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Item 1. Business

2024-02-22 compared with 2023-02-23 · 213 added, 262 removed, 351 unchanged (58% of the section changed)

We are a global oncology company with a proprietary platform technology called Tumor Treating Fields ("TTFields"), which are electric fields that exert physical forces to kill cancer cells via a variety of mechanisms.

Our key priorities are to drive commercial adoption of Optune and Optune Lua, our commercial TTFields devices, and to advance clinical and product development programs intended to extend overall survival in some of the most aggressive forms of cancer.

Optune is approved by the U.S.

Our key priorities are to drive commercial adoption of Optune Gio ® and Optune Lua ® , our commercial TTFields therapy devices, and to advance clinical and product development programs intended to extend overall survival in some of the most aggressive forms of cancer.

Optune Gio is approved by the U.S.

Food and Drug Administration ("FDA") under the Premarket Approval ("PMA") pathway for the treatment of adult patients with newly diagnosed glioblastoma ("GBM") together with temozolomide, a chemotherapy drug, and for adult patients with GBM following confirmed recurrence after chemotherapy as monotherapy treatment.

We also have a CE certificate to market Optune for the treatment of GBM in the European Union ("EU"), as well as approval or local registration in the United Kingdom ("UK"), Japan, Canada and certain other countries.

Optune Lua is approved by the FDA under the Humanitarian Device Exemption ("HDE") pathway to treatment malignant pleural mesothelioma ("MPM") together with standard chemotherapies.

We also have a CE certificate to market Optune Gio for the treatment of GBM in the European Union ("EU"), as well as approval or local registration in the United Kingdom ("UK"), Japan, Canada and certain other countries.

Optune Lua is approved by the FDA under the Humanitarian Device Exemption ("HDE") pathway to treat malignant pleural mesothelioma and pleural mesothelioma (together, "MPM") together with standard chemotherapies.

We have also received CE certification in the EU and approval or local registration to market Optune Lua in certain other countries.

We market Optune and Optune Lua in multiple countries around the globe with the majority of our revenues coming from the use of Optune in the U.S., Germany and Japan.

We market Optune Gio and Optune Lua in multiple countries around the globe with the majority of our revenues coming from the use of Optune Gio in the U.S., Germany and Japan.

We are actively evaluating opportunities to expand our international footprint.

We believe the physical mechanisms of action behind TTFields therapy may be broadly applicable to solid tumor cancers.

We recently completed patient follow-up and announced top line results from our pivotal LUNAR study evaluating the use of TTFields in the treatment of non-small cell lung cancer ("NSCLC") together with standard therapies.

Patients treated with TTFields and standard therapies demonstrated a statistically significant and clinically meaningful improvement in overall survival over standard therapies alone.

The LUNAR study also showed a statistically significant and clinically meaningful improvement in overall survival when patients were treated with TTFields and immune checkpoint inhibitors, as compared to those treated with immune checkpoint inhibitors alone, and a positive trend in overall survival when patients were treated with TTFields and docetaxel versus docetaxel alone.

We expect to present full results of the LUNAR study at a future medical conference.

In addition to the LUNAR study, we are conducting pivotal studies evaluating the use of TTFields in the treatment of ovarian cancer, brain metastases from NSCLC ("brain metastases") and pancreatic cancer.

We are also conducting a pivotal study testing the potential survival benefit of initiating Optune concurrent with radiation therapy versus following radiation therapy in patients with newly diagnosed GBM.

We have one ongoing pilot study evaluating the use of TTFields in the treatment of stage 3 NSCLC and are designing several additional pilot and pivotal studies in partnership with oncology leaders to further explore the capabilities of TTFields.

We anticipate expanding our clinical pipeline over time to study the safety and efficacy of TTFields for additional solid tumor indications and combinations with other cancer treatment modalities.

We are focusing our research and development activities in areas of greatest anticipated value creation.

This includes non-small cell lung cancer, brain cancers, and pancreatic cancer.

In 2023, we announced results from our phase 3 LUNAR study evaluating the use of TTFields together with standard therapies following platinum-based treatment failure in the treatment of patients with metastatic non-small cell lung cancer ("NSCLC").

Patients treated with TTFields therapy and standard therapies demonstrated a statistically significant and clinically meaningful improvement in overall survival over standard therapies alone.

The LUNAR study also showed a statistically significant and clinically meaningful improvement in overall survival when patients were treated with TTFields therapy and immune checkpoint inhibitors, as compared to those treated with immune checkpoint inhibitors alone, and a positive trend in overall survival when patients were treated with TTFields therapy and docetaxel versus docetaxel alone.

In December 2023, we filed a PMA application with the FDA seeking approval for the use of TTFields therapy together with standard systemic therapies for the treatment of NSCLC following progression on or after platinum-based therapy.

In January 2024, we announced the FDA had accepted this submission for filing.

We are investing in pre-commercial launch activities and anticipate a decision in the second half of 2024.

We have several ongoing or planned trials which will further explore the use of TTFields therapy in the treatment of NSCLC, including the phase 3 METIS and LUNAR-2 trials, as well as the phase 2 KEYNOTE B36 and LUNAR-4 trials.

In addition to our trials in NSCLC, we have multiple ongoing or planned trials in our brain and pancreatic cancer programs, including the phase 3 TRIDENT, KEYNOTE D58 and PANOVA-3 trials, and the phase 2 PANOVA-4 trial.

We anticipate expanding our clinical pipeline over time to study the safety and efficacy of TTFields therapy for additional solid tumor indications and combinations with other cancer treatment modalities.

Our therapy is delivered through a medical device and we continue to advance our Products with the intention to extend survival and maintain quality of life for patients.

We have several product development programs underway that are designed to optimize TTFields delivery to the target tumor and enhance patient ease of use.

We have several product development programs underway that are designed to optimize the delivery of TTFields to the target tumor and enhance patient ease of use.

Our intellectual property portfolio contains hundreds of issued patents and numerous patent applications pending worldwide.

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In 2018, we granted Zai Lab (Shanghai) Co., Ltd.

("Zai") a license to commercialize Optune in China, Hong Kong, Macau and Taiwan ("Greater China") under a License and Collaboration Agreement (the "Zai Agreement").

The Zai Agreement also establishes a development partnership intended to accelerate the development of TTFields in multiple solid tumor cancer indications.

("Zai") a license to commercialize our Products in China, Hong Kong, Macau and Taiwan ("Greater China") under a License and Collaboration Agreement (the "Zai Agreement").

The Zai Agreement also establishes a development partnership intended to accelerate the development of TTFields therapy in multiple solid tumor cancer indications.

For additional information, see Note 12 to the Consolidated Financial Statements.

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Our track record of fundamental scientific research extends across more than two decades and, in all of our preclinical research to date, the application of TTFields has demonstrated a consistent anti-mitotic effect.

Recent preclinical work suggests that the well-established impairment created by the physical effect of TTFields to tumor cells results in a series of changes to cell processes that downregulate DNA damage response, interfere with cell movement and migration, and increase anti-tumor immunity.

Preclinical work suggests that the well-established impairment created by the physical effect of TTFields to tumor cells results in a series of changes to cell processes that downregulate DNA damage response, interfere with cell movement and migration, and increase anti-tumor immunity.

Research is ongoing to further refine and build upon our understanding of TTFields' several mechanisms of action.

Beyond our internal research efforts, we provide independent researchers with preclinical laboratory bench systems, known as inovitro™ and inovivo™, and we grant funding to support basic and translational research on TTFields.

We also support independent research through our Investigator-Sponsored Trials and Preclinical Material Transfer Agreement programs in order to enhance our understanding of the optimal use of TTFields.

TTFields is intended principally for use together with other standard-of-care cancer treatments.

There is a growing body of evidence that supports TTFields' broad applicability with certain other cancer therapies, including radiation therapy, certain chemotherapies and certain immunotherapies.

In our clinical research and commercial experience to date, TTFields has exhibited no systemic toxicity, with mild to moderate skin irritation being the most common side effect.

TTFields therapy is intended principally for use together with other standard-of-care cancer treatments.

There is a growing body of evidence that supports TTFields therapy's broad applicability with certain other cancer therapies, including radiation therapy, certain chemotherapies and certain immunotherapies.

In our clinical research and commercial experience to date, TTFields therapy has exhibited no systemic toxicity, with mild to moderate skin irritation being the most common side effect.

Our technology

TTFields therapy is delivered through a portable medical device.

The complete devices, called Optune and Optune Lua (for GBM and MPM treatment, respectively), include a portable electric field generator, arrays, rechargeable batteries and accessories.

The complete devices, called Optune Gio and Optune Lua (for head and thoracic treatment, respectively), include a portable electric field generator, arrays, rechargeable batteries and accessories.

Sterile, single-use arrays are placed directly on the skin in the region surrounding the tumor and connected to the electric field generator to deliver therapy.

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Our product development initiatives include, but are not limited to:

next generation arrays that

are thinner, lighter and more flexible, next generation array layout mapping software, development of a third generation device that optimizes the use of electric fields to treat tumors, and patient-centered software that enables scaled patient support as we prepare to treat larger patient populations across multiple indications.

continually improving our arrays to be thinner, lighter and more flexible, next generation array layout mapping software, development of a third generation device that optimizes the use of electric fields to treat tumors, and patient-centered software that enables scaled patient support as we prepare to treat larger patient populations across multiple indications.

Our ultimate goal is to optimize the energy delivered to patients' tumors, potentially improving efficacy.

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Our commercial business

Optune is currently marketed for the treatment of GBM, the most common form of primary brain cancer and an aggressive disease for which there are few effective treatment options.

Optune Gio is currently marketed for the treatment of GBM, the most common form of primary brain cancer and an aggressive disease for which there are few effective treatment options.

Optune Lua is currently marketed for the treatment of MPM, a rare cancer that has been strongly linked to asbestos exposure.

We market Optune and Optune Lua in multiple countries around the globe with the majority of our revenues coming from the use of Optune in the U.S., Germany and Japan.

We market Optune Gio and Optune Lua in multiple countries around the globe with the majority of our revenues coming from the use of Optune Gio in the U.S., Germany and Japan.

Treatment of newly diagnosed GBM

In 2015, we received FDA approval to market Optune for the treatment of adult patients with newly diagnosed supratentorial GBM in combination with temozolomide.

The FDA approved Optune for newly diagnosed GBM based on the EF-14 study ("EF-14"), which was a randomized pivotal clinical study which compared, post radiation, Optune plus temozolomide versus temozolomide alone for the treatment of newly diagnosed GBM.

In 2015, we received FDA approval to market Optune Gio (then known as Optune) for the treatment of adult patients with newly diagnosed supratentorial GBM in combination with temozolomide.

The FDA approved Optune Gio for newly diagnosed GBM based on the EF-14 study ("EF-14"), which was a randomized phase 3 clinical study which compared, post radiation, Optune Gio plus temozolomide versus temozolomide alone for the treatment of newly diagnosed GBM.

The primary endpoint of the study was progression-free survival and a powered secondary endpoint was overall survival.

In EF-14, Optune plus temozolomide demonstrated unprecedented five-year survival results.

In EF-14, Optune Gio plus temozolomide demonstrated unprecedented five-year survival results.

Median overall survival was extended by nearly five months (median overall survival of 20.9 months versus 16.0 months for temozolomide alone).

Median progression-free survival was extended by 2.7 months to 6.7 months for Optune plus temozolomide from 4.0 months for temozolomide alone.

Median progression-free survival was extended by 2.7 months to 6.7 months for Optune Gio plus temozolomide from 4.0 months for temozolomide alone.

The final EF-14 data were published in the Journal of the American Medical Association in 2017.

The following graph presents the overall survival data in the intent-to-treat population from our five-year analysis:

The extension of progression-free and overall survival in patients receiving Optune in combination with temozolomide in EF-14 was not specific to any prognostic subgroup or tumor genetic marker and was consistent regardless of MGMT methylation status, extent of resection, age, performance status or gender.

Optune was safely combined with temozolomide with no significant increase in serious adverse events compared with temozolomide alone.

The most common side effect related to Optune was mild to moderate skin irritation.

Quality of life data from a pre-specified analysis of EF-14 demonstrated that patients treated with Optune and temozolomide maintained quality of life over time and across predefined daily-functioning domains.

Both healthcare professionals and patients reported stable quality of life evaluation scores up to one year of Optune use.

Physical, role, social, emotional and cognitive functioning for patients treated with Optune and temozolomide all remained stable and comparable with patients treated with temozolomide alone.

The National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology® (NCCN Guidelines®) for Central Nervous Systems Cancers were updated to include alternating electric fields therapy (Optune) in combination with temozolomide following standard brain radiation therapy with concurrent temozolomide as a Category 1 recommended postoperative adjuvant treatment option for patients with newly diagnosed supratentorial GBM.

A post-hoc analysis of EF-14 showed that more time on Optune predicted increased survival in GBM patients.

An Optune monthly usage threshold as low as 50 percent correlated with significantly improved outcomes in patients treated with Optune together with temozolomide compared to patients treated with temozolomide alone.

The greater the patients’ monthly usage of Optune, the better their outcomes.

Patients who used Optune more than 90 percent of the time (n=43) had the greatest chance of survival:

The extension of progression-free and overall survival in patients receiving Optune Gio in combination with temozolomide in EF-14 was not specific to any prognostic subgroup or tumor genetic marker and was consistent regardless of MGMT methylation status, extent of resection, age, performance status or gender.

Optune Gio was safely combined with temozolomide with no significant increase in serious adverse events compared with temozolomide alone.

The most common side effect related to Optune Gio was mild to moderate skin irritation.

Quality of life data from a pre-specified analysis of EF-14 demonstrated that patients treated with Optune Gio and temozolomide maintained quality of life over time and across predefined daily-functioning domains.

Both healthcare professionals and patients reported stable quality of life evaluation scores up to one year of Optune Gio use.

Physical, role, social, emotional and cognitive functioning for patients treated with Optune Gio and temozolomide all remained stable and comparable with patients treated with temozolomide alone.

The National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology ® (NCCN Guidelines ® ) for Central Nervous Systems Cancers were updated to include alternating electric fields therapy (Optune Gio) in combination with temozolomide following standard brain radiation therapy with concurrent temozolomide as a Category 1 recommended postoperative adjuvant treatment option for patients with newly diagnosed supratentorial GBM.

A post-hoc analysis of EF-14 showed that more time on Optune Gio predicted increased survival in newly diagnosed GBM patients.

An Optune Gio monthly usage threshold as low as 50 percent correlated with significantly improved outcomes in patients treated with Optune Gio together with temozolomide compared to patients treated with temozolomide alone.

The greater the patients’ monthly usage of Optune Gio, the better their outcomes.

Patients who used Optune Gio more than 90 percent of the time (n=43) had the greatest chance of survival:

a median survival of 24.9 months from randomization and a five-year probability of survival of 29.3 percent.

A separate post-hoc analysis of EF-14 showed that higher intensities at the tumor bed were associated with increased survival in GBM patients.

Patients treated with Optune at higher intensities (greater than or equal to 1.06 V/cm;

n=119) had a median overall survival of 24.3 months compared to a median overall survival of 21.6 months for patients treated with Optune at lower intensities (less than 1.06 V/cm;

A separate post-hoc analysis of EF-14 showed that higher intensities at the tumor bed were associated with increased survival in newly diagnosed GBM patients.

Patients treated with Optune Gio at higher intensities (greater than or equal to 1.06 V/cm;

n=119) had a median overall survival of 24.3 months compared to a median overall survival of 21.6 months for patients treated with Optune Gio at lower intensities (less than 1.06 V/cm;

In these analyses, both time on therapy and higher intensity were associated with improved overall survival, independent of each other.

In addition, patients who used Optune at least 18 hours per day at higher intensity levels (n=78) had a median overall survival of 25.1 months (95% CI 20.8-39.4).

In addition, patients who used Optune Gio at least 18 hours per day at higher intensity levels (n=78) had a median overall survival of 25.1 months (95% CI 20.8-39.4).

Treatment of recurrent GBM

We initially received FDA approval for Optune in 2011 for use as a monotherapy treatment for adult patients with GBM, following confirmed recurrence after chemotherapy.

The FDA approved Optune based on the EF-11 study ("EF-11"), a randomized, pivotal clinical study.

We initially received FDA approval for Optune Gio in 2011 for use as a monotherapy treatment for adult patients with GBM, following confirmed recurrence after chemotherapy.

The FDA approved Optune Gio based on the EF-11 study ("EF-11"), a randomized, phase 3 clinical study.

EF-11 was a multi-center, active controlled clinical study of 237 adults with recurrent GBM.

Participants received either Optune as a monotherapy (n=120) or the physician’s choice of chemotherapy (n=117).

Participants received either Optune Gio as a monotherapy (n=120) or the physician’s choice of chemotherapy (n=117).

Chemotherapies chosen for the active control arm included mainly bevacizumab, nitrosoureas and temozolomide.

The primary endpoint was superiority in overall survival.

Overall survival for patients treated with Optune alone and active chemotherapy was 6.6 months and 6.0 months, respectively (p=0.27:

The study demonstrated that Optune provided clinically comparable survival with an overall better quality of life.

More objective radiological responses were observed in the Optune group than in the active control chemotherapy group (14 patients versus 7 patients).

Three patients in the Optune alone arm had a complete response versus no patients in the active chemotherapy arm.

In 2020, the EF-19 post-approval registry, which was a post-approval study required as a condition of FDA approval, confirmed the effectiveness and safety of Optune as monotherapy and further strengthened Optune's clinical profile in recurrent GBM.

The EF-19 study studied Optune as a monotherapy for the treatment of recurrent GBM in 192 patients compared to the 117 recurrent GBM patients who received best standard of care chemotherapy in Novocure’s EF-11 registration study.

Optune as monotherapy reduced the risk of death with fewer adverse events compared to best standard of care chemotherapy.

For patients who received at least one course of therapy, Optune prolonged survival by a median 1.7 months.

Overall survival for patients treated with Optune Gio alone and active chemotherapy was 6.6 months and 6.0 months, respectively (p=0.27:

The study demonstrated that Optune Gio provided clinically comparable survival with an overall better quality of life.

More objective radiological responses were observed in the Optune Gio group than in the active control chemotherapy group (14 patients versus 7 patients).

Three patients in the Optune Gio alone arm had a complete response versus no patients in the active chemotherapy arm.

In 2020, the EF-19 post-approval registry, which was a post-approval study required as a condition of FDA approval, confirmed the effectiveness and safety of Optune Gio as monotherapy and further strengthened Optune Gio's clinical profile in recurrent GBM.

The EF-19 study studied Optune Gio as a monotherapy for the treatment of recurrent GBM in 192 patients compared to the 117 recurrent GBM patients who received best standard of care chemotherapy in Novocure’s EF-11 registration study.

Optune Gio as monotherapy reduced the risk of death with fewer adverse events compared to best standard of care chemotherapy.

For patients who received at least one course of therapy, Optune Gio prolonged survival by a median 1.7 months.

No new safety signals were noted.

Treatment of MPM

In 2019, we received FDA approval via the HDE pathway to market Optune Lua (then known as NovoTTF-100L) for the treatment of adult patients with unresectable, locally advanced or metastatic MPM concurrent with pemetrexed and platinum-based chemotherapy.

and platinum-based chemotherapy.

The FDA approved Optune Lua for MPM based on the STELLAR study ("STELLAR").

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The median overall survival was 21.2 months for patients with epithelioid MPM (n=53) and 12.1 months for patients with non-epithelioid MPM (n=27).

62% of patients enrolled in STELLAR who used Optune Lua plus chemotherapy were still alive at one year, with 42% of patients alive at two

62% of patients enrolled in STELLAR who used Optune Lua plus chemotherapy were still alive at one year, with 42% of patients alive at two years.

The disease control rate in patients with at least one follow-up CT scan performed (n=72) was 97%.

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Our commercial markets

We have built a commercial organization and market Optune and Optune Lua for the treatment of GBM and MPM in multiple countries in North America, Europe and Asia.

We have built a commercial organization and market Optune Gio for the treatment of GBM in multiple countries in North America, Europe and Asia.

In 2024, we estimate that approximately:

• 15,000 people will be diagnosed with GBM or tumors that typically progress to GBM in the U.S.

Of this population, we estimate that approximately 8,200 patients who are candidates for treatment with Optune based upon the rate of disease progression and medical eligibility will actively seek treatment.

Of this population, we estimate that approximately 8,200 patients who are candidates for treatment with Optune Gio based upon the rate of disease progression and medical eligibility will actively seek treatment.

• 4,600 people will be diagnosed with GBM or tumors that typically progress to GBM in Germany.

Of this population, we estimate that approximately 2,500 patients who are candidates for treatment with Optune based upon the rate of disease progression and medical eligibility will actively seek treatment.

Of this population, we estimate that approximately 2,500 patients who are candidates for treatment with Optune Gio based upon the rate of disease progression and medical eligibility will actively seek treatment.

• 2,200 people will be diagnosed with GBM or tumors that typically progress to GBM in Japan.

Of this population, we estimate that approximately 1,200 patients who are candidates for treatment with Optune based upon the rate of disease progression and medical eligibility will actively seek treatment.

In 2023, we estimate that approximately 3,000 people are diagnosed with malignant plural mesothelioma in the U.S.

Of this population, we estimate that approximately 1,600 patients are candidates for treatment with Optune Lua based upon the rate of disease progression and medical eligibility.

We believe there are many more patients who could benefit from treatment with TTFields than are currently on therapy.

We continue to focus on increasing penetration for GBM and MPM.

Of this population, we estimate that approximately 1,200 patients who are candidates for treatment with Optune Gio based upon the rate of disease progression and medical eligibility will actively seek treatment.

We believe there are many more patients who could benefit from treatment with TTFields therapy than are currently on therapy.

We continue to focus on increasing penetration for GBM.

In the future, we anticipate strategically expanding into additional geographic markets and additional indications, pending regulatory approval.

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Healthcare providers must undergo a certification training in order to prescribe our Products.

With respect to the treatment of GBM, our sales and marketing efforts are principally focused on driving adoption with both neuro-oncologists and radiation oncologists.

Our sales and marketing efforts are principally focused on driving adoption of Optune Gio for the treatment of GBM among both neuro-oncologists and radiation oncologists.

In certain countries, neurosurgeons and medical oncologists also drive adoption.

We continue to focus on driving key academic center engagements.

With respect to the treatment of MPM, our sales and marketing efforts are principally focused on certification training, supporting the required Institutional Review Board approval process in certain geographies, and driving awareness among radiation oncologists and thoracic oncologists.

We believe the benefit of our education efforts will extend beyond MPM to future indications treated by the same prescribers.

We currently operate as a direct-to-patient distributor of our Products, except for Japan.

In Japan, we distribute Optune through hospitals and provide patient support services under a contractual arrangement with the hospital.

In Japan, we distribute Optune Gio through hospitals and provide patient support services under a contractual arrangement with the hospital.

Once an eligible patient is identified by a certified prescriber, the healthcare provider’s office submits a prescription order form and supporting documentation to us.

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We provide our Products directly to patients following receipt of a prescription order and a signed patient service agreement (except in Japan as described above).

The number of active patients on therapy and the amount of net

revenue recognized per active patient are our principal revenue drivers.

The number of active patients on therapy and the amount of net revenue recognized per active patient are our principal revenue drivers.

An active patient is a patient who is receiving treatment under a commercial prescription order as of the measurement date, including patients who may be on a temporary break from treatment and who plan to resume treatment in less than 60 days.

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We typically negotiate discounts from our list price with healthcare payers, and in certain cases we accept government-mandated discounts from our list prices in order to secure reimbursement for our Products.

We continue to work with payers to expand access to Optune for patients with GBM.

As of December 31, 2022, we have received national reimbursement for Optune in Austria, Germany, Israel, Japan, Sweden and Switzerland.

In February 2023, we finalized contract terms to establish national reimbursement in France for the treatment of adult patients with newly diagnosed GBM, pending official signatures and final publication in the Journal Officiel.

In the U.S., a substantial majority of Americans with private health insurance had coverage of Optune for newly diagnosed GBM and/or recurrent GBM as of December 31, 2022.

As of September 2019, Americans who are beneficiaries of the Medicare fee-for-service program also have coverage of Optune for newly diagnosed GBM.

We believe we have completed our administrative ramp-up towards processing Medicare claims and are efficiently pursuing appeals.

We are actively appealing Medicare fee-for-service coverage denials up to and including the Administrative Law Judge ("ALJ") process with Centers for Medicare and Medicaid Services ("CMS").

We are engaged in an initial dialogue with certain payers regarding access to Optune Lua for patients with MPM.

We anticipate that MPM claims during initial commercialization will go through an appeal process with payers, similar to our early experience with GBM.

We anticipate that our ability to gain meaningful coverage for Optune Lua will be dependent on inclusion in the relevant clinical guidelines for MPM.

We continue to work with payers to expand access to Optune Gio for patients with GBM.

As of December 31, 2023, we have received national reimbursement for Optune Gio in Austria, France, Germany, Israel, Japan, Sweden and Switzerland.

In the U.S., a substantial majority of Americans with private health insurance had coverage of Optune Gio for newly diagnosed GBM and/or recurrent GBM as of December 31, 2023.

As of September 2019, Americans who are beneficiaries of the Medicare fee-for-service program also have coverage of Optune Gio for newly diagnosed GBM.

We are actively appealing Medicare fee-for-service coverage denials up to and including the Administrative Law Judge ("ALJ") process with Centers for Medicare and Medicaid Services ("CMS") and believe the outstanding denied and appealed claims that were most accessible were largely exhausted in 2022.

Our development pipeline

Based on the results of our preclinical research, we have developed a pipeline strategy to advance TTFields through pilot and pivotal studies across multiple solid tumor types.

Based on the results of our preclinical research, we have developed a pipeline strategy to advance TTFields therapy through phase 2 and phase 3 studies across multiple solid tumor types.

We anticipate expanding our clinical pipeline over time to include additional solid tumor cancer indications.

Current Development Pipeline

The solid tumor cancers subject to our pilot and pivotal studies, as well as the studies themselves, are described in greater detail below.

In addition to our studies in tumors of the head, thorax and abdomen, we continue to conduct

research in our approved indications to further advance the scientific evidence supporting the use of TTFields in GBM and to gather additional information about our therapy's optimal use.

The solid tumor cancers subject to our phase 2 and phase 3 studies, as well as the studies themselves, are described in greater detail below.

In addition to our studies in tumors of the head, thorax and abdomen, we continue

to conduct research in our approved indications to further advance the scientific evidence supporting the use of TTFields therapy in GBM and to gather additional information about our therapy's optimal use.

GBM is the most common and aggressive form of primary brain cancer.

It is estimated that approximate 15,000 patients are diagnosed with GBM or tumors that typically progress to GBM each year in the U.S.

Following diagnosis, standard of care treatment includes surgical resection, followed by radiotherapy with concomitant chemotherapy, followed TTFields together with maintenance chemotherapy.

2-THE-TOP pilot study

David Tran, Chief of the Division of Neuro-Oncology at the University of Southern California Keck School of Medicine and co-Director of the USC Keck Brain Tumor Center, presented updated data from the pilot 2-THE-TOP study testing the safety and efficacy of TTFields together with pembrolizumab and temozolomide for the treatment of adult patients with newly diagnosed GBM.

As of May 24, 2021, 25 patients with a median age of 61 years were enrolled in the study, with a median follow-up of 14.7 months.

32% had biopsy only and 16% had partial resection.

72% had unmethylated MGMT and 12% had an IDH mutation.

48% were progression-free, and 60% were still alive.

Of the 19 patients with follow-up greater than 9 months, the median progression-free survival was at least 11.2 months compared to 6.7 months from the historical control study, EF-14, in which patients received TTFields and adjuvant temozolomide.

24% patients with measurable tumors achieved partial or complete response.

193,760 peripheral blood mononuclear cells were sequenced in 12 patients before pembrolizumab and detected robust post-TTFields T cell activation in 11 of 12 patients via the T1IFN trajectory with a strong correlation with the TCRαβ clonal expansion Simpson index (Spearman coefficient r=-0.8, P=0.014).

The study defined a T cell-based gene signature of TTFields effects on TCRαβ clonal expansion.

The most common adverse events were thrombosis (16%), seizure (12%), and metabolic disturbances (8%).

In March 2022, Dr.

Tran presented updated results from the 2-THE-TOP study.

These preliminary results, which are based on a median follow-up time of 16.8 months, compared outcomes for 26 patients in the ongoing 2-THE-TOP study versus a historical, matched-control group of 26 patients from the EF-14 study.

For patients in the 2-THE-TOP study, median progression-free survival was 12.1 months, compared with 7.9 months for the matched-control patients in EF-14 (hazard ratio=0.46, p=0.033).

Patients in 2-THE-TOP had a median overall survival of 25.2 months, compared with 15.9 months for the matched-control patients in EF-14 (hazard ratio=0.38, p=0.020).

Of the 15 patients in 2-THE-TOP with measurable target lesions, six (40%) achieved partial to complete response and eight (53%) had stable disease.

The 2-THE-TOP study concluded that the triple combination of TTFields, temozolomide, and pembrolizumab is well tolerated and shows early evidence of efficacy in newly diagnosed GBM patients.

Patients will continue follow-up with survival and molecular data to be updated.

In 2022, we entered into a clinical collaboration agreement with MSD, a tradename of Merck & Co., Inc., ("MSD") to conduct the double-blind, placebo-controlled pivotal KEYNOTE D58 study of TTFields concomitant with pembrolizumab and maintenance temozolomide for the treatment of newly diagnosed GBM.

EF-33 pilot study

In October 2022, we announced preliminary data from our EF-33 pilot study, an open-label, single-arm study evaluating whether TTFields delivered at 200 kHz to the brain using high-intensity arrays in the treatment of recurrent GBM significantly improves the clinical outcomes of patients compared to using standard transducer arrays in 25 patients.

Among patients who used Optune as directed with for at least one month, median progression-free survival was 4.5 months compared to 2.2 months in the historical control, our pivotal EF-11 study.

Further, notwithstanding the increased dosage, EF-33 patients reported no TTFields-related toxicity.

TRIDENT pivotal study

In 2020, we enrolled the first patient in our TRIDENT study ("TRIDENT"), a pivotal study testing the potential survival benefit of initiating Optune concurrent with radiation therapy in patients with newly diagnosed GBM.

It is estimated that approximately 15,000 patients are diagnosed with GBM or tumors that typically progress to GBM each year in the U.S.

Following diagnosis, standard of care treatment includes surgical resection, followed by radiotherapy with concomitant chemotherapy, followed by TTFields therapy together with maintenance chemotherapy.

TRIDENT phase 3 trial

In January 2024, the final patient was enrolled in our TRIDENT trial ("TRIDENT"), a phase 3 study testing the potential survival benefit of initiating Optune Gio concurrent with radiation therapy and maintenance temozolomide in patients with newly diagnosed GBM.

The primary endpoint is overall survival.

Secondary endpoints include progression-free survival, survival rates at one and two years, overall radiological response, severity and frequency of adverse effects, pathological changes in

resected GBM tumors post treatment, quality of life, and correlation of overall survival to TTFields dose.

TRIDENT is designed to accrue 950 patients with a 24-month minimum follow-up period after the last patient enrolled.

Secondary endpoints include, but are not limited to, progression-free survival, survival rates at one and two years, overall radiological response, severity and frequency of adverse effects, pathological changes in resected GBM tumors post treatment, quality of life, and correlation of overall survival to TTFields dose.

TRIDENT was designed to accrue 950 patients with a 24-month minimum follow-up period after the last patient is enrolled.

Final data from the TRIDENT trial is anticipated in 2026.

2-THE-TOP phase 2 trial

In November 2023, Dr.

David Tran, Chief of the Division of Neuro-Oncology at the University of Southern California Keck School of Medicine and co-Director of the USC Keck Brain Tumor Center, presented updated data from the phase 2 2-THE-TOP study testing the safety and efficacy of TTFields therapy together with pembrolizumab and maintenance temozolomide for the treatment of adult patients with newly diagnosed GBM.

The primary endpoint was progression-free survival, as compared to a case-matched cohort of 56 patients from the EF-14 study.

Secondary endpoints included overall survival and toxicity.

A total of 26 patients were recruited to the study with a median age of 60.5 years.

Median progression-free survival was 12.0 months versus 5.8 months (hazard ratio=0.377, P=0.0026).

Median overall survival was 24.8 months versus 14.6 months in controls (hazard ratio=0.522, P=0.047).

Residual tumor size positively correlated with the objective response and survival.

Six of 15 (40%) patients with measurable disease achieved partial to complete response.

Molecular analyses confirmed robust T cell activation by TTFields via T1IFN-dependent plasmacytoid dendritic cells (Spearman coefficient=-0.8, P=0.014).

Successful clonal replacement of the most expanded T cell clones after pembrolizumab strongly predicted objective responses to the triple combination in a Cox hazard ratio fit model (concordance rate = 0.876, P = 0.031).

The most common adverse events were thromboses (15%), seizures (12%), and metabolic disturbances (8%).

Additional molecular analyses will be conducted and updated in the future.

The 2-THE-TOP study concluded that the triple combination of TTFields therapy, temozolomide, and pembrolizumab is well tolerated and demonstrated promising efficacy in newly diagnosed GBM patients.

In 2022, we entered into a clinical collaboration agreement with MSD, a tradename of Merck & Co., Inc., ("MSD") to conduct a double-blind, placebo-controlled phase 3 trial further exploring the efficacy of this therapy regimen.

The phase 3 KEYNOTE D58 trial will utilize the regimen of TTFields therapy concomitant with pembrolizumab and maintenance temozolomide for the treatment of newly diagnosed GBM.

Novocure and MSD are currently finalizing the design of the KEYNOTE D58 protocol, with trial launch anticipated in 2024.

Non-small cell lung cancer

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Surgery, which may be curative in a subset of patients, is usually used in early stages of the disease.

A combination of radiation, platinum-based chemotherapies, and immune checkpoint inhibitors, or targeted therapies, are the first line standard of care treatment for locally advanced or metastatic NSCLC.

A combination of radiation, platinum-based chemotherapies, and immune checkpoint inhibitors, or targeted therapies, are the first line standard of care treatment for locally advanced or metastatic

Today, the standard of care for second line treatment is evolving and often includes immune checkpoint inhibitors, docetaxel, platinum-based chemotherapy or pemetrexed.

EF-15 pilot study

In 2013, we published the results of our pilot study, the EF-15 study ("EF-15"), evaluating the safety and efficacy of TTFields in the treatment of advanced NSCLC.

EF-15 focused on the effects of treatment with TTFields in combination with standard of care pemetrexed chemotherapy.

Results of the pemetrexed pivotal FDA registration study were used as a historical control in this study.

A total of 42 patients were recruited to the study with a minimum follow-up of six months.

Efficacy results based on 41 evaluable patients showed both progression-free survival and overall survival for patients receiving TTFields in combination with pemetrexed increased compared to historical control data for pemetrexed alone.

Median time to in-field progression in the TTFields-treated group was 6.5 months (compared to 2.9 months in the historical control) and median overall survival was 13.8 months (compared to 8.3 months in the historical control).

Adverse events reported in this combination study were comparable to those reported with pemetrexed alone, suggesting minimal added toxicities due to TTFields.

LUNAR pivotal study

In 2017, we enrolled the first patient in our LUNAR study ("LUNAR"), a pivotal study testing the effectiveness of TTFields in combination with immune checkpoint inhibitors or docetaxel versus immune checkpoint inhibitors or docetaxel alone for patients with stage 4 NSCLC who progressed during or after platinum-based therapy.

It is estimated that approximately 46,000 patients receive second-line treatment for stage 4 NSCLC each year in the U.S.

The primary endpoint is superior overall survival of patients treated with TTFields plus immune checkpoint inhibitors or docetaxel versus immune checkpoint inhibitors or docetaxel alone.

We believe our protocol incorporates the evolving standard of care for second-line treatment of NSCLC.

TTFields is intended principally for use in combination with other standard-of-care treatments, and LUNAR was designed to generate data that contemplates multiple outcomes, all of which we believe will be clinically meaningful.

In 2021, we announced that an independent Data Monitoring Committee ("DMC") informed us that the pre-specified interim analysis for the LUNAR study was accelerated given the length of accrual and the number of events observed, to date.

The interim analysis included data from 210 patients accrued through February 2021.

After review of the interim analysis, the DMC concluded that the LUNAR study should continue with no evidence of increased systemic toxicity.

The DMC went on to comment that the continued accrual to 534 patients as proposed in the original protocol, given the current rate of accrual and the interim data presented, is likely unnecessary and possibly unethical for patients randomized to control.

For this reason, the DMC recommended an adjustment of accrual to approximately 276 patients with a 12-month follow-up following the enrollment of the last patient.

The DMC believed this amended protocol would provide adequate data regarding toxicity and efficacy, providing sufficient overall power, as well as potentially providing important information regarding efficacy within treatment subgroups.

In May 2021, the FDA approved our investigational device exemption supplement incorporating the recommended protocol changes and we enrolled our last LUNAR patient in November 2021.

In January 2023, we announced the LUNAR study met its primary endpoint, demonstrating a statistically significant and clinically meaningful improvement in overall survival for patients treated with TTFields and standard therapies compared to those treated with standard therapies alone.

overall survival when patients were treated with TTFields and docetaxel versus docetaxel alone.

Patient enrollment was well balanced between the immune checkpoint inhibitor and docetaxel cohorts of the experimental and control arms, and the control arms performed in line with prior studies.

TTFields therapy was well tolerated by patients enrolled in the experimental arm of the study.

The publication of full data from the LUNAR study is anticipated in 2023.

KEYNOTE B36 pilot study

In June 2022, we enrolled the first patient in our KEYNOTE B36 study, a pilot study evaluating the safety and efficacy of TTFields together with the anti-PD-1 therapy pembrolizumab for the treatment of first-line NSCLC, expanding our research in the lung cancer space.

This study is the result of a clinical study collaboration with MSD.

LUNAR phase 3 trial

In 2021, we enrolled the last patient in our LUNAR trial ("LUNAR"), a phase 3 study testing the effectiveness of TTFields therapy in combination with immune checkpoint inhibitors or docetaxel versus immune checkpoint inhibitors or docetaxel alone for patients with stage 4 NSCLC who progressed during or after platinum-based therapy.

It is estimated that approximately 30,000 patients actively seek treatment for stage 4 NSCLC after progressing during or after platinum-based therapy each year in the U.S.

The primary endpoint was superior overall survival of patients treated with TTFields therapy plus immune checkpoint inhibitors or docetaxel versus immune checkpoint inhibitors or docetaxel alone.

In June 2023, we presented positive results from the LUNAR study which met its primary endpoint with a statistically significant and clinically meaningful 3-month improvement in median overall survival with TTFields therapy added to standard therapies (hazard ratio=0.74, P=0.035).

Patients randomized to receive TTFields therapy together with standard therapies (n=137) demonstrated median overall survival of 13.2 months compared to 9.9 months in patients treated with standard therapies alone (n=139).

Patients randomized to receive TTFields therapy and physician’s choice immune checkpoint inhibitor (n=66) demonstrated a median overall survival of 18.5 months, a profound extension compared to the median overall survival of 10.8 months demonstrated by patients that received immune checkpoint inhibitor alone (n=68;

hazard ratio=0.63;

Patients randomized to receive TTFields therapy and docetaxel (n=71) had a positive survival trend with a median overall survival of 11.1 months vs 8.7 months (n=71;

hazard ratio=0.81, P=0.28).

TTFields therapy was well-tolerated with no added systemic toxicities and few grade 3 (no grade 4 or 5) device-related adverse events.

In August 2023, the data from the LUNAR study were published in The Lancet Oncology , and additional data detailing the LUNAR study have since been presented at multiple medical congresses.

In December 2023, we submitted a PMA application to the FDA based upon the LUNAR results, seeking approval for the use of TTFields therapy together with standard systemic therapies for the treatment of NSCLC following progression on or after platinum-based therapy, which has since been accepted for filing by the FDA.

We have also filed applications for use to the necessary regulatory bodies in Europe and Japan.

LUNAR-2 phase 3 trial

In July 2023, the FDA accepted the investigation device exemption for the LUNAR-2 clinical trial ("LUNAR-2"), a randomized, phase 3 study evaluating the efficacy of TTFields therapy concomitant with pembrolizumab and platinum-based chemotherapy for the treatment of patients with metastatic NSCLC.

The two primary endpoints of LUNAR-2 are overall survival and progression-free survival.

Secondary endpoints include, but are not limited to, progression-free survival and overall survival according to patient histology, progression-free survival and overall survival according to patient tumor proportion score, one-, two-, and three-year survival rates, objective response rate, duration of response, disease control rate and severity and frequency of adverse effects.

LUNAR-2 is designed to accrue 734 patients with a 21-month follow-up following the enrollment of the last patient.

KEYNOTE B36 phase 2 trial

In 2022, the first patient was enrolled in our KEYNOTE B36 trial ("KEYNOTE B36"), a phase 2 study evaluating the safety and efficacy of TTFields therapy together with the anti-PD-1 therapy pembrolizumab for the treatment of first-line metastatic NSCLC.

The primary endpoint is progression-free survival.

Secondary endpoints include, but are not limited to, overall survival, objective response rate, duration of response, disease control rate and severity and frequency of adverse effects.

Enrollment in KEYNOTE B36 is ongoing.

The trial is designed to accrue 100 patients with a 12-month minimum follow-up period after the last patient is enrolled.

KEYNOTE B36 is the result of a clinical study collaboration with MSD.

Brain metastases

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In metastasis, cancer cells break away from where they first formed (the primary cancer), travel through the blood or lymph system, and form new tumors (the metastatic tumors) in other parts of the body.

The exact incidence of brain metastases is unknown because no national cancer registry documents brain metastases, and estimates from scientific literature vary greatly based on the study methodology applied.

The exact incidence of brain metastases is unknown because no national cancer registry documents brain metastases, and estimates from

scientific literature vary greatly based on the study methodology applied.

It is estimated that between 100,000 and 240,000 new cases are diagnosed in the U.S.

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This practice results in a window of unmet need after localized surgery and SRS are used and before whole brain radiation therapy is administered to delay or prevent the additional spread of brain metastases.

METIS pivotal study

In 2016, we enrolled the first patient in our METIS study ("METIS"), a pivotal study testing the effectiveness of SRS plus TTFields compared to SRS alone in patients with brain metastases resulting from NSCLC.

METIS phase 3 trial

In March 2023, we enrolled the final patient in our METIS study ("METIS"), a phase 3 study testing the effectiveness of SRS plus TTFields therapy compared to SRS alone in patients with brain metastases resulting from NSCLC.

It is estimated that between 20 to 40% of patients with NSCLC develop brain metastases, with an estimated 38,000 to 77,000 patients diagnosed each year in the U.S.

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The primary endpoint of METIS is time to first intracranial progression.

Secondary endpoints include, among others, time to neurocognitive failure, overall survival and radiological response rate following study treatments.

The study is designed to accrue 270 patients with a minimum 12-month follow-up period following the final patient enrollment.

We anticipate completing enrollment of the METIS study in the first quarter of 2023.

Ovarian cancer

In the U.S., ovarian cancer ranks fifth in cancer deaths among women, with approximately 24,000 women diagnosed each year.

Ovarian cancer incidence increases with age, and the median age at time of diagnosis is 63 years old.

Physicians use different combinations of surgery and pharmacological therapies to treat ovarian cancer, depending on the stage of the disease.

Surgery is usually used in early stages of the disease and is usually combined with chemotherapy, including paclitaxel and platinum-based chemotherapy.

Unfortunately, the majority of patients are diagnosed at an advanced stage when the cancer has spread outside of the ovaries to include regional tissue involvement and/or metastases.

Platinum-based chemotherapy remains part of the standard of care in advanced ovarian cancer, but most patients with advanced ovarian cancer will have tumor progression or, more commonly, recurrence.

Almost all patients with recurrent disease ultimately develop platinum resistance, and the prognosis for this population remains poor.

INNOVATE pilot study

In 2018, we published the results of our pilot study in recurrent ovarian cancer, the INNOVATE study ("INNOVATE"), examining TTFields in combination with standard of care chemotherapy.

INNOVATE was a multi-center, non-randomized, open-label study designed to test the feasibility, safety and preliminary efficacy of TTFields in combination with weekly paclitaxel.

The paclitaxel control arm from the bevacizumab pivotal FDA registration study was used as a historical control in this study.

A total of 31 patients were recruited to the study with a minimum follow-up of six months.

Safety results suggested that TTFields in combination with weekly paclitaxel may be tolerable and safe as second-line treatment for patients with recurrent ovarian cancer.

Median progression-free survival in the TTFields-treated group was 8.9 months (compared to 3.9 months in the paclitaxel-alone historical control), and median overall survival was not yet reached.

The one-year survival rate was 61%.

Efficacy results based on the 31 evaluable patients suggested more than doubling of the progression-free survival and an improvement in overall survival among patients who received TTFields therapy with paclitaxel compared to paclitaxel alone.

INNOVATE-3 pivotal study

In 2019, we enrolled the first patient in our INNOVATE-3 study ("INNOVATE-3"), a pivotal study testing the effectiveness of TTFields with paclitaxel in patients with platinum-resistant ovarian cancer.

It is estimated that approximately 16,000 patients are diagnosed with platinum-resistant ovarian cancer each year in the U.S.

The primary endpoint of INNOVATE-3 is overall survival.

Secondary endpoints include progression-free survival, objective response rate, severity and frequency of adverse events, time to undisputable deterioration in health-related quality of life or death, and quality of life.

The study is designed to accrue 540 patients with 18-month follow-up after the last patient in.

In 2021, we announced that the final patient was enrolled in the pivotal INNOVATE-3 study.

In March 2022, we announced that an independent DMC conducted a pre-specified interim analysis for the study.

As part of the interim analysis, the DMC reviewed the safety data for all enrolled patients and completed an analysis of overall survival on the first 540 patients randomized in the study.

The interim analysis did not indicate a need to increase the patient sample size and the DMC recommended that the study should continue to final analysis as planned.

We anticipate that final data will be released in 2023, following completion of a minimum 18-month follow-up period.

The European Network for Gynaecological Oncological Trial groups ("ENGOT") and The GOG Foundation, Inc.

("GOG"), third-party clinical study networks, are collaborating with us on the study.

Secondary endpoints include, but are not limited to, time to neurocognitive failure, overall survival and radiological response rate following study treatments.

METIS is designed to accrue 270 patients with a minimum 12-month follow-up period following the final patient enrollment.

Top-line data is anticipated in the first quarter of 2024.

Pancreatic cancer

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Unfortunately, the majority of locally advanced cases are diagnosed once the cancer is no longer operable, generally leaving chemotherapy with or without radiation as the only treatment option.

PANOVA pilot study

In 2018, we published the results of our pilot study in advanced pancreatic adenocarcinoma, the PANOVA study ("PANOVA"), examining TTFields in combination with standard of care chemotherapy.

PANOVA-3 phase 3 trial

In February 2023, the final patient was enrolled in our PANOVA-3 trial ("PANOVA-3"), a phase 3 study evaluating the efficacy of TTFields therapy together with nab-paclitaxel and gemcitabine versus nab-paclitaxel and gemcitabine alone as a front-line treatment for unresectable locally advanced pancreatic cancer.

It is estimated that approximately 48,000 patients are diagnosed with unresectable pancreatic cancer each year in the U.S.

The primary endpoint of PANOVA-3 is overall survival.

Secondary endpoints include, but are not limited to, progression-free survival, local progression-free survival, objective response rate, one-year survival rate, quality of life, pain-free survival, resectability rate and frequency and severity of adverse events.

A pre-specified interim analysis was completed in July 2023, with the recommendation that the trial proceed to final analysis.

PANOVA-3 is designed to enrolled 556 patients with an 18-month minimum follow-up period after the last patient is enrolled.

Top-line data from the PANOVA-3 trial is anticipated in the fourth quarter of 2024.

PANOVA phase 2 trial

In 2018, we published the results of our phase 2 study in advanced pancreatic adenocarcinoma, the PANOVA study ("PANOVA"), examining TTFields therapy in combination with standard of care chemotherapy.

PANOVA was a multicenter, non-randomized, open-label study.

The study included 40 patients with locally advanced or metastatic pancreatic cancer whose tumors could not be removed surgically and who had not received chemotherapy or radiation therapy prior to the clinical study.

Patients were enrolled between 2014 and 2016 in two cohorts:

The first cohort of 20 patients received TTFields with standard doses of gemcitabine alone.

The second cohort of 20 patients received TTFields with standard doses of nab-paclitaxel plus gemcitabine.

In the first cohort, efficacy results showed that progression-free survival and overall survival of patients treated with TTFields combined with gemcitabine were more than double those of gemcitabine-treated historical controls.

Median progression-free survival in the TTFields-treated group was 8.3 months (compared to 3.7 months in the gemcitabine historical control), with locally advanced patients reaching a median progression-free survival of 10.3

months and patients with metastatic disease reaching a median progression-free survival of 5.7 months.

Patients were enrolled between 2014 and 2016 in two

The first cohort of 20 patients received TTFields therapy with standard doses of gemcitabine alone.

The second cohort of 20 patients received TTFields therapy with standard doses of nab-paclitaxel plus gemcitabine.

In the first cohort, efficacy results showed that progression-free survival and overall survival of patients treated with TTFields therapy combined with gemcitabine were more than double those of gemcitabine-treated historical controls.

Median progression-free survival in the TTFields therapy-treated group was 8.3 months (compared to 3.7 months in the gemcitabine historical control), with locally advanced patients reaching a median progression-free survival of 10.3 months and patients with metastatic disease reaching a median progression-free survival of 5.7 months.

The median overall survival for all patients was 14.9 months (compared to 6.7 months in the gemcitabine historical control).

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Of 11 patients with available CT scans, 5 (45%) had a partial response (compared to 7% with gemcitabine alone), 5 (45%) had stable disease, which means that the cancer is neither decreasing nor increasing in extent or severity, and 1 (10%) had progressive disease.

In the second cohort, efficacy results showed that progression-free survival and overall survival of patients treated with TTFields combined with nab-paclitaxel plus gemcitabine were more than double those of nab-paclitaxel plus gemcitabine-treated historical controls.

Median progression-free survival in the TTFields-treated group was 12.7 months (compared to 5.5 months in the nab-paclitaxel plus gemcitabine historical control) and median overall survival was not yet reached.

In the second cohort, efficacy results showed that progression-free survival and overall survival of patients treated with TTFields therapy combined with nab-paclitaxel plus gemcitabine were more than double those of nab-paclitaxel plus gemcitabine-treated historical controls.

Median progression-free survival in the TTFields therapy-treated group was 12.7 months (compared to 5.5 months in the nab-paclitaxel plus gemcitabine historical control) and median overall survival was not yet reached.

The one-year survival rate was 72% (compared to 35% in nab-paclitaxel plus gemcitabine historical control).

Of the 15 patients with available CT scans, 6 (40%) had a partial response (compared to 23% with the nab-paclitaxel plus gemcitabine alone), 7 (47%) had stable disease and 2 (13%) had progressive disease.

Safety results from both cohorts suggested that TTFields plus first-line chemotherapies nab-paclitaxel and/or gemcitabine may be tolerable and safe in patients with advanced pancreatic cancer.

Patients reported no serious adverse events related to TTFields.

PANOVA-3 pivotal study

In 2018, we enrolled the first patient in our PANOVA-3 study ("PANOVA-3"), a pivotal study testing the effectiveness of TTFields with nab-paclitaxel and gemcitabine versus nab-paclitaxel and gemcitabine alone as a front-line treatment for unresectable locally advanced pancreatic cancer.

It is estimated that approximately 43,000 patients are diagnosed with unresectable pancreatic cancer each year in the U.S.

The primary endpoint of PANOVA-3 is overall survival.

Secondary endpoints include progression-free survival, local progression-free survival, objective response rate, one-year survival rate, quality of life, pain-free survival, resectability rate and toxicity.

The study is designed to accrue 556 patients.

In February 2023, we announced that the final patient was enrolled in the pivotal PANOVA-3 study, beginning the minimum 18-month follow-up period.

A DMC will conduct a pre-specified interim analysis pursuant to the study protocol and final data is anticipated in 2024.

Liver cancer is a leading cause of cancer deaths worldwide and is the sixth leading cause of cancer deaths annually in the U.S.

The incidence of liver cancer is approximately 42,000 new cases annually in the U.S.

The five-year survival rate with existing standards of care is less than 20%.

Hepatocellular carcinoma is the most widespread type of cancer that originates from the liver.

Advanced liver cancer has spread either to the lymph nodes or to other organs and, because these cancers are widespread, they cannot be treated with surgery.

The current common standard treatment for patients with advanced disease and those who progressed on loco-regional therapy is systemic therapy with sorafenib, lenvatinib, or atezolizumab plus bevacizumab.

In 2021, we announced that the FDA granted breakthrough designation to the NovoTTF-200T System, a TTFields device intended for use together with atezolizumab and bevacizumab for the first-line treatment of patients with unresectable or metastatic liver cancer.

The designation offers us an opportunity to interact with FDA experts throughout the premarket review phase and allows for prioritized review of regulatory submissions.

HEPANOVA pilot study

In 2021, we announced the final results of our HEPANOVA study, a single-arm pilot study evaluating the safety and efficacy of TTFields in combination with sorafenib for the treatment of advanced hepatocellular cancer.

In 21 evaluable patients, HEPANOVA showed a 9.5% objective response rate and 76% disease control rate, as well as 5.8 months of progression free survival, compared to historical control data showing a 4.5% objective response rate and 43% disease control rate for patients treated with sorafenib alone.

These results are even more encouraging when considering the poor prognosis of the study population.

52% of the patients in HEPANOVA were categorized as Child-Pugh Class B, compared to 5% in the historical control, indicating significant liver functional compromise.

Additionally, research conducted to date has shown that TTFields anti-mitotic effect requires extended exposure to

the therapy for maximum impact.

This was a challenge given median patient treatment duration of only 10 weeks during the study.

Of the patients who received at least 12 weeks of therapy, the disease control rate reached 91% with an objective response rate of 18%.

These data demonstrate that TTFields have the potential to extend survival in advanced liver cancer.

Safety results from both cohorts suggested that TTFields therapy plus first-line chemotherapies nab-paclitaxel and/or gemcitabine may be tolerable and safe in patients with advanced pancreatic cancer.

Patients reported no serious adverse events related to TTFields therapy.

PANOVA-4 phase 2 trial

In 2023, the first patient was enrolled in the phase 2 PANOVA-4 trial ("PANOVA-4") evaluating the safety and efficacy of TTFields therapy together with atezolizumab, gemcitabine and nab-paclitaxel in the treatment of metastatic pancreatic cancer.

The primary endpoint of PANOVA-4 is disease control rate.

Secondary endpoints include, but are not limited to, overall survival, progression-free survival, one-year survival, objective response rate and frequency and severity of adverse events.

PANOVA-4 is designed to accrue 76 patients with a 12-month follow-up following enrollment of the last patient.

PANOVA-4 is the result of a clinical study collaboration with Roche.

Other Clinical Results

In addition to our current development pipeline, we have conducted phase 2 and phase 3 clinical trials exploring the use of TTFields therapy in a variety of other solid tumor cancers.

These trials are described in greater detail below.

Gastric cancer

Gastric cancer is the third leading cause of cancer deaths worldwide and the third leading cause of cancer deaths in China.

The incidence of gastric cancer is approximately 478,500 new cases annually in China, and approximately 26,000 new cases annually in the U.S.

The five-year overall survival rate of gastric cancer is approximately 36%.

Current therapies include surgery, chemotherapy, radiotherapy and targeted therapy.

A commonly used chemotherapy regimen in treating gastric cancer is XELOX, a combination of oxaliplatin and capecitabine.

In patients diagnosed with advanced gastric cancer that is no longer operable, combination chemotherapy extends progression-free survival and overall survival to 3-6 months and 8-14 months, respectively.

EF-31 pilot study

In June 2022, we announced the results from our EF-31 pilot study, a single-arm study evaluating the safety and efficacy of TTFields together with XELOX chemotherapy (and trastuzumab for HER2-positive patients) as first-line treatment for patients with unresectable gastric adenocarcinoma or gastroesophageal junction adenocarcinoma in partnership with Zai.

EF-31 phase 2 trial

In 2022, we announced the final results from our EF-31 phase 2 study, a single-arm study evaluating the safety and efficacy of TTFields therapy together with XELOX chemotherapy (and trastuzumab for HER2-positive patients) as first-line treatment for patients with unresectable gastric adenocarcinoma or gastroesophageal junction adenocarcinoma in partnership with Zai.

In 26 evaluable patients, the primary endpoint, confirmed objective response rate, was 50%, median progression-free survival was 7.8 months, duration of response was 10.3 months and median overall survival had not yet been reached with a one-year survival rate of 72%.

HEPANOVA phase 2 trial

In 2021, we announced the final results of our HEPANOVA phase 2 trial, a single-arm study evaluating the safety and efficacy of TTFields therapy in combination with sorafenib for the treatment of advanced hepatocellular cancer.

Ovarian cancer

INNOVATE-3 phase 3 trial

In August 2023, we announced preliminary results from the phase 3 INNOVATE-3 trial ("INNOVATE-3"), studying the effectiveness of TTFields therapy with paclitaxel in patients with platinum-resistant ovarian cancer.

INNOVATE-3 did not meet its primary endpoint of overall survival at the final analysis.

Patients randomized to receive TTFields therapy plus paclitaxel (n=280) demonstrated a median overall survival of 12.2 months compared to a median overall survival of 11.9 months in patients treated with paclitaxel alone (n=278) (hazard ratio=1.008).

Consistent with previously reported studies, TTFields therapy was well-tolerated with no added systemic toxicities.

Post-hoc analyses of the INNOVATE-3 results are ongoing and we expect to present findings at upcoming medical congresses.

Zai License and Collaboration Agreement

In 2018, we announced a strategic collaboration with Zai.

The collaboration agreement grants Zai a license to commercialize our Products in Greater China and establishes a development partnership intended to accelerate the development of TTFields in multiple solid tumor cancer indications.

Zai has launched Optune for the treatment of newly diagnosed GBM in Hong Kong and mainland China and is seeking marketing authorization for GBM in Taiwan.

Zai has also launched Optune Lua for the treatment of MPM in Hong Kong and has filed a Marketing Authorization Application for MPM in mainland China.

Zai has launched Optune Gio for the treatment of newly diagnosed GBM in Hong Kong and mainland China and is seeking marketing authorization for GBM in Taiwan.

For additional information, see Note 12 to the Consolidated Financial Statements.

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We have also filed several hundred additional patent applications worldwide, that, if issued, may protect aspects of our platform beyond the current last-to-expire patent in the relevant market.

These pending applications cover innovations relating to our arrays, field generators and software platform, in addition to other topics related to TTFields.

These pending applications cover innovations relating to our arrays, field generators and software platform, in addition to other topics related to TTFields therapy.

Our reliance on intellectual property involves certain risks, as described under the heading "Risk factors—Risks relating to intellectual property."

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These agreements generally provide that the individual must keep confidential and not disclose to other parties any confidential information developed or learned by the individual during the course of their relationship with us except in limited circumstances.

These agreements also generally provide that we own, or the individual is required to assign to us, all inventions conceived by the individual in the course of rendering services to us.

agreements also generally provide that we own, or the individual is required to assign to us, all inventions conceived by the individual in the course of rendering services to us.

Despite measures taken to protect our intellectual property, unauthorized parties may copy certain aspects of our products or obtain and use information that we believe is proprietary.

Pursuant to our strategic collaboration with Zai, we granted Zai a license to commercialize TTFields in Greater China.

Pursuant to our strategic collaboration with Zai, we granted Zai a license to commercialize TTFields therapy in Greater China.

For additional information, see Note 12 to the Consolidated Financial Statements.

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Our intellectual property portfolio is continuously expanding as we find new and unique ways to improve TTFields therapy.

We believe these intellectual property rights would provide an obstacle to the introduction of state of the art TTFields devices by a competitor.

However, competitors may be able to offer less sophisticated TTFields devices that utilize technology described in expired patents and/or choose to market their system(s) in countries where we have limited or no enforceable intellectual property rights.

We believe these intellectual property rights would provide an obstacle to the introduction of state of the art TTFields therapy devices by a competitor.

However, competitors may be able to offer less sophisticated TTFields therapy devices that utilize technology described in expired patents and/or choose to market their system(s) in countries where we have limited or no enforceable intellectual property rights.

Competitors could also pursue alternative technologies for the application of TTFields into a patient that we did not foresee or protect.

We are aware of a few third parties in the United States and China developing devices and filing for intellectual property protection related to TTFields.

We are aware of a few third parties in the United States and China developing devices and filing for intellectual property protection related to TTFields therapy.

Beginning in 2021, several of our early patents covering technology included in our Products began expiring in the U.S.

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In the UK, our Products and operations are subject to, inter alia, the Medical Devices Regulations 2002 and the Medical Devices (Amendment etc.) (EU Exit) Regulations 2020 (the "UK Regulations"), which implements the MDR and MDR like provisions into UK law.

certification, storage, recordkeeping, advertising, promotion, export and marketing and distribution, among other things, of our Products for current and future indications.

In addition, our Products must meet the requirements of a large and growing body of national, regional and international standards that govern the preclinical and clinical testing, manufacturing, labeling, certification, storage, recordkeeping, advertising, promotion, export and marketing and distribution, among other things, of our Products for current and future indications.

In the U.S., advertising and promotion of medical devices, in addition to being regulated by the FDA, is also regulated by the Federal Trade Commission and by state regulatory and enforcement authorities.

In the EU, advertising and promotion is subject to not only the general provisions of the MDR, but also general EU advertising rules on misleading and comparative advertising and unfair commercial practices, as implemented at the EU member state level, such as the Heilmittelwerbegesetz in Germany.

In the UK, advertising and promotion is subject to the UK Regulations, general guidance and enforcement of the Medicines and Healthcare products Regulatory Agency (MHRA), and adherence to the Association of British HealthTech Industries (ABHI) Code of Ethical Business Practices.

Promotional activities for FDA-regulated products of other companies have been the subject of government enforcement actions brought under healthcare laws and consumer protection statutes.

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Premarket approval (PMA) and Humanitarian Device Exemption (HDE) pathways

Optune and Optune Lua are classified as Class III devices as they are deemed to be life-sustaining devices.

Accordingly, we were required to receive PMA for Optune, which the FDA granted in April 2011 and October 2015 for the treatment of recurrent and newly diagnosed supratentorial GBM, respectively, in adult patients.

Optune Gio and Optune Lua are classified as Class III devices as they are deemed to be life-sustaining devices.

Accordingly, we were required to receive PMA for Optune Gio, which the FDA granted in April 2011 and October 2015 for the treatment of recurrent and newly diagnosed supratentorial GBM, respectively, in adult patients.

We expect that we will be required to receive PMA for the use of our Products for future indications.

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During the PMA review period, the FDA will typically request additional information or clarification of the information already provided.

Also, an advisory panel of experts from outside the FDA may be convened to review and evaluate the application and provide recommendations to the FDA as to the approvability of the device.

Also, an advisory panel of experts from outside the FDA may be convened to review and evaluate the application and provide recommendations to the FDA

as to the approvability of the device.

The FDA may or may not accept the panel’s recommendation.

In addition, the FDA will generally conduct a pre-approval inspection of the manufacturing facility or facilities to ensure compliance with the QSR.

Prior to approval of the Optune PMA for the treatment of recurrent GBM, we and our critical component suppliers were each inspected by the FDA.

Prior to approval of the Optune Gio PMA for the treatment of recurrent GBM, we and our critical component suppliers were each inspected by the FDA.

New PMAs or PMA supplements are required for modifications that affect the safety or effectiveness of our devices, including, for example, certain types of modifications to a device’s indication for use, manufacturing process, labeling and design.

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The FDA may review a company’s decisions when reviewing the PMA Annual Report and require the filing of an application.

As is typical with medical device companies, we have received approval for a number of post-approval PMA supplements for GBM, including for modifications to Optune’s electric field generator, arrays, software, manufacturing processes and labeling.

As is typical with medical device companies, we have received approval for a number of post-approval PMA supplements for GBM, including for modifications to Optune Gio’s electric field generator, arrays, software, manufacturing processes and labeling.

Future modifications may be considered by us as the need arises, some of which we may deem to require a PMA supplement application and others to require reporting in our PMA Annual Report.

For class III devices intended to treat disease affecting 8,000 individuals or less per year in the U.S., called Humanitarian Use Devices ("HUD"), the FDA has a separate marketing authorization pathway called the HDE.

Approval basis for an HDE is a "reasonable assurance of safety" and that the probable benefit to health outweighs risk of injury from its use, which means a traditional pivotal study usually is not required to support approval.

Approval basis for an HDE is a "reasonable assurance of safety" and that the probable benefit to health outweighs risk of injury from its use, which means a traditional phase 3 study usually is not required to support approval.

In 2019, the FDA approved Optune Lua (then known as "NovoTTF-100L") for the treatment of MPM under the HDE pathway.

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Such studies are conducted in the post-market setting with the approved device, often to address the long-term use of the device or other discrete questions that may have been raised based on the clinical data from the IDE clinical study.

The FDA required a post-approval registry study as a condition of approval for Optune for recurrent GBM, which we completed.

The FDA required a post-approval registry study as a condition of approval for Optune Gio for recurrent GBM, which we completed.

Clinical studies involving pharmacological/immunological therapy candidates may be regulated under FDA’s drug regulations, Unless exempt, such studies require authorization from FDA of an Investigational New Drug Application ("IND") for a specified number of patients and study sites.

As with IDE studies, IND studies are subject to extensive monitoring, recordkeeping and reporting requirements, must be conducted under the oversight of an IRB, must comply with FDA drug or biologic regulations, and are required to obtain informed consent that complies with FDA requirements and state and federal privacy and human subject protection regulations.

IND clinical studies can be suspended at any time by us, the FDA or an IRB for various reasons, including a belief that the risks to study subjects outweigh the anticipated benefits.

IND clinical studies can be

suspended at any time by us, the FDA or an IRB for various reasons, including a belief that the risks to study subjects outweigh the anticipated benefits.

Even if an IND study is completed, the results of clinical testing may not be sufficient to obtain FDA approval to market the product.

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In addition, as of May 25, 2021, in the absence of a new MRA, Switzerland is now considered a non-EU “third country” with respect to medical devices, meaning that movement of our Products bearing a CE mark from the EEA to Switzerland is subject to additional requirements.

In the UK, we may continue to market and sell our Products under the CE mark until June 2023.

Thereafter, our Products will be regulated under the UK Regulations.

In the UK, we were able to market and sell our Products under the CE mark until June 2023.

Thereafter, our Products have been regulated under the UK Regulations.

In the EEA, before carrying out a clinical investigation with a non-CE marked device to assess its safety or performance when in accordance with its intended use, the study sponsor must receive a positive opinion from the local ethics committee and approval from the national competent authority in the relevant EEA member states in which the clinical investigation will be conducted.

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• approval of product modifications that affect the safety or effectiveness of one of our devices that has been approved or is the subject of a CE Certificate;

• Medical Device Reporting regulations of the FDCA and medical device vigilance, which require that manufacturers comply with FDA or equivalent competent authority requirements in other jurisdictions to report if their device may have caused or contributed to a death or serious injury, or has malfunctioned in a way that would likely cause or contribute to a death or serious injury if the malfunction of the device or a similar device were to recur;

way that would likely cause or contribute to a death or serious injury if the malfunction of the device or a similar device were to recur;

• post-approval restrictions or conditions, including post-approval study commitments;

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• operating restrictions or partial suspension or total shutdown of production;

• refusing or delaying our requests for approval of device candidates or a modified version of Optune;

• refusing or delaying our requests for approval of device candidates or a modified version of Optune Gio;

• withdrawal of PMA/HDE approvals or suspension, variation or withdrawal of CE Certificates that have already been granted;

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Certain states require that DME providers maintain an in-state location.

Although we believe we are in compliance with all applicable federal and state regulations regarding accreditation and licensure requirements and similar requirements in other jurisdictions, if we are found to be noncompliant, we could lose our accreditation or licensure in such states or our supplier rights under such federal healthcare programs, which could prohibit us from selling our current or future devices to patients in such state or to that federal healthcare program.

licensure in such states or our supplier rights under such federal healthcare programs, which could prohibit us from selling our current or future devices to patients in such state or to that federal healthcare program.

Healthcare regulatory matters

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The majority of states also have statutes or regulations similar to the federal Anti-Kickback Statute, Stark Law and False Claims Act laws, which apply to items and services reimbursed under Medicaid and other state programs, or, in several states, that apply regardless of the payer (e.g., including private/commercial payors or cash-pay scenarios).

Numerous federal and state laws and regulations, including the Health Insurance Portability and Accountability Act of 1996 as amended by the Health Information Technology for Economic and Clinical Health Act ("HITECH" and collectively "HIPAA"), govern the collection, dissemination, use, security and privacy of individually identifiable

health information.

We believe we are in substantial compliance with such applicable laws and regulations, including HIPAA.

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To achieve commercial success for our Products, we believe we must continue to develop and grow our sales and marketing, patient support and research and development teams, along with the necessary staff to support it.

This need accounts for the significant increase in the number of employees in 2021.

Developing and managing a growing organization is a difficult, expensive and time consuming process.

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Because our current Products require, and we anticipate our future Products will require, physician training and education, we expect that our sales and marketing and patient support teams will continue to grow substantially as we expand our approved indications and markets.

The ongoing COVID-19 pandemic also creates challenges to our ability to recruit and retain effective and experienced employees.

In 2021, we instituted a COVID-19 vaccine mandate for all employees (subject to certain exceptions).

Some employees chose to leave our company in response to this mandate and while the pandemic continues, this mandate may limit our ability to recruit new employees.

In November 2023, we announced a series of actions to strengthen and optimize our business operations to support near-term growth drivers and long-term value creation.

The plan included a reduction in headcount of approximately 200 employees or 13% of our then current workforce.

Field-based commercial and field-based medical employees were minimally affected.

We expect that the workforce reduction, along with other actions, will enable us to fund future growth priorities without an associated increase in expected forward operating cash burn.

We continue to

focus resources on our global commercial infrastructure and launch preparation ahead of our anticipated indication in metastatic non-small cell lung cancer and on high-potential research and development programs.

Available information

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What changed 10-K

Item 1. Business