CROWN Trial

2026ASCO ANNUAL MEETING --- PFS in the ITT Population (7-Year Follow-Up) The median duration of follow-up for PFS was 83.0 months (95% CI, 81.2-86.3) in the lorlatinib arm and 77.2 months (95% CI, 36.8-not evaluable) in the crizotinib arm Lorlatinib Crizotinib 100 (n=149) (n=147) 90 Events, n 62 119 PFS, median NR 9.1 80 70% (95% CI), months (68.5-NR) (7.4-10.9) 70 65% 63% HR (95% CI) 0.19 (0.13-0.26) 60% 60 57% 55% PFS, % 50 40 7 new PFS events occurred 30 between 5 and 7 20 15% 10% 10% years with 8% 10 7% 3% lorlatinib: 4 progression 0 events and 3 0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 68 72 76 80 84 88 92 96 100 deaths (not Months No. at risk treatment related) Lorlatinib 149 126 118 111 103 96 93 89 87 81 81 79 78 75 73 71 69 68 66 65 62 38 28 9 2 0 Crizotinib 147 107 70 42 30 19 16 16 11 10 9 9 9 8 8 7 6 6 6 5 2 2 0 0 0 0 At the time of this analysis, median PFS by investigator was still not reached with lorlatinib a confidence interval, MR, harard ratio, ITT, infention to boat, NR, not reached; PFS, progression free survival 2026 ASCO #ASCO26 PRESENTED BY Tony S.K. Mok, MD (tony@clo.cuhk.edu.hk) ASCO - OF ORICAL ANNUAL MEETING Presentation - property of the - and ABCO Permission required for - contact KNOWLEDGE CONQUERS CANCER --- PFS in Prespecified Patient Subgroups Number of events/ Number of patients, n (%) number of patients (n/N) Subgroup Lorlatinib Crizotinib Lorlatinib Crizotinib Hazard ratio (95% CI) All patients (stratified) 149 (100) 147 (100) 62/149 119/147 0.19 (0.13-0.26) All patients (unstratified) 149(100) 147 (100) 62/149 119/147 0.20 (0.15-0.28) Presence of brain metastases Yes 35 (23) 38 (26) 18/35 34/38 0.08 (0.04-0.19) No 114 (77) 109 (74) 44/114 85/109 0.23 (0.16-0.34) Ethnic origin Asian 66 (44) 65 (44) 30/66 51/65 0.24 (0.15-0.39) Non Asian 83 (56) 82 (56) 32/83 68/82 0.18 (0.11-0.28) ECOG performance status 0-1 146 (98) 138 (94) 60/146 111/138 0.20 (0.14-0.28) Gender Male 65 (44) 56 (38) 29/65 48/56 0.23 (0.14-0.38) Female 84 (56) 91 (62) 33/84 71/91 0.19 (0.12-0.29) Age < 65 years 89 (60) 103 (70) 29/89 86/103 0.15 (0.10-0.24) >65 years 60 (40) 44 (30) 33/60 33/44 0.27 (0.16-0.46) Smoking status Never 81 (54) 94 (64) 34/81 78/94 0.17 (0.11-0.27) Current/former 68 (46) 52 (35) 28/68 40/52 0.26 (0.16-0.44) Extent of disease Metastatic 135 (91) 139 (95) 55/135 114/139 0.19 (0.13-0.26) Histology Adenocarinoma 140 (94) 140 (95) 55/140 113/140 0.19 (0.13-0.26) 0.0625 0.25 0.5 1 2 Favors lorlatinib Favors crizotinib PFS benefit was consistent across all prespecified subgroups, including those with/without brain metastases and Asian/non-Asian patients CI, confidence interval; ECOG, Eastern Cooperative Oncology Group: PFS, progression free survival 2026 ASCO #ASCO26 PRESENTED BY: Tony S. K. Mok, MD (tony@clo.cuhk.edu.hk) ASCO AMERICAN SOCIETY OF CLINICAL ONCOLOGY ANNUAL MEETING Presentation is property of the author and ASCO Permission required for reuse, contact permissions@asco.org KNOWLEDGE CONQUERS CANCER

CROWN: A Randomized, Global, Phase 3 Study Primary endpoint Lorlatinib 100 mg once daily Key eligibility criteria n=149 PFS by BICR Stage IIIB/IV ALK+ NSCLC Key secondary endpoint No prior systemic treatment for OS Stratified by: metastatic disease Presence of brain metastases Other secondary endpoints ECOG PS 0-2 Randomized (yes vs no) PFS by investigator Asymptomatic treated or untreated 1:1 Ethnicity ORR by BICR and investigator CNS metastases were permitted N=296 (Asian vs non-Asian) IC ORR, IC TTP. DOR, IC DOR, TTR and IC TTR by BICR and 21 extracranial measurable target Crizotinib 250 mg twice daily investigator lesion (RECIST 1.1) with no prior radiation required n=147 Safety Quality of life No crossover between treatment arms was permitted Biomarker analyses In this post hoc analysis with 7 years of follow-up, we present investigator-assessed efficacy outcomes, safety, and biomarker analyses (data cutoff: October 31, 2025) At data cutoff, the required number of OS events for a protocol-specified second interim analysis (at least 139 deaths) has not been reached; 123 of 296 (42%) discontinued the study in both arms due to death ALK, anaplastic tymphoma knase; BICR binded independent central review, CNS, central nervous system DOR, duration of response ECOG Eastern Cooperative Oncology Group HR, hazard ratio; IC intracranial NSCLC non-small cell lung cancer, ORR, objective response rate, OS, overall survival PFS. progression free survival PS performance status, RECIST Response Evaluation Critena in Sold Tumors TTP. time to tumor progression TTR, time to tumor response *Defined as the time from randomization to RECIST defined progression or death due to any cause 2026 ASCO #ASCO26 PRESENTED BY: Tony S. K. Mok. MD (tony@clo.cuhk.edu.hk) ASCO AMERICAN CUNCAL ONCOLOGY ANNUAL MEETING Presentation property of the author and ASCO Permission required for - permissions@asco.org KNOWLEDGE CONQUERS CANCER --- PFS in the ITT Population (7-Year Follow-Up) The median duration of follow-up for PFS was 83.0 months (95% CI, 81.2-86.3) in the lorlatinib arm and 77.2 months (95% CI, 36.8-not evaluable) in the crizotinib arm Lorlatinib Crizotinib 100 (n=149) (n=147) 90 Events, n 62 119 PFS, median NR 9.1 80 70% (95% CI), months (68.5-NR) (7.4-10.9) 70 65% 63% HR (95% CI) 0.19 (0.13-0.26) 60% 60 57% 55% PFS, % 50 40 7 new PFS events occurred 30 between 5 and 7 20 15% 10% 10% years with 8% 10 7% 3% lorlatinib: 4 progression 0 events and 3 0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 68 72 76 80 84 88 92 96 100 deaths (not Months No. at risk treatment related) Lorlatinib 149 126 118 111 103 96 93 89 87 81 81 79 78 75 73 71 69 68 66 65 62 38 28 9 2 0 Crizotinib 147 107 70 42 30 19 16 16 11 10 9 9 9 8 8 7 6 6 6 5 2 2 0 0 0 0 At the time of this analysis, median PFS by investigator was still not reached with lorlatinib CI, confidence interval HR, hazard ratio, ITT, intention to treat, NR not reached PFS, progression free survival 2026 ASCO #ASCO26 PRESENTED BY: Tony S. K. Mok, MD (tony@clo.cuhk.edu.hk) ASCO CUNICAL ONCOLOGY ANNUAL MEETING Presentation - property of the author and ASCO Permission required for - conted KNOWLEDGE CONQUERS CANCER --- Time to IC Progression by Brain Metastases With baseline brain metastases Without baseline brain metastases Lorlatinib Crizotinib Lorlatinib Crizotinib (n=35) (n=38) (n=114) (n=109) Events, n 5 26 Events, n 4 40 Time to IC progression, NR 7.2 Time to IC progression, NR 23.9 months, median (95% CI) (NR-NR) (3.7-11.0) months, median (95% CI) (NR-NR) (16.4-30.8) HR (95% CI) 0.03 (0.01-0.13) HR (95% CI) 0.04 (0.02-0.12) 96% 96% 96% 96% 96% 96% 100 100 90% 90 83% 83% 83% 83% 83% 90 Patients without IC progression, % 80 80 70 Patients without IC progression, % 70 60 60 50 50 40 40 30 30 49% 33% 20 20 33% 29% 29% 10 10 22% 0 0 0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 68 72 76 80 84 88 92 96100 0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 68 72 76 80 84 88 92 96100 No. at risk Months No. at risk Months Loriatinib 35 32 29 28 28 26 26 25 22 22 20 20 20 20 20 20 18 18 18 18 17 11 7 3 1 0 — Lortatinib 114 96 90 84 77 72 70 67 67 64 64 61 61 60 58 56 54 51 51 50 47 30 22 6 1 0 — Crizotinib 109 86 63 41 31 21 19 18 12 10 10 10 9 8 8 7 6 6 6 5 2 2 0 0 0 0 Sustained plateau in time to IC progression indicates a prolonged protective effect against the development of new brain metastases and a sustained control of the existing ones CI, confidence interval HR, hazard ratio, IC intracranial; NR, not reached 2026 ASCO #ASCO26 PRESENTED BY: Tony S.K. Mok, MD (tony@clo.cuhk.edu.hk) ASCO CUNICAL ONCOLOGY ANNUAL MEETING Presentation - property of the author and ASCO Permission required for - contact KNOWLEDGE CONQUERS CANCER --- Conclusions After 7 years of follow-up in the phase 3 CROWN study, with lorlatinib treatment: PFS exceeds 7 years with 7-year PFS of 55% 2026ASCO ANNUAL MEETING Patients without progression within 24 months on lorlatinib had a 79% probability of being alive and free of progression at 7 years PFS benefit was consistent across all prespecified subgroups 7-year IC time to progression was 92%, with a sustained plateau from 30 months onward, indicating long-term CNS protection OS follow-up is ongoing and results will be presented in the future No new safety signals were identified, and all treatment-related discontinuations occurred within the first 26 months ctDNA analysis showed no emerging new ALK resistance mutations Early progressors had a higher number of alterations and a higher tumor mutation burden compared with long-term responders ALK inaplistic tymphoms knase CNS contral norvous system, clDNA, circulating turnor DNA K. intracranial os, overall survival PFS, progression free survival 2026 ASCO #ASCO26 PRESENTED BY: Tony S. K. Mok, MD (tony@clo.cuhk.edu.hk) ASCO AMERICAN CUNICAL CHOCOLOGY ANNUAL MEETING Presentation - property of the author and ASCO Permission wgared for - contact KNOWLEDGE CONQUERS CANCER

2026ASCO PFS in the ITT Population (7-Year Follow-Up) ANNUAL MEETING The median duration of follow-up for PFS was 83.0 months (95% CI, 81.2-86.3) in the lorlatinib arm and 77.2 months (95% CI, 36.8-not evaluable) in the crizotinib arm Lorlatinib Crizotinib 100 (n=149) (n=147) 90 Events, n 62 119 PFS. median NR 9.1 80 70% (95% CI), months (68.5-NR) (7.4-10.9) 70 65% 63% HR (95% CI) 0.19 (0.13-0.26) 60% 60 57% 55% PF PFS, % 50 40 7 new PFS events occurred 30 between 5 and 7 20 15% 10% 10% years with 8% 10 7% 3% lorlatinib: 4 progression 0 events and 3 0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 68 72 76 80 84 88 92 96 100 deaths (not Months No. at risk treatment related) - Lorlatinib 149 126 118 111 103 96 93 89 87 81 81 79 78 75 73 71 69 68 66 65 62 38 28 9 2 0 - Crizotinib 147 107 70 42 30 19 16 16 11 10 9 9 9 8 8 7 6 6 6 5 2 2 0 0 0 0 At the time of this analysis, median PFS by investigator was still not reached with lorlatinib C, confidence intervet HR haved rate, ITE, visition to treat, NR, not eached, PFS, progression the survival 2026 ASCO ASCO26 PRESENTED RY: Tony $. K. Mok, MD (tony@clo.cuhk.edu.hk) ASCO ANNUAL MEETING I I - - seried KNOWLEDGE CONQUERS CANCER LOSS SSO ASCO A SCO ASCO --- ASCO Estimated Proportion of PFS Events With Lorlatinib MEETING Conditional PFS beyond 2 years PFS Measure estimate Estimated proportion of PFS events 100 PFS at years 70% PFS at years 55% 90 *Conditional 80 79% 70% PFS (7Y/2Y) 20% 70 "Estimated as the ratio of the 10% 55% Kaplan-Meler PFS estimates at 7 60 5% and 2 years: (55%/70%) 2% PF PFS, % 3% 50 3% 2% 40 30 20 10 0 Year 1 Year 2 Year 3 Year 4 Year 5 Year 6 Year 7 No. at risk - Lorlatinib 149 126 118 111 103 96 93 89 87 81 81 79 78 75 73 71 69 68 66 65 62 38 28 9 2 0 Patients without a PFS event in the first 24 months on lorlatinib have a 79%* probability of remaining alive and progression-free at 7 years PFS, progression free survival 2026 ASCO PRESENTED BY: Tony S.K. Mok, MD (tony@clo.cuhk.edu.hk) #ASCO26 ASCO ANNUAL MEETING I property author ASCO Permission I - I contact KNOWLEDGE CONQUERS CANCER ASCO ASCO ASCO ASCO ASCO ASCO

2026ASCO ANNUAL MEETING --- PFS in the ITT Population (7-Year Follow-Up) The median duration of follow-up for PFS was 83.0 months (95% CI, 81.2-86.3) in the lorlatinib arm and 77.2 months (95% CI, 36.8-not evaluable) in the crizotinib arm Lorlatinib Crizotinib 100 (n=149) (n=147) 90 Events, n 62 119 PFS, median NR 9.1 80 70% (95% CI), months (68.5-NR) (7.4-10.9) 70 65% 63% HR (95% CI) 60% 0.19 (0.13-0.26) 60 57% 55% PFS, % 50 40 7 new PFS 30 events occurred between 5 and 7 20 15% 10% 10% years with 8% 10 7% 3% lorlatinib: 4 progression 0 events and 3 0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 68 72 76 80 84 88 92 96 100 deaths (not Months No. at risk treatment related) Lorlatinib 149 126 118 111 103 96 93 89 87 81 81 79 78 75 73 71 69 68 66 — 65 62 38 28 9 2 0 Crizotinib 147 107 70 42 30 19 16 16 11 10 9 9 9 8 8 7 6 6 6 5 2 2 0 0 0 0 - At the time of this analysis, median PFS by investigator was still not reached with lorlatinib CI, confidence interval; HR, hazard ratio; ITT, intention to treat; NR, not reached; PFS, progression-free survival 2026 ASCO PRESENTED BY: Tony S. K. Mok, MD (tony@clo.cuhk.edu.hk) ASCO AMERICAN SOCIETY OF #ASCO26 CURICAL OHCOLOGE ANNUAL MEETING Presentation is property of the author and ASCO Permission required for reuse; contact permissions@asco.org. KNOWLEDGE CONQUERS CANCER

2026A ANNUAL N 2026ASCO ANNUAL MEETING 1 ASCO ASCO ASO ASCO ASCO ASCO --- PFS in the ITT Population (7-Year Follow-Up) The median duration of follow-up for PFS was 83.0 months (95% CI, 81.2-86.3) in the lorlatinib arm and 77.2 months (95% CI, 36.8-not evaluable) in the crizotinib arm Loriatinib Crizotinib 100 (n=149) (n=147) 90 Events, n 62 119 PFS. median NR 9.1 80 70% (95% CI), months (68.5-NR) (7.4-10.9) 70 65% 63% HR (95% CI) 0.19 (0.13-0.26) 60% 60 57% 55% PFS, - 50 40 7 new PFS events occurred 30 between 5 and 7 20 15% 10% 10% years with 10 % 7% 3% forlatinib: 4 progression 0 events and 3 0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 68 72 76 80 84 88 92 96 100 deaths (not Months No. at risk treatment related) - Lorlatinib 149 126 118 111 103 96 93 89 87 81 81 79 78 75 73 71 69 68 66 65 62 38 28 9 2 0 Crizotinib 147 107 70 42 30 19 16 16 11 10 9 9 9 8 8 7 6 6 6 5 2 2 0 0 0 0 At the time of this analysis, median PFS by investigator was still not reached with lorlatinib a confidence information HI, have nation nimber for frood, NNL - marched RS progression Income survival 2026 ASCO #ASCO26 - Tony 5. K. Mok, MD (tony@clo.cuhk.edu.hk) ASCO WREN I ANNUAL MEETING Presentation - Permission - - - - Commission CANCER --- Estimated Proportion of PFS Events With Lorlatinib Conditional PFS beyond 2 years PFS Measure estimate Estimated proportion of PFS events 100 PFS at 2 years 70% PFS at 7 years 55% 90 *Conditional 80 79% 70% PFS (7Y/2Y) 20% 70 "Estimated as the ratio of the 10% 55% Kaplan-Meier PFS estimates at 7 60 5% and 2 years: (55% / 70%) 2% PFS, % 3% 50 3% 2% 40 30 20 10 0 Year 1 Year 2 Year 3 Year 4 Year 5 Year 6 Year 7 No. at risk Lorlatinib 149 126 118 111 103 96 93 89 87 81 81 79 78 75 73 71 69 68 66 65 62 38 28 9 2 0 Patients without a PFS event in the first 24 months on lorlatinib have a 79%* probability of remaining alive and progression-free at 7 years PFS, progression-free survival 2026 ASCO #ASCO26 PRESENTED BY: Tony S. K. Mok, MD (tony@clo.cuhk.edu.hk) ASCO AMERICAN SOCIETY OF CUNICAL ONCOLOGY ANNUAL MEETING Presentation is property of the author and ASCO Permission required for reuse, contact permissions@asco.org KNOWLEDGE CONQUERS CANCER

PFS in the ITT Population (7-Year Follow-Up) 20 The median duration of follow-up for PFS was 83.0 months (95% CI, 81.2-86.3) in the lorlatinib arm and 77.2 AN months (95% CI, 36.8-not evaluable) in the crizotinib arm Lorlatinib Crizotinib 100 (n=149) (n=147) Events, n 62 119 90 PFS, median NR 9.1 80 (95% CI), months (68.5-NR) (7.4-10.9) 70% 65% HR (95% CI) 0.19 (0.13-0.26) 70 63% 60% 57% 55% 60 PFS, % 50 7 new PFS 40 events occurred between 5 and 7 30 years with 15% 10% lorlatinib: 4 20 10% 8% 7% 3% progression 10 events and 3 56 60 64 68 72 76 80 84 88 92 96 100 0 24 28 32 36 40 44 48 52 deaths (not 0 4 8 12 16 20 treatment related) Months No. Lorlatinib at risk 149 126 118 111 103 96 93 89 16 87 11 81 10 81 9 79 9 78 9 75 8 73 8 71 7 69 6 68 6 66 6 65 5 62 2 38 2 28 0 9 0 0 2 0 0 Crizotinib At 147 the 107 time 70 42 of 30 this 19 analysis, 16 median PFS free survival by investigator was still not reached with lorlatinib CI, confidence interval; HR, hazard ratio, ITT, intention to treat, NR, not reached, PFS, progression ASCO - CIRCA - KNOWLEDGE CONQUERS CANCER BY: Tony S.K. Mok, MD (tony@clo.cuhk.edu.hk) ASCO #ASCO26 PRE Presentation SENTED is property of the aufhor and ASCO Permission required for reuse, contact permissions@asco org ENAL MEETING 2026ASCO ASCO ANNUAL MEETING ASCO ASCO CO --- Time to IC Progression by Brain Metastases With baseline brain metastases Without baseline brain metastases Lorlatinib Crizotinib Lorlatinib Crizotinib (n=35) (n=38) (n=114) (n=109) Events, n 5 26 Events, n 4 40 Time to IC progression, NR 7.2 Time to IC progression, NR 23.9 months, median (95% CI) (NR-NR) (3.7-11.0) months, median (95% CI) (NR-NR) (16.4-30.8) HR (95% CI) 0.03 (0.01-0.13) HR (95% CI) 0.04 (0.02-0.12) 96% 96% 96% 96% 96% 96% 100 100 90% 90 83% 83% 83% 83% 83% 90 Patients without IC progression, % 80 Patients without IC progression, % 80 70 70 60 60 50 50 40 40 30 30 49% 33% 33% 20 29% 20 29% 10 22% 10 0 0 0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 68 72 76 80 84 88 92 96100 0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 68 72 76 80 84 88 92 96 100 Months No. at risk Months No. at risk Lorlatinib 35 32 29 28 28 26 26 25 22 22 20 20 20 20 20 20 18 18 18 18 17 11 7 3 1 0 - Lorlatinib 114 96 90 84 77 72 70 67 67 64 64 61 61 60 58 56 54 51 51 50 47 30 22 6 1 0 Crizotinib 38 21 12 5 3 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 - Crizotinib 109 86 63 41 31 21 19 18 12 10 10 10 9 8 8 7 6 6 6 5 2 2 0 0 0 0 Sustained plateau in time to IC progression indicates a prolonged protective effect against the development of new brain metastases and a sustained control of the existing ones CI, confidence interval; HR, hazard ratio; IC, intracranial; NR, not reached PRE SENTED BY: Tony S. K. Mok, MD (tony@clo.cuhk.edu.hk) ASCO AMERICAN ONCE 6 ASCO #ASCO26 KNOWLEDGE CONQUERS CANCER Presentation is property of the author and ASCO Permission required for reuse, contact permissions@asco.org JAL MEETING 2026ASCO ANNUAL MEETING ASCO --- Baseline Lorlatinib ctDNA Genetic Alterations in EP and LTR With 10 Early progressors (EP; n=22) Long-term responders (LTR; n=30) 5 0 59% ALK 57% 59% ALK EML4 53% 60% EML4 TP53 17% 23% TP53 ATM 10% Early progressors had a higher median number 18% ATM ZFHX3 3% 18% ZFHX3 CHEK2 of altered genes (10 VS 6) and a higher median 0% CHEK2 14% NOTCH3 7% NOTCH3 14% blood-based tumor mutation burden (7.7 VS 5.1) NTRK3 0% NTRK3 14% ARID1A 10% ARID1A compared with long-term responders 14% NF1 0% NF1 14% KRAS 0% KRAS 14% TP53 mutations were observed in 50% of MYC 0% MYC 9% CIC 3% CIC 9% SPEN samples from early progressors compared with 7% SPEN 9% APC 3% APC 17% in long-term responders 9% MTOR 3% MTOR 9% PREX2 7% PREX2 9% KDM5C 3% KDM5C 9% PCDH15 3% PCDH15 Alterations 9% ROS1 3% ROS1 Treatment Early progressors are patients who had PFS 9% 3% TET1 SNV TET1 Lorlatinib Indel events within 12 months of the start of the study 9% ARID2 3% ARID2 3% ATRX CNA focal amp 9% ATRX Fusion PFS status Long-term responders are patients who were PDGFRA 3% PDGFRA 9% Early alive with no documented progression at 84 9% DICER1 3% DICER1 Late months. 9% BRIP1 3% BRIP1 9% IGR 13% IGR ROBO2 ROB02 5% 10% 5% CDC73 7% CDC73 BRCA1 7% BRCA1 Early progressors had a higher number of 5% 5% PBRM1 7% PBRM1 DNMT3B 10% DNMT38 alterations and a higher tumor mutation 0% SETD2 0% SETD2 10% Treatment Treatment burden compared with long-term PFS status PFS status responders EP, early progressor, LTR, long term responder, PFS, progression free survival 6 ASCO PRE SENTED BY: Tony S.K. Mok, MD (tony@clo.cuhk.edu.hk) ASCO INDICAL 10000000 CINCA - #ASCO26 KNOWLEDGE CONQUERS CANCER JAL MEETING Presentation is property of the author and ASCO. Permission required for reuse, contact permissions@aso.org. 2026ASCO ANNUAL MEETING ASSO --- Key Takeaway Point/Conclusion Results from this 7-year analysis show that lorlatinib as a single agent is able to persistently control the disease, both systemically and intracranially, over the entire duration of treatment and has the potential to transform advanced ALK-positive NSCLC into a chronic condition for a substantial proportion of patients ALK, anaplastic ymphoma kinase; NSCLC, non-small cell lung cancer ASCO AND SOCIETY CIRICAL INCOLOGIA KNOWLEDGE CONQUERS CANCER SENTED BY: Tony S.K. Mok, MD (tony@clo.cuhk.edu.hk) ASCO #ASCO26 PRE Presentation is property of the author and ASCO. Permission required for reuse, contact permissions@asco.org TRAL MEETING 2026ASCO ANNUAL MEETING ASCO ASCO ASCO CO

PFS in the ITT Population (7-Year Follow-Up) The median duration of follow-up for PFS was 83.0 months (95% CI, 81.2-86.3) in the lorlatinib arm and 77.2 months (95% CI, 36.8-not evaluable) in the crizotinib arm Lorlatinib Crizotinib 100 (n=149) (n=147) 90 Events, n 62 119 PFS, median NR 9.1 80 70% (95% CI), months (68.5-NR) (7.4-10.9) 70 65% 63% HR (95% CI) 0.19 (0.13-0.26) 60% 60 57% 55% PFS, % 50 40 7 new PFS events occurred 30 between 5 and 7 20 15% years with 10% 10% 8% 10 7% 3% lorlatinib: 4 progression 0 events and 3 0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 68 72 76 80 84 88 92 96 100 deaths (not Months treatment related) No. at risk Lorlatinib 149 126 118 111 103 96 93 89 87 81 81 79 78 75 73 71 69 68 66 65 62 38 28 9 2 0 Crizotinib 147 107 70 42 30 19 16 16 11 10 9 9 9 8 8 7 6 6 6 5 2 2 0 0 0 0 At the time of this analysis, median PFS by investigator was still not reached with lorlatinib CI, confidence interval; HR, hazard ratio; ITT, intention to treat; NR, not reached; PFS, progression-free survival. 2026 ASCO PRE SENTED BY: Tony S. K. Mok, MD (tony@clo.cuhk.edu.hk) ASCO AMERICAN SOCIETY OF CUNICAL ONCOLOGY #ASCO26 ANNUAL MEETING Presentation is property of the author and ASCO Permission required for reuse, contact permissions@asoo.org KNOWLEDGE CONQUERS CANCER

PFS in the ITT Population (7-Year Follow-Up) The median duration of follow-up for PFS was 83.0 months (95% CI, 81.2-86.3) in the lorlatinib arm and 77.2 months (95% CI, 36.8-not evaluable) in the crizotinib arm Lorlatinib Crizotinib 100 (n=149) (n=147) 90 Events, n 62 119 PFS, median NR 9.1 80 70% (95% CI), months (68.5-NR) (7.4-10.9) 70 65% 63% HR (95% CI) 0.19 (0.13-0.26) 60% 60 57% 55% PFS, % 50 40 7 new PFS events occurred 30 between 5 and 7 20 15% years with 10% 10% 8% 10 7% 3% lorlatinib: 4 progression 0 events and 3 0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 68 72 76 80 84 88 92 96 100 deaths (not Months No. at risk treatment related) - Lorlatinib 149 126 118 111 103 96 93 89 87 81 81 79 78 75 73 71 69 68 66 65 62 38 28 9 2 0 Crizotinib 147 107 70 42 30 19 16 16 11 10 9 9 9 8 8 7 6 6 6 5 2 2 0 0 0 0 At the time of this analysis, median PFS by investigator was still not reached with lorlatinib CI, confidence interval, HR, hazard ratio; III, intention to troat; NR, not reached, PFS, progression froo survival 2026 ASCO #ASCO26 PRESENTED BY: Tony S. K. Mok, MD (tony@clo.cuhk.edu.hk) ASCO AMERICAN OCEN OF CLINCIN CHICOLOGY ANNUAL MEETING Presentation a property of the author and ASCO. Permission required for reuse, contact permissions@usco.org ENOWLEDOE CONQUERS CANCER

Time to IC Progression by Brain Metastases With baseline brain metastases Without baseline brain metastases Lorlatinib Crizotinib Lorlatinib Crizotinib (n=35) (n=38) (n=114) (n=109) Events, n 5 26 Events, n 4 40 Time to IC progression, NR 7.2 Time to IC progression, NR 23.9 months, median (95% CI) (NR-NR) (3.7-11.0) months, median (95% CI) (NR-NR) (16.4-30.8) HR (95% CI) 0.03 (0.01-0.13) HR (95% CI) 0.04 (0.02-0.12) 96% 96% 96% 96% 96% 96% 100 100 90% 90 83% 83% 83% 83% 83% 90 at Patients without IC progression, % 80 Patients without IC progression, % 80 70 70 60 60 50 50 40 40 30 30 49% 33% 20 33% 20 29% 10 29% 10 22% 0 0 0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 68 72 76 80 84 88 92 96 100 0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 68 72 76 80 84 88 92 96 100 No. risk Months No. at risk Months Loriatinib 35 32 29 28 28 26 26 25 22 22 20 20 20 20 20 20 18 18 18 18 17 11 7 3 1 0 Lorlatinib 114 96 90 84 77 72 70 67 67 64 64 61 61 60 58 56 54 51 51 50 47 30 22 6 1 0 Crizotinib 38 21 12 5 3 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 Crizotinib 109 86 63 41 31 21 19 18 12 10 10 10 9 8 8 7 6 6 6 5 2 2 0 0 0 0 Sustained plateau in time to IC progression indicates a prolonged protective effect against the development of new brain metastases and a sustained control of the existing ones CI, confidence interval; HR, hazard ratio; IC, intracranial; NR, not reached. 2026 ASCO PRESENTED BY: Tony S. K. Mok, MD (tony@clo.cuhk.edu.hk) #ASCO26 ASCO AMERICAN SOCIETY OF CLINICAL ONCOLOGY ANNUAL MEETING Presentation is property of the author and ASCO. Permission required for reuse; contact permissions@asco.org KNOWLEDGE CONQUERS CANCER

Background & Methods CROWN (NCT03052608): A Randomized, Global, Phase 3 Study Lorlatinib is a preferred standard-of-care first-line therapy for Key eligibility criteria Lorlatinib 100 mg once daily Stage IIIB/IV ALK+ NSCLC patients with advanced ALK-positive NSCLC No prior systemic treatment for Stratified by: metastatic disease Presence of brain metastases (yes vs no) Randomized Ethnicity (Asian vs non-Asian) At 5 years of follow-up, median PFS by investigator was not ECOG performance status 0-2 1:1 reached with lorlatinib vs 9.1 months with crizotinib Asymptomatic treated or untreated CNS Crizotinib 250 mg twice daily metastases were permitted >1 extracranial measurable target lesion No crossover between treatment arms was permitted (RECIST 1.1) with no prior radiation We report long-term outcomes from the phase 3 CROWN required Primary endpoint: PFS by BICR proor Secondary endpoints: overall survival (key secondary endpoint), study after 7 years of follow-up PFS by investigator, objective response, IC objective response, IC time to progression, DOR, IC DOR, safety, and biomarker analyses Results Median PFS was still not reached with lorlatinib and Time to IC progression was still not reached with lorlatinib and 16.4 months with In the lorlatinib arm, no emerging new ALK resistance mutations 9.1 months with crizotinib after ~7 years of follow-up crizotinib; no new IC progression events occurred after the first 30 months were detected in the ctDNA samples at end of treatment HR (95% CI): 0.19 (0.13-0.26) HR (95% CI): 0.06 (0.03-0.12) 100 100 94% 92% 92% 92% 92% 92% 90 90 The safety profile of lorlatinib was similar to that reported in the 80 80 primary analysis of the CROWN study and in subsequent follow- 70% 65% up analyses 70 63% 70 60% 60 57% 55% PFS,% 40 30 Patients without progression, 60 The most common any-grade all-causality AEs were 50 50 hypercholesterolemia (73%), hypertriglyceridemia (71%), and edema (58%) 40 30 There was no increase in the frequency of patients with 37% 20 15% 20 25% 25% maximum grade 3 or 4 AEs since the 5-year analysis (77%) Lorlatinib 10% 10% 10 8% Lorlatinib 22% 7% 3% 22% Crizotinib 10 16% Crizotinib No new treatment-related AEs led to treatment 0 0 discontinuation after the first 26 months 0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 68 72 76 80 84 88 92 96 100 0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 68 72 76 80 84 88 92 96 Months Months AE, adverse event; ALK, anaplastic lymphoma kinase; BICR, blinded independent central review; CNS, central nervous system; ctDNA, circulating tumor DNA; DOR, duration of response; ECOG, Eastern Cooperative Oncology Group; IC, intracranial; NSCLC, non-small cell lung cancer; PFS, progression- free survival. Results from this 7-year analysis show that lorlatinib as a single agent is able to persistently control the disease, over the entire duration of treatment and has the potential to transform advanced ALK-positive NSCLC into a chronic disease for a substantial proportion of patients

Efficacy in Patients With and Without Dose Reduction Within 26 Weeks PFS Time to IC progression With dose reduction Without dose reduction With dose reduction Without dose reduction (n=23) (n=98) (n=24) (n=99) Events, n 6 36 Events, n 0 6 PFS, Time to IC progression, NR NR NR NR months, median months, median (95% CI) (NR-NR) (NR-NR) (79.8-NR) (81.9-NR) 100 (95% CI) 100 90 90 80 80 70 PFS, % Patients without IC 70 60 progression, % 60 50 50 40 40 30 30 20 20 10 10 0 0 0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 68 72 76 80 84 88 92 96 100 0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 68 72 76 80 84 88 92 96 100 No. at risk Months No. at risk Months With dose 23 21 20 18 17 15 15 15 14 13 12 12 12 12 11 11 10 10 9 7 5 3 0 0 0 0 — With dose 24 21 20 18 17 15 15 15 14 13 13 13 13 13 11 11 11 11 10 8 5 3 0 0 0 0 reduction reduction -- Without 98 96 86 79 76 75 72 70 67 66 66 64 61 60 59 57 56 55 55 37 24 12 5 2 0 0 -- Without 99 96 88 82 79 78 75 73 70 68 68 67 66 64 63 58 58 57 57 39 25 12 5 2 0 0 dose dose reduction reduction Long-term efficacy with lorlatinib was similar between patients with and without dose reduction within 26 weeks. PFS and IC TTP were also consistent across lorlatinib dose levels (100, 75, or 50 mg) CI, confidence interval; IC, intracranial; NR, not reached, PFS, progression-free survival 2026 ASCO #ASCO26 PRESENTED BY: Tony S. K. Mok, MD (tony@clo.cuhk.edu.hk) ASCO AMERICAN SOCIETY OF CLINICAL ONCOLOGY ANNUAL MEETING Presentation is property of the author and ASCO Permission required for reuse, contact permissions@asco.org KNOWLEDGE CONQUERS CANCER --- Conclusions After 7 years of follow-up in the phase 3 CROWN study, with lorlatinib treatment: PFS exceeds 7 years with 7-year PFS of 55% Patients without progression within 24 months on lorlatinib had a 79% probability of being alive and free of progression at 7 years PFS benefit was consistent across all prespecified subgroups 7-year IC time to progression was 92%, with a sustained plateau from 30 months onward, indicating long-term CNS protection OS follow-up is ongoing and results will be presented in the future No new safety signals were identified, and all treatment-related discontinuations occurred within the first 26 months ctDNA analysis showed no emerging new ALK resistance mutations Early progressors had a higher number of alterations and a higher tumor mutation burden compared with long-term responders ALK, anaplastic lymphoma kinase; CNS, central nervous system, ctDNA circulating tumor DNA IC, intracranial OS, overall survival PFS, progression-free survival 2026 ASCO PRESENTED BY: Tony S. K. Mok, MD (tony@clo.cuhk.edu.hk) ASCO AMERICAN SOCIETY OF #ASCO26 CUNICAL ONCOLOGY ANNUAL MEETING Presentation is property of the author and ASCO Permission required for reuse, contact permissions@asco.org KNOWLEDGE CONQUERS CANCER

SCO MEETING Lorlatinib: Mechanism of Action Lorlatinib is a highly potent third-generation ALK Molecular structure of ofatinib TKI, specifically developed to penetrate the Macrocycle compound) blood-brain barrier and is retained in the CNS at 0 the therapeutic levels¹² F. N it is known to have broad activity against most known ALK resistance mutations¹² N in addition, orlatinib has shown in viro activity N 0 against ROS1 and NTRK mutations H2N N N -- . a ASCO MASCOON - - ASCO - --- CROWN: A Randomized, Global, Phase 3 Study Primary endpoint Lorlatinib 100 mg once daily Key eligibility criteria n=149 PFS by BICR Key secondary endpoint Stage IIIB/IV ALK+ NSCLC OS No prior systemic treatment for Stratified by: Presence of brain metastases Other secondary endpoints metastatic disease ECOG PS 0-2 (yes vs no) PFS by investigator Randomized Ethnicity ORR by BICR and investigator Asymptomatic treated or untreated 1:1 (Asian vs non-Asian) №296 IC ORR, IC TTP, DOR, IC DOR, CNS metastases were permitted TTR and IC TTR by BICR and 21 extracranial measurable target Crizotinib 250 mg twice daily investigator lesion (RECIST 1.1) with no prior n=147 Safety radiation required Quality of life No crossover between treatment arms was permitted Biomarker analyses In this post hoc analysis with 7 years of follow-up, we present investigator-assessed efficacy outcomes, safety, and biomarker analyses (data cutoff: October 31, 2025) At data cutoff, the required number of OS events for a protocol-specified second interim analysis (at least 139 deaths) has not been reached; 123 of 296 (42%) discontinued the study in both arms due to death ALK, anaplastic lymphoma knase, BICR, blinded independent central review, CNS central nervous system DOR duration of response, ECOG. Eastem Cooperative Oncology Group HR, hazard ratio, IC, intracranal, NSCLC, non- small cell lung cancer, ORR, objective response rate, OS, overall survival, PFS, progression-tree survival, PS. performance status; RECIST, Response Evaluation Criteria in Solid Tumors TIP, time to the progression; TTR, time in under response. Defined as the time from randomization to RECIST defined progression or death due to any cause. 2026 ASCO PRE SENTED IT: Tony S. K. Mok, MD (tony@clo.cuhk.edu.hk) ASCO - CANCA #ASCO26 ANNUAL MEETING Presentation . property of the author and ASCO Permission required for - contact permissions@aste.com ENQUILED CONQUERS CANCER 2026ASCO ANNUAL MEETING SCO ASCO ASCO ASCO ASCO ASCO ASCO ASCO CO ASCO --- PFS in the ITT Population (7-Year Follow-Up) The median duration of follow-up for PFS was 83.0 months (95% CI, 81.2-86.3) in the lorlatinib arm and 77.2 months (95% CI, 36.8-not evaluable) in the crizotinib arm Lorlatinib Crizotinlb 100 (n=149) (n=147) 90 Events, n 62 119 PFS, median NR 9.1 80 70% (95% CI), months (68.5-NR) (7.4-10.9) 70 65% 63% HR (95% CI) 0.19 (0.13-0.26) 60% 60 57% 55% PFS, % 50 40 7 new PFS events occurred 30 between 5 and 7 20 15% 10% 10% years with 8% 10 7% 3% lorlatinib: 4 progression 0 events and 3 0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 68 72 76 80 84 88 92 96 100 deaths (not Months No. at risk treatment related) Lorlatinib 149 126 118 111 103 96 93 89 87 81 81 79 78 75 73 71 69 68 66 65 62 38 28 9 2 0 Crizotinib 147 107 70 42 30 19 16 16 11 10 9 9 9 8 8 7 6 6 6 5 2 2 0 0 0 0 At the time of this analysis, median PFS by investigator was still not reached with lorlatinib Cl, confidence interval; HR, hazard ratio; U. intention to treat; NR, not reached; PFS, progression-free survival. 2026 ASCO PRE SENTED BY: Tony S. K. Mok, MD (tony@clo.cuhk.edu.hk). #ASCO26 ASCO AMERICAN SOCIETY OF CLINICAL CHICOLOGY ANNUAL MEETING Presentation is property of the author and ASCO Permission required for reuse; contact permissions@asco.org KNOWLEDGE CONQUERS CANCER --- Adverse Events AEs of special interest Lorlatinib Crizotinib 58% Edema 43% No increase in frequency of grade 3 or 4 AEs since the 5-year analysis (77%) 71% Hypertnglycoridomia® 6% - Majority were due to an increase in lipid values 73% Hypercholosterotemia® 4% Despite higher rates of hyperlipidemia with lorlatinib, no increase in cardiovascular AEs was 46% Peripheral neuropathy 16% observed compared with crizotinib 45% Weight gain 13% Frequency of CNS AEs was consistent with longer 30% Cognitive offects 7% follow-up; most were grade 1 or 2 Dose reductions were reported in 34% of patients 21% Mood effects 7% in the lorlatinib group; median time to dose 5% Psychotic offects 1% reduction was 25 weeks Grade 1/2 All treatment-related discontinuations (5%) 6% Speech offects 0% Grade 1/2 Grade 3/4 Grade 3/4 occurred within the first 26 months 100 80 60 40 20 0 0 20 40 60 80 100 Incidence, % Incidence, % Safety profile of lorlatinib was consistent with prior AE, adverse event; CNS, central nervous system. analyses with no new safety signals with longer follow-up Comprised 0 cluster of AEs that may represent similar clinical symptoms or syndromos. 2026 ASCO PRE SENTED BY: Tony S. K. Mok, MD (tony@clo.cuhk.edu.hk) #ASCO26 ASCO AMERICAN SOCIETY OF CLINICAL ONCOLOGY ANNUAL MEETING Presentation is property of the author and ASCO Permission required for reuse, contact permissions@asco org. KNOWLEDGE CONQUERS CANCER

PFS in the ITT Population (7-Year Follow-Up) The median duration of follow-up for PFS was 83.0 months (95% CI, 81.2-86.3) in the lorlatinib arm and 77.2 months (95% CI, 36.8-not evaluable) in the crizotinib arm Lorlatinib Crizotinib 100 (n=149) (n=147) 2026ASCO ANNUAL MEETING 90 Events, n 62 119 PFS, median NR 9.1 80 70% (95% CI), months (68.5-NR) (7.4-10.9) 70 65% 63% HR (95% CI) 0.19 (0.13-0.26) 60% 60 57% 55% PFS, % 50 40 7 new PFS events occurred 30 between 5 and 7 20 15% years with 10% 10% 8% 10 7% 3% lorlatinib: 4 progression 0 events and 3 0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 68 72 76 80 84 88 92 96 100 deaths (not Months No. at risk treatment related) — Lorlatinib 149 126 118 111 103 96 93 89 87 81 81 79 78 75 73 71 69 68 66 65 62 38 28 9 2 0 Crizotinib 147 107 70 42 30 19 16 16 11 10 9 9 9 8 8 7 6 6 6 5 2 2 0 0 0 0 At the time of this analysis, median PFS by investigator was still not reached with lorlatinib CL confidence interval HR hazard ratio, 111. intention to treat, NR not reached PFS, progression free survival 2026 ASCO #ASCO26 PRESENTED BY ST. Tony S.K. Mok, MD (tony@clo.cuhk.edu.hk) ASCO - CORREAL ANNUAL MEETING Presentation property the author and ASCO Permission required for - contact permissions@asco.org KNOWLEDGE CONQUERS CANCER Γ 2026 ASCO J ANNUAL MEETING --- Time to IC Progression in the ITT Population Lorlatinib Crizotinib 100 94% 92% 92% 92% 92% 92% (n=149) (n=147) 2026ASCO 90 ANNUAL MEETING Events, n 9 66 Patients without IC progression, % 80 Time to IC NR 16.4 70 progression, (NR-NR) (12.7-21.9) 60 months, median 50 (95% CI) 40 HR (95% CI) 0.06 (0.03-0.12) 30 37% 20 25% 25% 22% 10 22% 16% Tumor assessments, including brain 0 MRI, have been performed every 8 0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 68 72 76 80 84 88 92 96 weeks up to 5 years and every 16 No. at risk Months weeks afterwards in all patients - Lorlatinib 149 128 119 112 105 98 96 92 89 86 84 81 81 78 78 76 72 69 69 68 64 41 29 9 2 — Crizotinib 147 107 75 46 34 22 19 18 12 12 10 10 9 8 8 7 6 6 6 5 2 2 0 0 0 throughout the study No new IC progression events occurred after the first 30 months on lorlatinib CI, confidence interval HR, hazard ratio, IC intracranial ITT. intention to treat MRI, magnetic resonance maging NR, not reached 2026 ASCO #ASCO26 PRE MNITORY Tony S. K. Mok, MD (tony@clo.cuhk.edu.hk) ASCO CURRENT ORCOLOGY ANNUAL MEETING Presentation . property of the author and ASCO Permission required for - contact permissione@asco.org KNOWLEDGE CONQUERS CANCER 2026 ASC ANNUAL MEET

CROWN: A Randomized, Global, Phase 3 Study Primary endpoint Lorlatinib 100 mg once daily Key eligibility criteria n=149 PFS by BICR Stage IIIB/IV ALK+ NSCLC Key secondary endpoint No prior systemic treatment for OS Stratified by: metastatic disease Presence of brain metastases Other secondary endpoints ECOG PS 0-2 Randomized (yes vs no) PFS by investigator Asymptomatic treated or untreated 1:1 Ethnicity ORR by BICR and investigator CNS metastases were permitted N=296 (Asian vs non-Asian) IC ORR, IC TTP, DOR, IC DOR, TTR and IC TTR by BICR and ≥1 extracranial measurable target Crizotinib 250 mg twice daily investigator lesion (RECIST 1.1) with no prior radiation required n=147 Safety Quality of life No crossover between treatment arms was permitted Biomarker analyses In this post hoc analysis with 7 years of follow-up, we present investigator-assessed efficacy outcomes, safety, and biomarker analyses (data cutoff: October 31, 2025) At data cutoff, the required number of OS events for a protocol-specified second interim analysis (at least 139 deaths) has not been reached; 123 of 296 (42%) discontinued the study in both arms due to death ALK, anaplastic ymphoma kinase; BICR, blinded independent central review; CNS, central nervous system; DOR, duration of response; ECOG, Eastern Cooperative Oncology Group; HR, hazard ratio; IC, intracranial; NSCLC, non-small cell lung cancer; ORR, objective response rate; OS, overall survival; PFS, progression-free survival; PS, performance status; RECIST, Response Evaluation Criteria in Solid Tumors; TTP, time to tumor progression; TTR, time to tumor response. *Defined as the time from randomization to RECIST-defined progression or death due to any cause. 2026 ASCO #ASCO26 PRESENTED BY: Tony S. K. Mok, MD (tony@clo.cuhk.edu.hk) ANNUAL MEETING ASCO AMERICAN SOCIETY OF Presentation is property of the author and ASCO. Permission required for reuse, contact permissions@asco.org. CUNICAL ONCOLOGY KNOWLEDGE CONQUERS CANCER --- PFS in the ITT Population (7-Year Follow-Up) The median duration of follow-up for PFS was 83.0 months (95% CI, 81.2-86.3) in the lorlatinib arm and 77.2 months (95% CI, 36.8-not evaluable) in the crizotinib arm Lorlatinib Crizotinib 100 (n=149) (n=147) 90 Events, n 62 119 PFS, median NR 9.1 80 70% (95% CI), months (68.5-NR) (7.4-10.9) 70 65% 63% HR (95% CI) 60% 0.19 (0.13-0.26) 60 57% 55% PFS, % 50 40 7 new PFS 30 events occurred between 5 and 7 20 15% 10% 10% years with 8% 10 7% 3% lorlatinib: 4 0 progression 0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 68 72 76 events and 3 80 84 88 92 96 100 deaths (not Months No. at risk treatment related) - Lorlatinib 149 126 118 111 103 96 93 89 87 81 81 79 78 75 73 71 69 68 66 65 62 38 28 9 2 0 - Crizotinib 147 107 70 42 30 19 16 16 11 10 9 9 9 8 8 7 6 6 6 5 2 2 0 0 0 0 At the time of this analysis, median PFS by investigator was still not reached with lorlatinib CI, confidence interval; HR, hazard ratio; U. intention to treat; NR, not reached; PFS, progression-free survival 2026 ASCO #ASCO26 PRESENTED BY: Tony S. K. Mok, MD (tony@clo.cuhk.edu.hk) ASCO AMERICAN SOCIETY OF CUNICAL ONCOLOGY ANNUAL MEETING Presentation is property of the author and ASCO. Permission required for reuse; contact permissions@asco.org KNOWLEDGE CONQUERS CANCER --- Estimated Proportion of PFS Events With Lorlatinib Conditional PFS beyond 2 years PFS Measure estimate Estimated proportion of PFS events PFS at 2 years 70% 100 PFS at 7 years 55% 90 *Conditional 79% 80 70% PFS (7Y/2Y) 20% 70 *Estimated as the ratio of the 10% 55% Kaplan-Meier PFS estimates at 7 60 and 2 years: (55% / 70%) 5% 2% 3% PFS, % 3% 50 2% 40 30 20 10 0 Year 1 Year 2 Year 3 Year 4 Year 5 Year 6 Year 7 No. at risk — Lorlatinib 149 126 118 111 103 96 93 89 87 81 81 79 78 75 73 71 69 68 66 65 62 38 28 9 2 0 Patients without a PFS event in the first 24 months on lorlatinib have a 79%* probability of remaining alive and progression-free at 7 years PFS, progression-free survival. 2026 ASCO PRE SENTED BY: Tony S. K. Mok, MD (tony@clo.cuhk.edu.hk) #ASCO26 ASCO AMERICAN SOCIETY or CUPICAL CHICOLOGY ANNUAL MEETING Presentation is property of the author and ASCO Permission required for reuse, contact permissions@asco.org. KNOWLEDGE CONQUERS CANCER --- Time to IC Progression in the ITT Population Lorlatinib Crizotinib 100 94% 92% 92% 92% 92% 92% (n=149) (n=147) 90 Events, n 9 66 Patients without IC progression, % 80 Time to IC NR 16.4 70 progression, (NR-NR) (12.7-21.9) 60 months, median (95% CI) 50 HR (95% CI) 0.06 (0.03-0.12) 40 30 37% 20 25% 25% 22% 22% 10 16% Tumor assessments, including brain 0 MRI, have been performed every 8 0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 68 72 76 80 84 88 92 96 weeks up to 5 years and every 16 No. at risk Months weeks afterwards in all patients — Lorlatinib 149 128 119 112 105 98 96 92 89 86 84 81 81 78 78 76 72 69 69 68 64 41 29 9 2 — Crizotinib 147 107 75 46 34 22 19 18 12 12 10 10 9 8 8 7 6 6 6 5 2 2 0 0 0 throughout the study No new IC progression events occurred after the first 30 months on lorlatinib CI, confidence interval; HR, hazard ratio; IC, intracranial; ITT, intention to treat; MRI, magnetic resonance imaging; NR, not reached 2026 ASCO #ASCO26 PRESENTED BY: Tony S. K. Mok, MD (tony@clo.cuhk.edu.hk) ASCO AMERICAN SOCIETY OF DUPICAL CHCOLOGY ANNUAL MEETING Presentation is property of the author and ASCO. Permission required for reuse, contact permissions@asco.org KNOWLEDGE CONQUERS CANCER

100 Lorlatinib (n = 149) Crizotinib (n = 147) 90 Events, n 55 115 PFS, months, median NR (64.3 to NR) 9.1 (7.4 to 10.9) (95% CI) 80 HR (95% CI) 0.19 (0.13 to 0.27) 70 70% 60 65% 63% PFS (%) 60% 50 40 30 15% 20 10% 10% 8% 10 0 0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 68 72 76 80 Time (months) Number at risk Lorlatinib 149 126 118 111 103 96 93 89 87 81 81 79 77 74 67 45 26 14 4 1 0 Crizotinib 147 107 70 42 30 19 16 16 11 10 9 9 9 8 6 4 2 0 0 0 0

100 Lorlatinib (n = 149) Crizotinib (n = 147) 90 Events, n 55 115 PFS, months, median NR (64.3 to NR) 9.1 (7.4 to 10.9) (95% CI) 80 HR (95% CI) 0.19 (0.13 to 0.27) 70 70% 60 65% 63% PFS (%) 60% 50 40 30 15% 20 10% 10% 8% 10 0 0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 68 72 76 80 Time (months) Number at risk Lorlatinib 149 126 118 111 103 96 93 89 87 81 81 79 77 74 67 45 26 14 4 1 0 Crizotinib 147 107 70 42 30 19 16 16 11 10 9 9 9 8 6 4 2 0 0 0 0

100 Lorlatinib (n = 149) Crizotinib (n = 147) 90 Events, n 55 115 PFS, months, median NR (64.3 to NR) 9.1 (7.4 to 10.9) (95% CI) 80 HR (95% CI) 0.19 (0.13 to 0.27) 70 70% 60 65% 63% PFS (%) 60% 50 40 30 15% 20 10% 10% 8% 10 0 0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 68 72 76 80 Time (months) Number at risk Lorlatinib 149 126 118 111 103 96 93 89 87 81 81 79 77 74 67 45 26 14 4 1 0 Crizotinib 147 107 70 42 30 19 16 16 11 10 9 9 9 8 6 4 2 0 0 0 0

At 60.2 Months of Median Follow-Up, Median PFS by Investigator Was Still Not Reached With Lorlatinib 100 Lorlatinib Crizotinib 90 (n=149) (n=147) 80 Events, n 55 115 TO PFS, median NR 9.1 60 (95% CI), (64.3-NR) (7.4-10.9) PFS, % 50 months 40 HR (95% CI) 0.19 (0.13-0.27) 30 20 10 0 0 4 6 12 16 20 24 28 32 36 40 44 48 52 50 00 64 68 72 78 50 No. at risk Time, months - Lorialinib 149 120 116 111 103 96 93 89 87 61 61 79 77 74 67 45 26 14 4 1 0 - Crizotinib 147 107 70 42 30 19 16 10 11 10 9 0 9 a 6 4 2 0 0 0 0 HR, - - MR, - insulanc) 05, - - FEE - - 2024 ASCO #ASCO24 - - Benjamin J. Belomon ASCO - | ANIMALLAS MEETING - - - - - - o - CONDITIONS

[Slide 1] Lorlatinib Showed Superior PFS Benefit Irrespective of Presence or Absence of Baseline Brain Metastases With Baseline Brain Metastases Without Baseline Brain Metastases Lorlatinib Crizotinib Lorlatinib Crizotinib (n=35) (n=38) (n=114) (n=109) Events n 16 34 Events, n 39 81 100 PFS, median NR 6.0 100 PFS, median NR 10.8 (95% CI). months (32.9-NR) (3.7-7.6) (95% CI). months (64.3-NR) (9.0-12.8) 90 90 HR (95% CI) 0.08 (0.04-0.19) HR (95% CI) 0.24 (0.16-0.36) 80 80 70 70 63% 60 53% 60 50 50 40 40 30 30 20 20 10% 10 10 0 0 0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 68 72 76 80 0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 68 72 76 80 No. at risk Time, months Time, months No. at risk Lorlatinib 35 31 29 28 28 26 26 25 23 20 20 20 19 18 15 10 7 5 2 0 - Lorlatinib 114 95 89 83 75 70 67 64 64 61 61 59 58 56 52 35 19 9 2 1 0 Crizotinib 38 22 11 4 3 1 0 0 0 0 - Crizotinib 109 85 59 38 27 18 16 16 11 10 9 9 9 8 6 4 2 0 0 HR. hazard ratio; NR. not reached; PFS, progression-free survival 2024 ASCO #ASCO24 PRESENTED BY: Benjamin J. Solomon (Ben.Solomon@petermac.org) ASCO AMERICAN SOCIETY OF CLINICAL ONCOLOGY ANNUAL MEETING Presentation is property of the author and ASCO Permission KNOWLEDGE CONQUERS CANCER

Current Post Hoc Analyses at 5 Years Endpoint evaluation by BICR stopped after the 3-year analysis Lorlatinib 100 mg once daily Current analyses Key eligibility criteria n=149 Data cutoff: October 31, 2023 Stage IIIB/IV ALK+ NSCLC No prior systemic treatment for Stratified by: metastatic disease Presence of brain metastases Investigator Assessed ECOG PS 0-2 Randomized (yes VS no) PFS' Asymptomatic treated or untreated 1:1 Ethnicity ORR and IC ORR CNS metastases were permitted N=296 (Asian vs non-Asian) DOR and IC DOR 21 extracranial measurable target lesion (RECIST 1.1) with no prior Crizotinib 250 mg twice daily IC TTP radiation required n=147 Safety No crossover between treatment arms was permitted Biomarker analyses The median duration of follow-up for PFS was 60.2 months (95% CI, 57.4-61.6) in the lorlatinib arm and 55.1 months (95% CI, 36.8-62.5) in the crizotinib arm CNS, central nervous system; DOR, duration of response ECOG, Eastern Cooperative Oncology Group IC, intracranial, ORR, objective response rate NSCLC, non small cell kng cancer, PFS. progression that survival, PS performance - RECIST, Response Evaluation Criteria in Solid Tumors, TTP, time to tumor progression. Defined as the time from randomization to RECIST-defined progression or death due to any cause 2024 ASCO #ASCO24 PRE SENTED BY: Benjamin J. Solomon (Ben.Solomon@petermac.org ASCO - seceive GREA I ANNUAL MEETING Presentation is property of N author ed ASCO Permission required for - contact KNOWLEDGE CONDUCES CANCER --- At 60.2 Months of Median Follow-Up, Median PFS by Investigator Was Still Not Reached With Lorlatinib 100 Lorlatinib Crizotinib 90 (n=149) (n=147) 80 Events, n 55 115 70 PFS, median NR 9.1 60 (95% CI), (64.3-NR) (7.4-10.9) FS, % 50 months 40 HR (95% CI) 0.19 (0.13-0.27) 30 20 10 0 0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 68 72 76 80 No. at risk Time, months - Lorlatinib 149 126 118 111 103 96 93 89 87 81 81 79 77 74 67 45 26 14 4 1 0 - Crizotinib 147 107 70 42 30 19 16 16 11 10 9 9 9 8 6 4 2 0 0 0 0 HR, hazard ratio, NR, not reached, os, overall survival, PFS, progression-free survival 2024 ASCO #ASCO24 PRESENTED IT Benjamin J. Solomon (Ben.Solomon@petermac.org) ASCO ONE INCOUDING ANNUAL MEETING Presentation is property of the author and ASICO Permission required for - contact permissions) KNOWLEDGE CONDUERS CANCELL