, 40 mg, • Data readout: Q2 2020 mg in patients with active rheumatoid arthritis compared to prednisolone 20 mg in patients with active RA in spite of stable treatment with conventional and/or s.c./i.v. biological DMARDs (Disease-modifying antirheumatic drugs)
Secondary endpoints: Other • To further assess the efficacy of AZD9567, 40 mg, compared to prednisolone 20 mg in patients with active rheumatoid arthritis in spite of stable treatment with conventional and/or s.c./i.v. biological DMARDs • (e g SJC 66/TJC68, ACR response criteria) • To evaluate the pharmacokinetic profile of AZD9567
100 Approved medicines Late-stage development AZD0284 (RORγ inverse agonist) Early development Plaque psoriasis vulgaris Oncology
Trial Population Patients Design Endpoints Status
Phase I Healthy subjects 80 Part 1 (SAD) • Safety and tolerability and PK following • FPCD: Q3 2016 • Seven different dose levels investigated vs. placebo oral administration with single ascending • LPCD: Q2 2017 NCT02976831 • Oral administration dose
• Preliminary assessment of the effect of CVRM food on the single dose PK parameters of AZD0284
Part 2 (MAD) • Safety and tolerability & PK in healthy • FPCD: Q1 2017 • Three different dose levels investigated vs. placebo in healthy subjects following administration of • LPCD: Q1 2017 subjects multiple ascending oral doses • Oral administration • PoM confirmed by demonstrating that oral dosing of AZD0284 reduces IL-17 secretion by ex vivo stimulated whole
blood T cells R&I
Phase I Healthy subjects 6 A single centre, open-label, non-randomised, single dose trial • Determination of absolute bioavailability • FPCD: Q1 2017 performed in 6 healthy male subjects aged 18 to 65 years, of AZD0284 • LPCD: Q1 2017 NCT03029741 inclusive. The trial will assess the absolute bioavailability of a • Safety and tolerability of AZD0284 single oral dose of AZD0284 and the pharmacokinetics (PK) of a single intravenous (IV) microdose of [14C] AZD0284 in healthy male and female subjects. Oral AZD0284 and [14C] AZD0284 intravenous solution are referred to as the investigational
products in this trial Other
101 Approved medicines Late-stage development MEDI0618 (PAR2 antagonist mAb) Early development Osteoarthritis pain Oncology
Trial Population Patients Design Endpoints Status
Phase I Painful osteoarthritis of the knee 64 (healthy • SAD • Safety, tolerability and PK • FPCD: Q4 2019 volunteers) • Up to 8 i.v. cohorts are planned vs. placebo
NCT02508155 • 1 s.c. cohortis planned vs. placebo CVRM
Europe only
R&I Other
102 Approved medicines Late-stage development MEDI1341 (alpha-synuclein mAb) Early development Parkinson’s Disease Oncology
Trial Population Patients Design Endpoints Status
Phase I Healthy volunteers 48 • SAD • Safety, tolerability, PK, PD • FPCD: Q4 2017 • Up to 6 i.v. cohorts are planned vs. placebo • Data anticipated: H1 2021 NCT03272165
US only CVRM
R&I Other
103 Approved medicines Late-stage development AZD4041 (orexin 1 receptor antagonist) Early development Opioid use disorder Oncology
Trial Population Patients Design Endpoints Status
Phase I Healthy volunteers 48 healthy • Randomised, double blind, single ascending dose • Safety, tolerability, PK, PD • FPCD: Q4 2019 volunteers • Up to 6 cohorts are planned vs. placebo • Data anticipated: H2 2020 NCT04076540
Single centre in US only CVRM Partnered with Eolas Therapeutics Inc
and NIH.
R&I Other
104 Approved medicines Late-stage development AZD5634 (ENaC, inhaled) Early development Cystic Fibrosis Oncology
Trial Population Patients Design Endpoints Status
Phase I Healthy volunteers 56 A randomised, single-blind, placebo-controlled trial to assess the • Safety and tolerability • FPCD: Q1 2016 safety, tolerability and pharmacokinetics of AZD5634 following • PK/PD • Data readout: Q4 2016 NCT02679729 single-ascending inhaled doses (Part A) and after single inhaled
and intravenous doses (Part B) in healthy subjects CVRM
• Arm 1: AZD5634 following inhaled administration of SAD (Part A) and following administration of single inhaled and i.v. doses (Part B)
• Arm 2: placebo
Phase Ib Patients with cystic fibrosis 9 A randomised blinded placebo-controlled, cross-over trial to • Safety and tolerability • FPCD: Q2 2017 assess the effect of AZD5634 on mucociliary clearance as well as • PK/PD • Data readout: Q2 2018
NCT02679729 safety, tolerability, and PK parameters following single inhaled R&I dose administration to patients with cystic fibrosis
• Arm 1: subjects were administered single dose of placebo in period 1 and AZD5634 in period 2
• Arm 2: subjects were administered single dose of AZD5634 in
period 1 and placebo in period 2 Other
105 Approved medicines Late-stage development MEDI7352 (NGF TNF bispecific mAb) Early development Osteoarthritis pain Oncology
Trial Population Patients Design Endpoints Status
Phase I Painful osteoarthritis of the knee 160 • SAD & MAD • Safety, tolerability, PK, PD • FPCD: Q1 2016 • Up to 12 i.v. cohorts are planned vs. placebo • Data anticipated: H2 2020
NCT02508155 • 1 s.c. cohorts are planned vs. placebo CVRM Europe only
Phase II Painful diabetic neuropathy 271 • Multiple dose trial • Dose response, safety, tolerability, PK, • FPCD Q4 2018 NCT03755934 • Up to 4 i.v. cohorts are planned vs. placebo PD • Data anticipated: 2021
Europe only
R&I Other
106 Approved medicines Late-stage development Other biologics Early development Infections Oncology
Trial Compound Population Patients Design Endpoints Status
Phase II Anti-Staph AT Intubated ICU 213 • Placebo-controlled, single-dose, dose-ranging • Efficacy and safety • FPCD: Q4 2014 (suvratoxumab, • Route of administration: intravenous • Data readout: Q4 2018 EudraCT 2014- MEDI4893)
001097-34 CVRM
Phase II Anti-Pseudomonas Intubated ICU 195 • Placebo-controlled, single-dose, dose-ranging • Efficacy and safety • FPCD: Q2 2016 A mAb (MEDI3902) • Route of administration: intravenous • Data anticipated: H2 2020
NCT02696902
R&I Other
107 List of abbreviations
14C Radioactive isotope of carbon, Carbon 14 CHF Chronic heart failure FLAP 5-lipoxygenase-activating protein 1L, 2L, 3L 1st, 2nd or 3rd line CKD Chronic kidney disease FPDC First patient commenced dosing 5-FU 5-fluorouracil CLL Chronic lymphocytic leukaemia FPG Fasting plasma glucose A2AR Adenosine A2A receptor CMAX Maximum observed plasma concentration GA Gestational age ACQ Asthma control questionnaire C-MET Tyrosine-protein kinase Met GBM Glioblastoma ACR American college of rheumatology response scoring system CNS Central nervous system gBRCAm or ADA Anti-drug antibodies COPD Chronic obstructive pulmonary disease tBRCAm Germline or tumour BRCA mutation somatic ADC Antibody-drug conjugate CR Complete response GEJ Gastric/gastro-oesophageal junction ADP Adenosine diphosphate CRC Colorectal cancer GFF Glycopyrronium and formoterol fumarate AE Adverse Event CrCl Creatinine clearance GLP-1 Glucagon-like peptide-1 AI Auto-injector CRR Complete response rate GMFRs Geometric mean fold rises AKT Protein kinase B CTC Circulating tumour cell GMTs Geometric mean titers ALK Anaplastic large-cell lymphoma kinase CTLA-4 Cytotoxic T-lymphocyte–associated antigen 4 HAI Haemagglutination-inhibition APFS Accessorised pre-filled syringe CV Cardiovascular HbA1c Hemoglobin A1c AQLQ Asthma quality of life questionnaire CVOT Cardiovascular outcomes trial HCC Hepatocellular carcinoma AS Albuterol sulphate CVRM Cardiovascular renal and metabolism HD High dose ATM Ataxia-telangiectasia mutated kinase CXCR2 C-X-C Motif chemokine receptor 2 HDL-C High-density lipoprotein cholesterol ATR Ataxia telangiectasia and rad3-related protein DB Double blind HER2 Human epidermal growth factor receptor 2 AUC Area under curve DC Disease control HF Heart failure B7RP B7-related protein-1 DCR Disease control rate HFpEF Heart failure with preserved ejection fraction BA Bioavailability DDI Drug-drug Interaction HFrEF Heart failure with reduced ejection fraction BAFF B-cell activating factor dECG Differentiated electrocardiogram HGFR Met/hepatocyte growth factor receptor BCG Bacillus Calmette–Guérin DFS Disease free survival HGSC High grade serous carcinoma BCMA B-cell maturation antigen DLBCL Diffuse large B-cell lymphoma hHF Hospitalisation for heart failure BDA Budesonide albuterol DLT Dose-limiting toxicity HIF-PHI Hypoxia inducible factor - prolyl hydroxylase inhibitor BFF Budesonide and formoterol fumarate DMARDs Disease-modifying antirheumatic drugs HNSCC Head and neck squamous-cell carcinoma BGF Budesonide, glycopyrronium and formoterol fumarate DNA Deoxyribonucleic acid HPV Human papillomavirus BICR Blinded independent central review DoCR Durability of complete response HRD Homologous recombination deficiency BID Bis in die (twice per day) DoR Duration of response HRRm Homologous recombination repair mutation BIG Big ten cancer research consortium DPI Dry powder inhaler i inhibitor BMD Bone mineral density DXA Dual energy X-ray absorptiometry IA Investigator-assessed BMI Body mass index EBRT External beam radiation therapy ICS Inhaled corticosteroid BRCAwt Breast cancer wild-type gene ECG Electrocardiogram ICU Intensive care unit BRD4 Bromodomain-containing protein 4 EFS Event-free survival IDFS Invasive disease-free survival BTC Biliary tract carcinoma eGFR Estimated glomerular filtration rate IL Interleukin BTK Bruton's tyrosine kinase EGFR Epidermal growth factor receptor i.m. Intramuscular CA-125 Cancer antigen 125 ER Oestrogen receptor IRC Independent review committee CAD Coronary artery disease ERK Extracellular signal-regulated kinase ISS Investigator-sponsored studies CBR Clinical benefit rate ESR Externally sponsored trial i.v. Intraveneous CCL20 Chemokine (C-C motif) ligand 20 ESR1 Oestrogen receptor 1 J-SD Japanese single dose CD Cluster of differentiation ESSC Esophageal squamous cell carcinoma Ki67 Protein that is encoded by the MKI67 gene in human CDK Cyclin-dependent kinase FDC Fixed-dose combination CE Clinically evaluable FeNO Fractional nitric oxide concentration in exhaled breath CHD Coronary heart disease FEV Forced-expiratory volume Chemo Chemotherapy FGFR Fibroblast growth factor receptor 108 List of abbreviations
LABA Long acting beta agonist PASI Psoriasis area severity index SAE Serious adverse event LAMA Long acting muscarinic agonist PBD Pyrrolobenzodiazepine SBRT Stereotactic body radiation therapy LCAT Lecithin-cholesterol acyltransferase pCR Pathological complete response s.c. Subcutaneous LCM Lifecycle management PD Pharmacodynamics SCLC Small cell lung cancer LN Lupus nephritis PD-1 Programmed cell death protein 1 SD Stable disease LOCS III Lens opacities classification system III PDAC Pancreatic ductal adenocarcinoma SGLT2 Sodium-glucose transport protein 2 LPCD Last patient commenced dosing PDE4 Phosphodiesterase type 4 SGRM Selective glucocorticoid receptor modulator LV Left ventricle PD-L1 Programmed death-ligand 1 SGRQ Saint George respiratory questionnaire m Mutation PET Positron-emission tomography SJC Swollen joint count mAb Monoclonal antibody PFS Progression free survival SLE Systemic lupus erythematosus MABA Muscarinic antagonist-beta2 agonist PgR Progesterone receptor SLL Small lymphocytic lymphoma MACE Major adverse cardiac events PI3K Phosphoinositide 3-kinase SMAD Single and multiple ascending dose trial MAD Multiple ascending dose PIK3CA Phosphatidylinositol 3 kinase catalytic alpha gene SoC Standard of care MCC Mucociliary clearance PK Pharmacokinetics sPGA Static physicians global assessment score MCL Mantle cell lymphoma PLL Prolymphocytic leukaemia STAT3 Signal transducer and activator of transcription 3 MCL1 Myeloid leukemia cell differentiation protein 1 pMDI Pressurised metered dose inhaler sUA Serum uric acid mCRPC Metastatic castrate-resistant prostate carcinoma PN Plexiform neurofibromas T2DM Type 2 Diabetes Mellitus MD Medium dose POC Proof of concept T790M Threonine 790 substitution with methionine MDI Metered-dose inhaler POM Proof of mechanism TACE Transarterial Chemoembolization MDS Myelodysplastic syndrome pPCI Primary percutaneous coronary intervention TEAEs Treatment-emergent adverse events MEK Mitogen-activated protein kinase PR Partial response TID Ter in die (three times a day) MET Tyrosine-protein kinase Met pre-BD Pre-bronchodilator TJC Tender joint count MI Myocardial infarction PRO Patient reported outcome TKI Tyrosine kinase Inhibitor MMT Mixed meal test PRR Recurrent platinum resistant TLR Toll-like receptor 9 MPO Myeloperoxidase PS Propensity score TNBC Triple negative breast cancer mPR Major pathological response PSA Prostate-specific antigen TNF Tumour necrosis factor MRI Magnetic resonance imaging PSC Pulmonary sarcomatoid carcinoma TSLP Thymic stromal lymphopoietin MTD Maximum tolerated dose PSMA Prostate-specific membrane antigen TTF Time to treatment failure NaC Sodium channel PTEN Phosphatase and tensin homolog gene TTNT Time to next therapy NCI National cancer institute (US) Q2,3,4,8W Quaque (every) two, three... weeks TTP Time to tumour progression NCPV Noncalcified plaque volume QD Quaque in die (once a day) UACR Urine albumin creatinine ratio NF1 Neurofibromatosis type 1 QID Quarter in die (four times a day) UMEC Umeclidinium NGF Nerve growth factor QOD Quaque altera die (every other day) URAT1 Uric Acid Transporter 1 NHL Non-Hodgkin’s lymphoma QoL Quality of Life VEGF Vascular endothelial growth factor NIH National Institute of Health (US) QTcF Corrected QT interval by Fredericia YTE Triple-amino-acid (M252Y/S254T/T256E [YTE]) substitution NKG2a Natural killer cell C-type lectin receptor G2A RA Rheumatoid Arthritis NME New molecular entity RAAS Renin–angiotensin–aldosterone system NRG National clinical trials network in oncology (US) RECIST Response evaluation criteria in solid tumours NSCLC Non-small cell lung cancer RFS Relapse-free survival OCS Oral corticosteroid rhLCAT Recombinant human Lecithin-cholesterol acyltransferase OD Once daily RORγ Related orphan receptor gamma OGTT Oral glucose tolerance test r/r Relapsed/refractory ORR Objective response rate RT Radiation therapy OS Overall survival SABA Short-acting beta2-agonist PARP Poly ADP ribose polymerase SAD Single ascending dose 109 Clinical trials appendix H1 2020 results update