TROPION-Breast01 Trial

[Slide 1] Are we administering cytotoxics in a too complicated way? Author Dose Schedule N ORR MS (mo) Irinotecan Baker 100 mg/m²/wk X 4 41 6 (15%) 6.2 Fukuoka 100 mg/m²/wk X 4 72 23 (22%) 10.5 Negoro 100 mg/m²/wk X 3 67 23 (34%) NA Douillard 350 mg/m² q 3wk 19 4 (21%) NA Ahn 299 80 (26%) 12.4 Paz Ares 299 41 (14%) 11.1 2024 ASCO #ASCO24 PRESENTED BY) Egbert F Smit MD PhD ASCO INSTRUCAN # GINCAL ANNUAL MEETING Presentation 5 property if the who and ASCO Permission required for RUNE word or ENDWLEDGE CONQUERS CANCER

[Slide 1] Passion for Innovation. Compassion for Patients.™ Daiichi-Sankyo Press Release Datopotamab Deruxtecan Demonstrated Statistically Significant and Clinically Meaningful Progression-Free Survival Benefit in Patients with HR Positive, HER2 Low or Negative Breast Cancer in TROPION-Breast01 Phase 3 Trial First phase 3 results in breast cancer for Daiichi Sankyo and AstraZeneca's datopotamab deruxtecan Plans for global regulatory submissions are underway Tokyo, Munich and Basking Ridge, NJ — (September 22, 2023) — Positive topline results from the TROPION-Breast01 phase 3 trial showed datopotamab deruxtecan (Dato-DXd) demonstrated a statistically significant and clinically meaningful improvement for the primary endpoint of progression- free survival (PFS) compared to investigator's choice of chemotherapy in patients with inoperable or metastatic hormone receptor (HR) positive, HER2 low or negative (IHC 0, IHC 1+ or IHC 2+/ISH-) breast cancer previously treated with endocrine-based therapy and at least one systemic therapy. Datopotamab deruxtecan is a specifically engineered TROP2 directed DXd antibody drug conjugate (ADC) being jointly developed by Daiichi Sankyo (TSE: 4568) and AstraZeneca (LSE/STO/Nasdaq: AZN). Data for the dual primary endpoint of overall survival (OS) were not mature at this interim analysis and the trial will continue as planned to assess OS. --- [Slide 2] First Phase III results in breast cancer for AstraZeneca and Daiichi Sankyo's datopotamab deruxtecan Plans for global regulatory submissions underway Positive high-level results from the TROPION-Breast01 Phase III trial showed datopotamab deruxtecan (Dato-DXd) demonstrated a statistically significant and clinically meaningful improvement for the primary endpoint of progression-free survival (PFS) compared to investigator's choice of chemotherapy in patients with inoperable or metastatic hormone receptor (HR)-positive, HER2-low or negative (IHC 0, IHC 1+ or IHC 2+/ISH-) breast cancer previously treated with endocrine-based therapy and at least one systemic therapy. A trend in improvement for the dual primary endpoint of overall survival (OS) was observed for datopotamab deruxtecan versus chemotherapy. Data for OS were not mature at this interim analysis and the trial will continue as planned to assess OS.

[Slide 1] TROPION-Breast01 Study Design1 Randomized, phase 3, open-label, global study (NCT05104866) Key inclusion criteria: Dato-DXd 6 mg/kg IV Day 1 Q3W Endpoints: Patients with HR+/HER2- breast (n=365) cancer* (HER2- defined as IHC Dual primary: PFS by 0/1+/2+; ISH negative) BICR per RECIST v1.1, 1:1 and OS Previously treated with 1-2 lines of Investigator's choice of chemotherapy (inoperable/metastatic Secondary endpoints setting) chemotherapy (ICC) included: ORR, as per protocol directions PFS (investigator Experienced progression on ET and (eribulin mesylate D1,8 Q3W; vinorelbine D1,8 Q3W; assessed), TFST, for whom ET was unsuitable gemcitabine D1,8 Q3W; capecitabine D1-14 Q3W) safety, PROs ECOG PS 0 or 1 (n=367) Randomization stratified by: Lines of chemotherapy in unresectable/metastatic setting (1 vs 2) Treatment continued until PD, unacceptable tolerability, Geographic location (US/Canada/Europe VS ROW) or other discontinuation criteria Previous CDK4/6 inhibitor (yes vs no) Detailed description of the statistical methods published previously. *Per American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines. ICC was administered as follows: eribulin mesylate, 1.4 mg/m2 IV on Days and 8. Q3W; vinorelbine, 25 mg/m2 IV on Days and 8. Q3W; or gemcitabine, 1000 mg/m2 IV on Days 1 and 8, Q3W; capecitabine, 1000 or 1250 mg/m2 orally twice daily on Days to 14, Q3W (dose per standard institutional practice). CDK4/6, cyclin-dependent kinase 4/6; D. day; ECOG PS, Eastern Cooperative Oncology Group 1. Bardia A, et al. performance status; ET, endocrine therapy: IHC. immunchistochemistry: ISH, in-situ hybridization: IV. intravenous; PD. progressive disease: PROs, patient-reported outcomes; Q3W, every 3 weeks: Future Oncol 2023; RECIST. Response Evaluation Criteria in Solid Tumors: ROW. rest of world; TFST. time to first subsequent therapy. doi: 0.2217/fon-2023-0188. --- [Slide 2] TTD in Global Health Status/Quality of Life 1.0 TTD* in GHS/QoL (confirmed) 0.8 Probability of no deterioration 0.6 0.4 0.2 Dato-DXd (n=365) ICC (n=367) 0.0 0 3 6 9 12 15 18 No. at risk Time from randomization (months) Dato-DXd 365 145 90 37 6 1 0 ICC 367 101 54 19 3 1 0 Median TTD, months Median TTD, months TTD* (first instance) HR (95% CI) (confirmed) HR (95% CI) Dato-DXd ICC Dato-DXd ICC GHS/QoL 3.4 2.1 0.85 (0.68-1.06) 9.0 4.8 0.76 (0.58-0.98) TTD in pain, physical functioning and GHS/QoL are secondary endpoints The primary analysis was based on time to first deterioration, defined as the time from date of randomization to date of first deferioration Sensitivity analysis was based on time to confirmed deterioration, which required deterioration to be confirmed at a subsequent timepoint Deterioration was defined as change from baseline that reached a clinically meaningful deterioration threshold (16 6 for GHS/QoL and pain, 13.3 for physical functioning). GHS/QoL global health status/quality of Me; TTD. time to deterioration San Antonio Breast Cancer Symposium® @SABCSSanAntonio --- [Slide 3] Progression-Free Survival 1.0 PFS by investigator assessment 0.8 Dato-DXd ICC Median PFS, months 6.9 4.5 Probability of PFS 0.6 (95% CI) (5.9-7.1) (4.2-5.5) 55.2% HR (95% CI) 0.64 (0.53-0.76) 0.4 34.7% 36.9% Dato-DXd (n=365) 21.7% ICC (n=367) 0.2 20.9% 9.9% 0.0 0 3 6 9 12 15 18 Number at risk Time from randomization (months) Dato-DXd 365 272 185 74 19 4 0 ICC 367 216 110 43 11 2 0 PFS by BICR (primary endpoint)1: Median 6.9 vs 4.9 months; HR 0.63 (95% CI 0.52-0.76); P<0.0001 Data cut-off: 17 July 2023. 1. Bardia A, et al. Oral Presentation at ESMO 2023; Abstract LBA11. --- [Slide 4] Overall Safety Summary Dato-DXd ICC # Most common TRAEs leading to dose interruption: TRAEs, n (%)1 (n=360) (n=351) - Dato-DXd: fatigue*, infusion-related reaction, ILD, stomatitis (each 1%) All grades 337 (94) 303 (86) — ICC: neutropenia (17%), leukopenia (3%) Grade ≥3 75 (21) 157 (45) Associated with dose reduction 75 (21) 106 (30) . No TRAEs led to discontinuation in ≥1% of patients in either arm Associated with dose interruption 43 (12) 86 (25) Associated with discontinuation 9 (3) 9 (3) . One treatment-related death in the ICC arm due to febrile neutropenia Associated with death 0 1 (0.3) Serious TRAEs 21 (6) 32 (9) Grade ≥3 17 (5) 31 (8) "Fatigue includes the preferred terms of fatigue, asthenia, and malaise. "Neutropenia includes the preferred terms neutropenia and neutrophil count decreased Leukopenia includes the preferred terms of white blood cell count decreased and leukopenia. 1. Bardia A. et al. Oral Presentation ILD, interstitial lung disease; TRAEs, treatment-related adverse events. at ESMO 2023; Abstract LBA11.

[Slide 1] ADCs in ABC HR+/HER2- No cross trial comparison : Different populations, targets Destiny-04 Destiny-06 TROPION-01 TROPiCS-02 Target/ HER2 low HER2 low TROP2 TROP2 Population At least 1 line First line At least 1 line At least 2 lines CT max 2 CT max 2 CT max 4 Design T-DXd vs ICC T-DXd VS ICC Dato-DXd vs SG vs ICC ICC PFS months 10.1 vs 5.4 13.2 vs 8.1 6.9 vs 4.9 5.5 vs 4.0 HR 0.51 HR 0.64 HR 0.63 HR 0.66 0.40-0.64 0.54-0.76 0.52-0.76 0.53-0.83 os months 23.9 vs 17.5 Not mature 18.6 vs 18.3 14.4 vs 11.2 HR 0.64 HR 1.01 HR 0.79 0.48-0.86 0.83-1.22 0.65-0.96 ORR 52.6% VS 16.3% 56.5% vs 32.2% 36.4% VS 22.9% 21% VS 14% « crossover NR 20% 24% NR ADC" D ESMO ON AIR ESMO

[Slide 1] Overall Survival 1.0 Dato-DXd ICC 0.9 0.8 os events, n (%) 223 (61) 213 (58) 0.7 Median OS, months 18.6 18.3 Probability of os 0.6 (95% CI) (17.3-20.1) (17.3-20.5) 0.5 HR (95% CI) 1.01 (0.83-1.22) 0.4 0.3 Maturity: 59.6% 0.2 Dato-DXd (n=365) Median follow-up: 22.8 months 0.1 ICC (n=367) Protocol prespecified OS sensitivity 0 0 3 6 9 12 15 18 21 24 27 30 33 36 analysis based on the stratification Number at risk Time from randomisation (months) factors according to the eCRF*: HR 0.99 (95% CI: 0.82-1.20) Dato-DXd 365 349 331 299 259 227 180 118 49 12 1 ICC 367 335 309 283 249 213 175 123 51 9 1 Data cutoff: 24 July 2024. Pre-specified P-value boundary for OS analysis: α=0.0427. *Mis-stratification between interactive response technology and eCRF <5%. eCRF, electronic case report form. > ESMO ON AIR ESMO