Slide 1: Meet AZN management: ASCO 2019 Breakout 3: early-stage pipeline
Marquis_CONFERENCE AZ2019 Meet AZN management: ASCO 2019 Breakout 3: early-stage pipeline Susan Galbraith, Senior Vice President, Oncology R&D, early stage Jean-Charles Soria, Senior Vice President, Oncology R&D, early stage 3 June 2019
Slide 2: Forward-looking statements
Forward-looking statements In order, among other things, to utilise the 'safe harbour' provisions of the US Private Securities Litigation Reform Act 1995, we are providing the following cautionary statement: this document contains certain forward-looking statements with respect to the operations, pe
Slide 3: Rich early to mid-stage pipeline
Rich early to mid-stage pipeline Tumour drivers and resistance DNA damage response (DDR) Immuno-oncology (IO) capivasertib (AKT1 inhibitor) adavosertib (WEE15 inhibitor) monalizumab (NKG2A9 mAb10) • breast, prostate cancers, Phase III to start • solid cancers, Phase II • head & neck, colorectal, Pha
Slide 4: Tumour drivers and resistance: early breast
Tumour drivers and resistance: early breast Building on an established franchise Capivasertib (AZD5363): targeting AKT AZD9833 (SERD, oral) OS in overall population OS in PIK3CA1/AKT/PTEN2 altered 100 100 Overall Survival (%) 75 75 Overall Survival (%) 50 50 25 25 0 0 0 6 12 18 24 30 36 42 0 6 12 18
Slide 5: Tumour drivers and resistance: cell death
Tumour drivers and resistance: cell death Haematologic cancers the next wave of innovation Targeting distinct nodes of cell death AZD5991 (MCL1 inhibitor) AZD5991 (MCL1i1): AZD4573 (CDK92i): AZD0466 (Bcl23/xL4i): Single dose of AZD5991 achieves tumour regression in nanomedicine to novel macrocylic d
Slide 6: DNA damage response: Lynparza and beyond
DNA damage response: Lynparza and beyond Developing chemo-free regimens, extending survival Launch adavosertib (WEE1) / ceralasertib (ATR) Lynparza combinations Expand Lynparza beyond BRCA (prostate cancer, Deliver next-generation ovarian cancer) DDR medicines: AZD1390 (ATM inhibitor), AZD2811 (auro
Slide 7: DNA damage response: pipeline
DNA damage response: pipeline The next wave of potential DDR medicines A broad pipeline targeting complementary aspects of DNA damage repair and cell cycle regulation AZD2811: targeting Aurora Kinase B AZD2811 Aurora Bi adavosertib Death in WEE1i mitosis or subsequent G1 phase Prevent repair M G2 Ly
Slide 8: Broad IO pipeline: enhancement of antitumour immunity
Broad IO pipeline: enhancement of antitumour immunity Fully harnessing immune system to eliminate tumours 1 2 3 No effective Suboptimal or exhausted Antitumour immunity Goal: highly-active antitumour immunity antitumour immunity suppressed by TME1 antitumour immunity ‘Cold’ tumour Example: PD-L1+ tu
Slide 9: Developing an adenosine franchise
Developing an adenosine franchise Reversing tumour immunosuppression Targeting adenosine pathway AZD4635: targeting A2aR IMMUNE RESPONSE Pro-inflammatory Immunosuppressive Cancer ↓ T effectors ↑ MDSC1 therapy ↑ Tregs2 ↓ NK3 cells ↑ Dendritic cell ↑ Fibroblast ↑ Tregs ↑ Macrophage ↑ Angiogenesis ↑ Su
Slide 10: Next-generation checkpoints
Next-generation checkpoints Utilising the innate and adaptive immune system Monalizumab: targeting NKG2A MEDI5752: PD-1/CTLA-4 bispecific Tumour: increased efficacy Periphery: increased safety PD-1 CTLA-4 CTLA-4 X CTLA-4 α PD-1 α CTLA-4 MEDI5752 α CTLA-4 MEDI5752 Internalisation and degradation of P
Slide 11: Oncolytic viruses offer multiple mechanisms of action
Oncolytic viruses offer multiple mechanisms of action Leveraging internal and external expertise MEDI5395: NDV-GMCSF Collaboration with Transgene Not a select agent; suitable for world-wide development 1 IFN1γ production, Th21 education F- Protein Cleavage site modification 2 T cell memory and homeo
Slide 12: Q&A
Q&A 12
Slide 13: Use of AstraZeneca conference call, webcast and presentation slides
Use of AstraZeneca conference call, webcast and presentation slides The AstraZeneca webcast, conference call and presentation slides (together the ‘AstraZeneca Materials’) are for your personal, non- commercial use only. You may not copy, reproduce, republish, post, broadcast, transmit, make availab