#1Passion for Innovation. Compassion for Patients™ Daiichi-Sankyo ESMO Highlights 2023 DAIICHI SANKYO CO., LTD. Oct 24th (Japan), 2023#2Forward-Looking Statements Daiichi-Sankyo Management strategies and plans, financial forecasts, future projections and policies, and R&D information that Daiichi Sankyo discloses in this material are all classified as Daiichi Sankyo's future prospects. These forward looking statements were determined by Daiichi Sankyo based on information obtained as of today with certain assumptions, premises and future forecasts, and thus, there are various inherent risks as well as uncertainties involved. As such, please note that actual results of Daiichi Sankyo may diverge materially from Daiichi Sankyo's outlook or the content of this material. Furthermore, there is no assurance that any forward-looking statements in this material will be realized. Regardless of the actual results or facts, Daiichi Sankyo is not obliged and does not have in its policy the duty to update the content of this material from the date of this material onward. Some of the compounds under discussion are investigational agents and are not approved by the FDA or any other regulatory agency worldwide as a treatment for indications under investigation. Efficacy and safety have not been established in areas under investigation. There are no guarantee that these compounds will become commercially available in indications under investigation. Daiichi Sankyo takes reasonable care to ensure the accuracy of the content of this material, but shall not be obliged to guarantee the absolute accuracy, appropriateness, completeness and feasibility, etc. of the information described in this material. Furthermore, any information regarding companies, organizations or any other matters outside the Daiichi Sankyo Group that is described within this material has been compiled or cited using publicly available information or other information, and Daiichi Sankyo has not performed in-house inspection of the accuracy, appropriateness, completeness and feasibility, etc. of such information, and does not guarantee the accuracy thereof. The information described in this material may be changed hereafter without notice. Accordingly, this material or the information described herein should be used at your own judgment, together with any other information you may otherwise obtain. This material does not constitute a solicitation of application to acquire or an offer to sell any security in the United States, Japan or elsewhere. This material disclosed here is for reference purposes only. Final investment decisions should be made at your own discretion. Daiichi Sankyo assumes no responsibility for any damages resulting from the use of this material or its content, including without limitation damages related to the use of erroneous information. 2#3ESMO Highlights 2023 Agenda ESMO presentations ✓ TROPION-Lung01 study TLR ✓ TROPION-Lung05 Ph2 study results ✓ TROPION-Breast01 study TLR ✓ BEGONIA study longer follow-up data ✓ DESTINY-Pan Tumor02 primary analysis data ✓ DS-6000 Ph1 study OVC subgroup analysis data ✓ DS-7300 Ph1/2 study updated data (extract) 2 Q&A Speakers Ken Takeshita Head of Global R&D Daiichi-Sankyo Mark Rutstein Head of Global Oncology Clinical Development Content will be delivered on-demand after the meeting 3#4Datopotamab deruxtecan (Dato-DXd) vs docetaxel in previously treated advanced/metastatic (adv/met) non-small cell lung cancer (NSCLC): Results of the randomized phase 3 study TROPION-Lung01 Myung-Ju Ahn,1,a Aaron Lisberg, 2,a,b Luis Paz-Ares,³ Robin Cornelissen, 4 Nicolas Girard, 5 Elvire Pons-Tostivint, 6 David Vicente Baz, Shunichi Sugawara, Manuel Angel Cobo,⁹ Maurice Pérol, 10 Céline Mascaux, 11 Elena Poddubskaya, 12 Satoru Kitazono, 13 Hidetoshi Hayashi, 14 Jacob Sands, 15 Richard Hall, 16 Yong Zhang, 17 Hong Zebger-Gong, 18 Deise Uema, 17 Isamu Okamoto 19 aEqual contribution as first author. Indicates presenting author. 1Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea; 2David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; ³Hospital Universitario 12 de Octubre, CNIO-H120 Lung Cancer Unit, Universidad Complutense & CiberOnc, Madrid, Spain; 4Erasmus MC Cancer Institute, Rotterdam, The Netherlands; 5Institut Curie, Paris, France; 6Centre Hospitalier Universitaire de Nantes, Nantes, France; Hospital Universitario Virgen Macarena, Seville, Spain; 8Sendai Kousei Hospital, Sendai, Japan; FEA Oncología Médica, Medical Oncology Intercenter Unit, Regional and Virgen de la Victoria University Hospitals, IBIMA, Málaga, Spain; 10 Centre Léon Bérard, Lyon, France; 11Hôpitaux Universitaires de Strasbourg (CHRU), Strasbourg, France; 12Vitamed LLC, Moscow, Russia; 13The Cancer Institute Hospital of JFCR, Tokyo, Japan; 14Kindai University, Osaka, Japan; 15Dana-Farber Cancer Institute, Boston, MA, USA; 16University of Virginia Health System, Charlottesville, VA, USA; 17Daiichi Sankyo, Inc, Basking Ridge, NJ, USA; 18 Daiichi Sankyo Europe GmbH, Munich, Germany; 19 Kyushu University Hospital, Fukuoka, Japan Daiichi-Sankyo 4#5Background Standard-of-care, second-line chemotherapy for metastatic 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 payload directly into tumor cells¹ Promising antitumor activity was seen with Dato-DXd in patients with adv/met NSCLC in the phase 1 TROPION-PanTumor01 trial (26% ORR)1 Dato-DXd: Humanized anti-TROP2 IgG1 mAb²-5 Deruxtecan H H.C- Daiichi-Sankyo HO -CH₂ Cleavable tetrapeptide-based linker Topo-l inhibitor payload (DXd) Image is for illustrative purposes only; actual drug positions may vary. ADC, antibody-drug conjugate; adv/met, advanced/metastatic; Dato-DXd, datopotamab deruxtecan; IgG1, immunoglobulin G1; mAb, monoclonal antibody; NSCLC, non-small cell lung cancer; ORR, objective response rate; TROP2, trophoblast cell-surface antigen 2. 1. Shimizu T, et al. J Clin Oncol. 2023;41:4678-4687. 2. Okajima D, et al. Mol Cancer Ther. 2021;20:2329-2340. 3. Nakada T, et al. Chem Pharm Bull (Tokyo). 2019;67:173-185. 4. Ogitani Y, et al. Clin Cancer Res. 2016;22:5097-5108. 5. Ogitani Y, et al. Cancer Sci. 2016;107:1039-1046. 5#6Daiichi-Sankyo TROPION-Lung01 Study Design Randomized, Phase 3, Open-Label, Global Study (NCT04656652) Key Eligibility Criteria NSCLC (stage IIIB, IIIC, or IV) ECOG PS of 0 or 1 • No prior docetaxel Without actionable genomic alterationsª Dato-DXd 6 mg/kg Q3W (N=299) • 1 or 2 prior lines, including platinum CT and anti-PD-(L)1 mAb therapy With actionable genomic alterations • Positive for EGFR, ALK, NTRK, BRAF, ROS1. • MET exon 14 skipping, or RET 1 or 2 prior approved targeted therapies + platinum-based CT, and ≤1 anti-PD-(L)1 mAb Enrollment period: 19 February 2021 to 7 November 2022. R 1:1 Docetaxel Dual Primary Endpoints • PFS by BICR OS Secondary Endpoints • ORR by BICR • 75 mg/m² Q3W (N=305) DOR by BICR • Safety Stratified by: histology, actionable genomic alteration,c anti-PD-(L)1 mAb included in most recent prior therapy, geographyd BICR, blinded independent central review, CT, chemotherapy; DOR, duration of response; ECOG PS, Eastern Cooperative Oncology Group performance status; mAb, monoclonal antibody; NSCLC, non-small cell lung cancer, ORR, objective response rate; OS, overall survival; PD-(L)1, programmed cell death 1 (ligand 1); PFS, progression-free survival; Q3W, every 3 weeks; R, randomized. *Patients with KRAS mutations in the absence of known actionable genomic alterations are eligible; must meet prior therapy requirements for patients without actionable genomic alterations. "Squamous vs non-squamous. *Presence vs absence. "United States/Japan/Western Europe vs rest of world. 6#7Demographics and Baseline Characteristics Daiichi-Sankyo Dato-DXd Docetaxel Characteristic Dato-DXd N=299 Docetaxel N=305 Characteristic N=299 N=305 Age, median (range), years 63 (26-84) 64 (24-88) Current or former smoker, n (%) 238 (80) 251 (82) Present 50 (17) 51 (17) Male, n (%) 183 (61) 210 (69) Actionable genomic alterations, n (%) EGFR mutation 39 (13) 45 (15) Asian 119 (40) 120 (39) White 123 (41) 126 (41) Brain metastasis at baseline, n (%) b 50 (17) 47 (15) Race, n (%) 1 167 (56) 174 (57) Black or African American 6 (2) 4 (1) Prior lines of therapy, Othera 51 (17) 55 (18) 2 108 (36) 102 (33) n (%) ≥3 22 (7) 28 (9) 0 89 (30) 94 (31) ECOG PS, n (%) 1 210 (70) 211 (69) Platinum containing 297 (99) 305 (100) Non-squamous 234 (78) 234 (77) Previous systemic therapy, n (%) Histology, n (%) Squamous 65 (22) 71 (23) Anti-PD-(L)1 Targeted 263 (88) 268 (88) 46 (15) 50 (16) ECOG PS, Eastern Cooperative Oncology Group performance status; PD-(L)1, programmed cell death 1 (ligand 1). *Race data missing for 8 patients in each arm. "Patients who are no longer symptomatic and who require no treatment with corticosteroids and anticonvulsants and have recovered from acute toxic effects of radiation are eligible. In the Dato-DXd arm, 2 patients did not receive prior treatment with a platinum-containing therapy and 1 patient with actionable genomic alterations did not receive previous targeted therapy, deviating from the protocol. Data cutoff 29 March 2023. 7#8Patient Disposition Disposition, n (%) Dato-DXd Docetaxel N=297 N=290 Treatment status Ongoing on study treatment 52 (18) 17 (6) 245 (83) 273 (94) Discontinued from study treatment Treatment duration 118 (40) 168 (58) 0-3 months 73 (25) 66 (23) >3 to ≤6 months 47 (16) 34 (12) >6 to ≤9 months 59 (20) 22 (8) >9 months Primary reason for treatment discontinuation 39 (13) 46 (16) Adverse event Progressive disease 173 (58) 180 (62) 9 (3) 11 (4) Clinical progression Withdrawal/physician decision 12 (4) 23 (8) 10 (3) 10 (3) Death 2 (1) 3 (1) Other Median study follow-up: Dato-DXd - 13.1 months; docetaxel - 13.0 months Daiichi-Sankyo 8#9Progression-Free Survival: ITT 100 80 Median (95% CI), monthsa HR P-value Dato-DXd Docetaxel 4.4 (4.2-5.6) 3.7 (2.9-4.2) 0.75 (0.62-0.91) PFS probability, % 60 50 40.8 40 30.1 20 20 + Censored 28.2 17.8 0.004 Prespecified 0.008 boundary (2-sided) 0 T 0 2 со 8 10 No. at risk: Time since randomization, months Dato-DXd 299 216 156 96 74 46 Docetaxel 305 186 120 63 42 19 Dato-DXd ORR (95% CI), %b DOR (95% CI), mo 26.4 (21.5-31.8) 7.1 (5.6-10.9) 12 14 16 18 24 14 10 7 NO 2 0 O O 0 Docetaxel 12.8 (9.3-17.1) 5.6 (5.4-8.1) CR, complete response; DOR, duration of response; HR, hazard ratio; ITT, intention to treat; ORR, objective response rate; PFS, progression-free survival; PR, partial response. *Median PFS follow-up was 10.9 (95% CI, 9.8-12.5) and 9.6 (95% CI, 8.2-11.9) months for Dato-DXd and docetaxel, respectively. "Included 4 CRs and 75 PRs for Dato-DXd and 39 PRs for docetaxel. Daiichi-Sankyo 9#10PFS in Key Subgroups Age at randomization <65 years Sex ≥65 years Male Female 60/95 Race Asian Events/n Dato-DXd Docetaxel 118/162 115/155 95/137 103/150 136/183 158/210 77/116 76/119 82/120 HR H 0.67 0.83 0.79 0.71 0.77 Non-Asian Smoking status Never Former/current Brain metastasis at With baseline Without 131/172 36/61 33/52 177/238 184/251 33/50 31/47 180/249 187/258 129/177 0.76 0.67 0.77 0.64 0.76 Non-squamous Histology Squamous 156/229 168/232 50/73 0.63 Actionable genomic Absent 57/70 189/252 184/255 1.38 0.84 alterationsa Present 24/47 34/50 0.38 *Regardless of histology. 0 0.5 1.5 2 Hazard ratio 2.5 Daiichi-Sankyo 10#11PFS by Histology 100 80 Non-squamous (with and without AGAs) Median (95% CI), months HR Dato-DXd 100 Docetaxel 5.6 (4.4-7.0) 3.7 (2.9-4.2) 80- PFS probability, % 50 T 40 20 + Censored 0.63 (0.51-0.78) ORR, % 31.2 12.8 DOR, months 7.7 5.6 PFS probability, % 10 20 + Censored Daiichi-Sankyo Squamous (with and without AGAs) Median (95% CI), months HR Dato-DXd Docetaxel 2.8 (1.9-4.0) 3.9 (2.8-4.5) 1.38 (0.94-2.02) ORR, % 9.2 12.7 DOR, months 5.9 8.1 0 2 6 0 8 10 12 14 16 18 0 2 6 8 10 12 14 16 18 Time since randomization, months Time since randomization, months No. at risk Dato-DXd 229 178 134 86 68 41 20 Docetaxel 232 135 90 50 32 14 10 No. at risk 0 Dato-DXd 70 38 22 10 0 0 Docetaxel 73 51 30 13 03 65 4 3 1 0 10 5 3 PFS HR for non-squamous without AGAs: 0.71 (0.56, 0.91) AGA, actionable genomic alteration; DOR, duration of response; HR, hazard ratio; ORR, objective response ratel PFS, progression-free survival. Squamous subset included 3 patients with AGAS 11#12Daiichi-Sankyo Interim Overall Survival: ITT 100 80 Median (95% CI), monthsa HR Dato-DXd 12.4 (10.8-14.8) Docetaxel 11.0 (9.8-12.5) 0.90 (0.72-1.13) OS probability, % 60- 40 40 20 20 + Censored 2 4 60 10 12 14 16 18 20 20 22 Time since randomization, months No. at risk Dato-DXd 299 273 243 201 166 121 85 56 Docetaxel 305 273 239 193 156 115 76 42 32 33 14 6 29 13 4 Non-squamous HR (95% CI): 0.77 (0.59-1.01); Squamous HR (95% CI): 1.32 (0.87-2.00) Trial is continuing to final OS analysis HR, hazard ratio; ITT, intention to treat, OS, overall survival. *Median OS follow-up was 11.8 (95% CI, 11.3-12.7) and 11.7 (95% CI, 10.9-12.9) months for Dato-DXd and docetaxel, respectively. Information fraction at interim analysis (events/total events required): 74%. 12#13Overall Safety Summary TRAES, n (%) Dato-DXd N=297 Docetaxel N=290 • 257 (87) 252 (87) All grades Grade ≥3 73 (25) 120 (41) Associated with dose reduction 58 (20) 85 (29) • Associated with dose delay 49 (17) 31 (11) Associated with discontinuation 23 (8) 34 (12) • Associated with deatha 3 (1) 2 (1) Serious TRAES 30 (10) 36 (12) Grade ≥3 25 (8) 33 (11) Daiichi-Sankyo The median treatment durations for Dato-DXd and docetaxel were 4.2 and 2.8 months, respectively Fewer grade ≥3 TRAES were observed with Dato-DXd compared with docetaxel Fewer TRAES leading to dose reductions or discontinuations were seen with Dato-DXd compared with docetaxel ILD, interstitial lung disease; TRAE, treatment-related adverse event. *Investigator assessed. Dato-DXd: 2 cases of ILD/pneumonitis and 1 case of sepsis; docetaxel: 1 case of ILD/pneumonitis and 1 case of septic shock. The safety analysis set included all randomized patients who received 21 dose of the study drug. 13#14TRAES Occurring in ≥10% of Patients Dato-DXd N=297 Docetaxel N=290 System organ class Preferred term, n (%) Blood and lymphatic system Any grade Grade ≥3 Any grade Grade ≥3 Anemia Neutropeniaª Gastrointestinal Stomatitis 43 (15) 11(4) 59 (20) 12(4) 2(1) 76 (26) 11(4) 68 (23) 140 (47) 19(6) 45 (16) 3(1) Nausea 100 (34) 7(2) 48 (17) 3(1) Vomiting 38 (13) 3 (1) 22(8) 1 (0.3) Constipation 29 (10) 0 30 (10) 0 Diarrhea 28 (9) 1 (0.3) 55 (19) 4(1) General Asthenia 55 (19) 8 (3) 55 (19) 5(2) Fatigue 34 (11) 2(1) 40 (14) 6(2) Metabolism and nutrition Decreased appetite 68 (23) 1 (0.3) 45 (16) 1 (0.3) Skin and subcutaneous Alopecia 95 (32) 0 101 (35) 1 (0.3)b Rash 36 (12) 0 18 (6) 0 Pruritus 30 (10) 0 12(4) 0 TRAE, treatment-related adverse event. *This category includes the preferred terms "neutropenia" and "neutrophil count decreased". "Includes an event incorrectly reported as grade 3. • Stomatitis and nausea were the most Daiichi-Sankyo frequent TRAEs seen with Dato-DXd and were predominantly grade 1 or 2 Hematologic toxicities, including neutropenia and febrile neutropenia, were more common with docetaxel • No new safety signals were observed with Dato-DXd 14#15Daiichi-Sankyo Adverse Events of Special Interest Dato-DXd N=297 Docetaxel N=290 AESI, n (%) Stomatitis/oral mucositisa All grades 160 (54) 59 (20) Grade ≥3 19 (6) 4 (1) Ocular eventsb All grades 57 (19) 27 (9) Grade ≥3 5 (2)c 0 Adjudicated drug-related ILDd 25 (8) 12 (4) All grades Grade ≥3 Grade 5 10 (3) 7 (2) 4 (1) 1 (0.3) • Stomatitis/oral mucositis associated with Dato-DXd resulted in a low rate of discontinuation (0.7%) Dry eye was the most common ocular event seen with Dato-DXd (6.1%; primarily grade ≤2), followed by increased lacrimation (5.4%) Seven adjudicated drug-related grade 5 ILD events • • Primary cause of death in 4 out of 7 was attributed to disease progression by investigator Non-squamous: 4 of 232 patients (1.7%); Squamous: 3 of 65 patients (4.6%)e IRRs were observed in 24 patients (8%) with either Dato-DXd or docetaxel; all were grade ≤2 with the exception of 1 grade 3 event AESI, adverse event of special interest; ILD, interstitial lung disease; IRR, infusion-related reaction; MedDRA, Medical Dictionary for Regulatory Activities; PT, preferred term; SMQ, standardized MedDRA query; SOC, system organ class. AESIs listed in this slide are treatment emergent and include all PTs that define the medical concept. *Events included the selected PTs oral mucositis/stomatitis, oropharyngeal pain, mouth ulceration, odynophagia, dysphagia, oral pain, glossitis, pharyngeal inflammation, aphthous ulcer, and oral mucosa erosion. "Ocular events included selected PTs from the corneal disorder SMQ and selected relevant PTs from the eye disorder SOC. "Included 4 cases of keratitis and 1 case of ulcerative keratitis. "ILD includes events that were adjudicated as ILD and related to use of Dato-DXd or docetaxel (includes cases of potential ILD/pneumonitis based on MedDRA v26.0 for the narrow ILD SMQ, selected terms from the broad ILD SMQ, and PTs of respiratory failure and acute respiratory failure). *Among treated patients, histology information per the case report form. 15#16Conclusions . . • 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 no new safety signals were observed with Dato-DXd Grade ≥3 ILD was seen, highlighting the need for careful monitoring and adherence to ILD management guidelines The interim OS findings favor Dato-DXd, and the trial is continuing to final analysis Dato-DXd is a potential new meaningful therapy for patients with previously treated non-squamous NSCLC ADC, antibody-drug conjugate; ILD, interstitial lung disease; NSCLC, non-small cell lung cancer, OS, overall survival; PFS, progression-free survival; TRAE, treatment-related adverse event. Daiichi-Sankyo 16#17TROPION-Lung05: Datopotamab deruxtecan (Dato-DXd) in previously treated non-small cell lung cancer with actionable genomic alterations Luis Paz-Ares,¹ Myung-Ju Ahn,² Aaron Lisberg,³ Satoru Kitazono, 4 Byoung Chul Cho, 5 George Blumenschein Jr, Elaine Shum, 7 Elvire Pons Tostivint, Yasushi Goto,⁹ Kiyotaka Yoh,10 Rebecca Heist, 11 Paul Baas, 12 David Planchard, 13 Maurice Pérol, 14 Enriqueta Felip, 15 Wu-Chou Su, 16 Hong Zebger-Gong, 17 Lan Lan, 18 Chelsea Liu, 18 Jacob Sands 19 ¹Hospital Universitario 12 de Octubre, Madrid, Spain; 2Samsung Medical Center, Seoul, South Korea; ³David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; 4The Cancer Institute Hospital of JFCR, Tokyo, Japan; 5Severance Hospital, Seoul, South Korea; 6The University of Texas MD Anderson Cancer Center, Houston, TX, USA; NYU Langone Health Perlmutter Cancer Center, New York, NY, USA; University Hospital of Nantes, Nantes, France; National Cancer Center Hospital, Tokyo, Japan; 10National Cancer Center Hospital East, Kashiwa, Japan; 11Massachusetts General Hospital Cancer Center, Boston, MA, USA; 12The Netherlands Cancer Institute, Amsterdam, the Netherlands; 13 Gustave Rouss, Villejuif, France; 14Centre Léon Bérard, Lyon, France; 15Vall d'Hebron University Hospital and Vall d'Hebron Institute of Oncology, Barcelona, Spain; 16 National Cheng Kung University Hospital, Tainan, Taiwan; 17Daiichi Sankyo Europe GmbH, Munich, Germany; 18Daiichi Sankyo, Inc, Basking Ridge, NJ, USA; 19Dana-Farber Cancer Institute, Boston, MA, USA Daiichi-Sankyo 17#18Daiichi-Sankyo • • Introduction and Study Design Dato-DXd is a TROP2-directed ADC consisting of a humanized anti-TROP2 IgG1 monoclonal antibody covalently linked to a highly potent topoisomerase I inhibitor payload via a plasma-stable, tumor-selective, tetrapeptide-based cleavable linker¹ ⚫ In the phase 1 TROPION-Pan Tumor01 study, Dato-DXd showed promising efficacy in patients with actionable genomic alterations2 TROPION-Lung05 (NCT04484142) is a phase 2, single-arm study evaluating Dato-DXd in patients with advanced or metastatic NSCLC with actionable genomic alterations that progressed on or after targeted therapy and platinum-based chemotherapy • Endpointsa Primary: ORR by BICR Secondary: Screening Key inclusion criteria Treatment . Stage IIIB, IIIC, or IV NSCLC • Presence of ≥1 actionable genomic alteration (EGFR, ALK, ROS1, Dato-DXd NTRK, BRAF, MET exon 14 skipping, or RET) 6 mg/kg Q3W • By investigator: ORR • ECOG PS of 0 or 1 • ≥1 line of targeted therapy • 1 or 2 prior cytotoxic agent-containing therapies in the metastatic setting By BICR and investigator: DOR, DCR, CBR, PFS, TTR OS, safety, PK, immunogenicity • Radiographic disease progression after targeted therapy ADC, antibody-drug conjugate, BICR, blinded independent central review, CBR, clinical benefit rate; Dato-DXd, datopotamab deruxtecan, DCR, disease control rate; DOR, duration of response, ECOG PS, Eastern Cooperative Oncology Group performance status; IgG1, immunoglobulin G1; NSCLC, non-small cell lung cancer; ORR, objective response rate; OS, overall survival; PFS, progression-free survival; PK, pharmacokinetics; Q3W, every 3 weeks; TROP2, trophoblast cell-surface antigen 2; TTR, time to response. *The primary completion date will occur when all patients have had either a minimum of 9 months of follow-up after the start of study treatment or have discontinued from the study. 1. Okajima D, et al. Mol Cancer Ther. 2021;20:2329-2340.2. Shimizu T, et al. J Clin Oncol. Published online June 16, 2023. 18#19Patient Characteristics and Disposition Demographic characteristics Relative Frequency of Genomic Alterationsb-d Daiichi-Sankyo Median age (range), years Female, n (%) Histology, n (%) Adenocarcinoma History of brain metastasis, n (%) a Median prior lines of therapy for adv/met disease Prior lines of therapy, n (%) ≥3 prior lines of therapy for adv/met disease Prior platinum chemotherapy Prior anti-PD-1/anti-PD-L1 immunotherapy ≥2 prior lines of targeted therapies for indicated genomic alteration Dato-DXd (N=137) 60 (29-79) 83 (61) ALK rearrangement 25% 130 (95) EGFR mutatione 57% 70 (51) 3 137 (100) 98 (72) 137 (100) 49 (36) 82 (60) Disposition ROS1 rearrangement 7% RET rearrangement 6% MET exon 14 skipping BRAF mutation 4% 3% At the time of data cutoff (December 14, 2022): Median (range) treatment duration was 4 (1-21) months 60 participants (44%) were ongoing in study 20 participants (15%) were ongoing on study treatment adv/met, advanced/metastatic, Dato-DXd, datopotamab deruxtecan; PD-1, programmed cell death 1 protein; PD-L1, programmed cell death 1 ligand 1. *Patients with clinically inactive brain metastases and patients with treated brain metastases who are no longer symptomatic, require no treatment with corticosteroids or anticonvulsants, and have recovered from radiotherapy may be included in the study. *Patients whose tumors harbor KRAS mutations, in the absence of the genomic alterations EGFR, ALK, ROS1, NTRK, BRAF, MET exon 14 skipping, and RET, were excluded from the study. Three patients had tumors with MET amplification. *Patients had co-occurring alteration types; thus, percentages do not sum to 100%. *Protocol requires enrollment of 50% of patients with EGFR-mutated tumors, among whom 80% should have received prior osimertinib. 19#20Efficacy Summary Daiichi-Sankyo Best Percent Change From Baseline in Sum of Diameters of Target Lesions No. of prior systemic lines for advanced or metastatic disease 1/2 23 n (%) [95% CI]a Median DOR (95% CI), months 7.0 (4.2-9.8) All Response per BICR treated Patients with EGFR Patients with 100. patients 80- (N=137) 60- ORR confirmed, 49 (35.8) [27.8-44.4] mutations (N=78) 34 (43.6) [32.4-55.3] 7.0 (4.2-10.2) ALK rearrangement (N=34) 8 (23.5) [10.7-41.2] 7.0 (2.8-8.4) Best percentchange 40- 20- 0- -40- -60- -80- +: Ongoing participant -100- DCR confirmed, n (%) 108 (78.8) [71.0-85.3] 64 (82.1) [71.7-89.8] 25 (73.5) [55.6-87.1] [95% CI]a + + +++ Patient Percent Change From Baseline in Sum of Diameters of Target Lesions in Patients With Confirmed CR/PR Median PFS, (95% CI), monthsb 5.4 (4.7-7.0) 5.8 (5.4-8.3) 4.3 0 (2.6-6.9) -25 BOR: In the overall population (N=137), 4 patients (3%) achieved a CR and 45 (33%) achieved a PR Percentchange ㅎㅎ -75 -50 Confirmed BOR CR PR EGFR subset: Among patients with sensitizing or T790M mutations (N=68), the ORR was 49.1% in those previously treated with osimertinib -100 -125 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 Months 15 16 17 18 19 20 BICR, blinded independent central review; BOR, best overall response; CR, complete response; DCR, disease control rate; DOR, duration of response; ORR, objective response rate; PFS, progression-free survival; PR, partial response. *The 2-sided 95% Cls are based on the Clopper-Pearson exact binomial method. "Median PFS and PFS probabilities are based on the Kaplan-Meier method. "Per BICR. 20 20#21Safety Summary TEAEs Occurring in ≥15% of Patients; All Grades (N=137) a Nausea 35 23 2 Stomatitis 29 20 10 Alopecia 36 16b Constipation 23 9 Decreased appetite 12 12 4 Fatigue 12 21 10 4 Vomiting 14 8 1 Anemia 456 Daiichi-Sankyo 137 patients (100%) experienced TEAEs (grade ≥3, 47%) • 129 (94%) experienced treatment-related TEAEs (grade ≥3, 29%) • 34 (25%) experienced serious AEs (grade ≥3, 5%) • 30 (22%), 13 (10%), and 2 (2%) patients experienced TEAES associated with dose reduction, dose withdrawal, and death,c respectively AESI Incidence by Graded n(%) Total Grade 1 Grade 2 Grade ≥3 Grade 1 Oral mucositis/stomatitis 90 (66) 45 (33) 30 (22) 15 (11) Grade 2 Grade ≥3 Ocular surface toxicity 36 (26) 26 (19) 7 (5) 3 (2)f IRR 22 (16) 15 (11) 7 (5) 0 Adjudicated drug-related 5 (4) 1 (1) 3 (2) 1 (1)g ILD Asthenia 7 7 COVID-19 10 5 1 21 Rash 12 4 Cough 10 4 0 20 40 Patients, % 60 AE, adverse event; AESI, adverse event of special interest; CTCAE, common terminology criteria for adverse event; ILD, interstitial lung disease; IRR, infusion-related reaction; TEAE, treatment-emergent adverse event. "Due to rounding, summed rates may not reflect total percentage of TEAES. "Includes an event reported as Grade 3 incorrectly per CTCAE grades. "Two deaths were associated with disease progression, unrelated to study drug by investigator. "AESIs listed in this slide include all preferred terms defined by the medical concept. "Dry eye was the most commonly reported ocular surface toxicity (n=15 [11%]). Patients with grade 3 ocular surface toxicity had corneal disorder, cornea verticillata, and punctate keratitis. "One case of ILD was reported as a grade 3 event by investigator, and the patient died due to disease progression per investigator. The same event was adjudicated as a grade 5 event. 21#22Conclusions Encouraging antitumor activity was observed with Dato-DXd treatment in a heavily pretreated NSCLC population with actionable genomic alterations, including patients with EGFR mutations and ALK rearrangements Dato-DXd had a manageable safety profile, characterized by a low incidence of hematologic or drug-related grade ≥3 toxicities. Nausea and stomatitis were the predominant AEs seen, consistent with previously reported data in NSCLC The ongoing, randomized, phase 3 TROPION-Lung01 study (NCT04656652) is assessing Dato-DXd vs docetaxel in patients with pretreated adv/met NSCLC, including those with actionable genomic alterations adw/met, advanced/metastatic, AE, adverse event; Dato-DXd, datopotamab deruxtecan; NSCLC, non-small cell lung cancer. Daiichi-Sankyo 22#23Datopotamab deruxtecan (Dato-DXd) vs chemotherapy in previously- treated inoperable or metastatic hormone receptor-positive, HER2- negative (HR+/HER2-) breast cancer: Primary results from the randomised Phase 3 TROPION-Breast01 trial Aditya Bardia, Komal Jhaveri,² Seock-Ah Im,³ Sonia Pernas,4 Michelino De Laurentiis, 5 Shusen Wang,6 Noelia Martínez Jañez,7 Giuliano Borges,³ David W. Cescon,9 Masaya Hattori, 10 Yen-Shen Lu, 11 Erika Hamilton, 12 Qingyuan Zhang, 13 Junji Tsurutani, 14 Kevin Kalinsky, 15 Lu Xu,16 Neelima Denduluri,17 Hope S. Rugo, 18 Binghe Xu, 19* Barbara Pistilli20* *Contributed equally 1Massachusetts General Hospital Cancer Center, Boston, MA, USA; 2Memorial Sloan Kettering Cancer Center, New York, NY, USA, and Weill Cornell Medical College, New York, NY, USA; 3Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul National University, Seoul, Republic of Korea; 4Institut Català d'Oncologia, IDIBELL, L'Hospitalet, Barcelona, Spain; 5Istituto Nazionale Tumori Napoli IRCCS "Fondazione Pascale", Napoli, Italy; 6Cancer Center of Sun Yet-sen University, Guangzhou, China; 'Ramón y Cajal University Hospital, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain; 8Catarina Pesquisa Clínica, Santa Catarina, Brazil; 9Princess Margaret Cancer Centre/UHN, Toronto, ON, Canada; 10Aichi Cancer Center, Nagoya, Japan; 11National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan; 12Sarah Cannon Research Institute / Tennessee Oncology, Nashville, TN, USA; 13Harbin Medical University Cancer Hospital, Harbin, China; 14Showa University Hospital, Tokyo, Japan; 15Winship Cancer Institute at Emory University, Atlanta, GA, USA; 16AstraZeneca, New York, NY, USA; 17AstraZeneca, Arlington, VA, USA; 18University of California San Francisco Comprehensive Cancer Center, San Francisco, CA, USA; 19 National Cancer Center / National Clinical Research Center for Cancer / Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; 20 Gustave Roussy Cancer Center, Villejuif, France Daiichi-Sankyo 23#24• 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 HR+/HER2- MBC2-5 Chemotherapy is utilised widely for management of endocrine-resistant HR+/HER2- MBC, but is associated with low response rate, poor prognosis, and significant toxicity including myelosuppression and peripheral neuropathy6 TROP2-directed ADCs can have significant toxicities including diarrhoea, neutropenia and thrombocytopenia7,8 Daiichi-Sankyo ADC, antibody-drug conjugate; HER2-, human epidermal growth factor receptor 2-negative; HR+, hormone receptor-positive; MBC, metastatic breast cancer; TROP2, trophoblast cell surface antigen 2. 1. Sung H et al. CA Cancer J Clin 2021;71:209-49; 2. Gennari A, et al. Ann Oncol 2021;32:1475-1495; 3. Wolff AC, et al. J Clin Oncol 2023;41:3867-72; 4. Moy B, et all. J Clin Oncol 2023;41:1318-20; 5. Moy B, et al. J Clin Oncol 2022;40:3088-90; 6. Kuderer NM, et al. Nat Rev Clin Oncol 2022;19:681-97; 7. Rugo HS, et al. J Clin Oncol 2022;40:3365-76; 8. Yin Y et al. Mini Oral at ESMO 2023; presentation 380MO. 24#25Daiichi-Sankyo • • Background: Dato-DXd Dato-DXd is a TROP2-directed ADC, that selectively delivers a potent Topo-l inhibitor payload directly into tumor cells, 1 and has several unique properties*: - - Optimised drug to antibody ratio ≈ 4 Stable linker-payload Tumour-selective cleavable linker - Bystander antitumour effect Dato-DXd previously demonstrated promising antitumour activity and a manageable safety profile with a convenient Q3W schedule in pre-treated patients with metastatic HR+/HER2- breast cancer² *The clinical relevance of these features is under investigation. Based on animal data. Dato-DXd, datopotamab deruxtecan; IgG1, immunoglobulin G1; Q3W, every 3 weeks; Topo-1, topisomerase I. Dato-DXd: Humanised anti-TROP2 IgG1 monoclonal antibody 0 Deruxtecan H H "NH H H₂C. HO -CH3 Cleavable tetrapeptide-based linker Topo-l inhibitor payload (DXd) Image is for illustrative purposes only; actual drug positions may vary. 1. Okajima D, et al. Mol Cancer Ther 2021;20:2329-40; 2. Meric-Bernstam F, et al. Poster presentation at SABCS 2022: abstract PD13-08. 25#26Daiichi-Sankyo TROPION-Breast01 Study Design1 Randomised, phase 3, open-label, global study (NCT05104866) Key inclusion criteria: • Patients with HR+/HER2- breast cancer* (HER2-defined as IHC 0/1+/2+; ISH negative) 1:1 Previously treated with 1-2 lines of chemotherapy (inoperable/metastatic setting) Experienced progression on ET and for whom ET was unsuitable ECOG PS 0 or 1 Dato-DXd 6 mg/kg IV Day 1 Q3W (n=365) Investigator's choice of chemotherapy (ICC) as per protocol directions* (eribulin mesylate D1,8 Q3W; vinorelbine D1,8 Q3W; gemcitabine D1,8 Q3W; capecitabine D1-14 Q3W) (n=367) • Endpoints: Dual primary: PFS by BICR per RECIST v1.1, and OS • Key secondary: ORR, PFS (investigator assessed) and safety Randomisation stratified by: " " Lines of chemotherapy in unresectable/metastatic setting (1 vs 2) Geographic location (US/Canada/Europe vs ROW) • Previous CDK4/6 inhibitor (yes vs no) ⚫ Treatment continued until PD, unacceptable tolerability, or other discontinuation criteria Detailed description of the statistical methods published previously 1 *Per American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines. TICC was administered as follows: eribullin mesylate, 1.4 mg/m² IV on Days 1 and 8, Q3W; capecitabine, 1000 or 1250 mg/m² orally twice daily on Days 1 to 14, Q3W (dose per standard institutional practice); vinorelbine, 25 mg/m² IV on Days 1 and 8, Q3W; or gemcitabine, 1000 mg/m² IV on Days 1 and 8, Q3W. BICR, blinded independent central review; CDK4/6, cyclin-dependent kinase 4/6; ECOG PS, Eastern Cooperative Oncology Group performance status; ET, endocrine therapy; IV, intravenous; ORR, objective response rate; OS, overall survival; PD, progressive disease; PFS, progression-free survival; RECIST, Response Evaluation Criteria in Solid Tumors; ROW, rest of world. 1. Bardia A, et al. Future Oncol 2023; doi: 10.2217/fon-2023-0188. 26#27TROPION-Breast01 Statistical Methods¹ • • Primary efficacy analysis performed in intention-to-treat population and analysed by treatment group - Primary analysis of PFS 419 PFS events - Interim OS analysis at the time of the primary PFS analysis • The final analysis of OS will be conducted at ~ 444 OS events - • · PFS analysed using log-rank test utilising stratification factors Study considered positive if PFS and/or OS analysis statistically significant Daiichi-Sankyo 1. Bardia A, et al. Future Oncol 2023; doi: 10.2217/fon-2023-0188. 27#28Patient Disposition Screened (n=1003) Randomised (n=732) Daiichi-Sankyo Dato-DXd (n=365)* • Ongoing study treatment (n=93) Discontinued study treatment (n=267) - Progressive disease (n=229) Adverse event (n=11) ICC (n=367)* Ongoing study treatment (n=39) Discontinued study treatment (n=312) - Progressive disease (n=240) ICC: • Eribulin mesylate: n=220 Vinorelbine: n=38 • Capecitabine: n=76 1 Patient decision (n=13) —- Death (n=2) - Other (n=12) - Adverse event (n=10) 1 Patient decision (n=32) - Death (n=7) - Other (n=23) Median study follow-up: 10.8 months *360 and 351 patients received treatment with Dato-DXd and ICC, respectively. • Gemcitabine: n=33 Data cut-off. 17 July 2023. 28#29Demographics and Baseline Characteristics Age, median (range), years Female, n (%) Dato-DXd (n=365) 56 (29-86) 360 (99) ICC (n=367) 54 (28-86) 363 (99) Daiichi-Sankyo Race, n (%) Ethnicity, n (%) Black or African American / Asian / White / Other* 4 (1) 146 (40) 180 (49) / 35 (10) 7 (2) / 152 (41) /170 (46) / 38 (10) Hispanic or Latino / Not Hispanic or Latinot 40 (11)/322 (88) 43 (12) / 318 (87) Prior lines of chemotherapy, n (%) 1/2 229 (63) / 135 (37) 225 (61) / 141 (38) Prior CDK4/6 inhibitor, n (%) Yes/No 299 (82) / 66 (18) 286 (78) / 81 (22) Prior taxane and/or anthracycline, n (%) Taxane and/or Anthracycline 330 (90) Neither 35 (10) 339 (92) 28 (8) *Including not reported. "Ethnicity missing: 3 patients in Dato-DXd group; 6 patients in ICC group. *In the inoperable/metastatic setting; one patient in the Dato-DXd group had 3 prior lines of chemotherapy; one patient in the ICC group had 4 prior lines. 29 29#30Progression-Free Survival PFS by BICR: primary endpoint Probability of PFS 1.0 0.9- 0.8 0.7 0.6- 0.5 0.4 0.3 0.2- 0.1 0. 0 Number at risk Dato-DXd 365 ICC 367 365 Dato-DXd (n=365) ICC (n=367) 3 249 205 38.5% 6 53.3% Dato-DXd ICC Median PFS, months (95% CI) 6.9 (5.7-7.4) 4.9 (4.2-5.5) HR (95% CI) 0.63 (0.52-0.76) <0.0001 P-value 37.5% 25.5% I 18.7% I 14.6% i I + 9 12 15 Time from randomisation (months) 158 93 66 26 15 8 4 Cl, confidence interval; HR, hazard ratio PFS by investigator assessment: Median 6.9 vs 4.5 months; HR 0.64 (95% CI 0.53-0.76) Daiichi-Sankyo 30 30#31PFS by BICR Across Subgroups Events/n Hazard Dato-DXd ICC ratio All patients 212/365 235/367 0.63 Age at randomisation <65 years 163/274 190/295 0.64 ≥65 years Race Asian 49/91 88/146 45/72 0.65 101/152 0.70 Non-Asian 109/187 119/183 0.59 ECOG performance status 0 119/197 136/220 0.73 1 91/165 98/145 0.52 Geographic region US, Canada, Europe 110/186 112/182 0.62 Rest of World* 102/179 123/185 0.66 Number of previous lines 1 128/229 145/225 0.65 of chemotherapy 2 84/135 90/141 0.60 Prior use of CDK4/6 Yes inhibitor No 177/299 190/286 35/66 45/81 0.62 0.70 and/or anthracycline Prior use of taxane Taxane alone Both taxane and anthracycline Neither taxane nor anthracycline 48/80 47/71 0.62 Anthracycline alone 9/14 141/236 155/247 16/21 0.46 0.70 14/35 17/28 0.34 0.25 0.5 0.75 1 1.5 Size of circle is proportional to the number of events across both treatment groups. *Three patients from Canada were incorrectly stratified to Rest of World. Hazard Ratio Daiichi-Sankyo 31#32Response and Interim OS Response Rate 45 40 10 525322505 15 ORR Complete response (0.5%) • 36.4% Partial response ORR 22.9% ° Patients with response, % *Information fraction: 39%. Dato-DXd ICC (n=365) (n=367) ORR, confirmed objective response rate by BICR OS: Dual Primary Endpoint OS data not mature:* Median follow-up 9.7 months A trend favouring Dato-DXd was observed: — HR 0.84 (95% CI 0.62-1.14) • The study is continuing to the next planned analysis for OS 32 Daiichi-Sankyo#33Overall Safety Summary Daiichi-Sankyo • • Median treatment duration was 6.7 months with Dato-DXd and 4.1 months with ICC Rate of grade ≥23 TRAES in the Dato-DXd group was less than half that in the ICC group Fewer TRAEs leading to dose reductions or interruptions with Dato-DXd compared with ICC TRAES, n (%) Dato-DXd (n=360) ICC (n=351) All grades 337 (94) 303 (86) Grade ≥3 75 (21) 157 (45) Associated with dose reduction 75 (21) 106 (30) Associated with dose interruption 43 (12) 86 (25) • Associated with discontinuation 9 (3) 9 (3) 0 1 (0.3) Associated with death Serious TRAES 21 (6) 32 (9) Grade ≥3 17 (5) 31 (8) TRAES, treatment-related adverse events. 33#34Daiichi-Sankyo Dato-DXd (n=360) ICC (n=351) Preferred term, n (%) Any Grade Grade ≥3 Any Grade Grade ≥3 Blood and lymphatic system Anaemia 40 (11) 4 (1) 69 (20) Neutropenia* 39 (11) 4 (1) 149 (42) Eye Dry eye 78 (22) 2 (1) 27 (8) Gastrointestinal Nausea 184 (51) 5 (1) 83 (24) Stomatitis 180 (50) 23 (6) 46 (13) Vomiting 71 (20) 4 (1) 27 (8) Constipation 65 (18) 0 32 (9) TRAES Occurring in ≥15% of Patients and AESIS System Organ Class • • Most TRAEs were grade 1-2 and manageable AESIs Oral mucositis/stomatitis: led to treatment discontinuation in one patient in the Dato-DXd group Ocular events: most were dry eye; one patient discontinued treatment in the Dato-DXd group Adjudicated drug-related ILD:S rate was low; mainly grade 1/2 7 (2) • 108 (31) 0 2 (1) 9 (3) • 2 (1) 0 General Fatigue Skin and subcutaneous Alopecia 85 (24) 6 (2) 64 (18) 7 (2) Adjudicated drug-related ILD Dato-DXd ICC All grades, n (%) 9 (3) 0 131 (36) 0 72 (21) 0 Grade ≥3, n (%) 2 (1)1 0 *Neutropenia includes the PTs neutropenia and neutrophil count decreased. "Oral stomatitis/mucositis events included PTs of aphthous ulcer, dysphagia, glossitis, mouth ulceration, odynophagia, oral mucosal blistering, oral pain, oropharyngeal pain, pharyngeal inflammation, stomattis, tongue ulceration; all grade: 59% with Dato-DXd, 17% with ICC; grade 3: 7% with Dato-DXd, 3% with ICC. #Ophthalmologic assessments were required at screening, and then every 3 cycles from C1D1 and at end of therapy; ocular events included selected PTs from Corneal Disorder SMQ and select relevant PTs from Eye Disorder SOC; all grade: 49% with Dato-DXd, 23% with ICC; grade 3: 1% with Dato-DXd (one patient with dry eye, one patient with punctate kerattis, and one patient with dry eye and ulcerative kerafts), 0% with ICC. $ILD includes events that were adjudicated as ILD and related to use of Dato-DXd or ICC (includes cases of potential ILD/pneumonitis, based on MedDRA v23.0 for the narrow ILD SMQ, selected terms from the broad ILD SMQ, and PTs of respiratory failure and acute respiratory failure). One adjudicated drug-related grade 5 ILD event attributed to disease progression by investigator. ILD, interstitial lung disease; PTs, preferred terms; SMQ, standard MedDRA query; SOC, system organ class. 34#35Daiichi-Sankyo Conclusions • • • 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 PFS with Dato-DXd compared with ICC - - Consistent PFS benefit observed across subgroups Higher ORR with Dato-DXd and a trend at interim OS favouring Dato-DXd Overall, Dato-DXd demonstrated a favourable and manageable safety profile, with no new safety signals - Most AESIs were grade 1-2 - Patients receiving Dato-DXd had fewer grade ≥3 TRAES (less than half that with ICC), as well as fewer TRAES leading to dose interruption/reduction compared with ICC Results support Dato-DXd as a potential new therapeutic option for patients with metastatic HR+/HER2- breast cancer 35#36Datopotamab Deruxtecan (Dato-DXd) + Durvalumab (D) as First-Line (1L) Treatment for Unresectable Locally Advanced/Metastatic Triple-Negative Breast Cancer (a/mTNBC) Updated Results From BEGONIA, a Phase 1b/2 Study Professor Peter Schmid, FRCP, MD, PhD Barts Cancer Institute, Queen Mary University of London, London, UK P. J. Wysocki, C. X. Ma, Y. H. Park,³ R. Fernandes, 4 S. Lord, 5 R. D. Baird, 6 C. Prady,7 K. H. Jung, J. Asselah,9 R. Huisden, 10 R. Stewart, 10 K. Heider, 10 P. Vukovic, 10 N. Denduluri, 11 Z. Nowecki 12 1Jagiellonian University Medical College, Krakow, Poland; 2Washington University School of Medicine, St. Louis, MO, USA; 3Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea; 4Schulich School of Medicine & Dentistry, Western University, London Health Sciences Centre, London, Ontario, Canada; 5University of Oxford, Oxford, UK; 6Cancer Research UK Cambridge Centre, Cambridge, UK; 7Sherbrooke University, Centre intégré de cancérologie de la Montérégie, CISSS Montérégie Centre, Greenfield Park, Quebec, Canada; 8Asan Medical Center - University of Ulsan, College of Medicine, Seoul, Korea; McGill University Health Centre, Montreal, Québec, Canada; 10AstraZeneca, Cambridge, UK; 11AstraZeneca, Gaithersburg, MD, USA; 12Maria Skłodowska-Curie National Research Institute of Oncology, Warsaw, Poland Daiichi-Sankyo 36#37The BEGONIA Study (NCT03742102) Rationale Immune checkpoint inhibitors + chemotherapy is the standard of care for patients with PD-L1 positive a/mTNBC; still, most progress within a year (median PFS-9-10 months) 1.2 BEGONIA is evaluating combinations of durvalumab (D), an anti-PD-L1 antibody, with other novel therapies in first-line a/mTNBC Dato-DXd is a TROP2-directed ADC with a TOPO I inhibitor payload and a tumour- selective cleavable linker³ At median 7.2 months follow-up, ORR was 74% for patients treated with Dato-DXd + D in BEGONIA+ Eligibility criteria Females aged ≥18 years • Unresectable a/m TNBC + No prior treatment for Stage IV TNBC ⚫ ≥12 months since prior taxane therapy • ECOG PS 0-1 ♦ Adequate organ function ◆ Measurable disease per RECIST v1.1 ◆ No prior treatment with checkpoint inhibitor ◆ No prior treatment with TOPO I-based ADC* Study Design Treatment arms Arm 1: Paclitaxel (P) + D (N=20) Arm 2: Capivasertib + P + D (N=30) Part 1 Part 2 expansion Arm 5: Oleclumab +P + D (N=30) Arm 6: T-DXd + D (N=30) Safety run-in (up to Simon 6 patients) Arm 7: Dato-DXd 6 mg/kg + D 1120 mg (N=30) Q3W until PD 2-stage futility analysis for Part 2 expansion* Arm 8: Dato-DXd + D. PD-L1 positive (N=30) 1° endpoint: Safety and tolerability 2° endpoints: ORR, PFS, DOR, OS Arms that meet expansion criteria enrol additional 27 patients 1° endpoint: ORR 2° endpoints: PFS, DoR, PFS6, OS We report updated results with longer follow-up for patients from Parts 1 and 2 treated with Dato-DXd + D in BEGONIA Arm 7 *ADC-cohort-specific criteria. "Currently enrolling; a safety run-in will not accur for this arm as Dato-DXd+ D was already evaluated and found to be tolerable with no dose-limiting toxicities reported. "Novel treatment combinations may enter Part 2 expansion if confirmed ORR is at least 57%. 1. Cortes J. et al. Lancet. 2020:396/10265):1817-1828. 2. Emens LA, et al. J Natl Cancer Inst. 2021;113(8):1005-1016. 3. Bardia A. et al. Presented at SABOS 2022. P6-10-03. 4. Schmid P, et al. Presented at SABCS 2022. PD11-08. ADC, antibody-drug conjugate; almTNBC, advanced metastatic triple-negative breast cancer; Dato-DXd, datopolamab deruxtecan; DoR, duration of response; D, durvalumab; ECOG PS, Eastem Cooperative Oncology Group performance status; ORR, objective response rate; OS, overall survival; PD. progressive disease; PD-L1. programmed death ligand-1; PFS progression-free survival; PFS6. progression-free survival at 6 months; 03W, every 3 weeks: RECIST, Response Evaluation Criteria In Solid Tumors; T-DXd, trastuzumab deruxtecan; TOPO I, topoisomerase I; TROP2, trophoblast cell- surface antigen 2. Daiichi-Sankyo 37#3862 patients treated BEGONIA Arm 7: Dato-DXd + Durvalumab Disposition and Baseline Characteristics 33 (53%) discontinued treatment (1 or more reasons may have been reported) 26 (42%) disease progressiona 10 (16%) due to an adverse eventb 4 (7%) patient decisiona 29 (47%) treatment ongoing Median follow-up: 11.7 (range, 2-20) months Characteristic Age, median (range), years No prior treatment, n (%) Prior treatments for early-stage disease, n (%) Radiotherapy Cytotoxic chemotherapy Taxane Anthracycline Platinum compound Dato-DXd + D N=62 53 (31-74) 26 (42) 30 (48) 33 (53) 26 (42) 29 (47) 9 (15) 10 (16) 1 (2) Targeted therapy 37 (60) Visceral metastases, n (%) 42 (68) Lymph node metastases, n (%) PD-L1 expression, dn (%) 7 (11) High (TAP ≥10%) 54 (87) Low (TAP <10%) Unknown/Missing 1 (2) Hormonal therapy *Discontinued all study drugs. "Discontinued any study drug. "Defined as liver/hepatic and/or respiratory metastases. *PD-L1 expression was assessed by immunohistochemistry using the VENTANA PD-L1 (SP263) Assay, and expression was defined as the percentage of the tumour area populated by tumour or immune cells with membranous staining (TAP). A sample was considered PD-L1 high if it had ≥10% TAPPD-L1 expression. Dato-DXd, datopotamab deruxtecan; D, durvalumab; PD-L1, programmed cell death ligand-1; TAP, tumour area positivity. Data cutoff: 02 Feb 2023 Daiichi-Sankyo 38#39Best change from baseline in target lesion size (%) BEGONIA Arm 7: Dato-DXd + Durvalumab Antitumour Responses in 1L a/mTNBC 100 Confirmed ORR was 79% (49/62; 95% CI, 66.8–88.3) with 6 CR and 43 PR ◆ Antitumour responses were observed regardless of PD-L1 expression level as assessed by 2 separate PD-L1 assays and scoring methods 50- 0 -50- H High # PD-L1 expression L Low -100 U Unknown/Missing SP263 PD-L1 TAP 10% cutoff LLLHLLLLHLLHH 22C3 PD-L1 CPS 10 cutoff LL LLHLLLLHLLHHLLLLLU Progressive disease Stable disease LLL HLLLLLLL HLHLLLLL Not evaluable Partial response .L LHLLL LLLHLHLL Complete response Dotted lines indicate thresholds for partial response (-30%) and progressive disease (20%). PD-L1 expression was assessed by 1) immunohistochemistry using the VENTANA PD-L1 (SP263) Assay with expression defined as the percentage of the tumour area populated by tumour or immune cells with membranous staining (TAP), or 2) immunohistochemistry using the 2203 antibody with expression defined as the number of PD-L1-staining tumour cells, lymphocytes, and macrophages, divided by the total number of viable tumour cells, multiplied by 100 (CPS). *Ifthe best percentage change from baseline of target lesions cannot be calculated due to progression, withdrawal, or death, the value is imputed at +20%.***Patients with PD as best overall response. *Unconfirmed response. 1L, first line; a/m TNBC, advanced/metastatic triple-negative breast cancer; CI, confidence interval; CPS, combined positive score; CR, complete response; Dato-DXd, datopotamab deruxtecan; ORR, objective response rate; PD-L1, programmed cell death ligand-1; PR, parial response; TAP, tumour area positivity. Data cutoff. 02 Feb 2023 Daiichi-Sankyo 39#40Probability of progression-free survival 1.0 BEGONIA Arm 7: Dato-DXd + Durvalumab Progression-Free Survival and Duration of Response Median PFS was 13.8 months (95% CI, 11.0-NC) Median DoR was 15.5 months (95% CI, 9.92-NC) Durva + Dato-DXd (N=62) 0.9 0.8 0.7 0.6 0.5 0.4. 0.3 0.2 0.1 0.0 T T 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 Time from first dose date (months) Duration and onset of objective response 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0.0 T Durva + Dato-DXd (N=62) 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 Time from first dose date (months) Number of patients at risk Durva + Dato-DXd 62 61 56 55 54 52 45 40 37 32 24 23 18 18 14 13 13 2 2 0 Number of patients at risk Durva + Dato-DXd 49 49 49 47 46 42 35 30 28 21 18 17 17 13 13 12 1 1 0 Kaplan-Meier analysis was performed. Circles indicate censored observations. CI, confidence interval; Dato-DXd, datopotamab deruxtecan; DoR, duration of response; NC, not calculable; PFS, progression-free survival. Data cutoff: 02 Feb 2023 40 Daiichi-Sankyo#41BEGONIA Arm 7: Dato-DXd + Durvalumab Safety Summary Patients, n (%) Any AEs Grade 3/4 Any treatment-related AEsa Grade 3/4 Any serious AEs Treatment-related AEs leading to discontinuation of any treatments AEs leading to deathb Dose adjustments Dato-DXd dose reduction Dato-DXd dose delay Durvalumab dose delay "Per investigator assessment. "Patient died due to dehydration, unrelated to treatment. AE, adverse event; Dato-DXd, datopotamab deruxtecan; D, durvalumab. Dato-DXd+ D N=62 62 (100) 35 (57) 62 (100) 27 (44) 14 (23) 6 (10) 10 (16) 1 (2) 18 (29) 28 (45) 31 (50) Daiichi-Sankyo Data cutoff. 02 Feb 2023 41#42BEGONIA Arm 7: Dato-DXd + Durvalumab Adverse Events Most frequently reported adverse events (≥15%) (N=62) The most common AEs were gastrointestinal and generally of low grade (Table) AE preferred term Any grade, n (%) Grade 3/4, n (%) Nausea 40 (65) 0 Stomatitis 40 (65) 7 (11) Alopecia 31 (50) 0 Constipation 29 (47) 1 (2) Fatigue 28 (45) Rash 20 (32) 1 (2) 0 Vomiting 16 (26) 1 (2) Amylase increased 13 (21) 11 (18) COVID-19 13 (21) 0 Dry eye 13 (21) 0 Decreased appetite 12 (19) 1 (2) Pruritus 10 (16) 0 Cough 10 (16) 0 AE, adverse event; AESI, adverse event of special interest; ILD, interstitial lung disease. Stomatitis was the most common AE leading to Dato-DXd dose reduction (11 patients) There were 3 (5%) adjudicated treatment-related ILD/pneumonitis events (2 grade 2 events, 1 grade 1 event) Limited rates of diarrhea (13% any grade, 1 grade 3 event) and neutropenia (5% any grade, 1 grade 3 event) were reported The most frequent AESIS for Arm 7 were stomatitis (65%), rash (32%), dry eye (21%), hypothyroidism (14.5%), and keratitis (14.5%) Daiichi-Sankyo Data cutoff: 02 Feb 2023 42#43BEGONIA Arm 7: Dato-DXd + Durvalumab Conclusions Dato-DXd + durvalumab continues to demonstrate robust, durable responses in first-line a/mTNBC in a biomarker-unselected population with median 11.7 months of follow-up Confirmed ORR was 79% (95% CI, 66.8–88.3), responses observed regardless of PD-L1 expression Median DoR was 15.5 months (95% CI, 9.92-NC) Median PFS was 13.8 months (95% CI, 11.0-NC) The combination of Dato-DXd + durvalumab had a tolerable and manageable safety profile, with no new safety signals Comprehensive toxicity management guidelines were implemented during the course of the study BEGONIA is currently enrolling for Arm 8, Dato-DXd + durvalumab in a PD-L1-high population a/mTNBC, advanced/metastatic triple-negative breast cancer; CI, confidence interval; Dato-DXd, datopotamab deruxtecan; DoR, duration of response; NC, not calculable; ORR, objective response rate; PD-L1, programmed death ligand-1; PFS, progression-free survival. 43 33 Daiichi-Sankyo#44Trastuzumab deruxtecan (T-DXd) for pretreated patients with HER2-expressing solid tumors: primary analysis from the DESTINY-Pan Tumor02 (DP-02) study Funda Meric-Bernstam, MD; a Vicky Makker; Ana Oaknin; Do-Youn Oh; Susana Banerjee; Antonio González-Martín; Kyung Hae Jung; Iwona Ługowska; Luis Manso; Aránzazu Manzano; Bohuslav Melichar; Salvatore Siena; Daniil Stroyakovskiy; Anitra Fielding; Yan Ma; Soham Puvvada; Jung-Yun Lee On behalf of the DESTINY-PanTumor02 investigators aUniversity of Texas MD Anderson Cancer Center, Houston, TX, USA October 23, 2023 | 16:40-16:45 CEST Daiichi-Sankyo 44#45DESTINY-Pan Tumor02: a Phase 2 study of T-DXd for HER2-expressing solid tumors An open-label, multicenter study (NCT04482309) • Key eligibility criteria Advanced solid tumors not eligible for curative therapy • 2L+ patient population ⚫ HER2 expression (IHC 3+ or 2+) Endometrial cancer Cervical cancer Daiichi-Sankyo - Local test or central test by Hercep Test if local test T-DXd Ovarian cancer not feasible (ASCO/CAP gastric cancer scoring 1)a 5.4 mg/kg Q3W Bladder cancer • Prior HER2-targeting therapy allowed · ECOG/WHO PS 0-1 Baseline characteristics • ⚫ 267 patients received treatment; 202 (75.7%) based on local HER2 testing 40 per cohortb Other tumorsc Biliary tract cancer - 111 (41.6%) patients were IHC 3+ based on HER2 test (local or central) at enrollment, primary efficacy analysis (all patients) 75 (28.1%) patients were IHC 3+ on central testing, sensitivity analysis on efficacy endpoints (subgroup analyses) Pancreatic cancer Primary endpoint • Confirmed ORR (investigator) Secondary endpoints DOR, DCR, PFS, OS Exploratory analysis • Subgroup analyses by HER2 status Primary analysis data cutoff: Jun 8, 2023 Median follow up: 12.75 mo • • Safety • Median age was 62 years (23-85) and 109 (40.8%) patients had received ≥3 lines of therapy *Patients were eligible for either test. All patients were centrally confirmed; 'planned recruitment, cohorts with no objective responses in the first 15 patients were to be closed; "patients with tumors that express HER2, excluding tumors in the tumor- specific cohorts, and breast cancer, non-small cell lung cancer, gastric cancer, and colorectal cancer 2L, second-line; ASCO, American Society of Clinical Oncology; CAP, College of American Pathologists; DCR, disease control rate; DOR, duration of response; ECOG, Eastern Cooperative Oncology Group; HER2, human epidermal growth factor receptor 2; IHC, immunohistochemistry; ORR, objective response rate; OS, overall survival; PFS, progression-free survival; PS, performance status; Q3W, every 3 weeks; T-DXd, trastuzumab deruxtecan; WHO, World Health Organization 1. Hofmann M, et al. Histopathology. 2008;52:797–805 45#46Objective response and duration of response Daiichi-Sankyo 100 Endometrial Cervical Ovarian Bladder Othera BTC Pancreatic 90 84.6 75.0 Confirmed ORR by investigator (%) 80 70 57.5 63.6 60 56.3 56.3 50 40 30 20 50.0 47.1 45.0 40.0 39.0 36.8 35.0 10 All IHC 3+ IHC 2+ All IHC 3+ IHC 2+ קון IHC 3+ IHC 2+ All IHC 3+ IHC 2+ All IHC 3+ 30.0 44.4 0° IHC 2+ 18.8 22.0 All IHC 3+ IHC 2+ All IHC 3+ IHC 2+ 4.0 5.3 0.0 0.0 0 n= 40 13 17 40 8 00 20 40 Median DOR, months (95% CI)b NR (9.9, NR) 14.2 11 19 11.3 41 16 20 40 9 16 41 16 14 25 2 19 8.7 22.1 8.6 5.7 (4.1, NR) (4.1, 22.1) (4.3, 11.8) (4.1, NR) (2.1, NR) (NR, NR) All patients (N=267) IHC 3+ (n=75) IHC 2+ (n=125) ORR,% (95% CI) 37.1 (31.3, 43.2) 11.3 (9.6, 17.8) 61.3 (49.4, 72.4) 27.2 (19.6, 35.9) 22.1 (9.6, NR) Median DOR, months (95% CI)b 9.8 (4.3, 12.6) Analysis of ORR by investigator was performed in patients who received >1 dose of T-DXd; all patients (n=267; including 67 patients with IHC 1+ [n=25], IHC 0 [n=30], or unknown IHC status [n=12] by central testing) and patients with centrally confirmed HER2 IHC 3+ (n=75) or IHC 2+ (n=125) status. Analysis of DOR was performed in patients with objective response who received ≥1 dose of T-DXd; all patients (n=99; including 19 patients with IHC 1+ [n=6], IHC 0 [n=9], or unknown IHC status [n=4] by central testing) and patients with centrally confirmed HER2 IHC 3+ (n=46) or IHC 2+ (n=34) status. *Responses in extramammary Paget's disease, head and neck cancer, oropharyngeal neoplasm, and salivary gland cancer, bincludes patients with a confirmed objective response only BTC, biliary tract cancer; CI, confidence interval; DOR, duration of response; HER2, human epidermal growth factor receptor 2; IHC, immunohistochemistry; NR, not reached; ORR, objective response rate; T-DXd, trastuzumab deruxtecan 46#47Efficacy endpoint: PFS and OS by HER2 status Daiichi-Sankyo K-M estimates of PFS by investigator assessment (All cohorts) 1.0 0.8 Median PFS in months (95% CI) All cohorts: IHC 3+ 11.9 (8.2, 13.0) All cohorts: IHC 2+ 5.4 (4.2, 6.0) All cohorts: Total 6.9 (5.6, 8.0) PFS events, n (%): 203 (76%) Probability of PFS 0.6 0.4 0.2- 0.0 0 3 53% 30% 21% T 6 9 12 15 18 21 Time from first dose (months) 15% 24 24 27 30 33 Probability of OS 1.0 0.8- 0.6 0.2 - K-M estimates of OS (All cohorts) Median OS in months (95% CI) ― All cohorts: IHC 3+ 21.1 (15.3, 29.6) All cohorts: IHC 2+ 12.2 (10.7, 13.5) All cohorts: Total 13.4 (11.9, 15.5) OS events, n (%): 176 (66%) 0.0 0 -3 75% 9 56% 39% 30% T T 24 27 30 33 12 15 18 21 Time from first dose (months) Number at risk, month Number at risk, month All cohorts: IHC 3+ 75 63 51 39 34 23 19 12 1 0 All cohorts: IHC 2+ 125 78 50 31 20 18 13 9 3 1 0 All cohorts: IHC 3+ 75 All cohorts: IHC 2+ 125 69 61 56 51 45 39 29 113 88 75 62 43 31 All cohorts: Total 267 185 132 89 68 51 39 25 6 2 10 All cohorts: Total 267 239 194 165 143 108 86 65 34 10 228 13 4 20 22 12 UN 2 0 4 0 Circle indicates a censored observation CI, confidence interval; HER2, human epidermal growth factor receptor 2; IHC, immunohistochemistry; K-M, Kaplan-Meier; OS, overall survival; PFS, progression-free survival 47#48Skip in ESMO Highlight presentation Efficacy endpoint: PFS by HER2 status per cohort Daiichi-Sankyo Median PFS in months (95% CI) Endometrial cancer: IHC 3+ NR (7.3, NR) Endometrial cancer: IHC 2+ 8.5 (4.6, 15.1) -Endometrial cancer: Total 11.1 (7.1, NR) " -O -0 3 6 9 12 15 18 21 -2 24 T 27 30 33 Time from first dose (months) 370 17 40 215 12 14 == 11 10 10 11 7 31 27 21 956 157 8 4 16 14 528 0 1 0 2 1 1 0 All cohorts Probability of PFS 1.0- 0.8- 0.6- Median PFS in months (95% CI) All cohorts: IHC 3+ 11.9 (8.2, 13.0) All cohorts: IHC 2+ 5.4 (4.2, 6.0) All cohorts: Total 6.9 (5.6, 8.0) 1.0- 0.4- 0.2- 0.0- Endometrial cancer Probability of PFS 0.8- 0.6- 0.4- 0.2- 0.0 T -O 0 3 -8 T 6 9 12 -2 T 15 18 21 24 27 30 33 33- Time from first dose (months) Number at risk, month All cohorts: IHC 3+ 75 63 51 39 34 23 19 All cohorts: IHC 2+ 125 78 50 31 20 18 All cohorts: Total 267 185 132 89 68 51 ៩៨ 13 39 212 12 1 9 3 25 6 010 2 0 1 Number at risk, month Endometrial cancer: IHC 3+ 13 Endometrial cancer: IHC 2+ 0 Endometrial cancer: Total 276 1.0- Cervical cancer Probability of PFS 0.8- 0.6- 0.4- 0.2- 0.0 Median PFS in months (95% CI) Cervical cancer: IHC 3+ NR (3.9, NR) Cervical cancer: IHC 2+ 4.8 (2.7, 5.7) Cervical cancer: Total 7.0 (4.2, 11.1) 1.0- Ovarian cancer Probability of PFS 0.8- Median PFS in months (95% CI) Ovarian cancer: IHC 3+ 12.5 (3.1, NR) Ovarian cancer: IHC 2+ 4.1 (2.3, 12.6) Ovarian cancer: Total 5.9 (4.0, 8.3) 0.6- 0.4- 0.2- 0.0- T 0 3 6 9 -CO 12 T 15 T T 18 21 T 24 27 T D- -n 0 3 16 Time from first dose (months) 9 Time from first dose (months) T - T - - 12 15 18 21 24 27 30 Number at risk, month Number at risk, month Cervical cancer: IHC 3+ 8 Cervical cancer: IHC 2+ 20 Cervical cancer: Total 40 28 0000 8 12 752 6 5 3 3 1 1 0 Ovarian cancer: IHC 3+ 11 10 3 0 Ovarian cancer: IHC 2+ 19 11 20 14 9 6 3 1 1 0 Ovarian cancer: Total 40 28 17 551 652 16 4 4 4 12 11 9 27 326 0 1 1 1 1 00 Circle indicates a censored observation Cl, confidence interval; HER2, human epidermal growth factor receptor 2; IHC, immunohistochemistry; NR, not reached; PFS, progression-free survival 40 48#49Skip in ESMO Highlight presentation Efficacy endpoint: PFS by HER2 status per cohort Daiichi-Sankyo Bladder cancer Probability of PFS 1.0- 0.8- 0.6- 0.4- Number at risk, month 0.2 0.0- -3 6 -00 9 12 Median PFS in months (95% CI) Bladder cancer: IHC 3+ 7.4 (3.0, 11.9) Bladder cancer: IHC 2+ 7.8 (2.6, 11.6) Bladder cancer: Total 7.0 (4.2, 9.7) tumors Other Probability of PFS 1.0- 0.8- 0.6- 0.4- 0.2- 0.0- Median PFS in months (95% CI) Other tumors: IHC 3+ 23.4 (5.6, NR) Other tumors: IHC 2+ 5.5 (2.8, 8.7) Other tumors: Total 8.8 (5.5, 12.5) T 15 18 21 24 -O T 0 -3 6 9 12 15 18 21 24 27 Time from first dose (months) Number at risk, month 145 0 Other tumors: IHC 3+ 9 9 3 1 0 Other tumors: IHC 2+ 16 9 3 1 0 Other tumors: Total 40 31 862 7 6 3 24 18 320 125 2 1 1 1 9 7 4 012 00 Time from first dose (months) Bladder cancer: IHC 3+ Bladder cancer: IHC 2+ Bladder cancer: Total 1984 16 12 20 14 41 29 219 9 6 3 13 8 5 23 14 8 Median PFS in months (95% CI) Pancreatic cancer: IHC 3+ 5.4 (2.8, NR) Pancreatic cancer: IHC 2+ 2.8 (1.4, 9.1) Pancreatic cancer: Total 3.2 (1.8, 7.2) 9 12 15 15 Time from first dose (months) 1.0- Biliary tract cancer Probability of PFS 0.8- 0.6- Median PFS in months (95% CI) Biliary tract cancer: IHC 3+ 7.4 (2.8, 12.5) Biliary tract cancer: IHC 2+ 4.2 (2.8, 6.0) Biliary tract cancer: Total 4.6 (3.1, 6.0) 1.0- 0.4- 0.2- 0.0- 0 3 Pancreatic cancer Probability of PFS 0.8- 0.6- 0.4- 0.2- 0.01 0- 61 9 T T T 12 15 18 5 CO -a 21 24 Fo 0 دلي T 3 -6 -a Time from first dose (months) Number at risk, month Number at risk, month Biliary tract cancer: IHC 3+ 16 11 9 5 5 3 2 2 0 Pancreatic cancer: IHC 3+ 2 1 1 0 Biliary tract cancer: IHC 2+ 14 10 3 1 1 1 1 1 0 Pancreatic cancer: IHC 2+ 19 8 6 4 Biliary tract cancer: Total 41 27 14 6 6 4 3 3 0 Pancreatic cancer: Total 25 11 7 4 Circle indicates a censored observation CI, confidence interval; HER2, human epidermal growth factor receptor 2; IHC, immunohistochemistry; NR, not reached; PFS, progression-free survival 22 22 0 18 22 T 21 24 00 22 49 49#50Safety summary Most common drug-related TEAEs (>10%) Daiichi-Sankyo n (%) All patients (N=267) Nausea 3.7 55.1 Fatigueb 7.1 40.1 Any drug-related TEAES 226 (84.6) Neutropenia 19.1 32.6 Anemia 10.9 27.7 Drug-related TEAEs Grade ≥3 109 (40.8) Diarrhea 3.7 Vomiting 1.5 Serious drug-related TEAES 36 (13.5) Decreased appetite 1.5 755 25.8 24.7 17.6 Thrombocytopeniad 5.6 17.2 Drug-related TEAEs associated with dose discontinuations 23 (8.6) Drug-related TEAEs associated with dose interruptions 54 (20.2) Alopecia Increased transaminasese 0.4 Leukopenia 2.6 0 16.9 10.1 Grade ≥3 Any grade 10.1 10 30 20 40 Patients experiencing drug-related TEAEs (%) 50 60 Drug-related TEAEs associated 54 (20.2) with dose reductions ILD/pneumonitis adjudicated Drug-related TEAEs associated 4 (1.5)a with deaths as T-DXd related, n (%) All patients (N=267) Grade 1 7 (2.6) Grade 2 17 (6.4) Grade 3 1 (0.4) Grade 4 0 Grade 5 3 (1.1) Any grade 28 (10.5) Analyses were performed in patients who received 21 dose of T-DXd (N=267); median total treatment duration 5.6 months (range 0.4-31.1) *Included pneumonia (n=1), organizing pneumonia (n=1), pneumonitis (n=1), and neutropenic sepsis (n=1); 'category includes the preferred terms fatigue, asthenia, and malaise; "category includes the preferred terms neutrophil count decreased and neutropenia; "category includes the preferred terms platelet count decreased and thrombocytopenia; "category includes the preferred terms aspartate aminotransferase increased, alanine aminotransferase increased, gamma-glutamyltransferase increased, hypertransaminasemia; fcategory includes the preferred terms white blood cell count decreased and leukopenia ILD, interstitial lung disease; T-DXd, trastuzumab deruxtecan; TEAE, treatment-emergent adverse event 50#51Conclusions Daiichi-Sankyo The robust response rates and survival outcomes are encouraging and were observed across tumor types in heavily pretreated patients T-DXd demonstrated clinically meaningful activity across a broad range of HER2-expressing solid tumors: ORR: 37.1% in all patients and 61.3% in patients with IHC 3+ • Durable responses: median DOR 11.3 months in all patients and 22.1 months in patients with IHC 3+ Durable responses led to clinically meaningful progression-free and overall survival outcomes: • PFS: 6.9 months in all patients and 11.9 months in patients with IHC 3+ OS: 13.4 months in all patients and 21.1 months in patients with IHC 3+ The safety of T-DXd was consistent with the known profile DESTINY-Pan Tumor02 supports the potential role of T-DXd as a tumor-agnostic therapy for patients with HER2-expressing solid tumors DOR, duration of response; HER2, human epidermal growth factor receptor 2; IHC, immunohistochemistry; ORR, objective response rate; OS, overall survival; PFS, progression-free survival; T-DXd, trastuzumab deruxtecan 51#52Raludotatug deruxtecan (R-DXd; DS-6000) monotherapy in patients with previously treated ovarian cancer (OVC): subgroup analysis of a first-in-human Phase 1 study Kathleen Moore, 1,2 Alexander Philipovskiy,2,3 Kenichi Harano, 4 Brian Rini, 5 Kazuki Sudo, Shigehisa Kitano, David R. Spigel, 2,8 Jie Lin, Madan G. Kundu,⁹ Amine Bensmaine, 10 Yusuke Myobatake,⁹ Erika Hamilton 2,8 1Oklahoma University, Oklahoma City, OK, USA; 2Sarah Cannon Research Institute, Nashville, TN, USA; ³Florida Cancer Specialists, Lake Mary, FL, USA; 4National Cancer Center Hospital East, Kashiwa, Japan; "Vanderbilt- Ingram Cancer Center, Nashville, TN, USA; National Cancer Center Hospital, Tokyo, Japan; 7Japanese Foundation for Cancer Research, Tokyo, Japan; 8Tennessee Oncology, PLLC, Nashville, TN, USA; Daiichi Sankyo, Inc., Basking Ridge, NJ, USA; 10Daiichi Sankyo, Inc., Rueil-Malmaison, France. Daiichi-Sankyo 52 62#53Background • The emergence of platinum resistance in recurrent OVC is inevitable; these patients have a clear need for novel treatments¹ Mirvetuximab soravtansine-gynx received accelerated approval from the FDA for the treatment of patients with platinum-resistant, FRa-positive OVC (ORR: 31.7%, median DOR: 6.9 months)² • Expression of CDH6 is observed in -65-85% of patients with OVC3,4 Raludotatug deruxtecan (R-DXd; DS-6000) is a CDH6-directed ADC composed of three parts: a humanized anti-CDH6 IgG1 mAb, covalently linked to a topoisomerase I inhibitor payload via a tetrapeptide-based cleavable linker5 R-DXd was designed with 7 key attributes Humanized anti-CDH6 IgG1 mAba Deruxtecan H H₂C- ན་ཚིག་ NH H HỒ CH Cleavable tetrapeptide-based linker Topoisomerase I inhibitor payload (DXd) Payload mechanism of action: topoisomerase I inhibitor5.b High potency of payload 5.b High drug-to-antibody ratio=85,b Payload with short systemic half-life 6.b.c Tumor-selective cleavable linker5.b Stable linker-payload 5.b Bystander antitumor effect5,b *Image is for illustrative purposes only; actual drug positions may vary. "The clinical relevance of these features is under investigation. *Based on animal data. ADC, antibody-drug conjugate; CDH6, cadherin 8; DOR, duration of response; DXd, deruxtecan; FDA, United States Food and Drug Administration; FRa, folate receptor alpha; IgG1, immunoglobulin G1; mAb, monoclonal antibody; ORR, objective response rate; OVC, ovarian cancer. 1. Richardson DL, et al. JAMA Oncol. 2023;9:851-859; 2. ELAHERE™ (mirvetuximab soravtansine-gynx) prescribing information. Accessed September 1, 2023; 3. Bartolomé RA, et al. Mol Oncol. 2021;15:1849-1885; 4. Shintani D, et al. Gynecol Oncol. 2022:188(Suppl. 1):S118: 5. Suzuki H, et al. Ann Oncol. 2021:32(Suppl. 5):S381-5375; 8. Nakada T, et al. Chem Pham Bull (Tokyo). 2019:87:173–185. Daiichi-Sankyo 53#54Daiichi-Sankyo First-in-human phase 1 study of R-DXd (NCT04707248)1,2 Subgroup analysis of patients with OVC who received R-DXd at 4.8–8.0 mg/kga Part A Dose escalation: R-DXd IV Q3W Part B Dose expansion: R-DXD IV Q3W 9.6 mg/kg 8.0 mg/kg OVC cohort: 4.8 mg/kg OVC cohort: 6.4 mg/kg 6.4 mg/kg 4.8 mg/kg 3.2 mg/kg OVC cohort: 5.6 mg/kg OVC cohort: 8.0 mg/kg 1.6 mg/kg Enrollment criteria: • • Advanced/metastatic OVC not amenable to SOC therapy ECOG PS 0-1 Prior taxane and platinum-based chemotherapy No previous CDH6-targeting agents or ADCs with a linked topoisomerase I inhibitor . Patients were not selected based on tumor CDH6 expression • " Key primary objectives: Safety and tolerability Determine MTD and RDES for dose expansion Determine ORR per RECIST v1.1 for dose expansion Key secondary objectives: . PK: ADC, total anti-CDH6 antibody, and the DXd payload Antitumor activity per RECIST v1.1 Immunogenicity 34.8-8.0 mg/kg R-DXd dose cohorts were initially prioritized for dose expansion due to a favorable benefit/risk profile. ADC, antibody-drug conjugate; CDHB, cadherin 6; ECOG PS, Eastern Cooperative Oncology Group performance status; IV, intravenous; MTD, maximum tolerated dose; ORR, objective response rate; OVC, ovarian cancer; PK, pharmacokinetics; Q3W, every 3 weeks; RDE, recommended doses for expansion; RECIST 1.1, Response Evaluation Criteria in Solid Tumors version 1.1; SOC, standard of care. 1. ClinicalTrials.gov. https://classic.clinicaltrials.gov/ct2/show/NCT04707248. Accessed July 20, 2023; 2. Data on file. Daiichi Sankyo, Inc. DS6000-A-U101 protocol, version 3; 20:20. 54#55Baseline demographics and disease characteristics Data cutoff: July 14, 2023 Received 4.8-8.0 mg/kg R-DXd (OVC population; N=60) Daiichi-Sankyo OVC (4.8-8.0 mg/kg) N=60 4.8 mg/kga (n=13) 5.6 mg/kga (n=8) 6.4 mg/kgb (n=24) 8.0 mg/kg (n=15) Age, median years (range) ECOG PS, n (%) 66 (42-82) Ongoing on treatment: n=9 Ongoing on treatment: n=8 Ongoing on treatment: n=13 Ongoing 0 22 (36.7) on treatment: n=3 1 38 (63.3) Platinum-resistant diseasee, n (%) 55 (91.7) Discontinued (n=27) Number of prior systemic regimens, median (range) 4 (1-13) Received prior systemic therapy, n (%) PD (n=14) Clinical progression (n=2) TEAE (n=9) Otherd (n=2) Bevacizumab 41 (68.3) PARP inhibitor 39 (65.0) • Median treatment duration: 18 weeks (range: 3-115) • 12 (20%) patients received treatment for ≥6 months • 3 (5%) patients received treatment for ≥18 months Baseline tumor CDH6 expression H-score, median (range) 125 (0-250) "Enrollment ongoing. "Enrollment completed. "As of October 2022, the patients who were still receiving R-DXd at 8.0 mg/kg were dose-reduced to receive R-DXD 6.4 mg/kg. "Death (n=1) and informed consent withdrawn (n=1). "Defined as tumor progression during or within 6 months after completion of prior platinum therapy. Five patients had tumor progression 6 months after platinum therapy. CDH8, cadherin 8; ECOG PS, Eastern Cooperative Oncology Group performance status; OVC, ovarian cancer; PARP, poly adenosine diphosphate-ribose polymerase; PD, progressive disease; TEAE, treatment-emergent adverse event. 55#56Daiichi-Sankyo Safety profile of R-DXd is manageable Patients with OVC who received R-DXd at 4.8-8.0 mg/kg Overview of TEAES n (%) N=60 Most common (≥10%) treatment-related TEAES Preferred term n (%) N=60 Any TEAEs 57 (95.0) All grades Grade ≥3 TEAE with CTCAE Grade ≥3 31 (51.7) TEAE associated with drug discontinuation 9 (15.0) Nausea 35 (58.3) 1 (1.7) TEAE associated with dose interruption 22 (36.7) Fatigue 27 (45.0) 2 (3.3) Vomiting 20 (33.3) 1 (1.7) TEAE associated with dose reduction 15 (25.0) " Any treatment-related CTCAE Grade ≥3 TEAE Treatment-related TEAE associated with death • 要 3.3% (2/60) of patients in the 4.8-8.0 mg/kg cohort experienced Grade 5 ILD; both occurred in the 8.0 mg/kg cohort and were adjudicated as treatment-related 8.9% (4/45) of patients in the 4.8-6.4 mg/kg cohort experienced ILD (all Grade 2), of which 2 were adjudicated as treatment-related As of October 2022, the 8.0 mg/kg cohort was closed due to a higher incidence of serious and Grade ≥3 TEAEs and lack of a favorable benefit/risk ratiob Further dose assessment is ongoing at three doses: 4.8, 5.6 and 6.4 mg/kg Data cutoff: July 14, 2023. "Grade 5 ILD. 6/15 (40.0%) patients in the 8.0-mg/kg OVC cohort experienced serious and Grade 23 TEAEs. CTCAE, Common Terminology Criteria for Adverse Events; ILD, interstitial lung disease; OVC, ovarian cancer; TEAE, treatment-emergent adverse event. Alopecia Malaise 22 (36.7) Anemia 17 (28.3) 11 (18.3) 2 (3.3)a Decreased neutrophil count 15 (25.0) 7 (11.7) Diarrhea 16 (26.7) 1 (1.7) Decreased appetite 15 (25.0) 1 (1.7) Decreased platelet count 10 (16.7) 3 (5.0) 7 (11.7) 0 6 (10.0) 0 56 99#57Preliminary efficacy data for R-DXd are promising in pretreated OVC patients Best % change from baseline in sum of diameters of target lesions Data cutoff: July 14, 2023. *CR + PR + stable disease. 80 • 60 40 40 20 20 -20 40 -60 -80 -100 0. ☐ • Confirmed ORR: 46% in the 4.8-8.0 mg/kg OVC cohort (23/50; 95% CI: 32–61); one CR and 22 PRs 。 4 unconfirmed responses were ongoing at data cutoff Disease control ratea: 98% 4.8 mg/kg 8.0 mg/kg Starting dose level | 4.8 mg/kg (n=9) 5.6 mg/kg (n=4) 6.4 mg/kg (n=23) 8.0 mg/kg (n=13) The efficacy evaluable population included patients who received 21 dose of study treatment and completed 21 post-baseline tumor assessment or discontinued treatment for any reason. Change from baseline in target tumor size was assessed per RECIST v1.1. Two patients with no measurable lesions at baseline and one patient who discontinued and did not have a post-baseline tumor assessment were not included in the waterfall plot. CI, confidence interval; CR, complete response; ORR, objective response rate; OVC, ovarian cancer; PR, partial response; RECIST v1.1, Response Evaluation Criteria in Solid Tumors version 1.1. 57 40 Daiichi-Sankyo#58Daiichi-Sankyo Preliminary efficacy data for R-DXd are promising in pretreated OVC patients 70 50 30 • Median time to response: 6 weeks (95% CI: 5-11) Median DORª: 11.2 months (95% CI: 3.0-NE) Median PFSb: 7.9 months (95% CI: 4.4-12.4) Data cutoff: July 14, 2023. % Change from baseline in sum of diameters of target lesions 10 -10 10 -30 550 -50 -70 -90 -110 -130 0 2 4 6 8 4.8 mg/kg (n=9) 10 T 12 14 16 Time (months) from first dose of study drug Starting dose level ■5.6 mg/kg (n=4) T 18 T T 20 20 22 24 26 6.4 mg/kg (n=23) 8.0 mg/kg (n=13) *Median follow-up for DOR: 5.8 months (range: 1.4-16.8). "Median follow-up for PFS: 5.6 months (range: 0.03-25.1). The efficacy evaluable population included patients who received 21 dose of study treatment and completed 21 post-baseline tumor assessment or discontinued treatment for any reason. Change from baseline in target tumor size was assessed per RECIST v1.1. Two patients with no measurable lesions at baseline and one patient who discontinued and did not have a post-baseline tumor assessment were not included in the spider plot. CI. confidence interval; DOR, duration of response; NE, not estimable, OVC, ovarian cancer, PFS, progression-free survival; RECIST v1.1. Response Evaluation Criteria in Solid Tumors version 1.1. 58 50#59Daiichi-Sankyo Conclusions • • • • R-DXd is the first CDH6-directed ADC to demonstrate promising efficacy in patients with heavily pretreated platinum-resistant OVC who were not selected based on tumor CDH6 expression 。 ORR: 46% in the 4.8-8.0 mg/kg OVC cohort; one CR and 22 PRs ● Median DOR: 11.2 monthsª 。 Median PFS: 7.9 monthsb Safety profile is manageable, and toxicities are consistent with those observed with other DXd ADCs 1,2 Based on the accumulated overall safety, tolerability, PK and efficacy profile of R-DXd, the 8.0 mg/kg cohort was closed, and further assessment is ongoing at three dose levels: 4.8 mg/kg, 5.6 mg/kg and 6.4 mg/kg These data support further clinical evaluation of R-DXd in a late-phase study in patients with OVC *Median follow-up for DOR: 5.8 months (range: 1.4-16.8). "Median follow-up for PFS: 5.6 months (range: 0.03-25.1). ADC, antibody-drug conjugate; CDH8, cadherin 8; CI, confidence interval; CR, complete response; DOR, duration of response; DXd, deruxtecan; ORR, objective response rate; OVC, ovarian cancer; PFS, progression-free survival; PK, pharmacokinetics; PR, partial response. 1. Guo Z, et al. J Clin Pham Ther 2022:47:1837-1844; 2. Jänne PA, et al. Cancer Discov. 2022;12:74-89. 59 59#60A few data from poster presentation Ifinatamab Deruxtecan (I-DXd; DS-7300) in patients with advanced solid tumors: Updated clinical and biomarker results from a phase 1/2 study Manish R. Patel,1,2 Toshihiko Doi,³ Takafumi Koyama, 4 Gerald S. Falchook, 5 Claire Friedman, 6 Sarina A. Piha-Paul, Martin Gutierrez, Mark Awad, Ahmad Mattour, 10 Taroh Satoh, 11 Naoko Okamoto, 12 Jasmeet Singh, 12 Naoto Yoshizuka, 12 Meng Qian, 12 Xiaozhong Qian, 12 Brittany P. Tran, 12 Ololade Dosunmu,² Pengcheng Lu, 2 Melissa L. Johnson² 1Florida Cancer Specialists and Research Institute, Sarasota, FL, USA; 2Sarah Cannon Research Institute, Nashville, TN, USA; ³National Cancer Center Hospital East, Chiba, Japan; 4National Cancer Center Hospital, Tokyo, Japan; 5Sarah Cannon Research Institute at HealthONE, Denver, CO, USA; 6Memorial Sloan Kettering Cancer Center, New York, NY, USA; 7The University of Texas MD Anderson Cancer Center, Houston, TX, USA; John Theurer Cancer Center, Hackensack University Medical Center, Hackensack, NJ, USA; Dana-Farber Cancer Institute, Boston, MA, USA; 10Henry Ford Health System, Detroit, MI, USA; 11Osaka University Hospital, Osaka, Japan; 12Daiichi Sankyo, Inc., Basking Ridge, NJ, USA Daiichi-Sankyo 60 60#61Efficacy Analysis in Select Tumor Types (≥4.8 mg/kg cohort) A) SCLC³ 100 Starting dose level SCLC n=21 11 (52.4; 29.8-74.3) 1 (4.8) 10 (47.6) Efficacy population (24.8 mg/kg) 80 6.4 mg/kg 8.0 mg/kg 120 mg/kg 16.0 mg/kg Confirmed ORR, n (%; 95% CI) 60 40 Confirmed CR, n (%) Confirmed PR, n (%) TTR, median (95% CI), months DOR, median (95% CI), months 1.2 (1.2-1.4) • 5.9 (2.8-7.5) 2 & 9 Median PFS, months (95% CI) 5.6 (3.9-8.1) Median OS, months (95% CI) 12.2 (6.4-NE) Best percentage change in sum of diameters from baseline in target Jesions -100 Daiichi-Sankyo Follow-up, median (95% CI), months Safety population (all doses) Number of prior systemic regimens, median (range) Platinum-based chemotherapy, n (%) Immunotherapy, n (%) Irinotecan or topotecan, n (%) Topotecan, n (%) 11.7 (4.6-12.9) n=22 2 (1-7) 22 (100) 18 (81.8) 5 (22.7) 3 (13.6) In the ≥4.8 mg/kg population, the confirmed ORR was 27.3% (38/139; 95% CI: 20.1%-35.5%) • ORRS in the tumor types selected in this analysis were as follows: -SCLC: 11/21 (52%) patients achieved a PR (n=10) or CR (n=1) -ESCC: 6/28 (21%) patients achieved a PR See next slide for mCRPC and sqNSCLC "One patient received both. Change from baseline in target lesions was assessed per RECIST v1.1. All 21 patients were evaluable at baseline, but one did not have any post-baseline tumor assessments, and so was not included in the waterfall plot. B) ESCC 100 Starting dose level 80 14.8 mg/kg 8.0 mg/kg 120 mg/kg 8 9 & 0 Best percentage change in sum of diameters from baseline in target Jesions Efficacy population (24.8 mg/kg) Confirmed ORR, n (%; 95% CI) Confirmed PR, n (%) TTR, median (95% CI), months DOR, median (95% CI), months ESCC n=28 6 (21.4; 8.3-41.0) 6 (21.4) 1.4 (1.2-NE) 3.5 (2.4-NE) Median PFS, months (95% CI) 2.8 (2.1-5.5) Median OS, months (95% CI) 7.0 (4.8-12.2) Follow-up, median (95% CI), months 14.9 (6.3-NE) Safety population (all doses) n=29 Number of prior systemic regimens, median (range) Cisplatin/carboplatin/oxaliplatin, n (%) 4 (1-7) 29 (100) Taxane, n (%) 21 (72.4) Immunotherapy, n (%) -100 27 (93.1) Change from baseline in target lesions was assessed per RECIST v1.1. Of 28 patients with measurable disease at baseline, three did not have post-baseline tumor assessments, and so were not included in the waterfall plot. the 61#62Efficacy Analysis in Select Tumor Types (≥4.8 mg/kg cohort) C) mCRPC Starting dose level Best percentage change in sum of diameters from baseline in target Jesions 100 Efficacy population (24.8 mg/kg) 80 6.4 mg/kg 8.0 mg/kg 12.0 mg/kg 16.0 mg/kg Confirmed ORR, n (%; 95% CI)- Confirmed PR, n (%) 60 40 Confirmed ORR in patients with liver mets at baseline (27/59, 45.8% of mCPRC efficacy population 24.8 mg/kg), n (%) 8 0 8 9 80 TTR, median (95% CI), months* DOR, median (95% CI), months- Median PFS, months (95% CI) Daiichi-Sankyo mCRPC n=73 15 (25.4; 15.0-38.4) 15 (25.4) 9 (33.3) 1.4 (1.2-2.6) 6.4 (3.0-10.0) 5.3 (4.1-6.9) 13.0 (10.3-16.0) 16.6 (14.5-18.6) ⚫The sqNSCLC expansion cohort was the latest expansion cohort to open and is ongoing, hence the relatively short duration of follow-up . ORRS in the tumor types selected in this analysis were as follows: -mCRPC: 15/59 (25%) patients achieved a PR -sqNSCLC: 4/13 (31%) patients achieved a PR Median OS, months (95% CI)b Follow-up, median (95% CI), months Safety population (all doses) n=75 Number of prior systemic regimens, median (range) Taxane, n (%) NHA_n (%) 6 (1-11) 61 (81.3) 72 (96.0) -100 "The ORR is calculated based on 59 patients who received 21 dose 24.8 mg/kg, had measurable disease at baseline, >2 postbaseline scans, and/or discontinued treatment for any reason at data cutoff. *n=73, including patients with bone metastases who were not evaluable for ORR Change from baseline in target lesions was assessed per RECIST v1.1. Two patients did not have any post-baseline tumor assessments and were not included in the waterfall plot. D) sqNSCLC 100 Starting dose level Efficacy population (24.8 mg/kg) Best percentage change in sum of diameters from baseline in target lesions, -20 89 8 8 80 4.8 mg/kg 12.0 mg/kg 16.0 mg/kg 60 40 Confirmed ORR, n (%; 95% CI) Confirmed PR, n (%) TTR, median (95% CI), months 20 0 -100 DOR, median (95% CI), months Follow-up, median (95% CI), months Safety population (all doses) Number of prior systemic regimens, median (range) Platinum-based chemotherapy, in (9) Immunotherapy, n (%) Taxane, n (%) sqNSCLC n=13 4 (30.8, 9.1-61.4) 4 (30.8) 1.3 (0.7-NE) 4.1 (2.8-NE) 5.2 (1.7-NE) n=18 3 (1-12) 18 (100) 18 (100) 16 (88.9) Change from baseline in target lesions was assessed per RECIST v1.1. One patient did not have any post-baseline tumor assessments and was not included in waterfall plot. Since enrollment in the sqNSCLC cohort is ongoing, analyses of PFS and OS in this cohort are not yet mature. 19 62#63Most Common (>15% of Study Total) TEAEs, Regardless of Causality Daiichi-Sankyo System organ class preferred All Grade term, n (%)³ grades 23 SCLC (n=22) ESCC (n=29) mCRPC (n=75) sqNSCLC (n=18) Study total (N=174) All Grade All Grade grades ≥3 grades 23 All Grade grades 23 All Grade grades 23 Nausea 13 (59.1) 1 (4.5) 13 (44.8) 1 (3.4) 51 (68.0) 2 (2.7) 11 (61.1) 2 (11.1) 105 (60.3) 6 (3.4) Anemia 6 (27.3) 1(4.5) 12(41.4) 8 (27.6) 27 (36.0) 15 (20.0) 4 (22.2) 3 (16.7) 57 (32.8) 33 (19.0) IRRad 3 (13.6) 0 11 (37.9) 0 25 (33.3) 0 5 (27.8) 0 57 (32.8) 0 Decreased appetite 5(22.7) 1 (4.5) 11 (37.9) 2 (6.9) 24 (32.0) 0 4 (22.2) 0 56 (32.2) 3 (1.7) Fatigue 11 (50.0) 0 6 (20.7) 0 32 (42.7) 1 (1.3) 1 (5.6) 0 55 (31.6) 1 (0.6) Vomiting 6 (27.3) 0 2 (6.9) 0 Diarrhea 3 (13.6) 0 2 (6.9) 0 33 (44.0) 2 (2.7) 5 (27.8) 1 (5.6) 54 (31.0) 3 (1.7) 21 (28.0) 2 (2.7) 3 (16.7) 1 (5.6) 30 (17.2) 3 (1.7) . No new safety signals were observed; the safety profile was consistent with previous reports • The most common TEAEs associated with drug discontinuation were pneumonitis (n=3) and ILD (n=2) • The most common (≥3%) Grade ≥3 TEAEs were anemia (19.0%), neutropenia (4.0%), and nausea and lymphocyte count decreased (3.4% each) • Overall, 10/174 patients (5.7%) had confirmed ILD that was adjudicated as drug- related; 5 of these cases led to drug discontinuation. Most cases of ILD were Grade 1 or 2 (n=8); one Grade 4 ILD occurred in the 12 mg/kg cohort, and one Grade 5 ILD occurred in the 16 mg/kg cohort Pyrexia 4 (18.2) 0 6 (20.7) 0 11 (14.7) 0 3 (16.7) 0 30 (17.2) 0 Constipation 4 (18.2) 1(4.5) 6 (20.7) 1 (3.4) 13 (17.3) 0 3 (16.7) 0 29(16.7) 2 (1.1) aAdverse events were coded using MedDRA, version 25.1. Includes patients with SCLC, ESCC, mCRPC, sqNSCLC and other tumor types. Prophylactic premedication for nausea, vomiting, and IRR was not permitted for primary prophylaxis during Cycle 1 of dose escalation. dFor Grade 2 IRRs, prophylactic medication (with or without corticosteroids) was administered for ≤24 hours at the discretion of the investigator before subsequent administration of I-DXd. 63#64ESMO Highlights 2023 Agenda ESMO presentations ✓ TROPION-Lung01 study TLR ✓ TROPION-Lung05 Ph2 study results ✓ TROPION-Breast01 study TLR ✓ BEGONIA study longer follow-up data ✓ DESTINY-Pan Tumor02 primary analysis data ✓ DS-6000 Ph1 study OVC subgroup analysis data ✓ DS-7300 Ph1/2 study updated data (extract) 2 Q&A Speakers Ken Takeshita Head of Global R&D Daiichi-Sankyo Mark Rutstein Head of Global Oncology Clinical Development Content will be delivered on-demand after the meeting 64#65Contact address regarding this material Daiichi Sankyo Co., Ltd. Corporate Communications Department TEL: +81-3-6225-1125 Email: [email protected] Daiichi-Sankyo