FLAURA2 Trial

[Slide 1] FLAURA 2 vs. Real world Data Characteristic Osimertinib + Platinum- Osimertinib Monotherapy Japanese cohort (n=538) US cohort (n=1323) Pemetrexed (N = 279) (N = 278) Median age (range) - yr 61 (26-83) 62 (30-85) 71 (33-92) 70 (35-89) Sex - no. (%) Male 106 (38) 109 (39) 186 (34.6) 413 (31.2) Female 173 (62) 169 (61) 352 (65.4) 910 (68.8) EGFR mutation at randomization - no. (%) Exon 19 deletion 169 (61) 168 (60) 264 (49.1) 631 (48) L858R mutation 106 (38) 107 (38) 244 (45.4) 692 (52) WHO performance-status score - no. (%) 0 104 (37) 102 (37) 171 (31.8) 1 174 (62) 176 (63) 280 (52.0) 1096 (83) 2 1 (<1) 0 61 (11.3) 3 0 0 26 (4.8) 227 (17) Survival PFS 25.5 months 16.7 months 20.1 months OS NR NR 42.0 months 28.6 months os @24mo 79% 73% 71.6% 65% FLAURA trial eligibility - Eligible 330 (61.3) FLAURA trial eligibility - Ineligible 208 (38.7) Planchard NEJM 2023, Sakata Clin Lung Cancer 2025, Sabari JTO 2025

[Slide 1] on Lung Cancer SEPTEMBER 6-9, 2025 BARCELONA, SPAIN FLAURA2 phase III study¹ Osimertinib 80 mg (QD) + Patients with untreated locally N=557 pemetrexed 500 mg/m2 + advanced / metastatic EGFRm NSCLC Maintenance carboplatin AUC5 or cisplatin 75 mg/m2 osimertinib 80 mg (QD) + R Key inclusion criteria: pemetrexed 500 mg/m2 (Q3W) 1:1 (Q3W for 4 cycles for platinum-based treatments) Follow-up: Aged >18 years Stratified by: Race RECIST v1.1 assessment at 6 and Pathologically confirmed (Asian Chinese / 12 weeks, then Q12W until RECIST non-squamous NSCLC Asian non-Chinese / Treatment beyond PD allowed per investigator discretion v1.1-defined radiological PD non-Asian) Ex19del / L858R (local / central test) EGFRm test Survival follow-up for Q12W until (local central) WHO PS 0/1 WHO PS data cut-off for the planned final (0/1) OS analysis Stable CNS metastases were allowed Brain scans at baseline Osimertinib 80 mg (QD) (MRI / CT; mandatory) Primary endpoint: Investigator-assessed PFS (RECIST v1.1)1 os was a key secondary endpoint* Secondary endpoints included: OS, TFST, DoR, DCR, PFS2, TSST, HRQoL Final os analysis performed at 57% maturity NCT04035486 1. Planchard N Engl J Med 2023: 1935-1948 "For statistical significance of os, two-sided p-value of less than 0.04953. as determined by the BrienFleming spending rule, was required AUC. area under the curve; CNS, central nervous system; CT. computed tomography DCR, disease control rate DoR, duration of response; receptor mutated x19del exon 19 deletion HROoL health-related quality of life: MRI. magnetic resonance imaging; NSCLC non-small cell lung cancer; os, overall survival; PD. progressive disease PFS. progression-free survival --- [Slide 2] SEPTEMBER 2025 BARCELONA, SPAIN First subsequent treatment (FST) CTx was the most common FST (74%) after osi + CTx - os benefit with osi + CTx was observed despite SoC CTx 44% of FSTs were rechallenge with platinum CTx being the most common FST after osi mono 14% 14% Osi + CTx Osi mono 5% 3% 8% 7% 3% 69% received a FST 30% 77% received a FST No FST FST after discontinuing No FST FST after discontinuing osi due to PD* osi due to PD* 72% 44% n=127 n=185 Received FST Received FST (n=88) (n=143) Platinum-based CTx Non-platinum-based CTx EGFR targeted therapy (other than osi), mono or combo Osi + targeted agent / investigational drug (no CTx) Other Subsequent treatment was per investigator choice Data cutoff 12 June 2025 "Denominator (127 forosi CTxand 185 for asimanoj is menumber of patients who discontinued osimertinib due progresson. Other included ADCs, immunotherapies (PD-(L)1 inhibitors). other investigational inticancer therapies, antangiogeric therapies (VEGF(R) nhibitors]. catequentinib hy ydrochloride savolitinib, and unspecified herbal and traditional anticancer medicines D. Planchard First-line Osimertinib Chemotherapy Versus Osimertinib Monotherapy in GFRm Advanced NSCLC: EGFR, epidermal growth factor receptor, FST. first subsequent treatment; mono, monotherspy; os, overall survival; FLAURA2 Final Overall Survival osi, osmerting PD, progressive deease PD(L)1, programmed cell (ligand)- SoC, standard of care; VEGF(R), vascular endothelial growth factor (receptor)

[Slide 1] Classic EGFR first-line therapy may no longer be one size fits all, to the benefit of patie Osimertinib remains an option for standard, low- risk classic EGFR mut and those with borderline functional status I will tel what to Addition of chemotherapy to osimertinib or amivantamab to lazertinib may improve outcomes, particularly in those with higher risk features (TP53, ctDNA, brain/liver mets) Subcutaneous amivantamab solves some MARIPOSA issues, but not all It's yet to be determined whether sub Q ami + laz will take on FLAURA2 or find middle ground as a chemo-free regimen ctDNA continues to emerge as a biomarker - clinical trials

[Slide 1] ASLC 2025 World Conference #WCLC25 on Lung Cancer SEPTEMBER BARCELONA, SPAIN What is the tradeoff with upfront combination treatment? Osimertinib Osimertinib-Pemetrexed-carboplatin Amivantamab-Lazertinib Study FLAURA FLAURA2 MARIPOSA Efficacy PFS 18.9 m PFS 25.5 m PFS 23.7 m os 38.6 m V 31.8 m os 47.5 m V 37.6 m (HR 0.77) os Not reached V 36.7 m (HR 0.75) Side effects Diarrhoea 42% Diarrhoea 46% Diarrhoea 32% (all grades) Rash 22% Rash 30% Rash 64% Paronychia 27% Paronychia 26% Paronychia 69% Neutropenia 4% Neutropenia 25% Infusion related reaction 65% Neutrophil count decreased 7% Neutrophil count decreased 24% Peripheral edema 38% Anaemia 11% Anaemia 48% (G3 20%) Venous thromboembolism 40% Creatinine increase 14% Anaemia 27% Supportive care Emollient cream, steroid Emollient cream, steroid creams Emollient cream, steroid creams creams Cytopenias/ mouthwashes Prophylactic antibiotics, anticoagulation Schedule Daily oral tablet Daily oral tablet, Daily oral tablet, Visit every 2-3 months Iv Infusion once every 3 weeks Infusion/ subcut once per week for first 4 weeks; once every 2 weeks thereafter Financial $ $$ $$$$

[Slide 1] LASIC 2025 Санция ...... FLAURA2 phase III study¹ Osimertinib 80 mg (QD) Patients with untreated locally pemetrexed 500 mg/m2 Maintenance N=557 carboplatin AUCS osimertinib 80 mg (QD)+ advanced metastatic EGFRm NSCLC X cisplatin 75 mg/m2 pemetrexed 500 mg/m2 (Q3W) Follow-up: R Q3W for 4 cycles for 1:1 Key inclusion criteria: platinum-based treatments) RECIST v1.1 assessment at 6 and Stratified by: 12 weeks, then Q12W until RECIST Aged a18 years Race v1. 1-defined radiological PD Pathologically confirmed Asian Channel Auan not Cheese Treatment beyond PD allowed per investigator discretion non- squamous NSCLC Survival follow-up for Q12W until NOT Asian) data cut-off for the planned final Ex19del L858R (local central test) ECFRm test (kkal) central) OS analysis WHO PS 0/1 WHO PS (0/1) Stable CNS metastases were allowed Osimertinlb 80 mg (QD) Brain scans at baseline (MRI CT: mandatory) OS was a key secondary endpoint* Primary endpoint: Investigator-assessed PFS (RECIST v1.1)¹ Final OS analysis performed at 57% maturity Secondary endpoints included: OS, TFST, DoR, DCR, PFS2. TSST, HRQoL NC004335406 Panchard Hall NEW in for agenticance MOS CT. computed/tomography. determined DCR, disease control sate spending WR n/a Inspense voured (orm AUC area under one CMS revers cystem not sancer. - 05 HROSL PD. progressive qualify and MRI, PFS superic Sold magno savial funds PFS2, information - second payment in subsequent we NSCLC 1SST, exament time to second 00 and any CXW. restrent every (weeks) out, WHO PS RECIST WordHealth Organization status Parchast - I --- [Slide 2] IASLC 2025 World Conference #WCLC25 on Lung Cancer SEPTEMBER & 2023 BARCELONA, SPAIN FLAURA2: Overall survival No. Events / Median os, no. patients (%) months (95% CI) Median OS with osi + CTx was 47.5 months 144 / 279 (52) 47.5 (41.0, NC) Osi + CTx Osi mono 171 / 278 (62) 37.6 (33.2, 43.2) 1.0 2 years HR (95% CI) 0.77 (0.61, 0.96); p=0.02 80% 3 years 0.8 63% 72% 4 years 0.6 49% Probability of os 51% 0.4 41% 0.2 Median follow-up (censored patients), months (range): Osi + CTx 51.2 (0.2-60.4); Osi mono 51.3 (0.1-60.1) 0.0 0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60 63 Time from randomisation (months) No. risk 279 267 258 253 245 240 236 226 218 202 196 183 170 158 143 123 105 71 36 16 1 278 0 267 260 257 252 245 229 214 195 180 165 152 137 131 118 103 93 61 38 16 1 0 D Planchard First line Osimertinib Chemotherapy Vomus Cometime Montherary a EGFRm Advanced NSCLC FLAURAZ Final Overall Survival Tick marks indicate censored data A two sided p-value of <0 04953 was considered to indicate statistical significance at this final OS analysis Data cut-off: 12 June 2025 CI, confidence interval; CTx, chemotherapy; HR, hazard ratio; mono, monotherapy; NC, not calculable; OS, overall survival; osi, osimertinib --- [Slide 3] LASIC 2025 Санция ...... FLAURA2 phase III study¹ Osimertinib 80 mg (QD) Patients with untreated locally pemetrexed 500 mg/m2 Maintenance N=557 carboplatin AUCS osimertinib 80 mg (QD)+ advanced metastatic EGFRm NSCLC X cisplatin 75 mg/m2 pemetrexed 500 mg/m2 (Q3W) Follow-up: R Q3W for 4 cycles for 1:1 Key inclusion criteria: platinum-based treatments) RECIST v1.1 assessment at 6 and Stratified by: 12 weeks, then Q12W until RECIST Aged a18 years Race v1. 1-defined radiological PD Pathologically confirmed Asian Channel Auan not Cheese Treatment beyond PD allowed per investigator discretion non- squamous NSCLC Survival follow-up for Q12W until NOT Asian) data cut-off for the planned final Ex19del L858R (local central test) ECFRm test (kkal) central) OS analysis WHO PS 0/1 WHO PS (0/1) Stable CNS metastases were allowed Osimertinlb 80 mg (QD) Brain scans at baseline (MRI CT: mandatory) OS was a key secondary endpoint* Primary endpoint: Investigator-assessed PFS (RECIST v1.1)¹ Final OS analysis performed at 57% maturity Secondary endpoints included: OS, TFST, DoR, DCR, PFS2. TSST, HRQoL NC004335406 Panchard Hall NEW in for agenticance MOS CT. computed/tomography. determined DCR, disease control sate spending WR n/a Inspense voured (orm AUC area under one CMS revers cystem not sancer. - 05 HROSL PD. progressive qualify and MRI, PFS superic Sold magno savial funds PFS2, information - second payment in subsequent we NSCLC 1SST, exament time to second 00 and any CXW. restrent every (weeks) out, WHO PS RECIST WordHealth Organization status Parchast - I

[Slide 1] FIRST-LINE FLAURA SECOND-LINE THIRD-LINE Amivantamab + Platinum Doublet Docetaxel Osimertinib Platinum Doublet +/- ADC Therapy? Osimertinib Amivantamab HER3-DXd or Dato-DXd? Lazertinib? Ivonescimab + Platinum Doublet? And +/- resistance-matched therapies FIRST-LINE FLAURA2 SECOND-LINE THIRD-LINE Single Agent Docetaxel Osimertinib + Platinum Doublet Chemo HER3-DXd or Dato-DXd? Docetaxel Amivantamab Combinations? And +/- resistance-matched therapies FIRST-LINE MARIPOSA SECOND-LINE THIRD-LINE Platinum Doublet +/- Docetaxel Amivantamab + Lazertinib EGFR TKI HER3-DXd or Dato-DXd? ADC Therapy? Ivonescimab + Platinum Doublet? Platinum Doublet And +/- resistance-matched therapies

[Slide 1] 05:48 Tony Mok Combination VS single agent osimertinib Overall improvement in PFS doesn't imply that all patients have equal benefit from the combination therapy TP53, brain met, and liver met and are prognostic but not a predictive biomarker for combination approach Baseline cfDNA for EGFR mutation at FLAURA 2 is predictive for the combination while residual cfDNA for EGFR mutation may be predictive in MARIPOSA We will need prospective study to confirm.

[Slide 1] Potential sequencing approaches in the coming future PFS data with subsequent FLAURA 18.9 8.3 lines FLAURA 18.9 6.3 FLAURA 18.9 5.7 * 5.5 "If MET+, PFS amivantamab + lazertinib: 12 months FLAURA 18.9 7.4 5.5 FLAURA 2 29.4 5.1 5.5 FLAURA 2 29.4 5.5 5.5 FLAURA 2 29.4 7.4 5.5 MARIPOSA 23.7 5.5 5.5 MARIPOSA 23.7 5.5 5.5 0 5 10 15 20 25 30 35 40 45 Ph III: Amivantamab Lazertinib + CT Phase III: Amivantamab + CT Cohort D/A: Amivantamab + Lazertinib Platinum-based CT Teliso-\ + Osimertinib in MET+ Patritumab Deruxtecan Soria NEJM 2017 Passaro -AoO 2023 - Besse ASCO 2023 (cohort D) Yang ASCO 2023 Horinouchi - ESMO Asia 2023 Planchard NEJM 2024 Shu ASCO 2022 (cohort A) . Yu JCO 2023 (PFS based on BIRC) 2024 ASCO PRESENTED BY: Jordi Remon #ASCO24 ASCO AMERICAN SOCIETY OF CLINICAL ONCOLOGY ANNUAL MEETING Presentation is property of the author and ASCO. Permission required for reuse: contact permissions@asco.c KNOWLEDGE CONQUERS CANCER