METIS Trial

[Slide 1] 10:12 AM - 10:24 AM ABSTRACT 2007: High-dose almonertinib in treatment-naive EGFR-mutated NSCLC with CNS metastases: Efficacy and biomarker analysis. Presenting Author: Yun Fan 10:24 AM - 10:36 AM ABSTRACT 2008: Results from METIS (EF-25), an international, multicenter phase III randomized study evaluating the efficacy and safety of tumor treating fields (TTFields) therapy in NSCLC patients with brain metastases. Presenting Author: Minesh P. Mehta 10:36 AM - 10:48 AM Jarushka Naidoo, MBBCh-Discussant Beaumont RCSI Cancer Center Pushing the Envelope in Non-Small Cell Lung Cancer Brain Metastases

[Slide 1] Abstract #2008. Session Date: Monday, June 3, 2024. Time: 8:00 AM-11:00 AM 2024 ASCO ANNUAL MEETING Topline Results from METIS (EF-25), an International, Multicenter Phase III Randomized Study Evaluating the Efficacy and Safety of Tumor Treating Fields (TTFields) Therapy in Patients With Non-Small Cell Lung Cancer (NSCLC) with Brain Metastases Minesh P. Mehta,' Vinai Gondi,² Manmeet S. Ahluwalia,¹ David Roberge,³ Rosanda Ilic,4 Terence T. Sio,⁵ Daniel M. Trifiletti,6 Thierry Muanza, Ana M. Krpan,8 Naren Ramakrishna,⁹ John Fiveash,¹⁰ Philippe Metellus," Chiachien J. Wang,12 Loic Feuvret,13 Jinming Yu, Zhengfei Zhu,¹⁵ Christian Freyschlag, 16 Tibor Csöszi," Paul D. Brown,13 Maciej Harat;¹⁹ on behalf of the METIS study investigators Cancy Mark R USE Nothwesten Medicine Cancer Center and Northwestern Medicine Proton Center, Warrenville, IL, US; CHUM, AKYSTUAN OC, CHEASE Cincal Center of Service Neurosurgery Clinic-Department kx Neuroncology Befraue Serbix Department of Radiation Oncology, Mayo CRK Plant AZ. US Department of Change Mayo Clinic tax FL us Montroal Neurological Institute AcGal University, Montreal, Canada: Sevena ОФАР Hearth Canar Ortanuty FL US The University of Alabama at Birmingham Birmingham, AL, USA "Hópital PINE Clarval France ЧИЗ Knighton Cancer Center, Shreve LA US Lym HCL Lyon France: Shandong Cancer Hospital Jinan China University Starghai Carcer Center Shagna China Mulinate University motrux metruck Austria Megyei Hebenyl Gdza STAX Hungary: "Department of Radiation Oncotyx Mayo Cinic, Ruchester, MN, US: "Department of Neurooncology and Flanciszer Memorial Oneoingy Center буфоки Poland JUN ASCO BASCON Book wa MO. Man Carve india MILTING ASCO --- [Slide 2] NSCLC With Brain Metastases: Strong Unmet Need ~170k cases of brain metastases annually in the United States¹ — >50% have lung cancer as the underlying cause² — More than 50% of NSCLC patients develop BM either initially or subsequently2 Prognosis for NSCLC BM without driver mutations is poor³ SRS is effective local therapy but limited due to multiple intracranial relapses. WBRT can overcome this, but with known cognitive decline4,5 A strong unmet need exists for therapies that improve intracranial relapse while limiting cognitive decline BM, brain molastases; NSCLC, non-small cell lung cancer, SRS, stereolactic rediosurgery, WBRT, whole brain radiotherapy 1. Rapp SR, et al. J Clin Oncol. 2015,33(15): 1653-1659. 2. Cagney DN, et al. Neuro Oncol 2017,19(11): 1511-1521 3. Sperduto PW, el al. JAMA Oncol 2017;3(6):827-831. 4. Chang EL, et al. Lancet Oncol. 2009;10(11) 1037-1044 5. Brown P ot al JAMA 2016, 316(4): 401-409 ASCO AMERICAN SOCIETY OF 2024 ASCO PRE SENTED BY: Minesh P. Mehta, MD. Miami Cancer Institute CLINICAL ONCOLOGY #ASCO24 ANNUAL MEETING Presentation is property of the author and ASCO Permason required for - contact permissions@ason.org KNOWLEDGE CONQUERS CANCER --- [Slide 3] Primary Endpoint: Time to First Intracranial Progression $ or Neurologic Death Favors TTFields Arm 1.0 0.8 Probability of Intracranial Progression 0.6 BSC TTFields + BSC 0.4 0.2 HR=0.67 (0.48-0.93); P=0.0158 0 0 4 8 12 18 24 36 49 Follow up (Months) TTFields therapy with BSC 149 95 65 52 36 29 24 12 7 3 1 BSC 149 101 71 50 41 33 23 11 7 3 0 TTFields + BSC BSC TTFields P-value BSC + BSC (n=149) (n=149) (n=149) (n=149) Median Time to Intracranial Progression* (95% CI), months 21.9 (8.3-NE) 11.3 (7.6-NE) 0.0158 Neurologic 9 10 Progression rate at 12 months (95% CI) 57.8% (49.0-65.7) deaths, n 41.6% (32.4-50.5) 0.005 Progression rate at 18 months (95% CI) 46.9% (37.3-56.0) 61.2% (52.3-68.9) 0.0132 Deaths from 53 44 other reasons, n "Primary endpoint measured as per RANO- BM over course of study based on independent radiology review BSC, best supportive care, patients in both arms could receive systemic NSCLC treatment Cl, confidence interval, HR, hazard ratio, NE, not evaluable; TTFields, Tumor Treating Fields 2024 ASCO PRE SENTED BY: Minesh P. Mehta, MD. Miami Cancer Institute ASCO AMERICAN SOCIETY OF #ASCO24 CLINICAL ONCOLOGY ANNUAL MEETING Presentation 6 property of the suthor and ASCO Permission required for reuse, contact KNOWLEDGE CONQUERS CANCER --- [Slide 4] 15 Conclusions The pivotal, phase 3 METIS trial met its primary endpoint - Time to 1st intracranial progression was significantly prolonged (21.9 vs 11.3 months; P=0.0158) - EQ-5D QoL deterioration-free survival was prolonged in the TTFields arm TTFields was well-tolerated (device-related grade ≥3 was only 2.4%), in line with previous studies These are topline data; remaining detailed analysis are ongoing TTFields therapy should be evaluated as an adjunctive therapy to SRS in patients with NSCLC BM without targetable oncogenic driver mutations BM, brain metastases, BSC, best supportive care, patients in both arms could receive systemic NSCLC treatment, NSCLC, non-small cell ung cancer, QoL, quality of life; SRS, stereolactic radiosurgery, TTFields, Tumor Treating Fields 2024 ASCO PRE SENTED BY: Minesh P. Mehta, MD, Miami Cancer Institute ASCO AMERICAN SOCIETY OF #ASCO24 CLINICAL ONCOLOGY ANNUAL MEETING Presentation a property of the author and ASCO Permission required for read, contact permissors@asco.org KNOWL CONQUERS

[Slide 1] Primary Endpoint: Time to First Intracranial Progression or Neurologic Death Favors TTFields Arm 1.0 0.8 0.6 BSC TTFields + BSC 0.4 0.2 HR=0.67 (0.48-0.93); P =0.0158 0 0 4 8 12 18 24 36 49 Follow up (Months) TTFields therapy with BSC 149 95 65 52 36 29 24 12 7 3 1 BSC 149 101 71 50 41 33 23 11 7 3 0 TTFields + BSC BSC TTFields P-value BSC 4 BSC (n=149) (n=149) (n=149) (n=149) Median Time to Intracranial Progression* (95% CI), months 21.9 (8.3-NE) 11.3 (7.6-NE) 0.0158 Neurologic 9 10 Progression rate at 12 months (95% CI) 41.6% (32.4-50.5) 57.8% (49.0-65.7) 0.005 deaths, n Progression rate at 18 months (95% CI) 46.9% (37.3-56.0) 61.2% (52.3-68.9) 0.0132 Deaths from 53 44 other reasons, n *Primary endpoint measured as per RANO BM over course of study based on independent radiology review BSC, best supportivo care, patients in both arms could receive systemic NSCLC treatment CI, confidence interval HR hazard ratio; NE, not evaluable, TTFields, Tumor Treating Fields 2024 ASCO PRE SENTED BY Minesh P. Mehta, MD. Miami Cancer Institute ASCO AMERICAN SOCIETY OF #ASCO24 CLINICAL ONCOLOGY ANNUAL MEETING Presentation . property of the author and ASCO Permission required b me contact KNOWLEDGE CONQUERS CANCER

[Slide 1] Conclusions The pivotal, phase 3 METIS trial met its primary endpoint - Time to 1st intracranial progression was significantly prolonged (21.9 vs 11.3 months; P=0.0158) - EQ-5D QoL deterioration-free survival was prolonged in the TTFields arm TTFields was well-tolerated (device-related grade 3 was only 2.4%), in line with previous studies These are topline data; remaining detailed analysis are ongoing TTFields therapy should be evaluated as an adjunctive therapy to SRS in patients with NSCLC BM without targetable oncogenic driver mutations BM brain mekastases BSC best supportive can patients in both WTH could receive systemic NSOLC treatment NSCLC Oct Quality SRS stereotactic Treating 2024 ASCO PRESENTED BY Minesh P Mehta MD. Miami Cancer Institute #ASCO24 ASCO CHOCOLATE ANNUAL MEETING Presentation - - KNOWLEDGE CONQUERS CANCER 2024 ASCO ANNUAL MEETING --- [Slide 2] 6 METIS Trial: Study Design 1st intracranial 2nd intracranial TTFields progression: progression: therapy n=298 with BSC Salvage TTFields Salvage TTFields therapy + BSC therapy + BSC Adults with Randomized SRS* N=15 Survival NSCLC BM (1:1) follow-up Stratification 1-4 vs 5-10 BM 1st intracranial 2nd intracranial Prior systemic therapy Y/N Histology BSC progression: progression: Key Inclusion Criteria: Salvage therapy Salvage therapy Newly diagnosed BM from NSCLC + BSC + BSC1 1 inoperable or 2-10 supra/infratentorial BM suitable for SRS KPS >70 Receive systemic NSCLC treatment Study sites: 78 (enrolled; 298 pts randomized) Key Exclusion Criteria: Enrollment: October 2016-March 2023 Known mutations with available targeted agents (ALK, EGFR, ROS-1, and B-RAF genes) Data cut off: 5th December 2023 Prior WBRT Registration number: NCT02831959 Leptomeningeal or recurrent BM to 358 hiday Surgery BSC NSOLO EGFR characted radosurgery 2024 ASCO #ASCO24 PRE SENTES - Minesh P. Mehta MD. Miami Cancer Institute ASCO AMERICAN SOCIETY OF CLINICAL ANNUAL MEETING Presentation . property and ABOO Permission required for House contact KNOWLEDGE CONQUERS CANCER 2024 ASCC ANNUAL MEETIN

[Slide 1] METIS data at #ASCO24 novocure®

[Slide 1] the efficacy ACHIEVE Study singlant NSCLC with Il study CNS evaluating metastases and safety Primary 12-month endpoint PFS rate per RECIST 1.1 Key Eligibility Criteria Aged 18-75 years Aumolertinib 165 mg (QD) Secondary endpoints Histologically or cytologically confirmed NSCLC N=63 ORR, DoR, DCR ECOG PS 0-1 Intracranial PFS (iPFS), iORR, EGFR Ex19del / L858R mutation iDoR, iDCR& No prior systemic therapy for advanced NSCLC OS At least one extracranial target lesion and one ctDNA* ctDNA* intracranial lesion with a baseline longest fragmentomes# Safety fragmentomes* diameter of at least 5 (C1D1) (C2D1) Enrollment period: Jul 6,2021 to Aug 31,2022 T Intracranial efficacy was evaluated using enhanced MRI The cutoff date: Jan 31, 2024 This trail is registered at Clinical NCT04808752 # Patients with eptomeningeal metastases (LMs) were excluded $ * Patients previously treated with brain radiotherapy were excluded & # ctDNA cfDNA Evaluation were fragmentomes detected by were NGS calculated using commercially with internally available developed panels targeting 520 cancer-related genes SCO EETING #ASCO24 Presentation PRE SENTED is BY: property NSCLC Dr of Yun the Fan. with and CNS Evaluation ASCO. Permission metastases, of the efficacy including and biomarker safety of analysis. high dose Almonertinib in untreated EGFR-mutated efficacy of both intracranial and extracranial lesions was algorithms done according MedSR to RECIST 1.1 ASCO AC --- [Slide 2] 10 Best Tumor Change from Baseline in Target Lesions CEFS (N=49) Intracranial ITT (N=63) Systemtic 40 Systembe 30 20 * 10 Best change from -100 $ terget lession (%* -90 -80 -70 0 -10 -20 -30 -40 -50 -60 Patents Patients ORR: 88.9% (95%CI, 78.4, 95.4) ORR: 87.8% (95%CI, 75.2, 95.4) >50% tumor reduction: 87.5% of systemic responders iORR: 85.7% (72.8, 94.1); iCR: 22.4% 4. 2 "Based on standard RECIST version 1.1; 3.CI, confidence interval; 1. ITT, intention-to-treat population; cEFR, CNS evaluable-for-response set; The concordance between CNS and systemic RECIST, Response Evaluation Criteria in Solid Tumors. response: 81.6% 2024 ASCO ANNUAL MEETING #ASCO24 Presentation PRE SENTED BY: NSCLC Dr Yun Fan. with CNS Evaluation metastases, of the efficacy including and biomarker safety of analysis. high dose Almonertinib in untreated EGFR-mutated paperty of the author and ASCO Permission required for more contact permissions@asco org. ASCO AMERICAN SOCIETY OF CLINICAL ONCOLOGY KNOWLEDGE CONQUERS CANCER --- [Slide 3] METIS Trial: Study Design 2nd intracranial 1st intracranial progression: TTFields progression: therapy+ Salvage+ TTFields Salvage* TTFields with BSC therapy + BSC9 therapy + BSC n=298 Survival Adults with Randomized SRS* N=15 follow-up NSCLC BM (1:1) 1st intracranial 2nd intracranial Stratification: 1-4 VS 5-10 BM Prior systemic therapy Y/N progression: progression: Histology BSC Salvage+ therapy Salvage+ therapy Key Inclusion Criteria: Newly diagnosed BM from NSCLC + BSC$ + BSC / inoperable or 2-10 supra/infratentorial BM suitable for SRS KPS >70 Receive systemic NSCLC treatment Key Exclusion Criteria: Study sites: 78 (enrolled; 298 pts randomized) Known mutations with available targeted agents Enrollment: October 2016-March 2023 (ALK, EGFR, ROS-1, and B-RAF genes) Prior WBRT Leptomeningeal or recurrent BM Data cut off: 5th December 2023 Registration number: NCT02831959 as albwed intracranial homa nance knase, Scale progression TTFields BM, NSCLC, brain therapy non-small metastases, was cell administered BSC, lung best cancer, supportive at pts, 150kHz patients; care, for ≥18 patients ROS. h/day. TOS in #Surgery, both proto-oncogene arms repeat could SRS, receive 1; SRS, WBRT. systemic stereotactic $Follow NSCLC up radiosurgery; and treatment; MRI Q8W. TTFields, B-RAF, Patients B-Raf Tumor in the proto-oncogene; Treating control arm Fields; were EGFR, WBRT, offered epidermal whole to cross brain growth over radiotherapy. to factor the TTFields receptor, arm HF-SRS, and receive hypofractionated TTFields therapy with or without salvage stereotactic radiosurgery; --- [Slide 4] 10 Primary or Endpoint: Neurologic Time Death to First Favors Intracranial TTFields Progression Arm 1.0 BSC 08 TTFields + BSC of Propression 0.6 0.4 0.2 HR=0.67 (0.48-0.93); P=0.0158 49 36 0 0 8 12 18 24 4 Follow up (Months) 3 1 TTFields therapy with BSC 149 95 65 52 36 29 24 12 7 BSC 101 71 50 41 33 23 7 3 0 149 11 TTFields TTFields + BSC BSC BSC P-value + BSC (n=149) (n=149) (n=149) (n=149) Median Time to Intracranial Progression* (95% CI), months 21.9 (8.3-NE) 11.3 (7.6-NE) 0.0158 Neurologic 9 10 Progression rate at 12 months (95% CI) 41.6% (32.4-50.5) 0.005 deaths, n 57.8% (49.0-65.7) Progression rate at 18 months (95% CI) 46.9% (37.3-56.0) 61.2% (52.3-68.9) 0.0132 Deaths from Primary endpoint measured as per RANO-8M over course of study based on independent radiology review. other reasons, n 53 44 BSC best supportive care, patients in both ams could receive systemic NSCLC treatment, CI, confidence interval, HR, hazard ratio; NE, not evaluable; TTFields, Tumor Treating Fields. 2024 ASCO #ASCO24 PRE SENTED BY: Minesh P. Mehta, MD, Miami Cancer Institute ANNUAL MEETING Presentation property of he author and ASCO Permission required for reuse, contact permissions@asco.org ASCO AMERICAN SOCIETY OF CLINICAL ONCOLOGY KNOWLEDGE CONQUERS CANCER