Astrazeneca Plc · LSE:AZN
Astrazeneca — Investor Day (September 2024)
55 slides from Astrazeneca's investor day presentation, Sep 16, 2024
Slide 1: Meet AZN Management: WCLC and ESMO 2024
Meet AZN Management: WCLC and ESMO 2024 Investor event 16 September 2024
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: AstraZeneca @ WCLC and ESMO 2024 Agenda
AstraZeneca @ WCLC and ESMO 2024 AstraZeneca ambition in oncology – Pascal Soriot, Chief Executive Officer Agenda Key oncology themes at WCLC and ESMO – Susan Galbraith, EVP, Oncology R&D Dato-DXd – patient selection – Susan Galbraith, EVP, Oncology R&D Prof. Thomas Powles, Professor of Genitourinar
Slide 4: Speakers and panelists
AstraZeneca @ WCLC and ESMO 2024 Speakers and panelists ASTRAZENECA LEADERSHIP KEY EXTERNAL EXPERTS Dave Fredrickson Prof. Thomas Powles Pascal Soriot EXECUTIVE VICE PRESIDENT, UROLOGY MEDICAL ONCOLOGIST, CHIEF EXECUTIVE OFFICER UNIVERSITY OF LONDON AND ONCOLOGY BUSINESS DIRECTOR OF BARTS CANCER CEN
Slide 5: Furthering our Oncology ambition
Furthering our Oncology ambition Pascal Soriot Chief Executive Officer 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: Investing in disruptive categories to drive 2030+ growth
Investing in disruptive categories to drive 2030+ growth Weight management ADCs and Cell therapy and Gene therapy and Next-gen IO bispecifics and risk factors Radioconjugates T-cell engagers gene editing Establish and Develop scalable cell Replace systemic Make cure possible lead in new Replace exis
Slide 8: AstraZeneca – ambition in oncology
AstraZeneca – ambition in oncology Attack cancer from Lead with Treat earlier and smarter multiple angles innovative technology Treatment journey today Data and AI in clinical trials HER2 Accelerating computational TROP2 pathology and QCS Future treatment journey Improving patient outcomes through d
Slide 9: 17 positive oncology readouts since beginning of 2023
17 positive oncology readouts since beginning of 2023 DESTINY-PanTumor02 ADAURA DUO-O FLAURA-2 MATTERHORN AEGEAN Enhertu Tagrisso Imfinzi | Lynparza Tagrisso Imfinzi Imfinzi multiple HER2- OS benefit in advanced ovarian combination regimen first IO + CTx to show resectable NSCLC expressing tumours a
Slide 10: AstraZeneca presence at WCLC and ESMO 2024
AstraZeneca presence at WCLC and ESMO 2024 Susan Galbraith Executive Vice President, Oncology R&D 10
Slide 11: >130 abstract acceptances at WCLC and ESMO
>130 abstracts acceptances 41 oral presentations 74 poster presentations 5 Plenary presentations • QCS-NMR for prediction of Presidential plenary • NIAGARA (LBA5) Presidential plenary efficacy of Dato-DXd (PL02.11) • GEMINI-Gastric (1422P) • NeoCOAST-2 (PL02.07) Presidential plenary • BLUESTAR (606O
Slide 12: WCLC and ESMO 2024 data mark key steps in delivering oncology ambition
WCLC and ESMO 2024 data mark key steps in delivering oncology ambition NIAGARA NeoCOAST-2 Treat earlier and smarter Imfinzi + CTx Dato-DXd + Imfinzi First perioperative IO regimen to extend OS in MIBC Unprecedented pCR observed in early-stage NSCLC Part of broader Imfinzi bladder cancer programme Un
Slide 13: Dato-DXd – patient selection
Dato-DXd – patient selection Susan Galbraith Executive Vice President, Oncology R&D 13
Slide 14: Why is Dato-DXd different from other TROP2 ADCs?
Why is Dato-DXd different from other TROP2 ADCs? Internalisation is a critical component of Dato-DXd mechanism of action Dato-DXd has a differentiated design compared to Plasma-stable linker plays important role in other TROP2-directed ADCs understanding Dato-DXd mechanism of action1 Dato-DXd mAb co
Slide 15: Novel biomarker solution – QCS-NMR for Dato-DXd
Novel biomarker solution – QCS-NMR for Dato-DXd QCS measures features linked to biological effect unlike conventional IHC Challenges of conventional IHC assessed by visual scoring for Dato-DXd QCS IHC TROP2 is highly expressed across tumour and Distinguish tumour vs normal normal tissue Quantify mem
Slide 16: TROP2 QCS-NMR – what is Quantitative Continuous Scoring?
WCLC TROP2 QCS-NMR – 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 f
Slide 17: TROP2 QCS-NMR – cut-points optimised for PFS in TROPION-Lung01
WCLC TROP2 QCS-NMR – cut-points were optimised for PFS in TROPION-Lung01 NSQ/Non-AGA patients 100 Approximately two-thirds of non-squamous PFS survival probability, % patients were TROP2 QCS-NMR+ 75 QCS-NMR biomarker 50 p=0.00054 identified in 76% TROP2 QCS NMR+ 25 TROP2 QCS NMR− TROPION- 66% 63% (3
Slide 18: TROP2 QCS-NMR status predictive of efficacy in TROPION-Lung01
WCLC TROP2 QCS-NMR – TROP2 QCS-NMR status was predictive of efficacy in TROPION-Lung01 Non-squamous/non-AGA BEP (n=221) Overall BEP (n=352) TROP2 QCS-NMR+ TROP2 QCS-NMR– TROP2 QCS-NMR+ TROP2 QCS-NMR– 100 Dato-DXd n=68 Docetaxel n=72 Dato-DXd n=40 Docetaxel n=41 100 Dato-DXd n=107 Docetaxel n=107 Dat
Slide 19: Five 1L Dato-DXd trials ongoing, significant share of potential $5bn+ PYR
Five 1L Dato-DXd trials ongoing, representing significant share of potential $5bn+ PYR1 Robust 1L programme informed by PD-L1 <50% and unknown (~75%) PD-L1 ≥50% (~25%) learnings from TROPION-Lung01 Building on EGFRm evidence base AGA (~30%) TROPION-Lung14 (EGFRm ~50% of AGAs) Dato-DXd + Tagrisso • T
Slide 20: Real-world implementation of QCS follows path of companion diagnostics
Potential real-world implementation of QCS follows same path as other companion diagnostics Centralised testing model Future option for decentralised testing model Slide scanner Image analysis system TROP2 IHC Assay Institutions send 3 slides or Institutions can elect to bring testing in-house with
Slide 21: NIAGARA
NIAGARA Prof. Thomas Powles Urology Medical Oncologist, University of London and Director of Barts Cancer Centre 21
Slide 22: High unmet need remains in muscle-invasive bladder cancer (MIBC)
ESMO High unmet need remains in muscle-invasive bladder cancer (MIBC) • Neoadjuvant cisplatin-based chemotherapy with radical cystectomy improves overall survival vs radical cystectomy alone and has been the recommended treatment for MIBC for the past 40 years2-4, however, ~50% of patients experienc
Slide 23: NIAGARA Phase III trial design in cisplatin-eligible MIBC
ESMO NIAGARA is Phase III trial of patients with cisplatin- eligible MIBC who were planned for radical cystectomy Neoadjuvant Adjuvant 4 cycles 8 cycles Endpoints • Cisplatin-eligible MIBC (cT2–T4aN0/1M0) Dual primary endpoints: Imfinzi 1500 mg iv q3w Imfinzi Radical cystectomy • UC or UC with N=106
Slide 24: NIAGARA multiple testing procedure across endpoints
ESMO NIAGARA was designed with a multiple testing procedure across key primary and secondary endpoints • MTP with alpha-exhaustive recycling and gatekeeping strategy used across dual primary endpoints and then 5% alpha (2-sided) secondary endpoints of OS and 5-year OS • One pCR analysis was planned
Slide 25: Baseline characteristics were generally well balanced
ESMO Baseline characteristics were generally well balanced Imfinzi Comparator Imfinzi Comparator arm arm arm arm Characteristics N=533 N=530 Characteristics N=533 N=530 Age Median, years Tumour stage1, % T2N0 40 40 65 (34–84) 66 (32–83) (range) >T2N0 60 60 Sex, % Male 82 82 PD-L1 High 73 73 Race, %
Slide 26: Imfinzi regimen improved event-free survival vs comparator arm
ESMO Imfinzi regimen improved event-free survival vs comparator arm Imfinzi arm Comparator arm N=533 N=530 Number of events, n (%) 187 (35.1) 246 (46.4) 1.0 12 months Median EFS (95% CI), months NR (NR–NR) 46.1 (32.2–NR) 76.0% 24 months HR (95% CI) 0.68 (0.56–0.82) 0.8 67.8% Stratified log-rank P va
Slide 27: Consistent benefit for EFS across key subgroups
ESMO Consistent benefit for EFS across key subgroups Subgroup Category N Hazard ratio (95% CI) All patients 1063 0.68 (0.56–0.82) Age at randomisation <65 years 499 0.71 (0.53–0.94) ≥65 years 564 0.67 (0.52–0.86) Sex Male 870 0.71 (0.58–0.88) Female 193 0.56 (0.35–0.88) Race White 712 0.71 (0.56–0.8
Slide 28: Demonstrated improvement in overall survival with Imfinzi arm
ESMO Demonstrated improvement in overall survival with Imfinzi arm Imfinzi arm Comparator arm N=533 N=530 12 months 1.0 24 months Number of deaths, n (%) 136 (25.5) 169 (31.9) 89.5% HR (95% CI) 0.75 (0.59–0.93) 82.2% Stratified log-rank P value1 0.0106 0.8 Probability of survival 86.5% 0.6 75.2% 0.4
Slide 29: Consistent OS benefit across subgroups
ESMO Consistent OS benefit across subgroups Subgroup Category N Hazard ratio (95% CI) All patients 1063 0.75 (0.59–0.93) Age at randomisation <65 years 499 0.70 (0.49–0.98) ≥65 years 564 0.80 (0.59–1.07) Sex Male 870 1.02) 0.80 (0.62–1.03) Female 193 0.56 (0.32–0.94) Race White 712 0.70 (0.53–0.90)
Slide 30: Imfinzi regimen generally well tolerated
ESMO Imfinzi regimen generally well tolerated Imfinzi arm Comparator arm Overall study period (unless otherwise stated) N=530 N=526 AEs of any cause, n (%) 527 (99) 525 (100) Maximum grade 3 or 4 368 (69) 355 (68) Serious AEs 326 (62) 287 (55) Outcome of death 27 (5) 29 (6) Leading to discontinuatio
Slide 31: Common AEs in line with known profile for the regimen
ESMO Common AEs in line with known profile for the regimen Proportion of patients with AE (%) Nausea Nausea 54 1.5 1.0 49 Anaemia Anemia 39 13.8 15.0 41 Constipation Constipation 39 0.8 0.8 39 Fatigue Fatigue 36 1.5 1.9 32 Urinary tract infection UTI 30 14.2 13.3 29 Decreased Decreased appetite appe
Slide 32: Conclusions
ESMO Conclusions • NIAGARA is the first Phase 3 perioperative immunotherapy study in MIBC and has demonstrated a statistically significant and clinically meaningful improvement in EFS and OS • EFS and OS benefits with Imfinzi were consistent across subgroups • The pCR results and the significant OS
Slide 33: AstraZeneca in bladder cancer
AstraZeneca in bladder cancer Sunil Verma SVP, Global Head, Oncology Franchise 33
Slide 34: NIAGARA establishes AstraZeneca as a key player in bladder cancer
NIAGARA establishes AstraZeneca as a key player in $1bn+* bladder cancer NIAGARA addresses significant need in MIBC NMIBC MIBC 1L mUC ~70% ~20% ~10% ~120k MIBC patients High risk pts ~45% Cisplatin-eligible ~50% NILE across G8 NILE NIAGARA Imfinzi + POTOMAC Neoadj. Imfinzi / gemcitabine/ Imfinzi + g
Slide 35: Multiple reasons for confidence in NIAGARA success
Multiple reasons for confidence in NIAGARA success IO and CTx approach PACIFIC AEGEAN ADRIATIC demonstrated efficacy in early-stage disease MATTERHORN NIAGARA Imfinzi well Experience from other HCPs confident using characterised indications e.g. lung, breast perioperative IO safety profile HCP and p
Slide 36: Q&A Session I
Q&A Session I AstraZeneca @ WCLC and ESMO 2024 ASTRAZENECA LEADERSHIP KEY EXTERNAL EXPERTS Dave Fredrickson Prof. Thomas Powles Pascal Soriot EXECUTIVE VICE PRESIDENT, UROLOGY MEDICAL ONCOLOGIST, CHIEF EXECUTIVE OFFICER UNIVERSITY OF LONDON AND ONCOLOGY BUSINESS DIRECTOR OF BARTS CANCER CENTRE Susan
Slide 37: Driving the ADC revolution
Driving the ADC revolution Matt Hellmann VP, Early Oncology Development 37
Slide 38: Expanding leadership position in growing ADC market
Expanding leadership position in growing ADC market Growing global ADC market, estimated Well positioned to lead with different payloads and externally to exceed $45bn by 20301 opportunity for combinations across portfolio Other Payloads + alternative TOPO1 MTIs MoAs FRα match disease biology CD30 C
Slide 39: AstraZeneca ADC programme designed to address unmet need across multiple tumour types
AstraZeneca ADC programme designed to address unmet need across multiple tumour types Six wholly owned clinical-stage ADCs Novel ADCs at ESMO 2024 PRECLINICAL PHASE I PHASE II PHASE III INDICATIONS OF INTEREST AZD8205 B7H4 B7H4 (B7H4) Breast, BTC, ovarian, Puxitatug samrotecan AZD5335 DAR 8 endometr
Slide 40: PK profiles of AZD8205 and AZD5335 demonstrate linker stability
PK profiles of AZD8205 and AZD5335 demonstrate stability of linker in AstraZeneca platform and support Q3W dosing AZD82051 AZD53352 Similar ADC and mAb profiles confirm AstraZeneca 100 100 platform linker-payload Plasma concentration (nM) Plasma concentration (nM) Anti-FRα Anti-B7H4 mAB mAB ADC stab
Slide 41: AZD8205 – promising efficacy in heavily pre-treated patients
ESMO AZD8205 – promising efficacy in heavily pre-treated patients with ovarian, breast and endometrial cancer 20.5% ORR with doses ≥1.6 mg/kg across B7-H4 levels B7H4 exciting new target highly expressed in range of solid tumours 50 EC OC BC CCA 40 (PR: 3/7) (PR: 3/17) (PR: 3/12) (PR: 0/10) 30 Preli
Slide 42: AZD5335 – differentiated efficacy in platinum-resistant ovarian cancer
ESMO AZD5335 – differentiated efficacy in heavily pretreated patients with platinum-resistant relapsed ovarian cancer Overall ORR1 of 34.2% with responses observed at all doses 55.6% cORR in FRα high at doses ≥1.6 mg/kg 100 AZD5335 dose 0.8 mg/kg 80 1.6 mg/kg 41.7% ORR in FRα low 2.0 mg/kg 60 2.4 mg
Slide 43: Next-generation IO bispecifics
Next-generation IO bispecifics Cristian Massacesi Chief Medical Officer & Oncology Chief Development Officer 43
Slide 44: 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 45: rilvegostomig – preliminary response rates in CPI-naïve metastatic NSCLC
WCLC rilvegostomig – encouraging preliminary response rates and durable responses in CPI-naïve metastatic NSCLC Responses observed across CPI-naïve NSCLC Durable responses across both PD-L1 40 TPS ≥50% and 1-49% subgroups * * * * * → → → → →→ →→ → → →→ →→→→→ → →→→→→ → → →→→→→→→→ →→→ Ch Ch Ch ChCh ba
Slide 46: rilvegostomig – differentiated safety profile enables CTx combination in gastric and GEJ cancers
ESMO rilvegostomig – differentiated safety profile enables CTx combination in gastric and GEJ cancers Durable responses for rilvegostomig + CTx in locally advanced/ metastatic gastric and GEJ cancers Favourable 62.5% cORR, mPFS of 8.3 months across ITT In CPS ≥5 cORR was 81.3% and mPFS was 11.1 mont
Slide 47: volrustomig + CTx – promising activity in PD-L1<1% population
WCLC volrustomig + CTx – promising activity, particularly in PD-L1<1% population, a group with high unmet need 43.7% ORR in non-squamous patients with 84.9% DCR (n=119) Meaningful ORR, durable responses 100 PD-L1 TC: NE <1% 1 – 49% ≥50% and encouraging PFS in PD-L1 TC <1% 80 60 Best change from base
Slide 48: Closing remarks
Closing remarks Dave Fredrickson Executive Vice President, Oncology Business 48
Slide 49: AstraZeneca – ambition in oncology
AstraZeneca – ambition in oncology Illustrative only, not to scale Launching NMEs1 Beyond 2030 AZD0120 Sustained leadership in AZD0486 disruptive categories camizestrant ADCs • Radioconjugates • IO bispecifics Existing portfolio1 Dato-DXd • cell therapy • T-cell engagers rilvegostomig saruparib Broa
Slide 50: Significant oncology news flow across key medicines through 2025
Significant oncology news flow across key medicines through 2025 2024 2025 Imfinzi Tagrisso Enhertu Dato-DXd Dato-DXd + Imfinzi Imfinzi + ceralasertib ADRIATIC LAURA DESTINY-Breast06 TROPION-Breast01 AVANZAR LATIFY ASCO plenary (June 2024) ASCO plenary (June’24) ASCO LBA (June 2024) regulatory decis
Slide 51: Q&A Session II
Q&A Session II AstraZeneca @ WCLC and ESMO 2024 ASTRAZENECA LEADERSHIP Pascal Soriot Dave Fredrickson EXECUTIVE VICE PRESIDENT, CHIEF EXECUTIVE OFFICER ONCOLOGY BUSINESS Susan Galbraith Cristian Massacesi CHIEF MEDICAL OFFICER & EXECUTIVE VICE PRESIDENT, ONCOLOGY CHIEF ONCOLOGY R&D DEVELOPMENT OFFIC
Slide 52: Appendix
Appendix Lung and breast tumour maps 52
Slide 53: AstraZeneca in lung cancer
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 54: AstraZeneca in breast cancer
A P P E N D I X | Oncology tumour maps AstraZeneca in breast cancer Ambition to eliminate breast cancer as a cause of death established SoC Early Metastatic Neoadjuvant Adjuvant 1st line 2nd line 3rd line 4th line + Est. epi (G7) 540k 125k 90k 65k 55k Enhertu ± THP NSTà residual disease à HER2-posit
Slide 55: Glossary
Glossary 1/2/3L 1st/2nd/3rd line GC gastric cancer PTEN phosphatase and tensin homolog AAV adeno-associated viruses GEJC gastroesophageal junction adenocarcinoma PIK3CA phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic AGA actionable genomic alterations GLP-1 glucagon-like-peptide-1 subunit a