Clinical trials appendix

Full year and Q4 2020 results update Movement since Q3 2020 update

New to Phase I New to Phase II New to Pivotal trial New to registration

NME NME NME NME AZD3366 AZD8233 AZD7442 COVID-19 Vaccine AstraZeneca [EU] 1 CD39L3 CV disease hypercholesterolemia CV disease COVID-19 long-acting antibody combination SARS-CoV-2 COVID vaccine prevention and treatment of COVID-19 AZD3427 MEDI6570 Lifecycle Management # ThP CV disease LOX-1 mAb CV disease monalizumab + (INTERLINK-1) Farxiga/Forxiga2 Dapa-CKD [US, EU, JP & CN] 1 NKG2a mAb + EGFR mAb 2L+ relapsed metastatic head and SGLT2 inhibitor renal outcomes and CV mortality in AZD5305 Imfinzi + imaradenant# (AZD4635) + cabazitaxel neck squamous cell cancer patients with CKD PARP1Sel solid tumours PD-L1 mAb + A2aR inhibitor + Lifecycle Management prostate cancer Breztri MEDI5752 + Axitinib LABA/LAMA/ICS asthma PD-1/CTLA-4 bispecific mAb + Additional indication VEGF advanced renal cell adavosertib# Enhertu# DESTINY-Breast05 carcinoma Wee1 inhibitor uterine serous cancer HER2 targeting antibody drug conjugate HER2-positive post- neoadjuvant high-risk breast cancer MEDI9253 AZD5718 rNDV IL12 solid tumor FLAP CKD Farxiga/Forxiga2 DAPA-MI SGLT2 inhibitor prevention of heart failure and CV death Lifecycle Management following a myocardial infarction in patients without type-2 Enhertu# DESTINY-PanTumour01 diabetes HER2 targeting antibody drug conjugate HER2- expressing solid tumors Imfinzi# + CRT KUNLUN PD-L1 mAb + CRT locally advanced esophageal squamous cell Fasenra ARROYO carcinoma IL-5R mAb atopic dermatitis Imfinzi# + CTx MATTERHORN Fasenra HILLIER PD-L1 mAb + CTx neoadjuvant/adjuvant gastric cancer IL-5R mAb chronic spontaneous urticaria Tagrisso +/- CTx neoadjuvant NeoADAURA EGFR inhibitor +/- CTx stage II/III resectable EGFRm NSCLC

Phase progressions based on first patient dose achievement. ¶ Registrational Phase II/III trial # Partnered and/or in collaboration 1 Submission accepted 2 2 Farxiga in the US; Forxiga in ROW Movement since Q3 2020 update

Removed from Phase I Removed from Phase II Removed from Phase III Removed from registration

NME NME Additional indication NME AZD5153 abediterol# Imfinzi# + tremelimumab KESTREL COVID-19 Vaccine AstraZeneca# [EU] 1 BRD4 inhibitor solid tumours, haematological LABA asthma / COPD PD-L1 mAb + CTLA-4 mAb 1st-line HNSCC SARS-CoV-2 COVID vaccine malignancies imaradenant# (AZD4635) Lifecycle Management Lifecycle Management 2 AZD5634 A2aR inhibitor prostate cancer Farxiga/Forxiga DETERMINE-Preserved Brilinta3 THALES [US] 1 inhaled ENaC cystic fibrosis SGLT-2 inhibitor heart failure with preserved P2Y12 acute ischaemic stroke or oleclumab + imaradenant# (AZD4635) ejection fraction transient ischaemic attack AZD6615 CD73 mAb + A2aR inhibitor prostate cancer Farxiga/Forxiga2 DETERMINE-Reduced hypercholesterolemia CV disease Symbicort SYGMA [CN] 1 SGLT-2 inhibitor heart failure with reduced velsecorat ejection fraction ICS/LABA as-needed use in mild asthma AZD9496 inhaled SGRM asthma / COPD selective oestrogen, oestrogen receptor +ve Tagrisso ADAURA [US] 1 breast cancer Lifecycle Management EGFR inhibitor adjuvant EGFRm NSCLC Calquence CALAVI BTK inhibitor COVID-19

Phase progressions based on first patient dose achievement. ¶ Registrational Phase II/III trial # Partnered and/or in collaboration 1 Approved 2 Farxiga in the US; Forxiga in ROW 3 Brilinta in the US and Japan; Brilique in ROW

3 Q4 2020 new molecular entity (NME)1 pipeline

Phase I Phase II Phase III Under Review 21 New Molecular Entities 21 New Molecular Entities 10 New Molecular Entities 0 New Molecular Entities

AZD0466 adavosertib# capivasertib# + abiraterone CAPItello-281 Imfinzi#+tremelimumab Imfinzi#+monalizumab# BCL2/xL haematological and solid Wee1 ovarian / uterine serous / solid AKT+abiraterone PTEN deficient metastatic PD-L1+CTLA-4 solid tumours PD-L1+NKG2a solid tumours tumours tumours hormone sensitive prostate cancer

Imfinzi#+tremelimumab+chemo AZD2811 nanoparticle capivasertib#+fulvestrant CAPItello-291 AZD1390 Imfinzi#+tremelimumab PD-L1+CTLA-4 1L PDAC oesophageal Aurora solid tumours, haematological AKT+fulvestrant locally-advanced glioblastoma PD-L1+CTLA-4 biliary tract oesophageal SCLC malignancies (inoperable) or metastatic breast cancer

AZD4573 Imfinzi+# camizestrant (AZD9833) Imfinzi#+tremelimumab capivasertib+chemotherapy CAPItello-290 CDK9 haematological malignancies PD-L1+MEK solid tumours SERD ER+ breast PD-L1+CTLA-4 gastric cancer AKT+chemotherapy mTNBC 1L

Imfinzi+FOLFOX+ Imfinzi#+/-tremelimumab+chemo AZD5305 IPH5201# capivasertib# (platform) COLUMBIA1 POSEIDON PARP1Sel solid tumours CD39 solid tumours AKT prostate PD-L1+chemo+VEGF+multiple novel PD-L1+/-CTLA-4+SoC 1L NSCLC

Imfinzi (platform) HUDSON MEDI1191 Imfinzi+Lynparza# BAYOU Imfinzi#+/-tremelimumab+CRT ADRIATIC AZD5991 PD-L1+multiple novel ONC therapies MCL1 haematological malignancies IL12 mRNA solid tumours PD-L1+PARP bladder PD-L1+/-CTLA-4+CRT LS-SCLC post IO NSCLC

AZD7648# Imfinzi# (platform) BALTIC MEDI2228 Lynparza#+AZD6738 VIOLETTE Imfinzi#+tremelimumab HIMALAYA DNAPK solid and haematological PD-L1+CTLA-4, WEE1+Carboplatin, BCMA ADC multiple myeloma PARP+ATR breast PD-L1+CTLA-4 1L HCC tumours ATR+PARP ES-SCLC R/R

Imfinzi# (platform) COAST AZD8701 MEDI5395 MEDI5752 Imfinzi#+tremelimumab+SoC NILE PD-L1+multiple novel ONC therapies FOXP3 solid tumours rNDV GMCSF solid tumours PD-1/CTLA-4 solid tumours PD-L1+CTLA-4+SoC 1L urothelial cancer NSCLC

Calquence (platform) PRISM MEDI5752+Axitinib Imfinzi# (platform) NeoCOAST oleclumab+chemo or Imfinzi#+ Lynparza#+Imfinzi# DUO-E BTK + multiple novel onc therapies r/r PD-1/CTLA-4+VEGF advanced renal PD-L1+multiple novel ONC therapies oleclumab+chemo CD73+chemo or PARP+PD-L1 1L endometrial cancer aggressive NHL cell carcinoma NSCLC PD-L1+CD73+chemo pancreatic

Imfinzi# + imaradenant# (AZD4635) + Post-1L Tagrisso (platform) ORCHARD Calquence+ceralasertib MEDI9253 Lynparza#+Imfinzi#+bevacizumab DUO-O cabazitaxel EGFR+multiple novel ONC therapies BTK+ATR haematological tumours rNDV IL12 solid tumours PARP+PD-L1+VEGF 1L PD-L1+A2aR+CTx prostate cancer EGFRm NSCLC

Tagrisso combo# TATTON monalizumab#+cetuximab INTERLINK-1 Imfinzi#+adavosertib# Imfinzi#+Lynparza# ORION Tagrisso+# SAVANNAH EGFR+MEK/MET advanced EGFRm NKG2a+EGFR 2L+ relapsed metastatic PD-L1+Wee1 solid tumours PD-L1+PARP 1L mNSCLC EGFR+MET advanced EGFRm NSCLC NSCLC HNSCC

Imfinzi#+RT (platform) CLOVER Imfinzi#+MEDI0457# PD-L1+RT HNSCC NSCLC SCLC PD-L1+DNA HPV vaccine HNSCC

Phase progressions based on first patient dose achievement. 1 Includes novel combinations and additional indications for assets where the lead is not yet launched. 4 # Partnered and/or in collaboration; ¶ Registrational Phase II/III trial Oncology Precision medicine approach being explored Q4 2020 new molecular entity (NME)1 pipeline

Phase I Phase II Phase III 14 New Molecular Entities 21 New Molecular Entities 5 New Molecular Entities

AZD4041# AZD7442 AZD0284 anifrolumab# MEDI3506 1 receptor antagonist opioid use long-acting antibody combination RORg psoriasis / respiratory Type I IFN receptor lupus nephritis IL-33 AD / COPD / asthma / COVID-19 disorder COVID-19

AZD0449 AZD8154 anifrolumab# MEDI5884# brazikumab¶ Inhaled JAK inhibitor asthma Inhaled PI3Kgd asthma Type I IFN receptor SLE SC cholesterol modulation cardiovascular IL23 crohns disease

nirsevimab# AZD1402# AZD9977 AZD4831 MEDI6012 RSV mAb-YTE passive RSV inhaled IL-4Ra asthma MCR CV disease MPO HFpEF LCAT cardiovascular immunisation

MEDI0618# AZD2373 AZD5718 MEDI6570 PT027 PAR2 antagonist mAb osteooarthritis Podocyte health nephropathy FLAP coronary artery disease / CKD LOX-1 CV disease ICS/SABA asthma pain

MEDI7352 AZD2693 MEDI1341# AZD7986# tezepelumab# NAVIGATOR SOURCE NGF/TNF OA pain / painful diabetic nonalcoholic steatohepatitis alpha synuclein parkinson's disease DPP1 COPD TSLP severe uncontrolled asthma neuropathy

AZD3366 MEDI1814# AZD8233 navafenterol# CD39L3 CV disease amyloidβ alzheimer's disease hypercholesterolemia cardiovascular MABA COPD

AZD3427 MEDI8367 AZD8601# suvratoxumab Under review Relaxin ThP CV disease avb8 chronic kidney disease VEGF-A cardiovascular α-Toxin Staphylococcus pneumonia 1 New Molecular Entity

AZD9567 tezepelumab# anifrolumab# TULIP SGRM chronic inflammatory diseases TSLP atopic dermatitis Type I IFN receptor SLE

brazikumab tezepelumab# IL23 ulcerative colitis TSLP COPD

cotadutide verinurad GLP-1/ T2D / obesity / NASH / URAT-1 CKD / HFpEF DKD

MEDI3506 IL-33 diabetic kidney disease

Phase progressions based on first patient dose achievement. 1 Includes novel combinations and additional indications for assets where the lead is not yet launched 5 # Partnered and/or in collaboration; ¶ Registrational Phase II/III trial BioPharmaceuticals Precision medicine approach being explored Q4 2020 lifecycle management (LCM)1 pipeline

Phase I Phase II Phase III Under Review 1 Project 8 Projects 30 Projects 0 Projects

Imfinzi#+azacitidine# Enhertu# DESTINY-CRC-01 Calquence# Imfinzi# CALLA Imfinzi#+CTx TOPAZ-1 PD-L1+azacitidine MDS ADC colorectal cancer BTK inhibitor 1st line MCL PD-L1 adj. locally-advanced cervical cancer PD-L1+CTx 1L biliary tract cancer

Enhertu# DESTINY-Gastric02 Calquence# Imfinzi# PEARL Imfinzi#+VEGF EMERALD-2 ADC gastric BTK inhibitor r/r CLL, high risk PD-L1 1L metastatic NSCLC PD-L1+VEGF adjuvant HCC

Enhertu# DESTINY-Lung01 Calquence#++ Imfinzi# post-SBRT PACIFIC-4 Imfinzi#+VEGF+TACE EMERALD-1 ADC NSCLC BTK+BCL-2+anti-CD20 1st line CLL PD-L1 post-SBRT stage I/II NSCLC PD-L1+VEGF+TACE locoregional HCC

Enhertu# DESTINY-PanTumor01 Lynparza# LYNK-003 Calquence+R-CHOP ESCALADE Imfinzi# POTOMAC HER2 targeting ADC HER2-expressing PARP platinum sensitive 1L colorectal BTK+R-CHOP 1L DLBCL PD-L1 non muscle invasive bladder cancer solid tumours cancer

Enhertu# DESTINY-PanTumor02 Imfinzi#+CRT KUNLUN Enhertu# DESTINY-Breast02 Lynparza# OlympiA HER2 targeting ADC HER2-expressing PD-L1+CRT locally-advanced esophageal ADC breast PARP gBRCA adjuvant breast solid tumours squamous cell carcinoma

Imfinzi# (platform) BEGONIA Enhertu# DESTINY-Breast03 Imfinzi#+CRT PACIFIC-2 Lynparza# SOLO-3 PD-L1 1L mTNBC ADC breast PD-L1+CRT NSCLC PARP BRCAm PSR ovarian

Imfinzi#+CRT PACIFIC-5 (China) Imfinzi# (platform) MAGELLAN Enhertu# DESTINY-Breast04 Lynparza+abiraterone# PROpel PD-L1+CRT locally-advanced stage III PD-L1 1L mNSCLC ADC breast PARP+NHA prostate cancer NSCLC

Lynparza# (basket) MK-7339-002 / Tagrisso +/- CTx neoadjuvant Enhertu# DESTINY-Breast05 Imfinzi#+Ctx MERMAID-1 LYNK002 NeoADAURA EGFR stage II/III resectable ADC breast PD-L1 stage II-III adjuvant NSCLC PARP HRRm cancer EGFRm NSCLC

Imfinzi#+CTx neoadjuvant AEGEAN Tagrisso LAURA Enhertu# DESTINY-Breast06 PD-L1+CTx locally-advanced stage II-III EGFRm locally-advanced unresectable ADC breast NSCLC NSCLC

Imfinzi# + FLOT MATTERHORN Imfinzi#+CTx NIAGARA Tagrisso+chemo FLAURA2 PD-L1+CTx neo-adjuvant/adjuvant gastic PD-L1+CTx muscle invasive bladder cancer EGFR+chemo 1L adv EGFRm NSCLC

Phase progressions based on first patient dose achievement. 1 Includes significant LCM projects and parallel indications for assets beyond Phase III 6 # Partnered and/or in collaboration; ¶ Registrational Phase II/III trial Oncology Precision medicine approach being explored Q4 2020 lifecycle management (LCM)1 pipeline

Phase I Phase II Phase III Under Review 0 Projects 3 Projects 9 Projects 1 Project

Fasenra ARROYO Breztri Farxiga/Forxiga DAPA-CKD IL-5R chronic spontaneous urticaria LABA/LAMA/ICS asthma SGLT2 CKD

Farxiga/Forxiga DAPA-MI Fasenra HILLIER SGLT2 prevention of HF and CV death IL-5R atopic dermatitis following a myocardial infarction

roxadustat# Farxiga/Forxiga DELIVER HIF-PH inhibitor chemo induced anaemia SGLT2 HFpEF

Fasenra MANDARA IL-5R EGPA

Fasenra MESSINA IL-5R eosinophilic esophagitis

Fasenra NATRON IL-5R hypereosinophilic syndrome

Fasenra# OSTRO, ORCHID IL-5R nasal polyps

Fasenra# RESOLUTE IL-5R COPD

roxadustat# HIFPH anaemia MDS

Phase progressions based on first patient dose achievement. 1 Includes significant LCM projects and parallel indications for assets beyond Phase III 7 # Partnered and/or in collaboration; ¶ Registrational Phase II/III trial BioPharmaceuticals Precision medicine approach being explored Estimated key regulatory submission acceptances

brazikumab crohns disease

capivasertib + fulvestrant locally advanced or Fasenra mBC CAPItello-291 severe asthma (China) capivasertb + CTx 1L mTNBC nirsevimab PT027 asthma CAPItello-290 passive RSV immunisation Imfinzi + tremelimumab HCC Imfinzi + tremelimumab + CRT LDS-SCLC capivasertb + abiraterone PTEN deficient Lynparza + Imfinzi endometrial cancer AZD7442 SARS-CoV-2 HIMALAYA ADRIATIC mHSPC CAPItello-281 DUO-E tezepelumab asthma Imfinzi +/- tremelimumab NSCLC Imfinzi + tremelimumab + SoC urothelial Lynparza +Imfinzi + bevacizumab ovarian

NME Koselugo NF1 (China / Japan) NAVIGATOR POSEIDON NILE DUO-O H1 2021 H2 2021 2022 2022+ Calquence r/r CLL, high risk Enhertu Enhertu Calquence + R-CHOP 1L DLBCL Imfinzi non muscle invasive bladder POTOMAC ELEVATE-RR DESTINY-Breast03 DESTINY-Breast02 ESCALADE Imfinzi + CRT NSCLC Imfinzi NSCLC Enhertu Calquence + venetoclax + Lynparza platinum sensitive 1L colorectal

LCM PACIFIC-2 PEARL DESTINY-Breast04 obinutuzumab 1L CLL AMPLIFY LYNK-003 COVID-19 Vaccine AstraZeneca Lynparza breast Imfinzi + CTx biliary tract Calquence 1L MCL monalizumab + cetuximab 2L+ relapsed metastatic SARS-CoV-2 (US / Japan) OLYMPIA TOPAZ-1 ECHO HNSCC INTERLINK-1 Fasenra nasal polyps Lynparza + abiraterone prostate Imfinzi + VEGF + TACE locoregional HCC Enhertu Tagrisso stage II/III resectable EGFRm NSCLC OSTRO PROPEL EMERALD-1 DESTINY-Breast05 NeoADAURA Lynparza ovarian Enhertu Tagrisso locally adv. unresectable NSCLC LAURA SOLO-3 DESTINY-Breast06 Imfinzi + CRT LA ESCC Tagrisso + CTx EGFRm NSCLC Duaklir Genuair COPD (China) KUNLUN FLAURA2 Farxiga HF (HFpEF) Imfinzi + CRT NSCLC Imfinzi + chemo muscle invasive bladder DELIVER PACIFIC-5 (China) NIAGARA Imfinzi neoadjuvant NSCLC Breztri asthma roxadustat anemia in MDS AEGEAN KALOS, LOGOS Xigduo XR/Xigduo Imfinzi + CRT neo-adjuvant/adjuvant gastric Farxiga prevention of HF and CV death following a type-2 diabetes (China) MATTERHORN myocardial infarction DAPA-MI Imfinzi + CTx stage II-III adjuvant NSCLC Fasenra COPD MERMAID-1 RESOLUTE Imfinzi + VEGF adjuvant HCC Fasenra eosinophilic esophagitis EMERALD-2 MESSINA Imfinzi post-SBRT NSCLC Fasenra EGPA PACIFIC-4 MANDARA Imfinzi cervical Fasenra HES Note. NME section includes novel combinations and additional indications for assets where the lead is not yet launched CALLA NATRON Imfinzi adjuvant NSCLC Fasenra nasal polyps BR.31 ORCHID (China / Japan) Oncology BioPharmaceuticals 8 Designations 5 17 12 36 29 Accelerated approvals Breakthrough / PRIME1 / Sakigake2 Fast Track Priority Review / RTOR3 Orphan Lynparza ovarian cancer SOLO-2 (US) Tagrisso EGFRm T790M NSCLC (US) MEDI3902 Psl-PcrV pneumo Px (US) Tagrisso EGFRm T790M NSCLC (JP) Lynparza ovarian cancer SOLO-2 (US) Tagrisso EGFRm T790M NSCLC (US) Lynparza prostate cancer PROFOUND (US) savratoxumab Staph HAP (US) Tagrisso EGFRm T790M NSCLC (US) Lumoxiti HCL PLAIT (US) Imfinzi bladder cancer (US) Imfinzi bladder cancer 1L (US) Imfinzi NSCLC (US) Imfinzi bladder cancer 2L (US) Lumoxiti HCL PLAIT (EU) Calquence MCL (US) Calquence MCL (US) nirsevimab (MEDI8897) RSV mAB (US) Tagrisso NSCLC AURA3 (US) Crestor paediatric (US) Enhertu unresectable or HER2+ MBC 3L Imfinzi stage III NSCLC 1L PACIFIC (US) Imfinzi HNSCC HAWK (US) Calquence MCL (US) VEGFR tki (US) DESTINY-Breast01 (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 RSV mAB (US) Tagrisso EGFRm T790M NSCLC (CN) Tagrisso NSCLC FLAURA (US) AZD3241 MPO (EU) nirsevimab RSV mAB (EU)1 Farxiga HFrEF (US) Imfinzi stage III NSCLC PACIFIC (EU) Calquence CLL 1L (US) selumetinib NFI type 1 SPRINT (US) Farxiga chronic kidney disease (US) Imfinzi stage III NSCLC PACIFIC (JP) Calquence MCL (US) Enhertu DESINTY-BREAST01 (US) cotadutide non-alcoholic steatohepatitis (US) Lynparza tablet (US) Calquence WM (US) Calquence CLL (US) Farxiga MI RRCT DAPA-MI (US) Lynparza tablet (CN) Calquence CLL 1L (EU) Enhertu gastric cancer (JP)2 Lynparza breast cancer OLYMPIAD (JP) selumetinib thyroid cancer ASTRA (US) Enhertu HER2+/HER2low gastric 3L Tagrisso NSCLC 1L FLAURA (JP) Lynparza breast cancer OLYMPIAD (JP) DESTINY-Gastric01 (US) Lumoxiti HCL PLAIT (US) Lynparza ovarian cancer SOLO-2 (JP) Enhertu HER2mut NSCLC 2L+ Lynparza ovarian SOLO-1 (US) Koselugo/ selumetinib NFI type 1 SPRINT (US) DESTINY-Lung01 (US) Lynparza ovarian SOLO-1 (CN) Koselugo/ selumetinib NFI type 1 SPRINT (EU) Tagrisso adjuvant NSCLC ADAURA (US) Breztri Aerosphere (PT010) COPD (CN) Lynparza POLO (US) Forxiga CKD DAPA-CKD (US) Tagrisso NSCLC 1L FLAURA (CN) Fasenra EGPA (US) Breztri Aerosphere (PT010) (CN) Fasenra HES (US) Lokelma hyperkalaemia (CN) saracatinib IPF (US) Lynparza pancreatic 1L (US) Imfinzi +/-treme+SOC SCLC 1L CASPIAN (US) Enhertu DESINTY-BREAST01 (US) Fasenra EoE (US) ACCELERATED APPROVAL, these regulations allowed medicines for serious conditions that addressed an unmet medical need to be approved based on a surrogate endpoint. Farxiga HF DAPA-HF (US) Imfinzi +treme HCC 1L HIMALAYA (US) Imfinzi +/-treme+SOC SCLC 1L CASPIAN (US) Lynparza pancreatic cancer POLO (JP) BREAKTHROUGH DESIGNATION is a process designed to expedite the development and review of medicines which may demonstrate substantial Lynparza prostate PROfound (US) Enhertu HER2+/HER2low gastric 3L improvement over available therapy. 1PRIME is a scheme launched by the EMA to enhance support for the development of medicines that target an unmet DESTINY-Gastric01 (US) medical need. 2SAKIGAKE is aimed at early introduction of innovative medicines, medical devices, etc. that are initially developed in Japan. Lynparza +Avastin ovarian 1L PAOLA-1 (US) Koselugo/ selumetinib NFI type 1 SPRINT (US) Koselugo /selumetinib NFI type 1 SPRINT (JP) FAST TRACK is a process designed to facilitate the development, and expedite the review of medicines to treat serious conditions and fill an unmet Calquence CLL ELEVATE-TN, ASCEND3 (US) Imfinzi+CTx biliary tract 1L TOPAZ-1 (US) medical need. 3REAL-TIME ONCOLOGY REVIEW (RTOR) and Project Orbis is an initiative of the FDA Oncology Centre of Excellence (OCE) providing a Brilinta stroke THALES (US) Imfinz+/- tremelimumab HCC 1L HIMALAYA (EU) framework for concurrent submission and review of oncology products among international partners. Imfinzi Q4W regimen NSCLC, bladder (US) PRIORITY REVIEW DESIGNATION is the US FDA’s goal to take action on an application within 6 months. Tagrisso adjuvant NSCLC ADAURA (US) ORPHAN DRUG DESIGNATION, intended for treatment, diagnosis or prevention of rare diseases/disorders that affect fewer than 200,000 patients in the Enhertu HER2+/HER2low gastric 3L US, or that affect more than 200,000 patients but are not expected to recover the costs of developing and marketing a treatment drug. DESTINY-Gastric01 (US) Lynparza prostate PROfound (CN) Oncology BioPharmaceuticals Forxiga CKD DAPA-CKD (US) 9 Forxiga CKD DAPA-CKD (JP) Oncology – approved medicines and late-stage pipeline Approved medicines Late-stage development Tagrisso (highly-selective, irreversible EGFRi) Early development NSCLC Oncology

Trial Population Patients Design Endpoints Status

Phase III Adjuvant EGFRm NSCLC 682 • Arm 1: Tagrisso QD following complete tumour resection, with • Primary endpoint: DFS • FPCD: Q4 2015 ADAURA or without chemo • Secondary endpoints: DFS Rate, OS, OS • LPCD: Q1 2019 • Arm 2: placebo Rate, QoL • Data readout: Q2 2020

NCT02511106 • Trial unblinded due to efficacy CVRM Global trial - 25 countries • DFS primary endpoint met

Phase III Maintenance therapy in 200 • Arm 1: Tagrisso • Primary endpoint: PFS (BICR) • FPCD: Q4 2018 LAURA patients with • Arm 2: placebo • Secondary endpoints: CNS PFS, OS, • Data anticipated: 2022+ locally advanced, DoR, ORR, DCR NCT03521154 Global trial - 17 countries unresectable EGFRm Stage III NSCLC whose disease has not progressed following

platinum-based R&I chemoradiation therapy Phase III Real world setting in adult 3,020 Single-arm trial - Tagrisso • Primary endpoints: OS and safety • FPCD: Q3 2015 ASTRIS patients with advanced or • Secondary endpoint: PFS • LPCD: Q4 2017 metastatic, EGFRm T790M+ Global trial - 16 countries NCT02474355 NSCLC

Phase II EGFR TKI treatment-naïve 150 Single arm trial - Tagrisso • Primary Endpoint: proportion of patients • FPCD: Q2 2018 ELIOS patients with locally-advanced with a given tumour genetic and or metastatic EGFRm NSCLC Global trial - five countries proteomic marker at the point of disease NCT03239340 progression as defined by the investigator Other • Secondary endpoint: PFS, ORR, DoR

Phase I Patients with EGFRm NSCLC 8 Single-arm trial - Tagrisso • Primary Endpoints: assessments of brain • FPCD: Q4 2018 ODIN-BM with brain metastases standard uptake value (SUV) and • LPCD: Q1 2020 (PK) • Data anticipated: H1 2021 NCT03463525 • Secondary endpoints: PK

11 Approved medicines Late-stage development Tagrisso (highly-selective, irreversible EGFRi) Early development NSCLC, combinations Oncology

Trial Population Patients Design Endpoints Status

Phase III Neoadjuvant EGFRm NSCLC 351 Arm 1: placebo plus plus pemetrexed/carboplatin or • Primary endpoint: mPR • FPCD Q1 2021 NeoADAURA pemetrexed/cisplatin • Secondary endpoints cPR, EFS, DFS, • Data anticipated: 2022+ Arm 2: Tagrisso plus pemetrexed/carboplatin or OS

NCT04351555 pemetrexed/cisplatin CVRM Arm 3: Tagrisso

Global trial – 23 countries

Phase III 1st-line EGFRm NSCLC 586 Arm 1: Tagrisso plus pemetrexed/carboplatin or • Primary endpoint: PFS • FPCD: Q4 2019 FLAURA2 pemetrexed/cisplatin • Secondary endpoints: OS, LOS, ORR • Data anticipated: 2022+ Arm 2: Tagrisso DoR, Depth of response, PFS2. QoL, PK NCT04035486

Global trial – 22 countries R&I

Phase II Advanced EGFRm NSCLC 182 Modular design platform trial: • Primary endpoint: ORR • FPCD: Q3 2019 ORCHARD patients who have progressed • Module 1: Tagrisso + savolitinib • Secondary endpoints: PFS, DoR, OS, • Data anticipated: 2022+ on first line Tagrisso treatment • Module 2: Tagrisso + safety and tolerability NCT03944772 • Module 3: Tagrisso + • Module 4: carboplatin + pemetrexed + Imfinzi • Module 5: Tagrisso + • Module 6: Tagrisso + • No intervention: observational cohort Other Global trial - 8 countries

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: 2022+ NSCLC who have progressed Global trial and OS NCT03778229 following treatment with Tagrisso Phase Ib Advanced EGFRm NSCLC 344 • Arm 1: Tagrisso + Imfinzi • Safety, tolerability, pharmacokinetics and • FPCD: Q3 2014 TATTON TKI failure • Arm 2: Tagrisso + savolitinib preliminary anti-tumour activity • Data anticipated: H2 2020 • Arm 3: Tagrisso + selumetinib NCT02143466 Enrolment to Tagrisso + Imfinzi arm will not restart

Global trial

12 Approved medicines Late-stage development Imfinzi (PD-L1 mAb) Early development NSCLC, early disease Oncology

Trial Population Patients Design Endpoints Status

Phase III Completely resected 332 • Arm 1: Imfinzi + SoC chemo Primary endpoint: • FPCD: Q3 2020 MERMAID-1 Stage II and III NSCLC • Arm 2: placebo + SoC chemo • DFS • Data anticipated: 2022+ Secondary endpoint

NCT04385368 • DFS, OS, CVRM

Phase III Completely resected 284 • Arm 1: Imfinzi Primary endpoint: • Initiating MERMAID-2 Stage II-III NSCLC • Arm 2: placebo • DFS • Data anticipated: 2022+ Secondary endpoint NCT04642469 • DFS, PFS, OS

Phase III Neoadjuvant NSCLC patients 800 • Arm 1: Imfinzi + platinum-based chemo Primary endpoint: • FPCD: Q1 2019 AEGEAN Stage II and III resected • Arm 2: placebo + platinum-based chemo • mPR, EFS • Data anticipated: 2022+ NSCLC Secondary endpoint

NCT03800134 (incl. EGFR/ALK positive) • pCR R&I 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 resected • Arm 2: placebo • DFS • LPCD Q1 2020 NSCLC • Data anticipated: 2022+ NCT02273375 (incl. EGFR/ALK positive) Global trial Secondary endpoint: Partnered • OS

Phase III Unresected, locally-advanced 300 • Arm 1: Imfinzi i.v. Q4W + chemo/RT Primary endpoint: • FPCD: Q2 2018 PACIFIC-2 NSCLC • Arm 2: placebo + chemo/RT • PFS • LPCD: Q3 2019 • ORR • Data anticipated: H1 2021 NCT03519971 ex US global trial Secondary endpoint:

• OS Other

Phase III Imfinzi with SBRT in 630 • Arm 1: Imfinzi i.v. Q4W with definitive SBRT Primary endpoint: •FPCD: Q2 2019 PACIFIC-4 unresected, Stage I/II NSCLC • Arm 2: placebo with definitive SBRT • PFS •Data anticipated: 2022+ Secondary endpoint: NCT03833154 • OS

Phase III Unresected, locally-advanced 360 • Arm 1: Imfinzi i.v. Q4W following chemo/RT Primary endpoint: • FPCD: Q1 2019 PACIFIC-5 NSCLC • Arm 2: placebo following chemo/RT • PFS • Data anticipated: 2022+ Secondary endpoint: NCT03706690 ex US global trial, China focus • OS

Phase II/III Lung Master Stage IV squamous NSCLC 140 • Subtrial A: Imfinzi (non-match for other biomarker driven Primary endpoints: • FPCD: Q2 2014 Protocol patients subtrials) i.v. Q2W single arm Imfinzi Phase II only • ORR • Data anticipated: 2022+ • Subtrial B: PI3K inhibitor vs. • PFS NCT02154490 Biomarker-targeted • Subtrial C: CDK4/6 inhibitor vs, docetaxel • OS 2L therapy • Subtrial D: AZD4547 (FGFR inhibitor) vs. docetaxel Partnered • Subtrial E: C-MET/HGFR Inhibitor + vs. erlotinib 13 Approved medicines Late-stage development Imfinzi (PD-L1 mAb) +/- treme (CTLA-4 mAb) Early development Lung cancer, advanced disease Oncology

Trial Population Patients Design Endpoints Status

Phase III NSCLC 1L 650 • Arm 1: Imfinzi Q4W Primary endpoint: • FPCD: Q1 2017 PEARL • Arm 2: chemotherapy • OS • LPCD: Q1 2019 • Data anticipated: 2022 NCT03003962 Asia trial CVRM

Phase III NSCLC 1L 1,000 • Arm 1: Imfinzi + chemo Primary endpoint: • FPCD: Q2 2017 POSEIDON • Arm 2: Imfinzi + tremelimumab + chemo • OS • LPCD: Q4 2018 • Arm 3: SoC • PFS • Data readout: Q4 2019 NCT03164616 • PFS primary endpoint met • OS data anticipated: H1 2021

Phase II NSCLC 1L 200 • Arm A1: Imfinzi Primary endpoint: • FPCD: Q1 2019 MAGELLAN • Arm A2: Imfinzi + danvatirsen • Safety & tolerability • Data anticipated: 2022+

• Arm A3: Imfinzi + oleclumab Secondary endpoint: R&I NCT03819465 • Arm A3: MEDI5752 • ORR, DoR, PFS, OS, PK, ADA • Arm B1: Imfinzi + Investigator's choice of chemo • Arm B2: Imfinzi + danvatirsen + Investigator's choice of chemo • Arm B3: Imfinzi + oleclumab + Investigator's choice of chemo • Arm B4: MEDI5752

Phase III Limited stage SCLC 1L 600 • Arm 1: Imfinzi + tremelimumab (4 doses) Primary endpoints: • FPCD: Q4 2018 ADRIATIC following platinum-based • Arm 2: Imfinzi • PFS • Data anticipated: 2022 concurrent chemoradiation • Arm 3: placebo • OS

NCT03703297 therapy Other

Phase III Extensive stage SCLC 1L 805 • Arm 1: Imfinzi + tremelimumab + EP (carboplatin or cisplatin + Primary endpoint: • FPCD: Q1 2017 CASPIAN etoposide) • OS • LPCD: Q2 2018 • Arm 2: Imfinzi + EP (carboplatin or cisplatin + etoposide) • Data readout: Q2 2019 NCT03043872 • Arm 3: EP (carboplatin or cisplatin + etoposide) • OS Primary endpoint met for Imfinzi monotherapy • OS primary endpoint not met for Imfinzi + tremelimumab

Phase II SCLC 72 • Arm A: Imfinzi + tremelimumab Q4W • Primary endpoint: ORR • FPCD: Q4 2016 BALTIC • Arm B: adavosertib and carboplatin BID • Data anticipated: 2022+ • Arm C: ceralasertib and Lynparza NCT02937818

14 Approved medicines Late-stage development Imfinzi (PD-L1 mAb) Early development Other cancers, early disease Oncology

Trial Population Patients Design Endpoints Status

Phase III Non-muscle invasive bladder 975 • Arm 1: BCG (Induction + maintenance) Primary endpoints: • FPCD: Q2 2018 POTOMAC cancer • Arm 2: Imfinzi + BCG (Induction only) • DFS • LPCD: Q4 2020 • Arm 3: Imfinzi + BCG (Induction + maintenance) • Data anticipated: 2022+

NCT03528694 CVRM

Phase III Muscle-invasive bladder 960 • Arm 1: Imfinzi in combination with + cisplatin, Coprimary endpoints: • FPCD: Q4 2018 NIAGARA cancer Imfinzi maintenance • pCR • Data anticipated: 2022+ • Arm 2: gemcitabine + cisplatin • EFS NCT03732677

Phase III Locoregional HCC 710 • Arm 1: TACE in combination with Imfinzi Primary endpoint • FPCD: Q1 2019 EMERALD-1 • Arm 2: TACE in combination with Imfinzi + bevacizumab PFS for Arm 1 vs Arm 3 • Data anticipated: 2022 • Arm 3: TACE in combination with placebo

NCT03778957 Secondary endpoint R&I PFS for Arm 2 vs Arm 3 , 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: 2022+ • Arm 3: placebo + placebo NCT03847428 Secondary endpoint: • RFS Arm 1 vs Arm 3, OS, RFS at 24m

Phase III Locally advanced, 600 • Arm 1: Imfinzi + definitive CRT Primary endpoint: • FPCD: Q4 2020 KUNLUN unresectable ESCC • Arm 2: placebo + definitive CRT • PFS • Data anticipated: 2022+

Secondary endpoint: Other NCT04550260 • OS

Phase III Resectable GC/GEJC 900 • Arm 1: Imfinzi + FLOT Primary endpoint: • FPCD: Q4 2020 MATTERHORN • Arm 2: placebo + FLOT • EFS • Data anticipated: 2022+

NCT04592913 Secondary endpoint: • OS Arm 1 vs Arm 2 • pCR Arm 1 vs Arm 2

15 Approved medicines Late-stage development Imfinzi (PD-L1 mAb) +/- treme (CTLA-4 mAb) Early development Other cancers, advanced disease Oncology

Trial Population Patients Design Endpoints Status

Phase III Bladder cancer 1L 885 • Arm 1: Imfinzi + tremelimumab + SoC Primary endpoints: • FPCD: Q4 2018 NILE • Arm 2: Imfinzi + SoC • PFS • Data anticipated: 2022+ • Arm 3: SoC • OS

NCT03682068 CVRM

Phase III HNSCC 1L 823 • Arm 1: Imfinzi Primary endpoints: • FPCD: Q4 2015 KESTREL • Arm 2: Imfinzi + tremelimumab • OS • LPCD Q1 2017 • Arm 3: SoC Secondary endpoint: • Data readout: Q1 2021 NCT02551159 • Primary endpoint not met • PFS, ORR, DoR, safety, biomarkers

Phase III HCC 1L 1,324 • Arm 1: Imfinzi + tremelimumab Primary endpoint: • FPCD: Q4 2017 HIMALAYA • Arm 2: Imfinzi • OS • LPCD: Q4 2019

• Arm 3: Secondary endpoint: • Data anticipated: H2 2021 R&I 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 • LPCD: Q4 2016 pancreatic ductal- • Arm 3 tremelimumab (pancreatic ductal-adenocarcinoma) • Data readout: Q4 2018 NCT02527434 adenocarcinoma Secondary endpoints: • Safety, DoR

Phase III BTC 1L 757 • Treatment Arm 1 Imfinzi + gemcitabine + cisplatin Primary endpoint: • FPCD Q2 2019

TOPAZ-1 • Treatment Arm 2 placebo + gemcitabine + cisplatin • OS • Data anticipated: 2022 Other 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: 2022+ Secondary NCT03830866 Global trial • OS, CR rate, DoR, ORR, safety/tolerability

16 Approved medicines Late-stage development Imfinzi (PD-L1 mAb) +/- treme (CTLA-4 mAb) Early development Other cancers, advanced disease Oncology

Trial Population Patients Design Endpoints Status

Phase III Advanced solid malignancies 1,200 • Arm 1: Imfinzi • Primary endpoint: safety • FPCD: Q2 2017 STRONG • Arm 2: Imfinzi + tremelimumab • Data anticipated: 2022+

NCT03084471 CVRM

Phase I Solid tumours 80 • Arm 2 SCLC: Imfinzi + tremelimumab + carboplatin + etoposide • Safety • FPCD: Q1 2016 NCT02658214 • Arm 3 TNBC: Imfinzi + tremelimumab + chemo • LPCD: Q1 2019 • Arm 4 TNBC: Imfinzi + tremelimumab + chemo • Data anticipated: 2022+ • Arm 5 GEJ: Imfinzi + tremelimumab + oxaliplatin + 5-FU + leucovorin • Arm 6 PDAC: Imfinzi + tremelimumab + chemo • Arm 7 ESSC: Imfinzi + tremelimumab + chemo

Phase I HNSCC, NSCLC, SCLC 102 • HNSCC Arm 1 • Safety • FPCD: Q2 2018 R&I • NSCLC Arm 1 • Data anticipated: H1 2021 CLOVER • NSCLC Arm 2 • NSCLC Arm 3 NCT03509012 • SCLC Arm 2 • SCLC Arm 3 • SCLC Arm 4

Phase II mTNBC 1L 110 • Arm 1 Imfinzi + paclitaxel Primary endpoint: • FPCD: Q1 2019

BEGONIA • Arm 2 Imfinzi + paclitaxel + capivasertib • Safety and tolerability • Data anticipated: 2022+ Other • Arm 4 Imfinzi + paclitaxel + danvatirsen NCT03742102 • Arm 5 Imfinzi + paclitaxel + oleclumab Secondary endpoint: • Arm 6 Imfinzi + Enhertu • ORR, PFS, DoR, OS, PK, ADA

Global trial

17 Approved medicines Late-stage development Lynparza (PARP inhibitor) Early development Multiple cancers Oncology

Trial Population Patients Design Endpoints Status

Phase III BRCAm adjuvant breast 1,836 • Arm 1: Lynparza BiD 12 month duration • Primary endpoint: invasive disease-free • FPCD: Q2 2014 OlympiA cancer • Arm 2: placebo 12-month duration survival (IDFS) • LPCD: Q2 2019 • Secondary endpoint: distant disease-free • Data anticipated: H1 2021

NCT02032823 Global trial partnership with BIG and NCI/NRG survival and OS CVRM

Partnered

Phase III 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

R&I Other

18 Approved medicines Late-stage development Lynparza (PARP inhibitor) Early development Imfinzi combinations Oncology

Trial Population Patients Design Endpoints Status

Phase III Advanced ovarian cancer 1L 1,256 Non tBRCAm (tumour BRCA) patients Primary endpoint: • FPCD: Q1 2019 DuO-O • Arm 1: bevacizumab • PFS • Data anticipated: 2022+ • Arm 2: bevacizumab + Imfinzi

NCT03737643 • Arm 3: bevacizumab + Imfinzi + Lynparza Secondary endpoints: CVRM • OS, PFS2 tBRCAm patients • bevacizumab (optional) + Imfinzi + Lynparza

Global trial

Phase III Advanced and recurrent endometrial 699 • Arm 1: chemo + Imfinzi placebo followed by Imfinzi placebo Primary endpoint • FPCD: Q2 2020 DUO-E cancer 1L and Lynparza placebo • PFS • Data anticipated: 2022+ • Arm 2: chemo + Imfinzi followed by Imfinzi + Lynparza

NCT04269200 placebo Secondary endpoints: R&I • Arm 3: chemo + Imfinzi followed by Imfinzi + Lynparza • OS, PFS2, ORR, DoR

Global Trial

Phase II Stage IV NSCLC whose disease has 250 • Arm 1: Imfinzi + Lynparza Primary endpoint: • FPCD Q1 2019 ORION not progressed following SoC chemo • Arm 2: Imfinzi + placebo • PFS • Data anticipated: H1 2021 + Imfinzi Maintenance therapy 1L NCT03775486 Global trial Secondary enpoints: • OS, ORR, DoR, PFS in HRRm, PK, ADA

Phase II Platinum-Ineligible unresectable 154 • Arm 1: Imfinzi + Lynparza • Primary endpoint: PFS • FPCD: Q2 2018 Other BAYOU Stage IV urothelial cancer • Arm 2: Imfinzi + placebo • LPCD: Q3 2019 • Secondary endpoints: OS, DoR, ORR, • Data anticipated : H1 2021 NCT03459846 Global trial PFS in HRRm, PFS6, PK, ADA, PRO

Phase I / II gBRCAm ovarian cancer 2L+ 148 • Arm 1: Lynparza + Imfinzi Primary endpoints: • FPCD: Q2 2016 MEDIOLA gBRCAm HER2-negative breast • Dose until progression • DCR at 12 weeks • LPCD: Q2 2017 cancer 1-3L • Safety and tolerability NCT02734004 SCLC 2L+ Global trial Gastric cancer 2L+

Phase I / II gBRCAm ovarian cancer 2L+ 115 • Arm 1: Lynparza + Imfinzi Primary endpoints: • FPCD: Q2 2018 MEDIOLA Non-gBRCAm ovarian cancer 2L+ • Arm 2: Lynparza + Imfinzi • DCR at 12 weeks • LPCD: Q2 2020 (Ovarian expansion) Non-gBRCAm ovarian cancer 2L+ • Arm 3: Lynparza + Imfinzi + bevacizumab • ORR • Dose until progression • Safety and tolerability NCT02734004 Global trial

19 Approved medicines Late-stage development Lynparza (PARP inhibitor) Early development Other combinations Oncology

Trial Population Patients Design Endpoints Status

Phase III Advanced ovarian cancer 1L 806 • Arm 1: Lynparza maintenance therapy for two years or until Primary endpoint: • FPCD: Q2 2015 PAOLA-1 maintenance disease progression • PFS • LPCD: Q2 2018 • Arm 2: placebo for two years or until disease progression • Data readout: Q3 2019

NCT02477644 Secondary endpoints: • Primary endpoint met CVRM Externally sponsored Global trial • OS, PFS2

Phase III Metastatic castration-resistant 720 • Arm 1: Lynparza + abiraterone Primary Endpoint: • FPCD: Q4 2018 PROpel prostate cancer 1L • Arm 2: placebo + abiraterone • rPFS • Data anticipated: H2 2021 Global trial Secondary endpoints: NCT03732820 • TFST, TTPP, OS

Phase II TNBC 350 • Arm 1: Lynparza + ceralasertib • PFS • FPCD: Q2 2018 • Arm 2: Lynparza • ORR / OS • Data anticipated: H2 2021

VIOLETTE Trial conducted in 15 countries: North America, Europe and Asia • Safety and tolerability R&I NCT03330847

Phase II/III Recurrent platinum 680 • Arm 1: chemo Primary endpoints: • FPCD: Q2 2016 GY005 resistant/refractory ovarian • Arm 2: cediranib + Lynparza • PFS, OS • Data anticipated: 2022+ cancer • Arm 3: cediranib NCT02502266 • Arm 4: Lynparza Secondary endpoints: Externally sponsored US/Canada sites • ORR, QoL, safety

Phase II HRRm or HRD-positive 370 • Arm 1: Lynparza Primary endpoints: • FPCD: Q1 2019 LYNK-002 advanced cancer • ORR

Global trial Other NCT03742895 Secondary endpoints: Partnered • DOR, OS, PFS, AE, Prog by CA-125

Phase III Advanced colorectal cancer 525 • Arm 1: bevacizumab + 5-FU maintenance Primary endpoints: • FPCD: Q3 2020 LYNK-003 1L maintanence • Arm 2: bevacizumab + Lynparza maintenance • PFS • Data anticipated: 2022+ • Arm 3: Lynparza maintenance NCT04456699 Secondary endpoints: Partnered Global trial • OS, ORR, DoR, AEs

Phase II Ovarian post-PARPi 192 • Arm 1: Lynparza + ceralasertib Primary endpoint • Initiating maintenance PSR • Arm 2: Lynparza • PFS • Data anticipated: 2022+ DUETTE • Arm 3: placebo Secondary endpoints Global trial • TTSP, ORR, OS NCT04239014 • Safety and tolerability

20 Approved medicines Late-stage development Enhertu ( deruxtecan, HER2 ADC) Early development Breast cancer Oncology

Trial Population Patients Design Endpoints Status

Phase II HER2-positive, unresectable and/or 230 Randomised, open label, sequential assignment Primary endpoint ORR • FPCD: Q4 2017 DESTINY-Breast01 metastatic breast cancer patients • Enhertu • LPCD: Q4 2018 previously treated with trastuzumab Secondary end points DoR, CBR, CBR, • Data readout: Q2 2019

NCT03248492 emtansine PFS, OS • Primary objective met CVRM

Phase III HER2-positive, unresectable and/or 600 Randomised open label parallel assignment Primacy endpoint PFS • FPCD: Q4 2018 DESTINY-Breast02 metastatic breast cancer pretreated with • Enhertu • Data anticipated H2 2021 prior standard of care HER2 therapies, Physicians choice of Secondary endpoints OS, ORR, DoR, CBR NCT03523585 including • + capecitabine • Trastuzumab + capecitabine

Phase III HER2-positive, unresectable and/or 500 Randomised open label parallel assignment Primary endpoint PFS • FPCD: Q4 2018 DESTINY-Breast03 metastatic breast cancer patients • Enhertu • Data anticipated H2 2021 previously treated with trastuzumab and • Ado-trastuzumab emtansine Secondary endpoints OS, ORR, DoR, CBR NCT03529110 taxane R&I

Phase III HER2-low, unresectable and/or 540 Randomised open label parallel assignment Primary end point PFS • FPCD: Q4 2018 DESTINY-Breast04 metastatic breast cancer patients • Enhertu • Data anticipated H2 2021 • Physicians choice of SoC chemo (choice of capecitabine, Secondary end points OS, DoR, ORR NCT03734029 eribulin, gemcitabine, paclitaxel or nab-paclitaxel) Phase III High-risk HER2-positive patients with 1,600 Randomised open label parallel assignment Primary end point IDFS • FPCD: Q4 2020 DESTINY-Breast05 residual invasive breast cancer following • Enhertu • Data anticipated 2022+ neoadjuvant therapy • Ado-trastuzumab emtansine Secondary end points DFS, OS, DRFI, NCT04622319 BMFI

Phase III HER2-Low, HR+ breast cancer patients 850 Randomised open label parallel assignment Primary end point PFS • FPCD Q2 2020 Other DESTINY-Breast06 whose disease has progressed on • Enhertu • Data anticipated 2022+ endocrine therapy in the metastatic • Investigator's choice standard of care chemotherapy Secondary end points OS, DoR, ORR NCT04494425 setting (capecitabine, paclitaxel, nab-paclitaxel)

Phase Ib/II HER2-positive metastatic breast cancer 350 Randomised open label sequential assignment Primary end point AE, SAE • FPCD: Q1 2021 DESTINY-Breast07 • Enhertu • Data anticipated 2022+ • Enhertu + Imfinzi Secondary end points ORR, PFS, DoR, OS NCT04538742 • Enhertu + • Enhertu + paclitaxel • Enhertu + Imfinzi + paclitaxel Phase Ib HER2-low metastatic breast cancer 185 Non-Randomised open label parallel assignment Primary end point AE, SAE • FPCD: Q1 2021 DESTINY-Breast08 • Enhertu + capecitabine • Data anticipated 2022+ • Enhertu + Imfinzi + paclitaxel Secondary end points ORR, PFS, DoR, OS NCT04556773 • Enhertu + capivasertib • Enhertu + anastrozole • Enhertu + Faslodex 21 Approved medicines Late-stage development Enhertu (, HER2 ADC) Early development Gastric cancer Oncology

Trial Population Patients Design Endpoints Status

Phase II HER2-overexpressing advanced gastric 233 Randomised open label parallel assignment Primary end point ORR • FPCD: Q4 2017 DESTINY-Gastric01 or gastroeosophogeal junction • Enhertu • LPCD: Q2 2019 adenocarcinoma patients who have • SoC chemo Secondary end points PFS, OS, DoR, • Data readout Q1 2020

NCT03329690 progressed on two prior treatment DCR, TTF, range of PK endpoints • Primary endpoint met CVRM regimens Asian trial 2 countries

Phase II HER2-positive gastric cancer that cannot 79 Open label single group assignment Primary endpoint ORR • FPCD: Q4 2019 DESTINY-Gastric02 be surgically removed or has spread • Enhertu • Data anticipated: H2 2021 Secondary endpoints PFS, ORR, OS, DoR NCT04014075

Phase Ib/II HER2-overexpressing gastric or 220 • Open label parallel assignment Part 1 • FPCD Q2 2020 R&I DESTINY-Gastric03 gastroeosophogeal junction cancer • Part 1: To determine recommended Phase 2 dose Primary endpoint safety patients • 5 Arms combine Enhertu with standard of care NCT04379596 (5-FU, capecitabine, oxaliplatin) and / or Part 2 Primary endpoint ORR

• Part 2: To assess efficacy of the selected combinations Secondary end points • Arm 2A Standard chemotherapy (control) DoR, DCR, PFS, OS, range of PK • Arm 2B Enhertu monotherapy endpoints, ADAs • Arm 2C Enhertu with chemotherapy

• Arm 2D Enhertu with chemotherapy and durvalumab Other Global trial 8 countries Phase III HER2-positive gastric cancer or gastro- 490 Open label randomised parallel group assignment Primary endpoint: OS • Initiating DESTINY-Gastric04 esophageal junction adenocarcinoma • Enhertu Secondary endpoints: ORR, DoR, PFS, patients who have progressed on or after • SoC chemo DcR, safety NCT04704934 a trastuzumab-containing regimen and have not received any additional systemic therapy

22 Approved medicines Late-stage development Enhertu (trastuzumab deruxtecan, HER2 ADC) Early development Other cancers Oncology

Trial Population Patients Design Endpoints Status

Phase II HER2-over-expressing or mutated, 170 Non randomised parallel group assignment Primary endpoint ORR • FPCD Q2 2018 DESTINY-Lung01 unresectable and/or metastatic NSCLC • Enhertu • Data anticipated H2 2021 Secondary endpoints DoR, PFS, OS

NCT03505710 CVRM

Partnered Phase II HER2-Mutated, Unresectable and/or 150 Randomised parallel group assignment Primary endpoint: ORR • FPCD Q1 2021 DESTINY-Lung02 Metastatic NSCLC • Arm 1 Enhertu 6.4 mg/kg Secondary endpoints: DoR, DCR, PFS, OS, • Arm 2 Enhertu 5.4mg/kg PK NCT04644237

Partnered

Phase Ib HER2-over-expressing, unresectable 120 Non randomised parallel group assignment Primary endpoint: safety • Initiating R&I DESTINY-Lung03 and/or metastatic NSCLC • Arm 1 Enhertu + Cisplatin + Imfinzi Secondary endpoints: ORR, DoR, DCR, • Arm 2 Enhertu + Carboplatin + Imfinzi PFS, OS, range of PK endpoints NCT04686305 • Arm 3 Enhertu + Pemetrexed + Imfinzi

• Arm 4 Enhertu + Imfinzi Other

23 Approved medicines Late-stage development Enhertu (trastuzumab deruxtecan, HER2 ADC) Early development Other cancers Oncology

Trial Population Patients Design Endpoints Status

Phase II HER2 expressing tumours 280 Non randomised single group assignment Primary endpoint: ORR • FPCD Q4 2020 DPT02 • Enhertu Secondary endpoints: DoR, DCR, PFS, OS

NCT04482309 CVRM

Phase II HER2m expressing tumours 100 Non-randomised single group assignment Primary endpoint: ORR • FPCD Q1 2021 DPT01 • Enhertu Secondary endpoints: DoR, DCR, PFS, PK

NCT04639219 R&I

Phase II HER2-expressing advanced colorectal 90 Non randomised single group assignment Primary endpoint ORR • FPCD Q1 2018 DESTINY-CRC01 cancer • Enhertu • LPCD Q2 2019 Secondary endpoints PFS, OS, DoR, • Data readout: Q2 2020 NCT03384940 range of PK endpoints • Primary endpoint met

Phase I Advanced solid malignant tumours 278 Non randomised single group assignment Primary end points ORR, number of • FPCD Q3 2015 J101 • Enhertu subjects with AEs, tumour response • Data read out Q3 2018

NCT02564900 Secondary endpoints PK Other

Phase I HER2-expressing locally 115 • Non randomised parallel group assignment Primary end points DLT, ORR • FPCD Q2 2020 advanced/metastatic breast or NSCLC • Enhertu + NCT04042701 Secondary endpoints DoR, DCR, PFS, Global trial 2 countries TTR, OS

Phase I HER2-expressing breast and urothelial 99 • Non randomised sequential assignment Primary end points DLT, ORR, TEAEs • FPCD Q3 2018 cancer • Enhertu + NCT03523572 Secondary endpoints DoR, DCR, PFS, Global trial 7 countries TTR, OS, ORR (investigator)

24 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 – IRC PFS (A vs C) • FPCD: Q1 2019 fit • Arm B: Calquence + venetoclax + obinutuzumab • Secondary - IRC PFS (B vs C); INV PFS • Data anticipated: 2022+ ACE-CL-311 • Arm C: FCR or BR (A vs C; B vs C) NCT03836261

Phase III Relapsed/refractory CLL 306 • Arm A: Calquence • Primary endpoint: IRC assessed PFS • FPCD Q3 2016 ACE-CL-309 (ASCEND) • Arm B: + idelalisib or bendamustine (investigator’s (arm A vs. Arm B) • Data readout: Q2 2019

NCT02970318 choice) • Secondary endpoints: INV-assessed • Primary endpoint met R&I ORR, OS, DoR, PROs

Phase III Relapsed/refractory high risk 533 • Arm A: Calquence • Primary endpoint: PFS • FPCD: Q2 2015 ACE-CL-006 (ELEVATE-RR) CLL • Arm B: • Secondary endpoints: comparison of • Data readout: Q1 2021 incidence of infections, RTs (Richter’s • Primary endpoint met 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: 2022 • Secondary endpoints: IA, PFS, ORR,

NCT02972840 DoR, time to response, OS Other

Phase III DLBCL 600 Calquence + rituximab, cyclophosphamide, doxorubicin, • Safety, ORR • FPCD: Q2 2020 ESCALADE vincristine, and prednisone • Data anticipated: 2022+ NCT04529772

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: 2022+ 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 25 Approved medicines Late-stage development Calquence (BTK inhibitor) Early development Blood cancers Oncology

Trial Population Patients Design Endpoint(s) Status

Phase I/II B-cell malignancies 40 Dose escalation and expansion trial of the combination of • Safety • FPCD: Q1 2015 ACE-LY-001 Calquence and ACP-319 (Pi3K inhibitor) • ORR • Data anticipated: H1 2020

NCT02328014 CVRM

Phase I/II Haematological malignancies 161 Calquence + pembrolizumab • Safety • FPCD: Q1 2015 ACE-LY-005 • Secondary endpoints: ORR, DoR, PFS, • Data anticipated: 2021 OS, TTNT (time to next therapy) NCT02362035

Phase I/II Waldenstrom 106 Calquence monotherapy • ORR • FPCD: Q3 2014 ACE-WM-001 microglobulinaemia • Data readout: Q4 2019

NCT02180724 R&I Phase Ib Relapsed/refractory de novo 21 Calquence monotherapy • Safety • FPCD: Q3 2014 ACE-LY-002 activated B-cell DLBCL • Data anticipated: H2 2019

NCT02112526

Phase Ib MCL 70 Calquence in combination with bendamustine and rituxumab • Safety • FPCD: Q1 2016 ACE-LY-106 • Arm A: treatment naive • Data anticipated: 2022+ • Arm B: relapsed/refractory NCT02717624 • Arm C: treatment naïve: Calquence + venetoclax + rituxumab

• Safety • FPCD: Q1 2015

Phase Ib Relapsed/refractory MM 28 • Arm A: Calquence Other ACE-MY-001 • Arm B: Calquence + • Data readout: Q2 2019

NCT02211014

Phase I Relapsed/refractory follicular 80 • Arm A: Calquence • Safety • FPCD: Q1 2015 ACE-LY-003 • Arm B: Calquence + rituximab • Data anticipated: 2022+ • 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: 2022+ • Arm B: treatment naïve OS NCT02296918 Calquence + venetoclax + rituxumab • Arm C: relapsed/refractory 26 • Arm D: treatment naïve Approved medicines Late-stage development Calquence (BTK inhibitor) Early development Blood and other cancers Oncology

Trial Population Patients Design Endpoint(s) Status

Phase I Japanese adults with 34 • Calquence monotherapy • Safety • FPCD: Q2 2017 advanced B-cell malignancies • Dose confirmation and expansion • PK • Data anticipated: 2022+ • 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 2021 ceralasertib NCT03328273

Phase I/II B-cell malignancies r/r 25 • Part 1: Calquence daily + vistusertib daily • MTD and optimal dosing schedule FPCD: Q3 2017 LY-110 • Part 2: Calquence daily + vistusertib 5 days on/2 days off • Safety Data anticipated: H2 2020

NCT03205046 R&I

Phase III CLL TN and r/r 600 • Arm A: treatment naïve • Safety Data anticipated: 2022+ 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 + ceralasertib • Secondary outcomes; ORR, DOR, PFS, Data anticipated: 2021 • Arm 3: Calquence + Hu5F9G4 + Rituxan OS

NCT03527147 • Arm 4: Calquence + AZD5153 Other An open-label platform trial with trial centres in US and UK

Phase Ib/II ≥ 2L glioblastoma multiforme 52 • Arm A: Calquence 200mg BID • Safety, ORR • FPCD: Q1 2016 ACE-ST-209 • Arm B: Calquence 400mg QD • Data anticipated: H2 2019

NCT02586857

Phase I/II Chinese adults r/r MCL and r/r 105 • Part 1: R/r B-cell MalignanciesPhase II • Safety, ORR • FPCD: Q2 2020 D8220C0007 CLL • Part 2: Cohort A: r/r MCL • Part 2: Cohort B: r/r CLL NCT03932331

Phase I Healthy volunteers 28 Part 1: Rel bioavailabilty for capsule vs tablet • Safety • FPCD: Q2 2019 D8220C00018 Part 2: Rel bioavailabilty for oral solution of tablet • Data anticipated: H1 2021 NCT04488016

27 28 Paediatric neurofibromatosistumours1, solidtype Koselugo Efficacy studyEfficacy I China Phase/ PK/ Safety Partnered study PK Safety I Japan/ Phase PartneredLeadtrial) (Merck NCT03745989 inhibitor) Koselugo Phase Partnered NCT01362803 SPRINT II Phase Trial Ib + MK - 8353(ERK adult NF1 adult Pediatric (2 patients Paediatric solid tumours Advanced NF1Paediatric Population ( selumetinib Inoperable - 17 yearsold),17 NF1 - PN 32 9 (dose escalation 80 (Stratum 2)25 (stratum 50 1) Patients - 12 trial) , MEK inhibitor) • • • arm Singlewith phases;3 Koselugo Open • Design Phase Single Koselugo Long term term Follow(60mths LongLSD) uppost LSD) post (24mths phaseExpansion cycles), Doseforconfirmation (n=6 3phase • • - Stratum Stratum PN no2: relatedmorbidity enrolmentat present morbidity relatedenrolmentStratum PN at 1: present label Phase I clinical study to assess clinical PK of assess andI to Phase safety study label Ib arm: arm: inJapanesepaediatricNF1 open in participants with advanced solid solid participants in tumours advancedwith Koselugo - label trial MK of label 25mg/m - 8353 in combination combination within 8353 2 BID BID strata: with2 - PN patients PFS) Efficacy Secondary:(ORR, Primary: • • • • • • • Endpoints effect endpointsSecondaryof Primary safety endpoints AE an to Trialdue discontinuations drug AEs DLTs outcomes/QoL Durationfunctionalresponseandof volumetric ratebymeasured MRI Complete Safety/tolerability and PK PK Safety/tolerabilityand partial and complete responsecomplete partial and PK/anti DoR ; TTR; TTR; ; - tumour ; FPCD: Q42020 • • • • • • Status Earlydevelopment Late Approved medicines FPCD: Q32020 FPCD: Q12019 Primary met endpoint Q1Data2019 readout: LPCD:Q42016 FPCD: Q32015 - stage development

Other R&I CVRM Oncology Approved medicines Late-stage development Lumoxiti (,CD22 mAb) Early development Blood cancer Oncology

Trial Population Patients Design Endpoints Status

Phase III Adults with relapsed or 80 • Multicentre, single-arm, open-label Phase III trial • Primary endpoint: rate of durable CR • FPCD: Q2 2013 PLAIT refractory HCL • Lumoxiti i.v. at the recommended dose (complete response): CR maintained for • Data readout: Q3 2017 > 180 days • Primary endpoint met

NCT01829711 • Secondary endpoints CVRM • Efficacy: CR rate, ORR, Duration of Partnered CR and ORR, TTR, PFS • Safety and tolerability

• PK and immunogenicity

R&I Other

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 R&I

Phase II EGFRm/MET amplified 56 • Tagrisso and savolitinib contribution of components • Primary endpoint: ORR • FPCD: Q4 2020 advanced NSCLC • Secondary endpoint: PFS, DoR, OS • Data anticipated: 2022

NCT04606771 Other

30 Approved medicines Late-stage development Capivasertib (AKT inhibitor) Early development Breast cancer, prostate cancer Oncology

Trial Population Patients Design Endpoints Status

Phase III Locally advanced or 800 Double-blind randomised comparative trial • PFS • FPCD Q3 2019 CAPItello-290 metastatic TNBC • Arm 1: capivasertib + paclitaxel • OS • Data anticipated: 2022+ • Arm 2: placebo + paclitaxel

NCT03997123 CVRM

Phase III Locally advanced (Inoperable) 834 Double-blind randomised comparative trial • PFS • FPCD Q2 2020 CAPItello-291 or metastatic HR+/HER2− • Arm 1: capivasertib + Faslodex • Data anticipated: 2022+ breast cancer • Arm 2: placebo +Faslodex

NCT04305496 R&I

Phase III De novo PTEN deficient 1,000 Double-blind randomised comparative trial • rPFS • FPCD Q3 2020 CAPItello-281 metastatic hormone sensitive • Arm 1: capivasertib + abiraterone • Data anticipated 2022+ prostate cancer • Arm 2: placebo + abiraterone

NCT04493853 Other

31 Approved medicines Late-stage development Monalizumab (NKG2a mAb) Early development Cancers Oncology

Trial Population Patients Design Endpoints Status

Phase III Recurrent or Metastatic 600 • Arm A: monalizumab + cetuximab i.v. • Primary: OS • FPCD: Q4 2020 INTERLINK-1 SCCHN, 2L • Arm B: placebo + cetuximab i.v. • Secondary: PFS, ORR, DoR • Data anticipated: 2022+

NCT04590963 CVRM

Global trial R&I

Phase I/II Advanced solid tumours 381 Escalation phase Primary endpoints: • FPCD: Q2 2016 • monalizumab + Imfinzi i.v. • Safety • Data anticipated: 2022 NCT02671435 • Exploration Phase: Objective Response Expansion phase per RECIST • monalizumab + Imfinzi i.v. recommended dose • Secondary endpoints include tumour Exploration phase response (OR, DC, DoR, PFS and OS), • monalizumab + Imfinzi i.v. recommended dose + SoC systemic immunogenicity, pharmacokinetics, therapy with or without biologic agent and monalizumab in pharmacodynamics

combination with a biologic agent in adult subjects with CRC Other Global trial

32 Approved medicines Late-stage development Camizestrant (AZD9833, oral SERD) Early development Breast cancer Oncology

Trial Population Patients Design Endpoints Status

Phase III ER+ HER2- breast cancer 1,342 A randomised, multicentre, double-blind, Phase III trial of • Primary endpoint: PFS • FPCD: Q1 2021 camizestrant plus versus anastrozole plus palbociclib • Secondary endpoint: OS, PFS2 • Data anticipated: 2022+ NCT04711252 for the treatment of patients with oestrogen receptor-positive,

HER2-negative advanced breast cancer who have not received CVRM any systemic treatment for advanced disease

Phase I ER+ breast cancer 266 • Open label multicentre trial of camizestrant administered • Primary outcome measures: safety and • FPCD: Q4 2018

orally in patients with advanced ER+ HER2 negative breast tolerability R&I NCT03616587 cancer. The trial design allows an escalation of dose with • Secondary outcome measures: multiple intensive safety monitoring to ensure the safety of patients. dose PK of AZD9833 alone and in The trial will determine the maximum tolerated dose of combination with palbociclib AZD9833 as monotherapy and in combination with palbociclib antitumour activity or abemeciclib. 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 camizestrant alone and in combination with Palbociclib or

Phase II ER+ breast cancer 288 • Randomised, open-label, parallel-group, multicentre trial • Primary outcome measure: mPFS • FPCD: Q2 2020

aimed to compare the efficacy and safety of oral camizestrant Other NCT04214288 versus intramuscular (IM) Faslodex in women with advanced breast cancer. Phase II ER+ breast cancer 84 • Randomised, open-label, parallel-group, multicentre trial to • Primary outcome measure: change in ER • FPCD: Q4 2020 investigate the biological effects of camizestrant in women expression between pre- and on- NCT04588298 with ER positive, HER2 negative primary breast cancer treatment tumour biopsies Phase I ER+ breast cancer 18 • Open-label study designed to evaluate the safety, tolerability, • Primary outcome measures: safety and • FPCD: Q4 2020 pharmacokinetics, and anti-tumour activity of camizestrant in tolerability NCT04541433 Japanese women with endocrine resistant ER+ HER2- breast • Secondary outcome measures: multiple cancer that is not amenable to treatment with curative intent. dose PK of AZD9833 Phase I Healthy volunteers 32 • Randomsied, open-label study to determine the relative • Primary outcome measure: relative • FPCD: Q3 2020 of different oral camizestrant tablet formulations bioavailability of AZD9833 delivered as • LPCD: Q4 2020 NCT04546347 and an camizestrant oral solution, the effect of food on the different tablet formulations and the effect • Data anticipated H1 2021 pharmacokinetics of an oral camizestrant tablet formulation, of food and the absolute bioavailability of camizestrant study in healthy post-menopausal female volunteers. 33 Approved medicines Late-stage development Datopotamab deruxtecan (TROP2 ADC) Early development NSCLC Oncology

Trial Population Patients Design Endpoints Status

Phase III NSCLC (without actionable 590 Randomised, open label • Primary endpoints: PFS, OS • FPCD: Q4 2020 TROPION-Lung01 mutation) • Datopotamab deruxtecan • Secondary endpoints: ORR, DoR, TTR, • Data anticipated: 2022+ • Docetaxel DCR, PK, anti-drug antibodies

NCT04656652 CVRM Partnered Global trial

Phase II NSCLC (with actionable 150 Randomised, open label • Primary endpoint: ORR • Initiating TROPION-Lung05 mutation) • Datopotamab deruxtecan • Secondary endpoint: DOR, PFS, OS, safety, PK, anti-drug antibodies NCT04484142 Global trial

Partnered R&I

Phase I NSCLC 350 Open label, two-part (dose escalation, dose expansion) • Primary endpoint: safety • FPCD: Q1 2018 TNBC • Datopotamab deruxtecan • Secondary endpoint: PK, antitumor NCT03401385 activity, anti-drug antibodies

Partnered Japan, US Other Phase I NSCLC (without actionable 86 Open label, combination with pembrolizumab, two-part (dose • Primary endpoint: safety • FPCD: Q4 2020 TROPION-Lung02 mutation) escalation, dose expansion) • Secondary endpoint: ORR, DOR, • Datopotamab deruxtecan + pembrolizumab • PFS, OS, PK, anti-drug antibodies NCT04526691 Partnered Japan, US

Phase I NSCLC (without actionable 74 Open label, combination with Imfinzi, two-part (dose • Primary endpoint: safety • Initiating TROPION-Lung04 mutation) escalation, dose expansion) • Secondary endpoint: : ORR, DOR, • Datopotamab deruxtecan + Imfinzi • PFS, OS, PK, NCT04612751 Partnered US, Japan

34 Oncology – early-stage development Approved medicines Late-stage development Imfinzi (PD-L1 mAb) Early development Cancer Oncology

Trial Compound Population Patients Design Endpoints Status

Phase I/II Imfinzi Solid tumours 1,022 • Dose escalation: 5 cohorts at Q2W and 1 cohort at Q3W • Safety • FPCD: Q3 2012 STUDY 1108 • Dose expansion: 16 tumour type cohorts at the Q2W MTD • Optimal biologic dose • LPCD: Q4 2016 defined during dose escalation • Secondary endpoints include PK, • Data readout: Q2 2020

NCT01693562 • Dose exploration: cohort at 20mg Q4W immunogenicity and antitumour activity CVRM

Global trial - nine countries

Phase I Imfinzi, azacitidine Myelodysplastic 79 Dose escalation and dose expansion trial • Safety and tolerability of monotherapy • FPCD: Q2 2014 syndrome • Part 1: Imfinzi and combination • Data anticipated: Q2 2020 NCT02117219 • Part 2 Arm 1: Imfinzi and tremelimumab • Secondary endpoints include duration of • Part 2 Arm 2: Imfinzi, tremelimumab and azacitidine response, PFS and OS, PK and immunogenicity Global trial - four countries

Phase I MEDI9090 Solid tumours 42 Multi-centre, open-label, single-arm trial for adult subjects • Safety, PK, number of subjects reporting • FPCD: Q3 2016 R&I infusion related reaction • LPCD: Q1 2017 NCT02900157 US and Japan trial centers • Data readout: Q2 2020

Phase II Imfinzi NSCLC 340 5 modules encompassing 16 cohorts • Primary outcome; ORR • FPCD: Q1 2018 HUDSON Lynparza • Module 1; Imfinzi and Lynparza • Secondary outcomes; efficacy including • Data anticipated: 2022+ vistusertib • Module 2; Imfinzi and danvatirsen OS, PFS, DCR, and safety and NCT03334617 ceralasertib • Module 3; Imfinzi and ceralasertib (AZD6738) tolerability, DoR (AZD6738) • Module 4; Imfinzi and vistusertib danvatirsen • Module 5; Imfinzi and oleclumab oleclumab • Module 6; Imfinzi and Enhertu

Enhertu • Module 7; Imfinzi and cedirinib Other cediranib • Module 8; Ceralasertib

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 189 • Arm A: Imfinzi Primary • FPCD: Q4 2018 COAST unresectable • Arm B: Imfinzi + oleclumab • OR per RECIST v1.1 • Data anticipated: H2 2021 • Arm C: Imfinzi + monalizumab NCT03822351

Phase II Imfinzi Resectable, early 84 • Arm A: Imfinzi Primary • FPCD: Q1 2019 NeoCOAST stage NSCLC • Arm B: Imfinzi + oleclumab • Major pathological response rate • Data anticipated: H2 2021 • Arm C: Imfinzi + monalizumab NCT03794544 • Arm D: Imfinzi + danvatirsen

36 Approved medicines Late-stage development Imfinzi (PD-L1 mAb) Early development Cancer Oncology

Trial Compound Population Patients Design Endpoints Status

Phase Ib/II Imfinzi 1L metastatic MSS- 112 • Part 1 S1 FOLFOX + bevacizumab + Imfinzi + oleclumab Primary • FPCD: Q3 2019 COLUMBIA 1 CRC • Part 2 Control 1 FOLFOX + bevacizumab • Part 1: Safety • Data anticipated: H2 2020 • Part 2 E1 FOLFOX + bevacizumab + Imfinzi + oleclumab • Part 2: Efficacy - OR

NCT04068610 Secondary CVRM • Part 1: Efficacy – OR, BOR, DoR, PFS • Part 2: Safety and Efficacy ( BOR,

DoR, DC, PFS, OS)

R&I Other

37 Approved medicines Late-stage development Imfinzi (PD-L1 mAb) + Early development tremelimumab (CTLA-4 mAb) Oncology Cancer

Trial Population Patients Design Endpoints Status CVRM Phase Ib/II Hepatocellular carcinoma 545 • Arm A: Imfinzi + tremelimumab • Primary endpoints: Safety & tolerability, • FPCD: Q4 2015 STUDY 22 • Arm B: Imfinzi 2L DLTs • Data anticipated: H2 2020 • Arm C: tremelimumab 2L • Secondary endpoints: ORR, DoR, OS NCT02519348 • Arm D: Imfinzi + tremelimumab • Arm E: Imfinzi in combination with bevacizumab

Phase Ib NSCLC 459 • Dose escalation: minimum 5 cohorts exploring various treme Primary endpoints: • FPCD: Q4 2013 STUDY 006 (Immunotx naïve and Q4W and Imfinzi i.v. Q4W dose combinations, higher dose • Safety • LPCD: Q4 2016 Immunotx pretreated patient levels and alternate Q2 schedule added with amendment • Optimal biologic dose for the combination • Data readout: Q3 2020

NCT02000947 cohorts) • Dose expansion: MTD for the combination in escalation to be • OR R&I explored in expansion • Secondary endpoints include antitumour activity, PK and immunogenicity North American, EU and ROW trial centres

Phase I Solid tumours (basket trial) 380 • Dose expansion: MTD for the combination in escalation to be Primary endpoints: • FPCD: Q4 2014 STUDY 10 explored in expansion cohorts specific for each of 7 tumour • Safety • LPCD: Q2 2017 types • Optimal biologic dose for the combination • Data readout: Q4 2020 NCT02261220 • Dose exploration: 2 cohorts exploring various Q4W treme and • Secondary endpoints include Imfinzi dose combinations and 2 cohorts exploring various Q2W anti-tumour activity, PK/PD and treme and Imfinzi dose combinations immunogenicity

North American, EU and ROW trial centres Other

38 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: H1 2021 NCT03162224 neck cancer Secondary endpoints:

PK, ADA, DCR, OS, PFS

R&I Other

39 Approved medicines Late-stage development AZD0466 (Bcl2/xL inhibitor) Early development Cancer Oncology

Trial Population Patients Design Endpoints Status

Phase I Advanced hematologic 102 Monotherapy dose escalation, consisting of two arms: • Primary: safety • FPCD: Q4 2019 malignancies or solid tumours • Arm A: Patients with low risk for tumour lysis syndrome (solid • Secondary: PK, anti-tumour activity • Data anticipated: H2 2021 NCT04214093 tumours, , myelomas)

• Arm B: Patients with high risk for tumour lysis syndrome CVRM

(relapsed/refractory haem malignancies)

R&I Other

40 Approved medicines Late-stage development MEDI1191 (IL12 modRNA) Early development Cancer Oncology

Trial Population Patients Design Endpoints Status

Phase I Advanced solid tumours 87 First-time-in-human Phase I, open-label, dose-escalation and • Primary endpoint: safety and tolerability • FPCD: Q2 2019 expansion trial of MEDI1191 administered intratumourally as • Data anticipated: 2022 NCT03946800 monotherapy and in combination with Imfinzi • Secondary endpoints: PK,

immunogenicity and efficacy

CVRM

R&I Other

41 Approved medicines Late-stage development AZD1390 (ATM inhibitor) Early development Cancer Oncology

Trial Population Subjects Design Endpoints Status

Phase I Recurrent glioblastoma 132 • Primary: investigate the safety, • FPCD Q2 2018 eligible for re-irradiation, brain • Designed to evaluate the safety, tolerability and PK of tolerability, and MTD of AZD1390 • Data anticipated: 2022 NCT03423628 metastases and AZD1390 in combination with radiation therapy in patients with administered in combination with radiation

leptomeningeal disease, GBM and brain metastases from solid tumours therapy in brain malignancies CVRM newly-diagnosed glioblastoma patients • Dose and schedule of AZD1390 administration will be adjusted during assessment of safety and tolerability during this Phase I trial

Conducted across seven sites in USA and UK

R&I Other

42 Approved medicines Late-stage development Adavosertib (WEE-1 inhibitor) Early development

Ovarian cancer, uterine serous cancer, solid tumours Oncology

Trial Population Patients Design Endpoints Status

Phase II Platinum-resistant (PR) 95 • Arm B: paclitaxel + adavosertib • Primary endpoint: ORR • FPCD: Q1 2015 ovarian cancer • Arm C: carboplatin + adavosertib • LPCD: Q2 2018 D6010C00004 • Secondary endpoints: DoR, PFS, OS, • Data readout: Q3 2019

Global trial DCR, safety and tolerability CVRM NCT02272790

Phase I Advanced solid tumours 56 • Dose escalation trial to determine MTD (adavosertib + Imfinzi) • Safety and tolerability • FPCD: Q4 2015 • LPCD: Q4 2018 D6015C00002 Conducted in US • Data readout Q4 2019

NCT02617277

Phase II Uterine serous carcinoma 120 • Adavosertib monotherapy • Primary endpoint: ORR • FPCD: Q4 2020 • Phase IIb, open-label, single-arm, multi-center study • Secondary endpoints: DoR, depth of D601HC00002 • Global trial response, PFS R&I

NCT04590248 Other

43 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 142 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: H2 2021

NCT03489525 • Determination of MTD CVRM • Secondary endpoints: pPK, immunogenicity, ORR, DCR, DoR, PFS,

OS

R&I Other

44 Approved medicines Late-stage development AZD2811NP (AURN) Early development Cancer Oncology

Trial Population Patients Design Endpoints Status

Phase I Solid tumours 72 • Arm 1: AZD2811NP dose escalation • Safety and tolerability • FPCD: Q4 2015 • Arm 2: AZD2811NP dose expansion SCLC • PK and efficacy • Data anticipated: H1 2021

NCT02579226 CVRM

Phase I AML/high-risk MDS 124 • Part A: AZD2811NP monotherapy / azacitidine combination / • Safety and tolerability • FPCD: Q3 2017 venetoclax combination dose escalation cohorts • PK and efficacy • Data anticipated: 2022+ NCT03217838 • Part B: AZD2811NP monotherapy / azacitidine combination / venetoclax combination dose expansions to further explore the

tolerability, PK and clinical activity

R&I Other

45 Approved medicines Late-stage development AZD4573 (CDK9 inhibitor) Early development Cancer Oncology

Trial Population Patients Design Endpoints Status

Phase I Relapsed/refractory 45 Arm 1: dose escalation in haematological malignancies excluding Primary: • FPCD: Q4 2017 haematologic malignancies AML/ALL/high-risk MDS/CMML/CLL. • safety/PK; • Data anticipated: H1 2021 NCT03263637 Secondary:

Arm 2: dose escalation in relapsed or refractory AML, ALL, high- • efficacy CVRM risk MDS, CMML, CLL and Richter's syndrome.

i.v. route of administration

Trial conducted in NL, UK, GE

Phase I/II Relapsed/refractory 78 Modular design platform trial: Primary: • Initiating

haematologic malignancies • Module 1: AZD4573 + Calquence (100mg twice daily) • Safety (Part A) R&I NCT04630756 combination • ORR (Part B) • Arm 1: dose setting (DLBCL, all comers); ramp-up across 3 Secondary: dose levels (Part A) • Safety, anti-tumour activity (Part B) • Arm 2: dose expansion (GCB vs. non-GCB DLBCL); target • PK (Parts A & B) dose (Part B) • I.V. route of administration • Trial conducted in10 countries across North America, EU,

ROW Other

46 Approved medicines Late-stage development AZD4635 (A2AR inhibitor) Early development Cancer Oncology

Trial Population Patients Design Endpoints Status

Phase I Phase Ia: patients with 313 Phase Ia – solid tumours or mCPRC: Primary outcome measure: • FPCD: Q2 2016 advanced solid tumours • AZD4635 monotherapy • Safety and tolerability • Data anticipated: H1 2021 NCT02740985 • AZD4635 + Imfinzi • AZD4635 + abiraterone Phase Ib: Secondary outcome measures: CVRM Post-immunotherapy NSCLC • AZD4635 + enzalutamide • Preliminary assessment of anti-tumour Other post-immunotherapy • AZD4635 + Imfinzi + oleclumab activity • AZD4635 + docetaxel. solid tumours Phase Ib: AZD4635 monotherapy or AZD4635 + Imfinzi dose Immune checkpoint-naïve expansions in NSCLC, mCRPC, CRC and other post- mCRPC Immune checkpoint- immunotherapy and immune checkpoint-naïve solid tumours naïve CRC Other immune checkpoint- Conducted at sites in the US

naïve solid tumours R&I Phase I Healthy male volunteers 21 • Part A 2-period randomised crossover trial of single doses of Primary outcome measures: • FPCD: Q4 2018 AZD4635, nanosuspension or solid oral formulation in fasted • Cmax and exposure (AUC) of AZD4635 • LPCD: Q2 2019 NCT03710434 state solid oral formulation and nano- • Part B, 4-period, open-label, randomised, crossover trial of suspension single doses of AZD4635 in the same subjects from Part A to assess food effect, pH effect and formulation variants Both parts conducted at a site in the UK

Phase II Prostate cancer 60 ARM 1: AZD4635 + Imfinzi • Primary outcome measure: Efficacy; • FPCD: Q3 2019 Other ARM 2: AZD4635 + oleclumab (ORR and PSA response) • Data anticipated: H1 2021 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 • LPCD: Q3 2020 NCT03980821 Conducted at sites in Japan Secondary outcome measure: • PK and preliminary anti-tumour activity

Phase II Prostate cancer 160 ARM A: AZD4635 + Imfinzi • Primary outcome measure: Efficacy • FPCD: Q3 2020 ARM B: AZD4635+ Imfinzi + cabazitaxel (rPFS) • Data anticipated: 2022+ NCT04495179 Conducted at sites in US, Europe, UK and Korea • Secondary outcome measure: Efficacy (OS, PSA response, ORR, DoR)

47 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: H1 2021 NCT03205176

Dose escalation of AZD5153 in combination with Lynparza in CVRM

platinum resistant/refractory HGS patients.

R&I Other

48 Approved medicines Late-stage development AZD5305 (PARP inhibitor) Early development Solid tumours Oncology

Trial Population Patients Design Endpoints Status

Phase I Advanced, metastatic HER2 612 A modular phase I/IIa, open-label, multicentre trial to assess the • Primary endpoint: safety/tolerability & PK • FPCD: Q4 2020 neg. with BRCAm, PALB2m or safety, tolerability, pharmacokinetics, pharmacodynamics and • Data anticipated: 2022+ NCT04644068 RAD51C/Dm Breast cancer preliminary efficacy of ascending doses of AZD5305 as • Secondary endpoints: efficacy

monotherapy and in combination with anti-cancer agents in CVRM patients with advanced solid malignancies Advanced, metastatic TNBC

BRCAm, PALB2m or RAD51C/Dm PSR ovarian cancer

HRD+ve1 (non-BRCAm or PALB2m or RAD51C/Dm) R&I PSR ovarian cancer

PSR ovarian cancer Other

49 Approved medicines Late-stage development MEDI5395 (rNDV GMCSF) Early development Cancer Oncology

Trial Population Patients Design Endpoints Status

Phase I Select advanced solid 188 First-time-in-human Phase I, open-label, dose-escalation and • Primary endpoint: safety and tolerability • FPCD: Q4 2019 tumours expansion arm of MEDI5395 in combination with Imfinzi • Data anticipated: 2022+ NCT03889275 • Secondary endpoints: PK, PD,

immunogenicity and efficacy

CVRM

R&I Other

50 Approved medicines Late-stage development MEDI5752 (PD-1/CTLA-4 bispecific mAb) Early development Cancer Oncology

Trial Population Patients Design Endpoints Status

Phase I/IIa Advanced solid tumours 261 Open-label, dose-escalation and dose-expansion: Primary endpoints: • FPCD: Q2 2018 • dose-escalation: safety & determination • Data anticipated: 2022+ NCT03530397 • Dose-escalation: MEDI5752 i.v. of MTD

• dose-expansion: assessment of CVRM • Dose-expansion: MEDI5752 i.v. as monotherapy and in antitumour activity based on OR combination with chemotherapy Secondary endpoints: • Arm A: MEDI5752 i.v. • PK, ADA, tumoural baseline PD-L1, • Arm B: MEDI5752 i.v., pemetrexed and carboplatin assessment of antitumour activity • Arm C: Pembrolizumab, pemetrexed and carboplatin based on OR, DoR, DCR, PFS, OS

Phase Ib Advanced 77 Open-label, dose-escalation and dose-expansion to explore the Primary endpoint: • FPCD: Q3 2020 safety, tolerability and anti-tumour activity of MEDI5752 in • dose-escalation: safety & tolerability • Data anticipated: 2022+

NCT04522323 combination with axitinib: R&I Secondary endpoints: • PK, ADA and antitumour activity of MEDI5752 + axitinib based on PFS,

OR, DoR, DCR, TTR, OS Other

51 Approved medicines Late-stage development AZD5991 (MCL1 inhibitor) Early development Cancer Oncology

Trial Population Patients Design Endpoints Status

Phase I/Ib/IIa Relapsed/refractory 121 • Arm1: monotherapy dose escalation & expansions in • Primary: safety • FPCD: Q3 2017 haematologic malignancies relapsed/refractory haematological malignancies • Secondary: PK, efficacy • Data anticipated: H2 2021 NCT03218683 • Arm2: combination dose escalation (AZD5991+venetoclax) in

relapsed/refractory AML/MDS;. CVRM • i.v. route of administration

• US only

R&I Other

52 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: 2022+

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 2021 NCT03022409 • Arm 2: Lynparza

Trial conducted in US, France, Taiwan and the UK

Phase II Solid tumours 52 • Cohort A: ceralasertib; ATM-altered AST Cohort A: ORR • FPCD: Q1 2021 PLANETTE mCRPC • Cohort B: ceralasertib; ATM-altered mCRPC Cohort B: Composite RR • Data anticipated: 2022+ R&I

NCT04564027 Other

53 Approved medicines Late-stage development AZD7648 (selective DNA-PK inhibitor) Early development Advanced solid tumours Oncology

Trial Population Patients Design Endpoints Status

Phase I Advanced malignancies 234 • First in human modular dose escalation and dose expansion • Primary outcome measures: safety and • FPCD: Q4 2019 trial tolerability • Data anticipated: 2022 NCT03907969 • Secondary outcome measures: PK, • Arm 1 - AZD7648 monotherapy

Cytochromes P450, preliminary anti- CVRM • Arm 2 - AZD7648 + Pegylated Liposomal Doxorubicin tumour activity • Arm 3 - AZD7648 + Lynparza

• Countries: US, UK

R&I Other

54 Approved medicines Late-stage development

AZD8701 (FOXP3 antisense oligonucleotide) Early development Oncology Solid tumours

Trial Population Patients Design Endpoints Status

Phase I/Ib Advanced solid tumours 123 Dose escalation and dose expansion trial Primary endpoints: • FPCD: Q3 2020 NCT04504669 safety & tolerability • Data Anticipated: 2022+ CVRM Arm 1: AZD8701 monotherapy Arm 2: AZD8701 & Imfinzi combination therapy Secondary endpoints: PK, PD, preliminary anti-tumour activity Global trial - four countries - US, CA, FR, ES

i.v. route of administration

R&I Other

55 Approved medicines Late-stage development MEDI9253 (rNDV-IL12) Early development Solid tumours Oncology

Trial Population Patients Design Endpoints Status

Phase I Advanced solid tumours 86 First-time-in-human Phase I, open-label, dose-escalation and • Primary endpoint: safety and tolerability • FPCD: Q4 2020 expansion arm of MEDI9253 in combination with Imfinzi • Data anticipated: 2022+ NCT04613492 • Secondary endpoints: PK,

PD, immunogenicity and efficacy CVRM

R&I Other

56 Approved medicines Late-stage development Oleclumab (CD73 mAb) Early development Cancer Oncology

Trial Population Patients Design Endpoints Status

Phase I Advanced malignancies 348 Dose escalation phase Primary endpoints: • FPCD: Q3 2015 • oleclumab i.v. • Safety • Data anticipated: H1 2021

NCT02503774 • oleclumab i.v. + Imfinzi i.v. • Determination of MTD CVRM • Secondary endpoints include preliminary Dose expansion phase anti-tumour activity, PK, PD, • oleclumab i.v. recommended dose + Imfinzi i.v. immunogenicity and biomarker activity

US, South Korean and Australian trial centres

Phase Ib/II Pancreatic 339 • Arm A1: gemcitabine and nab paclitaxel i.v. Primary endpoints: • FPCD: Q2 2018 1L and 2L with prior • Arm A2: gemcitabine and nab paclitaxel i.v. + oleclumab i.v. • Safety and anti-tumour activity • Data anticipated: H2 2021 NCT03611556 gemcitabine-based • Arm A3: gemcitabine and nab paclitaxel i.v. + oleclumab i.v. +

chemotherapy Imfinzi i.v. • Secondary endpoints include PFS, PK, R&I • Arm B1: mFOLFOX (oxaliplatin, leucovorin, 5-FU) i.v. immunogenicity, safety and anti-tumour • Arm B2: mFOLFOX (oxaliplatin, leucovorin, 5-FU) i.v. + activity oleclumab i.v. • Arm B3: mFOLFOX (oxaliplatin, leucovorin, 5-FU) i.v. + oleclumab i.v. + Imfinzi i.v.

US, Norway, Spain and Australian trial centres Other

57 Approved medicines Late-stage development IPH5201 (CD39 mAb) Early development Solid tumours Oncology

Trial Population Patients Design Endpoints Status Phase I Advanced Solid tumours 204 • First time in human Phase I, open-label, dose- Primary endpoints: • FPCD: Q1 2020 escalation trial to determine MTD of IPH5201 as AE, SAE, DLT • Data anticipated: 2022 NCT04261075 monotherapy, or in combination with Imfinzi +/- Partnered oleclumab. Secondary endpoints: CVRM OR, DC, PK, ADA • Part 1: IPH5201 monotherapy dose escalation to MTD • Part 2: IPH5201 + Imfinzi dose escalation to MTD • Part 3: IPH5201 + Imfinzi + Oleclumab dose escalation to MTD • Route of Administration: IV

• Geographical Regions: 4 countries - US and 3 in EU.

R&I Other

58 BioPharmaceuticals – approved medicines and late-stage pipeline Approved medicines Late-stage development Farxiga (SGLT2 inhibitor) Early development Heart failure and chronic kidney disease Oncology

Trial Population Patients Design Endpoints Status

Phase III CHF patients with HFrEF 4,744 • Arm 1: Farxiga 10mg or 5 mg QD + SoC therapy • Primary endpoint: time to the first • FPCD: Q1 2017 Dapa-HF • Arm 2: placebo + SoC therapy occurrence of any of the components of • LPCD Q4 2018 the composite: CV death or • Data readout: Q3 2019 • Global trial - 20 countries • Primary endpoint met

NCT03036124 hospitalisation for HF or an urgent HF CVRM visit

Phase III Patients With CKD 4,304 • Arm 1: Farxiga 10mg or 5 mg QD • Primary endpoint: time to the first • FPCD: Q1 2017 Dapa-CKD • Arm 2: placebo occurrence of any of the components of • LPCD: Q2 2020 the composite: ≥50% sustained decline • Data readout: Q2 2020 NCT03036150 Global trial - 21 countries in eGFR or reaching ESRD or CV death • Primary endpoint met or renal death

Phase III CHF patients with HFpEF 6,100 • Arm 1: Farxiga 10mg QD • Primary endpoint: time to the first • FPCD: Q4 2018 R&I DELIVER • Arm 2: placebo occurrence of any of the components of • Data anticipated: H2 2021 the composite: CV death or NCT03619213 • Global trial - 21 countries hospitalisation for HF or an urgent HF visit

Phase III CHF patients with HFpEF 504 • Arm 1: Farxiga 10mg QD Family of primary endpoints: • FPCD: Q2 2019 DETERMINE-preserved • Arm 2: placebo • Change from baseline in the KCCQ- • LPCD: Q3 2020 TSS at Week 16. • Data readout: Q4 2020 • Global trial - 12 countries • Primary endpoints not met NCT03877224 • Change from baseline in the KCCQ-

PLS at Week 16. Other • Change from baseline in 6 min walking distance at Week 16

Phase III CHF patients with HFrEF 313 • Arm 1: Farxiga 10mg QD Family of primary endpoints: • FPCD: Q2 2019 DETERMINE-reduced • Arm 2: placebo • Change from baseline in the KCCQ- • LPCD Q1 2020 TSS at Week 16. • Data readout: Q4 2020 • Global trial - 9 countries • One primary endpoint met NCT03877237 • Change from baseline in the KCCQ- PLS at Week 16. • Change from baseline in 6 min walking distance at Week 16

Phase III Patients with myocardial 6,400 • Arm 1: Farxiga 10mg QD • Primary endpoint: time to the first • FPCD: Q4 2020 DAPA-MI infarction • Arm 2: placebo occurrence of any of the components of • Data anticipated: 2022+ the composite: hospitalization for HF or NCT04564742 • Global trial - 2 countries CV death

60 Approved medicines Late-stage development Brilinta (P2Y12 receptor antagonist) Early development Cardiovascular risk reduction Oncology

Trial Population Patients Design Endpoints (primary) Status

Phase III Patients with type-2 diabetes 19,000 • Arm 1: Brilinta 60mg BiD • Primary endpoint: composite of CV • FPCD: Q1 2014 THEMIS and coronary artery disease • Arm 2: placebo BID death, non-fatal MI and non-fatal stroke • LPCD: Q2 2016 without a previous history of on a background of acetylsalicylic acid if not contra-indicated or • Data readout: Q1 2019 NCT01991795 MI or stroke not tolerated • Primary endpoint met

Secondary endpoints: CVRM • Prevention of CV death Global trial – 42 countries • Prevention of MI • Prevention of ischaemic stroke • Prevention of all-cause death

Phase III Patients with acute ischaemic 11,000 • Arm 1: Brilinta 90mg BiD Primary endpoint: • FPCD: Q1 2018 THALES stroke or transient ischaemic • Arm 2: placebo BiD • Prevention of the composite of • LPCD: Q4 2019 attack on a background of acetylsalicylic acid if not contra-indicated or subsequent stroke and death at 30 days • Data readout: Q1 2020 NCT03354429 not tolerated • Primary endpoint met

Secondary endpoints include: R&I Global trial – 28 countries • Prevention of subsequent ischaemic stroke at 30 days

• Reduction of overall disability at 30 days Other

61 Approved medicines Late-stage development Lokelma (sodium zirconium cyclosilicate) Early development Hyperkalaemia Oncology

Trial Population Patients Design Endpoints Status Phase II Patients with chronic heart 182 • Arm 1: Lokelma 5g QD for 12 weeks. Option to uptitrate to 10 • Primary endpoint: difference between • FPCD: Q3 2018 PRIORITIZE HF failure and hyperkalaemia or and 15g QD or downtitrate to 5g QOD Lokelma and placebo in RAAS (renin– • LPCD: Q2 2020 at high risk of developing • Arm 2: placebo QD for 12 weeks angiotensin–aldosterone system) • Data readout: Q4 2020

NCT03532009 hyperkalaemia blockade treatment. CVRM Global trial – nine countries

Phase IIIb Patients with ESRD with 134 • Arm 1: Lokelma 5g QD for 8 weeks on non-dialysis days. • Primary endpoint: proportion of patients • FPCD: Q4 2020 DIALIZE China hyperkalemia and on stable Option to uptitrate to 10 and15g QD. who maintain a pre-dialysis serum K • Data readout:H2 2021 haemodialysis • Arm 2: placebo QD for 8 weeks on non-dialysis days between 4.0-5.0 mmol/L on 3 out of 4 NCT04217590 dialysis treatments following the long China interdialytic interval

Phase III Hyperkalaemia 337 Open-label Lokelma 10g TID for 48 hours followed by: • Primary endpoint: maintenance of • Initiating

HARMONIZE Asia • Arm 1: Lokelma 5g QD for 28 days normokalaemia • Data readout: 2022+ R&I • Arm 2: Lokelma 10g QD for 28 days NCT03528681 • Arm 3: placebo QD for 28 days

China, India Other

62 Approved medicines Late-stage development Roxadustat (HIF-PH inhibitor) Early development Anaemia Oncology

Trial Population Patients Design Endpoints Status

Phase III Anaemia in CKD in patients 922 • Arm 1: roxadustat • Primary endpoint: Haemoglobin response • FPCD: Q4 2012 ANDES not receiving dialysis • Arm 2: placebo • LPCD: Q3 2018 • Data readout: Q4 2018 NCT01750190 Global trial

• Primary endpoint met CVRM Partnered Sponsored by FibroGen

Phase III 597 • Arm 1: roxadustat • Primary endpoint: Haemoglobin response • FPCD: Q2 2013 ALPS • Arm 2: placebo • LPCD: Q4 2017 • Data readout: Q3 2018 NCT01887600 Global trial • Primary endpoint met Partnered Sponsored by Astellas

Phase III 616 • Arm 1: roxadustat • Primary endpoint: Haemoglobin response • FPCD: Q1 2014

DOLOMITES • Arm 2: darbepoetin alfa • LPCD: Q4 2019 R&I • Data readout: Q1 2020 NCT02021318 Global trial • Primary endpoint met Partnered Sponsored by Astellas

Phase III 2,781 • Arm 1: roxadustat • Primary efficacy endpoint: Haemoglobin • FPCD: Q3 2014 OLYMPUS • Arm 2: placebo response • LPCD: Q4 2018 • Data readout: Q4 2018 NCT02174627 Global trial • Primary safety objective: Contribute CV • Primary endpoint met safety data to pooled safety Sponsored by AstraZeneca

• analyses across the Phase III program Other Phase III Anaemia in CKD in patients 2,133 • Arm 1: roxadustat • Primary efficacy endpoint: Haemoglobin • FPCD: Q3 2014 ROCKIES receiving dialysis • Arm 2: epoetin alfa response • LPCD: Q3 2018 • Data readout: Q4 2018 NCT02174731 Global trial • Primary safety objective:Contribute CV • Primary endpoint met safety data to pooled safety Sponsored by AstraZeneca • analyses across the Phase III program

Phase III 741 • Arm 1: roxadustat • Primary endpoint: Haemoglobin response • FPCD: Q4 2014 SIERRAS • Arm 2: epoetin alfa • LPCD: Q3 2018 • Data readout: Q4 2018 NCT02273726 Global trial • Primary endpoint met Partnered Sponsored by FibroGen

Phase III 838 • Arm 1: roxadustat • Primary endpoint: Haemoglobin response • FPCD: Q4 2014 PYRENEES • Arm 2: epoetin alfa or darbepoetin alfa • LPCD: Q3 2018 • Data readout: Q3 2018 NCT02278341 Global trial • Primary endpoint met Partnered Sponsored by Astellas 63 Approved medicines Late-stage development Roxadustat (HIF-PH inhibitor) Early development Anaemia Oncology

Trial Population Patients Design Endpoints Status

Phase III Anaemia in newly initiated 1,043 • Arm 1: roxadustat • Primary endpoint: Haemoglobin response • FPCD: Q4 2013 HIMALAYAS dialysis patients • Arm 2: epoetin alfa • LPCD: Q3 2018 • Data readout: Q4 2018 NCT02052310 Global trial • Primary endpoint met Partnered Sponsored by FibroGen CVRM

Phase III Anaemia in lower risk MDS 184 Open label roxadustat lead-in • Primary endpoint: Proportion of patients • FPCD: Q3 2017 patients Arm 1: roxadustat achieving transfusion independence • Data anticipated: 2022 NCT03263091 Arm 2: placebo Sponsored by FibroGen Partnered US/global trial

Phase II/III Anaemia in lower risk MDS 175 Open label roxadustat lead-in • Primary endpoint: Haemoglobin

patients Arm 1: roxadustat response • FPCD: Q2 2018 R&I NCT03303066 Arm 2: placebo • Data anticipated: 2022 Partnered Sponsored by FibroGen China

Phase II Anemia in patients receiving 100 US • Primary endpoint: Maximum change in • FPCD: Q3 2019 chemotherapy treatment for hemoglobin within 16 weeks from • LPCD: Q3 2020 NCT04076943 non-myeloid malignancies baseline without RBC transfusion • Data anticipated: H1 2021

Partnered Sponsored by FibroGen Other

64 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 20 Open-label, 2-period ascending dose incomplete block, cross-over • To investigate the PK of aclidinium • Initiating volunteers trial bromide and its metabolites after single • Data anticipated: 2022+ NCT03276052 and multiple doses (BID) of aclidinium • aclidinium bromide 400 μg DPI bromide 200 μg, 400 μg and 800 μg • To evaluate the safety, and tolerability CVRM of aclidinium bromide 200 μg, 400 μg and Global trial – one Country 800 μg after single and multiple dose

administration (BID)

R&I Other

65 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: 2022+ • Arm 3: formoterol fumarate 12 μg DPI morning post-dose dose FEV1 Duaklir NCT03022097 • Arm 4: tiotropium 18 μg DPI Genuair 400/12 μg compared to CVRM Aclidinium bromide at Week 24 • Change from baseline in morning pre- Global trial – five countries dose (trough) FEV1 of Duaklir Genuair 400/12 μg compared to Formoterol fumarate at Week 24 • Change from baseline in trough FEV1 of Aclidinium bromide 400 µg compared to

placebo at Week 24

R&I Other

66 Approved medicines Late-stage development Breztri, Trixeo (PT010, LAMA/LABA/ICS, pMDI) Early development Asthma Oncology

Trial Population Patients Design Endpoints Status

Phase III Severe asthma 2,800 Treatments (24 to 52 week variable length) • Primary endpoint: Change from baseline • FPCD: Q1 2021 KALOS • BGF MDI 320/28.8/9.6µg BID pMDI in forced expiratory volume in 1 second • Data anticipated: 2022+ • BGF MDI 320/14.4/9.6µg BID pMDI (FEV1) area under the curve 0 to 3 hours

NCT04609878 • BFF MDI 320/9.6µg BID pMDI (AUC0-3) at Week 24 CVRM • Symbicort 320/9µg BID pMDI • Primary endpoint of Pooled Studies Randomised, double-blind, double dummy, parallel group and D5982C00007 and D5982C00008: Rate multicentre of severe asthma exacerbations

Multi-country • Secondary endpoint: Change from baseline in morning pre-dose trough FEV1 at Week 24

Severe asthma Treatments (24 to 52 week variable length) • Primary endpoint: Change from baseline • Initiating Phase III 2,800 R&I LOGOS • BGF MDI 320/28.8/9.6µg BID pMDI in forced expiratory volume in 1 second • Data anticipated: 2022+ • BGF MDI 320/14.4/9.6µg BID pMDI (FEV1) area under the curve 0 to 3 hours NCT04609904 • BFF MDI 320/9.6µg BID pMDI (AUC0-3) at Week 24 • Symbicort 320/9µg BID pMDI • Primary endpoint of Pooled Studies Randomised, double-blind, double dummy, parallel group and D5982C00007 and D5982C00008: Rate multicentre of severe asthma exacerbations

Multi-country • Secondary endpoint: Change from baseline in morning pre-dose trough

FEV1 at Week 24 Other

67 Approved medicines Late-stage development Daliresp/Daxas (PDE4 inhibitor, oral) Early development COPD Oncology

Trial Population Patients Design Endpoints Status

Post Launch COPD 124,080 • This is a retrospective cohort trial comparing COPD patients • Primary endpoint: all-cause mortality (up • Data anticipated: 2022+ PASS aged 40 years and older with new exposure to roflumilast with to five years) up to 5 unexposed (i.e., not roflumilast-exposed) COPD NCT03381573

controls matched by propensity score (PS), age, sex, and year CVRM of cohort entry. The trial is using electronic healthcare databases in the US (Military Health System database), Germany (German Pharmacoepidemiological Research Database), and Sweden (national databases including

healthcare, death, and demographics data).

R&I Other

68 Approved medicines Late-stage development Fasenra (IL5R mAb) Early development Severe, uncontrolled asthma Oncology

Trial Population Patients Design Endpoints Status

Phase III A multi-centre, open-label, 447 • Arm 1: Fasenra 30mg Q4W s.c. • Primary endpoint: safety and tolerability • FPCD: Q2 2016 MELTEMI safety extension trial with • Arm 2: Fasenra 30mg Q8W s.c. • LPCD: Q3 2019 Fasenra for asthmatic adults • Data readout: Q3 2020 on ICS plus LABA2 Agonist • Primary endpoint met NCT02808819 Global trial - 15 countries CVRM Age 18-75 years

Phase IIIb Severe eosinophilic 598 Arm 1: Fasenra 30mg Q8W s.c. • Primary endpoint: reduction of oral • FPCD: Q3 2018 PONENTE asthmatics receiving HD ICS corticosteroid dose • LPCD: Q3 2019 + LABA and chronic OCS with 38-week trial • Data anticipated: Q4 2020 NCT03557307 or without additional asthma Global trial – 16 countries • Primary endpoint met controller(s). Age 18 Years and older

D3250C00036 China Severe, uncontrolled asthma, 666 • Arm 1: Fasenra 30mg Q8W s.c. • Primary endpoint: annual asthma • FPCD: Q4 2017 ICS/LABA Trial (MIRACLE) despite background controller • Arm 2: placebo s.c. exacerbation rate • Data readout: 2022+ R&I medication, MD & HD ICS + • Secondary endpoints: assess pulmonary NCT03186209 LABA ± chronic OCS 56-week trial function, asthma symptoms, other

Age 12-75 years Global trial – 4 countries asthma control metrics Other

69 Approved medicines Late-stage development Fasenra (IL5R mAb) Early development Severe, uncontrolled asthma Oncology

Trial Population Patients Design Endpoints Status

Phase III Severe asthma, inadequately 2,133 • Arm 1: Fasenra 30mg Q4W s.c. • Primary endpoint: safety and tolerability • FPCD: Q4 2014 BORA controlled despite background • Arm 2: Fasenra 30mg Q8W s.c.* • Data readout: Q3 2018 controller medication, MD & • Primary endpoint met 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 162 • Arm 1: Fasenra 30mg Q4W s.c. • Primary endpoint: functionality, reliability, • FPCD: Q2 2015 GREGALE controlled despite background and performance of a pre-filled syringe • Data readout: Q2 2016

controller medication, MD & 28-week (adults) with Fasenra administered at home • Primary endpoint met R&I NCT02417961 HD ICS + LABA ± chronic Global trial – two countries OCS Age 18-75 years

Phase lll A double-blind, randomised, 46 • Arm 1 : Fasenra 30mg Q4W s.c. • Primary endpoint: safety and tolerability • FPCD Q4 2016 ARIA parallel group, placebo- • Arm 2: placebo s.c. • LPCD: Q2 2019 controlled multi-centre trial to • Primary endpoint: the effect of Fasenra • Data readout: Q4 2020 NCT02821416 evaluate the effect of Fasenra 37-week trial on allergen induced eosinophil changes • Primary endpoint met on allergen-induced in sputum and allergen-induced late inflammation in Mild, atopic asthmatic response asthmatic Other Age 18-65 years

Phase lll A multi-centre, randomised, 103 • Arm 1: Fasenra 30mg Q4W s.c. with one dose of seasonal Primary endpoints: • FPCD: Q3 2016 ALIZE double-blind, parallel group, influenza virus vaccine IM • 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 • 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 (IL5R mAb) Early development Severe, uncontrolled asthma, COPD Oncology

Trial Population Patients Design Endpoints Status

Phase III Severe asthma on ICS-LABA 121 Open label Fasenra 30mg Q4w • Primary endpoint: percentage of patients/ • FPCD: Q4 2016 GRECO Age 18-75 years caregivers who successfully self • Data readout: Q4 2017 28-week trial administer at home • Primary endpoint met

NCT02918071 Global trial - two countries CVRM

Phase lllb A multi-centre, randomised, 659 • Arm 1: Fasenra 30mg Q8W s.c. • Primary endpoint: rate of asthma • FPCD: Q3 2017 ANDHI double-blind, parallel group, • Arm 2: placebo s.c. exacerbations • LPCD: Q1 2019 placebo controlled, Phase IIIb • Secondary outcome measures: Saint • Data readout: Q4 2019 NCT03170271 trial to evaluate the safety and 24-week trial George Respiratory Questionnaire • Primary endpoint met efficacy of Fasenra 30 mg s.c. Global trial – 15 countries (SGRQ) in patients with severe asthma uncontrolled on SoC

treatment. R&I Age 18-75

Phase I Healthy volunteers 180 Open label trial to compare 30 mg Fasenra PK administered by • Primary endpoint: PK comparability • FPCD: Q1 2017 AMES age 18-55 years APFS or AI device • Data readout: Q3 2017

NCT02968914 8-week trial Global trial – two countries

Phase III Patients with moderate to very 868 • 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: 2022+ frequent exacerbations on a • Global trial 56 weeks NCT04053634 background triple therapy Other (ICS/LABA/LAMA)

Age 40-85 years

71 Approved medicines Late-stage development Fasenra (IL5R mAb) Early development Nasal polyposis and other eosinophilic diseases Oncology

Trial Population Patients Design Endpoints Status

Phase III Patients with severe bilateral 413 • Arm 1: Fasenra 30mg Q8W s.c. • Primary endpoint: effect of Fasenra on • FPCD: Q1 2018 OSTRO nasal polyposis who are still • Arm 2: placebo s.c. nasal polyp burden and on patient • LPCD: Q2 2019 symptomatic despite standard reported nasal blockage • Data readout: Q3 2020

NCT03401229 of care therapy 56-week trial • Co-primary enpoints met CVRM Global trial- 8 countries Age 18-75 years

Phase III Patients with eosinophilic 148 Arm 1: Fasenra 30mg Q8W s.c. • Primary endpoint: Change in endoscopic • FPCD: Q4 2019 ORCHID chronic rhinosinusitis with Arm 2: placebo Q8W s.c. total nasal polyp score and Change in • Data anticipated: 2022+ severe nasal polyposis mean nasal blockage score NCT04157335 56-week trial Age 18-75 years

Asian countries (4 countries) R&I

Phase III Patients with relapsing or 140 • Arm 1: Fasenra 30mg Q4W s.c. • Primary endpoint: Proportion of patients • FPCD: Q4 2019 MANDARA refractory EGPA on • Arm 2: mepolizumab 300mg Q4W s.c. achieving remission (BVAS=0 and OCS • Data anticipated: 2022+ corticosteroid therapy with or dose ≤ 4mg/day) at both weeks 36 and NCT04157348 without stable 52-week trial with a minimum 1 year open label extension 48. immunosuppressive therapy Global trial- 9 countries

Age 18 years and older Phase III Patients with HES (history of 120 • Arm 1: Fasenra 30mg Q4W s.c. • Primary endpoint: Time to first HES • FPCD Q3 2020

NATRON persistent eosinophilia >1500 • Arm 2: placebo Q4W s.c. worsening/flare. • Data anticipated: 2022 Other cells/μL with evidence of NCT04191304 end organ manifestations 24-week trial with a minimum 1 year open label extension attributable to eosinophilia) Global trial- 9-12 countries and signs or symptoms of HES worsening/flare at Visit 1

Age 12 years and older Phase III Documented diagnosis of EoE 170 • Arm 1: Fasenra 30mg Q4W s.c. • Primary endpoints: • FPCD Q4 2020 Age 12 to 65 years • Arm 2: placebo Q4W s.c. Histologic response at week 24 • Data anticipated: 2022 MESSINA 24-week double blind treatment period and open label period(s) Change from baseline in DSQ score at week 24 NCT04543409

72 Approved medicines Late-stage development Fasenra (IL5R mAb) Early development Dermatology Oncology

Trial Population Patients Design Endpoints Status Phase III Patients with symptomatic 120 • Arm 1: Fasenra regimen • Primary endpoint: • Initiating FJORD (newly diagnosed or relapsing) • Arm 2: placebo Proportion of patients with sustained (≥2 • Data anticipated: 2022+ Bullous Pemphigoid months) remission off OCS at 36 weeks

36-week double blind treatment period and open label period CVRM Global trial

Phase II Patients with moderate/severe 160 • Arm 1: Fasenra regimen 1 • Primary endpoint: • FPCD: Q4 2020 ARROYO Chronic Spontaneous • Arm 2: Fasenra regimen 2 Change from baseline in ISS7 at week 12 • Data anticipated: 2022+ Urticaria, and resistant to H1 • Arm 3: placebo treatment 24-week double blind treatment period and open label period

Global trial R&I

Phase II Patients with moderate to 160-200 • Arm 1: Fasenra regimen • Primary endpoint: • FPCD: Q4 2020 HILLIER severe Atopic Dermatitis • Arm 2: placebo Proportion of patients with an IGA 0/1 and a • Data anticipated: 2022+ despite treatment with topical decrease in IGA of ≥ 2 points at week 16 NCT04605094 medications 16-week double blind treatment period and open label periods

Global trial 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 1,061 • Arm 1: tezepelumab s.c. • Primary endpoint: Annual asthma • FPCD: Q1 2018 NAVIGATOR Age 12-80 years • Arm 2: placebo s.c. exacerbation rate • LPCD: Q3 2019 • Secondary endpoints: Change from • Data readout: Q4 2020

NCT03347279 52 week trial baseline in pre-BD FEV1, asthma related • Primary endpoint met CVRM QoL (AQLQ(S)+12), asthma control Partnered Global trial – 18 countries (ACQ-6)

Phase III Severe asthma 150 • Arm 1: tezepelumab s.c. • Primary endpoint: Reduction from • FPCD: Q2 2018 SOURCE Age 18-80 years • Arm 2: placebo s.c. baseline in daily OCS dose while not • LPCD: Q4 2019 losing asthma control • Data readout: Q4 2020 NCT03406078 48 week trial • Secondary endpoint: Annual asthma • Primary endpoint not met exacerbation rate

Partnered Global trial – seven countries R&I

Phase III Severe asthma ~975 • Arm 1: tezepelumab s.c. • Primary endpoint: Exposure adjusted • FPCD: Q1 2019 DESTINATION Age 12-80 years • Arm 2: placebo s.c. rates of AEs/SAEs Secondary endpoints: • LPCD: Q4 2020 Annual asthma exacerbation rate • Data anticipated: H2 2022 NCT03706079 Extension trial to NAVIGATOR and SOURCE. 52 week trial (subjects from NAVIGATOR); 56 week trial (subjects from Partnered SOURCE)

Global trial – 18 countries Other Phase III Severe asthma 216 • Arm 1: tezepelumab s.c. via autoinjector (AI) Primary endpoint: Proportion of health care • FPCD: Q2 2019 PATH-HOME Age 12-80 years • Arm 2: tezepelumab s.c. via accessorized pre-filled syringe professionals and patients /caregivers who • LPCD: Q3 2019 (APFS) successfully administrated tezepelumab in • Data readout: Q4 2020 • Primary endpoint met NCT03968978 clinic and at home with an APFS or an AI, 24 week trial respectively Partnered Global trial – 4 countries

74 Approved medicines Late-stage development Tezepelumab (TSLP mAb) Early development Severe, uncontrolled asthma & COPD Oncology

Trial Population Patients Design Endpoints Status

Phase II Severe asthma 116 • Arm 1: tezepelumab s.c. • Primary endpoint: number of airway • FPCD: Q4 2018 CASCADE Age 18-75 years • Arm 2: placebo s.c. submucosal inflammatory cells/mm2 of • LPCD: Q4 2019 28 week trial bronchoscopic biopsies • Data anticipated: H1 2021 CVRM NCT03688074 Global trial – five countries Partnered Phase III Severe asthma 396 • Arm 1: tezepelumab s.c. • Primary endpoint: Annual asthma • FPCD: Q3 2019 DIRECTION Age 18-80 years • Arm 2: placebo s.c. exacerbation rate • Secondary endpoints: Change from NCT03927157 52 week trial baseline in pre-BD FEV1, asthma related QoL (AQLQ(S)+12), asthma control

Partnered Regional Asia trial – three countries (ACQ-6) R&I

Phase III Severe asthma 65 Arm 1: tezepelumab s.c. • Primary endpoint: Number of patients • FPCD: Q2 2019 NOZOMI 12-80 years 52 week trial with adverse events • LPCD: Q4 2019 Local trial - Japan • Data anticipated: H1 2021 NCT04048343

Partnered

Phase IIa Moderate to very severe 282 • Arm 1: tezepelumab s.c. • Primary endpoint: Rate of moderate or • FPCD Q3 2019 COURSE COPD • Arm 2: placebo s.c. severe COPD exacerbations • Data anticipated: 2022+ Age 40-80 Other NCT04039113 52 week trial

Partnered Global trial – 10 countries

75 Approved medicines Late-stage development PT027 (SABA/ICS, pMDI) Early development Asthma Oncology

Trial Population Patients Design Endpoints Status

Phase III Moderate to severe asthma 3,100 Treatments (minimum 24-week treatment period) Primary endpoint: • FPCD: Q4 2018 MANDALA • BDA (budesonide albuterol) MDI 80/180 μg prn • Time to first severe asthma exacerbation • Data anticipated: H2 2021 • BDA MDI 160/180 μg prn NCT03769090 • AS (albuterol sulphate) MDI 180 μg prn Secondary endpoints: CVRM • Severe exacerbation rate (annualised) Managed by Avillion Randomised, double-blind, multi-centre, parallel group • Total corticosteroid exposure over the treatment period Multi-country • Asthma Control Questionnaire -5 change from baseline and responder analysis at Week 24 • Asthma quality of life questionnaire for 12 years and older/paediatric asthma quality of life questionnaire change from baseline R&I and responder analysis at week 24

Phase III Mild to moderate asthma 1,000 Treatments (12 week treatment period) Dual primary endpoints: • FPCD: Q2 2019 DENALI • BDA MDI 80/180 μg QID • Change from baseline in FEV1 AUC0-6 • Data anticipated: H2 2021 • BDA MDI 160/180 μg QID hours over 12 weeks NCT03847896 • BD MDI 160 μg QID • Change from baseline in trough FEV1 at • AS MDI 180 μg QID week 12 Managed by Avillion • placebo MDI QID

Randomised, double-blind, multi-centre and parallel-group Other

Multi-country

Phase III Asthma with exercise induced 60 Treatments (single dose) Primary endpoint: • FPCD Q1 2020 TYREE bronchoconstriction • BDA MDI 160/180 μg • The maximum percentage fall from • LPCD: Q3 2020 • placebo MDI QID post-dose, pre-exercise baseline in • Data Readout: Q4 2020 NCT04234464 forced expiratory volume in 1 second • Primary endpoint met Randomised, double-blind, multi-centre crossover (FEV1) observed up to 60 minutes post- Managed by Avillion exercise challenge Country: US

76 Approved medicines Late-stage development Anifrolumab (type I interferon receptor mAb) Early development Lupus (SLE / LN) Oncology

Trial Population Patients Design Endpoints Status

Phase III Moderate to severe SLE 450 • Arm 1: 300mg i.v. anifrolumab Q4W for 48 weeks • Primary endpoint: response in SLE • FPCD: Q4 2015 TULIP SLE 1 • Arm 2: 150mg i.v. anifrolumab Q4W for 48 weeks responder index at week 52 • LPCD: Q4 2017 • Arm 3: placebo i.v. Q4W for 48 weeks • Data readout: Q3 2018 • Primary endpoint not met

NCT02446912 CVRM

Phase III Moderate to severe SLE 360 • Arm 1: 300mg i.v. anifrolumab Q4W for 48 weeks • Primary endpoint: response in SLE • FPCD: Q4 2015 TULIP SLE 2 • Arm 2: placebo i.v. Q4W for 48 weeks responder index at week 52 • LPCD: Q4 2017 BICLA at week 52 • Data readout: Q3 2019 NCT02446899 • Primary endpoint met

Phase III Moderate to severe SLE 630 • Arm 1: 300mg i.v. anifrolumab Q4W for 152 weeks • Primary endpoint: extension to evaluate • FPCD: Q2 2016 TULIP LTE • Arm 2: placebo i.v. Q4W for 152 weeks long-term safety and tolerability • LPCD: Q4 2018 • Data anticipated: 2022+ NCT02794285 R&I

Phase ll Moderate to severe SLE 307 • Arm 1: 300mg i.v. anifrolumab Q4W for 48 weeks • Primary endpoint: response in SLE • FPCD: Q1 2012 patients • Arm 2: 1000mg i.v. anifrolumab Q4W for 48 weeks responder index at 6 months • LPCD: Q1 2015 NCT01438489 • Arm 3: placebo i.v. Q4W for 48 weeks • Data readout: Q3 2014

Phase II Moderate to severe SLE 218 • Arm 1: anifrolumab, i.v. Q4W for 104 weeks • Primary endpoint: open-label extension • FPCD: Q1 2013 patients to evaluate long-term safety and • Data readout: Q4 2018 NCT01753193 tolerability

Phase II​ Moderate to severe SLE 32​ • Arm 1: 150mg s.c. every other week​ • PK/PD, safety, tolerability, primary • FPCD: Q1 2017​

patients​ • Arm 2: 300mg s.c. every other week​ analysis at week 12, secondary analysis • LPCD: Q4 2017 Other NCT02962960​ • Arm 3: placebo s.c. every other week​​ at week 52​ • Data readout: Q1 2018​

Phase II Active Proliferative LN 150 • Arm 1: 900 mg i.v. Q4W for 12 weeks then 300mg i.v. • Response in proteinuria at week 52 • FPCD: Q4 2015 TULIP-LN1 anifrolumab Q4W for 36 weeks • LPCD: Q4 2018 • Arm 2: 300 mg i.v. anifrolumab Q4W for 48 weeks • Data anticipated: H1 2021 NCT02547922 • Arm 3: placebo i.v. Q4W for 48 weeks

77 Approved medicines Late-stage development Brazikumab (IL23 inhibitor) Early development Inflammatory bowel disease (Crohn’s disease, ulcerative colitis) Oncology

Trial Population Patients Design Endpoints Status

Phase IIb / III Crohn’s Disease 1,140 • Arm 1: brazikumab high IV dose on day 1, 29 and 57 + SC Primary • FPCD: Q4 2018 INTREPID brazikumab on day 85 and every 4 weeks through week 48 • Endoscopic response and clinical • Data anticipated: H2 2022 • Arm 2: brazikumab low IV dose on day 1, 29 and 57 + 240 mg remission at week 12 NCT03759288 SC brazikumab on day 85 and every 4 weeks through week 48 Secondary CVRM • Arm 3: adalimumab SC on day 1, 15, 29 and every 2 weeks • Endoscope response and clinical through week 50 remission at both weeks 12 and 52 • Arm 4: placebo • Endoscopic remission and clinical remission at week 52

Phase III Crohn’s Disease 1,000 • Open label extension • Safety of long-term treatment with • FPCD: Q2 2019 brazikumab • Data anticipated: 2022+

NCT03961815 R&I Phase II Ulcerative Colitis 375 • Arm 1: brazikumab dose 1 IV on day 1, 15 and 43 + SC Primary • FPCD: Q3 2018 EXPEDITION brazikumab from day 71 and every 4 weeks • Clinical remission at week 10 • Data anticipated: H2 2022 • Arm 2: brazikumab dose 2 IV on day 1, 15 and 43 + SC Secondary NCT03616821 brazikumab from day 71 and every 4 weeks • Sustained clinical remission at week 10 • Arm 3: brazikumab dose 3 IV on day 1, 15 and 43 + SC and 54 brazikumab from day 71 and every 4 weeks • Arm 4: vedolizumab 300 mg IV on day 1, 15 and 43 + IV vedolizumab from day 99 and every 8 weeks • Arm 5: placebo

Phase II Ulcerative Colitis 300 • Open label extension • Clinically significant adverse events • FPCD: Q1 2020 • Data anticipated: 2022+ Other NCT04277546

78 Approved medicines Late-stage development Nirsevimab (Respiratory syncytial virus mAb-YTE ) Early development Infection Oncology

Trial Population Patients Design Endpoints Status

Phase IIb 29-35 WK GA (Gestational 1,453 • Randomised, double-blind, placebo-controlled trial • Safety and efficacy • FPCD: Q4 2016 age) infants • Route of administration: intramuscular • LPCD: Q4 2017 NCT02878330 • Data readout: Q4 2018

• Primary endpoint met CVRM

Phase II/III High risk preterm (born 35 1,500 • Randomised, Double-blind, palivizumab-controlled • Primary: Safety and tolerability • FPCD: Q3 2019 weeks 0 day or less GA), CHD • Route of administration: intramuscular • Secondary: PK, ADA and descriptive • Data readout: H2 2021 MEDLEY and CLD infants eligible to efficacy receive palivizumab Global trial – 32 countries NCT03959488

Phase III Healthy infants (born 35 3,000 • Randomised, Double-blind, placebo-controlled • Primary: Efficacy • FPCD: Q3 2019 weeks 0 days or greater GA) • Route of administration: intramuscular • Secondary: Safety, PK, ADA • Data readout: 2022+

MELODY R&I Global trial – 31 countries NCT03979313

Phase II Immunocompromised 30 • Open-label, Uncontrolled, single-dose Study • Primary: Safety and tolerability • FPCD: Q3 2020 Japanese children who are ≤ • Route of administration: intramuscular • Secondary: PK, ADA, efficacy • Data readout: 2022+ Japan IC 24 months of age at the time of dose administration Japan only

NCT04484935 Other

79 Approved medicines Late-stage development AZD1222 (SARS-CoV-2) Early development Prevention of COVID-19 Oncology

Trial Population Patients Design Endpoints Status

Phase I/II Healthy adults 1,077 Single-blinded, randomised, controlled, multi-centre trial • Primary endpoint: efficacy and safety • FPCD: Q2 2020 COV001 (UK) Age 18-55 years • AZD1222 • Secondary endpoints: safety, • LPCD: Q2 2020 • Control vaccine: MenACWY

tolerability, reactogenicity, and CVRM NCT04324606 UK immunogenicity Partnered

Phase I/II Healthy adults 2,125 Adaptive, double-blinded, randomised placebo-controlled trial • Primary endpoint: efficacy, safety, and • FPCD: Q2 2020 COV005 (SA) Age 18-65 years • AZD1222 immunogenicity • LPCD: Q4 2020 • Placebo • Data anticipated: H1 2021 NCT04444674 HIV+ subgroup South Africa Partnered

Phase II/III Main efficacy trial: healthy 10,812 Single-blinded, randomised, controlled, multi-centre trial with • Primary endpoint: efficacy and safety • FPCD: Q2 2020 COV002 (UK) adults aged ≥18 years sequential age escalation/de-escalation immunogenicity sub- • Secondary endpoints: safety, • LPCD: Q4 2020 R&I studies that include prime boost tolerability, reactogenicity, and NCT04400838 Healthy adults 56 - <70 years • AZD1222 immunogenicity Partnered Healthy adults 70 years • Control vaccine: MenACWY Healthy children 5 – 12 years UK

Phase III Healthy adults 32,429 Adaptive, double-blinded, randomised placebo-controlled trial • Primary endpoints: efficacy, safety, • FPCD: Q3 2020 D8110C00001 (US, global) Age 18-65 years • AZD1222 tolerability, and reactogenicity • Data anticipated: H1 2021 • Placebo • Secondary endpoints: immunogenicity NCT04516746 US, with intent to expand to other countries

Phase III Health professionals and 10,414 Single-blinded, randomised, controlled multi-centre trial • Primary endpoint: efficacy • FPCD: Q2 2020 COV003 (Brazil) adults with high potential for • AZD1222 • Secondary endpoints: safety, • LPCD: Q4 2020 Other exposure to SARS-CoV-2 • Control vaccine: MenACWY tolerability, reactogenicity, and NCT04536051 Age 18-55 years Brazil immunogenicity Partnered

Phase III Healthy adults 100 Open-label, non-comparative trial • Primary endpoints: safety, tolerability • Paused

D8111C00001 Age ≥18 years Russia • Secondary endpoints: immunogenicity 19 NCT04540393 -

Phase I/II Healthy adults 256 Double-blinded, randomised, placebo-controlled multi-centre trial • Primary endpoints: safety, tolerability, • FPCD: Q3 2020 D8111C00002 Age ≥18 years • AZD1222 reactogenicity, immunogenicity • Placebo • Secondary endpoints: immunogenicity COVID NCT04568031 Japan

Phase I/II Healthy adults 400 Double-blinded, randomised, placebo-controlled multi-centre trial • Primary endpoints: safety, tolerability, • FPCD: Q4 2020 COV004 (Kenya) • AZD1222 reactogenicity, immunogenicity • Control vaccine: rabies • Secondary endpoints: immunogenicity Kenya 80 Approved medicines Late-stage development AZD7442 (LAAB combination of AZD8895 & AZD1061) Early development Prevention and treatment of COVID-19 Oncology

Trial Population Patients/Subjects Design Endpoints Status

Phase I Healthy adults 60 Double-blinded, randomised, placebo controlled, single ascending • Primary endpoint: safety, tolerability and • FPFD: August 2020 Age 18-55 years dose study PK • LPCD: October 2020

• Secondary endpoints: immunogenicity CVRM NCT04507256 AZD7442/placebo (10:2)

Single center, UK

Phase III Adults having 5,000 Double-blinded, randomized, placebo controlled, multi center study • Primary endpoint: positive symptomatic • FPCD: Q4 2020 PROVENT increased risk for inadequate to determine safety and efficacy illness post –dose • Data anticipated: H2 2021 D8850C00002 response to • Secondary endpoints: Incidence of active immunization or AZD7442/placebo (2:1) nucleocapsid antibodies, incidence of R&I NCT04625725 having increased risk for Pre-exposure emergency visits, incidence of PCR SARS-CoV-2 infection positive, incidence of ADA to AZD7442 Countries: USA, UK, Belgium, France, Spain in serum and AZD7442 serum concentrations

Phase III Adults with potential exposure 1,125 Double-blinded, randomized, placebo controlled, multi center study • Primary endpoint: positive symptomatic • FPCD: Q4 2020 STORMCHASER To an identified individual with to determine safety and efficacy illness post –dose • Data anticipated: H1 2021 D8850C00003 confirmed SARS-COV2 • Secondary endpoints: Incidence of infection and at risk of AZD7442/placebo (2:1) nucleocapsid antibodies, incidence of NCT04625972 developing COVID-19

COVID-19 related death, incidence of Other Post-exposure all cause mortality, incidence of ADA to Countries: USA and UK AZD7442 in serum and ZD7442 serum concentrations

PHASE III Adults with confirmed mild to 1,700 Double-blinded, randomized, placebo controlled, multi center study • Primary endpoint: efficacy in the • FPCD: Q1 2021

TACKLE moderate SARS-COV2 to determine safety and efficacy of AZD7442 for treatment of prevention of the composite endpoint of • Data anticipated: H1 2021 19 - infection. Symptomatic patients Covid-19 in non-hospitalized patients either severe COVID-19 or death from NCT04723394 with documented positive any cause through study Day 29 SARS-Cov-2 molecular test.

AZD7442/placebo (1:1) COVID

Countries: UK, Germany, Spain, Italy, Hungary, Russia, US, Mexico and Japan

81 Approved medicines Late-stage development COVID-19 trials Early development Treatment of COVID-19 Oncology

Trial Compound Population Patients Design Endpoints Status

Phase III Farxiga COVID-19 1,250 • Current SoC or current SoC + Farxiga • Primary outcome measures: time to first • FPCD: Q2 2020 DARE-19 occurrence of either death from any • LPCD: Q1 2021 cause or new/worsened organ • Data anticipated H1 2021

NCT04350593 dysfunction through 30 days of follow up CVRM or improving clinical recovery; hierarchical composite outcome measures including time to death from any cause through day 30, new/worsened organ dysfunction, clinical status at day 30 and hospital discharge before day 30 and alive at day 30

Phase II Farxiga COVID-19 1,407 • Current SoC or current SoC + Farxiga + • Primary Outcome Measures: time to • FPCD: Q4 2020

TACTIC-E incidence of the composite endpoint of: • Data anticipated H1 2021 R&I death, mechanical ventilation, NCT04393246 extracorporeal membrane oxygenation, cardiovascular organ support, or renal failure

Phase IIIa Pulmicort COVID-19 300 • Current SoC or SoC + Pulmicort • Primary outcome measures: proportion • FPCD: Q2 2020 TACTIC-COVID of patients in both arms fulfilling the • Data anticipated H1 2021 criteria for treatment failure NCT04355637

Phase IIIa Pulmicort COVID-19 478 • Current SoC or SoC + Pulmicort • Primary Outcome Measures: emergency • FPCD: Q2 2020

STOIC department attendance of hospitalisation • Data readout Q1 2021 Other related to COVID-19 NCT04416399

Phase IIIa Symbicort COVID-19 436 • Current SoC or SoC + Symbicort • Primary Outcome Measures: time (in • FPCD: Q2 2020 INHASCO days) to clinical improvement within 30 • Data anticipated H1 2021 days after randomisation

NCT04331054 19 - Phase II MEDI3506 COVID-19 180 • Current SoC or current SoC + MEDI3506 • Primary endpoints: time to a 2-point • FPCD: Q2 2020 ACCORD improvement on a 9-point category • Data anticipated H1 2021 ordinal scale, discharge from hospital, or considered fit for discharge whichever comes first by Day 29 COVID

82 BioPharmaceuticals – early-stage development Approved medicines Late-stage development Cotadutide (GLP-1-glucagon agonist) Early development Diabetes/CKD, NASH Oncology

Trial Population Patients Design Endpoints Status

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 volume • Part A LPCD: Q4 2018 s.c. • Secondary: safety • Data readout: Q1 2019

• Sweden, Netherlands, UK • Secondary: tolerability • Part B FPCD: Q1 2020 CVRM • Secondary: immunogenicity • LPCD: H1 2021

Phase II Overweight and 27 • Cotadutide or placebo s.c. • Primary: efficacy body weight loss • FPCD: Q4 2018 NCT03596177 obese patients with • UK • Secondary: change in total energy intake • LPCD: Q4 2019 type-2 diabetes • Secondary: change in total energy expenditure, active energy • Data readout: Q4 2020 expenditure, resting energy expenditure • Secondary: safety

Phase II Obese patients with 72 • Arm1: cotadutide high dose s.c. • Primary: safety and tolerability • FPCD: Q4 2019

NCT04019561 non-alcoholic fatty • Arm2: placebo high dose s.c. • Secondary: change in hepatic fat fraction, • LPCD: H1 2021 R&I 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 • Data Readout: H2 2021 alcoholic • US steatohepatitis (NASH)

Phase II A Study of Cotadutide 225 • Arm1: cotadutide 100 micrograms • Primary: efficacy change in UACR • FPCD: Q4 2020 NCT04515849 in participants who • Arm2: cotadutide 300 micrograms • Secondary: Change in HbA1c • LPCD: H2 2021 have chronic kidney • Arm3: cotadutide 600 micrograms • Secondary: Change in glucose measured by CGM • Data readout: H2 2021 disease with type 2 • Arm4: • Secondary: Effects on body weight

diabetes mellitus • Arm5: placebo • Secondary: Safety, tolerability, Immunogenicity Other Phase I Healthy adult patients 36 • Primary: to evaluate exposure following a single s.c of cotadutide at • FPCD: Q4 2019 NCT04091373 each of 3 different sites of injection • LPCD: Q1 2020 • Secondary: immunogenicity • Data readout: Q4 2020 • Secondary: safety and tolerability

84 Approved medicines Late-stage development Verinurad (URAT1 inhibitor) Early development CKD, HFpEF Oncology

Trial Population Patients Design Endpoints Status

Phase II Patients with: 725 • Arm A; Verinurad 12 mg + allopurinol 300 mg Ratio of urinary albumin to urinary • FPCD: Q3 2019 • sUA ≥6.0 mg/dL • Arm B Verinurad 7.5 mg + allopurinol 300 mg creatinine • Data anticipated: H2 2021 NCT03990363 • eGFR ≥25 mL/min/1.73 • Arm C; Verinurad 3 mg + allopurinol 300 mg Changes in eGFR, Cystatin C, and uric acid

m2 Chronic Kidney • Arm D; Verinurad placebo + allopurinol 300 mg CVRM Disease Epidemiology • Arm E; Verinurad placebo + allopurinol placebo Collaboration (CKD-EPI formula) This trial is multi-centre trial conducted in USA, China, Czech • Mean UACR between 30 Republic, France, Hungary, Israel, Italy, Mexico, Poland, mg/g and 5000 mg/g Romania, Slovakia, South Africa, Spain

Phase I Healthy volunteers 24 • Treatment A: Verinurad 24 mg ER8 formulation + 300 mg To assess the effect of a single dose of • FPCD: Q3 2020 • allopurinol verinurad given as either a 24 mg • Data readout: H2 2020 NCT03118739

• Treatment B: Verinurad 40 mg IR formulation + 300 mg extended-release (ER8) formulation R&I • allopurinol (therapeutic exposure) or a 40 mg • Treatment C: Matched placebos for both verinurad and immediate-release (IR) formulation (supra- allopurinol therapeutic exposure), both in combination The trial is a single-centre, randomised, placebo-controlled, with allopurinol 300 mg, on the QT interval double-blind, 3-period, cross-over trial conducted in Germany corrected for heart rate using Fridericia’s formula (QTcF) compared to placebo

Phase I Healthy volunteers 14 • Treatment A: Verinurad 7.5 mg ER8 formulation + 300 mg To quantify the effects of cyclosporine, a • FPCD: Q3 2020 Allopurinol under fasted conditions broad transporter inhibitor, and rifampicin, • LPCD: Q4 2020 NCT04532918 • Treatment B: Verinurad 7.5 mg IR formulation + 300 mg an OATP1B1/3 inhibitor,on verinurad • Data anticipated: H1 2021 allopurinol + cyclosporin 600 mg under fasted conditions pharmacokinetics (PK). Other • Treatment C: Verinurad 7.5 mg IR formulation + 300 mg allopurinol + rifampicin 600 mg under fasted conditions

The trial is a single-centre, randomised, open-label, 3-period, fixed sequence, trial conducted in Germany

Phase II Patients with heart failure with 435 • Arm A: verinurad 12 mg + allopurinol 300 mg Peak V02 Change from baseline at Week • FPCD: Q3 2020 preserved ejection fraction • Arm B: verinurad placebo + allopurinol 300 mg 28 in exercise capacity • Data readout: 2022+ NCT04327024 • Arm C: verinurad placebo + allopurinol placebo Change from baseline at Week 28 in The trial is a multi-centre trial conducted in Argentina, Australia, Kansas-City Cardiomyopathy Austria, Bulgaria, Canada, Germany, Mexico, Poland, Russia, Questionnaire-Total Symptom Score Slovakia South Korea, USA (KCCQ-TSS)

85 Approved medicines Late-stage development AZD2373 Early development Chronic kidney disease Oncology

Trial Population Patients Design Endpoints Status

Phase I Healthy volunteers 48 SAD Primary: • FPCD: Q1 2020 • Safety and tolerability NCT04269031 Dose escalation in 6 cohorts with 6 volunteers receiving

AZD2373 and 2 volunteers receiving placebo in each cohort Secondary; CVRM • PK parameters

Trial conducted in the US

R&I Other

86 Approved medicines Late-stage development AZD2693 (resolution of NASH) Early development NASH Oncology

Trial Population Patients Design Endpoints Status

Phase I Healthy volunteers 48 SAD Primary: • FPCD: Q4 2019 • Safety and tolerability • Data anticipated: H2 2021 NCT04142424 6 cohorts with 6 volunteers receiving AZD2693 and 2 volunteers

receiving placebo in each cohort Secondary; CVRM • PK Route of administration: subcutaneous injections

Trial conducted in the US.

Phase I NAFLD F0-F3 60 MAD Primary: • FPCD: Q1 2021 • Safety and tolerability • Data anticipated: H2 2021 NCT04142424 3 cohorts receiving AZD2693 and placebo in each cohort Secondary;

Route of administration: subcutaneous injections • PK R&I

Trial conducted in the US. Other

87 Approved medicines Late-stage development AZD3427 (relaxin) Early development Heart failure Oncology

Trial Population Patients Design Endpoints Status

Phase I SAD – Healthy Volunteers 96 • Multi-center single and multiple ascending dose study (SAD Safety & Tolerability • FPCD: Q4 2020 MAD – Heart Failure and MAD) planned in 96 participants (US) • Data anticipated: 2022+

NCT04630067 • Part A (SAD) will include 6 cohorts randomized to AZD3427 CVRM or placebo • Part B (MAD) will include cohorts randomized to AZD3427 or

placebo

R&I Other

88 Approved medicines Late-stage development AZD3366 Early development Cardiovascular disease Oncology

Trial Population Patients Design Endpoints Status

Phase I Healthy volunteers 87 SAD Primary: • FPCD: Q4 2020 • Safety and tolerability NCT04588727 Part A Dose escalation in 6 cohorts with 6 volunteers receiving

AZD3366 and 2 volunteers receiving placebo in each cohort Secondary; CVRM • PK parameters Part B 12 subjects receiving AZD3366 and ticagrelor and ASA

Trial conducted in the US

R&I Other

89 Approved medicines Late-stage development MEDI3506 (IL33 ligand mAb) Early development Diabetic kidney disease Oncology

Trial Population Patients Design Endpoints Status

Phase II Adult patients with diabetic 565 • Arm A- MEDI3506 Dose 1 + dapagliflozin • Efficacy and safety • FPCD: Q4 2019 kidney disease • Arm B- MEDI3506 Dose 2 + dapagliflozin NCT04170543 • Arm C- MEDI3506 Dose 3 + dapagliflozin

• Arm D- MEDI3506 Dose 4 + dapagliflozin CVRM • Arm E- placebo + dapagliflozin

This trial is multi-centre trial conducted in USA, Canada, Japan

and additional countries.

R&I Other

90 Approved medicines Late-stage development AZD4831 (MPO inhibitor) Early development Cardiovascular disease Oncology

Trial Population Patients Design Endpoints Status

Phase I Healthy patients c. 96 SAD trial (one trial site in Germany) • Safety and tolerability • FPCD: Q3 2016 • Planned to investigate 6 different dose levels vs. placebo but • PK parameters • LPCD: Q4 2016

NCT02712372 up to 10 cohort may be used • Data readout Q2 2017 CVRM

Phase I Healthy patients c. 40 MAD (one trial site in USA) • Safety and tolerability • FPCD: Q2 2017 • The planned number of cohorts is four but up to five cohorts • PK parameters • LPCD: Q4 2017 NCT03136991 may be included • Data readout: Q1 2018

Phase IIa HFpEF 96 Arm 1: AZD4831 • Primary endpoint: The change from • FPCD: Q4 2018 Arm 2: placebo baseline in MPO activity in % after • Data readout: H2 2020 NCT03756285 AZD4831 treatment R&I Global trial – five countries

Phase I Healthy patients 32 SAD trial in Japanese and Chinese patients • Safety and tolerability • FPCD Q1 2020

NCT04232345 • Data anticipated: H1 2021 Other

91 Approved medicines Late-stage development AZD5718 (FLAP inhibitor) Early development Cardiovascular disease Oncology

Trial Population Patients Design Endpoints Status

Phase IIa CAD 129 • Arm 1: AZD5718 Dose A • Primary endpoint: PD effect of AZD5718 • FPCD: Q4 2017 • Arm 2: AZD5718 Dose B by assessment of u-LTE4 • LPCD: Q4 2019

NCT03317002 • Arm 3: placebo CVRM Global trial – three countries in Europe

Phase I Healthy patients 6 hADME trial (one trial site in UK) • Mass balance, with routes and rates of • FPCD: Q2 2019 • Oral administration elimination of [14C]AZD5718. • LPCD: Q2 2019 NCT03948451 Open-label trial to characterize the absorption, distribution, • Metabolite profiling and structural metabolism and following a single oral dose of identification [14C]AZD5718 in healthy male volunteers • PK and total radioactivity

Phase I Healthy patients 14 BA trial (one trial site in UK) • To evaluate the pharmacokinetics and • FPCD: Q4 2019 R&I An open-label, randomized, 3-period, 3-treatment, crossover trial exposure of 3 different doses • LPCD: Q4 2019 NCT04087187 to assess the drug absorption into the blood after administration of AZD5718 of 3 doses of AZD5718 • Safety and tolerability

Phase I Healthy patients 12 BA trial (one trial site in UK) To evaluate: • FPCD: Q1 2020 The trial is a randomized, single-dose, open-label, combined 2x2 • The relative bioavailability of different • LPCD: Q1 2020 NCT04210388 dose and 3x3 dose crossover design in fixed sequence. formulations • Safety and tolerability

Phase IIb CKD 632 Interventional To evaluate: • FPCD: Q4 2020 A Phase IIb randomised, double-blind, placebo-controlled, multi- • dose-response efficacy Other NCT04492722 centre, dose-ranging trial of AZD5718 in participants with • Safety proteinuric CKD • pharmacokinetics (PK)

92 Approved medicines Late-stage development AZD8233 (PCSK9 inhibitor, sub-cutaneious) Early development Dyslipidemia Oncology

Trial Population Patients Design Endpoints Status

Phase I Healthy subjects 72 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.

Phase I Dyslipidemia 33 MAD Primary: • FPCD Q1 2020 • Safety and tolerability NCT04155645 Up to 3 cohorts with 8 subjects receiving AZD8233 and 3 subjects receiving placebo in each cohort Secondary; • PK and PD parameters Trial conducted in the US

Phase II Dyslipidemia 108 Subjects are randomized across four different treatment arms in a Primary: • FPCD: Q4 2020 R&I 1:1:1:1 ratio for a 12-week treatment period • Efficacy NCT04641299 Arm 1: High AZD8233 dose Arm 2: Medium AZD8233 dose Arm 3: Low AZD8233 dose Arm 4: placebo

Trial conducted in 3 countries (US, Slovakia and Denmark) Other

93 Approved medicines Late-stage development MEDI8367 Early development Chronic kidney disease Oncology

Trial Population Patients Design Endpoints Status

Phase I Healthy volunteers 70 Single ascending dose Primary: • FPCD: Q3 2020 CKD 6 cohorts • Safety and tolerability NCT04365218 Arm 1: MEDI8367

Arm 2: placebo Secondary; CVRM • PK parameters Subcutaneous administration • ADA

Trial conducted in the US

R&I Other

94 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, two in Germany) • Safety and tolerability • FPCD: Q1 2018 • Arm 1: AZD8601 Dose A NCTT03370887 • Arm 2: AZD 8601 Dose B

• Arm 3: placebo

R&I Other

95 Approved medicines Late-stage development AZD9977 Early development Heart failure Oncology

Trial Population Patients Design Endpoints Status

Phase I Healthy volunteers 27 MAD Primary: • FPCD: Q1 2018 Dose escalation in 3 cohorts with 6 subjects receiving AZD9977 • Safety and tolerability • LPCD: Q2 2018 NCT03435276 and 3 volunteers receiving placebo in each cohort • Data readout: Q3 2018

Secondary; CVRM Trial conducted in the UK. • PK parameters

Phase I Healthy volunteers 12 Bioavailability trial Primary: • FPCD: Q2 2018 Investigation of four different oral formulations of AZD9977 and • relative bioavailability vs. oral suspension • LPCD: Q2 2018 NCT03450759 influence of food. (reference) • Data readout: Q3 2018 • PK parameters Trial conducted in the UK.

Phase I HF 60 Proof of differentiation Primary: • FPCD Q4 2018 To compare the effect of AZD9977 with spironolactone on serum • serum potassium • LPCD Q1 2019 NCT03682497 potassium R&I

Phase I Healthy volunteers 14 DDI Primary: • FPCD: Q1 2019 To assess the effect of itraconazole on the pharmacokinetics of • PK parameters • LPCD: Q1 2019 NCT03843060 AZD9977 • Data readout: Q3 2019 Secondary; Trial conducted in the US • Safety and tolerability

Phase I Healthy volunteers 45 JSMAD Primary: • FPCD: Q1 2019 Single and multiple-ascending dose administration in Japanese • Safety and tolerability • LPCD: Q2 2019 NCT03801967 healthy volunteers. • Data readout: Q3 2019

Secondary; Other Trial conducted in the UK • PK parameters

Phase I Healthy volunteers 12 Bioavailability trial Primary: • FPCD: Q1 2019 Investigation of four different oral formulations of AZD9977 and • relative bioavailability vs. capsule • LPCD: Q2 2019 NCT03804645 influence of food. formulation (reference) • Data readout: Q3 2019 • PK parameters Trial conducted in the UK

Phase I Renal Impairment 32 Renal Impairment Primary: • FPCD: Q3 2020 NCT04469907 Single dose administration of AZD9977 conducted in participants • PK parameters • LPCD: H1 2021 with severe renal impairment and compared with matched • Data readout: H1 2021 participants with normal renal function Secondary: • Safety and tolerability Trial conducted in the US

Phase I Healthy volunteers 8 ADME Primary: • FPCD: Q1 2021 NCT04686591 Study of absorption-distribution-metabolism-excretion (ADME) of • Absolute bioavailability • LPCD: Q1 2021 14C-AZD9977 following a single oral dose and absolute • The mass balance, rates and routes of • Data readout: H2 2021 bioavailability of a single oral dose with respect to AZD9977 • elimination Trial conducted in the UK Secondary: 96 • Safety and tolerability Approved medicines Late-stage development Zibotentan ( receptor antagonist) Early development Chronic kidney disease Oncology

Trial Population Patients Design Endpoints Status

Phase IIb Chronic Kidney Disease 660 Global recruitment Primary Endpoint: • Initiating

Change in log-transformed UACR from CVRM NCT04724837 Part A: 132 participants equally randomised across 4 arms: baseline to week 12. Arm 1: Zibotentan dose A + Dapagliflozin 10 mg once daily. Arm 2: Zibotentan dose A once daily. Secondary Endpoints: Arm 3: Dapagliflozin 10 mg once daily. •Change in log-transformed UACR from baseline to Arm 4: Placebo once daily. week 12.

Part B: 528 participants equally randomised across 6 arms: •Change in blood pressure from baseline (Visit 2) to Arm 1: Zibotentan dose C + Dapagliflozin 10 mg once daily. week 12.

Arm 2: Zibotentan dose B + Dapagliflozin 10 mg once daily. R&I Arm 3: Zibotentan dose A + Dapagliflozin 10 mg once daily. •The least squares mean change of UACR at week 12 Arm 4: Zibotentan dose A once daily. from the 3 Zibo/Dapa dose groups and the Arm 5: Dapagliflozin 10 mg once daily. dapagliflozin monotherapy group. Arm 6: Placebo once daily. •Change in eGFR from baseline to week 1, week 12 and week 14.

•Change in eGFR from week 1 to week 12. Other

97 Approved medicines Late-stage development Biologics Early development Cardiovascular & metabolic diseases Oncology

Trial Compound Population Patients Design Endpoints Status

Phase IIb MEDI6012 Subjects 30-80 595 • 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) • LPCD: Q4 2020 EudraCT 2017- inclusive, (loading dose) prior to pPCI followed by a compared to placebo • Data anticipated: 2022+ 004521-32 presenting with second inpatient dose Secondary endpoints: CVRM acute STEMI of 150 mg or placebo on Day 3 by i.v. • Ejection Fraction at 10-12 weeks post-MI compared to placebo. push. • Change in NCPV in the coronary arteries from at10-12 • Cohort B: 6-dose regimen weeks post-MI compared with placebo 300 mg of MEDI6012 or placebo on day 1 • Myocardial mass and LV volumes at end-systole and end- prior to pPCI followed by a second diastole inpatient dose of 150 mg or placebo on day • Incidence of TEAEs and treatment-emergent SAEs. 3 and outpatient maintenance doses of 100 • LCAT mass and ADAs mg or placebo on days 10, 17, 24, and 31 by i.v. push. R&I

Phase IIa MEDI5884 Adults with stable 133 • MEDI5884 (5 dose cohorts) vs. placebo in • Safety profile in terms of AEs, vital signs, ECG, lab variables • FPCD Q4 2017 cholesterol CHD stable CHD patients • Changes in HDL-C over time • Data readout: Q4 2018 NCT03351738 modulation • PK, immunogenicity, and Apolipoprotein B

Phase I MEDI6570 Atherosclerotic 88 • SAD followed by multi ascending dose • Primary endpoints: Safety and tolerability • FPCD: Q4 2018 cardiovascular with 3 monthly doses in T2DM subjects • Data anticipated: 2021

NCT03654313 disease Other

Phase IIb MEDI6570 Post MI 792 Evaluation of anti-inflammatory potential of • Efficacy and safety • FPCD: Q42020 MEDI6570 and its effect on surrogates for NCT04610892 atherosclerotic and heart failure (HF) events . Subjects are randomized across four different treatment arms in a 1:1:1:1 ratio

Arm 1: High AZD6570 dose Arm 2: Medium AZD6570 dose Arm 3: Low AZD6570 dose Arm 4: Placebo

Trial conducted in 9 countries (US, Canada, Hungary, Japan, Czech Republic, Italy, Spain, Netherlands, Poland,)

98 Approved medicines Late-stage development AZD0449 (inhaled JAK-1 inhibitor) Early development Asthma Oncology

Trial Population Patients Design Endpoints Status

Phase I Healthy subjects and patients 156 SAD/MAD/Bridge trial (UK) Primary endpoint: • FPCD: Q4 2018 with mild asthma Part 1 SAD • Safety and tolerability • Data anticipated: H1 2021 NCT03766399 • Dose escalation in 6 cohorts with 6 subjects receiving

AZD0449 and 2 subjects receiving placebo in each cohort Secondary endpoint: CVRM • i.v. cohort with 2x6 subjects • PK parameters • FENO Part 2 MAD: • 2 cohorts of (6, 6,) mild asthmatics receiving two different doses of AZD0449 and (3,3) patients receiving placebo in each cohort • 1 cohort of 6 patients receiving 1 dose of AZD0449 and 2 patients receiving placebo

Part 3 bridge R&I • 1 cohort of 6 patients receiving 1 dose of AZD0449 (DPI formulation) and 2 patients receiving placebo. • Up to 18 mild asthmatic patients will receive AZD0449 (DPI) and 18 patients receiving placebo. Interim analysis planned after 9 +9 patients.

Trial conducted in the UK Other

99 Approved medicines Late-stage development AZD1402 (IL4 receptor alpha antagonist) Early development Asthma Oncology

Trial Population Patients Design Endpoints Status

Phase Ib Patients with mild asthma 84 PoM. Primary endpoint: • LPCD: Q3 2018 A dose-escalating, single blind trial to assess the • Safety and tolerability NCT03574805 safety, tolerability, and pharmacokinetics of multiple

doses of PRS-060 administered by oral Inhalation In Secondary endpoint: CVRM Partnered subjects with mild asthma • PK parameters • Potential immunogenicity • Change in FENO

Australia

R&I Other

100 Approved medicines Late-stage development MEDI3506 (IL33 ligand mAb) Early development COPD, atopic dermatitis, asthma Oncology

Trial Population Patients Design Endpoints Status

Phase II Adult subjects with atopic 152 Randomised, blinded, placebo-controlled trial to determine the • Primary: change from baseline at week • FPCD: Q4 2019 dermatitis efficacy and safety of three different doses of MEDI3506 by SC 16 in Eczema Area and Severity Index

NCT04212169 route vs placebo (EASI) score CVRM • Secondary: safety and other efficacy measures Conducted in US, Australia, Germany, Poland & UK

Phase II Adult participants with 228 Randomised, double-blind, placebo-controlled trial to evaluate the • Primary: change from baseline at week • FPCD: Q4 2020 uncontrolled moderate to efficacy, safety, pharmacokinetics (PK) and immunogenicity of 16 in FEV1 NCT04570657 severe asthma two different doses of MEDI3506 by SC route vs placebo • Secondary: safety and other efficacy measures Conducted in US, Argentina, Germany, Hungary, Poland & South R&I Africa

Phase II Adult subjects COPD and 322 Randomised, double-blind, placebo-controlled, parallel group, • Primary: change from baseline to week • Initiating chronic bronchitis proof of concept trial to evaluate the efficacy and safety of 12 in FEV1 NCT04631016 MEDI3506 as a single dose by SC route versus placebo • Secondary: safety and other efficacy measures Conducted in US, Canada, Denmark, Germany, Hungary,

Netherlands, Poland, South Africa, Spain Other

101 Approved medicines Late-stage development AZD7986 (DPP1) Early development COPD Oncology

Trial Population Patients Design Endpoints Status

Phase I Healthy volunteers 15 This is a phase I, non-randomised, fixed sequence, 3-period, • Safety and tolerability • FPCD: Q1 2016 drug-drug interaction trial to assess the PK of AZD7986 in healthy • PK/PD and DDI • Data readout: Q2 2016 NCT02653872 subjects when administered alone and in combination with

multiple doses of verapamil and itraconazole or diltiazem CVRM

• Arm 1: AZD7986 (alone) treatment period 1 • Arm 2: verapamil (with AZD7986) treatment period 2 • Arm 3: itraconazole (with AZD7986) treatment Period 3 • Arm 4: diltiazem (with AZD7986) treatment period 3

Phase I Healthy volunteers 89 A phase I, randomised, single-blind, placebo-controlled, 2-part • Safety and tolerability • FPCD: Q4 2014 R&I trial to assess the safety, tolerability, PK and food effect of single • PK/PD • Data readout: Q3 2016 NCT02303574 and multiple oral doses of AZD7986 in healthy volunteers. • Bioavailability

• Arm 1: AZD7986, single and multiple oral doses

• Arm 2: placebo, single and multiple doses Other

102 Approved medicines Late-stage development AZD8154 (PI3Kδ inhibitor) Early development Asthma Oncology

Trial Population Patients Design Endpoints Status

Phase I Healthy subjects 78 SAD/MAD Primary endpoint: • FPCD: Q3 2018 A Phase I trial to assess the safety, tolerability and PK of • Safety and tolerability • LPCD: Q3 2019 NCT03436316 AZD8154 following single dose administration and multiple dose • Data readout: Q4 2019

administration in healthy subjects Secondary endpoint: CVRM

• PK parameters

R&I Other

103 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 readout: Q3 2019

following 3 treatments sequence in the form of dry powder Secondary endpoints: CVRM • To characterize the pharmacokinetics of inhalation: AZD8871 following multiple inhaled • AZD8871 600 µg once daily doses • Anoro® Ellipta® (55 µg umeclidinium [UMEC]/ 22 µg • To assess safety and tolerability of vilanterol [VI]) once daily AZD8871

• Placebo

R&I Other

104 Approved medicines Late-stage development AZD9567 (SGRM, oral) Early development Respiratory Oncology

Trial Population Patients Design Endpoints Status

Phase I Healthy subjects 71 MAD trial with a total of 6 dose levels of AZD9567: 10 mg, 20mg, Primary endpoint: • FPCD: Q2 2016 40mg, 80mg and 125 mg as well as with 3 dose levels of • To assess the safety and tolerability of • Data readout: Q2 2018 NCT02760316 prednisolone: 5 mg, 20 mg and 40 mg AZD9567 following multiple oral

ascending doses in subjects with BMI CVRM between 28 and 38 kg/m2 and with a positive glucose tolerance test (7,8 to 11,0 mmol/L) Secondary endpoints: • To characterise the pharmacokinetics of AZD9567 following multiple oral administration of ascending doses • To characterise the pharmacodynamics of AZD9567 assessed as effect on

glucose homeostasis through OGTT (oral R&I glucose tolerance test) in comparison with prednisolone

Phase IIa Patients with active RA 21 A randomised, double-blind, parallel trial to assess the efficacy, Primary endpoint: • FPCD: Q1 2018 NCT03368235 safety and tolerability of AZD9567 compared to prednisolone 20 To assess the efficacy of AZD9567, 40 mg, • Data readout: Q2 2020 mg in patients with active rheumatoid arthritis compared to prednisolone 20 mg in patients with active RA in spite of stable treatment with conventional and/or s.c./i.v. biological DMARDs (Disease-modifying antirheumatic drugs)

Secondary endpoints: Other • To further assess the efficacy of AZD9567, 40 mg, compared to prednisolone 20 mg in patients with active rheumatoid arthritis in spite of stable treatment with conventional and/or s.c./i.v. biological DMARDs • (e g SJC 66/TJC68, ACR response criteria) • To evaluate the pharmacokinetic profile of AZD9567

105 Approved medicines Late-stage development AZD0284 (RORγ inverse agonist) Early development Plaque psoriasis vulgaris Oncology

Trial Population Patients Design Endpoints Status

Phase I Healthy subjects 80 Part 1 (SAD) • Safety and tolerability and PK following • FPCD: Q3 2016 • Seven different dose levels investigated vs. placebo oral administration with single ascending • LPCD: Q2 2017 NCT02976831 • Oral administration dose

• Preliminary assessment of the effect of CVRM food on the single dose PK parameters of AZD0284

Part 2 (MAD) • Safety and tolerability & PK in healthy • FPCD: Q1 2017 • Three different dose levels investigated vs. placebo in healthy subjects following administration of • LPCD: Q1 2017 subjects multiple ascending oral doses • Oral administration • PoM confirmed by demonstrating that oral dosing of AZD0284 reduces IL-17 secretion by ex vivo stimulated whole

blood T cells R&I

Phase I Healthy subjects 6 A single centre, open-label, non-randomised, single dose trial • Determination of absolute bioavailability • FPCD: Q1 2017 performed in 6 healthy male subjects aged 18 to 65 years, of AZD0284 • LPCD: Q1 2017 NCT03029741 inclusive. The trial will assess the absolute bioavailability of a • Safety and tolerability of AZD0284 single oral dose of AZD0284 and the pharmacokinetics (PK) of a single intravenous (IV) microdose of [14C] AZD0284 in healthy male and female subjects. Oral AZD0284 and [14C] AZD0284 intravenous solution are referred to as the investigational products in this trial

Phase Ib Patients with moderate to 15 This was a randomised, double-blind, placebo-controlled, multi- • Relative change from baseline of IL- • FPCD: Q4 2017 severe plaque psoriasis centre, parallel group 17A and CCL20 mRNA expression • LPCD: Q1 2018 Other NCT03310320 Phase Ib study, designed to evaluate the pharmacodynamic (PD) levels in lesional skin at Week 4. effects, clinical efficacy and • Percent improvement from baseline in safety of AZD0284 compared with placebo as measured by the individual PASI score at Week 4 relative change from baseline in Psoriasis Area and Severity Index (PASI) score and biomarkers associated with the mechanism of disease and AZD0284.

106 Approved medicines Late-stage development MEDI0618 (PAR2 antagonist mAb) Early development Osteoarthritis pain Oncology

Trial Population Patients Design Endpoints Status

Phase I Painful osteoarthritis of the knee 64 (healthy • SAD • Safety, tolerability and PK • FPCD: Q4 2019 volunteers) • Up to 8 i.v. cohorts are planned vs. placebo

NCT02508155 • 1 s.c. cohortis planned vs. placebo CVRM

Europe only

R&I Other

107 Approved medicines Late-stage development MEDI1341 (alpha-synuclein mAb) Early development Parkinson’s disease Oncology

Trial Population Patients Design Endpoints Status

Phase I Healthy volunteers 48 • SAD • Safety, tolerability, PK, PD • FPCD: Q4 2017 • Up to 6 i.v. cohorts are planned vs. placebo • Data anticipated: H1 2021 NCT03272165

US only CVRM

Phase I Parkinson's Disease 36 • MAD • Safety, tolerability, PK, PD • FPCD: Q3 2020 • Up to 3 i.v. cohorts are planned vs placebo • Data anticipated: 2022+ NCT04449484

• US only

R&I Other

108 Approved medicines Late-stage development AZD4041 (orexin 1 receptor antagonist) Early development Opioid use disorder Oncology

Trial Population Patients Design Endpoints Status

Phase I Healthy volunteers 48 healthy • Randomised, double blind, single ascending dose • Safety, tolerability, PK, PD • FPCD: Q4 2019 volunteers • Up to 6 cohorts are planned vs. placebo • Data anticipated: H1 2021 NCT04076540

Single centre in US only CVRM Partnered with Eolas Therapeutics Inc

and NIH.

R&I Other

109 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 2021

NCT02508155 • 1 s.c. cohorts are planned vs. placebo CVRM Europe only

Phase II Painful diabetic neuropathy 271 • Multiple dose trial • Dose response, safety, tolerability, PK, • FPCD Q4 2018 • Up to 4 i.v. cohorts are planned vs. placebo PD • Data anticipated: 2021 NCT03755934 Europe only

Phase Iib Painful osteoarthritis of the knee 300 • Multiple dose trial • Dose response, safety, tolerability, PK, • Initiating R&I • 3 active s.c. dose cohorts vs. placebo PD, ADA • Data anticipated 2022 NCT04675034

Global (8 countries) Other

110 Approved medicines Late-stage development Other biologics Early development Infections Oncology

Trial Compound Population Patients Design Endpoints Status

Phase II Anti-Staph AT Intubated ICU 213 • Placebo-controlled, single-dose, dose-ranging • Efficacy and safety • FPCD: Q4 2014 (suvratoxumab, • Route of administration: intravenous • Data readout: Q4 2018 EudraCT 2014- MEDI4893)

001097-34 CVRM

Phase II Anti-Pseudomonas Intubated ICU 195 • Placebo-controlled, single-dose, dose-ranging • Efficacy and safety • FPCD: Q2 2016 A mAb (MEDI3902) • Route of administration: intravenous • Data readout: Q4 2020

NCT02696902

R&I Other

111 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-oesophogeal junction ADP Adenosine diphosphate CRC Colorectal cancer GFF Glycopyrronium and formoterol fumarate AE Adverse Event CrCl Creatinine clearance GLP-1 Glucagon-like -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 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 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 BTK Bruton's EGFR receptor i.m. Intramuscular CA-125 Cancer antigen 125 ER Oestrogen receptor IRC Independent review committee CAD Coronary artery disease ERK Extracellular signal-regulated kinase ISS Investigator-sponsored studies CBR Clinical benefit rate ESR Externally sponsored trial i.v. Intraveneous CCL20 Chemokine (C-C motif) ligand 20 ESR1 Oestrogen receptor 1 J-SD Japanese single dose CD Cluster of differentiation ESSC Esophageal squamous cell carcinoma Ki67 Protein that is encoded by the MKI67 gene in human CDK Cyclin-dependent kinase FDC Fixed-dose combination LAAB Long acting antibody CE Clinically evaluable FeNO Fractional nitric oxide concentration in exhaled breath CHD Coronary heart disease FEV Forced-expiratory volume Chemo Chemotherapy FGFR receptor 112 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 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 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 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 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 113 Clinical trials appendix

Full year and Q4 2020 results update