Slide 1: ESMO 2023 Meet AZN Management
ESMO 2023 Meet AZN Management For investors and analysts 23 October 2023
Slide 2: Speakers and panelists
AstraZeneca @ ESMO 2023 Speakers and panelists KEY EXTERNAL EXPERT Pascal Soriot, Susan Galbraith, Sunil Verma, Dr Aaron Lisberg, Chief Executive Officer Executive Vice President, Global Head of Thoracic Medical Oncologist, Oncology R&D Oncology, Medical UCLA KEY EXTERNAL EXPERT Dave Fredrickson, Cr
Slide 3: Leading a revolution to redefine cancer care
Leading a revolution to redefine cancer care Pascal Soriot CHIEF EXECUTIVE OFFICER
Slide 4: 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 of 1995, AstraZeneca (hereafter ‘the Group’) provides the following cautionary statement: This document contains certain forward-looking statements wit
Slide 5: AstraZeneca @ ESMO 2023 Agenda
AstraZeneca @ ESMO 2023 AGENDA | Leading a revolution to redefine cancer care – Pascal Soriot, CEO Placing AstraZeneca data from ESMO 2023 into context Dr Aaron Lisberg, Medical Oncologist, UCLA Realising the transformative – Dr Aditya Bardia, Medical Oncologist, MGH potential of ADCs Susan Galbrait
Slide 6: AstraZeneca – leading a revolution to redefine cancer care
AstraZeneca – leading a revolution to redefine cancer care Proven track record, transforming the Establishing tumour area leadership oncology landscape Organisational design promoting collaboration across R&D and commercial Delivering treatments to patients with greatest unmet need novel medicines l
Slide 7: Establishing our tumour area leadership
Establishing our tumour area leadership Lung Breast Haematology GI GYN/GU AZD0486 (CD3xCD19 TCE) sabestomig (PD1/TIM3) Dato-DXd LM-305 (GPRC5D ADC) Dato-DXd capivasertib capivasertib volrustomig (PD1/CTLA4) AZD8205 (B7H4 ADC) camizestrant rilvegostomig (PD1/TIGIT) AZD5851 (GPC3 CAR-T) AZD5335 (FRα A
Slide 8: Exceptional momentum in oncology this year: key data highlights at ESMO 2023
AstraZeneca exceptional momentum in oncology this year Key data highlights at ESMO 2023 9 positive data read-outs to-date in 2023 >90 accepted abstracts TROPION-Breast01 positive Phase III HLR since H1 2023 26 oral presentations incl. • DUO-E (LBA41) • MATTERHORN (LBA73) • DESTINY-PanTumor02 (LBA34)
Slide 9: Transforming treatment with antibody drug conjugates: TROPION-Lung01
Transforming treatment with antibody drug conjugates TROPION-Lung01 Dr Aaron Lisberg T H O R A C I C M E D I C A L O N C O L O G I S T, U C L A
Slide 10: Background
Background Unmet need in 2L NSCLC Dato-DXd Standard-of-care, second-line chemotherapy for metastatic Humanised anti-TROP2 IgG1 mAb2-5 NSCLC is associated with a modest benefit and substantial toxicity Dato-DXd is a TROP2-directed ADC that selectively delivers a potent topoisomerase I inhibitor paylo
Slide 11: TROPION-Lung01 Phase III trial in 2L+ NSCLC
TROPION-Lung01 Phase III trial in 2L+ NSCLC Randomised Phase III open-label global trial • NSCLC (Stg. IIIB, IIIC, or IV) • ECOG PS 0 or 1 Endpoints • No prior docetaxel Dato-DXd Dual primary endpoints: Without AGA1 6mg/kg IV Q3W • PFS (BICR) • OS • 1-2 prior lines, including R platinum CTx and anti
Slide 12: TROPION-Lung01 – Baseline features
TROPION-Lung01 – Baseline features Dato-DXd Docetaxel Dato-DXd Docetaxel Characteristic Characteristic N=299 N=305 N=299 N=305 Age, median (range), years 63 (26, 84) 64 (24, 88) Current or former smoker, n (%) 238 (80) 251 (82) Male, n (%) 183 (61) 210 (69) Actionable Present 50 (17) 51 (17) genomic
Slide 13: TROPION-Lung01 – Patient disposition
TROPION-Lung01 – Patient disposition Dato-DXd Docetaxel Disposition N=297 N=290 Treatment status, n (%) Ongoing on study treatment 52 (18) 17 (6) Discontinued from study treatment 245 (83) 273 (94) Treatment duration, n (%) 0-3 months 118 (40) 168 (58) 3-6 months 73 (25) 66 (23) Median study follow-
Slide 14: TROPION-Lung01 – Progression-free survival in ITT
TROPION-Lung01 – Progression-free survival in ITT Dato-DXd Docetaxel Median PFS, months 4.4 3.7 (95% CI)1 (4.2, 5.6) (2.9,4.2) HR (95% CI) 0.75 (0.62, 0.91) P-value 0.004 Prespecified boundary 0.008 (2-sided) Dato-DXd Docetaxel ORR, % 26.4 12.8 (95% CI)2 (21.5, 31.8) (9.3, 17.1) DOR, mo. 7.1 5.6 (95
Slide 15: TROPION-Lung01 – PFS in key subgroups
TROPION-Lung01 – PFS in key subgroups 1 1. Regardless of histology. 16 PFS = progression-free survival; Dato-DXd = datopotamab deruxtecan; HR = hazard ratio. Collaboration partner: Daiichi Sankyo (Dato-DXd).
Slide 16: TROPION-Lung01 – PFS by histology
TROPION-Lung01 – PFS by histology With and without AGAs Non-squamous Squamous (with and without AGA) (with and without AGA) Dato-DXd Docetaxel Dato-DXd Docetaxel Median PFS, months 5.6 3.7 Median PFS, months 2.8 3.9 (95% CI) (4.4, 7.0) (2.9, 4.2) (95% CI) (1.9, 4.0) (2.8, 4.5) HR (95% CI) 0.63 (0.51
Slide 17: TROPION-Lung01 – Interim overall survival – ITT
TROPION-Lung01 – Interim overall survival – ITT Dato-DXd Docetaxel Median OS, months 12.4 11.0 (95% CI)1 (10.8, 14.8) (9.8, 12.5) HR (95% CI) 0.90 (0.72, 1.13) Information fraction at interim analysis (events/total events required): 74% Non-squamous HR (95% CI): 0.77 (0.59, 1.01); Squamous HR (95% C
Slide 18: TROPION-Lung01 – Overall safety summary
TROPION-Lung01 – Overall safety summary Dato-DXd Docetaxel TRAEs, n (%) N=297 N=290 Median treatment durations for Dato-DXd All grades 257 (87) 252 (87) and docetaxel were 4.2 and 2.8 months, respectively Grade ≥3 73 (25) 120 (41) Associated with dose reduction 58 (20) 85 (29) Fewer Grade ≥3 TRAEs w
Slide 19: TROPION-Lung01 – Adverse Events of Special Interest
TROPION-Lung01 – Adverse Events of Special Interest Dato-DXd Docetaxel Stomatitis/oral mucositis associated with Dato-DXd resulted in a AESI N=297 N=290 low rate of discontinuation (0.7%) Stomatitis/oral mucositis, n (%)1 All grades 160 (54) 59 (20) Dry eye was the most common ocular event seen with
Slide 20: TROPION-Lung01 – Summary
TROPION-Lung01 – Summary Dato-DXd is the first ADC to demonstrate a statistically significant improvement in PFS over docetaxel in patients with previously treated, locally advanced or metastatic NSCLC PFS benefit was primarily driven by patients with non-squamous histology Fewer Grade ≥3 TRAEs and
Slide 21: Transforming treatment with antibody drug conjugates: TROPION-Breast01
Transforming treatment with antibody drug conjugates TROPION-Breast01 Dr Aditya Bardia DIRECTOR OF BREAST CANCER RESEARCH PROGRAM, MASSACHUSETTS GENERAL H O S P I TA L
Slide 22: Background
Background Unmet need in HR+/HER2 – mBC HR+/HER2– breast cancer is the most common subtype of breast cancer, accounting for 60–70% of all cases1 Despite new therapeutic options becoming available, there remains an unmet need after endocrine therapy and one line of systemic therapy for patients with
Slide 23: TROPION-Breast01
TROPION-Breast01 Randomised, Phase III open-label global trial Treatment continued until PD, unacceptable tolerability, or other discontinuation criteria Endpoints HR+/HER2- breast cancer1 Dato-DXd Dual primary endpoints 6mg/kg IV Day 1 Q3W 1-2 prior lines of CTx in n=365 • PFS (BICR) inoperable/met
Slide 24: TROPION-Breast01 – Baseline features
TROPION-Breast01 – Baseline features Demographics and baseline characteristics were generally well balanced Dato-DXd (n=365) ICC (n=367) Age, median (range), years 56 (29–86) 54 (28–86) Female, n (%) 360 (99) 363 (99) Race, n (%) Black or African American / Asian / White / Other1 4 (1) / 146 (40) /
Slide 25: TROPION-Breast01 – PFS by BICR (primary endpoint)
TROPION-Breast01 – PFS by BICR (primary endpoint) Dato-DXd demonstrated statistically significant and clinically meaningful difference vs. ICC Dato-DXd ICC Median PFS, months 6.9 4.9 (95% CI) (5.7–7.4) (4.2–5.5) HR (95% CI) 0.63 (0.52–0.76) P-value <0.0001 PFS by investigator assessment: median 6.9
Slide 26: TROPION-Breast01 – PFS by BICR across subgroups
TROPION-Breast01 – PFS by BICR across subgroups Consistent benefit across key subgroups 1 Data cut-off: 17 July 2023. Size of circle is proportional to the number of events across both treatment groups. 1. Three patients from Canada were incorrectly stratified to Rest of World. PFS = progression-fre
Slide 27: TROPION-Breast01 – Response rate and interim OS
TROPION-Breast01 – Response rate and interim OS 50% greater response rate with Dato-DXd vs. ICC Response rate Overall survival: dual primary endpoint Complete response ORR Partial response OS data were not mature:1 36.4% 40 0.5% ― Median follow-up 9.7 months 35 Patients with response, % 30 ORR 25 v
Slide 28: TROPION-Breast01 – Overall safety summary
TROPION-Breast01 – Overall safety summary Favourable and manageable safety profile Dato-DXd ICC TRAEs, n (%) Median treatment duration was 6.7 months with Dato-DXd and (n=360) (n=351) 4.1 months with ICC All grades 337 (94) 303 (86) Grade ≥3 75 (21) 157 (45) Rate of Grade ≥3 TRAEs in the Dato-DXd gr
Slide 29: TROPION-Breast01 – TRAEs in ≥15% of Patients
TROPION-Breast01 – TRAEs in ≥15% of Patients No new safety signals observed Dato-DXd ICC System Organ Class (n=360) (n=351) Preferred term, n (%) Most TRAEs were Grade 1-2 and manageable Any Grade Grade ≥3 Any Grade Grade ≥3 Blood and lymphatic system disorders Anaemia 40 (11) 4 (1) 69 (20) 7 (2) AE
Slide 30: TROPION-Breast01 – Summary
TROPION-Breast01 – Summary TROPION Breast01 demonstrated that Dato-DXd provides both improved efficacy and safety compared with ICC for patients with HR+/HER2– disease TROPION-Breast01 met its dual primary PFS endpoint, demonstrating statistically significant and clinically meaningful improvement in
Slide 31: Realising the transformative potential of ADCs
Realising the transformative potential of ADCs Future ambition for Dato-DXd Susan Galbraith ONCOLOGY R&D
Slide 32: Unlocking the increasing value of Dato-DXd
Unlocking the increasing value of Dato-DXd 1 2 3 Beats conventional Best-in-class profile Broad potential in earlier monotherapy CTx supports IO combo lines and other tumour types TROPION-Lung01 TROPION-Lung02 TROPION-Lung07 TROPION-Breast01 TROPION-Lung04 TROPION-Lung08 v BEGONIA AVANZAR TROPION-Br
Slide 33: Dato-DXd beats conventional monotherapy CTx
1. Dato-DXd beats conventional monotherapy CTx TROPION-Lung01 filing underway1, TROPION-Breast01 data shared with regulators TROPION-Lung01 | 2L+ NSCLC TROPION-Breast01 | 2L+ HR+ mBC Clear benefit in easily identifiable non-squamous patients Benefit across ITT v v • Fewer Grade ≥ 3 TRAEs observed wi
Slide 34: Dato-DXd best-in-class profile supports IO combo
2. Dato-DXd best-in-class profile supports IO combo AE profile enables combination with Early efficacy data reinforces potential both IO and chemotherapy in Phase III combination trials % ORR Lower bone marrow toxicity confers better combinability with platinum chemotherapy Dato-DXd + pembro + CTx 5
Slide 35: Broad potential of Dato-DXd in earlier lines and other tumour types
3. Broad potential of Dato-DXd in earlier lines and other tumour types Early-stage 1L 2L+ TROPION-Lung07 TROPION-Lung08 AVANZAR TROPION-Lung01 108,000 145,000 CTx treated patients CTx treated patients in 1L NSCLC setting in 2-3L NSCLC Lung HLR >2024 Planned filing TROPION-Breast03 TROPION-Breast04*
Slide 36: Dato-DXd 1L NSCLC development programme
Dato-DXd 1L NSCLC development programme strengthened by TROPION-Lung01 learnings Est epi (US, Europe) – 1L NSCLC ~285k, ~70% IO sensitive PD-L1 <50% and unknown (~75%) PD-L1 ≥ 50% (~25%) Programme to be enriched for Biomarker driven targeted therapy (e.g., Tagrisso) non-squamous population (~30%) AG
Slide 37: AstraZeneca – leading the ADC revolution
AstraZeneca – leading the ADC revolution Establishing AstraZeneca portfolio of differentiated ADCs 1 Target and antibodies Clinical stage trials ongoing in lung, breast, haematology, GYN/GU, and GI Efficient delivery of antibody drug conjugate payload PRECLINICAL PHASE I PHASE II PHASE III INDICATIO
Slide 38: Next wave of ADCs and radioconjugates
AstraZeneca – next wave of ADCs and radioconjugates First-in-class targets Diversified warheads Novel radioconjugates Topoisomerase DNA intercalators + v v Microtubules PROTACS Leveraging surface proteomics Dual payloads for target identification Bispecifics Enabling biology driven combinations and
Slide 39: Advancing our leadership in immuno-oncology
Advancing our leadership in immuno-oncology Cristian Massacesi CHIEF DEVELOPMENT OFFICER, ONCOLOGY & CHIEF MEDICAL OFFICER Dave Fredrickson ONCOLOGY BUSINESS
Slide 40: DUO-E Phase III in advanced endometrial cancer
DUO-E Phase III in advanced endometrial cancer Sixth most common cancer in women with growing incidence over the coming decades CTx phase (6 cycles) Maintenance phase (cycles 7+) Platinum CTx Imfinzi placebo until progression + + Endpoints Newly diagnosed stage III– Imfinzi placebo Lynparza placebo
Slide 41: PFS benefit for both regimens across ITT
PFS benefit for both regimens across ITT Contribution of Lynparza demonstrated by longer PFS in the Imfinzi + Lynparza arm CTx + CTx + Imfinzi CTx Imfinzi + Lynparza N=241 N=238 N=239 Median (range) follow- 12.6 (0.0–31.6) 15.4 (0.0–29.1) 15.4 (0.0–31.7) up,1 months Events, n (%) 173 (71.8) 139 (58.
Slide 42: Consistent PFS benefit across key subgroups
Consistent PFS benefit across key subgroups CTx + Imfinzi à CTx + Imfinzi à Imfinzi + Imfinzi vs CTx Lynparza vs CTx All observed HR point estimates favoured the Imfinzi and Imfinzi + Lynparza arms vs. control Prespecified exploratory subgroup. Stratification factors (disease status [newly diagnosed
Slide 43: Early positive OS trend with both regimens
Early positive OS trend with both regimens CTx + CTx + Imfinzi CTx Imfinzi + Lynparza N=241 N=238 N=239 Events, n (%) 82 (34.0) 65 (27.3) 52 (21.8) Median OS (95% CI),1 25.9 (23.9–NR) NR (NR–NR) NR (NR–NR) months HR (95% CI) vs CTx2 0.77 (0.56–1.07); 0.59 (0.42–0.83); P=0.120 P=0.003 HR (95% CI) vs
Slide 44: Lynparza enhanced benefit in pMMR
Lynparza enhanced benefit in pMMR Consistent with previous trials, CTx + Imfinzi efficacy greatest in dMMR subgroup dMMR subgroup 20% of population pMMR subgroup 80% of population CTx CTx + Imfinzi CTx + Imfinzi + Lynparza CTx CTx + Imfinzi CTx + Imfinzi + Lynparza N=49 N=46 N=48 N=192 N=192 N=191 E
Slide 45: PD-L1 emerging as potential biomarker across ITT
PD-L1 emerging as potential biomarker across ITT PD-L1 positive TAP≥1%; 67% of population PD-L1 negative TAP<1%; 30% of population CTx CTx + Imfinzi CTx + Imfinzi + Lynparza CTx CTx + Imfinzi CTx + Imfinzi + Lynparza N=163 N=170 N=150 N=67 N=61 N=82 Events, n (%) 114 (69.9) 97 (57.1) 68 (45.3) Event
Slide 46: MATTERHORN Phase III trial in resectable GC/GEJC
MATTERHORN Phase III trial in resectable GC/GEJC Early efficacy signal with 12% improvement in key secondary endpoint pCR Clinically relevant pCR benefit Improved downstaging with RealFLOT trial supports pCR as with Imfinzi + FLOT Imfinzi + FLOT predictive for survival ∆12% DFS OS Odds ratio: 3.08 (
Slide 47: Reinforcing IO leadership
Reinforcing IO leadership Data at ESMO reinforces Imfinzi benefit, sets stage for next-wave IO bispecifics >70% of global growth driven by new launches: HIMALAYA (unresectable HCC), TOPAZ-1 (1L BTC), POSEIDON (1L NSCLC) Imfinzi LCM PACIFIC trials GU DUO-O ovarian cancer POTOMAC Non-muscle invasive b
Slide 48: Establishing Tagrisso as backbone TKI in EGFRm NSCLC
Establishing Tagrisso as backbone TKI in EGFRm NSCLC Dave Fredrickson ONCOLOGY BUSINESS
Slide 49: FLAURA2 potential new regimen for 1L EGFRm NSCLC
FLAURA2 potential new regimen for 1L EGFRm NSCLC Builds on established benefit and clinician experience with Tagrisso and CTx Tagrisso monotherapy (FLAURA)1 Tagrisso + CTx (FLAURA2)2 Tagrisso vs. EGFR-TKI comparator Tagrisso + CTx vs. Tagrisso monotherapy Demonstrated OS improvement of 6.8 months wi
Slide 50: Tagrisso as SoC backbone in 1L EGFRm NSCLC
Tagrisso as SoC backbone in 1L EGFRm NSCLC CNS data at ESMO reinforces FLAURA and FLAURA2 positioning Patients with CNS metastases at baseline CNS ORR 59% (cFAS, N=222) and 48% (cEFR, N=78) Tagrisso monotherapy remains 1L SoC ― Oral therapy with strong safety, proven tolerability ― Demonstrated OS o
Slide 51: Q&A Session
Q&A Session Participating speakers and panelists KEY EXTERNAL EXPERT Pascal Soriot, Susan Galbraith, Sunil Verma, Dr Aaron Lisberg, Chief Executive Officer Executive Vice President, Global Head of Thoracic Medical Oncologist, Oncology R&D Oncology, Medical UCLA KEY EXTERNAL EXPERT Dave Fredrickson,
Slide 52: Appendix
Appendix
Slide 53: TROPION-Breast04 Phase III in early TNBC
TROPION-Breast04 Phase III in early TNBC Neoadjuvant Dato-DXd + Imfinzi followed by adjuvant Imfinzi ± CTx vs SoC Neoadjuvant (24 weeks) Adjuvant (9 cycles) Endpoints Stage II-III unilateral or bilateral primary invasive Imfinzi Dato-DXd + Imfinzi breast cancer ± CTx Primary endpoints TNBC or HR-low
Slide 54: TROPION-Breast05 Phase III in 1L PD-L1+ mTNBC
TROPION-Breast05 Phase III in 1L PD-L1+ mTNBC Dato-DXd + Imfinzi vs pembrolizumab + CTx Endpoints Dato-DXd + Imfinzi Metastatic or locally Primary endpoints advanced inoperable TNBC • PFS (BICR) PD-L1+ (CPS ≥ 10 IHC 22C3) Pembrolizumab No prior treatment for advanced disease R + CTx Key secondary en
Slide 55: AstraZeneca in NSCLC
AstraZeneca in NSCLC ― Establishing Tagrisso as backbone TKI in EGFRm ― Imfinzi leading IO in unresectable ― Advancing best-in-class ADCs to replace systemic chemotherapy ― Delivering next-wave bispecifics to improve on PD1/PD-L1 ― Developing novel combinations, including IO + ADCs ― Investing behin
Slide 56: AstraZeneca in Breast Cancer
AstraZeneca in Breast Cancer All numbers are approximate. Illustrative settings and populations, not to scale. 1/2/3/4L = 1st/2nd/3rd/ 4th-line; est epi (G7) = estimated epidemiology across G7 (US, EU5, JP for drug treated patients. HER2 = human epidermal growth factor receptor 2; THP = docetaxel, t
Slide 57: AstraZeneca in HR-positive Breast Cancer
AstraZeneca in HR-positive Breast Cancer All numbers are approximate. Illustrative settings and populations, not to scale. HR = hormone receptor; est epi (G7) = estimated epidemiology across G7 (US, EU5, JP for drug treated patients; SoC = standard of care; ADC = antibody drug conjugate; ET = endocr
Slide 58: Complete and durable CNS responses in FLAURA2
Complete and durable CNS responses in FLAURA2 Deep, sustained CNS response observed for patient in FLAURA2 Patient with CNS leptomeningeal disease has an ongoing deep Tagrisso has clinically established activity in brain and durable sustained response with Tagrisso + CTx Tagrisso monotherapy (cEFR;
Slide 59: Improved CNS PFS by CNS BICR with Tagrisso + CTx
Improved CNS PFS by CNS BICR with Tagrisso + CTx cFAS - Measurable and non-measurable BM cEFR - Measurable BM cFAS (n=222) cEFR (n=78) Measurable + non-measurable BM Measurable BM n (%)2 Tagrisso + CTx (n=118) Tagrisso mono (n=104) Tagrisso + CTx (n=40) Tagrisso mono (n=38) Any CNS RECIST progressio