Astrazeneca Plc · LSE:AZN
Astrazeneca — Investor Day (September 2024)
40 slides from Astrazeneca's investor day presentation, Sep 9, 2024
Slide 1: Meet AZN Management: Lung Cancer and QCS
Meet AZN Management: Lung Cancer and QCS Investor event 09 September 2024 | Virtual Webcast This event is not for participants of the 2024 IASLC World Congress on Lung Cancer
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 of 1995, AstraZeneca (hereafter ‘the Group’) provides the following cautionary statement: This document contains certain forward-looking statements wit
Slide 3: Investor Deep Dive | Lung Cancer and QCS Agenda
Investor Deep Dive | Lung Cancer and QCS Agenda AstraZeneca ambition in - Dave Fredrickson, EVP, Oncology Business Lung Cancer Advancing ADC leadership | - Susan Galbraith, EVP, Oncology R&D Improving patient selection Leading in next-generation IO - Susan Galbraith, EVP, Oncology R&D Summary and co
Slide 4: AstraZeneca in Lung Cancer: Speakers and panelists
AstraZeneca in Lung Cancer Speakers and panelists Dave Fredrickson Susan Galbraith EXECUTIVE VICE PRESIDENT, EXECUTIVE VICE PRESIDENT, ONCOLOGY BUSINESS ONCOLOGY R&D Q&A only Sunil Verma Matt Hellmann SVP, GLOBAL HEAD, ONCOLOGY FRANCHISE VP, EARLY ONCOLOGY DEVELOPMENT Leora Horn VP, LATE CLINICAL DE
Slide 5: AstraZeneca ambition in Lung Cancer
AstraZeneca ambition in Lung Cancer Dave Fredrickson Executive Vice President, Oncology Business 5
Slide 6: Ambition – $80bn Total Revenue by 2030 & sustained 2030+ growth
Ambition – $80bn Total Revenue by 2030 & sustained 2030+ growth Working on “today, tomorrow and the day after" Beyond 2030 Illustrative only, not to scale ADCs and Radioconjugates Cell therapy and T-cell engagers Launching key NMEs $80bn Gene therapy AZD0120 rilvegostomig AZD0486 saruparib Next-gene
Slide 7: Pioneering in lung cancer – important step in achieving our strategic ambitions
Pioneering in lung cancer – important step in achieving our strategic ambitions Established leadership in early- and late-stage lung cancer NMEs in late-stage development Investigating novel modalities and combinations Dato-DXd Replace conventional (TROP2 ADC) chemotherapy Transforming care in all E
Slide 8: Strong Phase III pipeline momentum already in 2024
Strong Phase III pipeline momentum already in 2024 Lung cancer LAURA Tagrisso in Stg. III EGFRm NSCLC FLAURA2 OS data TROPION-Lung01 OS data Tagrisso + CTx in EGFRm 1L NSCLC Dato-DXd in 2-3L NSCLC ADRIATIC Imfinzi in LS-SCLC HIMALAYA 5yr OS DESTINY-Breast06 Imfinzi + Imjudo in HCC Enhertu in HER2-lo
Slide 9: Advancing ADC leadership
Advancing ADC leadership Susan Galbraith Executive Vice President, Oncology R&D 9
Slide 10: Dato-DXd strategy in lung cancer
Dato-DXd strategy in lung cancer 1 2 3 4 Advance novel Build on strong Demonstrate efficacy Improve patient combinations across evidence in EGFRm over chemotherapy in selection with QCS early and 1L advanced with Tagrisso late-line setting technology setting combination approach • TROPION-Lung01 Pha
Slide 11: Survival results numerically favoured Dato-DXd in overall population but did not reach statistical significance
Survival results numerically favoured Dato-DXd in overall population but did not reach statistical significance Dato-DXd Docetaxel Overall survival1 N=299 N=305 Median (95% CI), mo 12.9 (11.0–13.9) 11.8 (10.0–12.8) HR (95% CI) 0.94 (0.78–1.14) P value 0.530 Pre-specified boundary (2-sided) 0.045 1.
Slide 12: Clinically meaningful OS improvement seen in NSQ population
Clinically meaningful OS improvement seen in NSQ population Overall survival in non-squamous population Overall survival in squamous population Dato-DXd Docetaxel Dato-DXd Docetaxel Overall survival (N=234) (N=234) Overall survival (N=65) (N=71) Median (95% CI), mo 14.6 (12.4–16.0) 12.3 (10.7–14.0)
Slide 13: Improving patient selection
Improving patient selection Susan Galbraith Executive Vice President, Oncology R&D 13
Slide 14: Why isn’t IHC sufficient to predict Dato-DXd benefit?
Why isn’t IHC sufficient to predict Dato-DXd benefit? Conventional IHC scoring has not predicted Dato-DXd is a TROP2 directed ADC response to TROP2-directed ADCs in NSCLC1,2 with highly plasma-stable linker3,4 • Dato-DXd binds to membrane TROP2 and needs to be internalised for cytotoxic payload to b
Slide 15: What is Quantitative Continuous Scoring (QCS)?
What is Quantitative Continuous Scoring (QCS)? IHC with TROP2 Whole Slide Automated Image Patient Biomarker 1 Assay 2 Imaging 3 Analysis (QCS) 4 Status Determination + ≥75% of tumour cells with TROP2 NMR ≤0.56 -- <75% of tumour cells with TROP2 NMR ≤0.561 Differentiates tumour from Measures OD in ea
Slide 16: What is TROP2 QCS-NMR for Dato-DXd?
What is TROP2 QCS-NMR for Dato-DXd? Normalised Membrane Ratio (NMR) predictive for Cut-point for TROP2 QCS-NMR biomarker positivity Dato-DXd response in TROPION-PanTumor01 using samples from TROPION-Lung01 QCS-NMR cut-points optimised for PFS in Membrane OD Normalised TROPION-Lung01 NSQ/Non-AGA pati
Slide 17: Approximately two-thirds of non-squamous patients were TROP2 QCS-NMR+
Approximately two-thirds of non-squamous patients were TROP2 QCS-NMR+ 76% 66% 63% (n=39/51) (n=179/272) (n=140/221) 44% (n=35/80) Non-squamous Non-squamous, Non-squamous, Squamous non-AGA AGA Histology subgroup, BEP (n=352) • Overall/Grade ≥3 adverse event rates with Dato-DXd were similar regardless
Slide 18: TROP2 QCS-NMR status was predictive of efficacy in the non-squamous/non-AGA BEP
TROP2 QCS-NMR status was predictive of efficacy in the non-squamous/non-AGA BEP (n=221) TROP2 QCS-NMR+ TROP2 QCS-NMR– 100 Dato-DXd Docetaxel Dato-DXd Docetaxel n=68 n=72 n=40 n=41 ORR, % 36.8 15.3 22.5 12.2 75 Median PFS, months 7.2 4.1 4.0 4.4 PFS probability, % PFS HR (95% CI) 0.52 (0.35–0.78) 1.2
Slide 19: TROP2 QCS-NMR status was predictive of efficacy in the broader overall BEP
TROP2 QCS-NMR status was predictive of efficacy in the broader overall BEP (n=352) TROP2 QCS-NMR+ TROP2 QCS-NMR– 100 Dato-DXd Docetaxel Dato-DXd Docetaxel n=107 n=107 n=65 n=73 ORR, % 32.7 10.3 16.9 15.1 75 Median PFS, months 6.9 4.1 2.9 4.0 PFS probability, % PFS HR (95% CI) 0.57 (0.41–0.79) 1.16 (
Slide 20: NeoCOAST-2 investigates Dato-DXd combination with Imfinzi in NSCLC in platform trial
NeoCOAST-2 investigates Dato-DXd combination with Imfinzi in NSCLC in platform trial Neoadjuvant therapy for 4 cycles Q3W Adjuvant therapy for up to 1 year Arm 1: oleclumab + Imfinzi + Efficacy and safety follow-up oleclumab + Imfinzi platinum-doublet CTx1 (N=76) Key eligibility criteria: Arm 2: mon
Slide 21: Promising efficacy observed in Dato-DXd + Imfinzi + CTx compared with doublet CTx containing regimens
Promising efficacy observed in Dato-DXd + Imfinzi + CTx compared with doublet CTx containing regimens Encouraging pCR and mPR rates in Dato-DXd arm1 Higher pCR rates with increasing PD-L1 expression3 NeoCOAST-2 Arm 4 AEGEAN2 Dato-DXd + Imfinzi + CTx Imfinzi + CTx 41.2% (7/17) 33.3% 65.9% (5/15) 25.0
Slide 22: Dato-DXd + Imfinzi + CTx demonstrated strong and consistent benefit with manageable safety profile
Dato-DXd + Imfinzi + CTx demonstrated strong and consistent benefit with manageable safety profile Change in tumour area across PD-L1, Manageable safety profile stage and histology subgroups Neoadjuvant Post-surgery Adjuvant n (%) N=54 N=46 N=25 Any TEAE 53 (98.1) 24 (52.2) 11 (44.0) Any TRAE 52 (96
Slide 23: Early phase data drives confidence in 1L NSCLC trials
Early phase data drives confidence in 1L NSCLC trials Early efficacy data reinforces AE profile enables combination with IO and CTx potential in Phase III combination trials Dato-DXd + Imfinzi + CTx 66% mPR (n=29/44) NeoCOAST-2 Lower bone marrow toxicity confers mPR and pCR1 Dato-DXd + better combin
Slide 24: Learnings from recent Dato-DXd datasets
Learnings from recent Dato-DXd datasets • Dato-DXd showed clinically meaningful median overall survival improvement of 2.3 TROPION-Lung01 months vs docetaxel in previously treated patients final OS1 • Builds on previously met dual primary endpoint of progression-free survival • Results support poten
Slide 25: Next-wave IO bispecifics
Next-wave IO bispecifics Susan Galbraith Executive Vice President, Oncology R&D 25
Slide 26: Leading in next-wave IO bispecifics
Leading in next-wave IO bispecifics Rilvegostomig (PD-1/TIGIT) and volrustomig (PD-1/CTLA-4) unique bispecific design Unique bispecific mechanism of action Growing Phase III programme Cooperative binding in the presence of both checkpoint inhibitors Across tumour types both monotherapy and combinati
Slide 27: Rilvegostomig – promising anti-tumour activity and encouraging safety in mNSCLC in CPI pre-treated patients
Rilvegostomig – promising anti-tumour activity and encouraging safety in mNSCLC in CPI pre-treated patients ESMO 2023 | ARTEMIDE-01 40% Percentage change from baseline in target lesion size over 35% time at RP2D (750mg q3w, Parts A and B; N=54) 31.5% Change in target lesions from baseline (%) 100 30
Slide 28: Rilvegostomig – well tolerated in CPI-naïve mNSCLC
Rilvegostomig – well tolerated in CPI-naïve mNSCLC Patients in were CPI-naïve in Parts C and D Rilvegostomig was generally well tolerated N=95 40% received ≥1 dose of rilvegostomig and had ≥9 weeks follow-up 30% 16.7% 20% had prior chemotherapy for 10.5% metastatic disease1 10% 4.2% 13.5% 0% had liv
Slide 29: Rilvegostomig – encouraging preliminary response rates in CPI-naïve mNSCLC
Rilvegostomig – encouraging preliminary response rates in CPI-naïve mNSCLC in both PD-L1 TPS ≥50% and 1-49% subsets Robust ORR in PD-L1 TPS 1‒49% Stronger ORR in 750 mg cohort for PD-L1 TPS ≥50% 68.2% 61.8% (n=15/22)3 2 (n=21/34) 34.8% 29.0% (n=8/23)1 (n=9/31)1 750 mg, locally assessed 750 mg, centr
Slide 30: Volrustomig – promising efficacy in 1L NSQ NSCLC patients at ESMO 2022
Volrustomig – promising efficacy in 1L NSQ NSCLC patients at ESMO 2022 Phase I/II volrustomig ESMO 2022 | Strong efficacy in combination with CTx, First-in-human in NSCLC1,2 especially in PD-L1 negative NSCLC1 0 Best change from baseline (%) -10 Cohort 1A (n=66) -20 Cohort 1: non- -30 squamous (N=12
Slide 31: Volrustomig – large proportion of PD-L1 expression <1% enrolled
Volrustomig – large proportion of PD-L1 expression <1% enrolled, reflecting unmet need in this population Population of high unmet need Manageable safety profile for volrustomig + CTx Median number of cycles: 6 (range 1-39) 63.6% PD-L1 tumour cell expression <1% 100 97.1 % 75.7% 50 140 patients enro
Slide 32: Volrustomig – promising clinical activity, especially in patients with tumour PD-L1 TC <1%
Volrustomig – promising clinical activity, especially in patients with tumour PD-L1 TC <1% Nearly all patients achieved disease control Encouraging ORR in PD-L1 TC <1% 95.0% 84.9% (75.1-99.9) (77.2-90.8) 65.0% (40.8-84.6) 50.0% 43.7% 42.3% (18.7-81.3) (34.6-53.1) (31.2-54.0) ORR DCR ORR DCR ORR ORR
Slide 33: Lung cancer data reinforce potential for next-wave IO
Lung cancer data reinforce potential for next-wave IO Unique mechanism of action Encouraging efficacy in Phase III trials enhanced based Bispecific design allows for cooperative binding early phase trials on early-phase learnings rilvegostomig • Encouraging ORR rates and PFS for Synchronised, coordi
Slide 34: Summary
Summary Dave Fredrickson Executive Vice President, Oncology Business 34
Slide 35: AstraZeneca in lung cancer – proven execution
AstraZeneca in lung cancer – proven execution Attacking lung cancer from multiple angles Proven ability to deliver companion and with novel combinations diagnostics across portfolio Dato-DXd EGFRm testing rates GPC3 CAR-T AZD9592 (EGFR/cMET) AZD5335 (FRα) 85% >80% Enhertu AZD9793 (GPC3 TCE) Stage IV
Slide 36: Accelerating catalyst path into 2025
Accelerating catalyst path into 2025 Strong cadence of oncology read outs anticipated through 2025 with four pivotal trials in lung cancer Dato-DXd Imfinzi Imfinzi AVANZAR – 1L NSCLC POTOMAC – NMIBC VOLGA – MIBC Enhertu Enhertu Tagrisso DESTINY-Breast11 – DESTINY-Breast09 – SAFFRON – 2L EGFRm NSCLC
Slide 37: Join us in Barcelona for the Meet AstraZeneca Management Event at ESMO
Join us in Barcelona for the Meet AstraZeneca Management Event at ESMO Monday 16 September, 20:00 CEST Register and find more details at: https://www.astrazeneca.com/investor-relations.html 37
Slide 38: Appendix
38 Astrazeneca?
Slide 39: AstraZeneca in Lung Cancer: Oncology tumour maps
A P P E N D I X | Oncology tumour maps AstraZeneca in Lung Cancer Ambition for >50% of lung cancer patients to be eligible for AZN medicine by 2030 resectable unresectable metastatic Stg. I-III Stg. I-II Stg. III 1L 2L+ Leading the future of Est. epi (G7) ~200K ~30K ~70K ~350K ~290K lung cancer trea
Slide 40: Glossary
Glossary 1/2/3L 1st/2nd/3rd line GPC3 glypican-3 PIK3CA phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha AGA actionable genomic alterations HR hazard ratio PD-(L)1 programmed cell death (ligand) 1 AE adverse event HNSCC head and neck squamous cell carcinoma PFS progression-free