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Item 1. Business

2025-02-27 compared with 2024-02-22 · 155 added, 213 removed, 351 unchanged (51% of the section changed)

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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.

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.

Optune Gio is approved by the U.S.

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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 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.

Optune Lua is approved by the FDA under the PMA pathway for the treatment of adult patients with metastatic non-small cell lung cancer ("NSCLC") concurrent with PD-1/PD-L1 inhibitors or docetaxel following progression on or after a platinum-based regimen.

Optune Lua is also approved under the Humanitarian Device Exemption ("HDE") pathway for the treatment of adult patients with malignant pleural mesothelioma or 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 for the treatment of MPM.

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, France and Japan.

We are actively evaluating opportunities to expand our international footprint.

In June 2024, we presented results from the Phase 3 METIS clinical trial evaluating the use of TTFields therapy and best supportive care for the treatment of adult patients with 1-10 brain metastases from NSCLC following stereotactic radiosurgery ("METIS").

The METIS trial met its primary endpoint, demonstrating a statistically significant improvement in time to intracranial progression for patients treated with TTFields therapy and supportive care compared to patients treated with supportive care alone.

In December 2024, we announced the top-line results from the Phase 3 PANOVA-3 clinical trial evaluating the use of TTFields therapy together with gemcitabine and nab-paclitaxel for the treatment of adult patients with unresectable, locally advanced pancreatic cancer ("PANOVA-3").

The PANOVA-3 trial met its primary endpoint, demonstrating a statistically significant improvement in overall survival for patients treated with TTFields therapy, gemcitabine and nab-paclitaxel compared to patients treated with gemcitabine and nab-paclitaxel alone.

We intend to submit marketing applications to regulators in our key markets based on the results of the METIS and PANOVA-3 trials.

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

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 ongoing clinical trials which further explore the use of TTFields therapy in these solid tumor cancers, including the Phase 3 TRIDENT and KEYNOTE D58 trials in GBM, Phase 3 LUNAR-2 and Phase 2 LUNAR-4 trials in NSCLC, and Phase 2 PANOVA-4 trial in pancreatic cancer.

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

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.

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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.

Arrays are changed when hair growth or the hydrogel reduces array adhesion to the skin.

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.

Arrays are changed when hair growth or skin moisture reduces array adhesion to the skin.

The therapy is designed to be delivered continuously throughout the day and night, and efficacy is strongly correlated to time on therapy.

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Our arrays have been developed and are in use, either commercially or clinically, for application on the head, thorax and abdomen.

Through engineering efforts, we plan to continue to advance our Products to optimize TTFields therapy for patients.

We have several product development programs underway designed to extend survival and enhance quality of life.

Our product development programs are primarily focused on enhancements to the field generator, arrays and software applications.

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

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.

Through engineering efforts, we plan to continue to advance our Products to optimize TTFields therapy.

Our product development programs are primarily focused on enhancements to the field generator and arrays, as well as development of software applications intended to enhance the TTFields therapy experience for both patients and healthcare providers.

Any enhancements will be subject to applicable regulatory reviews and approvals.

Our commercial business

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 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.

Optune Gio is approved for use in multiple countries 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 approved for use in multiple countries for the treatment of MPM.

Optune Lua is also approved for use in the U.S.

for the treatment of NSCLC.

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 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 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 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.

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 based on the randomized Phase 3 EF-14 trial ("EF-14"), which compared Optune Gio plus temozolomide versus temozolomide alone for the treatment of newly diagnosed GBM post radiation.

The trial met its primary endpoint of progression-free survival and a powered secondary endpoint was overall survival.

Patients treated with Optune Gio and temozolomide exhibited 6.7 and 20.9 months of median progression-free and overall survival, respectively, compared to 4.0 and and 16.0 months in patients treated with temozolomide alone.

The extension of overall survival and progression-free survival in patients receiving Optune Gio with temozolomide 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.

Patients treated with Optune Gio and temozolomide had no significant increase in serious adverse events compared with those treated 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 final EF-14 data were published in the Journal of the American Medical Association in 2017.

Patients treated with Optune Gio and temozolomide also demonstrated stable and comparable quality of life compared to patients treated with temozolomide alone, when evaluating physical, role, social, emotional and cognitive functioning, Post-hoc analyses of EF-14 have shown that increased time on therapy and higher TTFields intensity at the tumor bed are associated with increased survival.

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

We received FDA approval for Optune Gio in 2011 for use as a monotherapy treatment for adult patients with GBM, following confirmed recurrence after chemotherapy based on the randomized Phase 3 EF-11 trial ("EF-11"), which compared Optune Gio versus physician's choice chemotherapy for the treatment of recurrent GBM..

Patients randomized to receive Optune Gio monotherapy demonstrated 6.6 months of median overall survival, compared to 6.0 months in patients treated with physician's choice chemotherapy.

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 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.

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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.

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 NSCLC

In 2024, we received FDA approval to market Optune Lua for the treatment of adult patients with metastatic NSCLC concurrent with PD-1/PD-L1 inhibitors or docetaxel following progression on or after a platinum-based regimen based on the results from the randomized Phase 3 LUNAR clinical trial ("LUNAR").

LUNAR evaluated the safety and efficacy of TTFields therapy when used together with immune checkpoint inhibitors or docetaxel (collectively, "standard therapies") versus standard therapies alone for patients with stage 4 NSCLC who progressed during or after platinum-based therapy.

The LUNAR trial met its primary endpoint Patients treated with TTFields therapy and standard therapies demonstrated median overall survival of 13.2 months (95% CI, 10.3-15.5 months) compared to 9.9 months (95% CI, 8.2-12.2 months) in patients treated with standard therapies alone (p=0.042, HR=0.76).

The one-year survival rate for patients treated with TTFields therapy and standard therapies was 53% (95% CI, 44%-61%) compared to 42% (95% CI, 34%-50%) in patients treated with standard therapies alone.

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

In 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.

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.

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

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STELLAR investigated safety and efficacy among 80 patients treated with Optune Lua plus standard of care chemotherapy.

In STELLAR, the median overall survival was 18.2 months (95% CI, 12.1-25.8 months) across all patients treated with Optune Lua plus chemotherapy.

Median overall survival was 18.2 months (95% CI, 12.1-25.8 months) across all patients treated with Optune Lua plus chemotherapy.

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).

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Our commercial markets

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:

We have built a commercial organization and market Optune Gio for the treatment of GBM in multiple countries and Optune Lua for the treatment of NSCLC in the U.S..

In 2025, we estimate that annually 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 Gio based upon the rate of disease progression and medical eligibility will actively seek treatment.

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

Of this population, approximately 2,500 patients are candidates for treatment with Optune Gio and will actively seek treatment.

Annual diagnoses rates per capita are similar in our other European active markets.

• 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 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.

Of this population, approximately 1,200 patients are candidates for treatment with Optune Gio and will actively seek treatment.

• 114,000 people will be diagnosed with metastatic NSCLC in the U.S.

We estimate that approximately 30,000 patients are candidates for second-line treatment with Optune Lua and will actively seek therapy.

We believe there are many more patients who could benefit from treatment with Optune Gio or Optune Lua and we continue to focus on increasing penetration for GBM and NSCLC.

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.

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.

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

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

Our sales and marketing efforts are principally focused on driving adoption of Optune Gio and Optune Lua among medical oncologists, specialty oncologists focused on treatment of the brain and thorax, and radiation oncologists.

We continue to focus on driving key academic center engagement across all indications.

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

In Japan, we distribute our Products 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 distribute our Products through hospitals in Japan with the hospitals receiving reimbursement from the government-mandated insurance program and in turn contracting with us for the equipment, supplies and services necessary to treat patients with our Product.

We maintain a monthly list price for our therapy in the U.S.

and set list prices outside of the United States that are approximately equivalent to this price, subject to currency fluctuations.

We maintain a monthly list price for our therapy.

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.

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As of December 31, 2024, we have received national reimbursement for Optune Gio in Austria, France, Germany, Israel, Japan, Sweden and Switzerland.

As of December 31, 2024 we have not yet received national reimbursement for Optune Lua for NSCLC in any of our active markets, however, we are seeking to obtain national reimbursement (and private insurance coverage, where available) in multiple countries.

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, 2024.

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.

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

We intend to pursue private

health insurance and Medicare coverage with CMS for Optune Lua for NSCLC.

We cannot be certain when we will obtain such coverage or if we will be able to obtain such coverage at reasonable rates.

Our development pipeline

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.

Based on the results of our preclinical and clinical research, we have developed a pipeline strategy to advance TTFields therapy through phase 2 and phase 3 studies across multiple solid tumor types where TTFields has shown efficacy, including GBM, NSCLC and pancreatic cancer.

Current Development Pipeline

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 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, 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

Lung cancer is the most common cause of cancer-related death worldwide, and NSCLC accounts for approximately 85% of all lung cancers.

It is estimated that approximately 193,000 patients are diagnosed with NSCLC each year in the U.S.

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

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

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

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.

In addition to our ongoing clinical trials, we continue to conduct research to further advance the scientific evidence supporting the use of TTFields therapy and to gather additional information about our therapy's optimal use.

Central Nervous System Indications

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.

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

each year with brain metastases estimated to occur in between 10% to 40% of all cancer patients.

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.

Brain metastases are commonly treated with a combination of surgery and radiation.

Chemotherapy is often given for the primary tumor, but many chemotherapy agents do not cross the blood brain barrier and are thus ineffective in the treatment of brain metastases.

Systemic therapies are often utilized to treat the primary tumor, but many systemic therapies do not cross the blood brain barrier and are thus ineffective in the treatment of brain metastases.

When brain metastases appear, they are either surgically removed or treated with radiation using stereotactic radiosurgery ("SRS") when possible.

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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.

with brain metastases resulting from NSCLC.

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

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.

In 2024, we presented data from the Phase 3 METIS trial, which evaluated the safety and efficacy of TTFields therapy and best supportive care ("BSC") compared to BSC alone in the treatment of adult patients with brain metastases resulting from NSCLC following stereotactic radiosurgery.

METIS met its primary endpoint, demonstrating a statistically significant improvement in time to intracranial progression in patients randomized to receive TTFields therapy.

Patients treated with TTFields therapy and BSC exhibited a median time to intracranial progression of 21.9 months compared to 11.3 months in patients treated with BSC alone (n=298;

Median TTFields therapy treatment duration was 16 weeks and median usage was 67%.

Consistent with previous studies, TTFields therapy was well-tolerated with sustained quality of life and neurocognitive function.

Baseline characteristics were well balanced between arms.

We estimate that approximately 16,000 patients meet the criteria of the METIS trial and actively seek treatment in the U.S.

We intend to submit the data from METIS to regulatory authorities and publish these findings in a peer-reviewed scientific journal.

In 2024, we received Breakthrough Device designation from the FDA for the use of TTFields therapy in the treatment of brain metastases from NSCLC and are currently in pre-submission discussions with the FDA in anticipation of filing a PMA application in 2025, with potential launch in 2026.

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

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.

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.

KEYNOTE D58 Phase 3 trial

In 2024, the FDA accepted the investigational new drug application for the randomized, double blind, placebo controlled Phase 3 KEYNOTE D58 clinical trial ("KEYNOTE D58").

KEYNOTE D58 is evaluating the use of TTFields therapy together with temozolomide and pembrolizumab for the treatment of adult patients with newly diagnosed GBM.

KEYNOTE D58 was designed to accrue 741 patients with a 24-month minimum follow-up period after the last patient is enrolled.

The primary endpoint is overall survival.

Secondary endpoints include, but are not limited to, progression-free survival, one and two-year survival rates, quality life and safety.

KEYNOTE D58 was designed and is being conducted as part of a clinical collaboration between Novocure and MSD, a tradename of Merck & Co., Inc.

KEYNOTE D58 is currently open and enrolling.

Torso Indications

Pancreatic cancer

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While overall cancer incidence and death rates are remaining stable or declining, the incidence and death rates for pancreatic cancer are increasing.

It is estimated that approximately 60,000 patients are diagnosed with pancreatic cancer each year in the U.S.

We estimate that approximately 60,000 patients are diagnosed with pancreatic cancer each year in the U.S.

Pancreatic cancer has a five-year relative survival rate of just 10 percent.

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

For patients with locally advanced pancreatic cancer involving encasement of arteries but no extra-pancreatic disease, the standard of care is surgery followed by chemotherapy with or without radiation.

For patients with locally advanced pancreatic cancer involving encasement of arteries but no extra-pancreatic disease, the standard of care is surgery followed by chemotherapy

with or without radiation.

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-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

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).

Median overall survival was not reached in locally advanced patients and 86% of patients were alive at end of follow up.

Patients with metastatic disease experienced a median overall survival of 8.3 months.

One-year survival was 55% (compared to 22% in the gemcitabine historical control).

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 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 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.

In 2024, we announced top-line results from the Phase 3 PANOVA-3 trial, which evaluated the safety and efficacy of TTFields therapy together with gemcitabine and nab-paclitaxel compared to gemcitabine and nab-paclitaxel alone for the treatment of unresectable, locally advanced pancreatic cancer.

PANOVA-3 met its primary endpoint, demonstrating a statistically significant improvement in overall survival in patients randomized to receive TTFields therapy.

Patients treated with TTFields therapy together with gemcitabine and nab-paclitaxel demonstrated 16.20 median overall survival compared to 14.16 months in patients treated with gemcitabine and nab-paclitaxel alone (n=571, HR=0.819, p=0.039).

The survival rate benefit for patients treated with TTFields therapy increased over time with a 13% improve in the overall survival rate at 12 months and a 33% overall survival rate at 24month.

Consistent with previous studies, TTFields therapy was well-tolerated.

We estimate that approximately 15,000 patients meet the criteria of the PANOVA-3 trial and actively seek treatment in the U.S.

We intend to share the PANOVA-3 data at an upcoming scientific congress, to submit these data for publication in a peer-reviewed scientific journal and to submit the data to regulatory authorities.

In 2024, we received Breakthrough Device designation from the FDA for the use of TTFields therapy in the treatment unresectable, locally advanced pancreatic cancer together with gemcitabine and nab-paclitaxel and are currently in pre-submission discussions with the FDA in anticipation of filing a PMA application in 2025, with potential launch in 2026.

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.

In 2024, we completed enrollment 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.

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

PANOVA-4 was designed and is being conducted as part of a clinical collaboration between Novocure and Roche.

Final data from the PANOVA-4 trial is anticipated in 2026.

Non-small cell lung cancer

Lung cancer is the most common cause of cancer-related death worldwide, and NSCLC accounts for approximately 85% of all lung cancers.

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

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.

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

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.

LUNAR-2 is designed

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

LUNAR-2 is currently open and enrolling.

LUNAR-4 Phase 2 trial

In 2024, the FDA accepted the investigation device exemption for the LUNAR-4 clinical trial ("LUNAR-4"), a Phase 2 trial evaluating the safety and efficacy of TTFields therapy concomitant with pembrolizumab for the treatment of patients with metastatic NSCLC following previous treatment with PD-1/PD-L1 inhibitor and platinum-based chemotherapy.

The primary endpoint of LUNAR-4 is overall survival.

Secondary endpoints include, but are not limited to, overall survival and progression-free survival according to patient histology and tumor proportion score, and safety.

LUNAR-4 is designed to accrue 69 patients with a 12-month follow-up following the enrollment of the last patient.

LUNAR-4 is currently open and enrolling.

Other Clinical Results

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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.

In 2024 , we presented 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.

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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.

An exploratory analysis of INNOVATE-3 found that pegylated liposomal doxorubicin (PLD) naive patients randomized to receive TTFields therapy and paclitaxel has a median overall survival of 16.0 months (n=113) compared to 11.7 months in PLD-naive patients treated with paclitaxel alone (n=88).

Zai License and Collaboration Agreement

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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 therapy in multiple solid tumor cancer indications.

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.

Zai has launched Optune Gio for the

treatment of newly diagnosed GBM in Hong Kong and mainland China, is seeking marketing authorization for GBM in Taiwan.

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

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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.

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.

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.

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.

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Presently, the traditional biotechnology, pharmaceutical and medical technology industries expend significant resources in developing novel and proprietary therapies for the treatment of solid tumors, including GBM, MPM and other indications that we are currently investigating.

As we work to increase market acceptance of our Products, we compete with companies commercializing or investigating other anti-cancer therapies, some of which are in clinical studies for GBM or MPM that currently specifically exclude patients who have been or are being treated with our Products.

As we work to increase market acceptance of our Products, we compete with companies commercializing or investigating other anti-cancer therapies, some of which are in clinical studies for GBM, NSCLC or MPM that currently specifically exclude patients who have been or are being treated with our Products.

The introduction of competing therapies could materially impact our business and financial results.

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The MDR replaced the Medical Device Directive ("MDD") on May 26, 2021.

In Switzerland, our Products and operations are subject to, inter alia, the Medical Devices Ordinance, which implements the MDR into Swiss law (See "Foreign approvals and CE mark" below).

In Switzerland, our Products and operations are subject to, inter alia, the Federal Act on Medicinal Products and Medical Devices and the the Medical Devices Ordinance, which implements the MDR into Swiss law (See "Foreign approvals and CE mark" below).

In Japan, our Products and operations are subject to regulation by the Pharmaceuticals and Medical Device Agency ("PMDA") under the Pharmaceuticals and Medical Devices Act ("PMD Act").

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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

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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FDA’s premarket clearance and approval requirements

Unless an exemption applies, before we can commercially distribute medical devices in the U.S., we must obtain, depending on the type of device, either prior 510(k) clearance or premarket approval ("PMA") from the FDA.

The FDA classifies medical devices into one of three classes.

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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.

Accordingly, we were required to obtain PMA approval 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 were also required to obtain PMA approval for Optune Lua for use concurrent with PD-1/PD-L1 inhibitors or docetaxel in adult patients with metastatic NSCLC who have progressed on or after a platinum-based regimen, which the FDA granted in October 2024.

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

A PMA must be supported by extensive data, including from technical tests, preclinical studies and clinical studies, manufacturing information and intended labeling to demonstrate, to the FDA’s satisfaction, the safety and effectiveness of a medical device for its intended use.

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.

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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 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.

As is typical with medical device companies, we have received approval for a number of post-approval PMA supplements for our approved Products, including for modifications to the 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.

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Even if a study is completed, the results of clinical testing may not adequately demonstrate the safety and efficacy of the device or may otherwise not be sufficient to obtain FDA approval to market the product in the U.S.

Post-approval studies are also typically required as a condition of PMA to reinforce the reasonable assurance of safety and effectiveness.

Post-approval studies are also typically required as a condition of PMA approval to reinforce the reasonable assurance of safety and effectiveness.

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.

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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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Following the issuance of this CE Certificate, we can draw up a declaration of conformity and affix the CE mark to the devices covered by this CE Certificate.

The time required to CE mark our devices or to obtain approval from other non-U.S.

authorities may be longer or shorter than that required for FDA approval.

The time required to CE mark our

devices or to obtain approval from other non-U.S.

authorities is not defined, and therefore may be longer or shorter than that required for FDA approval.

Moreover, the MDR, which became applicable on May 26, 2021, with transitional provisions for "legacy" devices under the MDD, imposed new, stricter requirements that we must comply with in order to obtain CE Certificates for new devices, and to renew the CE Certificates for our MDD-Products when these expire, or at the latest, December 31, 2027 or 2028, depending on the device, whichever comes first.

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• product listing and establishment registration, which helps facilitate FDA inspections and other regulatory action;

• QSR, which requires manufacturers, including third-party manufacturers, to follow stringent design, testing, control, documentation and other quality assurance procedures during all aspects of the manufacturing process for products marketed in the U.S.;

• the QSR, which requires manufacturers, including third-party manufacturers, to follow stringent design, testing, control, documentation and other quality assurance procedures during all aspects of the manufacturing process for products marketed in the U.S.;

• labeling regulations and FDA and equivalent competent authority in other jurisdictions requiring promotion be truthful and non-misleading and prohibiting the promotion of products for uncleared, unapproved or off-label uses;

• 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;

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;

• 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;

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

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Our devices could be subject to voluntary recall if we, the FDA or another applicable regulatory authority determine, for any reason, that our devices pose a risk of injury or are otherwise defective.

Moreover, the FDA and other applicable regulatory authorities can order a mandatory recall if there is a reasonable probability that our device would cause serious adverse health consequences or death.

Moreover, the FDA and other

applicable regulatory authorities can order a mandatory recall if there is a reasonable probability that our device would cause serious adverse health consequences or death.

The FDA has broad post-market and regulatory enforcement powers.

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To date, our facilities and those of our critical suppliers have been inspected by several relevant regulatory authorities in order to obtain regulatory approval of our Products.

No inspectional observations were identified were issued following these inspections.

Durable medical equipment accreditation and licensing and other requirements

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

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.

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.

Healthcare regulatory matters

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Although there are a number of statutory exceptions and regulatory safe harbors that protect certain common activities from prosecution under the law, the exceptions and safe harbors are drawn narrowly and practices that involve the provision of remuneration intended to induce ordering, purchasing, leasing or recommending of a medical device may be subject to scrutiny if they do not qualify for an exception or safe harbor.

In some cases, our practices may not meet all of the technical elements for protection under a federal Anti-Kickback Statute exception or safe harbor.

In some cases, our practices may not meet

all of the technical elements for protection under a federal Anti-Kickback Statute exception or safe harbor.

Similarly, as a supplier, we are also subject to the federal beneficiary anti-inducement statute, which prohibits us from offering any remuneration to a beneficiary of Medicare or Medicaid that is likely to influence that beneficiary’s choice of therapy, unless an exception applies.

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We have adopted policies and codes of conduct regarding our interactions with Covered Recipients and believe we are in material compliance with the Sunshine Act.

However, our failure to adhere to these requirements could materially adversely impact our business and financial results.

However, our failure to adhere to these requirements could materially adversely

impact our business and financial results.

Additionally, a number of states have transparency reporting requirements similar to (and in some cases broader than) the Sunshine Act, and regulations similar to the Sunshine Act have been adopted in foreign countries including a number of EU member states.

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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.

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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Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.

What changed 10-K

Item 1. Business