Clinical trials appendix Q1 2019 results update - AstraZeneca

Clinical trials appendix Q1 2019 results update - AstraZeneca
Clinical trials appendix
Q1 2019 results update
Clinical trials appendix Q1 2019 results update - AstraZeneca
The following information about AstraZeneca clinical trials in Phases I-IV has been
    created with selected information from clinicaltrials.gov to facilitate understanding
    of key aspects of ongoing clinical programmes and is correct to the best of the
    Company’s knowledge as of 31 March 2019, unless otherwise specified.

    It includes estimated timelines with regards to trial completion and first external
    presentations of primary data. These estimates are subject to change, as
    programmes recruit faster or slower than anticipated and many times are event
    driven.

    Project postings on clinicaltrials.gov are updated on a continuous basis as projects
    progress. For the most up to date information on our clinical programmes please
    visit clinicaltrials.gov


2
Clinical trials appendix Q1 2019 results update - AstraZeneca
List of abbreviations

    ADA      Anti-drug antibody                         ICS    Inhaled corticosteroid           pMDI   Pressurised metered dose inhaler
    ADC      Antibody-drug conjugate                    IM     Intra muscular                   PoC    Proof of concept
    AE       Adverse event                              IR     Immediate release                PR     Partial response
    AUC      Area under curve                           IV     Intravenous                      Q2W    Quaque (every) two weeks
    BD/BID   Bis in die (two times a day)               LABA   Long acting beta agonist         Q3W    Quaque (every) three weeks
    CE       Clinically evaluable                       LAMA   Long acting muscarinic agonist   Q4W    Quaque (every) four weeks
    CMAX     Maximum concentration absorbed             LCM    Lifecycle management             Q8W    Quaque (every) eight weeks
    CNS      Central nervous system                     LPCD   Last patient commenced dosing    QD     Quaque die (one time a day)
    DCR      Disease control rate                       MAD    Multiple ascending dose          QOD    Quaque altera die (every other day)
    DDI      Drug-drug interaction                      MDI    Metered-dose inhaler             QoL    Quality of life
    DFS      Disease free survival                      MTD    Maximum tolerated dose           SAD    Single ascending dose
    DLT      Dose-limiting toxicity                     NME    New molecular entity             SC     Subcutaneous
    DoR      Duration of response                       OCS    Oral corticosteroid              SoC    Standard of care
    DPI      Dry powder inhaler                         ORR    Objective response rate          TID    Ter In die (three times a day)
    FDC      Fixed-dose combination                     OS     Overall survival                 VEGF   Vascular endothelial growth factor
    FEV      Forced-expiratory volume                   PARP   Poly ADP ribose polymerase       XR     Extended release
    FPCD     First patient commenced dosing             PD     Pharmacodynamics
    HRRm     Homologous recombination repair mutation   PFS    Progression-free survival
                                                        PK     Pharmacokinetics
3
Clinical trials appendix Q1 2019 results update - AstraZeneca
Table of contents slide


    Movement since Q4 2018 update

    Q1 2019 NME pipeline

    Q1 2019 LCM pipeline



    Oncology
    Approved medicines and late-stage development

    Early-stage development


    Cardiovascular, Renal & Metabolism (CVRM), Respiratory & Other medicines
    Approved medicines and late-stage development

    Early-stage development




4
Movement since Q4 2018 update
           New to Phase I                                                                   New to Phase II                                                              New to Pivotal Study                               New to Registration
    Additional indication                         NME                                                                                                     NME                                                        Lifecycle Management
    MEDI7247                                      trastuzumab deruxtecan¶# DESTINY-Breast01                                                               Lynparza# + Imfinzi# + bevacizumab DUO-O                   Farxiga3 DECLARE-TIMI 58 [US & EU]1
    ASCT2 antibody drug conjugate solid           ADC HER2-positive, unresectable and/or metastatic breast cancer subjects previously treated             PARP inhibitor + PD-L1 mAb + VEGF inhibitor                SGLT2 inhibitor CV outcomes trial in patients
    tumours                                       with trastuzumab emtansine                                                                              1st-line ovarian cancer                                    with type-2 diabetes
                                                  Additional indication
                                                                                                                                                          Additional indication
                                                  capivasertib#
                                                                                                                                                          trastuzumab deruxtecan# DESTINY-Breast02
                                                  AKT inhibitor prostate cancer                                                                           ADC HER2-positive, unresectable and/or metastatic
                                                  Imfinzi# + Lynparza# ORION                                                                              breast cancer pretreated with prior standard of care
                                                  PD-L1 mAb + PARP inhibitor NSCLC                                                                        HER2 therapies, including trastuzumab emtansine
                                                  (oleclumab + chemotherapy) or (Imfinzi# + oleclumab + chemotherapy)                                     trastuzumab deruxtecan# DESTINY-Breast03
                                                  (CD73 mAb+chemo) or (PD-L1 mAb+CD73 mAb+chemo) metastatic pancreatic cancer                             ADC HER2-positive, unresectable and/or metastatic
                                                                                                                                                          breast cancer subjects previously treated with
                                                  trastuzumab deruxtecan¶# DESTINY-Gastric01                                                              trastuzumab and taxane
                                                  ADC HER2-overexpressing advanced gastric or gastroesophageal junction adenocarcinoma
                                                  patients who have progressed on two prior treatment regimens                                            trastuzumab deruxtecan# DESTINY-Breast04
                                                                                                                                                          ADC HER2-low, unresectable and/or metastatic breast
                                                  trastuzumab deruxtecan#                                                                                 cancer subjects
                                                  ADC HER2-expressing advanced colorectal cancer
                                                  trastuzumab deruxtecan#
                                                  HER2-over-expressing or -mutated, unresectable and/or metastatic NSCLC                                  Lifecycle Management
                                                                                                                                                          Calquence# + venetoclax + obinutuzumab
                                                  Lifecycle Management                                                                                    BTK inhibitor + BCL-2 inhibitor + anti-CD20 mAb 1st-line
                                                  Imfinzi# (platform) BEGONIA                                                                             chronic lymphocytic leukaemia
                                                  PD-L1 mAb breast cancer
                                                                                                                                                          Imfinzi# CALLA
                                                  Imfinzi# (platform) MEGELLAN                                                                            PD-L1 mAb adjuvant locally-advanced cervical cancer
                                                  PD-L1 mAb NSCLC
                                                  Imfinzi# + (oleclumab or monalizumab#) COAST
                                                  PD-L1 mAb + (CD73 mAb or NKG2A mAb) NSCLC
                                                  Imfinzi# + (oleclumab or monalizumab# or danvatirsen#) NeoCOAST
                                                  PD-L1 mAb + (CD73 mAb or NKG2A mAb or STAT3 inhibitor) NSCLC
                                                  Lynparza# (basket) MK-7339-002 / LYNK002
                                                  PARP inhibitor HRRm cancer

      Removed from Phase I                                                             Removed from Phase II                                                        Removed from Phase III                             Removed from Registration
    NME                                           NME                                                                                                                                                                Lifecycle Management
    Imfinzi# + dabrafenib + trametinib            AZD4547                                                                                                                                                            Farxiga3 DEPICT [US & JP]2
    PD-L1 mAb + BRAF inhibitor + MEK              FGFR inhibitor solid tumours                                                                                                                                       SGLT2 inhibitor type-1 diabetes
    inhibitor melanoma
                                                  AZD8186
    Imfinzi# + Iressa                             PI3k inhibitor solid tumours
    PD-L1 mAb + EGFR inhibitor NSCLC
                                                  Imfinzi# + MEDI0680
    AZD0156                                       PD-L1 mAb + PD-1 mAb solid tumours
    ATM inhibitor solid tumours
                                                  prezalumab#
    AZD4785                                       B7RP1 mAb primary Sjöogren’s syndrome
    KRAS inhibitor solid tumours
5
    ¶ Registrational Phase II/III trial   # Partnered   and/or in collaboration   1   Submission Accepted   2 Submission   Approved 3Farxiga in the US; Forxiga in ROW
Q1 2019 New Molecular Entity (NME)1 pipeline
Phase I                                                                                      Phase II                                                                                     Phase III                                   Under Review
21 New Molecular Entities                                                                    25 New Molecular Entities                                                                    14 New Molecular Entities                   0 New Molecular Entities

AZD1390                                      Imfinzi#+tremelimumab+chemo                   adavosertib#+chemotherapy                    Imfinzi#+tremelimumab                            trastuzumab deruxtecan# DESTINY-Breast02
glioblastoma                                 PD-L1+CTLA-4 1L PDAC oesophageal SCLC         Wee1+chemo ovarian cancer                    PD-L1+CTLA-4 gastric cancer                      ADC breast


AZD4573                                      Imfinzi+selumetinib#                          AZD2811#                                     Imfinzi#+tremelimumab                            trastuzumab deruxtecan# DESTINY-Breast03
CDK9 haematalogical malignancies             PL-L1+MEK solid tumours                       Aurora solid tumours                         PD-L1+CTLA-4 biliary tract oesophageal           ADC breast


AZD5153                                      MEDI2228                                      AZD4635                                      Imfinzi+Lynparza# BAYOU                          trastuzumab deruxtecan# DESTINY-Breast04
BRD4 solid tumours                           BCMA ADC multiple myeloma                     A2aR inhibitor solid tumours                 PD-L1+PARP bladder                               ADC breast


AZD5991                                      MEDI3726#                                     AZD6738                                      Lynparza#+adavosertib#                           Imfinzi#+tremelimumab DANUBE
MCL1 haematalogical malignancies             PSMA ADC prostate                             ATR solid tumours                            PARP+Wee1 solid tumours                          PD-L1+CTLA-4 1L bladder


AZD9496                                      MEDI5083                                      capivasertib#                                Lynparza#+AZD6738                                Imfinzi#+tremelimumab HIMALAYA
SERD ER+ breast                              CD40 ligand fusion protein solid tumours      AKT breast prostate                          PARP+ATR gastric                                 PD-L1+CTLA-4 1L HCC

                                                                                           Imfinzi#+(oleclumab or monalizumab# or
AZD9833                                      MEDI5752                                                                                   Lynparza#+AZD6738 or +adavosertib# VIOLETTE      Imfinzi#+tremelimumab KESTREL
                                                                                           danvatirsen#) NeoCOAST
SERD ER+ breast                              PD-1/CTLA-4 solid tumours                                                                  PARP+ATR or PARP+Wee1 breast                     PD-L1+CTLA-4 1L HNSCC
                                                                                           PD-L1+(CD73 or NKG2A or STAT3) NSCLC

                                             MEDI7247
Calquence+AZD6738                                                                          Imfinzi#+(oleclumab or monalizumab#) COAST   Lynparza#+Imfinzi MEDIOLA                        Imfinzi#+tremelimumab NEPTUNE
                                             ASCT2 ADC haematological malignancies solid
BTK+ATR haematalogical tumours                                                             PD-L1+(CD73 or NKG2A) NSCLC                  PARP+PD-L1 ovarian breast gastric SCLC           PD-L1+CTLA-4 1L NSCLC
                                             tumours

                                                                                           Imfinzi#+AZD5069 or Imfinzi#+danvatirsen#
Calquence+danvatirsen                        oleclumab                                                                                  oleclumab+chemo or Imfinzi#+oleclumab+chemo      Imfinzi#+tremelimumab+CRT ADRIATIC
                                                                                           PD-L1+(CXCR2 or STAT3) HNSCC bladder
BTK+STAT3 haematalogical malignancies        CD73 solid tumours                                                                         CD73+chemo or PD-L1+CD73+chemo pancreatic        PD-L1+CTLA-4+CRT LD-SCLC
                                                                                           NSCLC

Imfinzi#+adavosertib#                        oleclumab+AZD4635                             Imfinzi#+Lynparza# ORION                     Tagrisso combo# TATTON                           Imfinzi#+tremelimumab+SoC CASPIAN
PD-L1+Wee1 solid tumours                     CD73+A2aR EGFRm NSCLC                         PD-L1+PARP NSCLC                             EGFR+PD-L1/MEK/MET NSCLC                         PD-L1+CTLA-4+SoC 1L SCLC


Imfinzi#+RT (platform) CLOVER                oleclumab+Tagrisso                            Imfinzi#+MEDI0457#                           trastuzumab deruxtecan#¶ DESTINY-Breast01        Imfinzi#+tremelimumab+SoC NILE
PD-L1+RT HNSCC NSCLC SCLC                    CD73+EGFR EGFRm NSCLC                         PD-L1+DNA HPV vaccine HNSCC                  ADC breast                                       PD-L1+CTLA-4+SoC 1L urothelial cancer


Imfinzi#+tremelimumab                                                                      Imfinzi#+monalizumab#                        trastuzumab deruxtecan#¶ DESTINY-Gastric01       Imfinzi#+tremelimumab+SoC POSEIDON
PD-L1+CTLA-4 solid tumours                                                                 PD-L1+NKG2a solid tumours                    ADC gastric                                      PD-L1+CTLA-4+SoC 1L NSCLC


                                                                                           Imfinzi#+oleclumab                           trastuzumab deruxtecan#                          Lynparza#+Imfinzi#+bevacizumab DUO-O
                                                                                           PD-L1+CD73 solid tumours                     ADC colorectal cancer                            PARP+PD-L1+VEGF 1L ovarian


                                                                                                                                        trastuzumab deruxtecan#                          savolitinib# SAVOIR
                                                                                                                                        ADC NSCLC                                        MET pRCC


                                                                                                                                                                                         selumetinib#¶ SPRINT
                                                                                                                                                                                         MEK paediatric neurofibromatosis type-1

6     1
       includes novel combinations and additional indications for assets where the lead is not yet launched
                                                                                                                                                           Oncology              Cardiovascular, Renal & Metabolism, Respiratory, Other
      # Partnered and/or in collaboration; ¶ Registrational Phase II/III trial
Q1 2019 New Molecular Entity (NME)1 pipeline
    Phase I                               Phase II                                                                                  Phase III                                  Applications Under Review
    13 New Molecular Entities             22 New Molecular Entities                                                                 3 New Molecular Entities                   1 New Molecular Entity

    AZD0284                               abediterol#                                MEDI5884#                                      anifrolumab# TULIP                          PT010
    RORg psoriasis/respiratory            LABA asthma/COPD                           cholesterol modulation cardiovascular          Type I IFN receptor SLE                     LABA/LAMA/ICS COPD


    AZD0449                               anifrolumab#                               MEDI6012                                       PT027
    Inhaled JAK inhibitor asthma          Type I IFN receptor SLE SC                 LCAT cardiovascular                            ICS/SABA asthma


    AZD1402#                              anifrolumab#                               MEDI7352                                       tezepelumab# NAVIGATOR SOURCE
    inhaled IL-4Ra asthma                 Type I IFN receptor lupus nephritis        NGF/TNF osteoarthritis pain, painful           TSLP severe uncontrolled asthma
                                                                                     diabetic neuropathy

    AZD5634                               AZD1419#                                   MEDI8852
    inhaled ENaC cystic fibrosis          inhaled TLR9 asthma                        influenza A treatment


    AZD8154                               AZD4831                                    MEDI8897#
    Inhaled PI3Kgd asthma                 MPO HFpEF                                  passive RSV prophylaxis


    AZD8233                               AZD5718                                    PT010
    hypercholesterolemia cardiovascular   FLAP coronary artery disease               LABA/LAMA/ICS asthma


    AZD9977                               AZD7594                                    suvratoxumab
    MCR cardiovascular                    Inhaled SGRM asthma/COPD                   α-Toxin Staphylococcus pneumonia


    MEDI0700#                             AZD7986#                                   tezepelumab#
    BAFF/B7RP1 SLE                        DPP1 COPD                                  TSLP atopic dermatitis


    MEDI1341                              AZD8601#                                   verinurad
    alpha synuclein parkinson's disease   VEGF-A cardiovascular                      URAT-1 chronic kidney disease


    MEDI1814#                             AZD8871#
    amyloidβ alzheimer's disease          MABA COPD


    MEDI3506                              AZD9567
    IL-33 COPD                            SGRM RA/respiratory


    MEDI6570                              cotadutide
    LOX-1 CV disease                      GLP-1/glucagon type-2 diabetes / obesity

                                                                                                                             1
                                                                                                                              includes novel combinations and additional indications for assets where the lead is not yet launched
    MEDI7219                              MEDI3902
    anti-diabetic type-2 diabetes         Psl/PcrV Pseudomonas pneumonia                                                     # Partnered and/or in collaboration; ¶ Registrational Phase II/III trial

7                                                                                                                                                       Oncology           Cardiovascular, Renal & Metabolism, Respiratory, Other
Q1 2019 Lifecycle Management (LCM)1 pipeline
        Phase I                                      Phase II                                 Phase III                                                                           Applications Under Review
        1 Project                                    5 Projects                               20 Projects                                                                         0 Projects

                                                                                                                                     Imfinzi#+CTx neoadjuvant AEGEAN
        Imfinzi#+azacitidine#                       Imfinzi#                                  Calquence#
                                                                                                                                     PD-L1+CTx locally-advanced stage III
        PD-L1+azacitidine MDS                       PD-L1 solid tumours                       BTK inhibitor 1st line MCL
                                                                                                                                     NSCLC

                                                    Imfinzi# (platform) BEGONIA               Calquence#                             Imfinzi#+CTx NIAGARA
                                                    PD-L1 breast cancer                       BTK inhibitor 1st line CLL             PD-L1+CTx muscle invasive bladder
                                                                                                                                     cancer

                                                    Imfinzi# (platform) MAGELLAN              Calquence#                             Imfinzi#+VEGF+TACE EMERALD-1
                                                    PD-L1 NSCLC                               BTK inhibitor r/r CLL, high risk       PD-L1+VEGF+TACE locoregional HCC

                                                    Lynparza# (basket) MK-7339-002 /
                                                                                              Calquence#                             Lynparza# OlympiA
                                                    LYNK002
                                                                                              BTK inhibitor r/r CLL                  PARP gBRCA adjuvant breast
                                                    PARP HRRm cancer

                                                    Lynparza#+cediranib CONCERTO              Calquence#+venetoclax+obinutuzumab     Lynparza# POLO
                                                    PARP+VEGF recurrent Pt-R ovarian          BTK+BCL-2+anti-CD20 1st line CLL       PARP pancreatic cancer

                                                                                              Imfinzi# CALLA
                                                                                                                                     Lynparza# PROfound
                                                                                              PD-L1 adj. locally advanced cervical
                                                                                              cancer                                 PARP prostate cancer


                                                                                              Imfinzi# PEARL (China)                 Lynparza# SOLO-3
                                                                                              PD-L1 1L NSCLC                         PARP BRCAm PSR ovarian

                                                                                              Imfinzi# POTOMAC
                                                                                              PD-L1 non muscle invasive bladder      Lynparza+abiraterone# PROpel
                                                                                              cancer                                 PARP+NHA prostate cancer


                                                                                              Imfinzi#+CRT PACIFIC-2                 Tagrisso ADAURA
                                                                                              PD-L1+CRT NSCLC                        EGFR adj. EGFRm NSCLC

                                                                                              Imfinzi#+CRT PACIFIC-5 (China)         Tagrisso LAURA
                                                                                              PD-L1+CRT locally-advanced stage III   EGFRm locally advanced unresectable
                                                                                              NSCLC                                  NSCLC




    1
     Includes significant LCM projects and parallel indications for assets beyond Phase III
8   # Partnered and/or in collaboration; ¶ Registrational Phase II/III trial                                                                    Oncology            Cardiovascular, Renal & Metabolism, Respiratory, Other
Q1 2019 Lifecycle Management (LCM)1 pipeline
                 Phase I                                      Phase II                        Phase III                       Applications Under Review
                 0 Projects                                   0 Projects                      10 Projects                     4 Projects


                                                                                              Brilinta/Brilique HESTIA        Farxiga/Forxiga DECLARE
                                                                                              P2Y12 paeds w/ sickle cell      outcomes


                                                                                              Brilinta/Brilique THALES        Nexium (CN only)
                                                                                              P2Y12 stroke                    stress ulcer prophylaxis


                                                                                              Brilinta/Brilique THEMIS        saxagliptin+dapagliflozin metformin
                                                                                              P2Y12 diabetes & CAD outcomes   DPP4+SGLT2 type-2 diabetes


                                                                                              Epanova STRENGTH                Symbicort SYGMA
                                                                                              outcomes                        as needed in mild asthma


                                                                                              Farxiga/Forxiga
                                                                                              SGLT2 HFrEF


                                                                                              Farxiga/Forxiga
                                                                                              SGLT2 CKD


                                                                                              Farxiga/Forxiga DELIVER
                                                                                              SGLT2 HFpEF


                                                                                              Fasenra#
                                                                                              IL-5R COPD


                                                                                              Fasenra# OSTRO
                                                                                              IL-5R nasal polyposis


                                                                                              roxadustat#
                                                                                              HIFPH anaemia MDS




    1
     Includes significant LCM projects and parallel indications for assets beyond Phase III
9   # Partnered and/or in collaboration; ¶ Registrational Phase II/III trial                                                   Oncology             Cardiovascular, Renal & Metabolism, Respiratory, Other
Estimated key regulatory submission acceptances
              roxadustat anaemia in CKD (US)

                    selumetinib SPRINT

             Imfinzi + tremelimumab KESTREL

             Imfinzi + tremelimumab NEPTUNE                                        trastuzumab deruxtecan

             Imfinzi + tremelimumab DANUBE                                 Imfinzi + tremelimumab + CRT ADRIATIC
 NME



             Imfinzi +/- tremelimumab CASPIAN                                 Imfinzi + tremelimumab HIMALAYA                                PT027 asthma

            Imfinzi +/- tremelimumab POSEIDON           Lokelma (China)       Imfinzi + tremelimumab + SoC NILE                     Fasenra severe asthma (China)

       trastuzumab deruxtecan DESTINY-Breast01 (US)      Lumoxiti (EU)      Lynparza +Imfinzi +bevacizumab DUO-O                       tezepelumab NAVIGATOR

                       H2 2019                              2020                                                     2020+
                     Calquence CLL                       Imfinzi PEARL               Calquence 1L MCL                                       Brilinta HESTIA
 LCM




                     Lynparza POLO                     Lynparza PAOLA-1   Calquence +venetoclax+obinutuzumab 1L CLL                       Farxiga DAPA-CKD

                    Lynparza SOLO-3                   Lynparza PROFOUND               Imfinzi POTOMAC                                  Farxiga HFpEF DELIVER

                     Brilinta THEMIS                   Farxiga DAPA-HF                  Imfinzi CALLA                                  roxadustat anemia in MDS

                      Lokelma (JP)                      Brilinta THALES           Imfinzi BR.31 ADJUVANT                                Duaklir Genuair (China)

                Symbicort SYGMA (China)               Epanova STRENGTH             Imfinzi + CRT PACIFIC-2

                                                        Fasenra OSTRO          Imfinzi + CRT PACIFIC-5 (China)

                                                        Xigduo (China)            Imfinzi + chemo AEGEAN

                                                                                  Imfinzi + chemo NIAGARA

                                                                             Imfinzi + VEGF + TACE EMERALD-1

                                                                                     Lynparza OLYMPIA

                                                                               Lynparza + abiraterone PROPEL

                                                                                      Tagrisso LAURA

                                                                                      Tagrisso ADAURA


10                                                                                            Oncology            Cardiovascular, Renal & Metabolism, Respiratory, Other
Designations
                                            4
                         Accelerated approvals
                                                                                                        9
                                                                                     Breakthrough Therapy
                                                                                                                                                                   8
                                                                                                                                                              Fast Track
                                                                                                                                                                                                                      20
                                                                                                                                                                                                        Priority Review / PRIME
                                                                                                                                                                                                                                                                                   23
                                                                                                                                                                                                                                                                                  Orphan Drug

     Lynparza ovarian cancer SOLO-2 (US)                       Tagrisso EGFRm T790M NSCLC (US)                             MEDI3902 Psl-PcrV pneumo Px (US)                           Tagrisso EGFRm T790M NSCLC (JP)                             Lynparza ovarian cancer SOLO-2 (US)

     Tagrisso EGFRm T790M NSCLC (US)                           Lynparza prostate cancer PROFOUND (US)                      savratoxumab Staph HAP (US)                                Tagrisso EGFRm T790M NSCLC (US)                             Lumoxiti HCL PLAIT (US)

     Imfinzi bladder cancer (US)                               Imfinzi bladder cancer 1L (US)                              Imfinzi NSCLC (US)                                         Imfinzi bladder cancer 2L (US)                              Lumoxiti HCL PLAIT (EU)

     Calquence MCL (US)                                        Calquence MCL (US)                                          MEDI8897 RSV mAB (US)                                      Tagrisso NSCLC AURA3 (US)                                   Crestor paediatric (US)

                                                               Imfinzi stage III NSCLC 1L PACIFIC (US)                     Imfinzi HNSCC HAWK (US)                                    Calquence MCL (US)                                          cediranib VEGFR tki (US)

                                                               Tagrisso NSCLC 1L FLAURA (US)                               anifrolumab SLE (US)                                       Lynparza breast cancer OLYMPIAD (US)                        Iressa EGFRm NSCLC (US)

                                                               tezepelumab asthma (US)                                     Lynparza ovarian cancer SOLO-2 (US)                        roxadustat CKD (CN)                                         Tagrisso EGFRm T790M NSCLC (US)

                                                               MEDI8897 RSV mAB (US)                                       Tagrisso EGFRm T790M NSCLC (CN)                            Tagrisso NSCLC FLAURA (US)                                  AZD3241 MPO (EU)

                                                               selumetinib NFI type 1 SPRINT (US)                                                                                     Imfinzi stage III NSCLC PACIFIC (EU)                        Calquence CLL 1L (US)

                                                                                                                                                                                      Imfinzi stage III NSCLC PACIFIC (JP)                        Calquence MCL (US)

                                                                                                                                                                                      Lynparza tablet (US)                                        Calquence WM (US)

                                                                                                                                                                                      Lynparza tablet (CN)                                        Calquence WM (EU)

                                                                                                                                                                                      Lynparza breast cancer OLYMPIAD (JP)                        Calquence CLL 1L (EU)

                                                                                                                                                                                      Tagrisso NSCLC 1L FLAURA (JP)                               Calquence MCL (EU)

                                                                                                                                                                                      Lumoxiti HCL PLAIT (US)                                     selumetinib thyroid cancer ASTRA (US)

                                                                                                                                                                                      Lynparza ovarian SOLO-1 (US)                                Lynparza breast cancer OLYMPIAD (JP)

                                                                                                                                                                                      Lynparza ovarian SOLO-1 (CN)                                Lynparza ovarian cancer SOLO-2 (JP)

                                                                                                                                                                                      PT010 Triple MDI COPD (CN)                                  selumetinib NFI type 1 SPRINT (US)

                                                                                                                                                                                      MEDI8897 RSV mAB (EU)                                       selumetinib NFI type 1 SPRINT (EU)

                                                                                                                                                                                      Tagrisso NSCLC 1L FLAURA (CN)                               Lynparza pancreatic cancer POLO (US)

                                                                                                                                                                                                                                                  Fasenra EGPA (US)

                                                                                                                                                                                                                                                  Fasenra HES (US)
     Fast Track is a process designed to facilitate the development, and expedite the review of medicines to treat serious conditions and fill an unmet medical need.
     Breakthrough Designation is a process designed to expedite the development and review of medicines which may demonstrate substantial improvement over available therapy.                                                                     saracatinib IPF (US)
     Accelerated Approval, these regulations allowed medicines for serious conditions that addressed an unmet medical need to be approved based on a surrogate endpoint.
     Priority Review Designation is the US FDA’s goal to take action on an application within 6 months. PRIME is a scheme launched by the EMA to enhance support for the development of medicines that target an unmet medical need
     Orphan Drug Designation, intended for treatment, diagnosis or prevention of rare diseases/disorders that affect fewer than 200,000 patients in the US, or that affect more than 200,000 patients but are not expected to recover the costs of developing and marketing a treatment drug.


11                                                                                                                                                                                       Oncology                Cardiovascular, Renal & Metabolism, Respiratory, Other
AstraZeneca

Oncology – approved medicines and late-stage pipeline
Approved medicines




                                                                                                                                                                                             Oncology
                                                                                                                                                                 Late-stage development

 Tagrisso (highly-selective, irreversible EGFRi)                                                                                                                 Early development


 Non-small cell lung cancer (NSCLC)
 Trial         Population                       Patients   Design                                                   Endpoints                                    Status




                                                                                                                                                                                             CVRM
 Phase III     Adjuvant EGFRm                   700        • Arm 1: Tagrisso 80mg QD following complete tumour      • Primary endpoint: Disease Free Survival    • FPCD: Q4 2015
 ADAURA                                                      resection, with or without chemotherapy                  (DFS)                                      • LPCD: Q1 2019
                                                           • Arm 2: placebo                                         • Secondary endpoints: DFS Rate, OS,         • Data anticipated: 2020+
 NCT02511106                                                                                                          OS Rate, QoL
                                                           Global trial - 25 countries

 Phase III     Maintenance therapy in           200        • Arm 1: Tagrisso 80mg                                   • Primary endpoint: PFS (via blinded         • FPCD: Q3 2018
 LAURA         patients with                               • Arm 2: placebo                                           independent central review (BICR))         • Data anticipated: 2020+
                                                                                                                    • Secondary endpoints: CNS PFS, OS,
               locally advanced,




                                                                                                                                                                                             Respiratory
 NCT03521154   unresectable EGFRm+ Stage                   Global trial - 11 countries                                DoR, ORR, DCR
               III whose disease has not
               progressed following
               platinum-based
               chemoradiation therapy
 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: 2020+
               NSCLC who have progressed                   Global trial                                               and OS
 NCT03778229   following treatment with
               Tagrisso




                                                                                                                                                                                             Other
 Phase Ib      Advanced EGFRm TKI failure       308        • Arm 1: Tagrisso + Imfinzi                              • Safety, tolerability, pharmacokinetics     • FPCD: Q3 2014
 TATTON                                                    • Arm 2: Tagrisso + savolitinib                            and Preliminary anti-tumour activity       • Data anticipated: 2020
                                                           • Arm 3: Tagrisso + selumetinib
 NCT02143466                                               Enrolment to Imfinzi combination arms will not restart

                                                           Global trial
 Phase III     Real world setting in adult      3,020      Single-arm trial - Tagrisso 80mg                         • Primary endpoints: OS and safety           • FPCD: Q3 2015
 ASTRIS        patients with advanced or                                                                            • Secondary endpoint: PFS                    • LPCD: Q4 2017
               metastatic, EGFR T790M+                     Global trial - 16 countries
 NCT02474355

 Phase II      EGFR TKI treatment-naïve         150        Single arm trial – Tagrisso 80 mg                        • Primary Endpoint: proportion of patients   • FPCD: Q2 2018
 ELIOS         patients with locally-advanced                                                                         with a given tumour genetic and
               or metastatic EGFRm+                        Global trial - five countries                              proteomic marker at the point of disease
 NCT03239340                                                                                                          progression as defined by the
                                                                                                                      investigator
                                                                                                                    • Secondary endpoint: PFS, ORR, DoR




13
Approved medicines




                                                                                                                                                                                                         Oncology
                                                                                                                                                                             Late-stage development

 Imfinzi (PD-L1 mAb)                                                                                                                                                         Early development


 Non-small cell lung cancer (NSCLC), early use
 Trial                      Population                     Patients   Design                                                         Endpoints                               Status




                                                                                                                                                                                                         CVRM
 Phase III                  Adjuvant NSCLC patients        1,360      • Arm 1: Imfinzi mg/kg IV Q4W x 12m                            Primary endpoint:                       • FPCD: Q1 2015
 ADJUVANT BR.31             IB (≥4cm) – stage IIIA                    • Arm 2: placebo                                               • DFS                                   • Data anticipated: 2020+
                            resected NSCLC
 NCT02273375                (incl. EGFR/ALK positive)                 Global trial                                                   Secondary endpoint:
                                                                                                                                     • OS
 Partnered
 Phase II/III Lung Master   Stage IV squamous NSCLC        140        Umbrella trial with five arms based on biomarker expression:   Primary endpoints:                      • FPCD: Q2 2014
 Protocol                   patients                                  • Substudy A: Imfinzi (non-match for other biomarker driven    • ORR                                   • Data anticipated: 2020+
                                                                                                                                     • PFS




                                                                                                                                                                                                         Respiratory
                                                                        substudies) IVQ2W single arm Imfinzi Phase II only
 NCT02154490                Biomarker-targeted                        • Substudy B: PI3K inhibitor vs. docetaxel                     • OS
                            2L therapy                                • Substudy C: CDK4/6 inhibitor vs, docetaxel
 Partnered                                                            • Substudy D: AZD4547 (FGFR inhibitor) vs. docetaxel
                                                                      • Substudy E: C-MET/HGFR Inhibitor + erlotinib vs. erlotinib
 Phase III                  Unresected, locally-advanced   300        • Arm 1: Imfinzi IV Q4W + chemo/RT (radiation therapy)         Primary endpoint:                       • FPCD: Q2 2018
                            NSCLC                                     • Arm 2: placebo + chemo/RT                                    • PFS                                   • Data anticipated: 2020+
 PACIFIC-2                                                                                                                           • ORR
                                                                      ex US global trial                                             Secondary endpoint:
 NCT03519971                                                                                                                         • OS


 Phase III                  Imfinzi following SBRT in      630        •Arm 1: Imfinzi IV Q4W following definitive SBRT (radiation    Primary endpoint:                       •FPCD: Q1 2019




                                                                                                                                                                                                         Other
                            unresected, Stage I/II NSCLC              therapy)                                                       •PFS                                    •Data anticipated: 2020+
 PACIFIC-4                                                            •Arm 2: placebo following definitive SBRT                      Secondary endpoint:
                                                                                                                                     •OS
 NCT03833154

 Phase III                  Unresected, locally-advanced   360        Arm 1: Imfinzi IV Q4W following chemo/RT (radiation therapy)   Primary endpoint:                       • FPCD: Q1 2019
                            NSCLC                                     Arm 2: placebo following chemo/RT                              •   PFS                                 • Data anticipated: 2020+
 PACIFIC-5                                                                                                                           Secondary endpoint:
                                                                      ex US global trial, China focus                                •   OS
 NCT03706690

 Phase III                  Neoadjuvant NSCLC patients     300        Arm 1: Imfinzi + platinum-based chemotherapy                   Primary endpoint:                       • FPCD: Q1 2019
                            Stage II and III resected                 Arm 2: placebo + platinum-based chemotherapy                   •   Major Pathological Response (mPR)   • Data anticipated: 2020
 AEGEAN                     NSCLC                                                                                                    Secondary endpoint
                            (incl. EGFR/ALK positive)                                                                                •   Pathological complete response
 NCT03800134                                                                                                                             (pCR)




14
Approved medicines




                                                                                                                                                                                          Oncology
                                                                                                                                                            Late-stage development

 Imfinzi (PD-L1 mAb) +/- treme (CTLA-4 mAb)                                                                                                                 Early development


 Lung cancer, advanced
 Trial         Population                    Patients   Design                                                               Endpoints                      Status




                                                                                                                                                                                          CVRM
 Phase III     Limited disease- Small cell   600        • Arm 1: Imfinzi + tremelimumab (4 doses)                            Primary endpoints:             • FPCD: Q4 2018
 ADRIATIC      lung cancer (SCLC) 1L                    • Arm 2: Imfinzi                                                     • PFS                          • Data anticipated: 2020+
               following platinum-based                 • Arm 3: placebo                                                     • OS
 NCT03703297   concurrent chemoradiation
               therapy

 Phase III     NSCLC 1L                      650        • Arm 1: Imfinzi Q4W                                                 Primary endpoint:              • FPCD: Q1 2017
 PEARL                                                  • Arm 2: chemotherapy                                                • OS                           • LPCD: Q1 2019
                                                                                                                                                            • Data anticipated: 2020




                                                                                                                                                                                          Respiratory
 NCT03003962                                            Asia trial
 Phase III     NSCLC 1L                      960        • Arm 1: Imfinzi + tremelimumab                                      • Primary endpoint: OS         • FPCD: Q4 2015
 NEPTUNE                                                • Arm 2: SoC                                                         • Secondary endpoint: PFS      • LPCD: Q2 2017
                                                                                                                                                            • Data anticipated: H2 2019
 NCT02542293
 Phase III     NSCLC 1L                      1,000      • Arm 1: Imfinzi + CTx                                               Primary endpoint:              • FPCD: Q2 2017
 POSEIDON                                               • Arm 2: Imfinzi + tremelimumab + chemotherapy                       • OS                           • LPCD: Q3 2018
                                                        • Arm 3: SoC                                                                                        • Data anticipated: H2 2019
 NCT03164616
 Phase III     SCLC 1L                       795        • Arm 1: Imfinzi + tremelimumab + EP (carboplatin or cisplatin +     Primary endpoint:              • FPCD: Q1 2017




                                                                                                                                                                                          Other
 CASPIAN                                                  etoposide)                                                         • OS                           • LPCD: Q2 2018
                                                        • Arm 2: Imfinzi + EP (carboplatin or cisplatin + etoposide)                                        • Data anticipated: H2 2019
 NCT03043872                                            • Arm 3: EP (carboplatin or cisplatin + etoposide)
 Phase II      SCLC                          80         • Arm A: Imfinzi + tremelimumab Q4W                                  • Primary endpoint: ORR        • FPCD: Q4 2016
 BALTIC                                                 • Arm B: adavosertib and carboplatin BID                                                            • Data anticipated: 2020+
                                                        • Arm C: AZD6738 and Lynparza
 NCT02937818
 Phase II      NSCLC 1L                      200        •   Arm A1: Imfinzi                                                  Primary endpoint:              • FPCD: Q1 2019
 MAGELLAN                                               •   Arm A2: Imfinzi + danvatirsen                                    • Safety & tolerability        • Data anticipated: 2020+
                                                        •   Arm A3: Imfinzi + oleclumab                                      Secondary endpoint:
 NCT03819465                                            •   Arm B1: Imfinzi + Investigator's choice of chemo                 • ORR, DoR, PFS, OS, PK, ADA
                                                        •   Arm B2: Imfinzi + danvatirsen + Investigator's choice of chemo
                                                        •   Arm B3: Imfinzi + oleclumab + Investigator's choice of chemo




15
Approved medicines




                                                                                                                                                                                                           Oncology
                                                                                                                                                                               Late-stage development

 Imfinzi (PD-L1 mAb) +/- treme (CTLA-4 mAb)                                                                                                                                    Early development


 Other cancers, early disease
 Trial                        Population                    Patients   Design                                                          Endpoints                               Status




                                                                                                                                                                                                           CVRM
 Phase III                    Non-muscle invasive bladder   975        • Arm 1: BCG (Bacillus Calmette–Guérin) (Induction +            Primary endpoints:                      • FPCD: Q3 2018
 POTOMAC                      cancer                                     maintenance)                                                  • DFS                                   • Data anticipated: 2020+
                                                                       • Arm 2: Imfinzi + BCG (Induction only)
 NCT03528694                                                           • Arm 3: Imfinzi + BCG (Induction + maintenance)
 Phase III                    Muscle-invasive bladder       960        • Arm 1: Imfinzi in combination with gemcitabine + cisplatin,   Coprimary endpoints:                    • FPCD: Q1 2019
                              cancer                                     Imfinzi maintenance                                           •   pCR                                 • Data anticipated: 2020+
 NIAGARA                                                               • Arm 2: gemcitabine + cisplatin                                •   EFS




                                                                                                                                                                                                           Respiratory
 Phase III                    Locoregional Hepatocellular   600        • Arm A: Transarterial Chemoembolization (TACE) in              Primary endpoint                        • FPCD: Q1 2019
 EMERALD-1                    Carcinoma                                  combination with Imfinzi                                      PFS for Arm A vs Arm C                  • Data anticipated: 2020+
                                                                       • Arm B: Transarterial Chemoembolization (TACE) in
 NCT03778957                                                             combination with Imfinzi + Bevacizumab                        Secondary endpoint
                                                                       • Arm C: Transarterial Chemoembolization (TACE) in              PFS for Arm B vs Arm C , OS
                                                                         combination with Placebos
 Phase III                    Adjuvant Therapy in           888        •    Arm 1: Imfinzi + bevacizumab                               Primary endpoint:                       • Initiating
 EMERALD-2                    Hepatocellular Carcinoma                 •    Arm 2: Imfinzi + placebo                                   •   RFS for Arm 2 vs Arm 3
                                                                       •    Arm 3: placebo + placebo
                                                                                                                                       Secondary endpoint:
                                                                                                                                       •   RFS Arm 1 vs Arm 3, OS, RFS at 24
                                                                                                                                           mos




                                                                                                                                                                                                           Other
 pCR = Pathologic Complete Response
 EFS = event free survival
16
Approved medicines




                                                                                                                                                                                                             Oncology
                                                                                                                                                                               Late-stage development

 Imfinzi (PD-L1 mAb) +/- treme (CTLA-4 mAb)                                                                                                                                    Early development


 Other cancers, late disease
 Trial                        Population                      Patients   Design                                                     Endpoints                                  Status




                                                                                                                                                                                                             CVRM
 Phase III                    Cis-eligible and ineligible     1,005      • Arm 1: Imfinzi + tremelimumab                            Primary endpoints:                         • FPCD: Q4 2015
 DANUBE                       bladder cancer 1L                          • Arm 2: Imfinzi                                           • OS                                       • LPCD: Q1 2017
                                                                         • Arm 3: SoC                                                                                          • Data anticipated: H2 2019
 NCT02516241
 Phase III                    Bladder cancer 1L               885        • Arm 1: Imfinzi + tremelimumab + SoC                      Primary endpoints:                         • FPCD: Q3 2018
 NILE                                                                    • Arm 2: Imfinzi + SoC                                     • PFS                                      • Data anticipated: 2020+
                                                                         • Arm 3: SoC                                               • OS
 NCT03682068




                                                                                                                                                                                                             Respiratory
 Phase III                    HNSCC 1L                        823        • Arm 1: Imfinzi                                           Primary endpoints:                         • FPCD: Q4 2015
 KESTREL                                                                 • Arm 2: Imfinzi + tremelimumab                            • OS                                       • LPCD Q1 2017
                                                                         • Arm 3: SoC                                                                                          • Data anticipated: H2 2019
 NCT02551159
 Phase III                    Unresectable Hepatocellular     1,310      •   Arm 1: Imfinzi + tremelimumab (Regimen 1)              Primary endpoint:                          • FPCD: Q4 2017
 HIMALAYA                     Carcinoma (HCC) 1L                         •   Arm 2: Imfinzi + tremelimumab (Regimen 2)              • OS                                       • Data anticipated: 2020+
                                                                         •   Arm 3: Imfinzi                                         Secondary endpoint:
 NCT03298451                                                             •   Arm 4: sorafenib                                       • PFS, time to tumour progression (TTP),
                                                                                                                                       ORR

 Phase II                     Urothelial bladder cancer       76         • Arm 1 tremelimumab (urothelial bladder cancer)           Primary endpoint:                          • FPCD: Q4 2015




                                                                                                                                                                                                             Other
                              triple-negative breast cancer              • Arm 2 tremelimumab (triple-negative breast cancer)       • ORR                                      • Data readout: Q4 2018
                              pancreatic ductal-                         • Arm 3 tremelimumab (pancreatic ductal-adenocarcinoma)
 NCT02527434                  adenocarcinoma                                                                                        Secondary endpoints:
                                                                                                                                    • Safety, DoR

 Phase III                    Biliary Tract Carcinoma         474        •   Treatment Arm 1 Durvalumab + Gemcitabine + Cisplatin   Primary endpoint:                          • Initiating
 TOPAZ-1                      (BTC) 1L                                   •   Treatment Arm 2 Placebo + Gemcitabine + Cisplatin      •   OS

 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: 2020+
                                                                                                                                    Secondary
 NCT03830866                                                             Global trial                                               •   OS, PFS, CR rate, DoR, ORR, DoCR,
                                                                                                                                        safety/tolerability, PRO, PK/ADA




 pCR = Pathologic Complete Response
 EFS = event free survival
17
Approved medicines




                                                                                                                                                                                                         Oncology
                                                                                                                                                                             Late-stage development

 Imfinzi (PD-L1 mAb) +/- treme (CTLA-4 mAb)                                                                                                                                  Early development


 Other cancers
 Trial                            Population                    Patients   Design                                                             Endpoints                      Status




                                                                                                                                                                                                         CVRM
 Phase III                        Advanced solid malignancies   1,200      • Arm 1: Imfinzi                                                   • Primary endpoint: Safety     • FPCD: Q2 2017
 STRONG                                                                    • Arm 2: Imfinzi + tremelimumab                                                                   • Data anticipated: 2020+

 NCT03084471

 Phase I Combination in           Solid tumours                 80         • Arm 2 Small cell lung cancer (SCLC). Imfinzi + tremelimumab      • Safety                       • FPCD: Q1 2016
 Advanced Solid Tumours                                                      + carboplatin + etoposide                                                                       • LPCD: Q1 2019
                                                                           • Arm 3 TNBC (triple-negative breast cancer): Imfinzi +                                           • Data anticipated: 2020+
 NCT02658214                                                                 tremelimumab + chemo




                                                                                                                                                                                                         Respiratory
                                                                           • Arm 4 TNBC: Imfinzi + tremelimumab + chemo
                                                                           • Arm 5 Gastric/gastro-Oesophageal junction (GEJ): Imfinzi +
                                                                             tremelimumab + oxaliplatin + 5-fluorouracil (5FU) + leucovorin
                                                                             Arm 6 PDAC (pancreatic ductal adenocarcinoma): Imfinzi +
                                                                             tremelimumab + chemo
                                                                           • Arm 7 ESSC (esophageal squamous cell carcinoma): Imfinzi +
                                                                             tremelimumab + chemo

     Phase I Immunotherapy in     Head and neck squamous-       300        •   HNSCC Arm 1                                                    • Safety                       • FPCD: Q2 2018
     Combination With             cell carcinoma (HNSCC),                  •   NSCLC Arm 1                                                                                   • Data anticipated: 2020+
     Chemoradiation in Patients   Non-small-cell lung cancer               •   NSCLC Arm 2
     With Advanced Solid          (NSCLC), Small-cell lung                 •   NSCLC Arm 3
     Tumours                      cancer (SCLC)                            •   SCLC Arm 2




                                                                                                                                                                                                         Other
                                                                           •   SCLC Arm 3
     CLOVER                                                                •   SCLC Arm 4

     NCT03509012

 Phase II                         mTNBC (metastatic triple      100        •   Arm 1 Imfinzi + paclitaxel                                     Primary endpoint:              • FPCD: 1Q2019
 BEGONIA                          negative breast cancer) 1L               •   Arm 2 Imfinzi + paclitaxel + capivasertib                      • Safety and tolerability      • Data anticipated: 2020+
                                                                           •   Arm 3 Imfinzi + paclitaxel + selumetinib
 NCT03742102                                                               •   Arm 4 Imfinzi + paclitaxel + danvatirsen                       Secondary endpoint:
                                                                           •   Arm 5 Imfinzi + paclitaxel + oleclumab                         • ORR, PFS, DoR, OS, PK, ADA

                                                                           Global trial




18
Approved medicines




                                                                                                                                                                                                     Oncology
                                                                                                                                                                      Late-stage development

 Lynparza (PARP inhibitor)                                                                                                                                            Early development


 Ovarian and other cancers
 Trial         Population                        Patients   Design                                                        Endpoints                                   Status




                                                                                                                                                                                                     CVRM
 Phase III     BRCAm maintenance ovarian         391        • Arm 1: Lynparza tablets 300mg BID maintenance therapy for   • Primary endpoint: PFS                     •   FPCD: Q3 2013
 SOLO-1        cancer 1L                                      two years or until disease progression                      • Secondary endpoint: OS                    •   LPCD: Q1 2015
                                                            • Arm 2: placebo                                                                                          •   Data readout: Q2 2018
                                                                                                                                                                      •   Primary endpoint met
 NCT01844986                                                Global trial

 Phase III     PSR gBRCAm ovarian cancer         266        • Arm 1: Lynparza 300mg BID to progression                    • Primary endpoint: ORR                     •   FPCD: Q1 2015
 SOLO-3        3L+                                          • Arm 2: physician’s choice (single-agent chemotherapy)                                                   •   LPCD: Q2 2018
                                                                                                                                                                      •   Data readout: Q4 2018




                                                                                                                                                                                                     Respiratory
 NCT02282020                                                Global trial                                                                                              •   Primary endpoint met


 Phase III     BRCAm adjuvant breast             1,800      • Arm 1: Lynparza 300mg BiD                                   • Primary endpoint: invasive disease-free   • FPCD: Q2 2014
 OlympiA       cancer                                         12 month duration                                             survival (IDFS)
                                                            • Arm 2: placebo 12-month duration                            • Secondary endpoint: distant disease-
 NCT02032823                                                                                                                free survival and OS
                                                            Global trial partnership with BIG and NCI/NRG
 Partnered
 Phase III     BRCAm metastatic breast           302        • Arm 1: Lynparza 300mg BiD, continuous to progression        • Primary endpoint: PFS                     •   FPCD: Q2 2014
 OlympiAD      cancer                                       • Arm 2: physician’s choice:                                  • Secondary endpoint: OS                    •   LPCD: Q4 2015




                                                                                                                                                                                                     Other
                                                              capecitabine 2500mg/m2 x 14 q 21                                                                        •   Data readout: Q1 2017
 NCT02000622                                                  vinorelbine 30mg/m2 d 1, 8 q 21                                                                         •   Primary endpoint met
                                                              eribulin 1.4mg/m2 d 1, 8 q 21
                                                              to progression

                                                            Global trial
 Phase III     gBRCAm pancreatic cancer          154        • Arm 1: Lynparza tablets 300mg twice daily as maintenance    • Primary endpoint: PFS                     •   FPCD: Q1 2015
 POLO                                                         therapy until progression                                   • Secondary endpoint: OS                    •   LPCD: Q1 2019
                                                            • Arm 2: placebo tablets BID                                                                              •   Data readout: Q1 2019
 NCT02184195                                                                                                                                                          •   Primary endpoint met
                                                            Global trial

 Phase III     Metastatic castration-resistant   387        • Arm 1: Lynparza 300mg BID                                   • Primary endpoint: radiologic PFS          • FPCD: Q2 2017
 PROfound      prostate cancer                              • Arm 2: physician’s choice:                                  • Secondary endpoints: ORR, Time to         • LPCD: Q4 2018
               HRRm, 2L+                                      enzalutamide 160mg once daily                                 Pain Progression, OS                      • Data anticipated : H2 2019
 NCT02987543                                                  abiraterone acetate 1,000mg once daily

                                                            Global trial



19
Approved medicines




                                                                                                                                                                               Oncology
                                                                                                                                                   Late-stage development

 Lynparza (PARP inhibitor)                                                                                                                         Early development


 Imfinzi combinations, cancers
 Trial                 Population                           Patients   Design                                          Endpoints                   Status




                                                                                                                                                                               CVRM
 Phase III             Advanced ovarian cancer 1L           1,056      Non tBRCAm (tumour BRCA) patients               Primary endpoint:           • FPCD: Q1 2019
                                                                       •   Arm 1: bevacizumab                          •   PFS                     • Data anticipated: 2020+
 DuO-O                                                                 •   Arm 2: bevacizumab + Imfinzi
                                                                       •   Arm 3: bevacizumab + Imfinzi + Lynparza
 NCT03737643
                                                                       tBRCAm patients
                                                                       • bevacizumab (optional) + Imfinzi + Lynparza

                                                                       Global trial




                                                                                                                                                                               Respiratory
 Phase II              Stage IV NSCLC whose disease has     250        • Arm 1: Imfinzi + Lynparza                     Primary endpoint:           • FPCD Q1 2019
                       not progressed following SoC chemo              • Arm 2: Imfinzi + placebo                      • PFS                       • Data anticipated: 2020+
 DuO-L                 + Imfinzi Maintenance therapy 1L
 (ORION)                                                               Global trial

 NCT03775486
 Phase II              Platinum-Ineligible unresectable     150        • Arm 1: Imfinzi + Lynparza                     • Primary endpoint: PFS     • FPCD: Q1 2018
 BAYOU                 Stage IV urothelial cancer                      • Arm 2: Imfinzi + placebo                                                  • Data anticipated : 2020

 NCT03459846                                                           Global trial




                                                                                                                                                                               Other
 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           Small cell lung cancer (SCLC) 2L+               Global trial
                       Gastric cancer 2L+
 Phase I / II          gBRCAm ovarian cancer 2L+            140        •   Arm 1: Lynparza + Imfinzi                   Primary endpoints:          • FPCD: Q2 2018
 MEDIOLA               Non-gBRCAm ovarian cancer 2L+                   •   Arm 2: Lynparza + Imfinzi                   • DCR at 12 weeks
 (Ovarian expansion)   Non-gBRCAm ovarian cancer 2L+                   •   Arm 3: Lynparza + Imfinzi + bevacizumab     • ORR
                                                                       •   Dose until progression                      • Safety and tolerability
 NCT02734004
                                                                       Global trial
 Phase I / II          HER2-negative BRCAm breast           140        • Arm 1: Lynparza + Imfinzi                     Primary endpoints:          • Initiating
 MEDIOLA               cancer                                                                                          • DCR at 12 weeks
 (Breast expansion)    HER2-negative non-BRCA HRRm                     • Arm 2: Lynparza + Imfinzi                     • ORR
                       breast cancer                                                                                   • Safety and tolerability
 NCT02734004           Non-HRRm triple negative breast                 • Arm 3: Lynparza + Imfinzi + bevacizumab
                       cancer                                          • Dose until progression

                                                                       Global trial

20
Approved medicines




                                                                                                                                                                                                            Oncology
                                                                                                                                                                              Late-stage development

 Lynparza (PARP inhibitor)                                                                                                                                                    Early development


 Combinations, cancers
 Trial                  Population                        Patients   Design                                                            Endpoints                              Status




                                                                                                                                                                                                            CVRM
 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 anticipated: H2 2019
 NCT02477644
 Externally sponsored                                                Global trial

 Phase III              Metastatic castration-resistant   720        •    Arm 1: Lynparza + abiraterone                                Primary Endpoint:                      • FPCD: Q4 2018
                        prostate cancer 1L                           •    Arm 2: placebo + abiraterone                                 •   PFS                                • Data anticipated: 2020+
 PROPEL                                                               Global trial




                                                                                                                                                                                                            Respiratory
 NCT 03732820

     Phase II           Triple-negative breast cancer     450        •     Arm 1: AZD6738 + Lynparza                                   • PFS                                  • FPCD: Q2 2018
                        (TNBC)                                       •     Arm 2: adavosertib + Lynparza                               • ORR / OS                             • Data anticipated: 2020+
     VIOLETTE                                                        •     Arm 3: Lynparza                                             • Safety and tolerability
                                                                     Trial conducted in 15 countries: North America, Europe and Asia

 Phase III              Recurrent platinum sensitive      549        •    Arm 1: chemotherapy                                          Primary endpoint:                      •   FPCD: Q1 2016
 GY004                  ovarian cancer                               •    Arm 2: Lynparza                                              •   PFS                                •   Data anticipated: 2020+
                                                                     •    Arm 3: cediranib + Lynparza
 NCT02446600                                                                                                                           Secondary endpoints:
 Externally sponsored                                                US/Canada/Japan sites                                             •   OS, QoL, safety




                                                                                                                                                                                                            Other
 Phase II/III           Recurrent platinum                680        •    Arm 1: chemotherapy                                          Primary endpoints:                     •   FPCD: Q2 2016
 GY005                  resistant/refractory ovarian                 •    Arm 2: cediranib + Lynparza                                  •   PFS, OS                            •   Data anticipated: 2020+
                        cancer                                       •    Arm 3: cediranib
 NCT02502266                                                         •    Arm 4: Lynparza                                              Secondary endpoints:
 Externally sponsored                                                                                                                  •   ORR, QoL, safety
                                                                     •    US/Canada sites

 Phase II               HRRm or HRD-positive              370        •    Arm 1: Lynparza                                              Primary endpoints:                     •   FPCD: Q1 2019
 LYNK-002               advanced cancer                                                                                                •   ORR
                                                                     Trial conducted in 15 countries worldwide
 NCT03742895                                                                                                                           Secondary endpoints:
 Partnered                                                                                                                             •   DOR, OS, PFS, AE, Prog by CA-125




21
Approved medicines




                                                                                                                                                                                                             Oncology
                                                                                                                                                                               Late-stage development

 Trastuzumab deruxtecan (DS-8201, HER2 ADC)                                                                                                                                    Early development


 Breast and gastric cancers
 Trial               Population                                 Patients   Design                                                      Endpoints                               Status




                                                                                                                                                                                                             CVRM
 Phase II            HER2-positive, unresectable and/or         230        Randomised, open label, sequential assignment               Primary endpoint ORR                    • FPCD: Q3 2017
 DESTINY-Breast01    metastatic breast cancer subjects                     • Trastuzumab deruxtecan                                                                            • Data anticipated: H2 2019
                     previously treated With trastuzumab                                                                               Secondary end points DoR, CBR, CBR,
 NCT03248492         emtansine                                                                                                         PFS, OS
 Partnered


 Phase III           HER2-positive, unresectable and/or         600        Randomised open label parallel assignment                   Primacy endpoint PFS                    • FPC Q3 2018
 DESTINY-Breast02    metastatic breast cancer pretreated with              • Trastuzumab deruxtecan                                                                            • Data anticipated 2020+




                                                                                                                                                                                                             Respiratory
                     prior standard of care HER2 therapies,                Physicians choice of                                        Secondary endpoints OS, ORR, DoR, CBR
 NCT03523585         including trastuzumab emtansine                       • Lapatinib + capecitabine
 Partnered                                                                 • Trastuzumab + capecitabine


 Phase III           HER2-positive, unresectable and/or         500        Randomised open label parallel assignment                   Primary endpoint PFS                    • FPCD Q3 2018
 DESTINY-Breast03    metastatic breast cancer subjects                     • Trastuzumab deruxtecan                                                                            • Data anticipated 2020+
                     previously treated with trastuzumab and               • Ado-trastuzumab emtansine                                 Secondary endpoints OS, ORR, DoR,
 NCT03529110         taxane                                                                                                            CBR, PFS
 Partnered




                                                                                                                                                                                                             Other
 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 subjects                     • Trastuzumab deruxtecan                                                                            • Data anticipated 2020+
                                                                           • Physicians choice of SoC chemo (choice of capecitabine,   Secondary end points OS, DoR, ORR
 NCT03734029                                                                 eribulin, gemcitabine, paclitaxel or nab-paclitaxel)
 Partnered



 Phase II            HER2-overexpressing advanced gastric       220        Randomised open label parallel assignment                   Primary end point ORR                   • FPCD Q4 2017
 DESTINY-Gastric01   or gastroesophageal junction                          • Trastuzumab deruxtecan                                                                            • Data anticipated 2020
                     adenocarcinoma patients who have                      • SoC chemo                                                 Secondary end points PFS, OS, DoR,
 NCT03329690         progressed on two prior treatment                                                                                 DCR, TTF, range of PK endpoints
 Partnered           regimens




22
Approved medicines




                                                                                                                                                                                   Oncology
                                                                                                                                                         Late-stage development

 Trastuzumab deruxtecan (DS-8201, HER2 ADC)                                                                                                              Early development


 Other cancers
 Trial         Population                             Patients   Design                                     Endpoints                                    Status




                                                                                                                                                                                   CVRM
 Phase II      HER2-expressing advanced colorectal    90         Non randomised single group assignment     Primary end point ORR                        • FPCD Q1 2018
               cancer                                            •   Trastuzumab deruxtecan                                                              • Data anticipated 2020
 NCT03384940                                                                                                Secondary end points PFS, OS, DoR,
                                                                                                            range of PK endpoints
 Partnered


 Phase II      HER2-over-expressing or mutated,       80         Non randomised parallel group assignment   Primary end point ORR                        • FPCD Q2 2018
               unresectable and/or metastatic NSCLC              •   Trastuzumab deruxtecan                                                              • Data anticipated 2020




                                                                                                                                                                                   Respiratory
 NCT03505710                                                                                                Secondary end points DoR, PFS, OS

 Partnered

 Phase I       Advanced solid malignant tumours       278        Non randomised single group assignment     Primary end points number of subjects with   • FPCD Q3 2015
                                                                 •   Trastuzumab deruxtecan                 Aes, tumour response                         • Data read out Q2 2018
 NCT02564900
                                                                                                            Secondary end points PK
 Partnered




                                                                                                                                                                                   Other
23
Approved medicines




                                                                                                                                                                                                                      Oncology
                                                                                                                                                                                        Late-stage development

 Calquence (BTK inhibitor)                                                                                                                                                              Early development


 Blood cancers
 Trial                     Population                      Patients   Design                                                            Endpoint(s)                                     Status




                                                                                                                                                                                                                      CVRM
 Phase III                 Previously untreated chronic    535        • Arm A: chlorambucil + obinutuzumab                              • Primary endpoint: PFS (Arm A vs. Arm          • FPCD: Q2 2015
 ACE-CL-007 (ELEVATE-TN)   lymphocytic leukaemia (CLL)                • Arm B: Calquence + obinutuzumab                                   B)                                            • Data anticipated: H2 2019
                                                                      • Arm C: Calquence                                                • Secondary endpoints: IRC (independent
 NCT02475681                                                                                                                              review committee) assessed ORR, OS
                                                                                                                                          (Arm A vs. Arm B vs. Arm C)

     Phase III             Previously untreated CLL        780        • Arm A; Calquence + venetoclax (AV)                              • Primary - AV vs FCR/BR efficacy PFS           • FPCD: Q1 2019
                           fit                                        • Arm B: Calquence + venetoclax + obinutuzumab (AVG)              • Secondary AVG vs FCR/BR efficacy              • Data anticipated: 2020+
     ACE-CL-311                                                       • Arm C: fludarabine + cyclophosphamide + rituxumab (FCR)           PFS; AV vs FCR/BR and AVG vs




                                                                                                                                                                                                                      Respiratory
                                                                        OR bendamustine + rituximab (BR)                                  FCR/BR

 Phase III                 Relapsed/refractory CLL         306        • Arm A: Calquence                                                • Primary endpoint: IRC assessed PFS            • FPCD Q3 2016
 ACE-CL-309 (ASCEND)                                                  • Arm B: rituximab + idelalisib or bendamustine (investigator’s     (arm A vs. Arm B)                             • Data anticipated: H2 2019
 NCT02970318                                                            choice)                                                         • Secondary endpoints: INV-assessed
                                                                                                                                          ORR, OS, DoR, patient reported
                                                                                                                                          outcomes (PROs)

 Phase III                 Relapsed/refractory high risk   533        • Arm A: Calquence                                                • Primary endpoint: PFS                         • FPCD: Q2 2015
 ACE-CL-006 (ELEVATE-RR)   CLL                                        • Arm B: ibrutinib                                                • Secondary endpoints: comparison of            • Data anticipated: 2020+
                                                                                                                                          incidence of infections, RTs (Richter’s
 NCT02477696                                                                                                                              Transformation) and atrial fibrillation, OS




                                                                                                                                                                                                                      Other
 Phase III                 Previously untreated mantle     546        • Arm A: Calquence + bendamustine + rituximab                     • Primary endpoint: PFS by Lugano               • FPCD: Q1 2017
 ACE-LY-308                cell lymphoma (MCL)                        • Arm B: bendamustine + rituximab                                   Classification for non-Hodgkin's              • Data anticipated: 2020+
                                                                                                                                          Lymphoma (NHL)
 NCT02972840                                                                                                                            • Secondary endpoints: Investigator-
                                                                                                                                          assessed (IA) PFS, ORR; IRC-assessed
                                                                                                                                          ORR, DoR, time to response; OS
 Phase II                  Relapsed/ refractory CLL,       60         Calquence monotherapy                                             • ORR at 36 cycles                              • FPCD: Q1 2016
 ACE-CL-208                intolerant to ibrutinib                                                                                                                                      • Data anticipated: 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: 2020+
                           CLL/small lymphocytic                      • Arm B: Bone marrow biopsy
 NCT02337829               lymphoma (SLL)
 Phase I/II                CLL/SLL/Richter's               286        Calquence monotherapy                                             • Safety, PK, PD                                • FPCD: Q1 2014
 ACE-CL-001                transformation (RT)                        Dose escalation and expansion                                                                                     • Data anticipated: 2020+

 NCT02029443


24
Approved medicines




                                                                                                                                                                                             Oncology
                                                                                                                                                               Late-stage development

 Calquence (BTK inhibitor)                                                                                                                                     Early development


 Blood cancers
 Trial         Population                       Patients   Design                                                      Endpoint(s)                             Status




                                                                                                                                                                                             CVRM
 Phase I/II    B-cell Malignancies              126        Dose escalation and expansion trial of the combination of   • Safety                                • FPCD: Q1 2015
 ACE-LY-001                                                Calquence and ACP-319 (Pi3K inhibitor)                      • ORR                                   • Data anticipated: 2020

 NCT02328014
 Phase I/II    Haematological Malignancies      159        Calquence + pembrolizumab                                   • Safety                                • FPCD: Q1 2015
 ACE-LY-005                                                                                                            • Secondary endpoints: ORR, DoR, PFS,   • Data anticipated: 2020+
                                                                                                                         OS, TTNT (time to next therapy)
 NCT02362035




                                                                                                                                                                                             Respiratory
 Phase I/II    Waldenstrom                      106        Calquence monotherapy                                       • ORR                                   • FPCD: Q3 2014
 ACE-WM-001    Microglobulinaemia                                                                                                                              • Data readout: Q1 2018

 NCT02180724
 Phase Ib      Relapsed/refractory de novo      21         Calquence monotherapy                                       • Safety                                • FPCD: Q3 2014
 ACE-LY-002    activated B-cell diffuse large                                                                                                                  • Data anticipated: H2 2019
               B-cell lymphoma (DLBCL)
 NCT02112526
 Phase Ib      Mantle Cell Lymphoma (MCL)       76         Calquence in combination with bendamustine and rituximab    • Safety                                • FPCD: Q1 2016
 ACE-LY-106                                                • Arm A: Treatment naive                                                                            • Data anticipated: 2020+
                                                           • Arm B: Relapsed/refractory




                                                                                                                                                                                             Other
 NCT02717624                                               • Arm C: Treatment naïve: Calquence+venetoclax+Rituxan



 Phase Ib      Relapsed/refractory Multiple     28         • Arm A: Calquence                                          • Safety                                • FPCD: Q1 2015
 ACE-MY-001    Myeloma                                     • Arm B: Calquence + dexamethasone                                                                  • Data readout: Q4 2018

 NCT02211014
 Phase I       Relapsed/refractory Follicular   126        • Arm A: Calquence                                          • Safety                                • FPCD: Q1 2015
 ACE-LY-003    Lymphoma                                    • Arm B: Calquence + rituximab                                                                      • Data anticipated: 2020+
 NCT02180711

 Phase I       Relapsed/refractory CLL/         12         Calquence in combination with ACP-319                       • Safety, PK, PD                        • FPCD: Q3 2014
 ACE-CL-002    small lymphocytic lymphoma                  Dose escalation                                                                                     • Data anticipated: 2020
               (SLL)
 NCT02157324
 Phase I       CLL/SLL/Prolymphocytic           69         Calquence + obinutuzumab                                    • Safety, ORR                           • FPCD: Q4 2014
 ACE-CL-003    Leukaemia (PLL)                             • Arm A: Relapsed/refractory                                • Secondary endpoints: PD, PFS, TTNT,   • Data anticipated: 2020+
                                                           • Arm B: Treatment naïve                                      OS
 NCT02296918
                                                           Calquence + venetoclax + rituxumab
25                                                         • Arm C: Relapsed/refractory
                                                           • Arm D: Treatment naïve
Approved medicines




                                                                                                                                                                                                  Oncology
                                                                                                                                                                      Late-stage development

 Calquence (BTK inhibitor)                                                                                                                                            Early development


 Blood cancers
 Trial             Population                     Patients   Design                                                       Endpoint(s)                                 Status




                                                                                                                                                                                                  CVRM
 Phase I           Japanese Adults with           25         • Calquence monotherapy                                      • Safety                                    • FPCD: Q2 2017
                   Advanced B-cell Malignancies              • Dose confirmation and expansion                                                                        • Data anticipated: 2020+

 NCT03198650

     Phase I/II    CLL (chronic lymphocytic       62         • Arm A: AZD6738 monotherapy                                 • Identify dose of AZD 6738 and safety of   FPCD: Q1 2018
     CL-110        leukaemia) R/R                            • Arm B: Calquence + AZD6738                                   co-administration of Calquence +          Data anticipated: H1 2020
                                                                                                                            AZD6738




                                                                                                                                                                                                  Respiratory
     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: 2020

     NCT03205046




                                                                                                                                                                                                  Other
26
Approved medicines




                                                                                                                                             Oncology
                                                                                                               Late-stage development

 Calquence (BTK inhibitor)                                                                                     Early development


 Other cancers
 Trial         Population                      Patients   Design                               Endpoint(s)     Status




                                                                                                                                             CVRM
 Phase II      ≥ 2L advanced or metastatic     74         • Arm A: pembrolizumab               • ORR           • FPCD: Q2 2015
 ACE-ST-006    Head and neck squamous-cell                • Arm B: Calquence + pembrolizumab                   • Data readout: Q2 2018
               carcinoma (HNSCC)
 NCT02454179
 Phase II      ≥ 2L advanced or metastatic     74         • Arm A: pembrolizumab               • ORR           • FPCD: Q2 2015
 ACE-ST-007    Non-small-cell lung cancer                 • Arm B: Calquence + pembrolizumab                   • Data readout: 2017
               (NSCLC)
 NCT02448303




                                                                                                                                             Respiratory
 Phase II      Recurrent ovarian cancer        76         • Arm A: Calquence                   • ORR           • FPCD: Q4 2015
 ACE-ST-208                                               • Arm B: Calquence + pembrolizumab                   • Data readout: Q3 2018

 NCT02537444
 Phase II      ≥ 2L advanced or metastatic     73         • Arm A: Calquence                   • Safety        • FPCD: Q2 2015
 ACE-ST-003    pancreatic cancer                          • Arm B: Calquence + pembrolizumab                   • Data readout: Q3 2017

 NCT02362048
 Phase II      Platinum-resistant urothelial   75         • Arm A: pembrolizumab               • ORR           • FPCD: Q2 2015
 ACE-ST-005    bladder cancer                             • Arm B: Calquence + pembrolizumab                   • Data readout: Q1 2018




                                                                                                                                             Other
 NCT02351739
 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: H1 2019

 NCT02586857




27
Approved medicines




                                                                                                                                                                                                                         Oncology
                                                                                                                                                                                               Late-stage development

 Selumetinib (MEK inhibitor)                                                                                                                                                                   Early development


 Paediatric neurofibromatosis type 1
 Trial                        Population                     Patients              Design                                                           Endpoints                                  Status




                                                                                                                                                                                                                         CVRM
 Phase II                     Paediatric neurofibromatosis   50 (stratum 1)        • Single arm: selumetinib 25mg/m2 BID with 2 strata:             • Complete partial and complete response   • FPCD: Q3 2015
 SPRINT                       type 1 (NF1)                                              • Stratum 1: PN related morbidity present at enrolment        rate measured by volumetric MRI;         • LPCD: Q4 2016
                                                                                        • Stratum 2: No PN related morbidity present at enrolment   • Duration of response and functional      • Data readout: Q1 2019
 NCT01362803                                                                                                                                          outcomes/QoL
 Partnered
 Phase Ib                     Advanced solid tumours         80 (dose escalation   Phase Ib open-label trial of MK-8353 in combination with         • Dose-limiting toxicities (DLTs)          • FPCD: Q1 2019
 Selumetinib + MK-8353 (ERK                                      trial)               selumetinib in participants with advanced solid tumours       • Adverse Events (AEs)




                                                                                                                                                                                                                         Respiratory
 inhibitor)                                                                                                                                         • Study drug discontinuations due to an
                                                                                                                                                      AE
 NCT03745989

 Partnered (Merck Lead
 study)




                                                                                                                                                                                                                         Other
28
Approved medicines




                                                                                                                                                                                     Oncology
                                                                                                                                                         Late-stage development

 Savolitinib (MET inhibitor)                                                                                                                             Early development


 Papillary renal cell, NSCLC and other cancers
 Trial         Population                    Patients   Design                                                  Endpoints                                Status




                                                                                                                                                                                     CVRM
 Phase III     MET-driven, papillary renal   180        • Arm 1: savolitinib 600mg QD                           • Primary endpoint: PFS                  • FPCD: Q4 2017
               cell cancer                              • Arm 2: sunitinib 50mg QD (4 weeks on / 2 weeks off)   • Secondary endpoints include ORR, DoR   • Data anticipated: 2020
 NCT03091192                                                                                                      and OS
                                                        Global trial
 Partnered

 Phase I       Advanced cancer               ~70        • Dose escalation trial                                 • Safety and tolerability                • FPCD: Q2 2013
               (all comers)                                                                                                                              • Data anticipated: 2020+
 NCT01985555                                            Conducted in China




                                                                                                                                                                                     Respiratory
 Partnered



 Phase I       NSCLC                         64         • Dose escalation trial                                 • Safety and tolerability                • FPCD: Q2 2015
                                                                                                                                                         • Data readout: Q4 2018
 NCT02374645                                            Conducted in China




                                                                                                                                                                                     Other
 Phase II      Lung Pulmonary Sarcomatoid    92         • Single arm trial: savolitinib 600mg QD                • ORR                                    • FPCD: Q1 2017
               Carcinoma (PSC) and other                                                                                                                 • Data anticipated: 2020+
 NCT02897479   NSCLC                                    Conducted in China

 Partnered




29
Approved medicines




                                                                                                                                                                Oncology
                                                                                                                                       Late-stage development

 Cediranib (VEGF receptor inhibitor)                                                                                                   Early development


 Ovarian cancer
 Trial         Population                          Patients                            Design                     Endpoints                          Status




                                                                                                                                                                CVRM
 Phase IIb     Recurrent platinum resistant   62              • Cediranib 30mg + Lynparza 200mg bd   • ORR DoR, DCR, QoL. OS; Safety   • FPCD: Q1 2017
 CONCERTO      (PRR) ovarian cancer - heavily                                                                                          • LPCD: Q1 2019
               pre-treated BRCAwt
 NCT02889900




                                                                                                                                                                Respiratory
                                                                                                                                                                Other
30
AstraZeneca

Oncology – early-stage development
Approved medicines




                                                                                                                                                                                                                  Oncology
                                                                                                                                                                                    Late-stage development

 AZD1390 (ATM inhibitor, blood brain barrier)                                                                                                                                       Early development


 Cancer
 Trial             Population                           Subjects   Design                                                              Endpoints                                    Status




                                                                                                                                                                                                                  CVRM
 Phase I           Healthy volunteers                   8          •    Positron-Emission Tomography (PET) trial                       • Brain distribution of AZD1390 to assess    • FPCD: Q4 2017
                                                                                                                                         if [11C]AZD1390 crosses the blood brain    • Data anticipated: H2 2019
 NCT03215381                                                       •    [11C]AZD1390 microdose administered by IV bolus                  barrier in healthy volunteers

                                                                   Trial conducted in a single centre in Sweden

     Phase I       Recurrent Glioblastoma               c. 132                                                                         • Primary: Investigate the safety,           • FPCD Q2 2018
                   eligible for re-irradiation, brain              •  Designed to evaluate the safety, tolerability and PK of          tolerability, and MTD of AZD1390             • Data anticipated: 2020+
     NCT03423628   metastases and                                  AZD1390 in combination with radiation therapy in patients with      administered in combination with radiation




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

                                                                   Conducted across seven sites in USA and UK




                                                                                                                                                                                                                  Other
32
Approved medicines




                                                                                                                                                                                             Oncology
                                                                                                                                                                    Late-stage development

 Adavosertib (AZD1775, WEE-1 inhibitor)                                                                                                                             Early development


 Ovarian cancer, triple-negative breast cancer, small cell lung cancer (SCLC)
 Trial         Population                Patients   Design                                                             Endpoints                                    Status




                                                                                                                                                                                             CVRM
 Phase II      Platinum-resistant (PR)   97         • Arm B: paclitaxel + adavosertib                                  • Primary endpoint: ORR                      • FPCD: Q1 2015
               ovarian cancer                       • Arm C: carboplatin + adavosertib                                                                              • LPCD: Q2 2018
 NCT02272790                                                                                                           • Secondary endpoints: DoR, PFS, OS,
                                                    Global trial                                                         Disease Control Rate, safety and
                                                                                                                         tolerability

 Phase I       Advanced solid tumours    102        • Dose escalation trial to determine MTD (adavosertib +            • Safety and tolerability                    • FPCD: Q3 2015
                                                      Lynparza) followed by an expansions in SCLC                      • Secondary endpoints: Overall response
 NCT02511795                                                                                                             rate, Disease Control Rate, Duration of




                                                                                                                                                                                             Respiratory
                                                    Conducted in US, Canada                                              Response, PFS
 Phase I       Advanced solid tumours    55         • Dose escalation trial to determine MTD (adavosertib + Imfinzi)   • Safety and tolerability                    • FPCD: Q4 2015

 NCT02617277                                        Conducted in US

 Phase I       Advanced solid tumours    30         Part A: caffeine (200mg), omeprazole (20mg) and midazolam          • Primary endpoints:                         • FPCD: Q4 2017
                                                      (1mL of 2mg/mL syrup) followed 7-14 days later by adavosertib    • Part A: Plasma AUC, AUC0-t and CMAX
 D6014C00006                                          225mg bid for 2.5 days plus caffeine (200mg), omeprazole           for cocktail parent compounds
                                                      (20mg) and midazolam (1mL of 2mg/mL syrup) on day 3.               (midazolam, omeprazole and caffeine)
 NCT03333824                                        Part B: 7-14 days after end of Part A, adavosertib 225mg BID for   • Part B: dECG (Differentiated ECG)
                                                      2.5 days.                                                          intervals (QTcF) for absolute values and
                                                                                                                         time-matched change from baseline
                                                    Conducted in US




                                                                                                                                                                                             Other
 Phase I       Advanced solid tumours    54         adavosertib monotherapy once daily.                                • Safety and tolerability                    • FPCD: Q4 2017

 D6014C00007                                        Conducted in US and Europe

 NCT03313557




33
Approved medicines




                                                                                                                                                                                                                         Oncology
                                                                                                                                                                                           Late-stage development

 Capivasertib (AZD5363, AKT inhibitor)                                                                                                                                                     Early development


 Cancer
 Trial            Population                        Patients                 Design                                                             Endpoints                                  Status




                                                                                                                                                                                                                         CVRM
 Phase I          Breast and gynaecological         12-24 per arm (Parts E   AZD5363 400mg BD 4 days on 3 days off combined with 500mg           • Safety and tolerability                 • Data anticipated: H2 2019
                  cancers with PIK pathway          & F)                     fulvestrant [initially 12 patients per arm with option to expand to • ORR
 NCT01226316      mutation                                                   24 patients in one or more arms]                                    • Clinical Benefit Rate at 24 weeks
                                                                             • Part E arm 1: ER+ Breast with AKT-1 mutation (prior Faslodex        (CBR24)
                                                                                resistance)                                                        [Parts E & F only]
                                                                             • Part E arm 2: ER+ Breast with AKT-1 mutation (first exposure
                                                                                to Faslodex)
                                                                             • Part F arm 1: ER+ Breast with PTEN mutation (prior Faslodex
                                                                                resistance)




                                                                                                                                                                                                                         Respiratory
                                                                             • Part F arm 2: ER+ Breast with PTEN mutation (first exposure to
                                                                                Faslodex)
 Phase II (ESR)   Advanced / metastatic triple      140                      Randomised comparative                                             • Progression Free Survival                • Data readout: Q2 2018
                  negative breast cancer                                     ARM1: Paclitaxel + capivasertib                                    • Overall survival                         • Final OS data awaited
 NCT02423603      receiving 1L chemotherapy                                  ARM 2: Paclitaxel + placebo
                  with paclitaxel                                                                                                               Overall population and in sub-group with
 PAKT                                                                                                                                           tumours harbouring PIK3CA/AKT1/PTEN
                                                                                                                                                alterations



 Phase II (ESR)   Post menopausal women with        140                      Randomised comparative                                             • Progression Free Survival                • Data anticipated: H1 2019




                                                                                                                                                                                                                         Other
                  advanced ER+/Her2- breast                                  ARM 1: Faslodex + capivasertib                                     • Overall survival
 NCT01992952      cancer previously treated with                             ARM 2: Faslodex + placebo
                  aromatase inhibition                                                                                                          Overall population and sub-group with
 FAKTION                                                                                                                                        activation of the tumour PI3K/Akt/PTEN
                                                                                                                                                pathway (eg. PIK3CA/AKT1/PTEN
                                                                                                                                                alterations)


 Phase II (ESR)   Metastatic castration resistant   150                      Randomised comparative                                             • Progression Free Survival                • Data anticipated: 2020
                  prostate cancer eligible for                               ARM 1: Docetaxel + prednisolone + capivasertib
 NCT02121639      treatment with docetaxel                                   ARM 2: Docetaxel + prednisolone + placebo
                  chemotherapy
 PROCAID




34
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