Novocure (NVCR) overview. updated January 2018

Transcription

1 Novocure (NVCR) overview updated January 2018

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 February 23, 2017, 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 the treatment of adults with 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. 2

3 Optune indications for use and important safety information INDICATIONS Optune is intended as a treatment for adult patients (22 years of age or older) with histologically-confirmed glioblastoma multiforme (GBM). Optune with temozolomide is indicated for the treatment of adult patients with newly diagnosed, supratentorial glioblastoma following maximal debulking surgery, and completion of radiation therapy together with concomitant standard of care chemotherapy. For the treatment of recurrent GBM, Optune is indicated following histologically-or radiologically-confirmed recurrence in the supratentorial region of the brain after receiving chemotherapy. The device is intended to be used as a monotherapy, and is intended as an alternative to standard medical therapy for GBM after surgical and radiation options have been exhausted. CONTRAINDICATIONS Do not use Optune in patients with an active implanted medical device, a skull defect (such as, missing bone with no replacement), or bullet fragments. Use of Optune together with implanted electronic devices has not been tested and may theoretically lead to malfunctioning of the implanted device. Use of Optune together with skull defects or bullet fragments has not been tested and may possibly lead to tissue damage or render Optune ineffective. Do not use Optune in patients that are known to be sensitive to conductive hydrogels. In this case, skin contact with the gel used with Optune may commonly cause increased redness and itching, and rarely may even lead to severe allergic reactions such as shock and respiratory failure. 3

4 Optune indications for use and important safety information WARNINGS AND PRECAUTIONS Optune can only be prescribed by a healthcare provider that has completed the required certification training provided by Novocure (the device manufacturer). Do not prescribe Optune for patients that are pregnant, you think might be pregnant or are trying to get pregnant, as the safety and effectiveness of Optune in these populations have not been established. The most common ( 10%) adverse events involving Optune in combination with temozolomide were thrombocytopenia, nausea, constipation, vomiting, fatigue, medical device site reaction, headache, convulsions, and depression. The most common ( 10%) adverse events seen with Optune monotherapy were medical device site reaction and headache. The following adverse reactions were considered related to Optune when used as monotherapy: medical device site reaction, headache, malaise, muscle twitching, fall and skin ulcer. Use of Optune in patients with an inactive implanted medical device in the brain has not been studied for safety and effectiveness, and use of Optune in these patients could lead to tissue damage or lower the chance of Optune being effective. If the patient has an underlying serious skin condition on the scalp, evaluate whether this may prevent or temporarily interfere with Optune treatment. 4

5 building a global oncology platform ESTABLISHED COMMERCIAL BUSINESS First treatment in 10+ years to increase survival in newly diagnosed glioblastoma (GBM) 7,000+ GBM patients treated to date 68% year-over-year active patient growth Information above as of December 31, 2017.except where indicated BROADLY APPLICABLE MECHANISM OF ACTION Consistently exhibited anti-mitotic effect Recruiting for three phase 3 pivotal trials Completed phase 2 pilot trials in 112 patients across three indications DEMONSTRATED FINANCIAL PERFORMANCE 77% year-over-year revenue growth with more than $53 million Q net revenues GBM business beginning to fund the pipeline $186.6 million in cash and short-term equivalents as of September 30,

6 evolving treatment paradigms for solid tumor cancers USED ALONE OR IN COMBINATION TO TREAT SOLID TUMORS surgery radiation pharmacological treatments tumor treating fields (TTFields) Reduces size of a tumor prior to initiation of additional therapies Invasive to patient Unable to kill microscopic disease Kills cells when delivered at high doses Injures healthy tissues as well as cancer cells Numerous potentially toxic side effects Includes chemotherapy, targeted therapies and immuno-oncology Many treatments target specific patient subgroups Frequently accompanied by numerous side effects Electric fields tuned to specific frequencies Disrupts solid tumor cancer cell division Mild side effect profile with no known cumulative toxicity 6

7 we can leverage physics to fight cancer AN ELECTRIC FIELD EXERTS FORCES ON CHARGED OBJECTS TUMOR TREATING FIELDS USES ELECTRIC FIELDS TO DISRUPT CELL DIVISION MISALIGNED TUBULINS INTERFERE WITH FORMATION OF MITOTIC SPINDLE ALTERNATING ELECTRIC FIELDS DISRUPT CANCER CELL DIVISION MISALIGNED SEPTINS INTERFERE WITH FORMATION OF CONTRACTILE RING TUMOR TREATING FIELDS DESCRIBES ELECTRIC FIELDS THAT ALTERNATE 100,000 TO 300,000 TIMES PER SECOND TO TARGET CANCER CELLS CANCER CELL DEATH 7

8 proven superior long-term survival with Optune plus temozolomide in GBM Probability of survival TMZ alone 31% Intent-to-treat population 1 Median OS from Optune TMZ (n=466) randomization (months) TMZ alone (n=229) Stratified log-rank p= Optune + TMZ 43% p=0.001 HR (95% CI) 0.63 ( ) Median OS from diagnosis (months) Optune + TMZ 13% p= Overall Survival (months) 5% TMZ alone 1. Stupp R, Taillibert S, Kanner A, et al. Effect of Tumor- Treating Fields Plus Maintenance Temozolomide vs Maintenance Temozolomide Alone on Survival in Patients With Glioblastoma: A Randomized Clinical Trial. JAMA. 2017;318(23):

9 Optune plus TMZ consistently sustained superior rates of survival FIVE-YEAR SURVIVAL INTENT-TO-TREAT ANALYSIS 1 100% 90% 80% p=0.029 Optune + TMZ (n=466) TMZ alone (n=229) Survival rate (%) 70% 60% 50% 40% 30% 20% 10% 0% 73% 65% p= % p=0.004 p= % 26% p= % 16% 13% 8% 5% Year from randomization 1. Stupp R, Taillibert S, Kanner A, et al. Effect of Tumor-Treating Fields Plus Maintenance Temozolomide vs Maintenance Temozolomide Alone on Survival in Patients With Glioblastoma: A Randomized Clinical Trial. JAMA. 2017;318(23):

10 patients with compliance >90% had maximal survival benefit FIVE-YEAR SURVIVAL ANALYSIS IN MOST COMPLIANT PATIENTS (>90%) 1 100% 90% 80% 86% Optune + TMZ (n=43) TMZ alone (n=229) Survival rate (%) 70% 60% 50% 40% 30% 20% 10% 0% 65% 55% 31% 29% 29% 29% 16% 8% 5% Year from randomization 1. Ram Z, Kim CY, Nicholas GA and Toms S on behalf of EF-14 investigators. Compliance and treatment duration predict survival in a phase 3 EF-14 trial of Tumor Treating Fields with temozolomide in patients with newly diagnosed glioblastoma. Presented at: 2017 Society for Neuro Oncology; November 16-19, 2017; San Francisco, CA. Oral presentation ACTR

11 ADULT PATIENTS WITH RECURRENT AND NEWLY DIAGNOSED GBM global commercial presence global active markets as of September 30, 2017 ADULT PATIENTS WITH RECURRENT AND NEWLY DIAGNOSED GBM UNITED STATES 47 sales force colleagues UNITED STATES 663 certified centers EMEA 232 certified centers EMEA 10 sales force colleagues JAPAN 2 sales force colleagues JAPAN 150 certified centers certified centers sales force colleagues 11

12 successful commercial launch in GBM active patients at period end ,091 1,266 1,460 1,683 1, CONSECUTIVE QUARTERS OF ACTIVE PATIENT GROWTH SINCE INITIAL PRESENTATION OF EF-14 DATA 7,000+ PATIENTS TREATED TO DATE GLOBALLY 0 Q Q Q Q Q Q Q Q Q Q Q Q U.S. active patients EMEA and Japan active patients 12

13 broad applicability to solid tumors INDICATIONS IN-VITRO EVIDENCE IN-VIVO EVIDENCE FIRST IN HUMAN EVIDENCE Glioblastoma Malignant melanoma Non-small cell lung cancer Pancreatic cancer Breast cancer Mesothelioma Ovarian carcinoma Renal adenocarcinoma Cervical cancer Colorectal carcinoma Ependymoma Gastric adenocarcinoma Gliosarcoma Hepatocellular carcinoma Medulloblastoma Meningioma Small cell lung cancer Urinary transitional cell carcinoma 13

14 ongoing clinical trials PRE-CLINICAL PHASE II PILOT PHASE III PIVOTAL EXPECTED NEXT MILESTONE Brain metastases METIS trial last patient in 2019 with final data collection in 2020 Non-small cell lung cancer LUNAR trial last patient in 2019 with final data collection in 2021 Pancreatic cancer phase three pivotal trial first patient in 1H 2018 Ovarian cancer phase three pivotal trial first patient in 2H 2018 Mesothelioma STELLAR trial final data collection in 1H 2018 Trial ongoing Trial complete 14

15 tumor treating fields has consistently exhibited anti-mitotic effect EFFICACY ENDPOINTS EF-15 PHASE 2 PILOT TRIAL IN NSCLC (N=42) TTFIELDS WITH PEMETREXED 1 PEMETREXED- ALONE HISTORICAL RESULTS 2 TTFIELDS WITH GEMCITABINE 3 FIRST COHORT (N=20) PANOVA PHASE 2 PILOT TRIAL IN PANCREATIC CANCER GEMCITABINE- ALONE HISTORICAL RESULTS 4 TTFIELDS WITH NAB-PACLITAXEL PLUS GEMCITABINE 5 SECOND COHORT (N=20) NAB-PACLITAXEL PLUS GEMCITABINE HISTORICAL RESULTS 4 INNOVATE PHASE 2 PILOT TRIAL IN OVARIANCANCER (N=30) TTFIELDS WITH PACLITAXEL 6 PACLITAXEL- ALONE HISTORICAL RESULTS 7 Median PFS 5 months 2.9 months 8.3 months 3.7 months 12.7 months 5.5 months 8.9 months 3.9 months * Median OS 13.8 months 8.3 months 14.9 months 6.7 months Not yet reached 8.5 months Not yet reached 13.2 months One-year survival rate 57% 29.7% 55% 22% 72% 35% 61% Not provided Partial response rate 30% 7% 40% 23% Stable disease 30% 28% 47% 27% 1. Pless M., Droege C., von Moos R., et al. A phase I/II trial of Tumor Treating Fields (TTFields) therapy in combination with pemetrexed for advanced non-small cell lung cancer. Lung Cancer Sep;81(3): doi: /j.lungcan Hanna N., Shepherd F.A., Fossella F.V., et al. Randomized Phase III Trial of Pemetrexed Versus Docetaxel in Patients With Non Small-Cell Lung Cancer Previously Treated With Chemotherapy. J Clin Oncol May 1;22(9): doi: /JCO Rivera F., et al. PANOVA: A pilot study of TTFields concomitant with gemcitabine for front-line therapy of advanced pancreatic adenocarcinoma. In: 2016 Gastrointestinal Cancers Symposium; 2016 Jan 21-23; San Francisco, CA. Alexandria (VA): ASCO; Abstract Von Hoff D.D., Ervin T., Arena F.P., et al. Increased Survival in Pancreatic Cancer with nab-paclitaxel plus Gemcitabine. N Engl J Med Oct 31;369(18): doi: /NEJMoa Benavides M. et.al. PANOVA: A phase II study of TTFields (150kHz) concomitant with standard chemotherapy for front line therapy of advanced pancreatic adenocarcinoma In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Abstract CT Vergote I., et.al. INNOVATE: a phase II study of TTFields (200 khz) concomitant with weekly paclitaxel for recurrent ovarian carcinoma. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Abstract CT Poveda A.M., Selle F., Hiplert F. et al. Bevacizumab Combined With Weekly Paclitaxel, Pegylated Liposomal Doxorubicin, or Topotecan in Platinum-Resistant Recurrent Ovarian Cancer: Analysis by Chemotherapy Cohort of the Randomized Phase III AURELIA Trial. J of Clin Onc Nov 10;33(32): doi: /JCO * Median PFS reflects the weekly paclitaxel subgroup; Median PFS for all chemotherapies was 3.4 months 15

16 addressing large market segments with significant unmet medical needs BRAIN METASTASES NON-SMALL CELL LUNG CANCER PANCREATIC CANCER OVARIAN CANCER MESOTHELIOMA 225,000 CASES DIAGNOSED ANNUALLY IN TARGET MARKETS 1 630,000 CASES DIAGNOSED ANNUALLY IN TARGET MARKETS ,000 CASES DIAGNOSED ANNUALLY IN TARGET MARKETS ,000 CASES DIAGNOSED ANNUALLY IN TARGET MARKETS ,000 CASES DIAGNOSED ANNUALLY IN TARGET MARKETS 3,6-7 ~25% OF NSCLC PATIENTS DEVELOP BRAIN METS % FIVE YEAR SURVIVAL 3 8.7% FIVE YEAR SURVIVAL % FIVE YEAR SURVIVAL 3 9.1% FIVE YEAR SURVIVAL 3 1. Goetz P, Ebinu JO, Roberge D, Zadeh G. Current Standards in the Management of Cerebral Metastases. Intl J of Surg Onc. 2012;2012: doi: /2012/ Owen S, Souhami L. The management of brain metastases in non-small cell lung cancer. Frontiers in Oncology. 2014;4:248. doi: /fonc Howlader N, Noone AM, et al. SEER Cancer Statistics Review, , National Cancer Institute. Bethesda, MD, based on November 2016 SEER data submission, posted to SEER web site, April Ferlay J, Steliarova-Foucher E, et al. Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 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 January 2018). 6. Peto J, Decarli A, La Vecchia C, Levi F, Negri E. The European mesothelioma epidemic. Br J Cancer 1999;79: doi: /sj.bjc Robinson B.M. Malignant pleural mesothelioma: an epidemiological perspective. Ann Cardiothorac Surg. 2012; 1(4): doi: /j.issn X

17 multiple combination therapy opportunities Potentially complementary agents Radiation Taxanes Platinum-based regimens PARP inhibitors PD-1 inhibitors Tumor Treating Fields Multi-pronged mechanism of action Spindle disruption Septin mislocalization DNA repair prevention Potential solid tumor indications Brain metastases Lung cancer Mesothelioma Pancreatic cancer Ovarian cancer Pre-clinical evidence to date suggests additive or synergistic benefits with certain other cancer therapies 17

18 demonstrated financial performance global net revenues (USD in thousands) $60,000 $50,000 $50,109 77% $53,668 YEAR-OVER-YEAR REVENUE GROWTH $40,000 $34,880 $38,376 $30,000 $30,242 $20,000 $10,000 $0 $21,674 $17,919 $12,383 $13,053 $8,953 $5,208 $6,543 Q Q Q Q Q Q Q Q Q Q Q Q $33,087 $82,888 $177,033 FY 2015 FY 2016 FY 2017 (unaudited) U.S. net revenues EMEA and Japan net revenues $186.6 MILLION IN CASH AND SHORT-TERM EQUIVALENTS AS OF SEPTEMBER 30,

19 q selected financial highlights U.S. DOLLARS IN THOUSANDS Q Q % GROWTH Net revenues $ 50,109 $ 21, % Cost of revenues 15,153 11,118 36% Gross profit 34,956 10, % Research, development and clinical trials 9,273 10,233-9% Sales and marketing 16,387 15,865 3% General and administrative 15,215 12,723 20% Total operating costs and expenses 40,875 38,821 5% Operating income (loss) (5,919) (28,265) 79% Financial expenses, net 2,156 2,189-1% Income (loss) before income taxes (8,075) (30,454) 73% Income tax expense 3,423 3,174 8% Net income (loss) $ (11,498) $ (33,628 ) 66% Cash and cash equivalents $ 82,104 $ 115,822 Short-term investments 104, ,724 19

20 long term value creation beyond 2018 near-term opportunity Drive commercial adoption of Optune within GBM Expand coverage for GBM patients in currently active markets and establish access for GBM patients in new markets Progress mesothelioma towards commercialization Advance the clinical pipeline in multiple solid tumor indications Grow annual revenues while improving SG&A operating leverage long-term opportunity Launch Tumor Treating Fields platform for additional indications in large addressable markets Brain metastases from non-small cell lung cancer Non-small cell lung cancer Pancreatic cancer Ovarian cancer 20

21 commercial appendix

22 direct-to-patient distribution model PHYSICIAN SENDS PHYSICIAN OR NOVOCURE NOVOCURE NOVOCURE BILLS PHYSICIAN SEES PRESCRIPTION NOVOCURE USES DELIVERS OPTUNE PROVIDES 24/7 THIRD-PARTY PATIENT FOR ORDER TO NOVOCURE NOVOTAL SYSTEM TO CREATE ARRAY PLACEMENT MAP AND TRAINS PATIENT/FAMILY TECH SUPPORT AND SUPPLIES TRANSDUCER PAYER AND PATIENT 1 FOR EACH MONTH OF REGULAR COMPLIANCE MONITORING AND ARRAYS THERAPY FOLLOW-UP APPOINTMENTS NOVOCURE Novocure distributes product through hospitals in Japan. 1. Subject to patient assistance programs. 22

23 expanding U.S. commercial market access >210 96% MILLION COVERED LIVES IN THE U.S. AS OF SEPTEMBER 30, 2017 >178 MILLION CONTRACTED LIVES IN THE U.S. AS OF SEPTEMBER 30, 2017 OF AMERICANS WITH PRIVATE HEALTH INSURANCE 1,2 NOW HAVE POSITIVE COVERAGE OF OPTUNE 1. U.S. population insured with employers, nongroup insurance or Medicare Advantage plans 2. Appealing Medicare fee-for-service denials, impacting 20-25% of U.S. active patients 23

24 expanding global commercial market access MARKET STATUS REIMBURSEMENT STATUS GBM MARKET SIZE ESTIMATION Germany Receive reimbursement on case-by-case basis Pathway for national reimbursement via G-BA budgeted clinical trial established Q Clinical trial expected to begin 2H ,600 annual cases diagnosed Japan Commercial launch underway National reimbursement contract signed in Q ,500 annual cases diagnosed Switzerland Single-payer system National reimbursement application submitted Q annual cases diagnosed Austria Commercial launch underway National reimbursement contract signed in Q annual cases diagnosed 24

25 clinical appendix

26 TTFields are frequency-tuned to cell size to maximize effects on mitosis 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 26

27 transducer array placement abdominal array placement torso array placement pelvic array placement 27

28 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 for 1-10 brain metastases from non-small cell lung cancer 270 patients internationally, randomized 1:1 (TTFields vs supportive care) Last patient enrollment expected in 2019, twelve month follow-up after final patient enrollment Primary endpoint time to first intracranial progression Secondary endpoints include neurocognitive failure, overall survival, radiological response rate screening and baseline evaluation randomization 1:1 stereotactic radiosurgery stereotactic radiosurgery ttfields supportive care MRI q2m until progression MRI q2m until progression 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 2018 Jan]. Available from: NLM Identifier: NCT

29 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 testing safety and preliminary efficacy of TTFields at 150 khz together with pemetrexed in pretreated patients with locally advanced and/or metastatic non-small 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, data published in Lung Cancer in 2013 Primary endpoint severity and frequency of adverse events EFFICACY ENDPOINTS TTFIELDS WITH PEMETREXED 1 PEMETREXED-ALONE HISTORICAL RESULTS 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% 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 2018 Jan]. Available from: NLM Identifier: NCT Pless M., Droege C., von Moos R., et al. A phase I/II trial of Tumor Treating Fields (TTFields) therapy in combination with pemetrexed for advanced non-small cell lung cancer. Lung Cancer Sep;81(3): doi: /j.lungcan Hanna N., Shepherd F.A., Fossella F.V., et al. Randomized Phase III Trial of Pemetrexed Versus Docetaxel in Patients With Non Small-Cell Lung Cancer Previously Treated With Chemotherapy. J Clin Oncol May 1;22(9): doi: /JCO

30 SECOND LINE TREATMENT FOR ADVANCED NON-SMALL CELL LUNG CANCER LUNAR phase 3 pivotal trial initiated in 2017 A prospective, randomized controlled, multicenter trial testing efficacy and safety of TTFields at 150 khz in combination with docetaxel or immune checkpoint inhibitors for stage IV NSCLC patients following progression while on or after platinum based treatment 534 patients (TTFields plus docetaxel or immune checkpoint inhibitors vs docetaxel or immune checkpoint inhibitors alone) Last patient enrollment expected in 2019, eighteen month follow-up after final patient enrollment Primary endpoint overall survival (OS) (superiority) Secondary endpoints OS of TTFields + docetaxel vs docetaxel alone (superiority) OS of TTFields + immune checkpoint inhibitors vs immune checkpoint inhibitors alone (superiority) OS of TTFields + docetaxel vs immune checkpoint inhibitors alone (non-inferiority) progression on or after platinumbased therapy screening and baseline evaluation randomization 1:1 ttfields + immune checkpoint inhibitor/docetaxel immune checkpoint inhibitor/docetaxel CT q6w until progression CT q6w until progression three postprogression follow-up visits three postprogression follow-up visits survival follow up survival follow up Novocure, Ltd. Effect of Tumor Treating Fields (TTFields) (150 khz) as Second Line Treatment of Non-small Cell Lung Cancer (NSCLC) in Combination With PD-1 Inhibitors or Docetaxel (LUNAR) In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US) [cited 2018 Jan]. Available from: NLM Identifier: NCT

31 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 nabpaclitaxel 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 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 2018 Jan]. Available from: NLM Identifier: NCT

32 ADVANCED PANCREATIC CANCER phase 2 pilot PANOVA trial FIRST COHORT SECOND COHORT EFFICACY ENDPOINTS TTFIELDS WITH GEMCITABINE 1 GEMCITABINE- ALONE HISTORICAL RESULTS 2 TTFIELDS WITH NAB-PACLITAXEL PLUS GEMCITABINE 3 NAB-PACLITAXEL PLUS GEMCITABINE HISTORICAL RESULTS 2 Median PFS 8.3 months 3.7 months 12.7 months 5.5 months Median OS 14.9 months 6.7 months Not yet reached 8.5 months One-year survival rate 55% 22% 72% 35% Partial response rate 30% 7% 40% 23% Stable disease 30% 28% 47% 27% 1. Rivera F., et al. PANOVA: A pilot study of TTFields concomitant with gemcitabine for front-line therapy of advanced pancreatic adenocarcinoma. In: 2016 Gastrointestinal Cancers Symposium; 2016 Jan 21-23; San Francisco, CA. Alexandria (VA): ASCO; Abstract Von Hoff D.D., Ervin T., Arena F.P., et al. Increased Survival in Pancreatic Cancer with nab-paclitaxel plus Gemcitabine. N Engl J Med Oct 31;369(18): doi: /NEJMoa Benavides M. et.al. PANOVA: A phase II study of TTFields (150kHz) concomitant with standard chemotherapy for front line therapy of advanced pancreatic adenocarcinoma In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Abstract CT

33 ADVANCED PANCREATIC CANCER PANOVA 3 pivotal trial initiated in 2017 A prospective, randomized controlled, multicenter trial testing efficacy and safety of TTFields at 150 khz together with nab-paclitaxel plus gemcitabine as first-line treatment in patients with unresectable, locally advanced pancreatic cancer 556 patients internationally, randomized 1:1 (TTFields plus nab-paclitaxel plus gemcitabine vs nabpaclitaxel plus gemcitabine alone) IDE approved December 2017, first patient enrollment expected in 1H 2018 Primary endpoint overall survival (OS) Secondary endpoints include PFS, objective response rate, rate of resectability, quality of life screening and baseline evaluation randomization 1:1 ttfields + nab-paclitaxel + gemcitabine nab-paclitaxel + gemcitabine CT q8w until progression CT q8w until progression second line chemotherapy second line chemotherapy survival follow up survival follow up Novocure, Ltd. Effect of Tumor Treating Fields (TTFields, 150 khz) as Front-Line Treatment of Locally-advanced Pancreatic Adenocarcinoma Concomitant With Gemcitabine and Nab-paclitaxel (PANOVA-3) In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US) [cited 2018 Jan]. Available from: NLM Identifier: NCT

34 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 Primary endpoint severity and frequency of adverse events EFFICACY ENDPOINTS TTFIELDS WITH PACLITAXEL 1 PACLITAXEL-ALONE HISTORICAL RESULTS 2 Median PFS 8.9 months 3.9 months * Median OS Not yet reached 13.2 months One-year survival rate 61% 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 2018 Jan]. Available from: NLM Identifier: NCT Vergote I., et.al. INNOVATE: a phase II study of TTFields (200 khz) concomitant with weekly paclitaxel for recurrent ovarian carcinoma. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Abstract CT Poveda A.M., Selle F., Hiplert F. et al. Bevacizumab Combined With Weekly Paclitaxel, Pegylated Liposomal Doxorubicin, or Topotecan in Platinum-Resistant Recurrent Ovarian Cancer: Analysis by Chemotherapy Cohort of the Randomized Phase III AURELIA Trial. J of Clin Onc Nov 10;33(32): doi: /JCO * Median PFS reflects the weekly paclitaxel subgroup; Median PFS for all chemotherapies was 3.4 months 34

35 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 Last patient enrolled March 2017 with twelve month follow-up, interim data presented at IASLC 2016 Primary endpoint overall survival (OS) EFFICACY ENDPOINTS TTFIELDS WITH PEMETREXED AND CISPLATIN OR CARBOPLATIN 1 PEMETREXED AND CISPLATIN-ALONE HISTORICAL RESULTS 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% 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 2018 Jan]. Available from: NLM Identifier: NCT 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 2. Vogelzang N.J., Rusthoven J.J., Symanowski J., et al. Phase III Study of Pemetrexed in Combination With Cisplatin Versus Cisplatin Alone in Patients With Malignant Pleural Mesothelioma J Clin Oncol Jul 15;21(14): doi: /JCO