Clinical trials appendix Q3 2019 results update The following information about AstraZeneca clinical trials in Phases I-IV has been created with selected information from clinicaltrials.gov to facilitate understanding of key aspects of ongoing clinical programmes and is correct to the best of the Company’s knowledge as of 30 September 2019, unless otherwise specified.
It includes estimated timelines with regards to trial completion and first external presentations of primary data. These estimates are subject to change, as programmes recruit faster or slower than anticipated and many times are event driven.
Project postings on clinicaltrials.gov are updated on a continuous basis as projects progress. For the most up to date information on our clinical programmes please visit clinicaltrials.gov
2 Table of contents slide
Movement since Q2 2019 update Q3 2019 NME pipeline Q3 2019 LCM pipeline
Oncology
Approved medicines and late-stage development Early-stage development
Biopharmaceuticals Approved medicines and late-stage development Early-stage development
3 Movement since Q2 2019 update
New to Phase I New to Phase II New to Pivotal Study New to Registration
NME NME NME NME AZD6615 oleclumab+AZD4635 nirsevimab# (MEDI8897) trastuzumab deruxtecan#¶ DESTINY-Breast01 [US] 1 hypercholesterolemia CV disease CD73 mAb + A2aR inhibitor prostate cancer RSV mAb-YTE passive RSV immunization HER2 targeting antibody drug conjugate HER2-positive, unresectable and/or metastatic breast cancer subjects Additional indication Lifecycle Management previously treated with T-DM1 roxadustat# Fasenra# RESOLUTE hypoxia-inducible factor prolyl hydroxylase inhibitor chemotherapy IL-5R mAb COPD Lifecycle Management induced anaemia Brilinta3 THEMIS [US & EU] 1 Tagrisso + chemotherapy FLAURA2 EGFR inhibitor + chemotherapy 1st-line advanced EGFRm NSCLC P2Y12 receptor antagonist CV outcomes trial in patients with tezepelumab# coronary artery disease and type-2 diabetes without a TSLP mAb chronic obstructive pulmonary disease previous history of MI or stroke
Lifecycle Management Calquence ASCEND [US & EU] Imfinzi + FOLFOX + bevacizumab (platform) COLUMBIA 1 BTK inhibitor relapsed/refractory chronic lymphocytic PD-L1 mAb + chemo + VEGF + multiple novel oncology therapies leukaemia 1L metastatic microsatellite-stable colorectal cancer Calquence ELEVATE-RR [US & EU] BTK inhibitor 1st-line chronic lymphocytic leukaemia
Lynparza POLO [US & EU] 1 PARP inhibitor pancreatic cancer
Removed from Phase I Removed from Phase II Removed from Phase III Removed from Registration
NME NME NME Lifecycle Management MEDI0700# AZD1419# savolitinib# SAVOIR Farxiga4 DECLARE-TIMI 58 [US & EU] 2 BAFF/B7RP1 bispecific mAb systemic Inhaled TLR9 agonist asthma MET inhibitor papillary renal cell carcinoma SGLT2 inhibitor CV outcomes trial in patients with type-2 lupus erythematosus diabetes MEDI8852 Additional indication Influenza A mAb influenza A treatment Imfinzi#+tremelimumab NEPTUNE PD-L1 mAb + CTLA-4 mAb 1st-line NSCLC
¶ Registrational Phase II/III study # Partnered and/or in collaboration 1 Submission Accepted 2 Submission Approved 3 Brilinta in the US and Japan; Brilique in ROW 4 Farxiga in the US; Forxiga in ROW
4 Q3 2019 New Molecular Entity (NME)1 pipeline Phase I Phase II Phase III 20 New Molecular Entities 25 New Molecular Entities 14 New Molecular Entities
AZD1390 Imfinzi#+tremelimumab adavosertib# Imfinzi#+tremelimumab capivasertib+chemotherapy CAPItello-290 Imfinzi#+tremelimumab+SoC NILE glioblastoma PD-L1+CTLA-4 solid tumours Wee1 ovarian cancer, solid tumours PD-L1+CTLA-4 gastric cancer AKT+chemotherapy mTNBC 1L PD-L1+CTLA-4+SoC 1L urothelial cancer
AZD2811 Imfinzi#+/-tremelimumab+chemo AZD4573 Imfinzi#+tremelimumab+chemo Imfinzi#+tremelimumab Lynparza#+Imfinzi#+bevacizumab Aurora solid tumours, haematological POSEIDON CDK9 haematological malignancies PD-L1+CTLA-4 1L PDAC PD-L1+CTLA-4 biliary tract oesophageal DUO-O oesophageal SCLC malignancies PD-L1+/-CTLA-4+SoC 1L NSCLC PARP+PD-L1+VEGF 1L ovarian
AZD5153 AZD4635 Imfinzi+Lynparza# BAYOU Imfinzi#+/-tremelimumab+CRT ADRIATIC BRD4 solid tumours, haematological Imfinzi+selumetinib# selumetinib#¶ SPRINT A2aR inhibitor solid tumours PD-L1+PARP bladder PD-L1+/-CTLA-4+CRT LS-SCLC malignancies PD-L1+MEK solid tumours MEK paediatric neurofibromatosis type-1
AZD5991 MEDI1191 capivasertib# Lynparza#+adavosertib# Imfinzi#+/-tremelimumab+SoC CASPIAN trastuzumab deruxtecan# MCL1 haematological malignancies IL-12 mRNA solid tumours AKT breast PARP+Wee1 solid tumours PD-L1+/-CTLA-4+SoC 1L ES-SCLC DESTINY-Breast 02 ADC breast
AZD9496 MEDI2228 capivasertib# Lynparza#+AZD6738 VIOLETTE Imfinzi#+tremelimumab DANUBE trastuzumab deruxtecan# SERD ER+ breast BCMA ADC multiple myeloma AKT prostate PARP+ATR breast PD-L1+CTLA-4 1L bladder DESTINY-Breast 03 ADC breast
MEDI5083 Imfinzi# (platform) COAST Lynparza#+Imfinzi MEDIOLA AZD9833 Imfinzi#+tremelimumab HIMALAYA trastuzumab deruxtecan# CD40 ligand fusion protein solid PD-L1+multiple novel ONC therapies PARP+PD-L1 ovarian breast gastric SERD ER+ breast PD-L1+CTLA-4 1L HCC DESTINY-Breast 04 tumours NSCLC SCLC ADC breast
Imfinzi# (platform) NeoCOAST Calquence+ceralasertib (AZD6738) MEDI5752 oleclumab+AZD4635 Imfinzi#+tremelimumab KESTREL trastuzumab deruxtecan¶# PD-L1++multiple novel ONC therapies BTK+ATR haematological tumours PD-1/CTLA-4 solid tumours CD73+A2aR prostate cancer PD-L1+CTLA-4 1L HNSCC DESTINY-Gastric01 NSCLC ADC gastric
Calquence+danvatirsen MEDI7247 oleclumab+chemo or Imfinzi#+AZD4635 BTK+STAT3 haematological ASCT2 ADC haematological Imfinzi#+oleclumab+chemo PD-L1+A2aR solid tumours malignancies malignancies solid tumours CD73+chemo or PD-L1+CD73+chemo
Imfinzi#+AZD5069 or Imfinzi#+adavosertib# oleclumab+AZD4635 Tagrisso combo# TATTON Imfinzi#+danvatirsen# PD-L1+(CXCR2 PD-L1+Wee1 solid tumours CD73+A2aR EGFRm NSCLC EGFR+PD-L1/MEK/MET NSCLC Under Review or STAT3) HNSCC bladder NSCLC 1 New Molecular Entity
Imfinzi#+RT (platform) CLOVER oleclumab+Tagrisso Imfinzi#+Lynparza# ORION Tagrisso+savolitinib# SAVANNAH trastuzumab deruxtecan¶# PD-L1+RT HNSCC NSCLC SCLC CD73+EGFR EGFRm NSCLC PD-L1+PARP 1L mNSCLC EGFR+MET advanced EGFRm NSCLC DESTINY-Breast01 ADC breast Imfinzi#+MEDI0457# trastuzumab deruxtecan# PD-L1+DNA HPV vaccine HNSCC ADC colorectal cancer
Imfinzi#+monalizumab# trastuzumab deruxtecan# PD-L1+NKG2a solid tumours ADC NSCLC
1 includes novel combinations and additional indications for assets Imfinzi#+oleclumab where the lead is not yet launched PD-L1+CD73 solid tumours 5 # Partnered and/or in collaboration; ¶ Registrational Phase II/III study Oncology BioPharmaceuticals Q3 2019 New Molecular Entity (NME)1 pipeline
Phase I Phase II Phase III 14 New Molecular Entities 21 New Molecular Entities 5 New Molecular Entities
AZD0284 AZD9977 abediterol# cotadutide anifrolumab# TULIP RORg psoriasis/respiratory MCR cardiovascular LABA asthma/COPD GLP-1/glucagon type-2 diabetes / obesity Type I IFN receptor SLE
nirsevimab (MEDI8897)# AZD0449 MEDI1341# anifrolumab# MEDI3902 RSV mAb-YTE passive RSV Inhaled JAK inhibitor asthma Type I IFN receptor SLE SC alpha synuclein parkinson's disease Psl/PcrV Pseudomonas pneumonia immunisation
AZD1402# MEDI1814# anifrolumab# MEDI5884# PT027 inhaled IL-4Ra asthma amyloidβ alzheimer's disease Type I IFN receptor lupus nephritis cholesterol modulation cardiovascular ICS/SABA asthma
AZD5634 MEDI3506 AZD4831 MEDI6012 roxadustat# inhaled ENaC cystic fibrosis IL-33 COPD MPO HFpEF LCAT cardiovascular HIFPH anaemia MDS
MEDI7352 AZD6615 AZD5718 tezepelumab# NAVIGATOR SOURCE MEDI5117# China NGF/TNF osteoarthritis pain, painful hypercholesterolemia CV disease FLAP coronary artery disease TSLP severe uncontrolled asthma IL-6 YTE rheumatoid arthritis diabetic neuropathy
AZD8154 MEDI6570 AZD7594 roxadustat# Inhaled PI3Kgd asthma LOX-1 CV disease Inhaled SGRM asthma/COPD HIF-PH inhibitor chemo induced anaemia
AZD8233 MEDI7219 AZD7986# suvratoxumab Under Review hypercholesterolemia cardiovascular anti-diabetic type-2 diabetes DPP1 COPD α-Toxin Staphylococcus pneumonia 0 New Molecular Entities
AZD8601# tezepelumab# VEGF-A cardiovascular TSLP atopic dermatitis
AZD8871# tezepelumab# MABA COPD TSLP COPD
AZD9567 verinurad SGRM RA/respiratory URAT-1 chronic kidney disease
Breztri (PT010) LABA/LAMA/ICS asthma
1 includes novel combinations and additional indications for assets where the lead is not yet launched 6 # Partnered and/or in collaboration; ¶ Registrational Phase II/III study Oncology BioPharmaceuticals Q3 2019 Lifecycle Management (LCM)1 pipeline
Phase I Phase II Phase III Applications Under Review 1 Project 6 Projects 21 Projects 3 Projects
Imfinzi#+CTx NIAGARA Imfinzi#+azacitidine# Imfinzi# Calquence# Calquence# PD-L1+CTx muscle invasive bladder PD-L1+azacitidine MDS PD-L1 solid tumours BTK inhibitor 1st line MCL BTK inhibitor 1st line CLL cancer
Imfinzi# (platform) BEGONIA Calquence# Imfinzi#+CTx TOPAZ-1 Calquence# PD-L1 1L mTNBC BTK inhibitor r/r CLL, high risk PD-L1+CTx 1L biliary tract cancer BTK inhibitor r/r CLL
Imfinzi# (platform) MAGELLAN Calquence#+venetoclax+obinutuzumab Imfinzi#+VEGF EMERALD-2 Lynparza# POLO PD-L1 1L mNSCLC BTK+BCL-2+anti-CD20 1st line CLL PD-L1+VEGF adjuvant HCC PARP pancreatic cancer
Imfinzi+FOLFOX+bevacizumab (platform) Imfinzi# CALLA Imfinzi#+VEGF+TACE EMERALD-1 COLUMBIA1 PD-L1 adj. locally advanced cervical PD-L1+VEGF+TACE locoregional HCC PD-L1+chemo+VEGF+multiple novel cancer
Lynparza# (basket) MK-7339-002 / Imfinzi# PEARL Lynparza# OlympiA LYNK002 PARP HRRm cancer PD-L1 1L metastatic NSCLC PARP gBRCA adjuvant breast
Lynparza#+cediranib CONCERTO Imfinzi# post-SBRT PACIFIC-4 Lynparza# PROfound PARP+VEGF recurrent Pt-R ovarian PD-L1 post-SBRT stage I/II NSCLC PARP prostate cancer
Imfinzi# POTOMAC Lynparza# SOLO-3 PD-L1 non muscle invasive bladder PARP BRCAm PSR ovarian cancer
Imfinzi#+CRT PACIFIC-2 Lynparza+abiraterone# PROpel PD-L1+CRT NSCLC PARP+NHA prostate cancer
Imfinzi#+CRT PACIFIC-5 (China) Tagrisso ADAURA PD-L1+CRT locally-advanced stage III EGFR adj. EGFRm NSCLC NSCLC
Imfinzi#+CTx neoadjuvant AEGEAN Tagrisso LAURA PD-L1+CTx locally-advanced stage I-III EGFRm locally advanced unresectable NSCLC NSCLC
Tagrisso+chemo FLAURA2 EGFR+chemo 1L adv EGFRm NSCLC
1 Includes significant LCM projects and parallel indications for assets beyond Phase III 7 # Partnered and/or in collaboration; ¶ Registrational Phase II/III study Oncology BioPharmaceuticals Q3 2019 Lifecycle Management (LCM)1 pipeline
Phase I Phase II Phase III Applications Under Review 0 Projects 0 Projects 11 Projects 2 Projects
Brilinta/Brilique HESTIA Brilinta/Brilique THEMIS P2Y12 paeds w/ sickle cell P2Y12 diabetes & CAD outcomes
Brilinta/Brilique THALES Nexium (CN only) P2Y12 stroke stress ulcer prophylaxis
Epanova STRENGTH outcomes
Farxiga/Forxiga Dapa-CKD SGLT2 CKD
Farxiga/Forxiga DAPA-HF SGLT2 HFrEF
Farxiga/Forxiga DELIVER SGLT2 HFpEF
Farxiga/Forxiga DETERMINE-Preserved SGLT2 HFpEF
Farxiga/Forxiga DETERMINE-Reduced SGLT2 HFrEF
Fasenra# OSTRO IL-5R nasal polyposis
Fasenra# RESOLUTE IL-5R COPD
Symbicort SYGMA as needed in mild asthma
1 Includes significant LCM projects and parallel indications for assets beyond Phase III 8 # Partnered and/or in collaboration; ¶ Registrational Phase II/III study Oncology BioPharmaceuticals Estimated key regulatory submission acceptances
PT027 asthma
tezepelumab asthma NAVIGATOR
roxadustat anaemia in CKD (US) Imfinzi +tremelimumab bladder Imfinzi +tremelimumab HCC Fasenra severe asthma (China) OLYMPUS/ROCKIES DANUBE HIMALAYA
selumetinib NF1 Imfinzi + tremelimumab HNSCC Imfinzi +tremelimumab+SoC urothelial capivasertb + CTx SPRINT (US) KESTREL NILE CAPItello
Imfinzi +/-tremelimumab SCLC Lynparza +cediranib ovarian trastuzumab deruxtecan Imfinzi +tremelimumab+CRT LDS-SCLC Lumoxiti HCL (EU) CASPIAN GY004 DESTINY-Breast03 ADRIATIC NME Imfinzi +/-tremelimumab NSCLC selumetinib NF1 anifrolumab SLE trastuzumab deruxtecan trastuzumab deruxtecan Lynparza +Imfinzi + bevacizumab ovarian POSEIDON SPRINT (EU) TULIP DESTINY-Breast02 DESTINY-Breast04 DUO-O
H2 2019 H1 2020 H2 2020 2021 2021+
Symbicort mild astha (China) Farxiga HFrEF Brilinta stroke Epanova mxd dyslip Tagrisso EGFrm NSCLC Calquence 1L MCL SYGMA DAPA-HF THALES STRENGTH ADAURA
Symbicort mild asthma (EU) Farxiga HFrEF Fasenra nasal polyposis Calquence +venetoclax+obinutuzumab Tagrisso locally adv. unresectable NSCLC SYGMA DETERMINE OSTRO 1L CLL LAURA
Lynparza ovarian Farxiga CKD Imfinzi cervical Tagrisso+ CTx EGFRm NSCLC Calquence CLL (EU & Japan) SOLO-3 DAPA-CKD CALLA FLAURA2 LCM Lynparza ovarian Imfinzi+ CTx biliary tract Brilinta paeds w/ sickle cell roxadustat anemia in MDS PAOLA-1 TOPAZ-1 HESTIA
Lynparza prostate Imfinzi adjuvant NSCLC Imfinzi non muscle invasive bladder Bydureon Bcise type-2 diabetes (China) PROFOUND BR31 POTOMAC
Imfinzi + CRT NSCLC Imfinzi +chemo muscle invasive bladder Duaklir Genuair COPD (China) PACIFIC-2 NIAGARA
Imfinzi NSCLC Imfinzi post-SBRT NSCLC Farxiga HFpEF PEARL PACIFIC-4 DELIVER
Imfinzi neoadjuvant NSCLC Imfinzi +CRT NSCLC Fasenra COPD AEGEAN PACIFIC-5 (China) RESOLUTE
Imfinzi+VEGF+TACE locoregional HCC Imfinzi +VEGF adjuvant HCC nirsevimab passive RSV immunisation EMERALD-1 EMERALD-2
Lynparza breast OLYMPIA
Lynparza +abiraterone prostate PROPEL
9 Note. NME section includes novel combinations and additional indications for assets where the lead is not yet launched Oncology BioPharmaceuticals Designations 4 13 10 23 25 Accelerated approvals Breakthrough / PRIME / Sakigake Fast Track Priority Review Orphan Drug
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)
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) 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)
trastuzumab deruxtecan breast cancer (US) Lynparza tablet (US) Calquence WM (US)
Calquence CLL (US) Lynparza tablet (CN) Calquence WM (EU)
trastuzumab deruxtecan gastric cancer (JP) Lynparza breast cancer OLYMPIAD (JP) Calquence CLL 1L (EU)
Tagrisso NSCLC 1L FLAURA (JP) Calquence MCL (EU)
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)
FAST TRACK is a process designed to facilitate the development, and expedite the review of medicines to treat serious conditions and fill an Breztri Aerosphere (PT010) COPD (CN) selumetinib NFI type 1 SPRINT (US) unmet medical need. Tagrisso NSCLC 1L FLAURA (CN) selumetinib NFI type 1 SPRINT (EU) BREAKTHROUGH DESIGNATION is a process designed to expedite the development and review of medicines which may demonstrate Breztri Aerosphere (PT010) (CN) Lynparza pancreatic cancer POLO (US) substantial improvement over available therapy. PRIME is a scheme launched by the EMA to enhance support for the development of medicines that target an unmet medical need. SAKIGAKE Lokelma hyperkalaemia (CN) Fasenra EGPA (US)
ACCELERATED APPROVAL, these regulations allowed medicines for serious conditions that addressed an unmet medical need to be approved Lynparza pancreatic 1L (US) Fasenra HES (US) based on a surrogate endpoint. trastuzumab deruxtecan breast cancer (US) saracatinib IPF (US) PRIORITY REVIEW DESIGNATION is the US FDA’s goal to take action on an application within 6 months. Imfinzi +/-treme+SOC SCLC 1L CASPIAN (US) ORPHAN DRUG DESIGNATION, intended for treatment, diagnosis or prevention of rare diseases/disorders that affect fewer than 200,000 patients in the US, or that affect more than 200,000 patients but are not expected to recover the costs of developing and marketing a treatment Fasenra EoE (US) drug.
10 Oncology BioPharmaceuticals AstraZeneca
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 anticipated: 2021+
NCT02511106 CVRM Global trial - 25 countries
Phase III Maintenance therapy in 200 • Arm 1: Tagrisso • Primary endpoint: PFS (BICR) • FPCD: Q3 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 chemoradiation therapy
Phase III Real world setting in adult 3,020 Single-arm trial - Tagrisso • Primary endpoints: OS and safety • FPCD: Q3 2015 Respiratory 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
12 Approved medicines Late-stage development Tagrisso (highly-selective, irreversible EGFRi) Early development NSCLC, combinations Oncology
Trial Population Patients Design Endpoints Status Phase III 1st-line EGFRm NSCLC 586 Arm 1: Tagrisso plus Pemetrexed/Carboplatin or • Primary endpoint: PFS • FPCD: Q3 2019 FLAURA2 Pemetrexed/Cisplatin • Secondary endpoints: OS, LOS, ORR • Data anticipated: 2021+ Arm 2: Tagrisso DoR, Depth of response, PFS2. QoL, PK
NCT04035486 CVRM Global trial – 5+ countries
Phase II Advanced EGFRm NSCLC 150 Modular design platform study: • 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 – no study drug
Global trial - 8 countries Respiratory 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: 2020 Other • Arm 3: Tagrisso + selumetinib NCT02143466 Enrolment to Imfinzi combination arms will not restart
Global trial
13 Approved medicines Late-stage development Imfinzi (PD-L1 mAb) Early development NSCLC, early use Oncology
Trial Population Patients Design Endpoints Status
Phase III Adjuvant NSCLC patients 1,360 • Arm 1: Imfinzi mg/kg i.v. Q4W x 12m Primary endpoint: • FPCD: Q1 2015 ADJUVANT BR.31 IB (≥4cm) – stage IIIA • Arm 2: placebo • DFS • Data anticipated: 2021 resected NSCLC NCT02273375 (incl. EGFR/ALK positive) Global trial Secondary endpoint: CVRM • OS Partnered
Phase II/III Lung Master Stage IV squamous NSCLC 140 Umbrella trial with five arms based on biomarker expression: Primary endpoints: • FPCD: Q2 2014 Protocol patients • Substudy A: Imfinzi (non-match for other biomarker driven • ORR • Data anticipated: 2021+ substudies) i.v. Q2W single arm Imfinzi Phase II only • PFS NCT02154490 Biomarker-targeted • Substudy B: PI3K inhibitor vs. docetaxel • OS 2L therapy • Substudy C: CDK4/6 inhibitor vs, docetaxel Partnered • Substudy D: AZD4547 (FGFR inhibitor) vs. docetaxel • Substudy E: C-MET/HGFR Inhibitor + erlotinib vs. erlotinib Phase III Unresected, locally-advanced 300 • Arm 1: Imfinzi i.v. Q4W + chemo/RT Primary endpoint: • FPCD: Q2 2018
NSCLC • Arm 2: placebo + chemo/RT • PFS • Data anticipated: H2 2020 Respiratory PACIFIC-2 • ORR ex US global trial Secondary endpoint: NCT03519971 • OS
Phase III Imfinzi following SBRT in 630 • Arm 1: Imfinzi i.v. Q4W following definitive SBRT Primary endpoint: •FPCD: Q2 2019 unresected, Stage I/II NSCLC • Arm 2: placebo following definitive SBRT • PFS •Data anticipated: 2021+ PACIFIC-4 Secondary endpoint:
• OS Other NCT03833154 Phase III Unresected, locally-advanced 360 • Arm 1: Imfinzi i.v. Q4W following chemo/RT Primary endpoint: • FPCD: Q1 2019 NSCLC • Arm 2: placebo following chemo/RT • PFS • Data anticipated: 2021 PACIFIC-5 Secondary endpoint: ex US global trial, China focus • OS NCT03706690
Phase III Neoadjuvant NSCLC patients 300 • Arm 1: Imfinzi + platinum-based chemo Primary endpoint: • FPCD: Q1 2019 Stage II and III resected • Arm 2: placebo + platinum-based chemo • mPR • Data anticipated: H2 2020 AEGEAN NSCLC Secondary endpoint (incl. EGFR/ALK positive) • pCR NCT03800134
14 Approved medicines Late-stage development Imfinzi (PD-L1 mAb) +/- treme (CTLA-4 mAb) Early development Lung cancer, advanced Oncology
Trial Population Patients Design Endpoints Status
Phase III Limited disease- 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 CVRM
Phase III NSCLC 1L 650 • Arm 1: Imfinzi Q4W Primary endpoint: • FPCD: Q1 2017 PEARL • Arm 2: chemotherapy • OS • LPCD: Q1 2019 • Data anticipated: 2021 NCT03003962 Asia trial Phase III NSCLC 1L 1,000 • Arm 1: Imfinzi + chemo Primary endpoint: • FPCD: Q2 2017 POSEIDON • Arm 2: Imfinzi + tremelimumab + chemo • OS • LPCD: Q3 2018 • Arm 3: SoC • PFS • Data anticipated: Q4 2019 NCT03164616
Phase III SCLC 1L 795 • Arm 1: Imfinzi + tremelimumab + EP (carboplatin or cisplatin + Primary endpoint: • FPCD: Q1 2017 Respiratory 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 arm
Phase II SCLC 80 • Arm A: Imfinzi + tremelimumab Q4W • Primary endpoint: ORR • FPCD: Q4 2016 BALTIC • Arm B: adavosertib and carboplatin BID • Data anticipated: 2021 • Arm C: AZD6738 and Lynparza
NCT02937818 Other
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: 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
15 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: Q3 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: Q1 2019 cancer Imfinzi maintenance • pCR • Data anticipated: 2021+ NIAGARA • Arm 2: gemcitabine + cisplatin • EFS
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: 2021 • Arm C: TACE in combination with placebo NCT03778957 Secondary endpoint 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+ Respiratory • Arm 3: placebo + placebo NCT03847428 Secondary endpoint: • RFS Arm 1 vs Arm 3, OS, RFS at 24 mos Other
pCR = Pathologic Complete Response EFS = event free survival 16 Approved medicines Late-stage development Imfinzi (PD-L1 mAb) +/- treme (CTLA-4 mAb) Early development Other cancers, late 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 anticipated: H1 2020
NCT02516241 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 • Data anticipated: H1 2020 NCT02551159
Phase III HCC 1L 1,310 • Arm 1: Imfinzi + tremelimumab Primary endpoint: • FPCD: Q4 2017
HIMALAYA • Arm 2: Imfinzi • OS • LPCD: Q3 2019 Respiratory • 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:
• Safety, DoR Other
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: 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
17 Approved medicines Late-stage development Imfinzi (PD-L1 mAb) +/- treme (CTLA-4 mAb) Early development Other cancers 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 Combination With • NSCLC Arm 1 • Data anticipated: 2021+ Chemoradiation in Patients • NSCLC Arm 2 With Advanced Solid • NSCLC Arm 3 Respiratory Tumours • SCLC Arm 2 • SCLC Arm 3 CLOVER • SCLC Arm 4 NCT03509012
Phase II mTNBC 1L 100 • Arm 1 Imfinzi + paclitaxel Primary endpoint: • FPCD: Q1 2019
BEGONIA • Arm 2 Imfinzi + paclitaxel + capivasertib • Safety and tolerability • Data anticipated: H2 2020 Other • Arm 4 Imfinzi + paclitaxel + danvatirsen NCT03742102 • Arm 5 Imfinzi + paclitaxel + oleclumab Secondary endpoint: • ORR, PFS, DoR, OS, PK, ADA Global trial
18 Approved medicines Late-stage development Lynparza (PARP inhibitor) Early development Ovarian and other cancers Oncology
Trial Population Patients Design Endpoints Status Phase III BRCAm maintenance ovarian 391 • Arm 1: Lynparza tablets BID maintenance therapy for two years • Primary endpoint: PFS • FPCD: Q3 2013 SOLO-1 cancer 1L or until disease progression • Secondary endpoint: OS • LPCD: Q1 2015 • Arm 2: placebo • Data readout: Q2 2018 • Primary endpoint met CVRM NCT01844986 Global trial
Phase III PSR gBRCAm ovarian cancer 266 • Arm 1: Lynparza BID to progression • Primary endpoint: ORR • FPCD: Q1 2015 SOLO3 3L+ • Arm 2: physician’s choice (single-agent chemo) • LPCD: Q2 2018 • Data readout: Q4 2018 NCT02282020 Global trial • Primary endpoint met
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: 2021 Respiratory NCT02032823 Global trial partnership with BIG and NCI/NRG survival and OS
Partnered
Phase III BRCAm metastatic breast 302 • Arm 1: Lynparza 300mg BiD, continuous to progression • Primary endpoint: PFS • FPCD: Q2 2014 OlympiAD cancer • Arm 2: physician’s choice: • Secondary endpoint: OS • LPCD: Q4 2015 capecitabine 2500mg/m2 x 14 q 21 • Data readout: Q1 2017 NCT02000622 vinorelbine 30mg/m2 d 1, 8 q 21 • Primary endpoint met
eribulin 1.4mg/m2 d 1, 8 q 21 Other to progression
Global trial
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 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
19 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 1,056 Non tBRCAm (tumour BRCA) patients Primary endpoint: • FPCD: Q1 2019 • Arm 1: bevacizumab • PFS • Data anticipated: 2021+ DuO-O • Arm 2: bevacizumab + Imfinzi • Arm 3: bevacizumab + Imfinzi + Lynparza CVRM NCT03737643 tBRCAm patients • bevacizumab (optional) + Imfinzi + Lynparza
Global trial
Phase II Stage IV NSCLC whose disease has 327 • Arm 1: Imfinzi + Lynparza Primary endpoint: • FPCD Q1 2019 not progressed following SoC chemo • Arm 2: Imfinzi + placebo • PFS • Data anticipated: 2021+ ORION + Imfinzi Maintenance therapy 1L Global trial Secondary enpoints: NCT03775486 • OS, ORR, DoR, PFS in HRRm, PK, ADA Respiratory Phase II Platinum-Ineligible unresectable 150 • Arm 1: Imfinzi + Lynparza • Primary endpoint: PFS • FPCD: Q1 2018 BAYOU Stage IV urothelial cancer • Arm 2: Imfinzi + placebo • Data anticipated : H1 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 Other 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
20 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 • Primary endpoint met CVRM Externally sponsored Global trial
Phase III Metastatic castration-resistant 720 • Arm 1: Lynparza + abiraterone Primary Endpoint: • FPCD: Q4 2018 PROpel prostate cancer 1L • Arm 2: placebo + abiraterone • PFS • Data anticipated: 2021 Global trial NCT03732820
Phase II TNBC 450 • Arm 1: AZD6738 + Lynparza • PFS • FPCD: Q2 2018 • Arm 2: Lynparza • ORR / OS • Data anticipated: 2021 VIOLETTE Trial conducted in 15 countries: North America, Europe and Asia • Safety and tolerability NCT03330847 Respiratory Phase III Recurrent platinum sensitive 549 • Arm 1: chemo Primary endpoint: • FPCD: Q1 2016 GY004 ovarian cancer • Arm 2: Lynparza • PFS • Data anticipated: H1 2020 • Arm 3: cediranib + Lynparza NCT02446600 Secondary endpoints: Externally sponsored US/Canada/Japan sites • OS, QoL, safety
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+ Other cancer • Arm 3: cediranib NCT02502266 • Arm 4: Lynparza Secondary endpoints: Externally sponsored • ORR, QoL, safety • US/Canada sites
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
21 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 (Arm A vs. Arm B vs. Arm C)
NCT02475681 CVRM
Phase III Previously untreated CLL 780 • Arm A; Calquence + venetoclax • Primary - AV vs FCR/BR efficacy PFS • FPCD: Q1 2019 fit • Arm B: Calquence + venetoclax + obinutuzumab • Secondary AVG vs FCR/BR efficacy • Data anticipated: 2021+ ACE-CL-311 • Arm C: FCR or BR PFS; AV vs FCR/BR and AVG vs FCR/BR
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 Respiratory ACE-CL-006 (ELEVATE-RR) CLL • Arm B: ibrutinib • Secondary endpoints: comparison of • Data anticipated: 2021+ incidence of infections, RTs (Richter’s NCT02477696 Transformation) and atrial fibrillation, OS
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 Other 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+
NCT02029443
22 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: 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: Q1 2018
NCT02180724
Phase Ib Relapsed/refractory de novo 21 Calquence monotherapy • Safety • FPCD: Q3 2014
ACE-LY-002 activated B-cell DLBCL • Data anticipated: H2 2019 Respiratory
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: 2020+ • Arm B: relapsed/refractory NCT02717624 • Arm C: treatment naïve: Calquence + venetoclax + rituxumab Other
Phase Ib Relapsed/refractory MM 28 • Arm A: Calquence • Safety • FPCD: Q1 2015 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 23 • Arm C: relapsed/refractory • Arm D: treatment naïve Approved medicines Late-stage development Calquence (BTK inhibitor) Early development Blood 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
Phase III CLL TN and r/r 600 • Arm A: treatment naïve • Safety Data anticipated: 2021+ Respiratory 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 study with trial centres in US and UK
24 Approved medicines Late-stage development Calquence (BTK inhibitor) Early development Other cancers Oncology
Trial Population Patients Design Endpoint(s) Status
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 CVRM Respiratory Other
25 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 study • 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 NCT01829711 > 180 days • Primary endpoint met • Secondary endpoints Partnered • Efficacy: CR rate, ORR, Duration of CVRM CR and ORR, TTR, PFS • Safety and tolerability • PK and immunogenicity
Phase I Adults with relapsed or 49 • Open-label dose escalation Phase I trial • Primary endpoints: MTD and efficacy • FPCD: Q2 2007 refractory HCL • Lumoxiti i.v. • LPCD: Q1 2014 NCT00586924 • Data readout: Q2 2015
Partnered Respiratory Other
26 Approved medicines Late-stage development Trastuzumab deruxtecan (DS-8201, HER2 ADC) Early development Breast and gastric cancers Oncology
Trial Population Patients Design Endpoints Status
Phase II HER2-positive, unresectable and/or 230 Randomised, open label, sequential assignment Primary endpoint ORR • FPCD: Q3 2017 DESTINY-Breast01 metastatic breast cancer patients • Trastuzumab deruxtecan • LPCD: Q3 2018 previously treated with trastuzumab Secondary end points DoR, CBR, CBR, • Data readout: Q2 2019 NCT03248492 emtansine PFS, OS CVRM Partnered
Phase III HER2-positive, unresectable and/or 600 Randomised open label parallel assignment Primacy endpoint PFS • FPCD: Q3 2018 DESTINY-Breast02 metastatic breast cancer pretreated with • Trastuzumab deruxtecan • Data anticipated 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
Phase III HER2-positive, unresectable and/or 500 Randomised open label parallel assignment Primary endpoint PFS • FPCD: Q3 2018 DESTINY-Breast03 metastatic breast cancer patients • Trastuzumab deruxtecan • Data anticipated 2021 previously treated with trastuzumab and • Ado-trastuzumab emtansine Secondary endpoints OS, ORR, DoR, CBR Respiratory 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 • Trastuzumab deruxtecan • Data anticipated 2021 • Physicians choice of SoC chemo (choice of capecitabine, Secondary end points OS, DoR, ORR NCT03734029 eribulin, gemcitabine, paclitaxel or nab-paclitaxel) Other Partnered
Phase II HER2-overexpressing advanced gastric 220 Randomised open label parallel assignment Primary end point ORR • FPCD: Q4 2017 DESTINY-Gastric01 or gastroesophageal junction • Trastuzumab deruxtecan • LPCD: Q2 2019 adenocarcinoma patients who have • SoC chemo Secondary end points PFS, OS, DoR, • Data anticipated H1 2020 NCT03329690 progressed on two prior treatment DCR, TTF, range of PK endpoints Partnered regimens
27 Approved medicines Late-stage development Trastuzumab deruxtecan (DS-8201, HER2 ADC) Early development Other cancers Oncology
Trial Population Patients Design Endpoints Status
Phase II HER2-expressing advanced colorectal 90 Non randomised single group assignment Primary end point ORR • FPCD Q1 2018 cancer • Trastuzumab deruxtecan • Data anticipated 2020+ NCT03384940 Secondary end points PFS, OS, DoR, range of PK endpoints CVRM Partnered
Phase II HER2-over-expressing or mutated, 130 Non randomised parallel group assignment Primary end point ORR • FPCD Q2 2018 unresectable and/or metastatic NSCLC • Trastuzumab deruxtecan • Data anticipated 2020 NCT03505710 Secondary end points DoR, PFS, OS
Partnered
Phase I Advanced solid malignant tumours 278 Non randomised single group assignment Primary end points number of subjects with • FPCD Q3 2015 • Trastuzumab deruxtecan AEs, tumour response • Data read out Q3 2018 NCT02564900 Respiratory Secondary end points PK Partnered Other
28 Approved medicines Late-stage development Selumetinib (MEK inhibitor) Early development Paediatric neurofibromatosis type 1 Oncology
Trial Population Patients Design Endpoints Status
Phase II Paediatric NF1 50 (stratum 1) • Single arm: selumetinib 25mg/m2 BID with 2 strata: • Complete partial and complete response • FPCD: Q3 2015 SPRINT • Stratum 1: PN related morbidity present at enrolment rate measured by volumetric MRI; • LPCD: Q4 2016 • Stratum 2: no PN related morbidity present at enrolment • Duration of response and functional • Data readout: Q1 2019 NCT01362803 • Primary endpoint met
outcomes/QoL CVRM Partnered
Phase Ib Advanced solid tumours 80 (dose escalation Phase Ib open-label trial of MK-8353 in combination with • DLTs • FPCD: Q1 2019 Selumetinib + MK-8353 (ERK trial) selumetinib in participants with advanced solid tumours • AEs inhibitor) • Study drug discontinuations due to an AE NCT03745989
Partnered (Merck Lead study) Respiratory Other
29 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 Respiratory Other
30 Approved medicines Late-stage development Cediranib (VEGF receptor inhibitor) Early development Ovarian cancer Oncology
Trial Population Patients Design Endpoints Status
Phase IIb PRR ovarian cancer - heavily 62 • Cediranib 30mg + Lynparza 200mg BID • ORR, DoR, DCR, QoL. OS; Safety • FPCD: Q1 2017 CONCERTO pre-treated BRCAwt • LPCD: Q1 2019
NCT02889900 CVRM Respiratory Other
31 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 study • PFS • FPCD Q3 2019 metastatic TNBC • Arm 1: capivasertib + paclitaxel • OS • Data anticipated: 2021+ NCT03997123 • Arm 2: placebo + paclitaxel CVRM CAPItello-290
Phase II (ESR) Metastatic castration resistant 150 Randomised comparative • PFS • FPCD Q1 2014 prostate cancer eligible for • Arm 1: docetaxel + prednisolone + capivasertib • Data anticipated: H1 2020 NCT02121639 treatment with docetaxel • Arm 2: docetaxel + prednisolone + placebo chemotherapy PROCAID Respiratory Other
32 AstraZeneca
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 anticipated: H2 2019 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 Respiratory
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 infusion related reaction • Data anticipated: H1 2020 NCT02900157 US and Japan trial centers
Phase II Imfinzi NSCLC 260 5 modules encompassing 13 cohorts • Primary outcome; ORR • FPCD: Q1 2018 Lynparza • Module 1; Imfinzi and Lynparza • Secondary outcomes; efficacy including • Data anticipated: 2021+ Other HUDSON vistusertib • Module 2; Imfinzi and danvatirsen OS, PFS, DCR, and safety and ceralasertib • Module 3; Imfinzi and ceralasertib (AZD6738) tolerability, DoR NCT03334617 (AZD6738) • Module 4; Imfinzi and vistusertib danvatirsen • Module 5; Imfinzi and oleclumab oleclumab 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 34 NCT03794544 • Arm D: Imfinzi + danvatirsen 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 GEJ adenocarcinoma 114 • Arm A: Imfinzi + tremelimumab 2L • Primary endpoints: Safety & tolerability, • FPCD: Q2 2015 STUDY 21 • Arm B: Imfinzi 2L ORR, PFS • Data anticipated: H2 2019 • Arm C: tremelimumab 2L • Secondary endpoints: DCR, OS, DoR, NCT02340975 • Arm D: Imfinzi + tremelimumab 3L PD-L1 Expression • Arm E: Imfinzi + tremelimumab 2L & 3L
US and ROW trial centres
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 Respiratory
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 explored in expansion • Secondary endpoints include antitumour activity, PK and immunogenicity North American, EU and ROW trial centres Other 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: H1 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
Phase Ib DLBCL 32 • Arm A: Imfinzi • Primary endpoint: Safety & tolerability • FPCD: Q3 2016 STUDY 23 • Arm B: Imfinzi + tremelimumab • Secondary endpoints: OR, DC, DoR, • LPCD: Q4 2018 • Arm C: Imfinzi + AZD9150 PFS, OS, PK/PD, immunogenicity and • Data readout: Q3 2019 NCT02549651 US and European trial centres biomarkers
35 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 501 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 in adult subjects with pharmacodynamics CRC and monalizumab in combination with biologic agent in adult subjects with CRC Respiratory Global trial Other
36 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 Respiratory Other
37 Approved medicines Late-stage development MEDI1191 (IL-12 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 NCT03946800 expansion study of MEDI1191 administered intratumourally as • Data anticipated: 2021+ monotherapy and in combination with Imfinzi • Secondary endpoints: PK, immunogenicity and efficacy CVRM Respiratory Other
38 Approved medicines Late-stage development AZD1390 (ATM inhibitor) Early development Cancer Oncology
Trial Population Subjects Design Endpoints Status Phase I Healthy volunteers 8 • PET trial • Brain distribution of AZD1390 to assess if • FPCD: Q4 2017 [11C]AZD1390 crosses the blood brain • LPCD: Q1 2018 NCT03215381 • [11C]AZD1390 microdose administered by i.v. bolus barrier in healthy volunteers • Data readout: Q2 2018 CVRM Trial conducted in a single centre in Sweden
Phase I Recurrent glioblastoma c. 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: 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 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 Respiratory Other
39 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) 96 • 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 130 • 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 anticipated: H2 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 anticipated: H2 2019
NCT02617277 Respiratory
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 anticipated: H2 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 anticipated: H2 2019
NCT03313557
40 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: 2020+ NCT03489525 • Determination of MTD CVRM • Secondary endpoints: pPK, immunogenicity, ORR, DCR, DoR, PFS, OS Respiratory Other
41 Approved medicines Late-stage development AZD2811 (AURN) Early development Cancer Oncology
Trial Population Patients Design Endpoints Status
Phase I Solid tumours 72 • Arm 1: AZD2811 dose escalation • Safety and tolerability • FPCD: Q4 2015 • Arm 2: AZD2811 dose expansion SCLC • PK and efficacy • Data anticipated: H2 2020 NCT02579226 CVRM
Phase I AML/high-risk MDS 130 • Part A: AZD2811 monotherapy and azacytidine combination • Safety and tolerability • FPCD: Q3 2017 dose escalation cohorts • PK and efficacy • Data anticipated: 2020+ NCT03217838 • Part B: AZD2811 monotherapy and azacytidine combination dose expansions to further explore the tolerability, PK and clinical activity Respiratory Other
42 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 Respiratory Other
43 Approved medicines Late-stage development AZD4635 (A2AR inhibitor) Early development Cancer Oncology
Trial Population Patients Design Endpoints Status Phase I Phase Ia: patients with 295 Phase Ia – solid tumours or mCPRC: Primary outcome measure: • FPCD: Q2 2016 advanced solid tumours • AZD4635 monotherapy • Safety and tolerability • Data anticipated: 2020 NCT02740985 • AZD4635 + Imfinzi • AZD4635 + abiraterone Phase Ib: Secondary outcome measures: CVRM Post-immunotherapy NSCLC • AZD4635 + enzalutamide • PK of AZD4635 as monotherapy and Other post-immunotherapy • AZD4635 monotherapy (capsule formulation) combination with Imfinzi abiraterone and • AZD4635 + Imfinzi (capsule formulation) enzalutamide. solid tumours • AZD4635 + Imfinzi + oleclumab • Preliminary assessment of anti-tumour Immune checkpoint-naïve • AZD4635 + docetaxel. activity mCRPC Immune checkpoint- Phase Ib: AZD4635 monotherapy or AZD4635 + Imfinzi dose naïve CRC expansions in NSCLC, mCRPC, CRC and other post- Other immune checkpoint- immunotherapy and immune checkpoint-naïve solid tumours naïve solid tumours Conducted at sites in the US Phase I Healthy male volunteers 21 • Arm 1: Part A 2-period randomised crossover study of single Primary outcome measures: • FPCD: Q4 2018
doses of AZD4635, nanosuspension or solid oral formulation in • Maximum observed Cmax of AZD4635 • LPCD: Q2 2019 Respiratory NCT03710434 fasted state solid oral formulation and nano- • Arm 2: Part B, 4-period, open-label, randomised, crossover suspension study of single doses of AZD4635 in the same subjects from • Exposure to AZD4635 solid oral Part A. The treatments selected for Part B will depend on the formulation and nano-suspension outcome of interim analyses of AZD4635 exposure.
Both parts conducted at a site in the UK Other Phase II Prostate cancer 60 ARM 1: AZD4635 plus Imfinzi • Primary outcome measure: Efficacy; • FPCD: Q3 2019 ARM 2: AZD4635 plus 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
44 Approved medicines Late-stage development AZD5069 (CXCR2 antagonist) Early development Cancer Oncology
Trial Population Patients Design Endpoints Status Phase Ib/II Metastatic pancreatic ductal 16 Dose escalation and expansion arms: • Safety/efficacy trial • FPCD: Q1 2016 carcinoma • LPCD: Q3 2018 NCT02583477 Imfinzi in combination with nab-paclitaxel and gemcitabine • Data anticipated: H2 2019 Imfinzi in combination with AZD5069 CVRM Respiratory Other
45 Approved medicines Late-stage development MEDI5083 (CD40 Ligand fusion protein ) Early development + Imfinzi (PD-L1 mAb) Oncology Cancer
Trial Population Patients Design Endpoints Status CVRM Phase I Advanced solid tumours 204 Dose-escalation phase Primary endpoints: • FPCD: Q1 2017 • Part 1: MEDI5083 • Safety • Data anticipated: H1 2020 NCT03089645 • Part 2: MEDI5083 + Imfinzi i.v. • Determination of MTD
• Secondary endpoints: preliminary anti- Dose expansion phase tumour activity, pharmacokinetics, • Part 3: MEDI5083 recommended dose + Imfinzi i.v. pharmacodynamics, and immunogenicity
US and Australian trial centres Respiratory Other
46 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.
Dose and schedule from dose escalation may be applied in dose expansion phase in HGS ovarian cancer. Respiratory Other
47 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 263 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 : 2 cohorts with 2 arms each antitumour activity based on OR
Secondary endpoints: • PK, ADA, tumoural baseline PD-L1, assessment of antitumour activity based on OR, DoR, DC, PFS, OS Respiratory Other
48 Approved medicines Late-stage development AZD5991 (MCL1 inhibitor) Early development Cancer Oncology
Trial Population Patients Design Endpoints Status Phase I Relapsed/refractory 48 • Arm1: monotherapy dose escalation in relapsed/refractory • Primary: safety • FPCD: Q3 2017 haematologic malignancies haematological malignancies. Seven dose escalation cohorts. • Secondary: efficacy, PK • Data anticipated: 2021 NCT03218683 • Arm2: combination dose escalation (AZD5991+venetoclax) in relapsed/refractory AML;. Four dose escalation cohorts. CVRM • i.v. route of administration • US only Respiratory Other
49 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: 2020+ 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 Respiratory Other
50 Approved medicines Late-stage development Danvatirsen (AZD9150, STAT3 inhibitor) Early development Cancer Oncology
Trial Population Patients Design Endpoints Status Phase Ib/II HNSCC 405 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 2020
• 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)
Phase Ib/II NSCLC, advanced solid 213 Dose escalation advanced solid and blood cancers • Safety/efficacy trial • FPCD: Q1 2018 tumours • Arm A1: AZD9150 alternate week/Imfinzi • Data anticipated: H2 2020 Respiratory 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
51 Approved medicines Late-stage development MEDI7247 (PBD ADC mAb) Early development Cancer Oncology
Trial Population Patients Design Endpoints Status Phase I Relapsed/refractory 408 First-time-in-human Phase I, multi-centre, open-label, single-arm, • Primary endpoint: safety • FPCD: Q2 2017 NCT03106428 haematological malignancies dose-escalation, and dose-expansion trial for adult subjects • Data anticipated: 2021+ • Secondary endpoints: PK, immunogenicity and antitumour activity CVRM
Phase I/Ib Advanced or metastatic solid 336 Open-label, dose-escalation and dose-expansion • Primary endpoint: safety • FPCD: Q4 2018 tumours • Data anticipated: 2021+ NCT03811652 • Secondary endpoints: PK, immunogenicity and antitumour activity Respiratory Other
52 Approved medicines Late-stage development Oleclumab (MEDI9447, CD73 mAb) Early development Cancer Oncology
Trial Population Patients Design Endpoints Status Phase I Advanced malignancies 310 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 309 • 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: 2021+ NCT03611556 gemcitabine-based • Arm A3: gemcitabine and nab paclitaxel i.v. + oleclumab i.v. + Imfinzi i.v. chemotherapy • Secondary endpoints include PF, PD, • 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. Respiratory • 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 • Arm B: oleclumab i.v. + AZD4635 • Safety • Data anticipated: 2021+ NCT03381274 • ORR Secondary endpoints: Other US, South Korean and Taiwan trial centres • DoR, DCR, PFS, OS, PK and immunogenicity
53 Approved medicines Late-stage development AZD9496 (selective estrogen receptor degrader) 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 anticipated: H2 2019 NCT03236974 effects of AZD9496 and Faslodex in postmenopausal women AZD9496 or Faslodex
• Secondary outcome measures: CVRM with ER+, HER2- primary breast cancer. Patients will receive 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
Phase I ER+ breast cancer c. 50 • This is a Phase I open label multicentre trial of AZD9496 • Primary outcome measures: safety and • FPCD: Q4 2014 administered orally in patients with advanced ER+ HER2- tolerability • LPCD: Q2 2016 NCT02248090 breast cancer. The trial design allows an escalation of dose • Secondary outcome measures: single • Data readout: Q2 2017 with intensive safety monitoring to ensure the safety of and multiple dose PK of AZD9496 patients. The trial will determine the maximum tolerated dose. 4β-hydroxycholesterol concentration in
In addition, expansion cohort(s) at potential therapeutic blood Respiratory dose(s) in patients with or without ESR1 mutations will be • Anti-tumour activity enrolled to further determine the safety, tolerability, pharmacokinetics and biological activity of AZD9496
Phase I Healthy subjects 14 • This is a Phase I open label single centre trial to assess the • Primary outcome measures: PK for • FPCD: Q2 2016 pharmacokinetics and safety of different forms and AZD9496 and its metabolites • LPCD: Q3 2016 NCT02780713 formulations of AZD9496 in healthy subjects • Secondary outcome measures: safety • Data readout: Q2 2017
and tolerability and PK Other
54 Approved medicines Late-stage development AZD9833 (selective oestrogen receptor degrader) 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 Respiratory Other
55 AstraZeneca
BioPharmaceuticals - approved medicines and late-stage pipeline Approved medicines Late-stage development Farxiga (SGLT2 inhibitor) Early development Diabetes Oncology
Trial Population Patients Design Endpoints Status Phase III/IV Type-2 diabetes 17,190 • Arm 1: Farxiga 10mg QD + SoC therapy QD • Primary endpoints: superiority for MACE. • FPCD: Q2 2013 DECLARE with high risk for CV event • Arm 2: placebo + SoC therapy for type-2 diabetes Superiority for the composite endpoint of • LPCD: Q2 2015 CV death or hospitalisation for heart • Data Readout: Q3 2018 NCT01730534 Global trial – 33 countries failure • Met primary safety endpoint and one of CVRM two primary efficacy endpoints (hHF or CV death)
Phase III Type-1 diabetes 833 • Arm 1: Farxiga 5mg QD 52 weeks + insulin • Primary endpoint: adjusted mean change • FPCD: Q4 2014 DEPICT 1 • Arm 2: Farxiga 10mg QD 52 weeks + insulin from baseline in HbA1c at week 24 • LPCD Q2 2016 • Arm 3: placebo QD 52 weeks + insulin • Data readout: Q1 2017 NCT02268214 • Primary endpoint met Global trial – 17 countries Partnered
Phase III Type-1 diabetes 813 • Arm 1: Farxiga 5mg QD 52 weeks + insulin • Primary endpoint: adjusted mean change • FPCD: Q3 2015 DEPICT 2 • Arm 2: Farxiga 10mg QD 52 weeks + insulin from baseline in HbA1c at week 24 • LPCD: Q1 2017
• Arm 3: placebo QD 52 weeks + insulin • Data readout: Q4 2017 Respiratory NCT02460978 • Primary endpoint met Global trial – 14 countries Partnered Other
57 Approved medicines Late-stage development Farxiga (SGLT2 inhibitor) Early development Diabetes / cardiovascular risk reduction 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 Q3 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: Q1 2019 the composite: ≥50% sustained decline • Data anticipated: 2021 NCT03036150 Global trial - 20 countries in eGFR or reaching ESRD or CV death or renal death
Phase III CHF patients with HFpEF 4,700 • Arm 1: Farxiga 10mg QD • Primary endpoint: time to the first • FPCD: Q3 2018 DELIVER • Arm 2: placebo occurrence of any of the components of • Data anticipated: 2021+
the composite: CV death or Respiratory NCT03619213 • Global trial - 21 countries hospitalisation for HF or an urgent HF visit
Phase III CHF patients with HFpEF 400 • Arm 1: Farxiga 10mg QD • Primary endpoint: change from • FPCD: Q2 2019 DETERMINE-preserved • Arm 2: placebo baseline in 6 min walking distance at • Data anticipated: H1 2020 Week 16 NCT03877224 • Global trial - 12 countries Other
Phase III CHF patients with HFrEF 300 • Arm 1: Farxiga 10mg QD • Primary endpoint: change from • FPCD: Q2 2019 DETERMINE-reduced • Arm 2: placebo baseline in 6 min walking distance at • Data anticipated: H1 2020 Week 16 NCT03877237 • Global trial - 9 countries
58 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 • Data anticipated: H1 2020 attack on a background of acetylsalicylic acid if not contra-indicated or subsequent stroke and death at 30 days NCT03354429 not tolerated Secondary endpoints include: Global trial – 28 countries • Prevention of subsequent ischaemic stroke at 30 days
• Reduction of overall disability at 30 days Respiratory
Phase III Peadiatric 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: 2021+ of painful crisis and/or acute chest pain NCT03615924 Global trial – 18 countries Other
59 Approved medicines Late-stage development Epanova (omega-3 carboxylic acids) Early development Hypertriglyceridaemia Oncology
Trial Population Patients Design Endpoints Status Phase III Patients with 13,000 • Arm 1: Epanova 4g QD + statin • Primary endpoint: composite of MACE • FPCD: Q4 2014 STRENGTH (CVOT) hypertriglyceridaemia and high • Arm 2: placebo (corn oil) + statin • LPCD: Q2 2017 cardiovascular disease risk • Data anticipated: H2 2020 NCT02104817 Global trial – 22 countries CVRM
Phase III Japanese patients with 375 • Epanova 2g and 4g vs. placebo (after meal) daily for 52 weeks Primary endpoints: • FPCD: Q2 2015 hypertriglyceridaemia • Safety in Japanese patients • LPCD: Q1 2016 NCT02463071 Global trial – one country • percentage change in triglycerides • Data readout: Q2 2017
Phase III Severe hypertriglyceridaemia 162 • Arm 1: Epanova 2g QD • Primary endpoint: change in serum • FPCD: Q4 2013 EVOLVE II • Arm 2: placebo (olive oil) triglycerides over 12 weeks • LPCD: Q4 2014 • Data readout: Q4 2015 NCT02009865 Global trial – seven countries • Primary endpoint met Respiratory
Phase I Healthy Chinese subjects 14 Open-label trial to evaluate the pharmacokinetics of single and • Primary endpoints: plasma • FPCD: Q2 2018 China PK multiple doses of Epanova 4 g/day in Chinese healthy subjects concentrations versus time profile of EPA • LPCD: Q2 2018 and DHA to assess PK parameters • Data readout: Q4 2018 NCT03574142 Local trial – China Other
60 Approved medicines Late-stage development Lokelma (sodium zirconium cyclosilicate) Early development Hyperkalaemia Oncology
Trial Population Patients Design Endpoints Status Phase III Hyperkalaemia 248 Open-label Lokelma 10g TID for 48 hours followed by: • Primary endpoint: maintenance of • FPCD: Q1 2017 Harmonize Global • Arm 1: Lokelma 5g QD for 28 days normokalaemia • LPCD: Q1 2018 • Arm 2: Lokelma 10g QD for 28 days • Data readout: Q4 2018
NCT02875834 • Arm 3: placebo QD for 28 days • Primary endpoint met CVRM
Global trial – four countries
Phase II/III Hyperkalaemia 103 • Arm 1: Lokelma 5g TID for 48 hours • Primary endpoint: exponential rate of • FPCD: Q2 2017 • Arm 2: Lokelma 10g TID for 48 hours change in serum potassium • LPCD: Q1 2018 NCT03127644 • Arm 3: placebo TID for 48 hours • Data readout: Q3 2018 Japan • Primary endpoint met
Phase III Hyperkalaemia 150 • Arm 1: Open-label Lokelma 10g TID for up to 72 hrs followed • Primary endpoint: safety and tolerability • FPCD: Q3 2017 by Lokelma 5g QD for 12 months. Option to uptitrate to 10 as measured by adverse events • LPCD: Q3 2019 NCT03172702 and15g QD or downtitrate to 5g QOD (or 2.5g QD) reporting, vital signs, ECGs, physical • Data readout: Q3 2019 J-LTS examinations and safety laboratory • Primary endpoint met
Japan measurements Respiratory Phase I Healthy Subjects 22 • Arm 1: open-label Lokelma 5g QD for 4 days • Primary endpoint: mean change from • FPCD: Q4 2017 • Arm 2: open-label Lokelma 10g QD for 4 days baseline to Lokelma treatment period in • LPCD: Q4 2017 NCT03283267 urine potassium excretion • Data readout: Q1 2018 China
Phase IIIb Patients on haemodialysis 180 • Arm 1: Lokelma 5g QD for 8 weeks on non-dialysis days. • Primary endpoint: proportion of patients • FPCD: Q4 2017 DIALIZE with persistent pre-dialysis Option to uptitrate to 10 and15g QD. who maintain a pre-dialysis serum K • LPCD: Q4 2018
hyperkalaemia • Arm 2: placebo QD for 8 weeks on non-dialysis days between 4.0-5.0 mmol/L on 3 out of 4 • Data readout: Q1 2019 Other NCT03303521 dialysis treatments following the long • Primary endpoint met Global trial – four countries interdialytic interval Phase II Patients with chronic heart 280 • 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– at high risk of developing • Arm 2: placebo QD for 12 weeks angiotensin–aldosterone system) NCT03532009 hyperkalaemia blockade treatment. Global trial – nine countries
61 Approved medicines Late-stage development Roxadustat (HIF-PHI) 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 • Data anticipated: H2 2019 Sponsored by Astellas NCT02021318 Global trial Partnered Respiratory
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
Phase III Anaemia in CKD in patients 2,133 • Arm 1: roxadustat • Primary efficacy endpoint: Haemoglobin • FPCD: Q3 2014 Other 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 62 Approved medicines Late-stage development Roxadustat (HIF-PHI) 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 NCT03303066 Arm 2: placebo • Data anticipated: 2020+ Partnered Sponsored by FibroGen China Respiratory
Phase II Anemia in patients receiving 100 US • Primary endpoint: Maximum change in • FPCD: Q3 2019 chemotherapy treatment for hemoglobin within 16 weeks from • Data anticipated: H2 2020 NCT04076943 non-myeloid malignancies baseline without RBC transfusion Sponsored by FibroGen Partnered Other
63 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 • FPCD: Q2 2018 subjects trial bromide and its metabolites after single • Data anticipated: H2 2020 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 Respiratory Other
64 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: 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 Respiratory Other
65 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-study 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-study 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 8,000 Treatments (1-year treatment period) • Primary endpoint: rate of moderate or • FPCD: Q3 2015 ETHOS COPD (possible increase by • BGF MDI 320/14.4/9.6µg BID pMDI severe COPD exacerbations • LPCD: Q3 2018 4,000 after blinded • BGF MDI 160/14.4/9.6µg BID pMDI • Data readout: Q3 2019 NCT02465567 sample size re- • BFF MDI 320/9.6µg BID pMDI • Secondary endpoint: time to first • Primary endpoint met assessment) • GFF MDI 14.4/9.6µg BID pMDI moderate or severe COPD exacerbation Respiratory 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 66 Approved medicines Late-stage development PT027 (ICS/SABA, 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: 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/peadiatric asthma quality of life questionnaire change from baseline and responder analysis at week 24 Respiratory
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 2020 • BDA MDI 160/180 μg QID hours over 12 weeks • BD MDI 160 μg QID • Change from baseline in trough FEV1 at Managed by Avillion • AS MDI 180 μg QID week 12 • placebo MDI QID
Randomised, double-blind, multi-centre and parallel-group Other
Multi-country
67 Approved medicines Late-stage development Daliresp/Daxas (PDE4 inhibitor, oral) Early development COPD Oncology
Trial Population Patients Design Endpoints Status
Phase IV COPD 2,354 • 52W, randomised, DB with Daliresp 500µg OD vs. placebo, in • Primary endpoint: rate of moderate or • FPCD: Q4 2011 RESPOND COPD on top of ICS/LABA severe COPD exacerbations per subject • LPCD: Q1 2016 per year • Data readout: Q4 2016
NCT01443845 CVRM
Phase IV COPD 1,323 • 12W, randomised, DB to evaluate tolerability and PK of • Primary endpoint: percentage of • FPCD: Q2 2014 OPTIMIZE Daliresp 500μg OD with an up-titration regimen during the first participants prematurely discontinuing • LPCD: Q3 2015 4Ws, including an open label down-titration evaluating trial treatment for any reason during the • Data readout: Q4 2016 NCT02165826 tolerability and PK of 250µg Daliresp OD in patients not main period tolerating 500μg OD
Phase IIIb COPD 158 • 16W, randomised, placebo-controlled, DB, parallel-group trial to • Primary endpoint: number of • FPCD: Q1 2012 ROBERT assess the anti-inflammatory effects of Daliresp in COPD inflammatory cells CD8+ in bronchial • LPCD: Q1 2016 biopsy tissue specimen (sub-mucosa) • Data readout: Q4 2016 NCT01509677 measured at randomisation and at the
end of the intervention period Respiratory
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 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 Other healthcare, death, and demographics data).
68 Approved medicines Late-stage development Fasenra (IL-5R mAb) Early development Severe, uncontrolled asthma Oncology
Trial Population Patients Design Endpoints Status
Phase III A multi-centre, open-label, 770 • 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 on ICS plus LABA2 Agonist
NCT02808819 Global trial - 15 countries CVRM Age 18-75 years
Phase IIIb Severe eosinophilic 600 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: Q3 2017 ICS/LABA Trial (MIRACLE) despite background controller • Arm 2: placebo s.c. exacerbation rate • Data readout: 2021+ medication, MD & HD ICS + • Secondary endpoints: assess pulmonary
NCT03186209 LABA ± chronic OCS 56-week trial function, asthma symptoms, other Respiratory Age 12-75 years Global trial – 4 countries asthma control metrics Other
69 Approved medicines Late-stage development Fasenra (IL-5R mAb) Early development Severe, uncontrolled asthma Oncology
Trial Population Patients Design Endpoints Status
Phase III Severe asthma, inadequately 2,550 • 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 HD ICS + LABA ± chronic
NCT02258542 • 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 120 • 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 NCT02417961 HD ICS + LABA ± chronic Global trial – two countries OCS Age 18-75 years Respiratory
Phase lll A double-blind, randomised, 38 • 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 2019 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, 100 • 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
70 Approved medicines Late-stage development Fasenra (IL-5R mAb) Early development Severe, uncontrolled asthma Oncology
Trial Population Patients Design Endpoints Status
Phase III Severe asthma on ICS-LABA 120 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, 800 • 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 anticipated: Q4 2019 NCT03170271 trial to evaluate the safety and 24-week trial George Respiratory Questionnaire efficacy of Fasenra 30 mg s.c. Global trial – 15 countries (SGRQ) in patients with severe asthma Respiratory uncontrolled on SoC treatment. Age 18-75
Phase I Healthy volunteers 162 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
71 Approved medicines Late-stage development Fasenra (IL-5R mAb) Early development Nasal polyposis, other Oncology
Trial Population Patients Design Endpoints Status
Phase III Patients with severe bilateral 400 • 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 of care therapy
NCT03401229 56-week trial CVRM Global trial- 8 countries Age 18-75 years
Phase III Patients with relapsing or 140 • Arm 1: Fasenra 30mg Q4W s.c. • Primary endpoint: Proportion of patients • Initiating 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 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 Patients with HES (history of • Primary endpoint: Time to first HES • Initiating Phase III 120 • Arm 1: Fasenra 30mg Q4W s.c. Respiratory NATRON persistent eosinophilia >1500 • Arm 2: placebo Q4W s.c. worsening/flare. • Data anticipated: 2021+ cells/μL with evidence of 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 Other 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
72 Approved medicines Late-stage development Fasenra (IL-5R 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 Respiratory Other
73 Approved medicines Late-stage development Tezepelumab (TSLP mAb) Early development Severe, uncontrolled asthma Oncology
Trial Population Patients Design Endpoints Status
Phase III Severe asthma 1,060 • 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 152 • 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 • Data anticipated: H2 2020 losing asthma control NCT03406078 48 week trial • Secondary endpoint: Annual asthma exacerbation rate Partnered Global trial – seven countries Respiratory 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 Study 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 210 • 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) subjects /caregivers who successfully • Data anticipated: H2 2020 NCT03968978 administrated tezepelumab in clinic and at home with an APFS or an AI, Partnered Global trial – 4 countries respectively
74 Approved medicines Late-stage development Tezepelumab (TSLP mAb) Early development Atopic dermatitis, COPD Oncology
Trial Population Patients Design Endpoints Status
Phase IIb Patients with chronic atopic 300 A dose-ranging, double-blind, placebo-controlled study to evaluate The effect of tezepelumab compared with • FPCD: Q1 2019 dermatitis the safety and efficacy of tezepelumab alone or combined with placebo, assessed using the IGA and EASI topical corticosteroids in moderate-to-severe atopic dermatitis • Data anticipated: 2020+
NCT03809663 CVRM • Arm 1: tezepelumab HD, s.c. Q2W • Arm 2: tezepelumab MD, s.c. Q4W • Arm 3: tezepelumab LD, s.c. Q2W • Arm 4: placebo, s.c. Q2W or Q4W
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 NCT04039113 52 week trial
Partnered Global trial – 10 countries Respiratory Other
75 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: Q3 2015 TULIP SLE 1 • Arm 2: 150mg i.v. anifrolumab Q4W for 48 weeks responder index at week 52 • LPCD: Q3 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: Q3 2015 TULIP SLE 2 • Arm 2: placebo i.v. Q4W for 48 weeks responder index at week 52 • LPCD: Q3 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
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 Respiratory 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: 2021 NCT02547922 • Arm 3: placebo i.v. Q4W for 48 weeks
76 AstraZeneca
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 I Healthy adult subjects 64 • SAD s.c. administration • Primary: safety profile in terms of adverse events, vital signs, ECG, • FPCD: Q1 2015 • Germany telemetry, lab variables, nausea, immunogenicity and physical • LPCD: Q4 2015 NCT02394314 examination • Data readout: Q4 2015 CVRM
Phase II Adults with type-2 113 • MAD s.c. administration • Primary: efficacy MMT glucose AUC and body weight loss • FPCD: Q1 2016 diabetes • Secondary: efficacy HbA1c, fructosamine • LPCD: Q1 2017 NCT02548585 • Germany • Secondary: safety profile in terms of adverse events, vital signs, ECG, • Data readout: Q1 2017 Completed telemetry, lab variables, nausea, immunogenicity and physical examination
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 Respiratory
Phase II Overweight and 834 • Arm1: cotadutide low dose s.c. + metformin • Primary: efficacy HbA1c, body weight loss • FPCD: Q3 2017 Obese subjects with • Arm2: cotadutide mid dose s.c. + metformin • Secondary: percentage of subjects 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 subjects rescued or discontinued for lack of • Arm5: liraglutide s.c. + metformin glycaemic control • Secondary: PK and immunogenicity
US, Canada, Bulgaria, Czech Rep, Germany, Other Mexico, Russia, Slovakia
Phase I Adults with renal 37 • Arm1: Subjects with CrCl <20ml/min • Primary: PK • FPCD: Q3 2017 impairment cotadutide s.c. • Secondary: safety, tolerability and immunogenicity • LPCD: Q1 2018 NCT03235375 • Arm2: Subjects with CrCl 20-30ml/min • Data readout: Q3 2018 cotadutide s.c. • Arm3: Subjects with CrCl >90ml/min cotadutide s.c. • Arm4:Subjects with CrCl >30<60ml/min cotadutide s.c. • Germany, New Zealand
78 Approved medicines Late-stage development Cotadutide (MEDI0382, GLP-1-glucagon agonist) Early development Diabetes/obesity Oncology
Trial Population Patients Design Endpoints Status
Phase I Healthy adult subjects 22 • Open label, one sequence, cross-over • Effect of MEDI0382 on PK & PD of warfarin & esmolol • FPCD: Q4 2017 NCT03347968 cotadutide with warfarin and esmolol • Safety profile • LPCD: Q1 2018 US • Immunogenicity • Data readout: Q3 2018 CVRM
Phase I Healthy adult subjects 24 • Open label, cross-over, two period • Primary: AUC, plasma concentration • FPCD: Q4 2017 NCT03341013 • Single dose cotadutide formulation 2 s.c. • Secondary: PK • LPCD: Q4 2017 • Single dose cotadutide formulation 3 s.c. • Secondary: safety • Data readout: Q2 2018 US • Secondary: immunogenicity
Phase I Overweight/obese 32 • Arm1: single low dose of cotadutide or • Primary: safety, tolerability • FPCD: Q1 2018 NCT03385369 subjects of Japanese placebo (Japanese) • Secondary: PK • LPCD: Q2 2018 or Chinese descent • Arm2: single intermediate-low dose of • Secondary: immunogenicity • Data readout: Q3 2018 cotadutide or placebo (Japanese) • Arm3: single intermediate-high dose of
cotadutide or placebo (Japanese) Respiratory • Arm4: single high dose of cotadutide or placebo (Japanese) • Arm5: single intermediate-low dose of cotadutide or placebo (Chinese) • US
Phase II Overweight/obese 49 • Arm1: cotadutide + dapagliflozin • Primary: efficacy MMT glucose AUC • FPCD: Q3 2018 NCT03444584 subjects with type-2 • Arm2: placebo + dapagliflozin • Secondary: safety • LPCD: Q4 2018
diabetes • Germany, Hungary • Secondary: PK • Data readout: Q1 2019 Other • 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 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 • Secondary: immunogenicity
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 subjects with • UK • Secondary: change in total energy intake type-2 diabetes • Secondary: change in total energy expenditure, active energy
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 subjects week or 16 week titration period • Secondary: PK • LPCD: Q2 2019 • Secondary: immunogenicity • US
Phase II Overweight and 20 • Cotadutide or placebo s.c. • Primary: safety, tolerability • FPCD: Q1 2019 NCT03745937 obese subjects with • Germany • Secondary: PK • LPCD: Q2 2019 type-2 diabetes • Secondary: immunogenicity • Secondary: glucose control Respiratory Phase II Japanese preobese 61 • MAD s.c. administration • Primary: safety, glucose AUC, body weight • FPCD: Q3 2018 NCT03645421 or obese subjects • Japan • Secondary: HbA1c, FPG, fructosamine • LPCD: Q3 2018 with type-2 diabetes • Secondary: glucose control • Data readout: Q2 2019 • Secondary: PK, immunogenicity
Phase II Obese subjects with 72 • Arm1: cotadutide high dose s.c. • Primary: safety and tolerability • Initiating NCT04019561 non-alcoholic fatty • Arm2: placebo high dose s.c. • Secondary: change in hepatic fat fraction, 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 subjects 36 • Primary: to evaluate exposure following a single s.c of cotadutide at • Initiating NCT04091373 each of 3 different sites of injection • Secondary: immunogenicity • Secondary: safety and tolerability
80 Approved medicines Late-stage development AZD0449 (inhaled JAK-1 inhibitor) Early development Asthma Oncology
Trial Population Patients Design Endpoints Status
AZD0449 Healthy subjects and patients 156 SAD/MAD/Bridge trial (UK) Primary endpoint: • FPCD: Q4 2018 with mild asthma Part 1 SAD • Safety and tolerability Phase I • Dose escalation in 6 cohorts with 6 subjects receiving
AZD0449 and 2 subjects receiving placebo in each cohort Secondary endpoint: CVRM NCT03766399 • i.v. cohort with 8 subjects • PK parameters • FENO Part 2 MAD: • 3 cohorts of (6, 6, 18) subjects receiving three different doses of AZD0449 and (3,3, 12) subjects receiving placebo in each cohort
Part 3 bridge • 18 subjects will receive AZD0449 and 6 subjects receiving placebo
Trial conducted in the UK Respiratory Other
81 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 subjects (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 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 • Arm C: placebo abnormalities) • Data readout: Q3 2019 This trial is a single centre study conducted in the US PK outcomes (AUC, Cmax, tmax) Respiratory Other
82 Approved medicines Late-stage development AZD4831 (MPO inhibitor) Early development Cardiovascular disease Oncology
Trial Population Patients Design Endpoints Status AZD4831 (MPO) Healthy subjects 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 Phase I up to 10 cohort may be used • Data readout Q2 2017 CVRM NCT02712372
AZD4831 (MPO) Healthy subjects 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 Phase I may be included • Data readout: Q1 2018
NCT03136991
AZD4831 (MPO) HFpEF 96 Arm 1: AZD4831 • Primary endpoint: The change from • FPCD: Q4 2018 Arm 2: placebo baseline in MPO activity in % after Phase IIa AZD4831 treatment Global trial – five countries
NCT03756285 Respiratory Other
83 Approved medicines Late-stage development AZD5718 (FLAP inhibitor) Early development Cardiovascular disease Oncology
Trial Population Patients Design Endpoints Status
AZD5718 (FLAP) CAD 138 • Arm 1: AZD5718 Dose A • Primary endpoint: PD effect of AZD5718 • FPCD: Q4 2017 • Arm 2: AZD5718 Dose B by assessment of u-LTE4 Phase IIa • Arm 3: placebo CVRM NCT03317002 Global trial – three countries in Europe
AZD5718 (FLAP) Healthy subjects 6 hADME trial (one trial site in UK) • Mass balance, with routes and rates of • FPCD: Q2 2019 • Oral administration elimination of [14C]AZD5718. Phase I Open-label study to characterize the absorption, distribution, • Metabolite profiling and structural metabolism and excretion following a single oral dose of NCT03948451 identification [14C]AZD5718 in healthy male volunteers • PK and total radioactivity
AZD5718 (FLAP) Healthy subjects 14 BA trial (one trial site in UK) • To evaluate the pharmacokinetics and • FPCD: Q4 2019 An open-label, randomized, 3-period, 3-treatment, crossover exposure of 3 different doses Phase I study to assess the drug absorption into the blood after of AZD5718 Respiratory NCT04087187 administration of 3 doses of AZD5718 • Safety and tolerability Other
84 Approved medicines Late-stage development AZD6615 (anti-hypercholesterolemia) Early development Hypercholesterolemia Oncology
Trial Population Patients Design Endpoints Status
Phase I Healthy subjects 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. Respiratory Other
85 Approved medicines Late-stage development MEDI7219 (anti-diabetic) Early development Diabetes Oncology
Trial Population Patients Design Endpoints Status
Phase I Healthy Volunteers 130 • 5 part trial • Safety and tolerability • FPCD: Q1 2018 • Part A : SAD • Pharmacokinetics • Data anticipated: H1 2020 NCT03362593 • Part B, C & E : open label, single dose studies
• Part D : MAD CVRM Respiratory Other
86 Approved medicines Late-stage development AZD8233 (anti-hypercholesterolemia) Early development Hypercholesterolemia Oncology
Trial Population Patients Design Endpoints Status Phase I Healthy subjects 56 SAD Primary: • FPCD: Q3 2018 • Safety and tolerability • LPCD: Q3 2019 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. Respiratory Other
87 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 Respiratory Other
88 Approved medicines Late-stage development AZD9977 Early development Heart failure with preserved ejection fraction Oncology
Trial Population Patients Design Endpoints Status Phase I Healthy subjects 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 subjects receiving placebo in each cohort Secondary; CVRM • PK parameters Trial conducted in the UK.
Phase I Healthy subjects 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 HFpEF 60 Proof of differentiation Primary: • FPCD Q4 2018 • serum potassium • LPCD Q1 2019
NCT03682497 To compare the effect of AZD9977 with spironolactone on serum Respiratory potassium
Phase I Healthy subjects 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 subjects 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 subjects 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
89 Approved medicines Late-stage development Biologics Early development Cardiovascular & metabolic diseases Oncology
Trial Compound Population Patients Design Endpoints Status
Phase IIb MEDI6012 Subjects 30-80 414 • 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 CVRM second inpatient dose Secondary endpoints: 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.
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 Respiratory 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
90 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
Phase I Healthy subjects 6 A Phase I, single centre, open-label, non-randomised, single • Determination of absolute bioavailability • FPCD: Q1 2017
dose trial performed in 6 healthy male subjects aged 18 to 65 of AZD0284 • LPCD: Q1 2017 Respiratory NCT03029741 years, inclusive. The trial will assess the absolute bioavailability of • Safety and tolerability of AZD0284 a 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 Phase Ib Moderate to severe plaque 25 planned A randomised, double-blind, placebo-controlled, multi-centre, • Reduction from baseline to the end of 4 • FPCD:Q4 2017 psoriasis 5 completed parallel group Phase Ib study, designed to evaluate the weeks treatment, in gene expression • LPCD: Q2 2018 Other NCT03310320 9 dosed pharmacodynamic effects, clinical efficacy and safety of level of IL-17A and CCL20 relative to AZD0284 compared with placebo as measured by the relative placebo change from baseline in Psoriasis Area Severity Index (PASI • Change (percent improvement) in PASI • The trial was temporarily suspended ~5 score), other disease assessments of involved body surface area compared to placebo months due to preclinical findings. (BSA), static physicians global assessment score (sPGA), pruritis • Safety and tolerability and PK following 4 and biomarkers associated with the mechanism of disease and weeks oral administration with single • However, whilst the intention was to re- AZD0284 ascending dose open the DERMIS study, in the meantime, and for portfolio and prioritisation reasons, a decision was taken in Q3 2018 to end the study.
91 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: H2 2020 NCT03272165 US only CVRM Respiratory Other
92 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 70 PoM. Primary endpoint: • FPCD: Q3 2018 A dose-escalating, single blind trial to assess the • Safety and tolerability • LPCD Q2 2019 NCT03574805 safety, tolerability, and pharmacokinetics of multiple • Data anticipated: H2 2019 doses of PRS-060 administered by oral Inhalation In Secondary endpoint: CVRM Partnered subjects with mild asthma • PK parameters • Potential immunogenicity • ARM 1-4 (ARM 5 optional) (inhaled nebulizer) and matched • Change in FENO placebo
Australia
Phase I Healthy subjects 18 A randomised open label, 3-period, 3-treatment, crossover study Primary endpoint: • FPCD: Q2 2019 to assess the effect of Inhalation device and formulation on • PK parameters • LPCD: Q2 2019 NCT03921268 pharmacokinetics following a single Inhaled dose of AZD1402 in • Data readout: Q3 2019 healthy subjects Secondary endpoint: • Safety and tolerability
United Kingdom Respiratory Other
93 Approved medicines Late-stage development MEDI1814 (amyloid beta mAb) Early development Alzheimer’s disease Oncology
Trial Population Patients Design Endpoints Status Phase I Alzheimer’s disease & healthy 121 • SAD & MAD • Safety, tolerability • FPCD: Q2 2014 elderly • Up to 10 i.v. cohorts are planned vs. placebo • LPCD: Q2 2016 NCT02036645 • 2 s.c. cohorts are planned vs. placebo • Data readout: Q4 2016 CVRM US only Respiratory Other
94 Approved medicines Late-stage development MEDI3506 (IL-33 mAb) ligand Early development Chronic obstructive pulmonary disease (COPD) 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: H1 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)
Conducted in UK Respiratory Other
95 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 Phase I, randomised, single-blind, placebo-controlled trial to • Safety and tolerability • FPCD: Q1 2016 assess the safety, tolerability and pharmacokinetics of AZD5634 • PK/PD • Data readout: Q4 2016 NCT02679729 following 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 Phase Ib randomised blinded placebo-controlled, cross-over • Safety and tolerability • FPCD: Q2 2017 trial to assess the effect of AZD5634 on mucociliary clearance as • PK/PD • Data readout: Q2 2018 NCT02679729 well as safety, tolerability, and PK parameters following single inhaled dose administration to patients with cystic fibrosis
• Arm 1: subjects were administered single dose of placebo in Respiratory 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
96 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: H1 2020 NCT02508155 • 1 s.c. cohorts are planned vs. placebo CVRM Europe only
Phase II Painful diabetic neuropathy 271 • Multiple dose study • 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 Respiratory Other
97 Approved medicines Late-stage development 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 study to assess the PK, PD Primary endpoint: • FPCD: Q3 2019 and safety of 2-eeek treatment with inhaled AZD7594 in • PK, safety and tolerability following 2 • Data readout: H1 2020 NCT03976869 adolescents (12 to 17 Years) with asthma weeks treatment with AZD7594 CVRM Secondary endpoints • Changes from baseline in lung function, asthma control and plasma cortisol on day 15
Phase Iib Adult asthma patients (GINA 800 A Phase IIb randomised, double blind, placebo-controlled, Primary endpoint: • FPCD: Q1 2019 GRANIT 3), parallel arm, multi-centre study to assess efficacy and safety of • To assess efficacy of 5 doses of inhaled • LPCD; Q3 2019 multiple dose levels of AZD7594 DPI given once daily for 12 AZD7594 compared to placebo and • Data readout: H2 2019 estimate dose response using change NCT03622112 weeks, compared to placebo, in asthmatics symptomatic on low from baseline in trough FEV at week 12 dose ICS with fluticasone furoate (100 µg) as an open-label 1 active reference agent .
Key secondary endpoints Respiratory • Change from baseline in: FENO, PEF, ACQ, daily symptoms • CompEx • In a subset: 24 hour plasma cortisol, PK Other
98 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 study to assess the PK of AZD7986 in • PK/PD and DDI • Data readout: Q2 2016 NCT02653872 healthy 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 study to assess the safety, tolerability, PK and food effect of • PK/PD • Data readout: Q3 2016 NCT02303574 • Bioavailability single and multiple oral doses of AZD7986 in healthy volunteers. Respiratory
• Arm 1: AZD7986, single and multiple oral doses • Arm 2: placebo, single and multiple doses Other
99 Approved medicines Late-stage development AZD8154 (PI3Kgδ inhibitor) Early development Asthma Oncology
Trial Population Patients Design Endpoints Status Phase I Healthy subjects 54 SAD Primary endpoint: • FPCD: Q3 2018 A Phase I trial to assess the safety, tolerability and PK of • Safety and tolerability NCT03436316 AZD8154 following single dose administration in healthy subjects Secondary endpoint: CVRM • PK parameters Respiratory Other
100 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: H2 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 Respiratory Other
101 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 glucose tolerance test) in comparison with prednisolone Respiratory Phase IIa Patients with active RA 40 A Phase II, randomised, double-blind, parallel trial to assess the Primary endpoint: • FPCD: Q1 2018 NCT03368235 efficacy, safety and tolerability of AZD9567 compared to To assess the efficacy of AZD9567, 40 mg, prednisolone 20 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
102 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 IIb Anti-Respiratory 29-35 WK GA 1,453 • Randomised, double-blind, placebo-controlled trial • Safety and efficacy • FPCD: Q4 2016 Syncytial Virus (Gestational age) • Route of administration: intramuscular • Data readout: Q4 2018 NCT02878330 mAb-YTE infants nirsevimab (MEDI8897) 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: 2020 NCT02696902 Respiratory Other
103 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 study 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 104 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 105 Clinical trials appendix DRAFT Q3 2019 results update