11

Patient images reflect the health status of the patients at the time each photo was taken.

©2019 Novocure. All rights reserved. Optune, nCompass, and Novocure are trademarks of Novocure.

All other product names and trademarks are the property of their respective owners.

Released March 2019 US-OPT-02033

OPTUNE EDUCATIONAL PROGRAM

Tumor Treating Fields for Glioblastoma

2

Disclaimer

Novocure and its employees are not acting as health care professionals and cannot provide medical advice to patients

3

Learning Objectives

Optune Educational Program

TTFields, Tumor Treating Fields; GBM, glioblastoma multiforme.

Optune

Mechanism of

Action

Optune Clinical

Data

Optune Patient

Selection and

Management

Integrating

Optune into the

treatment plan

for GBM

Discussing Optune with

Patients and Caregivers

Goal: Provide an overview of Optune (TTFields) for the management of patients with GBM

444

Overview of Glioblastoma

5

Glioblastoma

Most prevalent and aggressive central nervous system cancer in adults1

– Disease prognosis depends on

Age1-3

Extent of surgical resection2,3

Tumor location1,3

Genetics4,5

Functional status2,3

Historically poor prognosis has been due to limited treatment options6

Image from the Armed Forces Institute of Pathology, public domain, via Wikimedia Commons (http://creativecommons.org/publicdomain/mark/1.0).

1. Ostrom QT, et al. Neuro Oncol. 2018;20(suppl 4):iv1-iv86. 2. Curran WJ, et al. J Natl Cancer Inst.1993;85(9):704-710. 3. Lamborn KR, et al. Neuro Oncol.

2004;6(3):227-235. 4. Hegi ME, et al. N Engl J Med. 2005;352(10):997-1003. 5. Verhaak RGW, et al. Cancer Cell. 2010;17(1):98-110.

6. Wilson TA, et al. Surg Neurol Int. 2014;5:64. doi: 10.4103/2152-7806.132138.

666

Optune Indications for Use and Important Safety Information

7

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.

Please see the Optune Instructions for Use (IFU) for complete information regarding the device’s indications, contraindications, warnings and

precautions at http://www.optune.com/hcp/instructions-for-use.aspx.

8

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.

Please see the Optune Instructions for Use (IFU) for complete information regarding the device’s indications, contraindications, warnings and

precautions at http://www.optune.com/hcp/instructions-for-use.aspx.

999

Understanding Optune

TTFields, Tumor Treating Fields.

10

What is Optune?

Optune is a wearable, FDA-approved device1

– Noninvasive and portable

– Classified as durable medical equipment

Complete system includes2

– Electric field generator

– Connection cable and box

– 4 transducer arrays

– 4 batteries and a charger

– Plug-in power supply

– Carrying bag

1. Optune Instructions for Use. Novocure 2019. 2. Optune Patient Information and Operation Manual. Novocure Inc. Released January 2019

QSD-QR-704-05. 3. Novocure (NVCR) overview. https://3sj0u94bgxp33grbz1fkt62h-wpengine.netdna-ssl.com/wp-

content/uploads/2019/01/201901_NVCR_Corporate_Presentation.pdf. Published January 2019. Accessed January 29, 2019.

To date, ˃10,000 patients with GBM treated with Optune3

11

How Does Optune Work?

Optune has been shown in clinical trials to safely deliver continuous therapy to the area of the brain where the GBM tumor is located1

Optune delivers therapy through the 4 adhesive patches,called transducer arrays, that are applied to the scalpand are connected to the device and battery1,2

When Optune is turned on, it creates low-intensity, wave-like electric fields called TTFields1

TTFields may interfere with GBM cancer cell division. This action slows or stops GBM cancer cells from dividing, and may cause them to die1

GBM, glioblastoma multiforme; TTFields, Tumor Treating Fields.

1. Optune Instructions for Use. Novocure 2019. 2. Optune Patient Information and Operation Manual. Novocure Inc. Released January 2019

QSD-QR-704-05.

Cancer cell begins to divide

TTFields interfere with the dividing

cancer cell

Cancer cell division slows down or stops. Some

cells even die

Brian is an Optune user

12

TTFields Chalk Talk

OPT-1297

141414

Clinical Data inNewly Diagnosed Glioblastoma

15

Stratification by

1. Resection (biopsy vs partial vs gross total)

2. MGMT promoter methylation status

Primary endpoint (ITT population): PFS

Secondary endpoint (PP population): OS

Additional secondary endpoints: PFS6, 1-y/2-y survival, ORR, safety, QoL

EF-14: Phase 3 Pivotal Trial Design1,2

*Treatment with Optune was continued for 24 months or until second progression, whichever occurred first unless prohibited by the patient’s clinical condition.1,2

GBM, glioblastoma multiforme; TMZ, temozolomide; RT, radiation therapy; 2L, second-line; SRS, stereotactic radiosurgery; ITT, intent-to-treat; PFS, progression-free survival;

PP, per protocol; OS, overall survival; PFS6, the percentage of patients alive and progression-free at 6 months; ORR, objective response rate; QoL, quality of life; MGMT, O6-

methylguanine-DNA methyltransferase.

1. Optune Instructions for Use. Novocure 2019. 2. Stupp R, et al. JAMA. 2017;318(23):2306-2316.

R

A

N

D

O

M

I

Z

E

D

2:1

Newly

diagnosed

GBM

N=700

Biopsy/

debulking

Radiation

+

TMZ

Enrollment

window

(4-7 weeks

after

RT + TMZ)

2L chemotherapy,

surgery, SRS, or

combination

TMZ

× 6 cycles

1st progression

Optune 18 h/day

+ TMZ

× 6 cycles

Optune +

2L chemotherapy,

surgery, SRS, or

combination*

2nd progression

or

24 months

16

EF-14: Progression-Free Survival1

ITT, intent to treat; TMZ, temozolomide; PFS, progression-free survival; CI, confidence interval; HR, hazard ratio.

1. Optune Instructions for Use. Novocure 2019. 2. Stupp R, et al; on behalf of EF-14 trial investigators. Slides presented at: AACR Annual Meeting

2017; April 1-5, 2017; Washington, DC.

ITT Population

Median PFS from randomization, mo1 6.7 4.0

95% CI, mo1 6.1-8.1 3.8-4.3

Stratified log-rank1 P <0.001

HR (95% CI)1 0.63 (0.52-0.76)

Median PFS from diagnosis, mo2 11.2 7.8

TMZ Alone(n=229)

Optune + TMZ(n=466)

All patients included in the EF-14 analysis had a minimum follow-up of 24 months.1

0 6 12 18 24 30Progression-Free Survival (months)

TMZ alone

Optune + TMZ1.0

0.9

0.8

0.7

0.6

0.5

0.4

0.3

0.2

0.1

0.0

Fra

cti

on

Su

rviv

al

17

EF-14: Overall Survival1

ITT, intent to treat; TMZ, temozolomide; CI, confidence interval; HR, hazard ratio; OS, overall survival.

1. Optune Instructions for Use. Novocure 2019. 2. Stupp R, et al; on behalf of EF-14 trial investigators. Slides presented at: AACR Annual Meeting

2017; April 1-5, 2017; Washington, DC.

ITT Population

Median OS from randomization, mo1 20.9 16.0

95% CI, mo1 19.1-22.6 13.9-18.2

Stratified log-rank1 P <0.001

HR (95% CI)1 0.63 (0.53-0.76)

TMZ Alone(n=229)

Optune + TMZ(n=466)

Median OS from diagnosis, mo2 24.5 19.8

2-year OS1 43% 31%

1.0

0.9

0.8

0.7

0.6

0.5

0.4

0.3

0.2

0.1

0.0

6 12 18 24 30 36 42 48 54 60

TMZ alone

Optune + TMZ

Overall Survival (months)

Fra

cti

on

Su

rviv

al

0

18

0

10

20

30

40

50

60

70

80

90

100

1 2 3 4 5

Optune + TMZ TMZ Alone

EF-14: Long-Term Survival Rates

Survival with Optune + TMZ vs TMZ alone was significantly higher at the 2-year landmark analysis and remained higher at 5 years

TMZ, temozolomide.

1. Optune Instructions for Use. Novocure 2019.

Year From Randomization

Su

rviv

al R

ate

73%

65%

43%

31%26%

16%20%

8%13%

5%

19

No. of Patients (%) Median Survival (months)

Subgroup Optune + TMZ TMZ Alone Hazard RatioOptune +

TMZTMZ

Alone

Overall 450 (100) 229 (100) 20.9 16.0

% of monthly time on Optune

>90† 43 (10) 24.9 16.0

80–90†

166 (37) 21.5 16.0

70–80†

91 (20) 21.7 16.0

60–70†

46 (10) 19.9 16.0

50–60†

42 (9) 18.0 16.0

30–50 40 (9) 17.9 16.0

30 22 (5) 18.2 16.0

EF-14: Monthly Time on Optune Impacts Overall Survival1,*

*From a post hoc analysis. †P <0.05 for Optune + TMZ compared to TMZ alone.

TMZ, temozolomide.

1. Toms SA, et al. J Neurooncol. 2019;141(2):467-473. 2. Optune Instructions for Use. Novocure 2019.

Optune should be used at least 75% of the time or ≥18 hours per day. Monthly time on Optune

was an independent predictor of improved overall survival with Optune1,2

Optune + TMZ Better TMZ Alone Better

1.21.00.40.20.0 0.80.6

20

EF-14: HCP- and Patient-Reported Quality of Life

*HCP-reported data collected per KPS assessment at baseline and then repeated monthly. Patient functional status via KPS (at multiple time points) measured patient independence in

activities of daily living.1 †Patient-reported data collected per EORTC QLQ-C30 at baseline and Months 3, 6, 9, and 12. This 30-question survey covered 5 daily-functioning domains (physical,

role, social, emotional, and cognitive).2

HCP, healthcare provider; QoL, quality of life; TMZ, temozolomide; KPS, Karnofsky Performance Score; HRQoL, health-related quality of life;

EORTC, European Organisation for Research and Treatment of Cancer; QLQ-C30, Quality of Life Core Questionnaire-C30.

1. Zhu JJ, et al. J Neurooncol. 2017;135(3):545-552. 2. Taphoorn MJB, et al. JAMA Oncol. 2018;4(4):495-504.

Both HCPs and patients reported stable QoL evaluation scores up to 1 year of Optune use

HCP-Reported

Karnofsky Performance Score1,*

Patient-Reported

Global Health Status2,†

Time of Evaluation

QoL over 12 months

120

12 Months

Me

an

KP

S

12 MonthsBaseline BaselineM

ea

n H

RQ

oL

Sc

ore

100

80

60

40

20

0

Optune + TMZ TMZ Alone

21

1 Adverse event 48 44

Blood and lymphatic system disorder* 13 11

Thrombocytopenia 9 5

Gastrointestinal disorders 5 4

Asthenia, fatigue, and gait disturbance 9 6

Infections 7 5

Injury, poisoning, and procedural complications (falls and medical device site reaction)

5 3

Metabolism and nutrition disorders (anorexia, dehydration, and hyperglycemia)

4 5

Musculoskeletal and connective tissue disorders 5 4

Nervous system disorders 24 20

Seizures 6 6

Respiratory, thoracic, and mediastinal disorders (pulmonary embolism, dyspnea, and aspiration pneumonia)

5 5

EF-14 Safety Summary: Incidence of Grade 3/4 Adverse Events in 5% of Patients1,2

*The numerically slightly higher incidence of hematological toxicity, fatigue, and some other adverse effects are due to the longer treatment duration and

observation time in the experimental group. The differences disappear when data are normalized to treatment duration.

TMZ, temozolomide.

1. Optune Instructions for Use. Novocure 2019. 2. Stupp R, et al. JAMA. 2017;318(23):2306-2316. 3. Novocure Data on File OPT-103.

TMZ Alone(n=216)

%

Optune + TMZ (n=456)

%

Safety Population

The most common (10%) adverse events involving Optune in combination with TMZ were thrombocytopenia, nausea, constipation, vomiting, fatigue, medical device site reaction, headache, convulsions, and depression3

22

EF-14: Summary of Outcomes for Optune + TMZ Compared With TMZ Alone

TMZ, temozolomide; PFS; progression-free survival; OS, overall survival; QoL, quality of life; AE, adverse event.

1. Optune Instructions for Use. Novocure 2019. 2. Toms SA, et al. J Neurooncol. 2019;141(2):467-473. 3. Taphoorn MJB, et al. JAMA Oncol.

2018;4(4):495-504.

Median PFS: 6.7 months vs 4.0 months (P <0.001)

Significantly improved PFS1

The most common device-related side effect with Optune was mild-to-moderate skin irritation

No significant increase in serious AEs or systemic side effects was seen when Optune was added to TMZ

Optune + TMZ have been safely combined1

Median OS: 20.9 months vs 16.0 months (P <0.001)

Percentage of monthly time on Optune was an independent predictor of improved OS

Long-term survival benefit that increased with more

time on Optune1,2

Patients in the study were able to maintain their mental, emotional, and physical well-being longer as measured up to 1 year

Maintained QoL over time and across predefined

daily-functioning domains3

232323

Resources and Additional Information

25

Primary Optune Patient Resources

Monthly Usage & Self-Management

Patient Scalp Care GuidelinesFirst Glance at Optune

Diagnosis Treatment Consideration

Understanding Optune

26

Additional Resources For Your Patients

Patient Video

Library DVD

nCompass BrochureBuddy Program Optune Insights nCompass Travel

Support Brochure

Optune.com Optune Facebook Page Optune YouTube Channel Patient MOA Video

27

Additional Resources For Your Practice

Optune Practice Resource Kit Optune ExchangeOptune.com/hcp

28

Optune Resources Are Available at Optune.com