Novocure (NVCR) R&D Day December 12, 2016 The St. Regis New York

Transcription

1 Novocure (NVCR) R&D Day December 12, 2016 The St. Regis New York

2 forward-looking statements This presentation contains certain forward-looking statements with respect to the business of Novocure and certain of its plans and objectives, including with respect to the development and commercialization of its lead product candidate, Optune, for a number of oncology indications. These forward-looking statements can be identified in this presentation by the fact that they do not relate only to historical or current facts. Forward-looking statements often use words expect, intend, anticipate, plan, may, should, would, could or other words of similar meaning. These statements are based on assumptions and assessments made by Novocure in light of industry experience and perception of historical trends, current conditions, expected future developments and other appropriate factors. By their nature, forward-looking statements involve risk and uncertainty, and Novocure's performance and financial results could differ materially from those expressed or implied in these forward-looking statements due to general financial, economic, regulatory and political conditions as well as more specific risks and uncertainties facing Novocure such as those set forth in its Annual Report on Form 10-K filed on March 1, 2016, or in subsequent quarterly filings with the U.S. Securities and Exchange Commission. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those described in this presentation. Novocure assumes no obligation to update or correct the information contained in this presentation, whether as a result of new information, future events or otherwise, except to the extent legally required. The statements contained in this presentation are made as at the date of this presentation, unless some other time is specified in relation to them, and service of this presentation shall not give rise to any implication that there has been no change in the facts set out in this presentation since such date. Nothing contained in this presentation shall be deemed to be a forecast, projection or estimate of the future financial performance of Novocure, except where expressly stated. As of the date of this presentation, Optune is only FDA-approved for glioblastoma, or GBM, and its approval for other indications is not certain. Novocure can provide no assurances regarding market acceptance of Optune or its successful commercialization, and can provide no assurances regarding the company s results of operations or financial condition in the future. This presentation is for informational purposes only and may not be relied upon in connection with the purchase or sale of any security. Novocure

3 opening remarks William Doyle Executive Chairman

4 agenda 12:00 1:00 p.m. ROUNDTABLE LUNCH WITH MANAGEMENT AND GUESTS 1:00 1:05 p.m. Opening remarks William Doyle Novocure 1:05 1:25 p.m. Intro to TTFields and preclinical overview Eilon Kirson, MD, PhD Novocure 1:25 1:50 p.m. Glioblastoma Zvi Ram, MD Tel Aviv Sourasky Medical Center 1:50 2:05 p.m. Brain metastases Vinai Gondi, MD Northwestern Medicine Proton Center 2:05 2:15 p.m. Non-small cell lung cancer Eilon Kirson, MD, PhD Novocure 2:15 2:30 p.m. BREAK 2:30 2:55 p.m. Pancreatic cancer Daniel D. Von Hoff, MD Translational Genomics Research Institute 2:55 3:10 p.m. Ovarian cancer Eilon Kirson, MD, PhD Novocure 3:10 3:25 p.m. Mesothelioma Uri Weinberg, MD, PhD Novocure 3:25 3:40 p.m. What s next for Tumor Treating Fields Eilon Kirson, MD, PhD Novocure 3:40 3:55 p.m. Novocure Engineering Mike Ambrogi Novocure 3:55 p.m. Closing comments William Doyle Novocure Novocure

5 Novocure speakers William Doyle Executive Chairman Eilon Kirson, MD, PhD Chief Science Officer and Head of Research & Development Uri Weinberg, MD, PhD Vice President of Research & Development Mike Ambrogi Chief Operating Officer Novocure

6 expert participants Zvi Ram, MD Prof. Zvi Ram serves as the Chairman of the Department of Neurosurgery at Tel Aviv Medical Center in Israel. After completion of his neurosurgical residency at Sheba Medical Center in Israel in 1991, Prof. Ram had joined the Surgical Neurology Branch at the National Institutes of Health in Bethesda, MD, where he led a variety of basic and clinical research projects, including paving the way and leading the first gene therapy trial for patients with brain tumors, as well as other innovative approaches for brain tumor therapy. Upon his return to Israel in 1994, Prof. Ram has launched an active clinical and academic career with emphasis on brain tumor therapy, pituitary surgery, and technology development projects with various companies, including the development and implementation of intraoperative MRI technology, High-Intensity Focused MRI-guided ultrasound for tumor ablation, spectroscopic brain mapping, novel drug distribution systems, and the use and modeling of convection-enhanced drug delivery systems and other innovative therapeutic approach for brain tumor. Prof. Ram has chaired the Tumor Section of the European Association of Neurosurgical Societies (EANS), is a member of the Executive Steering Committees and lead PI for several pharmaceuticals companies conducting multicenter international phase III clinical studies, Scientific advisor for biothechnology groups, and a member of editorial boards and reviewer for leading scientific journals in his areas of expertise. Prof. Ram's main clinical interests include surgery for complex brain tumors, including performance of Awake Craniotomies with intra-operative cortical mapping and white matter tracking when tumors are within or near functional brain regions, resection of pituitary tumors and complex benign tumors of the brain. Novocure

7 expert participants Vinai Gondi, MD Dr. Vinai Gondi is Director of Research at the Northwestern Medicine Chicago Proton Center and Director of CNS Radiation Oncology at the Northwestern Medicine Cancer Center Warrenville in Chicago, IL. He is an internationally recognized expert on the management of metastatic and primary brain tumors. His research focuses on technological advances such as proton therapy, intensity-modulated radiotherapy, and tumor-treating fields, to improve therapeutic efficacy and optimize overall quality of life of brain tumor patients. He serves as Principal Investigator on several cooperative NCI-sponsored clinical trials, including RTOG 0933, NRG CC001, NRG CC003, and NRG BN001, and serves as a member of the NRG Oncology Brain Tumor Core Committee. He has published over 35 peer-reviewed publications in such top-tiered journals as Journal of Clinical Oncology, Nature Reviews Neurology, JAMA Oncology, and International Journal of Radiation Oncology, Biology and Physics. He has presented his research at multiple international meetings, including three plenary presentations, and his research has been supported by funding from the NCI. He was instrumental in developing the METIS pivotal phase III trial for lung cancer patients with brain metastases. Novocure

8 expert participants Daniel D. Von Hoff, MD, FACP Daniel D. Von Hoff, M.D., F.A.C.P. is currently Physician in Chief, Distinguished Professor Translational Research Division at TGen (Translational Genomics Research Institute) in Phoenix, Arizona. He is also Chief Scientific Officer for HonorHealth Clinical Research Institute and is the Medical Director of Research at McKesson Specialty Healthcare and the Scientific Medical Officer for US Oncology Research and leader of the Translation Oncology Program (TOP) specializing in phase I clinical trials done in the US Oncology Research network. He also holds an appointment as Professor of Medicine, Mayo Clinic, Scottsdale, AZ. Dr. Von Hoff s major interest is in the development of new anticancer agents, both in the clinic and in the laboratory. He and his colleagues were involved in the beginning of the development of many of the agents we now use routinely, including: mitoxantrone, fludarabine, paclitaxel, docetaxel, gemcitabine, irinotecan, nelarabine, capecitabine, lapatinib, vismodegibm nab-paclitaxel, nal-iri, and others. At present, he and his colleagues are concentrating on the development of molecularly targeted therapies particularly for patients with advanced pancreatic cancer. Dr. Von Hoff has published more than 690 papers, 140 book chapters and over 1400 abstracts. Dr. Von Hoff received the 2010 David A. Karnofsky Memorial Award from the American Society of Clinical Oncology for his outstanding contributions to cancer research leading to significant improvement in patient care. Dr. Von Hoff was appointed to President Bush s National Cancer Advisory Board in Dr. Von Hoff is the past President of the American Association for Cancer Research (the world s largest cancer research organization), a Fellow of the American College of Physicians, and a member and past board member of the American Society of Clinical Oncology. He is a founder of ILEX Oncology, Inc. (acquired by Genzyme after Ilex had 2 agents, alemtuzumab and clofarabine approved by the FDA for patients with leukemia). Dr. Von Hoff is founder and the Editor Emeritus of Investigational New Drugs The Journal of New Anticancer Agents; and, past Editor-in-Chief of Molecular Cancer Therapeutics. He is a co-founder of the AACR/ASCO Methods in Clinical Cancer Research Workshop. Dr. Von Hoff is the leader of the SU2C Pancreatic Dream Team. He is also proud to have been a mentor and teacher for multiple medical students, medical oncology fellows, graduate students, and post-doctoral fellows. Novocure

9 introduction to TTFields and preclinical overview Eilon Kirson, MD, PhD Chief Science Officer and Head of R&D

10 VALIDATED ANTI-CANCER MODALITY tumor treating fields USED AS MONOTHERAPIES OR IN COMBINATION TO TREAT SOLID TUMORS SURGERY RADIATION PHARMACOLOGICAL TREATMENTS Most frequently employed therapy Reduces size of a tumor prior to initiation of additional therapies Kills cells when delivered at high doses Injures healthy tissues with numerous potential toxic side effects Includes chemotherapy, targeted therapies and immuno-oncology Limited by potential side effects Resistance can develop over time TUMOR TREATING FIELDS (TTFIELDS) Low-intensity, alternating electric fields Mild side effect profile No cumulative toxicity Can be used in combination with other treatment modalities Novocure

11 multi-pronged mechanism of action MITOTIC SPINDLE DAMAGE 1,2 CHROMOSOME MISALIGNMENT 1 Contractile ring mislocalization NSCLC NSCLC ABNORMAL CHROMOSOMAL SEGREGATION 1 CHROMOSOME MIS-SEGREGATION 3 Ovarian 1. Adapted from Giladi M., et al. Sci Rep, 2015; Dec 11; doi: /srep Porat Y, et al. (2014 November) Triflupromazine, an Approved Antipsychotic Drug, Enhances Tumor Treating Fields Treatment Effi cacy In Vitro. Poster session presented at the Society for NeuroOncology. Miami, FL. 3. Voloshin, T., et al. Int. J. Cancer, 2016; 139: doi: /ijc Ovarian Novocure

12 TREATMENT DOES NOT HARM NORMAL CELL GROWTH frequency tuned to specific cell types EFFECTS ON CELLS ARE FREQUENCY SPECIFIC AND INVERSELY RELATED TO CELL SIZE Normal Intestine Pancreatic Cancer NSCLC Ovarian Cancer GBM ~50 khz 150 khz 150 khz 200 khz 200 khz Novocure

13 TTFIELDS DELIVERY DESIGNED FOR HOME USE non-invasive, portable medical device Battery or wall-powered electric field generator Single-use transducer arrays replaced 2 3 times/week Should be used at least 18 hours/day Mild side-effect profile, no known systemic toxicity Novocure

14 REGIONAL TREATMENT ENABLES PERSONALIZATION individualized anti-cancer modality The effect of a tumor with a necrotic core on the magnitude of the electric field, for the AP arrays (left) and LR arrays (right). The direction of the electric field in and around the tumor is shown in the insets. Values greater than 3.5 V/cm are shown in dark red Miranda PC, Mekonnen A, Salvador R, Basser PJ. Physics in medicine and biology. 2014;59(15): doi: / /59/15/ Wenger C, Salvador R, Basser PJ, Miranda PC. Int J Radiat Oncol. 2016; 94(5): doi: /j.ijrobp Chaudhry A, Benson L, Varshaver M, et al. World J Surg Oncol. 2015;13:316. doi: /s NovoTAL User Manual QSD QR 700 Revision 1.4. Novocure January Novocure

15 15+ years of preclinical research Deep understanding of the underlying mechanism of TTFields Continuing investment in mechanism of action substantiation and applications Novocure

16 TTFields shown to reduce human glioma cell migration and invasion properties IBIDI CULTURE INSERT TO ASSESS WOUND HEALING 1 TIME LAPSE MICROSCOPY SYSTEM 1 1. Schneiderman, R.S. et al. (2016, April). Tumor Treating Fields (TTFields) Reduce Migration and Invasion Properties of Human Glioma Cancer Cells in Vitro. Poster session presented at the American Association for Cancer Research. New Orleans, LA. Novocure

17 TTFields shown to reduce human glioma cell migration and invasion properties TTFIELDS INHIBITED MIGRATION OF GLIOMA CELLS IN SCRATCH WOUND ASSAYS IN VITRO Schneiderman, R.S. et al. (2016, April). Tumor Treating Fields (TTFields) Reduce Migration and Invasion Properties of Human Glioma Cancer Cells in Vitro. Poster session presented at the American Association for Cancer Research. New Orleans, LA. Novocure

18 TTFields shown to reduce human glioma cell migration and invasion properties TTFIELDS INHIBITED GLIOMA CANCER CELL INVASIVE POTENTIAL IN VITRO TTFields frequency effect on glioma cell invasion is different from its peak antimitotic frequency TTFields inhibition of glioma cell migration in scratch wound assays is dependent upon electric field direction Schneiderman, R.S. et al. (2016, April). Tumor Treating Fields (TTFields) Reduce Migration and Invasion Properties of Human Glioma Cancer Cells in Vitro. Poster session presented at the American Association for Cancer Research. New Orleans, LA. Novocure

19 TTFields shown to induce autophagy in certain human cancer cell lines Novocure

20 TTFields shown to induce autophagy in certain human cancer cell lines TTFIELDS APPLICATION TO U87 GLIOMA CELL LINE LED TO INCREASE IN CELLULAR GRANULARITY Porat, Y. et al. (2016, April). Alternating Electric Fields (TTFields) Induce Autophagy in Human Cancer Cell Lines. Poster session presented at the American Association for Cancer Research. New Orleans, LA. Novocure

21 TTFields shown to induce autophagy in certain human cancer cell lines ELECTRON MICROGRAPHS REVEALED INCREASED LEVELS OF AUTOPHAGOSOME-LIKE STRUCTURES IN U87 GLIOMA CELLS TREATED WITH TTFIELDS Porat, Y. et al. (2016, April). Alternating Electric Fields (TTFields) Induce Autophagy in Human Cancer Cell Lines. Poster session presented at the American Association for Cancer Research. New Orleans, LA. Novocure

22 TTFields shown to induce autophagy in certain human cancer cell lines TTFIELDS UP-REGULATED AUTOGPHAGY IN U87 GLIOMA CELLS, REFLECTED BY INCREASED LC3-II LEVELS A B C D Time dependent accumulation of LC3 on autophagosomal membranes following TTFields application (24 hours and 48 hours) is demonstrated by fluorescent microscopy of cells stained with anti-lc3 antibody (green) and DAPI DNA stain (blue) (Figure A). Original magnifications: x40. Image analysis shows significantly higher levels of LC3 signal per cell following treatment at 48 hours (Figure B). Immunoblot reveals increased levels of the LC3-derived autophagosomal marker LC3-II, in the presence of chloroquine, indicating the enhancement of autophagic flux during application of TTFields. (Mean ± SEM; *P <.05, ***P <.001 from control group, student s t-test) (Figure C-D). Porat, Y. et al. (2016, April). Alternating Electric Fields (TTFields) Induce Autophagy in Human Cancer Cell Lines. Poster session presented at the American Association for Cancer Research. New Orleans, LA. Novocure

23 TTFields shown to interfere with DNA damage response Novocure

24 TTFields shown to interfere with DNA damage response TTFIELDS INTERFERED WITH DAMAGE REPAIR OF IONIZING RADIATION-INDUCED DNA DOUBLE STRAND REPAIR BY HOMOLOGOUS RECOMBINATION Control IR TTFields IR + TTFields Giladi M., et al. (2015, October) Tumor Treating Fields (TTFields) Sensitize Glioma Tumor Cells to Radiation Therapy by Delaying DNA Damage Repair Through Homologous Recombination. Poster session presented at the Annual Meeting of the American Society for Radiation Oncology, San Antonio, TX. Novocure

25 TTFields shown to interfere with DNA damage response TTFIELDS PLUS IONIZING RADIATION TRIGGERED MULTI-NUCLEATION AND MITOTIC ABNORMALITIES IN GLIOBLASTOMA CELLS Ho Kim, E., Jin Kim, Y., Sook Song, H. et al. Oncotarget, 2016; 7(38), doi: /oncotarget Novocure

26 TTFields are complementary to certain other anti-cancer therapies Chen DS, et al. Immunity. 2013; 39(1):1-10. doi: /j.immuni Novocure

27 TTFields are complementary to certain other anti-cancer therapies TTFIELDS DID NOT INHIBIT DEGRANULATION, CYTOKINE SECRETION OR ACTIVATION- MARKER PRESENTATION IN ACTIVATED T-CELLS Diamant, G.. et al. (2016, November). Evaluating the in-vitro effects of tumor treating fields on T cell responses. Poster session presented at the Society of NeuroOncology, Phoenix, AZ. Novocure

28 TTFields are complementary to certain other anti-cancer therapies TTFIELDS IN COMBINATION WITH ANTI-PD1 WERE THERAPEUTICALLY EFFECTIVE IN VIVO In a mouse model of Lewis Lung carcinoma, combination of TTFields and anti-pd-1 led to significant decrease in tumor volume compared to control mice and to mice treated with anti-pd-1 alone after 1 week of treatment TTFields did not adversely affect immune cell infiltration into tumors - TTFields applied to CD45+ cells did not inhibit immune function - CD45+ and specifically CD11b+/CD11c+ and CD11b+/F4/80+ cells from tumor in the combined treatment group exhibited higher tumor infiltration and elevated PD-L1 expression compared to control groups Combining TTFields with anti-pd-1 may achieve tumor control by further enhancing antitumor immunity Giladi, M. et al. (2016, May). Alternating Electric Fields (TTFields) Induce Immunogenic Cell Death Resulting in Enhanced Antitumor Efficacy When Combined With Anti-PD-1 Therapy. Poster session presented at the Annual Meeting of the American Association of Immunologists, Seattle, WA. Novocure

29 broad applicability to solid tumors Novocure

30 ongoing clinical trials PRE- CLINICAL PHASE 2 PILOT PHASE 3 PIVOTAL EXPECTED NEXT MILESTONE INDICATIONS Brain Metastases METIS trial last patient in 2019 NSCLC LUNAR first patient in 2017 Pancreatic Cancer phase three pivotal trial first patient in 2017 Ovarian Cancer finalization of phase three pivotal trial design Mesothelioma STELLAR trial last patient in 2017 Novocure

31 glioblastoma multiforme (GBM) Zvi Ram, MD Tel Aviv Sourasky Medical Center EF-14 Trial Investigator

32 GLIOBLASTOMA disease state and clinical presentation Most common and most aggressive primary malignant brain tumor in adults 1 Located generally in the cerebral hemispheres of the brain, but may be found anywhere in the brain or spinal cord One of a group of tumors referred to as gliomas - Develop from the lineage of star-shaped glial cells, called astrocytes, that are the glue-like support cells in the central nervous system - Classified as a Grade IV astrocytoma by WHO 2 Because GBM can grow very rapidly, symptoms usually caused by increased pressure in the brain - Can include headache, nausea, vomiting, drowsiness or seizures - Depending on tumor location, can include other symptoms like weakness on one side of the body, memory and/or speech difficulties, visual changes 1. Ostrom QT, Gittleman H, Jordan X, et al. Neuro-Oncology. 2016;18v1-v75. doi: /neuonc/now Louis D. N,, Ohgaki H,, Wiestler O.D, et al. Acta Neuropathologica. 2007;114(2): doi: /s Novocure

33 GLIOBLASTOMA epidemiology United States 1 GBM incidence of 12,500 cases annually Europe 2 GBM estimated incidence of 22,000 cases annually Japan 3 GBM incidence of 1,500 cases annually Incidence of GBM is approximately 3.2 per 100,000 people 1 GBM incidence increases in frequency with age and affects men more than women GBM represents 14.9% of all primary brain tumors and about 60-75% of all astrocytomas 1. Ostrom QT, Gittleman H, Jordan X, et al. Neuro-Oncology. 2016;18v1-v75. doi: /neuonc/now Europe defined as all countries where Optune has CE mark approval 3. Etsuko Nomura, Akiko Ioka, and Hideaki Tsukuma. J Clin. Oncol. (2011) 41 (2): doi: /jjco/hyq204 Novocure

34 GLIOBLASTOMA prior standard of care: the Stupp protocol Since approval of temozolomide in 2005, standard of care for newly diagnosed GBM has been the Stupp protocol pioneered by Dr. Roger Stupp 1 Standard treatment includes - Maximal debulking surgery, if feasible - Biopsy alone or subtotal resection, if maximal safe surgical resection not feasible - Radiation therapy (45-70 Gray) with concomitant low-dose temozolomide (TMZ) - Post radiation, high dose temozolomide (TMZ) given for five days every 28 days newly diagnosed GBM maximal debulking surgery / biopsy radiation therapy (RT) + temozolomide (TMZ) TMZ (6 cycles) MRI q2m until progression second line chemotherapy 1. Stupp R, Mason WP, van den Bent MJ, et al. N Engl J of Med 2005; 352: Novocure

35 MONOTHERAPY TREATMENT FOR RECURRENT GBM EF-11 phase 3 pivotal trial overall survival TTFIELDS (n=120) CHEMOTHERAPY (n=117) Median OS, months HR and p value HR=0.86, p= year survival 8% 0% n = 85 n = 13 Novocure

36 MONOTHERAPY TREATMENT FOR RECURRENT GBM PRiDe overall survival MEDIAN OS MONTHS PRiDe TTFields EF-11 TTFields EF-11 Physician Choice Chemo LOG-RANK (MANTEL-COX) TEST 1 p value PRIDE VS EF-11 TTFIELDS 1 HR % Cl The Patient Registry Dataset (PRiDe) is a post-marketing registry of all recurrent GBM patients who received Optune in a real-world, clinical practice setting in the United States between 2011 and Mrugala MM, Engelhard HH, Dinh Tran D, et al. Semin Oncol. 2014;41(5)(suppl 6):S4-S13. doi: /j.seminoncol Stupp R, Wong ET, Kanner AA, et al. Eur J Cancer. 2012;48(14): doi: /j.ejca Novocure

37 MONOTHERAPY TREATMENT FOR RECURRENT GBM PRiDe overall survival by recurrence 1.0 MEDIAN OS MONTHS 1st recurrence nd recurrence 8.5 3rd-5th recurrence 4.9 LOG-RANK (MANTEL-COX) TEST 1 Chi square df 2 P value < ST VS 2ND RECURRENCE HR % Cl P value ST VS 3RD-5TH RECURRENCE HR 0.3 The Patient Registry Dataset (PRiDe) is a post-marketing registry of all recurrent GBM patients who received Optune in a real-world, clinical practice setting in the United States between 2011 and Mrugala MM, Engelhard HH, Dinh Tran D, et al. Semin Oncol. 2014;41(5)(suppl 6):S4-S13. doi: /j.seminoncol % Cl P value < Novocure

38 COMBINATION THERAPY FOR NEWLY DIAGNOSED GBM EF-14 phase 3 pivotal trial initiated in 2009 A prospective, multicenter trial of TTFields together with temozolomide compared to temozolomide alone in patients with newly diagnosed GBM 83 centers; 695 newly diagnosed GBM patients randomized 2:1 (TTFields plus TMZ vs TMZ alone) Treated until second progression or 24 months Pre-specified interim analysis 18 months after enrollment of the 315th patient Endpoints: Primary endpoint progression-free survival (PFS) (intent to treat) Secondary endpoint overall survival (OS) (as treated) Novocure, Ltd. Effect of NovoTTF-100A Together With Temozolomide in Newly Diagnosed Glioblastoma Multiforme (GBM) In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US) [cited 2016 Dec]. Available from: NLM Identifier: NCT Novocure

39 COMBINATION THERAPY FOR NEWLY DIAGNOSED GBM EF-14 key inclusion and exclusion criteria INCLUSION CRITERIA Pathologic evidence of GBM (WHO criteria) >18 years old Received maximal debulking surgery, radiation therapy, and concomitant TMZ KPS >70 Treatment start >4 weeks from surgery Treatment start between 4-7 weeks from last dose of concomitant chemotherapy and radiation therapy Life expectancy >3 months EXCLUSION CRITERIA Progressive disease per Macdonald Criteria Active participation in another clinical trial Pregnant Significant comorbidities that would prevent maintenance TMZ (thrombocytopenia, neutropenia, hepatic or renal function impairment) Infratentorial tumor Evidence of increased intracranial pressure TMZ hypersensitivity Novocure, Ltd. Effect of NovoTTF-100A Together With Temozolomide in Newly Diagnosed Glioblastoma Multiforme (GBM) In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US) [cited 2016 Dec]. Available from: NLM Identifier: NCT Novocure

40 COMBINATION THERAPY FOR NEWLY DIAGNOSED GBM EF-14 key baseline characteristics INTENT-TO-TREAT POPULATION CHARACTERISTICS OPTUNE + TMZ (N=466) TMZ ALONE (N=229) Median age, years (range) 56 (19-83) 57 (19-80) Female sex, % Median KPS (range) 90 (60-100) 90 (70-100) Extent of resection, % Gross total resection Partial resection Biopsy Median time from diagnosis to randomization, mo (range) 3.8 ( ) 3.7 ( ) Duration of Therapy with TMZ, mo Median (range) 6 (0-51) 5 (0-33) Duration of Therapy with Optune, mo Median (range) 8.2 (0-82) 0 (0-0) Baseline characteristics were well balanced between the two treatment arms 1,2 ITT, intent-to-treat; TMZ, temozolomide; KPS, Karnofsky Performance Score; SD, standard deviation. 1. Stupp R, et al; on behalf of EF-14 trial investigators. Slides presented at the Society of NeuroOncology 21st Annual Meeting; November 17-20, 2016; Scottsdale, AZ. 2. Stupp R, et al; on behalf of EF-14 trial investigators. SNO Abstract LTBK-01. Neuro-Oncology In press Novocure

41 COMBINATION THERAPY FOR NEWLY DIAGNOSED GBM EF-14 key baseline characteristics (cont d) INTENT-TO-TREAT POPULATION MOLECULAR PROFILES, %, MGMT status Tissue available and tested Methylated Unmethylated Insufficient for testing IDH1 R132 mutation status OPTUNE + TMZ (N=466) TMZ ALONE Tissue available and tested Positive 7 5 Medications, % Antiepileptics Corticosteroids Adherence to Optune,* % (N=229) Baseline characteristics were well balanced between the two treatment arms 1, *Defined as 75% during the first 3 months of treatment. ITT, intent-to-treat; TMZ, temozolomide; MGMT, O6-methylguanine-DNA methyltransferase; IDH1, isocitrate dehydrogenase Stupp R, et al; on behalf of EF-14 trial investigators. Slides presented at: SNO 21st Annual Meeting; November 17-20, 2016; Scottsdale, AZ. 2. Stupp R, et al; on behalf of EF-14 trial investigators. SNO Abstract LTBK-01. Neuro-Oncology In press. Novocure

42 COMBINATION THERAPY FOR NEWLY DIAGNOSED GBM EF-14 incidence of grade 3/4 adverse events OPTUNE + TMZ (N=437) TMZ ALONE (N=207) N (%) N (%) SYSTEM ORGAN CLASS GRADE 3 GRADE 4 GRADE 3 GRADE 4 Blood and lymphatic system disorders Leukopenia Lymphopenia Neutropenia Thrombocytopenia < <1 1 Gastrointestinal disorders 5 <1 3 <1 General disorders and administration site conditions 9 <1 6 0 Fatigue Asthenia Gait disturbance Infections and infestations 7 <1 4 1 Procedural complications Fall Medical device site reaction NOTES Incidence of grade 3/4 adverse events seen in 2 % of patients Most common ( 10%) AEs involving Optune in combination with TMZ were thrombocytopenia, nausea, constipation, vomiting, fatigue, medical device site reaction, headache, convulsions, and depression. 1,2 TMZ, temozolomide. 1. Stupp R, et al; on behalf of EF-14 trial investigators. Slides presented at: SNO 21st Annual Meeting; November 17-20, 2016; Scottsdale, AZ. 2. Novocure Data on File OPT-103. Novocure

43 COMBINATION THERAPY FOR NEWLY DIAGNOSED GBM EF-14 incidence of grade 3/4 adverse events OPTUNE + TMZ (N=437) TMZ ALONE (N=207) N (%) N (%) SYSTEM ORGAN CLASS GRADE 3 GRADE 4 GRADE 3 GRADE 4 Metabolism and nutrient disorders Hyperglycemia 2 < Musculoskeletal and connective tissue disorders 4 <1 4 0 Nervous system disorders Aphasia Brain edema Convulsion Headache Hemiparesis Neurological decompensation < <1 < Psychiatric disorders Renal and urinary disorders Respiratory disorders Pulmonary embolism 2 < <1 2 2 Vascular disorders Hypertension <1 0 0 TMZ, temozolomide. 1. Stupp R, et al; on behalf of EF-14 trial investigators. Slides presented at: SNO 21st Annual Meeting; November 17-20, 2016; Scottsdale, AZ. 2. Novocure Data on File OPT-103. NOTES Incidence of grade 3/4 adverse events seen in 2 % of patients Most common ( 10%) AEs involving Optune in combination with TMZ were thrombocytopenia, nausea, constipation, vomiting, fatigue, medical device site reaction, headache, convulsions, and depression. 1,2 Novocure

44 COMBINATION THERAPY FOR NEWLY DIAGNOSED GBM EF-14 interim analysis EF-14 protocol prespecified one interim analysis to occur when the first 315 patients completed 18 months of follow-up 1,2 The primary endpoint of progression-free survival (PFS) was to be analyzed in the ITT population and the secondary endpoint of overall survival (OS) was to be analyzed in the PP population Population PFS* (ITT) INTERIM ANALYSIS 315 patients 18 months of follow-up from enrollment of the 315th patient P= required for trial to meet the primary endpoint of a significantly higher PFS in the Optune + TMZ arm OS (PP) P= required to meet the powered secondary end point; tested only if PFS was positive *The central MRI review was based on an independent, blinded radiological review. PFS, progression-free survival; ITT, intent-to-treat; OS, overall survival; PP, per protocol. 1. Optune Instructions for Use. Novocure Stupp R, et al. JAMA. 2015;314(23): doi: doi: /jama Novocure

45 EF-14 INTERIM ANALYSIS EF-14 enrollment and treatment randomization 1,2 n=315 Optune + TMZ n=210 TMZ n=105 intent-to-treat population (ITT) received any treatment n=203 received any treatment n=101 started 2nd cycle Optune + TMZ n=196 started 2nd cycle TMZ n=95 no major protocol violations n=196 TMZ, temozolomide. 1. Optune Instructions for Use. Novocure Stupp R, et al. JAMA. 2015;314(23): doi: doi: /jama no major protocol violations n=84 per-protocol population (PP) Novocure

46 EF-14 INTERIM ANALYSIS: INTENT-TO-TREAT POPULATION EF-14 progression free survival OPTUNE + TMZ (n=210) 1,2 TMZ ALONE (n=105) 1,2 Median PFS from randomization, mo % CI, mo Stratified log-rank p= HR (95% CI) ( ) Median PFS from diagnosis, mo *Both interim and long-term analyses are protocol pre-specified. 3,4 TMZ, temozolomide; ITT, intent-to-treat; PFS, progression-free survival; CI, confidence interval; HR, hazard ratio. 1. Optune Instructions for Use. Novocure Novocure

47 EF-14 INTERIM ANALYSIS: AS-TREATED POPULATION EF-14 overall survival OPTUNE + TMZ (n=196) 1,2 TMZ ALONE (n=84) 1,2 Median OS from randomization, mo % CI, mo Stratified log-rank p= HR (95% CI) ( ) Median OS from diagnosis, mo year OS 48% 32% *Both interim and long-term analyses are protocol pre-specified. 3,4 TMZ, temozolomide; PP, per protocol; OS, overall survival; CI, confidence interval; HR, hazard ratio. 1. Optune Instructions for Use. Novocure Novocure Data on File OPT Stupp R, et al. SNO Abstract LTBK-01. Neuro-Oncology In press. 4. Stupp R, et al; on behalf of EF-14 trial investigators. Slides presented at: SNO 21st Annual Meeting; November 17-20, 2016; Scottsdale, AZ. Novocure

48 EF-14 INTERIM ANALYSIS: INTENT-TO-TREAT POPULATION quality of life maintained Quality of life was not adversely affected by the continuous use of TTFields 1 Activities of daily living did not decline when TTFields were added to temozolomide therapy Cognitive function did not decline when TTFields were added to temozolomide therapy 1. Zhu J.J. et. al. Quality of Life, Cognitive Function and Functional Status in the EF-14 Trial: a Prospective, Multi-Center Trial of Tumor Treating Fields Together With Temozolomide (TMZ) Compared to TMZ Alone in Patients With Newly Diagnosed GBM, SNO presentation, (Friday, Nov. 20, 2015, 2:40-2:50 p.m., concurrent session 2A clinical trials phase II/III, abstract: 0761) Novocure

49 EF-14 INTERIM ANALYSIS: MAINTAINING TTFIELDS AFTER FIRST RECURRENCE TTFields with chemo versus chemo alone TTFIELDS + CHEMOTHERAPY (N=144) CHEMOTHERAPY ALONE (N=60) Median OS, mo Stratified log-rank 1 p= HR (95% CI) Kesari S. and Ram Z.; on Behalf of EF-14 Trial Investigators.Neuro-Oncology. 2015;17(Suppl 5):v14. doi: /neuonc/nov Novocure

50 EF-14 INTERIM ANALYSIS: MAINTAINING TTFIELDS AFTER FIRST RECURRENCE TTFields with bevacizumab versus bev. alone 55% of patients received bevacizumab (with or without chemo) as their second-line treatment choice TTFIELDS + BEVACIZUMAB (N=79) BEVACIZUMAB ALONE (N=30) Median OS, mo Stratified log-rank 1 p= HR (95% CI) Kesari S. and Ram Z.; on Behalf of EF-14 Trial Investigators.Neuro-Oncology. 2015;17(Suppl 5):v14. doi: /neuonc/nov Novocure

51 EF-14 LONG-TERM ANALYSIS EF-14 enrollment and treatment randomization 1,2 n=695 interim analysis Optune + TMZ n=210 TMZ n=105 long-term analysis* Optune + TMZ n=466 *26 patients crossed over at the time of FDA approval of crossover. TMZ, temozolomide. 1. Stupp R, et al. JAMA. 2015;314(23): doi: doi: /jama Stupp R, et al; on behalf of EF-14 trial investigators. Slides presented at: SNO 21st Annual Meeting; November 17-20, 2016; Scottsdale, AZ. TMZ n=229 Novocure

52 EF-14 LONG-TERM ANALYSIS: INTENT-TO-TREAT POPULATION EF-14 progression free survival OPTUNE + TMZ (n=466) 1,2 TMZ ALONE (n=229) 1,2 Median PFS from randomization, mo % CI, mo Stratified log-rank p< HR 2 (95% CI) 0.63 ( ) Median PFS from diagnosis, mo *Both interim and long-term analyses are protocol prespecified. 1,2 TMZ, temozolomide; ITT, intent-to-treat; PFS, progression-free survival; CI confidence interval; HR, hazard ratio. 1. Stupp R, et al; on behalf of EF-14 trial investigators. Slides presented at: SNO 21st Annual Meeting; November 17-20, 2016; Scottsdale, AZ. 2. Stupp R, et al; on behalf of EF-14 trial investigators. SNO Abstract LTBK-01. Neuro- Oncology In press. Novocure

53 EF-14 LONG-TERM ANALYSIS: INTENT-TO-TREAT POPULATION EF-14 overall survival OPTUNE + TMZ (n=466) 1,2 TMZ ALONE (n=229) 1,2 Median OS from randomization, mo % CI, mo Stratified log-rank p< HR (95% CI) 0.65 ( ) Median OS from diagnosis, mo *Both interim and long-term analyses are protocol prespecified. 1,2 TMZ, temozolomide; ITT, intent-to-treat; OS, overall survival; CI, confidence interval; HR, hazard ratio. 1. Stupp R, et al; on behalf of EF-14 trial investigators. Slides presented at: SNO 21st Annual Meeting; November 17-20, 2016; Scottsdale, AZ. 2. Stupp R, et al; on behalf of EF-14 trial investigators. SNO Abstract LTBK-01. Neuro- Oncology In press. 3. Novocure Data on File OPT-118. Novocure

54 EF-14 LONG-TERM ANALYSIS EF-14 subgroup analysis SUBGROUP NO. OF PATIENTS (%) HAZARD RATIO OPTUNE + TMZ 1 TMZ ALONE 1 MEDIAN SURVIVAL (MONTHS) Overall 695 (100) MGMT (central) Unmethylated 303 (44) Methylated 213 (31) Resection Biopsy 89 (13) Partial 234 (34) Gross total 372 (53) Age <50 y 194 (28) y 501 (72) KPS (67) < (33) Sex Female 222 (32) Male 473 (68) TMZ, temozolomide; MGMT, O6-methylguanine-DNA methyltransferase; KPS, Karnofsky Performance Score. 1. Stupp R, et al; on behalf of EF-14 trial investigators. Slides presented at: SNO 21st Annual Meeting; November 17-20, 2016; Scottsdale, AZ OPTUNE + TMZ BETTER TMZ ALONE BETTER Novocure

55 EF-14 LONG-TERM ANALYSIS EF-14 long-term survival rates 70% IMPROVEMENT IN SURVIVAL WITH TTFIELDS + TMZ (17%) VERSUS TMZ ALONE (10%) AT 4 YEARS (P=0.028) 1,2 TMZ, temozolomide; ITT, intent-to-treat. 1. Stupp R, et al; on behalf of EF-14 trial investigators. [SNO Abstract LTBK-01]. Neuro-Oncology In press. 2. Stupp R, et al; on behalf of EF-14 trial investigators. Slides presented at: SNO 21st Annual Meeting; November 17-20, 2016; Scottsdale, AZ. Novocure

56 COMBINATION THERAPY FOR NEWLY DIAGNOSED GBM consistency across EF-14 analyses PFS, progression-free survival; OS, overall survival; TMZ, temozolomide; ITT, intent-to-treat; PP, per protocol. 1. Optune Instructions for Use. Novocure Novocure Data on File OPT Stupp R, et al; on behalf of EF-14 trial investigators. Slides presented at: SNO 21st Annual Meeting; November 17-20, 2016; Scottsdale, AZ. 4. Stupp R, et al; on behalf of EF-14 trial investigators. SNO Abstract LTBK-01. Neuro- Oncology In press. Novocure

57 COMBINATION THERAPY FOR NEWLY DIAGNOSED GBM EF-14 summary EF-14 long-term analysis confirms conclusions of interim analysis TTFields are safe and can be combined with TMZ chemotherapy Toxicity is limited to local skin irritation and cutaneous reactions Adjuvant therapy with TTFields significantly prolongs progression-free and overall survival in patients with newly diagnosed GBM Novocure

58 brain metastases Vinai Gondi, MD Northwestern Medicine Proton Center METIS Principal Investigator

59 BRAIN METASTASES disease state and clinical presentation Most common form of brain cancer, exceeding the number of primary brain tumors by at least fourfold 1 and occurring in roughly 15% of all cancer patients 2 Brain metastases most frequently arise from lung, breast, skin, colorectal and kidney cancers 1 Blood-brain barrier (BBB) critical to role of metastases - Certain primary neoplasms able to damage BBB, allowing spread into brain - Once these have crossed into brain, BBB repairs itself and the metastasis is protected from many chemotherapies Symptoms usually caused by increased pressure in the brain - Can include headache, seizures, nausea, vomiting, or drowsiness - Depending on tumor location, can also include other focal neurological defects such as weakness on one side of the body, visual changes, motor dysfunction, cognitive dysfunction, or sensory changes 1. Goetz P, Ebinu JO, Roberge D, Zadeh G. Intl J of Surg Onc. 2012;2012: doi: /2012/ Bashour S.I., William W.N., Patel S., Rao G., Strom E., McAleer M.F., Guha-Thakurta N., Conrad C. and Ibrahim N.K., Chapter 1 - Brain Metastasis from Solid Tumors, In Brain Metastases from Primary Tumors, edited by M.A. Hayat,, Academic Press, San Diego, 2015, Pages 3-29, ISBN , doi: /b x. Novocure

60 BRAIN METASTASES epidemiology United States 1 Brain metastases estimated incidence of 98, ,000 cases annually Europe Brain metastases estimated incidence of 75,000 cases annually Japan Brain metastases estimated incidence of 13,000 cases annually Exact global incidence unknown, with estimates varying widely Occur in roughly 15% of cancer patients, though autopsy analyses have indicated higher incidence 2 1. Goetz P, Ebinu JO, Roberge D, Zadeh G. Intl J of Surg Onc. 2012;2012: doi: /2012/ Bashour S.I., William W.N., Patel S., Rao G., Strom E., McAleer M.F., Guha-Thakurta N., Conrad C. and Ibrahim N.K., Chapter 1 - Brain Metastasis from Solid Tumors, In Brain Metastases from Primary Tumors, edited by M.A. Hayat,, Academic Press, San Diego, 2015, Pages 3-29, ISBN , doi: /b x. Novocure

61 BRAIN METASTASES FROM NON-SMALL CELL LUNG CANCER (NSCLC) current prognosis Approximately 7.4% of NSCLC patients will have brain metastases at presentation and 25-30% will develop brain metastases during the course of their disease 1 Survival impacted by factors such as age, number of brain metastases, patient health status, presence of extracranial metastases, and presence of targetable mutations 1,2 - Median time to intracranial (IC) failure is approximately 7-9 months 3 - Median OS is approximately 7-13 months 3 1. Owen S, Souhami L. Frontiers in Oncology. 2014;4:248. doi: /fonc Sperduto, P. et al. JAMA Oncol. (2016) 2016 Nov 17. doi: /jamaoncol [Epub ahead of print] 3. See additional references next slide. Novocure

62 BRAIN METASTASES FROM NON-SMALL CELL LUNG CANCER references for time to IC failure and OS OVERALL SURVIVAL, MO % 1 YEAR SURVIVAL MEDIAN TIME TO IC FAILURE AUTHOR YEAR JOURNAL HISTOLOGY Williams et al J Neurooncol NSCLC Li et al Int J Cancer NSCLC Maor et al Int J Cancer NSCLC Regine et al Int J Radiat Oncol Biol Phys NA 9 36% - Pollock et al J Neurooncol NSCLC, Breast, Melanoma, renal % 8 Flannery et al Lung Cancer NSCLC Rades et al Cancer NSCLC - 45% - Kim et al Cancer NSCLC Mariya et al 2010 J Rad Res NSCLC 9 38% 9 Marko et al J Neurooncol NSCLC Kelly et al Int J Radiat Oncol Biol Phys NA Xu et al World Neurosurg NSCLC Xu et al Clin Transl Oncol NSCLC Smith et al J Neurosurgery NSCLC, Melanoma, Breast, Other % - Median % 7.7 Hazard rate Novocure

63 BRAIN METASTASES FROM NON-SMALL CELL LUNG CANCER current standard of care Due to failure of most chemotherapies to cross BBB, treatment of brain metastases has been largely confined to supportive care with surgery and radiation therapy Standard treatment includes - Surgical resection, usually limited to single metastasis - Stereotactic radiosurgery (SRS), to deliver a single high dose of irradiation - Post SRS, supportive care given during watchful waiting - Whole-brain radiotherapy (WBRT), usually utilized as salvage therapy due to detrimental neurocognitive effects newly diagnosed brain metastases stereotactic radiosurgery (SRS) monthly follow-up with supportive care MRI q2m whole-brain radiotherapy (WBRT) 1. Owen S, Souhami L. Frontiers in Oncology. 2014;4:248. doi: /fonc Novocure

64 BRAIN METASTASES FROM NON-SMALL CELL LUNG CANCER rationale for testing TTFields in brain mets TTFields shown to be effective and safe in glioblastoma patients (phase 3 pivotal EF- 14 trial in GBM) 1 Believe the device can be applied to other intracranial solid tumors In-vitro data has shown NSCLC sensitivity to TTFields at 150kHz 2 TTFields have been to shown to prevent metastatic seeding in-vivo 3 Phase 2 pilot data in primary NSCLC (EF-15) showed potential efficacy 4 TTFields at 150kHz were safe in a pilot trial of NSCLC brain metastasis patients (EF- 21/COMET) and have been shown not to harm cognitive function of GBM patients 5 when used in combination with temozolomide 1. Stupp R, et al. JAMA. 2015;314(23): doi: doi: /jama Pless M, Weinberg U, Betticher D, Giladi M, von Moos R, Schneiderman R, et al. Cancer Res 2012;72(8 (Suppl. 1)). p. abstract doi: / AM Kirson, E.D., Giladi, M., Gurvich, Z. et al. Clin Exp Metastasis. 2009; 26: doi: /s y 4. Pless M, et al. Lung Cancer. 2013;81(3): doi: /j.lungcan Zhu J.J. et al. Quality of Life, Cognitive Function and Functional Status in the EF-14 Trial: a Prospective, Multi-Center Trial of Tumor Treating Fields Together With Temozolomide (TMZ) Compared to TMZ Alone in Patients With Newly Diagnosed GBM, SNO presentation, (Friday, Nov. 20, 2015, 2:40-2:50 p.m., concurrent session 2A clinical trials phase II/III, abstract: 0761) Novocure

65 BRAIN METASTASES FROM NON-SMALL CELL LUNG CANCER METIS phase 3 pivotal trial initiated in 2016 A prospective, randomized controlled, multicenter trial testing efficacy, safety and neurocognitive outcomes of TTFields at 150 khz following stereotactic radiosurgery in advanced non-small cell lung cancer patients with 1-10 brain metastases 270 patients internationally, randomized 1:1 (TTFields vs supportive care) Twelve month follow-up after final patient enrollment Endpoints: Primary endpoint time to first cerebral progression Secondary endpoints include neurocognitive failure, overall survival, radiological response rate Novocure, Ltd. Effect of TTFields (150 khz) in Non-small Cell Lung Cancer (NSCLC) Patients With 1-10 Brain Metastases Following Radiosurgery (METIS) In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US) [cited 2016 Dec]. Available from: NLM Identifier: NCT Novocure

66 BRAIN METASTASES FROM NON-SMALL CELL LUNG CANCER key inclusion and exclusion criteria INCLUSION CRITERIA New diagnosis of brain metastases from histologically confirmed metastatic NSCLC 18 years old Life expectancy 3 months KPS 70 GPA inoperable brain metastasis or 2-10 brain lesions, confirmed by MRI At least 1 measurable lesion per RANO-BM Receiving optimal therapy for extracranial disease Prior clinical trial enrollment allowed, as long as no brain directed therapy included EXCLUSION CRITERIA Somatic tumor mutations for which targeted agents are available Single, operable brain metastasis Significant edema with risk of brain herniation Midline shift > 10mm Intractable seizures Infratentorial or leptomeningeal metastases Previously treated recurrent brain metastases or prior surgical resection for newly diagnosed brain metastases Severe comorbidities Implantable electronic medical devices Pregnant Novocure, Ltd. Effect of TTFields (150 khz) in Non-small Cell Lung Cancer (NSCLC) Patients With 1-10 Brain Metastases Following Radiosurgery (METIS) In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US) [cited 2016 Dec]. Available from: NLM Identifier: NCT Novocure

67 BRAIN METASTASES FROM NON-SMALL CELL LUNG CANCER clinical milestones and next steps NEXT STEPS Continued expansion of investigator and investigating site footprint Last patient enrollment expected in 2019 Data presentation expected to be twelve months following LPI First patient in Last patient in Data Enrolled in October 2016 Expected in 2019 Expected 12 months following last patient enrollment Novocure

68 non-small cell lung cancer Eilon Kirson, MD, PhD Chief Science Officer and Head of R&D Actor portrayal

69 NON-SMALL CELL LUNG CANCER disease state and clinical presentation Lung cancer is the most common cancer type worldwide 1 Smoking is the major risk factor for non-small cell lung cancer % of all lung cancers are non-small cell (NSCLC) 2 - Majority of NSCLC cases (40%) are adenocarcinomas, arising from the cells that normally secrete substances such as mucus - Squamous cells carcinomas (25-30% of NSCLCs) arise from flat cells lining the inner airways near the central lungs - Large cell carcinomas (10-15% of NSCLCs) appear in any part of the lung and tend to spread quickly Only a minority of NSCLC patients present with localized disease Symptoms include trouble breathing, coughing that does not abate, coughing up blood, chest pain, hoarseness, infection, wheezing 1. WHO (2016) GLOBOCAN 2012: Estimated Cancer Incidence, Mortality, and Prevalence Worldwide in 2012, Lyon, France (accessed December 2016) 2. Lung Cancer Non-Small Cell Detailed Guide. Atlanta: American Cancer Society, SEER Cancer Statistics Factsheets: Lung and Bronchus Cancer. National Cancer Institute. Bethesda, MD (accessed December 2016) Novocure

70 NON-SMALL CELL LUNG CANCER epidemiology United States 1 NSCLC incidence of 185,000 cases annually Europe 2 NSCLC incidence of 350,000 cases annually Japan 3 NSCLC incidence of 80,000 cases annually Incidence of NSCLC is approximately 16 per 100,000 people, varying widely on a geographic basis 3 Regional incidence variations directly reflect smoking prevalence 1. SEER Cancer Statistics Factsheets: Lung and Bronchus Cancer. National Cancer Institute. Bethesda, MD (accessed December 2016) 2. Ferlay J, Steliarova-Foucher E, Lortet-Tieulent J, Rosso S, Coebergh JWW, Comber H, Forman D, Bray F. Eur J Cancer. 2013;49(6): doi: /j.ejca WHO (2016) GLOBOCAN 2012: Estimated Cancer Incidence, Mortality, and Prevalence Worldwide in 2012, Lyon, France (accessed December 2016) Novocure

71 ADVANCED NON-SMALL CELL LUNG CANCER current prognosis Heterogeneity of patient demographics, tissue involvement and disease staging at presentation require personalized approaches Stage IIIB-IV defined as being locally advanced within the lungs or metastatic to lymph nodes and distant organs 1 Surgical resection usually only feasible for stage I-IIIA NSCLC patients 2 Prognosis for stage IIIB-IV remains poor, despite active research Median progression-free survival (PFS) is approximately 3-4 months 3,4 Median overall survival (OS) is approximately 13 months 4 1. Lung Cancer Non-Small Cell Detailed Guide. Atlanta: American Cancer Society, Molina JR, Yang P, Cassivi SD, Schild SE, Adjei AA. Mayo Clinic proceedings Mayo Clinic. 2008;83(5): doi: / Hanna N, Shepherd FA, Fossella FV, Pereira JR, De Marinis F, von Pawel J, et al. J Clin Oncol 2004;22(9): doi: /JCO Ciuleanu T, Brodowicz T, Zielinski C, Kim JH, Krzakowski M, Laack E, et al. Lancet 2009;374(9699): doi: /S (09) Novocure

72 SECOND LINE TREATMENT FOR ADVANCED NON-SMALL CELL LUNG CANCER evolving standard of care Since 1991, radiation with a combination of platinum-based chemotherapy has been the firstline standard of care for locally advanced or metastatic NSCLC 1 Standard treatment includes - Radiation therapy with concomitant platinum-based chemo (cisplatin/carboplatin) - Post-radiation, chemotherapy doublets may include docetaxel, gemcitabine, paclitaxel, and vinorelbine with platinum-based agents - At recurrence, second line treatment may include pemetrexed, docetaxel or immunotherapies Stage IIIB or IV NSCLC radiation therapy (RT) + cisplatin/carboplatin platinum-based doublet CT q2m until progression second or third line chemotherapy 1. Le Chevalier T, et al. J Natl Cancer Inst. 1991;83(6): doi: /jnci/ Molina JR, Yang P, Cassivi SD, Schild SE, Adjei AA. Mayo Clinic proceedings Mayo Clinic. 2008;83(5): doi: / Novocure

73 SECOND LINE TREATMENT FOR ADVANCED NON-SMALL CELL LUNG CANCER torso array placement DISTRIBUTION OF TTFIELDS AROUND THE LUNGS Bomzon, Z. et al. (2015 August) Modelling Tumor Treating Fields (TTFields) for the treatment of lung tumors. Poster session presented at the EMBC annual IEEE Engineering in Medicine and Biology Society. Milan, Italy. Novocure

74 SECOND LINE TREATMENT FOR ADVANCED NON-SMALL CELL LUNG CANCER phase 2 pilot EF-15 trial A prospective, open label, single-arm, non-randomized, multicenter study of TTFields at 150 khz to estimate efficacy and determine safety together with pemetrexed in pretreated patients with locally advanced nonsmall cell lung cancer versus historical controls 42 patients in Switzerland with locally advanced and/or metastatic non-small cell lung cancer Last patient enrolled May 2011 with six month follow-up Endpoints: Primary endpoint severity and frequency of adverse events, as well as feasibility based on compliance with TTFields therapy Secondary endpoints include progression free survival, overall survival, overall response rate Novocure, Ltd. NovoTTF-100L in Combination With Pemetrexed (Alimta ) for Advanced Non-small Cell Lung Cancer In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US) [cited 2016 Dec]. Available from: NLM Identifier: NCT Novocure

75 SECOND LINE TREATMENT FOR ADVANCED NON-SMALL CELL LUNG CANCER EF-15 key inclusion and exclusion criteria INCLUSION CRITERIA Histologically confirmed NSCLC Stage IV or IIIB disease with malignant pleural effusion, also locally advanced NSCLC not otherwise amenable to local treatment One line of prior chemotherapy Measurable disease 18 years old Life expectancy 3 months ECOG score of 0-2 Laboratory verification of adequate hemotologic, renal and hepatic function upon entry EXCLUSION CRITERIA Brain metastases or meningeal carcinomatosis Concurrent treatment with other experimental drugs or participation in other clinical trials Pregnant Other serious concomitant illness, including - Uncontrolled congestive heart failure or angina pectoris - History of myocardial infarction within 1 year - Uncontrolled hypertension or arrhythmias - Implanted pacemaker, defibrillator or deep brain stimulation device - History of neurologic or psychiatric disorders Novocure, Ltd. NovoTTF-100L in Combination With Pemetrexed (Alimta ) for Advanced Non-small Cell Lung Cancer In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US) [cited 2016 Dec]. Available from: NLM Identifier: NCT Novocure

76 SECOND LINE TREATMENT FOR ADVANCED NON-SMALL CELL LUNG CANCER EF-15 key baseline characteristics CHARACTERISTICS (N=42) NUMBER (%) 1 Median age, years (range) 63 (44-78) Gender Male 26 (63%) Female 15 (37%) ECOG performance status 0 or 1 2 unknown Disease stage, % IIIB (pleural effusion) IV Histology Adenocarcinoma Squamous cell Large cell Past treatments Surgery Radiation Time since diagnosis, median Time since last chemotherapy, median 31 (76%) 7 (17%) 3 (7%) 10 (24%) 31 (76%) 32 (78%) 7 (17%) 2 (5%) 5 (12%) 10 (24%) 45.4 weeks 14.9 weeks 1. Pless M, et al. Lung Cancer. 2013;81(3): doi: /j.lungcan Novocure

77 SECOND LINE TREATMENT FOR ADVANCED NON-SMALL CELL LUNG CANCER EF-15 incidence of adverse events GRADE 3-4 GRADE 1-2 GRADE 3-4 GRADE 1-2 SYSTEM ORGAN CLASS N (%) 1 N (%) 1 Constitutional Fatigue 1 (2%) 9 (22%) Asthenia 0 2 (5%) Insomnia 0 3 (7%) Night sweats 0 3 (7%) Fever 0 2 (5%) Cardiovascular Arrhythmia 0 1 (2%) Dermatology Rash/dermatitis/erythema Blister Pruritus Alopecia Ulceration Infectious Urinary 1. Pless M, et al. Lung Cancer. 2013;81(3): doi: /j.lungcan (2%) (24%) 3 (7%) 2 (5%) 1 (2%) 1 (2%) 2 (5%) 0 SYSTEM ORGAN CLASS Gastrointestinal Anorexia Diarrhea Nausea Constipation Vomiting Neurological Dizziness Neuropathy Pain Thoracic/chest/rib Limb Abdominal Headache Electric pain Cervical pain Respiratory Dyspnea Cough N (%) 1 2 (5%) 2 (5%) (2%) 0 2 (5%) (2%) 1 (2%) 4 (10%) 0 N (%) 1 3 (7%) 2 (5%) 3 (7%) 4 (10%) 3 (7%) 1 (2%) 2 (5%) 3 (7%) 4 (10%) 3 (7%) 3 (7%) (19%) 11 (27%) Novocure

78 SECOND LINE TREATMENT FOR ADVANCED NON-SMALL CELL LUNG CANCER phase 2 pilot EF-15 trial results EFFICACY ENDPOINTS TTFIELDS WITH PEMETREXED 1 PEMETREXED-ALONE HISTORICAL CONTROL 2 Median in-field PFS 6.5 months n/a Median PFS 5 months 2.9 months Median OS 13.8 months 8.3 months One-year survival rate 57% 29.7% Partial response rate 14.6% 9.1% 1. Pless M, et al. Lung Cancer. 2013;81(3): doi: /j.lungcan Hanna N, Shepherd FA, Fossella FV, Pereira JR, De Marinis F, von Pawel J, et al. J Clin Oncol 2004;22(9): doi: /JCO Novocure

79 SECOND LINE TREATMENT FOR ADVANCED NON-SMALL CELL LUNG CANCER planned LUNAR phase 3 pivotal trial Randomized pivotal trial, standard-of-care controlled 512 patients with second line NSCLC, all histologies Treatment groups: TTFields with PD-1 inhibitor or docetaxel (based on physician s choice) PD-1 inhibitor or docetaxel (based on physician s choice) Stratification factors: PD-1 inhibitor vs docetaxel Histology (squamous vs non-squamous) Endpoints: Primary overall survival (OS) (Superiority) Secondary - OS of TTFields + docetaxel vs docetaxel alone (superiority) - OS of TTFields + PD-1 inhibitor vs PD-1 inhibitor alone (superiority) - OS of TTFields + docetaxel vs PD-1 inhibitor alone (non-inferiority) Novocure

80 SECOND LINE TREATMENT FOR ADVANCED NON-SMALL CELL LUNG CANCER LUNAR design considerations Intended to facilitate accrual as standard of care treatments are included on both arms, regardless of reimbursement for PD-1 inhibitors Intended to enable data collection for different combinations with TTFields (immune therapy and taxanes) Will not compete with first line PD-1 NSCLC trials If PD-1 inhibitors move to first line, have chance at superiority data with taxanes in second line If PD-1 inhibitors fail in first line: - Two chances of success in second line: Superiority with PD-1 inhibitors Non-inferiority with taxanes compared to PD-1 inhibitors - Plan to have data on TTFields with taxanes to support potentially moving TTFields to first line (where standard of care includes taxanes) Novocure

81 SECOND LINE TREATMENT FOR ADVANCED NON-SMALL CELL LUNG CANCER planned LUNAR inclusion and exclusion criteria INCLUSION CRITERIA 18 years old Life expectancy 3 months Histologically confirmed unresectable, locally advanced or metastatic NSCLC ECOG score of 0-1 Assigned by physician to receive either docetaxel or PD-1 inhibitor per standard of care EXCLUSION CRITERIA Brain metastases or leptomeningeal spread Prior surgery or radiation in the lungs Severe comorbidities, including - Hematological, hepatic or renal dysfunction - Uncontrolled cardiovascular disease - Symptomatic arrhythmia - History of cerebrovascular accident - Active infection - History of psychiatric condition Concurrent experimental studies Implantable electronic medical devices Pregnant or breast-feeding Novocure

82 SECOND LINE TREATMENT FOR ADVANCED NON-SMALL CELL LUNG CANCER clinical milestones and next steps NEXT STEPS First patient enrollment anticipated in 1H 2017 First patient in Last patient in Data Expected 1H 2017 Expected 2-3 years following first patient enrolled Expected 18 months following last patient enrollment Novocure

83 break

84 pancreatic cancer Daniel D. Von Hoff, MD Translational Genomics Research Institute World-renowned expert in pancreatic cancer Actor portrayal

85 why would a doc interested in pancreatic cancer drug dev. be interested in TTFields Glioblastoma - Almost impossible to improve survival - TTFields did improve survival Pancreatic cancer is similarly difficult A new and different approach; new mechanisms of action are always interesting Image: Voloshin T, Munster M, Blatt R, et al. Int J of Cancer. 2016;139(12): doi: /ijc Novocure

86 in 2016, pancreatic cancer is still with us and it is still bad Currently the 4th leading cause of death from cancer in the U.S. (2nd leading cause by 2030) 1,2 The worst survival rate of any cancer Latest 2016 estimates 1-53,070 (27,670 men; 25,400 women) people diagnosed with the disease - 41,780 (21,450 men; 20,330 women) people will die from the disease (114 people a day) - Kills >300,000 worldwide Incidence increasing 0.8% - 1% / year - mostly because we are an aging population 1. Siegel, R. L., Miller, K. D. and Jemal, A. CA: A Cancer Journal for Clinicians, 2016; 66: doi: /caac Rahib L. et al. Cancer Res. 2014; 74 (11): ; doi: / CAN Novocure

87 pancreatic cancer kills more than 300,000 individuals each year worldwide Novocure

88 clinical staging of pancreatic cancer Resectable (localized): med survival = mo. - No encasement of celiac axis or superior mesenteric artery (SMA) - Patent superior mesenteric portal veins - No extra pancreatic disease Locally advanced: med survival = 6-10 months - Encasement of arteries - Venous occlusion (SMV or portal) - No extra pancreatic disease Metastatic: median survival 3-6 months (in past) Novocure

89 There is an unmet medical need for patients with locally advanced inoperable pancreatic cancer survival is still terrible

90 ADVANCED PANCREATIC CANCER current standard of care, but need to do better Resectable - Surgery followed by gemcitabine + capecitabine Locally Advanced - No current standard - Try to make operable chemotherapy with or without XRT Metastatic - First line Nab-paclitaxel + gemcitabine Folfirinox (folinic acid) +5FU +irinotecan + oxaliplatin - Second line Irinotecan liposome 1. Von Hoff, D.D. et al. N Engl J Med, 2013, 369: doi: /nejmoa Novocure

91 ADVANCED PANCREATIC CANCER based on biology: abdominal array placement DISTRIBUTION OF TTFIELDS AROUND THE PANCREAS Novocure

92 ADVANCED PANCREATIC CANCER phase 2 pilot PANOVA trial A prospective, open label, single-arm, non-randomized, multicenter study testing feasibility, safety and preliminary efficacy of TTFields at 150 khz together with gemcitabine or gemcitabine plus nab-paclitaxel in patients with advanced pancreatic cancer versus historical controls 40 patients in Europe with locally advanced or metastatic pancreatic cancer First cohort (n=20) of TTFields at 150 khz with gemcitabine Second cohort (n=20) of TTFields at 150 khz with gemcitabine and nab-paclitaxel Last patient enrolled May 2016 with six month follow-up Endpoints: Primary endpoint severity and frequency of adverse events, as well as feasibility based on compliance with TTFields therapy Secondary endpoints include progression free survival, overall survival, overall response rate Novocure, Ltd. Safety Feasibility and Effect of TTFields (150 khz) Concomitant With Gemcitabine or Concomitant With Gemcitabine Plus Nab-paclitaxel for Front-line Therapy of Advanced Pancreatic Adenocarcinoma (PANOVA) In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US) [cited 2016 Dec]. Available from: NLM Identifier: NCT Novocure

93 ADVANCED PANCREATIC CANCER PANOVA key inclusion and exclusion criteria INCLUSION CRITERIA Histologically confirmed, unresectable locally advanced or metastastatic pancreatic adenocarcinoma >18 years old Life expectancy >3 months Measurable or assessable disease ECOG score 0-1 Adequate bone marrow, liver, and kidney function No concurrent anti-tumor therapy beyond gemcitabine or nab-paclitaxel At least 4 weeks recovery from surgery No prior chemotherapy or radiation EXCLUSION CRITERIA Known brain metastases or meningeal carcinomatosis Any other malignancy requiring anti-tumor treatment in prior 3 years Significant comorbidity expected to affect prognosis or ability to receive combined therapy Implantable electronic medical devices Known allergies to medical adhesives, hydrogel, gemcitabine or nab-paclitaxel Pregnant Novocure, Ltd. Safety Feasibility and Effect of TTFields (150 khz) Concomitant With Gemcitabine or Concomitant With Gemcitabine Plus Nab-paclitaxel for Front-line Therapy of Advanced Pancreatic Adenocarcinoma (PANOVA) In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US) [cited 2016 Dec]. Available from: NLM Identifier: NCT Novocure

94 ADVANCED PANCREATIC CANCER phase 2 pilot PANOVA trial results FIRST COHORT 1 SECOND COHORT EFFICACY ENDPOINTS TTFIELDS WITH GEMCITABINE TTFIELDS WITH NAB- PACLITAXEL PLUS GEMCITABINE Median PFS 8.3 months 12.7 months Median OS 14.9 months Not yet reached One-year survival rate 55% 72% Partial response rate 30% 40% Stable disease 30% 47% Only 1 case of severe skin irritation related to TTFields 4 patients experienced mild to moderate skin irritation 9 patients reported severe adverse events unrelated to TTFields therapy 1. Rivera, F. Gallego, J., Guillen C. et al. (2016 June) A pilot study of TTFields concomitant gemcitabine for front-line therapy of advanced pancreatic adenocarcinoma. Poster session presented at ASCO GI. Chicago, IL. For historical reference, see Von Hoff, D.D. et al. N Engl J Med, 2013, 369: doi: /nejmoa Median PFS for gemcitabine-alone was 3.7 months; median OS for gemcitabine-alone was 6.7 months. Median PFS for nab-paclitaxel plus gemcitabine was 5.5 months; median OS for nab-paclitaxel plus gemcitabine was 8.5 months. Novocure

95 ADVANCED PANCREATIC CANCER planned phase 3 pivotal pancreatic cancer trial Protocol design in final stages of development First line, locally advanced, nonresectable, pancreatic cancer Patients randomized 1:1 (TTFields plus nab-paclitaxel + gemcitabine vs nab-paclitaxel + gemcitabine alone) Endpoints include Progression-free survival (PFS) Overall survival (OS) Incidence of down-staging to resectability Novocure

96 ADVANCED PANCREATIC CANCER clinical milestones and next steps NEXT STEPS Presentation of second cohort data at medical conference targeted for Q Publication of PANOVA data targeted for 2017 First patient in Last patient in Data Expected 2H 2017 Expected 2 years following first patient enrolled Expected 18 months following last patient enrollment Novocure

97 ovarian cancer Eilon Kirson, MD, PhD Chief Science Officer and Head of R&D Actor portrayal

98 OVARIAN CANCER disease state and clinical presentation Accounts for ~3% of cancers among women, but causes more deaths than any other cancer of the female reproductive system 1 Established risk factors include age and family history, with ~10% of cases occurring in women with BRCA1 and BRCA2 mutations 2 Approximately 85-90% of ovarian cancers arise from the epithelial cell lining covering the outer surface of the ovary Early tumors often cause no symptoms or can cause symptoms similar to other diseases - Only 14.8% of cases are diagnosed at the local stage 3 - Symptoms can include swelling or bloating, pelvic or abdominal pressure, abdominal pain, trouble eating or feeling full quickly, and feeling the need to urinate often or urgently 1. Ovarian Cancer Detailed Guide. Atlanta: American Cancer Society, Lynch HT, Casey MJ, Snyder CL, Bewtra C, Lynch JF, Butts M, Godwin AK. Mol Oncol. 2009;3(2): doi: /j.molonc SEER Cancer Statistics Factsheets: Ovarian Cancer. National Cancer Institute. Bethesda, MD (accessed December 2016) Novocure

99 OVARIAN CANCER epidemiology United States 1 Ovarian cancer incidence of 22,000 cases annually Europe 2 Ovarian cancer incidence of 65,000 cases annually Japan 3 Ovarian cancer incidence of 9,000 cases annually Incidence of ovarian cancer is approximately 11.9 per 100,000 women 1 Increases in frequency with age, with median age at time of diagnosis of 63 years old 1 1. SEER Cancer Statistics Factsheets: Ovarian Cancer. National Cancer Institute. Bethesda, MD (accessed December 2016) 2. Ferlay J, Steliarova-Foucher E, Lortet-Tieulent J, Rosso S, Coebergh JWW, Comber H, Forman D, Bray F. Eur J Cancer. 2013;49(6): doi: /j.ejca WHO (2016) GLOBOCAN 2012: Estimated Cancer Incidence, Mortality, and Prevalence Worldwide in 2012, Lyon, France (accessed December 2016) Novocure

100 RECURRENT OVARIAN CANCER current prognosis Approximately 80% of women with advanced ovarian cancer will have tumor progression or, more commonly, recurrence 1 Platinum-free interval a strong predictor of treatment success 1 - Classified as platinum-resistant if time to recurrence after completion of platinumbased treatment is <6 months - At first relapse, ~25% of patients have platinum-resistant cancer - Almost all patients with recurrent disease ultimately develop resistance Platinum-resistant population has a very poor prognosis - Median progression-free survival (PFS) after recurrence is approximately 3-4 months 2 - Median overall survival (OS) after recurrence is approximately months 2 1. Luvero D, Milani A, Ledermann JA. Therapeutic Advances in Medical Oncology. 2014;6(5): doi: / Pujade-Laurain E., et al. J of Clin Onc. 2014; 32(13): doi: /JCO Novocure

101 RECURRENT OVARIAN CANCER current standard of care Since 2003, weekly paclitaxel therapy has been the standard of care for patients with platinum-resistant recurrent ovarian cancer 1 Standard treatment includes - Platinum-based chemotherapy, used in combination with paclitaxel - At platinum resistance, third-line chemo may include paclitaxel, topotecan, or pegylated liposomal doxorubicin (PLD) recurrent ovarian cancer platinum-based chemotherapy +/- paclitaxel CT q3m until progression third line chemotherapy 1. Luvero D, Milani A, Ledermann JA. Therapeutic Advances in Medical Oncology. 2014;6(5): doi: / Novocure

102 RECURRENT OVARIAN CANCER pelvic array placement DISTRIBUTION OF TTFIELDS AROUND THE OVARIES Voloshin, T., et al. (2016), Alternating electric fields (TTFields) in combination with paclitaxel are therapeutically effective against ovarian cancer cells in vitro and in vivo. Int. J. Cancer, 139: doi: /ijc Novocure

103 RECURRENT OVARIAN CANCER phase 2 pilot INNOVATE trial A prospective, open label, single-arm, non-randomized, multicenter study testing feasibility, safety, toxicity and preliminary efficacy of TTFields at 200 khz together with weekly paclitaxel in patients with recurrent ovarian cancer versus historical controls 30 patients in Europe with recurrent ovarian cancer Last patient enrolled May 2016 with six month follow-up Endpoints: Primary endpoint severity and frequency of adverse events, as well as premature discontinuation of therapy due to skin toxicity Secondary endpoints include progression free survival, overall survival, overall response rate Novocure, Ltd. Safety, Feasibility and Effect of TTFields (200 khz) Concomitant With Weekly Paclitaxel in Recurrent Ovarian Carcinoma (INNOVATE) In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US) [cited 2016 Dec]. Available from: NLM Identifier: NCT Novocure

104 RECURRENT OVARIAN CANCER INNOVATE key inclusion and exclusion criteria INCLUSION CRITERIA Histologically confirmed ovarian cancer Recurrent ovarian cancer with prior therapy >18 years old Life expectancy >3 months Measurable disease according to RECIST criteria ECOG score 0-1 Treatment start >4 weeks from surgery Adequate bone marrow, liver and renal functions No concurrent anti-tumor therapy beyond weekly paclitaxel EXCLUSION CRITERIA Meningeal carcinomatosis or known brain mets Any other malignancy requiring anti-tumor treatment in prior 3 years Chemotherapy or radiotherapy within 4 weeks prior to treatment start Pregnant or breast feeding Significant comorbidities that would prevent combined therapy (uncontrolled cardiovascular disease, arrhythmia, infection, psychiatric) Implantable electronic medical device Grade 2 peripheral neuropathy Pregnant or breast feeding Novocure, Ltd. Safety, Feasibility and Effect of TTFields (200 khz) Concomitant With Weekly Paclitaxel in Recurrent Ovarian Carcinoma (INNOVATE) In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US) [cited 2016 Dec]. Available from: NLM Identifier: NCT Novocure

105 RECURRENT OVARIAN CANCER phase 2 pilot INNOVATE trial results EFFICACY ENDPOINTS TTFIELDS WITH PACLITAXEL PACLITAXEL-ALONE HISTORICAL CONTROL 1 Median PFS 8.9 months 3.9 months * Median OS Not yet reached 13.2 months One-year survival rate 61% 15 patients experienced mild to moderate skin irritation 2 cases of severe skin irritation due to TTFields were reported 13 patients reported severe adverse events unrelated to TTFields therapy 1. Pujade-Laurain E., et al. J of Clin Onc. 2015; 33(32): doi: /jco * Median PFS reflects the weekly paclitaxel subgroup; Median PFS for all chemotherapies was 3.4 months Novocure

106 RECURRENT OVARIAN CANCER clinical milestones and next steps NEXT STEPS Presentation of INNOVATE data at medical conference targeted for Q Publication of INNOVATE data targeted for 2017 Phase 3 pivotal trial design in recurrent ovarian cancer in development Novocure

107 mesothelioma Uri Weinberg, MD, PhD Vice President of Research & Development Actor portrayal

108 MALIGNANT PLEURAL MESOTHELIOMA disease state and clinical presentation Rare thoracic solid cancer strongly linked to asbestos exposure 1 Incidence increasing in countries where asbestos still in use 2 Long latency period of at least years following exposure 2 Tumors arise from the mesothelial lining of the pleural cavity, and belong to three main histological subtypes: epithelioid (50%), sarcomatoid (10%) or mixed (30-40%) 3 Typical presentation is in older patients with advanced clinical stage and other medical comorbidities - Symptoms can include cough, dyspnea, chest wall pain, pleural effusion, hoarseness, fatigue, weight loss, excessive sweating, fever, or swelling of the face and arms - Epithelioid histology responds better to treatments and is associated with better prognosis 2 1 Robinson B.M. Ann Cardiothorac Surg. 2012; 1(4): doi: /j.issn X Ai J. and Stevenson J.P. Oncologist. 2014; 19(9): doi: /theoncologist Mesothelioma Cancer Detailed Guide. Atlanta: American Cancer Society, Novocure

109 MALIGNANT PLEURAL MESOTHELIOMA epidemiology United States 1 Mesothelioma incidence of 3,000 cases annually Western Europe 2 Predicted peak incidence of 9,000 male deaths around the year 2018 Japan 3 Mesothelioma estimated incidence of 1,000 cases annually Incidence of mesothelioma varies markedly within and between countries 3 Highest annual rates of disease, ~30 cases per 1,000,000, reported in Australia and Great Britain With the exception of the U.S., incidence continues to increase worldwide Risk is greater in men, resulting from exposure to workplace asbestos and other inhaled silicates 1 SEER Cancer Statistics Review, Available at Updated June 14, Peto J, Decarli A, La Vecchia C, Levi F, Negri E. Br J Cancer 1999;79: doi: /sj.bjc Robinson B.M. Ann Cardiothorac Surg. 2012; 1(4): doi: /j.issn X Novocure

110 MALIGNANT PLEURAL MESOTHELIOMA current prognosis Malignant pleural mesothelioma generally involves local spread on one side of the chest - Stage I-III may be resectable, depending on spread and tissue subtype 1 - However, unresectable disease generally involves extensive growth, with regional lymph node spread and ipsilateral lung tissue involvement Given advanced age of patients, comorbidities, and limited treatment effectiveness, prognosis for malignant pleural mesothelioma remains poor - Median progression-free survival (PFS) is approximately 6 months 2 - Median overall survival (OS) is approximately 12 months 2 1 Mesothelioma Cancer Detailed Guide. Atlanta: American Cancer Society, Vogelzang NJ, Rusthoven JJ, Symanowski J, et al. J Clin Oncol. 2003;21: doi: /JCO Novocure

111 MALIGNANT PLEURAL MESOTHELIOMA current standard of care Since 2003, pemetrexed plus platinum-based therapy (cisplatin or carboplatin) has been the standard of care for patients with malignant pleural mesothelioma 1-3 Standard treatment includes - Surgical resection, feasible for only a minority of patients - First-line chemotherapy of pemetrexed plus carboplatin or cisplatin - Second-line chemotherapies, including oxaliplatin, gemcitabine or vinorelbine newly diagnosed malignant pleural mesothelioma surgical resection/ biopsy pemetrexed + cisplatin/carboplatin CT q6w until progression second line chemotherapy 1 Vogelzang NJ, Rusthoven JJ, Symanowski J, et al. J Clin Oncol. 2003;21: doi: /JCO Santoro A, O'Brien ME, Stahel RA, et al. J Thorac Oncol. 2008; 3(7): doi: /JTO.0b013e31817c73d6 3 Ai J. and Stevenson J.P. Oncologist. 2014; 19(9): doi: /theoncologist Novocure

112 FIRST LINE TREATMENT OF MALIGNANT PLEURAL MESOTHELIOMA phase 2 pilot STELLAR trial A prospective, open label, single-arm, non-randomized, multicenter study testing safety and preliminary efficacy of TTFields at 150 khz together with pemetrexed and cisplatin or carboplatin in patients with previously untreated malignant pleural mesothelioma versus historical controls 80 patients in Europe with unresectable, previously untreated malignant mesothelioma Actively recruiting patients since February 2015 Twelve month follow-up after final patient enrollment Endpoints: Primary endpoint overall survival (OS) Secondary endpoints progression free survival (PFS), response rate, treatment-emergent toxicity Novocure, Ltd. Safety and Efficacy of TTFields (150 khz) Concomitant With Pemetrexed and Cisplatin or Carboplatin in Malignant Pleural Mesothelioma (STELLAR) In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US) [cited 2016 Dec]. Available from: NLM Identifier: NCT Novocure

113 FIRST LINE TREATMENT OF MALIGNANT PLEURAL MESOTHELIOMA STELLAR key inclusion and exclusion criteria INCLUSION CRITERIA Pathologic evidence of malignant pleural mesothelioma (MPM) > 1 evaluable lesion according to RECIST ECOG performance status of 0-1 >18 years old Not candidate for curative treatment (surgery or radiotherapy) Treatment start >4 weeks from surgery Life expectancy >3 months Required contraceptive use, if applicable EXCLUSION CRITERIA Candidate for curative intent Previous chemotherapy or radiation Prior malignancy requiring anti-tumor treatment Significant comorbidities, esp. liver function impairment, renal impairment, coagulopathy, thrombocytopenia, neutropenia or anemia Factors affecting prognosis or compliance, (uncontrolled cardiovascular disease, arrhythmia, active infection, or psychiatric condition) Untreated brain metastases Implanted electronic medical devices Pregnant Novocure, Ltd. Safety and Efficacy of TTFields (150 khz) Concomitant With Pemetrexed and Cisplatin or Carboplatin in Malignant Pleural Mesothelioma (STELLAR) In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US) [cited 2016 Dec]. Available from: NLM Identifier: NCT Novocure

114 FIRST LINE TREATMENT OF MALIGNANT PLEURAL MESOTHELIOMA STELLAR key baseline characteristics CHARACTERISTICS (N=42) NUMBER (%) 1 Median age, years (range) 67 (43-78) Gender Male Female 34 (81%) 8 (19%) ECOG performance status 0 27 (64%) 1 15 (36%) Caucasian race 42 (100%) Histology Epithelioid Biphasic Sarcomatoid Unspecified 25 (59%) 5 (12%) 2 (5%) 10 (24%) Disease stage Stage III 36 (86%) Stage IV 6 (14%) Past smoker 22 (52%) 1. Cerasoli, G.L. International Association for the Study of Lung Cancer. OA22.01 STELLAR Interim Results of a Phase 2 Trial of TTFields with Chemotherapy for First Line Treatment of Malignant Mesothelioma. Oral Session: Novel Trials and Biomarkers in Malignant Pleural Mesothelioma. Wednesday, Dec. 7, 2016, 2:20 p.m. CET Novocure

115 FIRST LINE TREATMENT OF MALIGNANT PLEURAL MESOTHELIOMA STELLAR incidence of adverse events GRADE 3-4 ALL GRADES GRADE 3-4 ALL GRADES SYSTEM ORGAN CLASS Hematological disorders Anemia Leukopenia Neutropenia (non-febrile) Thrombocytopenia General & administration site conditions Fatigue Pain Hepatobiliary disorders Hepatoxicity Respiratory, thoracic & mediastinal disorders Dyspnea Skin and subcutaneous tissue disorders Rash Skin irritation N (%) 1 11 (26%) 6 (14%) 3 (7%) 6 (14%) 2 (4%) 2 (5%) 1 (2%) 1 (2%) 1 (2%) 1 (2%) 1 (2%) 1 (2%) 2 (5%) 1 (2%) 1 (2%) N (%) 1 22 (52%) 14 (33%) 2 (5%) 7 (17%) 23 (55%) SYSTEM ORGAN CLASS N (%) 1 N (%) 1 Gastrointestinal disorders 0 14 (33%) Infections and infestations 0 6 (14%) Injury, poisoning and procedural 0 1 (2%) Metabolism and nutrition 0 2 (5%) Musculoskeletal and connective tissue 0 2 (5%) Nervous system 0 2 (5%) Psychiatric disorders 0 1 (2%) Renal and urinary disorders 0 1 (2%) Vascular disorders 0 3 (7%) 1. Cerasoli, G.L. International Association for the Study of Lung Cancer. OA22.01 STELLAR Interim Results of a Phase 2 Trial of TTFields with Chemotherapy for First Line Treatment of Malignant Mesothelioma. Oral Session: Novel Trials and Biomarkers in Malignant Pleural Mesothelioma. Wednesday, Dec. 7, 2016, 2:20 p.m. CET Novocure

116 FIRST LINE TREATMENT OF MALIGNANT PLEURAL MESOTHELIOMA phase 2 pilot STELLAR trial results EFFICACY ENDPOINTS TTFIELDS WITH PEMETREXED AND CISPLATIN OR CARBOPLATIN 1 PEMETREXED AND CISPLATIN-ALONE HISTORICAL CONTROL 2 Median PFS 7.3 months 5.7 months Median OS Not yet reached 12.1 months One-year survival rate 79.7% 50.3% Interim data presented at IASLC in December 2016 with a cutoff date of July 12, Cerasoli, G.L. International Association for the Study of Lung Cancer. OA22.01 STELLAR Interim Results of a Phase 2 Trial of TTFields with Chemotherapy for First Line Treatment of Malignant Mesothelioma. Oral Session: Novel Trials and Biomarkers in Malignant Pleural Mesothelioma. Wednesday, Dec. 7, 2016, 2:20 p.m. CET 1 Vogelzang NJ, Rusthoven JJ, Symanowski J, et al. J Clin Oncol. 2003;21: doi: /JCO Novocure

117 FIRST LINE TREATMENT OF MALIGNANT PLEURAL MESOTHELIOMA phase 2 pilot STELLAR trial results PROGRESSION-FREE SURVIVAL (N=42) OVERALL SURVIVAL (N=42) Novocure

118 FIRST LINE TREATMENT OF MALIGNANT PLEURAL MESOTHELIOMA clinical milestones and next steps NEXT STEPS Last patient enrollment anticipated in 2017 Following last patient enrollment, 12 month follow up with data presentation expected in 2018 First patient in Last patient in Data Enrolled in February of 80 patients enrolled Expected in 2017 Expected 12 months following last patient enrollment Novocure

119 what s next for TTFields Eilon Kirson, MD, PhD Chief Science Officer and Head of R&D

120 unresectable hepatocellular carcinoma Incidence of approximately 39,000 new cases in US annually 1 Standard-of-care treatments include - Surgery, ablation (chemical/thermal/microwave/cryoablation) - Arterially directed therapies (embolization) - EBRT - Sorafenib Significant unmet medical need - Most cases diagnosed at advanced stage - Median OS only 6-20 months with five-year survival rate of 17.5% 1 TTFields intensity in the liver and surrounding tissues especially high (>3 V/cm) Hepatocellular carcinoma cells are sensitive to TTFields in-vitro (200 khz) Loco-regional therapies have led to improved outcomes 1. SEER Cancer Statistics Factsheets: Liver and Intrahepatic Bile Duct Cancer. National Cancer Institute. Bethesda, MD, (accessed December 2016) Novocure

121 advanced gastric cancer Incidence of approximately 26,000 new cases in the US annually Standard-of-care treatments include - Surgery - Radiation therapy - 5-FU/Capecitabine + cisplatin/oxaliplatin OR paclitaxel/docetaxel + cisplatin/carboplatin Significant unmet medical need worldwide - In Asian countries, incidence can be up to 10 fold higher than in the US (South Korea) - Majority of patients diagnosed as having advanced disease - Median OS only 5-8 months with five-year survival rates of 20-30% 1 TTFields intensity in the gastric/esophageal regions is very high (>3 V/cm) Gastric cancer cells sensitive to TTFields in-vitro (150 khz) Loco-regional control may lower morbidity and lead to prolonged disease control 1. SEER Cancer Statistics Factsheets: Stomach Cancer. National Cancer Institute. Bethesda, MD (accessed December 2016). Novocure

122 pediatric brain stem glioma Term brain stem glioma is a generic description referring to any tumor of glial origin arising in the brain stem, inclusive of the midbrain, pons, and medulla Two predominant histologies: - Diffuse (infiltrating) astrocytomas centered in the pons, also called diffuse intrinsic pontine glioma (DIPG) - Pilocytic astrocytomas, which occur throughout the brain stem Incidence: - Approximately 300 to 400 pediatric brain stem tumors diagnosed annually in the U.S. 1 - DIPG accounts for approximately 75% to 80% of pediatric brain stem tumors 1 - Most children with DIPG are diagnosed between the ages of 5 and 10 years 1 - Focal pilocytic astrocytomas in the brain stem occur less frequently 1 1. Warren KE. Frontiers in Oncology. 2012;2:205. doi: /fonc Novocure

123 brain stem glioma POTENTIAL APPLICATION FOR BOTH ADULTS AND PEDIATRICS Novocure

124 breast cancer prevention in BRCA1/2 women Novocure

125 prophylactic breast cancer therapy Novocure

126 Novocure engineering Mike Ambrogi Chief Operating Officer

127 second generation Optune system Received FDA approval of PMA supplement on July 13, 2016 Half the size and weight of the first generation Optune system, weighing 2.7 pounds Anecdotal reports suggest improved patient compliance and acceptance Novocure

128 tan transducer arrays Developing less conspicuous transducer array color in response to patient requests In final stages of development, with targeted release in 2017 (pending regulatory approval) Actor portrayal Novocure

129 second generation transducer arrays Developing streamlined transducer array with goal of minimizing impact of wires Designed to improve overall aesthetics of the array through the use of new materials Novocure

130 the connected patient Using secure infrastructure, planning mobile platform intended to improve patient communications Initial goal of collecting device data for compliance reporting and diagnostics Novocure