Astrazeneca Plc · LSE:AZN
Astrazeneca — ASCO 2022 investor event (American Society of Clinical Oncology Annual Meeting)
43 slides from Astrazeneca's conference presentation, Jun 6, 2022
Slide 1: Meet AZN management: ASCO Symposium 2022
Meet AZN management: American Society of Clinical Oncology (ASCO) Cancers Symposium 2022 For investors and analysts 6 June 2022
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: 1. AstraZeneca @ ASCO 2022
1. AstraZeneca @ ASCO 2022 Pascal Soriot Chief Executive Officer
Slide 4: Speakers
Dr Aleix Prat Pascal Soriot Senior Investigator, DESTINY- Chief Executive Officer Breast04 trial and Head Medical Oncology, Hospital Clínic of Barcelona David Fredrickson Susan Galbraith Executive Vice President, Executive Vice President, Speakers Oncology Business Oncology R&D Cristian Massacesi Su
Slide 5: Agenda
AstraZeneca @ ASCO 2022 Agenda 1 Pascal Soriot Enhertu: the story so far 2 Susan Galbraith Enhertu DESTINY-Breast04 trial 3 Dr Aleix Prat DESTINY-Breast04: redefining cancer treatment 4 Dave Fredrickson What’s next for AZ in Oncology? 5 Susan Galbraith 6 Q&A 5
Slide 6: AstraZeneca: Oncology 2025+
AstraZeneca: Oncology 2025+ Delivering growth through innovation Broad Innovative Strategic business Robust LCM and late-stage pipeline early-stage R&D development LoE profile Continued investment in Using precision approaches Supplementing the pipeline clinical stage pipeline and new modalities to
Slide 7: 108 abstracts with 96 presentations
108 abstracts with Data 96 presentations highlights • Enhertu in breast cancer • One plenary presentation DESTINY-Breast04 • Calquence in CLL • 9 oral presentations Five-year follow up from • 15 poster discussions ASCEND and ELEVATE-TN 4 years of Plenary • 71 posters • MEDI5752 in RCC Presentations
Slide 8: 2. Enhertu: the story so far
2. Enhertu: the story so far Susan Galbraith EVP Oncology R&D
Slide 9: Enhertu: best-in-class HER2-directed antibody drug conjugate
Enhertu: best-in-class HER2-directed antibody drug conjugate 1 Enhertu binding Achieved ✓ Target intensity/ density/clustering ❑ Improve on established HER2+ SoC in ADCC metastatic breast cancer TOP1i/DXd 3 ✓ activity ❑ Expand to multiple HER2-targetable tumour types 2 Internalisation Bystander acti
Slide 10: Enhertu has demonstrated efficacy across multiple cancer types
Enhertu has demonstrated efficacy across multiple cancer types Leading data in breast and expanding into gastric, lung and colorectal neo-adjuvant 1st-line metastatic 2nd-line metastatic 3rd-line metastatic neo-adjuvant post neo-adjuvant replace replace replace HER2-positive chemo + T-DM1 replace ch
Slide 11: Enhertu: potential for activity across spectrum of HER2 expression
Enhertu: potential for activity across spectrum of HER2 expression HER2-null potentially 5-20% HER2-positive HER2-positive breast breast cancer, IHC cancer 3+ 3+ HER2-positive breast cancer, IHC 3+ HER2-positive IHC 3+: ~2 million HER2breast cancer, IHC 3+ receptors per cell HER2-positive HER2-ultra
Slide 12: Results from the J101 Phase I trial paved the way for Enhertu in HER2-low
Results from the J101 Phase I trial paved the way for Enhertu in HER2-low breast cancer Best percentage change in sum Percentage change in of target lesion size from sum of target lesion size from baseline by IHC status baseline by IHC status Promising antitumor activity seen in heavily pretreated H
Slide 13: 3. Enhertu Phase III DESTINY-Breast04 trial
3. Enhertu Phase III DESTINY-Breast04 trial Dr Aleix Prat Senior Investigator, DESTINY- Breast04 trial, and Head Medical Oncology, Hospital Clínic of Barcelona
Slide 14: DESTINY-Breast04 trial design
DESTINY-Breast04 trial design First randomised Phase III trial of T-DXd for HER2-low mBC - An open label, multicenter trial T-DXd 5.4 mg/kg Q3W Patientsa (n = 373) Primary endpoint • HER2-low (IHC 1+ vs IHC 2+/ISH−), unresectable, and/or • PFS by BICR (HR+) HR+ ≈ 480 mBC treated with 1-2 prior lines
Slide 15: Baseline characteristics
Baseline characteristics Hormone receptor-positive All patients T-DXd TPC T-DXd TPC (n = 331) (n = 163) (n = 373) (n = 184) Age, median (range), years 57 (32-80) 56 (28-80) 58 (32-80) 56 (28-80) Female, n (%) 329 (99) 163 (100) 371 (99) 184 (100) Region, n (%) Europe + Israel 149 (45) 73 (45) 166 (4
Slide 16: Prior therapies
Prior therapies Hormone receptor-positive All patients T-DXd TPC T-DXd TPC (n = 331) (n = 163) (n = 373) (n = 184) Lines of systemic therapy (metastatic setting) Median number of lines (range) 3 (1-9) 3 (1-8) 3 (1-9) 3 (1-8) Number of lines, n (%) 1 23 (7) 14 (9) 39 (10) 19 (10) 2 85 (26) 41 (25) 10
Slide 17: Progression-free survival by blinded independent central review
Progression-free survival by blinded independent central review Hormone receptor positive Intention to treat Hormone receptor negative 100 100 Hazard ratio: 0.50 100 Hazard ratio: 0.46 Hazard ratio: 0.51 95% CI, 0.40-0.63 95% CI, 0.24-0.89 95% CI, 0.40-0.64 P <0.0001 Progression-Free Survival Probab
Slide 18: Overall survival by blinded independent central review
Overall survival by blinded independent central review Hormone receptor positive Intention to treat Hormone receptor negative Hazard ratio: 0.64 100 Hazard ratio: 0.48 100 95% CI, 0.48-0.86 Hazard ratio: 0.64 100 95% CI, 0.49-0.84 95% CI, 0.24-0.95 P = 0.0028 P = 0.0010 80 80 Overall Survival Probab
Slide 19: PFS subgroup analysis in HR+ cohort
PFS subgroup analysis in HR+ cohort PFS by blinded independent central review. Based on derived data, which includes protocol deviations. 19 CDK4/6 = cyclin-dependent kinase 4/6; IHC = immunohistochemistry; ISH = in situ hybridization; ECOG = Eastern Cooperative Oncology Group; T-DXd = trastuzumab d
Slide 20: Safety and tolerability
Safety and tolerability • Median treatment duration Safety analysis set – T-DXd: 8.2 months (range, 0.2-33.3) – TPC: 3.5 months (range, 0.3-17.6) T-DXd TPC n (%) (n = 371) (n = 172) • Most common TEAE associated with treatment discontinuation Total patient-years of exposure, yearsa 283.55 63.59 – T-
Slide 21: DESTINY-Breast04 establishes T-DXd as the new standard of care
DESTINY-Breast04 establishes T-DXd as the new standard of care in HER2-low, HR+/HR- mBC • T-DXd is the first HER2-targeted therapy to demonstrate unprecedented statistically significant Efficacy in All Patients and clinically meaningful improvement in PFS and OS (HR+ and HR−) versus TPC Progression-
Slide 22: 3. DESTINY-Breast04: redefining cancer treatment
3. DESTINY-Breast04: redefining cancer treatment Dave Fredrickson EVP Oncology Business
Slide 23: Enhertu: continuing to transform breast cancer
Enhertu: continuing to transform breast cancer 2019: DESTINY-Breast011 2021: DESTINY-Breast032 2022: DESTINY-Breast04 Probability of Progression-Free Survival 1.0 100 Progression-Free Survival probability, % 0.8 80 0.6 60 0.4 40 0.2 20 Censored: 68.5% Censor Events: 31.5% T-DXd (n = 261) T-DM1 (n =
Slide 24: HER2-low breast cancer: visible, but underserved
HER2-low breast cancer: visible, but underserved Patients are numerous and ready to be identified Detailed HER2-ultralow characterisation of HER2 status must become HER2-low/HR- standard HER2-low/HR+ procedure ~90%+ of breast cancer ~20% of HER2+ breast cancer Outcomes are currently poor ~32% 5-year
Slide 25: Enhertu transforms the treatment paradigm
Enhertu transforms the treatment paradigm for HR+ metastatic patients who see limited benefit from current standards of care chemotherapy 2L+ MONARCH-2: post treatment1, 3.4m to 4.4m Mayo Clinic RWE study2, MDACC RWE study3 2L+ ET monotherapy 3.1m Mayo Clinic RWE study chemotherapy 3L+ Mayo Clinic R
Slide 26: Establishing a new standard of care
Establishing a new standard of care Enhertu set to deliver greater benefit than all current therapies beyond second line ~60k HR+ patients in US, EU and Japan 1st line 2nd line 3rd line 4th line 5th line ET monotherapy ET + CDK4/6 inhibitors -Breast06 Other ET combinations -Breast06 1st chemotherapy
Slide 27: 5. What's next for AstraZeneca in Oncology?
5. What’s next for AstraZeneca in Oncology? Susan Galbraith EVP Oncology R&D
Slide 28: Dato-DXd could address triple negative patients
Dato-DXd could address “triple negative” patients TROPION-Breast02 Phase III in HER2-negative/HR-negative breast cancer BEGONIA Arm 7 TROPION-Breast02 (Dato-DXd + Imfinzi) TROP2 targeting in order to redefine TNBC Key eligibility criteria: • Locally recurrent inoperable or metastatic TNBC ORR% (CI):
Slide 29: Positioned to address the full spectrum of breast cancer
Positioned to address the full spectrum of breast cancer with potential for at least seven medicines in monotherapy and combinations Early 1st line 2nd line 3rd line 3rd line+ HER2+ HER2+ Enhertu + potential Enhertu + potential combinations combinations HER2+ HER2-high -displace THP -displace T-DM1,
Slide 30: Dato-DXd: initial TROP2 opportunities
Dato-DXd: initial TROP2 opportunities At least five new Phase III trials planned to commence in the next 18 months Resectable Unresectable Metastatic Stage IB - Stage IA Stage I-II Stage III 1st line 2nd line+ III Chemo- NSCLC Without AGA Surgery SBRT CRT -> IO TROPION-Lung08 TROPION-Lung01 therapy
Slide 31: Capivasertib: oral, potent and selective pan-AKT inhibitor
Capivasertib: oral, potent and selective pan-AKT inhibitor Updated overall survival data from Phase II trial that supported CAPItello-291 FAKTION Phase II trial CAPItello-291 Phase III trial Key eligibility criteria: • post-menopausal women with metastatic ER+ BC • suitable for ET. • < three lines o
Slide 32: AZD8205: ADC targeting B7-H4 protein
AZD8205: ADC targeting B7-H4 protein The first ADC engineered with AstraZeneca’s novel linker-warhead technology From histology to histogram: Encouraging preclinical efficacy quantitative continuous score-based and PARPi-selective combination data image analysis for B7-H4 Avg response, 3.5 mg/kg ORR
Slide 33: MEDI5752: a novel PD-1/CTLA-4 bispecific
MEDI5752: a novel PD-1/CTLA-4 bispecific Potential for improved therapeutic index versus components Deep responses seen across Durable clinical response in Phase I trial a range of tumours including RCC, TNBC, PDL1-low NSCLC, gastric, bladder and colorectal cancer 100 75 Best change in target lesion
Slide 34: MEDI5752 in advanced renal cell carcinoma
MEDI5752 in advanced renal cell carcinoma Deep and durable responses in immunotherapy-naïve patients 1500 mg dose expansion 750 mg dose expansion Emerging efficacy at 750mg responses responses looks similar to 1500mg Change from baseline (%) Change from baseline (%) monotherapy 100 80 100 60 80 40 6
Slide 35: Calquence: best-in-class BTK inhibitor
Calquence: best-in-class BTK inhibitor Superior, durable efficacy and tolerability profile supports long-term use ASCEND ELEVATE-TN relapsed/refractory CLL treatment naïve CLL Calquence + obintuzumab sees strong 84% PFS Calquence sees 62% PFS benefit at four years benefit at five years 35
Slide 36: 6. Question and Answer session
6. Question and Answer session
Slide 37: Panel
Dr Aleix Prat Pascal Soriot Senior Investigator, DESTINY- Chief Executive Officer Breast04 trial and Head Medical Oncology, Hospital Clínic of Barcelona David Fredrickson Susan Galbraith Executive Vice President, Executive Vice President, Panel Oncology Business Oncology R&D Cristian Massacesi Sunil
Slide 38: 7. Appendix
AstraZeneca 7. Appendix
Slide 39: DESTINY-Breast04
DESTINY- Breast04 39
Slide 40: Confirmed objective response rate
Confirmed objective response rate Confirmed Objective Response Rate Hormone receptor–positive Hormone receptor–negative 60 52.6%a 50.0% Complete Response 3.6 50 2.5 Partial Response 40 Percentage 30 49.2 20 16.3% 47.5 16.7% 0.6 10 5.6 15.7 0 11.1 T-DXd (n = 333) TPC (n = 166) T-DXd (n = 40) TPC (n =
Slide 41: Best change in target lesions (all patients)
Best change in target lesions (all patients) 100 T-DXd (n = 348) 100 TPC (n = 156) Best % Change in Sum of Diameters From Baseline 80 80 60 60 ** 40 * 40 * ** 41 20 20 * ** * 00 0 * *** * -20 * * * -20 * * ** ** -40 -40 * *** * -60 ** ** * ** -60 ** ** * * -80 * -80 IHC 1+ IHC 1+ IHC 2+/ISH− * IHC 2
Slide 42: Investor Relations
Andy Barnett Josie Afolabi andrew.barnett@astrazeneca.com josie.afolabi@astrazeneca.com Tom Waldron Morgan Sanford tom.waldron@astrazeneca.com morgan.sanford@astrazeneca.com Investor Christer Gruvris Philip Sparks Relations christer.gruvris@astrazeneca.com philip.sparks1@astrazeneca.com Lauren Swale
Slide 43: Use of AstraZeneca slides from conference calls and webcasts
Use of AstraZeneca slides from conference calls and webcasts 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 available to th
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