MARIPOSA Trial

[Slide 1] Available First Line Treatment Options for EGFRm NSCLC FLAURA1.2 FLAURA23.4 FLAURA2 MARIPOSA5.6 MARIPOSA5 Osimertinib Osimertinib Osi + Chemotherapy Osimertinib Amivantamab + Lazertinib (N=279) (N=279) (N=278) (N=429) (N=429) ORR 80% (75-85) 76% (70-80) 83% (78-87) 85% (81-88) 86% (83-89) 18.9 mo 16.7 mo 25.5 mo 16.6 mo 23.7 mo PFS, median (15.2-21.4) (14.1-21.3) (24.7-NC) (14.8-18.5) (19.1-27.7) PFS HR 0.62 (0.49-0.79) 0.70 (0.58-0.85) 38.6 months 36.7 month Not Reached OS, median Not Reported Not Reported (34.5-41.8) (33.4-41.0) (37.8 mo follow up) 0.90 (0.65-1.24; P = 0.52) 0.75 (0.61-0.92; P < 0.005) os HR *27% data maturity Final Analysis Route of PO PO + IV (q3 weeks) PO + IV (weekly, then q2 weeks) Administration Toxicity Low grade diarrhea, rash Fatigue, nausea, hematologic toxicities Dermatologic toxicities, infusion reactions and VTE Considerations FLAURA2 Primary Endpoint- PFS (Investigator-Assessed) 1 Soria JC, et al N Engl J Med 2018.378.113.25.2 Ramalingam SS et al N Engli J Med 2020,382.41-50 3 Planchard D, et al N Engl J MARIPOSA: Primary Endpoint- PFS (BICR) Med 2023,389 1935-1948 4 Valdiviezo N. FLCC 2024; 5 Cho BC et al N Engl J Med 2024 391 1486 1498 6 Yang JCH et al FLCC 2025 Zosia Piotrowska MD. MHS, Boston USA Organisers Partners Content of this presentation is copyrightand responsibility of the author Permission is required for re-use ESMD IASLC ESTRO ETOP-IBCSG

[Slide 1 — Treatment sequencing schematic, EGFRm NSCLC (Maurice Perol; ELCC 2025, Paris, 26-29 Mar 2025)] "Upfront treatment will determine the entire treatment sequence with a major impact on OS" First-line Osimertinib, mPFS 18.9m -> 2L: CT + amivantamab (mPFS ~5-6m) or CT + ivonescimab | TROP2/HER3 ADC | TKI rechallenge [Median PFS anchors verified vs NEJM: FLAURA osimertinib mono 18.9 mo (Soria NEJM 2018). Downstream mPFS values are approximate line-of-therapy estimates as labeled on the presenter's schematic.]

[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] Safety MARIPOSA Median duration of treatment AEs by preferred term (220% of Amivantamab + Osimertinib was 27.0 mo for amivantamab + participants in either group) lazertinib (n=421) (n=428) lazertinib and 22.4 mo for Any grade Grade >3 Any grade Grade >3 Related to EGFR Inhibition osimertinib Paronychia 291 (69) 49 (12) 127 (30) 2 (<1) Rash Safety profile was consistent with 271 (64) 73 (17) 136 (32) 3 (<1) Diarrhea 133 (32) 9 (2) 200 (47) 4 (<1) the primary analysis Dermatitis acneiform 127 (30) 37 (9) 55 (13) 0 AEs were mostly EGFR- and Stomatitis 126 (30) 5 (1) 92 (21) 1 (<1) MET-related and grades 1-21,2 Pruritus 107 (25) 2 (<1) 75 (18) 1 (<1) Related to MET Inhibition A minority of participants were Hypoalbuminemia 216 (51) 26 (6) 29 (7) 0 Peripheral edema prescribed antibiotics for rash (21%) 162 (38) 8 (2) 29 (7) 1 (<1) Other at study initiation2 Infusion-related reaction 275 (65) 27 (6) 0 0 ALT increased 170 (40) 28 (7) Few were on anticoagulation (5%) 66 (15) 8 (2) AST increased 139 (33) 15 (4) 68 (16) at baseline², with VTE occurring in 6 (1) Constipation 130 (31) 0 70 (16) 0 40% in the amivantamab + COVID-19 125 (30) 8 (2) 112 (26) 9 (2) lazertinib arm and 11% in the Anemia 114 (27) 20 (5) 112 (26) 10 (2) osimertinib arm Decreased appetite 114 (27) 4 (1) 84 (20) 7 (2) Nausea 99 (24) 5 (1) 65 (15) 1 (<1) Hypocalcemia 96 (23) 11 (3) 37 (9) 0 Asthenia 84 (20) 13 (3) 54 (13) 7 (2) Muscle spasms 84 (20) 3 (<1) 36 (8) 0 Thrombocytopenia 74 (18) 4 (1) 92 (21) 6 (1) VVE is grouped term, which included pulmonary embolism deep vein thrombosis, limb venous thrombosa vencus thrombosis thombosis superficial vein thrombosis, thombophiebitis, embolism, venous ambolism, jugular von thombosis signoid sinus elcc thrombosis axilary ven thrombosis pulmonary infarction vena cava thrombosa central venous catheterization portal vent Ivorbosis post thrombobe syndrome pulmonary thrombosa superior sapital anus thombosis transverse sun thombosa pelve venous thrombosis and superior venu cava syndrome 1 Cho BC. el al N Engl Med 2024,391(16) 1489-1498 2 Spira Al et al Presented at 2023 North America Conference on Lung Cancer (NACLC) December H 2023 Chicago, IL USA European Lung Cancer Congress 2025 --- [Slide 2] First Subsequent Therapy MARIPOSA Most common subsequent therapy class was chemotherapy-based regimens in both arms 5% 5% 28% 74% (129/175°) of 39% TKI-based regimens participants in 76% (195/258) of Chemotherapy-based the amivantamab + regimens participants in lazertinib arm were the osimertinib arm Other willing and able to were willing and able receive a subsequent to receive a therapy subsequent therapy 56% 67% MARIPOSA did not allow treatment crossover Amivantamab + lazertinib Osimertinib (n=129) (n=195) 74% received 2L therapy, suggesting a long-term treatment plan after 1L amivantamab + lazertinib is feasible Note: Percentages may not sum to 100 due to rounding "Denominator is the number of participants who had disease progression and discontinued randomized treatment no based regiment include TIG chemotherapy (5% in both arms) Other therapy included VEGF alone antbody-drug elcc conjugates ALK tyrosine after participant received and 1 participant monotherapy) MARIPOSA did European Lung Cancer Congress 2025

[Slide 1] Time Toxicity of Combination Therapy Over 2 months, total scheduled infusion time: Cycle 1 Subsequent cycles D1 Osimertinib I N/A, Q2-3 month clinic visits only 0 hours 30 min Cycle 1 Subsequent cycles (q3 week) D1 D1 Carboplatin/ Pemetrexed/ ( 6 hours Osimertinib (3 cycles) 2 hours 2 hours Cycle 1 Subsequent cycles (q2 week) D1 D2 D8 D15 D1 D15 D1 Amivantamab/ 38.5 hours Lazertinib 7 hours 8 hours 5.5 hours 4.5 hours 4.5 hours 4.5 hours 4.5 hours *Times provided include actual medication administration times for pre-medications and treatment per MGH protocol and drug prescribing information Data courtesy of Aubrey Lasko, RPH Zosia Piotrowska MD. MHS Boston USA Organisers Partners Content of this presentation is copyrightand responsibility of the author Permission is required for re-use ESMD -- IASLC - KINGDO esmate ESTRO L ETOP-IBCSG

[Slide 1 — Treatment sequencing schematic, EGFRm NSCLC (Maurice Perol; ELCC 2025)] "Upfront treatment will determine the entire treatment sequence with a major impact on OS" First-line options and downstream sequence: - Osimertinib monotherapy, mPFS 18.9m (FLAURA) — 33% no subsequent treatment (FLAURA); 27-29% die without further treatment (real-world) - Osimertinib + Pt-Pemetrexed, mPFS 25.5m (FLAURA2) — 54% who discontinued did not receive 2nd-line treatment - Amivantamab + lazertinib, mPFS 23.7m (MARIPOSA) — 26% who discontinued did not receive 2nd-line treatment [mPFS verified vs NEJM: FLAURA osi mono 18.9 mo (Soria 2018); FLAURA2 osi+chemo 25.5 mo investigator-assessed (Planchard 2023); MARIPOSA ami+laz 23.7 mo BICR (Cho 2024). MARIPOSA is FDA-approved (Aug 19 2024) 1L EGFRm NSCLC.]

[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] Key Takeaways The 5-year analysis of CROWN affirms lorlatinib as preferred 1L treatment for patients with metastatic ALK+ NSCLC PALOMA-3 findings demonstrate noninferior pharmacokinetic and clinical outcomes and improved patient experience with SC versus IV dosing of amivantamab, representing a clinically meaningful advance MARIPOSA subgroup analyses underscore the importance of continuing to investigate biomarker-driven treatment stratification approach for 1L treatment of patients with metastatic EGFR-mutated NSCLC Together, these studies represent commendable steps forward in the endeavor to strike the right balance with targeted therapies with optimal efficacy and improved tolerability We need to take the lessons learned from the tremendous progress made in select molecular subsets of NSCLC (such as ALK+) to improve outcomes across all subsets 2024 ASCO PRESENTED BY: Jessica J. Lin (jjin1@mgb.org) ASCO AMERICAN SOCIETY OF #ASCO24 CUNICAL ONCOLOGY ANNUAL MEETING Presentation is property of the author and ASCO Permission required for reuse contact KNOWLEDGE CONQUERS CANCER 2024 ASCO ANNUAL MEETING