Daiichi Sankyo Company, Limited · TSE:4568
Daiichi Sankyo — ASCO 2023 / ESMO Breast Cancer 2023
74 slides from Daiichi Sankyo's conference presentation, 2023
Slide 1: ASCO 2023/ESMO BC 2023 Presentation Materials (vol.1)
ASCO 2023/ESMO BC 2023 Presentation Materials (vol.1) ENHERTUⓇ ◆ DESTINY-Breast01, -02, and -03 - Krop, I. et al., ASCO 2023 #1006 Oral ◆ DESTINY-Breast02 - Fehm et al., ESMO Breast 2023 #186O Oral ◆ DESTINY-Breast04 - Cameron et al., ESMO Breast 2023, #192MO Oral ◆ DESTINY-Breast04 sub-analysis - M
Slide 2: Age-Specific Pooled Analysis of T-DXd in HER2-Positive mBC
An Age-Specific Pooled Analysis of Trastuzumab Deruxtecan (T-DXd) in Patients With HER2-Positive Metastatic Breast Cancer (mBC) From DESTINY-Breast01, -02, and -03 Ian Krop, Yale Cancer Center, New Haven, CT, USA Additional authors: Hans Wildiers, Sara Hurvitz, Javier Cortes, Seock-Ah Im, Hiroji Iwa
Slide 3: Disclosures
Disclosures Dr. lan Krop reports: * Research grant/funding (institution): Genentech, Pfizer, Macrogenics * Honoraria: Genentech/ Roche, AstraZeneca ¢ Consulting/Advisory Boards: Daiichi Sankyo, Genentech/Roche, Seattle Genetics, Macrogenics, Merck, AstraZeneca, Novartis ASCO 2023 #1006 Oral
Slide 4: Background
Background 4 ¢ Regardless of treatment, older patients with HER2-positive mBC tend to have sub-optimal efficacy and safety outcomes’ ¢ Patients 265 years of age are also often underrepresented in clinical trials? ¢ T-DXd is approved for use in patients with HER2-positive unresectable or mBC after a
Slide 5: Study Design
UY Daichi-Sankyo Study Design‘ DESTINY-Breast01 (N = 253) T-DXd + Unresectable and/or metastatic breast cancer + HER2-positive (centrally confirmed in archival tissue) af cli pate + Previously treated with T-DM1 (n= T-DXd Pool; N = 851 T-Dxd 5.4 mg/kg Q3W dade Gatgens (N = 608) (n = 406) Unresectabl
Slide 6: Baseline Characteristics
Baseline Characteristics? T-DXd Pool TPC (DB-02) T-DM1 (DB-03) <65 265 275 <65 265 275 <65 265 275 (n =673) (n =178) (n = 34) (n = 164) (n =38) (n=8) (n = 206) (n =57) (n=8) 51.5 (22.4-65.0) 69.9(65.0-96.0) 79.0 (75.0-96.0)] 52.2 (24.7-64.9) 70.8 (65.0-86.5) 78.8 (75.5-86.5) 51.1 (20.2-64.9) 68.7 (6
Slide 7: Baseline Characteristics (cont.)
Baseline Characteristics? (cont.) T-DXd Pool TPC (DB-02) 265 265 (n = 178) (n = 38) HER? Status, n (%) 3+ 563 (83.7) 151 (84.8) 24 (70.6) 131 (79.9) 28 (73.7) 7 (87.5) 181 (87.9) 51 (89.5) 6 (75.0) 2+ (ISH amplified) 107 (15.9) 26 (14.6) 40 (29.4) 3219.5) 10 (26.3) 4 (12.5) 24 (11.7) 6 (10.5) 2 (25.
Slide 8: Medical History and Comorbidities
Medical History and Comorbidities? T-DXd Pool TPC (DB-02) 265 Disorders Blood and lymphatic system disorders (Soc) 73 (10.8) 26 (14.6) 5 (14.7) 12(7.3) 6 (15.8) 1 (12.5) 14 (6.8) 6 (10.5) 4 (12.5) Anemia 416.1) 18 (10.1) 3 (8.8) 9 (5.5) 4(10.5) 1 (12.5) 6 (2.9) 2 (3.5) 1 (12.5) Cardiac disorders (SO
Slide 9: Prior Therapies
Prior Therapies? T-DXd Pool TPC (DB-02) T-DM1 (DB-03) 265 265 265 (n = 178) (n = 38) (n =57) Prior regimens in the metastatic setting, n (%) 0 1(0.1) 1 (0.6) ) ) 0 0 4 (0.5) 0 0 1 102 (15.2) 22(12.4) 5 (14.7) 9(55) 2(6.3) 0 74 (35.9) 28 (49.1) 5 (62.5) 2 188 (27.9) 45 (25.3) 6 (17.6) 59 (36.0) 14 (3
Slide 10: Descriptive Efficacy According to Age for T-DXd
Descriptive Efficacy According to Age for T-DXd? Median Progression Free Survival Median Overall Survival DESTINY-Breast01 DESTINY-Breast02 DESTINY-Breast03 a <65 Years <65 265 <65 265 <65 265 DESTINY Breast-01 m265 Years (n=140)) (n=44) | (m=321) (n=85) | (m=212) (n=49) mOS, months 28.1 30.9 NR 30.
Slide 11: Confirmed ORR by BICR with T-DXd
Confirmed ORR by BICR? with T-DXd DESTINY-Breast01 DESTINY-Breast02 DESTINY-Breast03 ' ' ' ' 90 ' ' BH Complete Response H | 78.8% 77.6% 80 1 70.7% ‘ 70 : 65.9% | Partial Response 62.1% 614% | ! 60 2 : H fs | | 5 : H @ 40 i 1] 57.1 59.2 a 1 57.0 50.6 1 30 55.0 sag |i i 20 ' ' 10 ' f ' ' 0 i Hl 265 <
Slide 12: Relative Dose Intensity
Relative Dose Intensity 110 —~ 100 & > 90 2 80 2 £ 70 o 8 60 98.297.4 400 899.6 1008 99.5 a 188.8 889.2 @ 50 82.08 79.1 Z ®B 40 id 30 20 T-DXd Pool Trastuzumab Capecitabine Lapatinib T-DM1 (DB-03) = <65 Years T ™265 Years TPC (DB-02) * Relative dose intensity was similar between <65 and 265 age grou
Slide 13: Overall Safety Summary
Overall Safety Summary? oes T-DXd Pool TPC (DB-02) T-DM1 (DB-03) 265 265 265 (n= 177) (n= 38) (n= 57) (renee) ‘reatment duration, mo on ee nag ay WEP MEY omene mmng agen TEAE, n(%) 665 (99.6) 177(100.0) 33(100.0) | 148(943) 37(97.4) (100.0) | 194(95.1) 55(96.5) 8 (100.0) Drug-related 653 (97.8) 176(
Slide 14: Most Common Drug-related TEAEs in ≥20% of Patients
Most Common Drug-related TEAEs in 220% of Patients 4 T-DXd Pool TPC (DB-02) T-DM1 (DB-03) <65 265 275 <65 265 275 <65, 265 275 (n = 668) (n = 177) (n = 33) (n = 157) (n = 38) (n =8) (n = 204) (n =57) (n =8) Any grade? drug-related TEAEs, n(%) | 653(97.8) 176(99.4) | 33(100.0) | 144(91.7) 36(94.7) 8
Slide 15: Most Common Grade ≥3 Drug-related TEAEs
Most Common Grade 23 Drug-related TEAEs in 25% of Patients — T-DXd Pool 265 (n= 177) 275 (n = 33) <65 (n = 157) TPC (DB-02) 265 (n= 38) T-DM1 (DB-03) <65 265 (n=204) (n=57) Grade 23* drug-related TEAEs, n (%) 291 (43.6) 96 (54.2) 13 (39.4) | 48(30.6) 12 (34.6) 5 (62.5) 82 (40.2) 28 (49.1) 3 (37.5) N
Slide 16: Adjudicated Drug-related ILD/Pneumonitis
T-DXd Pool <65 265 (n = 668) (n = 177) TPC (DB-02) T-DM11 (DB-03) <65 265 275 <65 265 (n = 157) (n = 38) (n =8) (n = 204) (n =57) Any grade, n (%) 79 (11.8) 31 (17.5) 6 (2.9) 2 (3.5) 4 (12.5) 1 21 (3.1) 7 (4.0) 3(1.5) 1 (1.8) 0 2 48 (7.2) 20 (11.3) 2(1.0) 1 (1.8) 1 (12.5) 3 4 (0.6) 3(1.7) 1 (0.5) 0
Slide 17: Conclusion
YO Conclusion wy, ¢ Results of this pooled analysis indicate that T-DXd remains an effective treatment option for patients 265 years of age = mPFS and confirmed ORR by BICR were similar with T-DXd in patients <65 and 265 years of age within each trial ¢ The safety profile of T-DXd was acceptable acr
Slide 18: Patient-Reported Outcomes from DESTINY-Breast02
PATIENT-REPORTED OUTCOMES FROM DESTINY-BREAST02, A RANDOMIZED PHASE 3 STUDY OF TRASTUZUMAB DERUXTECAN (T- DXd) VS TREATMENT OF PHYSICIAN’S CHOICE (TPC) IN PATIENTS WITH HER2-POSITIVE METASTATIC BREAST CANCER Tanja Fehm, Gynecology and Obstetrics, Universitaetsklinikum Düsseldorf AöR, Düsseldorf, Ger
Slide 19: Declaration of Interests
Declaration of Interests A ¢ Prof Fehm reports advisory board compensation from Daiichi Sankyo, Novartis, Roche, Pfizer, MSD, and Teva Pharmaceuticals ESMO BC 2023 #1860 Oral 19
Slide 20: DESTINY-Breast02 study design
DESTINY-Breast02 study design WY Randomized, open-label, multicenter, phase 3 study (NCT03523585) a ney eligibility criteria? T-Dxd Primary endpoint Centrally confirmed HER2-positive (IHC 3+ or 5.4 mg/kg Q3W + PFS (BICR®) IHC 2+/ISH+) unresectable or metastatic breast = 406) Key secondary endpoint c
Slide 21: Baseline characteristics
=, UY Baseline characteristics baat T-DXd Baseline Characteristics n= 406 n= 202 Age, median (range), years 54.2 (22.4-88.5) 54.7 (24.7-86.5) Region, n (%) Asia 112 (27.6) 52 (25.7) Europe 152 (37.4) 78 (38.6) North America 41 (10.1) 23 (11.4) Rest of world 101 (24.9) 49 (24.3) HER2 status (IHC),? n
Slide 22: Progression-free survival by blinded independent central review
Progression-free survival by blinded independent =, . Dalichi-Sankyn central review es 100 4 Median (95% Cl), months & Xd 2 0 17.8(14.3-20.8) _ 6.9 (5.5-8.4) s 7 + g en TDXid: 62.3% (05% C1, 57.0467 1) HR (95% Cl): 0.3589 (0.2840-0.4535) ° 4 TPC: 27.2% (95% Cl, 20.1-34.8) P< 0.000001 " fot : 2 T-DXd
Slide 23: DESTINY-Breast02: safety summary
DESTINY-Breast02: safety summary T-DXd TPC Type of Adverse Event, n (%) 4042 n= 195 Any-grade drug-related TEAE 394 (97.5) 180 (92.3) Drug-related Grade >3 TEAEs 167 (41.3) 60 (30.8) Serious drug-related TEAEs 46 (11.4) 15 (7.7) Drug-related TEAEs associated 58 (14.4) 10 (5.1) with drug discontinuat
Slide 24: HEOR endpoints
HEOR endpoints Questionnaire Description Measures of interest Main analyses EORTC QLQ-C30 Oncology-specific + Global health status (GHS)/quality of life (QoL)@ + Change from baseline questionnaire + Physical, emotional, and social functioning + Time to definitive + Pain symptoms deterioration (TDD)
Slide 25: Global health status and health-related quality of life
Global health status and health-related quality of life 200 oe eT ze T 6 7 Mean (SD) GHS score at baseline 64.6(21.7) 65.0(22.8) A 10-point absolute 305 value change is 2044 considered clinically meaningful ~40_| _._ T-DXd (baseline n = 391) TPC | T-DXd + _g9_| —-— TPC (baselinen = 187) n<,10% n<10%
Slide 26: Time to definitive deterioration of GHS/overall QoL
Time to definitive deterioration of EORTC QLQ-C30 GHS/overall QoL = 1007 TS en 3 = 04 Median (95%Cl) 14.1 (10.4-18.7) 5.9 (4.3-7.9) s HR (95% Cl): 0.5573 (0.4376-0.7099) 5 807 P< 0.00018 3 704 Patients with 3 events, n (%) 205 (50.5) 106 (52.5) 2 60-4 o 2 2 504 7 a 404 3 304 r=] = 204 = + Censor 2 1
Slide 27: TDD of physical functioning and pain symptoms
Time to definitive deterioration of EORTC QLQ-C30 physical functioning and pain symptoms Physical Functioning Pain Symptoms = 104 ___—s as ___ A = Median (95% Cl) 48.7 (15.5-22.9) 6.8 (5.7-8.8) SI 100 Median (95% Cl) 18.7 (14.1-23.8) 5.8 (5.0-7.0) § © 3 HR (95% Cl): 0.4637 (0.3575-0.6014) 5 HR (95%
Slide 28: Time to definitive deterioration of EQ-5D-5L VAS
Time to definitive deterioration of EQ-5D-5L VAS 2 1 ___—— ST ps & 294 Median(95%Cl)_ 16.6 (13.6-20.2) 7.3 (5.8-10.6) s HR (95% Cl): 0.5906 (0.4583-0.7610) 5 P< 0.0001» By te, g 70 ' Patients with 2 6H , events, n (%) 188 (46.3) 98 (48.5) 2 y, = 50-4 hat 7 a 40-4 2 a0 se = A nae penn nnnny = 2-4 a +
Slide 29: Time to definitive deterioration in PRO measures
=, Time to definitive deterioration in PRO measures 4 wLweeou ' Physical functioninge 18.7 (15.5-22.9) 6.8(5.7-88) — | 0.46 (0.36-0.60) <0,0001 Emotional functioning 21.4(16.9-NE) 10.7 (6.9-15.4) a! 0.67 (0.51-0.88) 0.0041 Social functioning? 18.7 (13.9-28.8) 6.3(4.9-8.8) —— | 0.54 (0.42-0.70) <0.00
Slide 30: Mean change from baseline in nausea/vomiting score
Mean change from baseline in EORTC QLQ-C30 nausea/vomiting score Worse nausea/ vomiting 70 7 | T-Dxd | TPO Tt 60 7] Mean (SD) nausea/vomiting o = score at baseline 8.3 (16.6) 8.1 (17-1) i) 50 r > Eg 1 i | 1 t 2 g o #0 A 10-point absolute value 1 1 °° Ge wT change is considered ' 4 Dy#z 4 Clinically
Slide 31: Conclusions
Conclusions onan * Overall HRQoL was maintained longer with T-DXd than with TPC, as suggested by mean change from baseline data ¢ Definitive deterioration of HRQoL was delayed for patients in the T-DXd arm, as indicated by the hazard ratios for TDD which favored T-DXd over TPC for all evaluable pres
Slide 32: DESTINY-Breast04 Subgroup Analyses in HER2-Low, ER-Low mBC
DESTINY-BREAST04 SUBGROUP ANALYSES OF TRASTUZUMAB DERUXTECAN VS TREATMENT OF PHYSICIAN’S CHOICE IN PATIENTS WITH HER2-LOW, ESTROGEN- RECEPTOR EXPRESSION IMMUNOHISTOCHEMISTRY 0-10% METASTATIC BREAST CANCER David A. Cameron, Institute of Genomics and Cancer, University of Edinburgh, Edinburgh, United
Slide 33: Declaration of Interests
Declaration of Interests ww, ¢ Dr. David Cameron has previously received consulting fees from Lilly, Novartis, and Sanofi, as well as payments or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from Lilly, Novartis, and Pfizer. Dr. Cameron has also
Slide 34: Background
—™, Background 4 * Asmall but clinically significant proportion (~2-3%) of breast cancer tumors are considered HER2-low (IHC 1+ or IHC 2+/ISH—) with low ER expression (IHC 1-10%)'? and less sensitivity to endocrine therapies * Rather than behaving like tumors with high ER expression (IHC >10%), HER2
Slide 35: DESTINY-Breast04 Study Design
DESTINY-Breast04 Study Design YO An open-label, multicenter study (NCT03734029)'3 : Xd Primary endpoint 5.4 mg/kg Q3W + PFS by BICR (HR+) Patients@ CESKY A) Key secondary endpoints4 + PFS by BICR (all patients) + OS (HR+ and all patients) * HER2-low(IHC 1+ vs IHC 2+/ISH-), unresectable, and/or mBC t
Slide 36: Baseline Demographic Characteristics of ER Subgroups
Baseline Demographic Characteristics of ER Sub Baseline Characteristic* Age ER-negative (IHC 0% T-DXd (n = 40) TPC (n= 18) T-DXd TE = 35) TPC (n= 17) roups Median (range), years 58.9 (36.6-78.9) 55.9 (32.6-80.5) 57.6 (31.5-76.4) 50.6 (32.6-69.7) Age < 65 years, n, (%) 30 (75.0) 13 (72.2) 31 (88.6) 1
Slide 37: PFS in Patients by ER Expression
PFS in Patients by ER Expression Patients with ER-negative (IHC 0%) 100 womeoey— asuaii) anaes) vanraravesien —__o4a tou «| Eo § Bo 2 = no a OTE TTS OTE RWHE HME ONT WHOM RAM a mm Tine, months Wo ais Torsn=a) 0 DDB wA DWH we 7 S544 4D 2O U Dac Sakyn es Patients with ER-low (IHC 1-10%) 10 1 Median (9
Slide 38: OS in Patients by ER Expression
OS in Patients by ER Expression Patients with ER-negative (IHC 0%) 1005 Median (95%) 182 (19.6.NE) 83(s6208) 1 azar Ratio (95% Ci) 0.48 (0240.95) eo] —>——_ = wo z 4 & «04 oY 8 8 1 1 12:19 14 15 10 47 18 19 20 21 22 23 24 25 20 27 28 Time, months No. at rik: TOXd(n=40) 40 30 38 37 90 MM 34 2 31-30 28
Slide 39: ORR in Patients by ER Expression
ORR in Patients by ER Expression on Patients with ER-negative (IHC 0%) a oO ORR 50.0 (95% Cl) (33.8-66.2) Lb oO 16.7 (3.6-41.4) N oO Confirmed ORR (%) = wo lo} oO 0 zm mT-DXd (n= 40) mTPC (n = 18) Confirmed ORR (%) Patients with ER-low (IHC 1-10%) ORR 57.1 59 (95% Cl) (39.4-737) — (0.1-28.7) 0 4 mT-
Slide 40: Most common TEAEs in ≥20% Patients with ER IHC 0-10%
Most common TEAEs in 220% Patients with ER IHC 0-10% ~~ Preferred Term, % Any K Nausea 17.3 40 34.4 0 Vomiting 40.0 1.3 21.9 0 Fatigue 37.3 8.0 40.6 9.4 Decreased appetite 34.7 1.3 25.0 3.1 Alopecia 33:3 0 313) 0 Constipation 33.3 0 21.9 0 Anemia 30.7 10.7 34.4 3.1 Diarrhea 29.3 21 21.9 oa Aspartate
Slide 41: Conclusions
Conclusions ww, * In this analysis, T-DXd showed better efficacy compared to TPC in terms of PFS, OS, and ORR in patients with HER2-low, ER-low (IHC 1-10%) mBC * These results are comparable with those seen for patients with HER2-low, ER-negative (IHC 0%) mBC * Consistent with the primary analysis o
Slide 42: Exploratory Biomarker Analysis of DESTINY-Breast04 (Poster)
‘Trastuzumab Deruxtecan Versus Treatment of Physician's Choice in Patients With HER2-Low, Hormone Receptor-Positive Unresectable and/or Metastatic Breast Cancer: Exploratory Biomarker Analysis of DESTINY-Breast04 ASCO 2023 #1020 Post a ayn tel A: pt ene harass A asl 1 emo Shean pn ms acon worn ect r
Slide 43: Detailed Safety Analysis of DESTINY-Breast04
TRASTUZUMAB DERUXTECAN (T-DXD) VS TREATMENT OF PHYSICIAN’S CHOICE (TPC) IN PATIENTS WITH HER2-LOW UNRESECTABLE AND/OR METASTATIC BREAST CANCER: A DETAILED SAFETY ANALYSIS OF THE RANDOMIZED, PHASE 3 DESTINY-BREAST04 TRIAL Hope S. Rugo, UCSF Helen Diller Family Comprehensive Cancer Center, San Francis
Slide 44: Declaration of Interests
Declaration of Interests Ad Advisory and/or consultancy roles: Puma, NAPO, Blueprint, Daichi Sankyo, and Scorpion Therapeutics Institutional research grant and/or funding: Astellas Pharma Inc.; AstraZeneca; Daiichi Sankyo, Inc.; Hoffmann-La Roche AG/Genentech, Inc.; Gilead Sciences, Inc.; GlaxoSmith
Slide 45: DESTINY-Breast04 Study Design
=, DESTINY-Breast04 Study Design 7] An open-label, multicenter study (NCT03734029)13 — Primary endpoint T-DXd + PFS by BICR (HR+) 5.4 mg/kg Q3W Patients? (n = 373) Key secondary endpoints4 + PFS by BICR (all patients) + OS (HR+ and all patients) * HER2-low(IHC 1+ vs IHC 2+/ISH-), unresectable, and/o
Slide 46: DESTINY-Breast04 Background
DESTINY-Breast04 Background 4 Va Efficacy in All Patients’ (HR+ and HR-) Progression-Free Survival (by BICR) T-DXd 9.9mo 5.1mo Hazard ratio: 0.50, P <0.0001 ~ XX T-DXd Overall Survival 23.4mo 16.8mo Hazard ratio: 0.64, P= 0.001 J T-DXd is the first HER2-directed therapy to demonstrate statistically
Slide 47: Exposure-Adjusted Incidence Rates Overview
=, UY alichi-Sankyo Exposure-Adjusted Incidence Rates? Overview. T-DXd TPC n= 373 n= 184 Safety analysis set?, n (%) 371 (99.5%) 172 (93.5%) . EAIRs were measured to Treatment duration, median (range), mo 8.2 (0.2-33.3) | 3.5 (0.3-17.6) account for differences in Exposure, patient-years® 283.55 63.5
Slide 48: Exposure-Adjusted Incidence Rates for Selected TEAEs
Exposure-Adjusted Incidence Rates for Selected TEAEs 1) in 210% of Patients TPC n=172 n(%) Any Grade Grade23 Any Grade Grade23 Total patient-years of exposure 283.5 63.6 Nausea 282 (76.0) 17 (4.6) 52 (30.2) 0 EAIR per patient-year 0.99 0.06 0.82 te) Vomiting 150 (40.4) 6 (1.6) 23 (13.4) 0 EAIR per p
Slide 49: Selected TEAEs: Time to Onset and Duration
= OY Selected TEAEs? for 210% of Patients oaarebe Median Time to First Onset Median Duration of First Event Nausea 85 mT-DXd m= TPC Nausea Vomiting Vomiting Anemia Anemia Neutropenia Neutropenia Thrombocytopenia Thrombocytopenia 129 LD 60 ad |\Non-evaluable 0 20 40 60 80 100 120 140 0 10 20 30 40 50
Slide 50: Incidence of Selected TEAEs by Cycle
Incidence of Selected TEAEs by Cyclea alichi-Sankyo Shading cutoffs g 5 10% >10 -<20% >20 - 530% >30 -<40% >40 - 550% >50 - $60% 17.3 19.8 49 46 Vomiting 10.6 10.6 64 43 08 Anemia 15.4 48 42 12.8 74 5.3 Neutropenia 13.5 84 67 16.0 153 Thrombocytopenia 12.7 17 15 58 37 08 Fatigue | 35 | 12.9 5.5 [| 3
Slide 51: Nausea and Vomiting
Nausea and Vomiting * 189/371 patients (50.9%) in the T-DXd arm and 64/172 patients (37.2%) in the TPC arm received antiemetic prophylaxis? Nausea Vomiting n (%) Dose reduction associated with N/V 17 (4.6) 4 (2.3) 3 (0.8) 1 (0.6) Drug interruption associated with N/V 5 (1.3) 4 (2.3) 0 0 Drug discont
Slide 52: Neutropenia and Febrile Neutropenia
Neutropenia and Febrile Neutropenia ¢ Treatment-related neutropenia and febrile neutropenia of any grade were less frequent in the T-DXd arm than the TPC arm (12.9% vs 18.0% and 0.3% vs 2.9%, respectively) ¢ Neutropenia and febrile neutropenia were associated with fewer drug interruptions and dose r
Slide 53: G-CSF Use for Neutropenia and Febrile Neutropenia
G-CSF Use for Neutropenia and Febrile Neutropenia T-DXd TPC n (%) n = 371 n=172 Patients treated with G-CSF within 28 days of onset 25 (6.7) 34 (19.8) G-CSF use for neutropenia 24 (6.5) 33 (19.2) G-CSF use for febrile neutropenia 1 (0.3) 2 (1.2) * Patients treated with G-CSF within 28 days of neutro
Slide 54: Drug-Related TEAEs Based on Age
Drug-Related TEAEs Based on Age <65 years n (%) Any grade drug-related TEAEs? 258 (89.3) 92 (73.0) 67 (81.7) 38 (82.6) Grade >3 drug-related TEAEs 115 (39.8) 71 (56.3) 39 (47.6) 28 (60.9) Most prevalent drug-related TEAEs (all grades)? Nausea 213(73.7) 27 (21.4) 58 (70.7) 14 (30.4) Vomiting 102 (35.
Slide 55: Adjudicated Drug-Related ILD
Adjudicated Drug-Related ILD * Adjudicated ILD occurred in 45 patients (12.1%) in the T-DXd arm versus in 1 patient (0.6%) in the TPC arm * Most ILD events were low in grade; 3 patients (0.8%) had grade 5 ILD in the T-DXd arm « At DCO, 31 patients (68.9%) in the T-DXd arm recovered, were recovering,
Slide 56: Re-Treatment After Grade 1 ILD
Re-Treatment in Patients After Occurrence of Grade 1 ILD m= Treatment duration beforeILD Female, 54 years (SD/SD) sILD duration Female, 41 years (PR/PR) a Retreatment duration ILD recurrence Female, 67 years (PR/PR) Female, 68 years (PR/PR) Female, 68 years (PR/PR) Female, 71 years (PR/PR) 1) 200 40
Slide 57: Conclusions
Conclusions « EAIRs for anemia, neutropenia, alopecia and fatigue were lower for T-DXd, whereas nausea, vomiting, thrombocytopenia and ILD were higher, compared to TPC * Treatment-related neutropenia and febrile neutropenia occurred more often in patients treated with TPC, compared to T-DXd * The in
Slide 58: T-DXd in HER2+ Metastatic Colorectal Cancer: DESTINY-CRC02
T-DXd in Patients With HER2-Overexpressing/Amplified (HER2+) Metastatic Colorectal Cancer (mCRC): Primary Results From the Multicenter, Randomized, Phase 2 DESTINY-CRC02 Study Kanwal Raghav, The University of Texas MD Anderson Cancer Center, Houston, TX, USA Additional authors: Salvatore Siena, Atsu
Slide 59: Disclosures
Disclosures Dr. Kanwal Raghav reports: ° Research grant/funding (institution): Daiichi Sankyo, Bayer, UCB BioSciences, Hibercell, Merck, Janssen, Eisai, AbbVie, Guardant, Innovent, Xencor ° Honoraria: Bayer, Daiichi Sankyo, Seagen ¢ Advisory Board: Daiichi Sankyo, Eisai/Merck, SAGA Diagnostics, Baye
Slide 60: Background and Objective
Background and Objective a °* HER2+ mCRC » HER2+ (IHC 3+ or IHC 2+/ISH+) mCRC represents about 2%-3% of mCRC'*, and is associated with resistance to EGFR-targeted therapy*> » Ongoing research has shown HER2-targeted therapies to be a promising strategy for patients with HER2+ mCRC, an area of unmet
Slide 61: DESTINY-CRC02 Study Design
a, DESTINY-CRCO2 Study Design ¥Y A randomized, blinded, 2-stage, 2-arm, multicenter, global, phase 2 study (NCT04744831) ° Stage 1 (randomized) was followed by Stage 2 (nonrandomized), which enrolled an additional 42 patients Stage 1 Stage 2 Primary endpoint: * cORR by BICR : : Secondary endpoints:
Slide 62: Baseline Characteristics
Baseline Characteristics T-DXd T-DXd 5.4 mg/kg Q3W 6.4 mg/kg Q3W Stage 1 Stage 2 fal Stage 1 n=40 n=42 N=82 N=40 Median age, years (range) 58.2 (26-78) 60.6 (30-84) 59.1 (26-84) 62.3 (35-81) Sex, n (%) Male 21 (52.5) 24 (57.1) 45 (54.9) 19 (47.5) Region, n (%) Asia-Pacific 25 (62.5) 22 (52.4) 47 (57
Slide 63: Baseline Characteristics (cont.)
Baseline Characteristics (cont.) onnete T-DXd T-DXd 5.4 mg/kg Q3W 6.4 mg/kg Q3W Stage 1 Stage 2 Stage 1 n=40 n=42 N=40 HER2/RAS status, n (%) IHC 2+ ISH+/wild-type 7 (17.5) 5 (11.9) 6 (15.0) IHC 2+ ISH+/mutant 1 (2.5) 5 (11.9) 0 IHC 3+/wild-type 27 (67.5) 29 (69.0) 28 (70.0) IHC 3+/mutant 5 (12.5) 3
Slide 64: Prior Treatment
Prior Treatment T-DXd T-DXd 5.4 mg/kg Q3W 6.4 mg/kg Q3W Stage 1 Stage 2 tal Stage 1 n=40 n=42 N=82 N=40 Median prior lines of systemic therapy, n (range) 4 (1-12) 3 (1-7) 3 (1-12) 4 (1-8) Systemic chemotherapy, n (%) 40 (100) 42 (100) 82 (100) 40 (100) Irinotecan 39 (97.5) 40 (95.2) 79 (96.3) 40 (10
Slide 65: Efficacy Results
D: Efficacy Results T-DXd T-DXd 5.4 mg/kg Q3W 6.4 mg/kg Q3W Stage 1 Stage 2 Total Stage 1 n=40 n=42 N=82 N=40 cORR, n (%) [95% Cl] 18 (45.0) [29.3-61.5] 13 (31.0) [17.6-47.1] 34 (37.8) [27.3-49.2] 11 (27.5) [14.6-43.9] CR 0 0 0 0 PR 18 (45.0) 13 (31.0) 31 (37.8) 11 (27.5) sD 20 (50.0) 20 (47.6) 40 (
Slide 66: Median Progression-Free Survival by BICR
Median Progression-Free Survival by BICR Progression-free Survival 1.0 08 06 0.4 0.2 0.0 T-DXd 5.4 mg/kg Q3W Total (N = 82) Median PFS 5.8 months (95% Cl, 4.6-7.0) + Censor --- 95% Cl a a a oO 1 2 3 4 5 6 7 8 9 10 11 12 Time, months 62 79 69 60 58 43 27 21 14 7 3 3 0 T 1 13° 14 Number of patients at
Slide 67: Median Overall Survival
Median Overall Survival T-DXd 5.4 mg/kg Q3W Total (N = 82) T-DXd 6.4 mg/kg Q3W Stage 1 (N = 40) 105 Median OS 4.0 q—__.ee Median OS 13.4 months (95% Cl, 12.5-16.8) NE (95% Cl, 9.9 mon\ 08 4 0.8 4 § 3 $ 0.6 4 $ 06 4 beans s S n a g re 5 04-4 5 04-4 > > fe} fo} 0.2 4 0.2 4 + Censor + Censor --- 95% Cl
Slide 68: Best Percentage Change in Sum of Diameters, 5.4 mg/kg
Best Percentage Change in Sum of Diameters by BICR | for T-DXd 5.4 mg/kg - T-DXd 5.4 mg/kg Q3W Total (N = 82) 100 A RAS mutant 80 4 60 4 Best % Change in Sum of Diameters from Baseline ~60 Patients -100 - Best minimumchange, % n Mean — Standard deviation Median Minimum Maximum 80 -25.8 29.15 -23.0 1
Slide 69: Best Percentage Change in Sum of Diameters, 6.4 mg/kg
Best Percentage Change in Sum of Diameters by BICR for T-DXd 6.4 mg/kg T-DXd 6.4 mg/kg Q3W Stage 1 (N = 40) 100 — A RAS mutant 80 + Daichi-Sankyo = aan ale Best % Change in Sum of Diameters from Baseline ° | -4o0 | -6o —| “60 > Patients -100 + Best minimumchange, % n Mean = Standard deviation Median
Slide 70: Best Overall Response by BICR by Subgroup
Best Overall Response by BICR by Subgroup With Le) T-DXd 5.4 mg/kg ORR, % (n/N) 95% Cla T All patients (5.4 mg/kg) N= 82 —— 37.8 (31/82) 27.3-49.2 | IHC 3+ rr . 3-59. HER? status 46.9 (30/64) 34.3-59.8 IHC 2+/ISH+ a | 5.6 (1/18) 0.1-27.3 ild- —_— 39.7 (27/68 7 RAS status Wild-type .7 (27/68) 28.0-52
Slide 71: Overall Safety Summary
Oo Overall Safety Summary ee T-DXd 4 Hier Q3w 6.4 mg/kg Q3W Stage 1 Stage 2 Stage 1 n (%) n= 418 2 N = 39 TEAEs AO (97.6) 42 (100) 82 (98.8) 39 (100) Drug-related 38 (92.7) 38 (90.5) 76 (91.6) 37 (94.9) TEAEs grade 23 20 (48.8) 21 (50.0) 41 (49.4) 23 (59.0) Drug-related 16 (39.0) 18 (42.9) 34 (41.0)
Slide 72: TEAEs in ≥20% of Patients
=, UY TEAEs in 220% of Patients? omen T-DXd 5.4 mg/kg Q3W Total T-DXd 6.4 mg/kg Q3W Stage 1 N= 83" N=39 n(%) ny-grade Grade 23 Any-grade Grade 23 Any TEAEs 82 (98.8) 41 (49.4) 39 (100) 23 (59.0) Nausea 48 (57.8) T (8.4) 22 (56.4) 0 Fatigue* 38 (45.8) 8 (9.6) 18 (46.2) 2 (5.1) Neutropenia‘ 25 (30.1)
Slide 73: Adjudicated Drug-Related ILD/Pneumonitis
Adjudicated Drug-Related ILD/Pneumonitis by Oo Independent Adjudication Committee T-DXd DXd 4 mg/kg Q3W 4 mg/kg Q3W Adjudicated as drug-related Stage 1 ILD/pneumonitis, n (%) N=39 Any grade 4 (9.8) 3 (7.1) 7 (8.4) 5 (12.8) Grade 1 1 (2.4) 0 4 (41.2) 2 (5.1) Grade 2 3 (7.3) 3 (7.1) 6 (7.2) 2 (5.1) Gr
Slide 74: Conclusions
Conclusions wy. ¢ Promising antitumor activity was observed in patients with HER2+ mCRC at both the T-DXd 5.4 mg/kg and 6.4 mg/kg doses Numerically higher CORR in patients who received T-DXd at 5.4 mg/kg than 6.4 mg/kg (37.8% and 27.5%, respectively) « Greater antitumor activity (ORR) was observed i
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