Slide 1: Pipeline: Oncology
Pipeline: Oncology Susan Galbraith, Head of Innovative Medicines Oncology iMed Mohammed Dar, Vice President, Oncology Clinical Development
Slide 2: AstraZeneca Oncology
AstraZeneca Oncology Common vision Bold ambition Redefine cancer treatment paradigm By 2020, we will be a recognised Restore patients’ lives leader in oncology, delivering 6 Eliminate cancer as cause of death new medicines to patients 4 key MoA & platforms 4 core disease areas Combinations Personali
Slide 3: Oncology: Combine therapies to change treatment paradigm
Oncology: Combine therapies to change treatment paradigm PD-L1 + CTLA-4 TORC1/2 + Faslodex Combination therapies may 1.5 enhance efficacy by: Control Tumour volume (cm3) tumour volume (mm3) Faslodex 1 • Targeting complementary AZD2014 pathways 0.5 AZD2014+Faslodex • Establishing synergistic Study da
Slide 4: Oncology: Personalised healthcare as key driver
Oncology: Personalised healthcare as key driver Tissue-based Single-gene Circulating Next-generation assay mutation analysis tumour DNA sequencing MEDI4736 Lynparza Iressa / AZD9291 Oncology portfolio (PD-L1) Tumour 4 – Pipeline: Oncology
Slide 5: Oncology: Smart development crucial to leadership
Oncology: Smart development crucial to leadership AZD9291 Potential filing less than 2½ years from first dose MEDI4736 (PD-L1) Leapfrog competition into early line of therapy PACIFIC study Iressa / AZD9291 First in ctDNA diagnostic testing MEDI4736 Good combinability enables novel triplet combinatio
Slide 6: Scientific leadership: Four key platforms
Scientific leadership: Four key platforms Tumour drivers Antibody drug and resistance DNA damage repair Immunotherapy conjugates • AZD9291 (EGFRm) • Olaparib (PARP) • MEDI4736 (PD-L1) • Moxetumomab (CD22) • Selumetinib (MEK) • Cediranib (VEGF)** • Tremelimumab (CTLA-4) • ADC-Spirogen* • AZD2014 (TOR
Slide 7: Scientific leadership: Tumour drivers & resistance
Scientific leadership: Tumour drivers & resistance • Highly altered signalling pathways in cancer • Interconnected pathways allow resistance / escape mechanisms • Multiple targets identified as potential tumour driver mutations Tumour 7 – Pipeline: Oncology
Slide 8: AZD9291: EGFR mutant selective inhibitor in lung cancer
AZD9291: Tumour drivers and resistance EGFR mutant selective inhibitor in lung cancer Strong evidence of monotherapy activity • Potentially first irreversible selective inhibitor of double EGFR mutations Best percentage change from baseline in target lesion* • Awarded FDA Breakthrough Therapy Design
Slide 9: AZD9291: Early efficacy in 1st line EGFRm NSCLC
AZD9291: Tumour drivers and resistance Early efficacy in 1st line EGFRm NSCLC Preliminary evidence of activity 1st line EGFRm in NSCLC brain mets A) A) Overall disease control rate (CR+PR+SD) = 95% A B) B) ) Clinical activity of AZD9291 in brain mets has been observed in a Phase I study in patients
Slide 10: AZD2014: Dual TORC1/2 inhibitor
AZD2014: Tumour drivers and resistance Dual TORC1/2 inhibitor Strong evidence of activity Differentiated clinical activity Dual TORC1/2 + paclitaxel* • Broad potential in breast, lung, ovarian cancer and lymphoma • Dual TORC1/2 and intermittent weekly dosing schedule to deliver better efficacy and t
Slide 11: AZD6094: Potent, selective cMET inhibitor of MET-driven tumours
AZD6094: Tumour drivers and resistance Potent, selective cMET inhibitor of MET-driven tumours Activity in MET-driven • Active in MET amplified and MET- papillary renal cell cancer (PRCC) mutant settings Best tumour assessment change from baseline (%) • First-in-class opportunity in papillary renal c
Slide 12: AZD9496: Oral selective estrogen receptor degrader (SERD)
AZD9496: Tumour drivers and resistance Oral selective estrogen receptor degrader (SERD) Greater tumour inhibition than Faslodex Undosed Controls • Improved potency and 2.0 PEG/Captisol vehicle Undosed control + vehicles Peanut oil vehicle bioavailability allows greater 1.8 Faslodex 5 mg x3 weekly s.
Slide 13: DNA Damage Repair (DDR): Targeting the Achilles heel of cancer
DNA Damage Repair (DDR): Targeting the Achilles heel of cancer • Highly altered pathways in cancer • Traditional chemotherapies depend on DDR pathways • Most extensive portfolio of DDR agents in the industry 13 – Pipeline: Oncology
Slide 14: Lynparza (olaparib): First-in-class PARP inhibitor
Lynparza (olaparib): DNA damage repair First-in-class PARP inhibitor Clinical benefit in BRCAm Ongoing Phase III programmes ovarian cancer Olaparib, n=74 Placebo, n=62 Median 11.2 mo 4.3 mo • BRCAm ovarian cancer: SOLO-2 (2015*), SOLO-1 (2016*) Proportion of patients progression-free 1.0 HR=0.18 95%
Slide 15: AZD1775: Wee1 inhibitor; encouraging data in ovarian cancer
AZD1775: DNA damage repair Wee1 inhibitor; encouraging data in ovarian cancer Wee1: Role in cell cycle progression Platinum-sensitive relapsed and DNA damage checkpoints ovarian cancer G2/M • 11/14 RECIST responses checkpoint • PFS 10.8 months • 13/14 GCIG responses (includes CA125 responses) Wee1 •
Slide 16: AZD2811: Aurora Kinase B inhibitor, AML proof of concept
AZD2811: DNA damage repair Aurora Kinase B inhibitor (AKBi): AML proof of concept Phase II: AKBi vs low-dose cytarabine Differentiated profile (LDAC) in elderly unfit AML AKBi vs LDAC • Novel mechanism of action: OCRR (+Cheson) +30% Regulates mitosis and Overall Survival (HR) 0.88 (0.49-1.58) chromo
Slide 17: Immuno-oncology (IO): Changing the treatment paradigms for cancer
Immuno-oncology (IO): Changing the treatment paradigms for cancer • An effective immune response is durable - possibly life-long • Cancer hijacks many immune pathways to escape destruction • Our robust pipeline allows identification of combinations that restore the immune response 17 – Pipeline: Onc
Slide 18: Immuno-oncology: Three major components to cancer immune response
Immuno-oncology (IO): Immunotherapy Three major components to cancer immune response 2. Optimizing T cell OX40 PD-L1 function and PD-1 CTLA-4 memory NME-4 NME-5 1. Antigen 3. Inhibition by presentation microenvironment HPV Vaccine* AZD9291 IDO* CXCR2 Radiotherapy BRAF/MEK* CCR4* STAT3 Iressa NME-1 N
Slide 19: MEDI4736 (PD-L1): Triplet w/dabrafenib and trametinib in BRAFm melanoma
MEDI4736 (PD-L1): Immunotherapy Triplet w/dabrafenib and trametinib in BRAFm melanoma Potential for well-tolerated, durable BRAFi/MEKi treatment effect benefit in BRAFm melanoma Increase in CD8 Tumour Infiltrated Lymphocytes (TILs) • Clinical data for BRAFi/MEKi provide rationale for “triplet” combi
Slide 20: MEDI6383 (OX40): Pathway drives potent, durable anti-tumour T cell immunity
MEDI6383 (OX40): Immunotherapy Pathway drives potent, durable anti-tumour T cell immunity Murine OX40: Phase I evidence of activity 3 unique OX40 molecules with distinctive biology Best tumour assessment change from baseline (%) 100 PD on day 56 80 SD on day 56+ 60 40 • Murine anti-human OX40 20 (ac
Slide 21: AZD9150: STAT3 and roles in tumour microenvironment
AZD9150: Immunotherapy STAT3 and roles in tumour microenvironment STAT3 inhibition decreases immune Durable responses in Phase I tolerance in tumour microenvironment monotherapy studies Nature Reviews Immunology 7, 41-51 A CR and PRs lasting > 1year in lymphoma and liver cancer studies Phase I oral
Slide 22: AZD5069: CXCR2 affects myeloid-derived suppressor cell trafficking
AZD5069: Immunotherapy CXCR2 affects myeloid-derived suppressor cell trafficking • First-in-class CXCR2 antagonist in oncology • Potential synergistic activity with MEDI4736 (PD-L1) • Phase I combination study of CXCR2 + MEDI4736 (PD-L1) expected to start in H1 2015 22 – Pipeline: Oncology
Slide 23: Immuno-oncology: Combinations address multiple immune pathways
Immuno-oncology (IO): Combinations address multiple immune pathways Antigen presentation PD-L1 EGFR T-cell activation combined with increased tumour visibility PD-L1 MEK/BRAF T-cell activation combined with increased antigen presentation PD-L1 HPV Vaccine T-cell activation combined with increased pr
Slide 24: Immuno-oncology: Unique indications, novel combos, speed of execution
Immuno-oncology (IO): Immunotherapy Unique indications, novel combos, speed of execution 1 2 3 Speed Differentiation Leadership • Rapid program expansion First or best-in-class Quickest path to approval • Adaptive decision-making agents • Patient selection Monotherapy MEDI4736 Combinations (PD-L1) D
Slide 25: MEDI4736 (PD-L1): Monotherapy; early, durable activity in multiple tumours
MEDI4736 (PD-L1): Immunotherapy Monotherapy; early, durable activity in multiple tumours* Total study population (10 mg/kg q2w) Ongoing responders Total 92% (33/36) RECIST response PD-L1+ 22% (18/81) PD-L1- 5% (12/233) Total 10% (36/352) Disease control rate at 12 weeks PD-L1+ 47% (38/81) PD-L1- 28%
Slide 26: MEDI4736 + tremelimumab: Encouraging efficacy for combination in NSCLC
MEDI4736 (PD-L1) + tremelimumab: Immunotherapy Encouraging efficacy for combination in NSCLC Tumour Tumourshrinkage shrinkagebyby Best change in tumour size by dose dosecohort cohort(n=18) (n=18) dose cohort (n=18) All patients ORR Stable disease MEDI4736+tremelimumab 28% (5/18) 28% (5/18) 26 – Pipe
Slide 27: MEDI4736 + tremelimumab: Potentially better response in PD-L1 negative tumours
MEDI4736 (PD-L1) + tremelimumab: Immunotherapy Potentially better response in PD-L1 negative tumours PD-L1 negative patients in NSCLC 70% (7/10) MEDI4736 (PD-L1) * MEDI4736 (PD-L1) + tremelimumab ** 42% (31/74) 30% (3/10) 10% (7/74) ORR ORR + SD * Mono: ORR 10% (7/74), 95%CI (3.9%, 18.5%) SD≥12weeks
Slide 28: MEDI4736 (PD-L1): Development in NSCLC
MEDI4736 (PD-L1): Immunotherapy Development in NSCLC First-mover advantage Fast-to-market monotherapy Early NSCLC ATLANTIC ARCTIC PACIFIC ADJUVANT Phase II Phase III Phase III Phase III 3L NSCLC 3L NSCLC Stage 3 unresectable Adjuvant NSCLC PD-L1 -positive NSCLC PD-L1 positive and unselected MEDI4736
Slide 29: NSCLC: Focus on medical need in PD-L1 negative disease
Non-small cell lung cancer (NSCLC): Immunotherapy Focus on medical need in PD-L1 negative disease Mutation status PD-L1 negative NSCLC KRAS/EGFR/ALK WT KRASm EGFRm ALKm PDL1 21k Dx+ 87k pts 24k pts • Largest segment of pts NSCLC PD-L1 status • Not addressed by marketed targeted therapies (EGFR, ALK)
Slide 30: MEDI4736 (PD-L1): Head and neck cancer (SCCHN)
MEDI4736 (PD-L1): Immunotherapy Head and neck cancer (SCCHN) After two MEDI4736 (PD-L1) Before MEDI4736 (PD-L1) infusion infusions (30 days) 96 year old patient who had progressed on cetuximab prior to study entry (HPV negative, PD-L1 positive) SCCHN=Squamous cell carcinoma of head and neck 30 – Pip
Slide 31: MEDI4736 (PD-L1): Head and neck cancer development
MEDI4736 (PD-L1): Immunotherapy Head and neck cancer development Fast-to-market First-mover advantage monotherapy combination therapy HAWK CONDOR EAGLE Phase II Phase II Phase III Platinum failures Platinum failures Platinum failures PD-L1 positive PD-L1 negative Unselected MEDI4736 (PD-L1) monother
Slide 32: Immuno-oncology: ongoing and planned combinations
Immuno-oncology (IO): 13 ongoing and 16 planned combinations to Immunotherapy address multiple immune pathways Ongoing studies Planned studies PD-L1 Ph III NSCLC PD-L1 + tremelimumab Ph III 3L NSCLC tremelimumab Ph III Mesothelioma PD-L1 +/- tremelimumab Ph I/II/III SCCHN Seq. AZD9291/selumetinib +
Slide 33: Summary
Summary Oncology poised to be transformational for the company Broad pipeline addresses multiple mechanisms and allows for optimal combination therapies to improve patient benefit Leadership in next-generation of science in oncology 33 – Pipeline: Oncology
Slide 34: Q&A
Q&A Mondher Mahjoubi, moderator Susan Galbraith Mohammed Dar Antoine Yver