Major R&D Pipeline: 3ADCs

HER3-DXd: NSCLC EGFR mutated NSCLC Ph1 study (combination with osimertinib): First patient dosed in June Presented interim results of Ph1 monotherapy EGFR mutated NSCLC cohort at ASCO 2021 Ph1 efficacy Ph1 safety Febrile neutropenia Hypoxia Daiichi-Sankyo Confirmed ORR 39% Median Duration 6.9 Median PFS 8.2 TEAEs grade ≥3 in 25% of patients (N=81) of Response months months d Platelet count decreased Neutrophil count decreased e 40 20 Confirmed BOR CR PR SD PD NE + Ongoing treatment Fatigue Anemia Dyspnea -20 Best % change in SoD (BICR) from baseline -40 -60 + + + +++ + + + + + + + Ex19del Ex19del Ex19de L858R Y1069C L858R R958H Ex19del G8T3R NRAS G13D Ex19de Ex19del L861Q L858R T790M L718/ T790M T790M T790M T790M Exc0ns 67249 A8/13 C797S E7096 C7975 C797S EML4-ALK Multiple CCND1 ERBB4 V9031 EGFR CCNE1 PIK3CA EGFR KRAS G128 PIK3CA N345 CDKN2A G136RT FIK3CAH1047R PIK3CA G/62 PIK3CA H1047R METY1248H CCND3 Ex19del T790M T790M AGK-BRAF BRAF V600E + + G719x L858R L861Q G724S T790M C797S ECFR MET CDKN2A KRAS A146 ERBB4L1227R ERBB4M501V Lymphocyte count decreased 0% 25% 50% 75% 100% White blood cell count decreased Hypokalemia Data cutoff: September 24, 2020. Includes thrombocytopenia. Includes neutropenia. Includes hemoglobin decreased. 9 Includes leukopenia. Includes lymphopenia. BICR, blinded independent central review, BOR, best overall response; CR, complete response; NE, not evaluable; PD, progressive disease; PR, partial response; SD stable disease; SoD, sum of diameters. Data cutoff: September 24, 2020. a Six patients had BORS of NE due to no adequate post-baseline tumor assessment and are not shown; 1 had BOR of NE due to SD too early (< 5 weeks) and is shown with hatched markings b Genomic alterations known to be associated with EGFR TKI resistance identified in assays of tumor tissue/ctDNA in blood, collected prior to treatment with HER3-DXd. ©CDKN2A A143V; PIK3CA E542K, E545K, E726K; ERBB2 K200N; ERBB3 Q847*, Q849*. Demonstrated promising efficacy in patients with diverse mechanisms of EGFR TKI resistance NSCLC: non small cell lung cancer, TKI: tyrosine kinase inhibitor Demonstrated manageable safety profile and low rate of discontinuations due to adverse events -80 -100 EGFR Activating Mutations Other EGFR Mutations Amplifications T790M C797C C7975 Ex19dal Ex19del Ex19del L858R L718Q CCNE1 FGFR3-TACC3 Ex19del MET R988C Ex19del T790M Ex19del KRAS G12A, Q61R Non-EGFR Mutations and Fusions 20 20

View entire presentation