Novocure (NVCR) Q2 2022 Earnings Call Transcript

Novocure (NVCR 0.33%)
Q2 2022 Earnings Call
Jul 28, 2022, 8:00 a.m. ET

Contents:

• Prepared Remarks
• Questions and Answers
• Call Participants

Prepared Remarks:

Operator

Good day, and welcome to the NovoCure Q2 2022 earnings call. [Operator instructions]. As a reminder, this call is being recorded. I would now like to turn the call over to Ingrid Goldberg.

Ingrid Goldberg -- Vice President, Finance and Investor Relations

Good morning, everyone, and thank you for joining us to review NovoCure's second quarter 2022 performance. I'm joined on the phone by our executive chairman, Bill Doyle; our CEO, Asaf Danziger; and our CFO, Ashley Cordova. Other members of our executive leadership team are also on the call and available for Q&A. For your reference, slides accompanying this earnings release can be found on our website, www.novocure.com, under quarterly report on our Investor Relations page.

Before we start, I would like to remind you that discussions during this conference call will include forward-looking statements and actual results could differ materially from those projected in these statements. These statements involve a number of risks and uncertainties, some of which are beyond our control and are described from time to time in our SEC filings. We do not intend to update publicly any forward-looking statement, except as required by law. Where appropriate, we will refer to non-GAAP financial measures to evaluate our business, specifically adjusted EBITDA, a measure of earnings before tax, interest, depreciation, amortization, and share-based compensation.

We believe adjusted EBITDA is an important metric as it removes the impact of earnings attributable to our capital structure, tax rate, and material noncash items and best reflects the financial value generated by our business. Reconciliations of non-GAAP to GAAP financial measures are included in our press release, earnings slides, and in our Form 8-K filed with the SEC today. These materials can also be accessed from our Investor Relations page of our website. Following our prepared remarks today, we will open the line for your questions.

I will now turn the call over to our executive chairman, Bill Doyle.

Bill Doyle -- Executive Chairman

Thank you, Ingrid, and good morning. Our mission at NovoCure is to extend survival in some of the most aggressive forms of cancer through the development and commercialization of our innovative therapy, Tumor Treating Fields. The second quarter was a period of solid execution and progress. Revenues were up 6% compared with the second quarter of 2021.

We released encouraging Phase 2 data in gastric cancer and announced a second partnership with global oncology leader, Merck. As we approach a series of pivotal milestones in the coming quarters, we feel a hum of excitement at NovoCure as our teams work toward data readouts and develop launch plans. We exited the quarter with 3,454 commercial active patients on TTFields therapy around the globe. Steady patient volumes in the U.S.

and increasing adoption in Japan offset a decrease in German active patient numbers as a result of updated coverage criteria. We are pushing a number of avenues intended to increase the adoption of TTFields therapy and reach more patients who may benefit from TTFields. In GBM, our focus is to drive greater adoption in academic institutions where we see a significant share of GBM patient flow. We are employing a multipronged strategy to engage practitioners in the academic setting to ensure they understand and can communicate the broad benefits of TTFields.

One of the most effective ways to drive greater adoption is with the ongoing generation of clinical data. Year to date, there are over 1,500 PubMed citations of TTFields, pointing to the increasing relevance of TTFields in the scientific community. Also this quarter, two key clinical data sets were presented, which we would like to highlight. External research intended to identify genomic factors associated with an increased response to Optune was published in the June volume of neuro-oncology.

Retrospective data were collected from 148 patients treated at six leading academic institutions. Consistent with the findings of the EF-14 randomized Phase 3 trial and other independent data sets presented to date, the use of Optune increased progression-free and overall survival in all patient cohorts and demonstrated a clear dose response with increased usage. Beyond the broadly applicable benefit, alterations in certain genetic signatures were associated with increased benefit from Optune. These results further validate the survival benefit for GBM patients shown in the EF-14 trial and shed light on potential predictive biomarkers associated with an even greater response, opening an interesting area for ongoing research.

At ASCO in June, the Charite University Hospital in Berlin presented a multi-country registry analysis of GBM patients in Austria, Germany, and Switzerland. The Charite analysis of real-world evidence showed a median overall survival of 35 months for patients treated with Optune plus chemotherapy, compared to 15 months for patients treated with chemotherapy alone. These registry data further underline the benefit of Optune with real-world experience and are consistent with the results we have observed in more than 25,000 GBM patients treated with Optune to date. The growing engagement and research on Optune and TTFields emanating from leading academic centers is very encouraging, and we believe indicative of the growing awareness and acceptance of Tumor Treating Fields therapy.

While we are preparing to launch in new cancer indications, we are committed to investing in GBM treatment innovation. To this end in May, we announced a second clinical collaboration with Merck. Together, we plan to conduct a double-blind placebo-controlled pivotal study of TTFields, together with pembrolizumab and temozolomide for the treatment of newly diagnosed GBM. This study will build upon the research recently published in the Journal of Clinical Investigation and will seek to confirm the promising data generated by Dr.

David Tran to the top Phase 2 study. This latest collaboration between NovoCure and Merck will continue the exploration of TTFields together with immunotherapies in a malignancy and in a region of the body where checkpoint inhibitors have not previously shown a therapeutic benefit. We are also exploring other new GBM treatment protocols. Our pivotal Trident study is evaluating the benefits of starting TTFields therapy concurrently with radiation therapy rather than following radiation therapy.

96 clinical sites are actively recruiting patients for Trident. Beyond clinical data and physician education, patient awareness is also critical to expanding adoption. We recently finalized a Opt For Optune social media campaign, which is scheduled to launch in the second half of this year. By engaging patients, caregivers, and physicians across the digital ecosystem, the Opt For Optune campaign is designed to instill confidence, inspire courage and prepare guide, and support patients on their GBM treatment journey.

Just as other physical treatment modalities evolved from their invention to their ultimate optimal use, we are making significant investments in product development as we seek to further improve outcomes. Array layout planning is an essential component of treatment with Optune as it allows the prescriber to optimize the intensity of therapy by adapting array configuration for each patient. Today, the NovoTAL System is used to create these individualized treatment plans. Maxpoint is our next-generation array layout planning system.

Maxpoint is designed to provide more precise targeting to increase the intensity of TTFields delivered to the tumor. This quarter, we advanced Maxpoint development with the initiation of an evidence generation program, which compares the dose volume metrics of Maxpoint-guided array layouts to NovoTAL-guided array layouts. We look forward to sharing data from the Maxpoint program in coming quarters. Additionally, our next-generation arrays, now known as the FlexArray, remain on track for a limited market release in Europe this year.

We believe these arrays have the ability to deliver a higher, more consistent intensity to the tumor bed without meaningfully increasing heat. Both the FlexArray and Maxpoint represent meaningful milestones in our product development journey and highlight our commitment to ongoing investment in product development initiatives. Beyond GBM, we are exploring the use of TTFields in a number of additional solid tumor indications in the torso and abdomen. In June, together with our partner, Zai Lab, we presented data from the EF-31 pilot study.

EF-31 evaluated the use of TTFields together with chemotherapy for the treatment of gastric cancer. Gastric cancer is prevalent and deadly with 5-year survival rates below 20%. We were excited by both the response rate and the durability of responses shown in the EF-31 data. EF-31 demonstrated an objective response rate of 50% and duration of response of 10.3 months, both notable improvements over historical controls.

We are very pleased with the signals generated from EF-31. We are eager to continue exploring the potential benefit of TTFields, together with standard-of-care therapies in a large randomized clinical study. Looking to the future and turning to our clinical pipeline. We are entering a period of potential transformation.

We have four Phase 3 clinical trials in new indications poised to read out in the near term. If successful, these readouts could increase the number of patients eligible for TTFields by approximately 14-fold. Lunar is our next pivotal trial to read out. As a reminder, Lunar is the first randomized study in our thoracic program and evaluates the use of TTFields together with docetaxel or physician's choice PD-1 inhibitor for the treatment of Stage IV second-line non-small cell lung cancer.

We completed enrollment of Lunar and commenced the final patients' 12-month follow-up in November of 2021. Given feedback received from all interested parties, we recognize a pivotal trial data release during the final week of the year is not ideal for investigators, clinicians, investors or potential patients. For that reason, we will be moving the top line data announcement to early Q1 2023. To be clear, our clinical operations and data collection efforts remain on track.

This decision to push the announcement was made to ensure optimal visibility and convenience for all audiences. Innovate-3, our pivotal study in recurrent ovarian cancer, is on track for a 2023 data release following an eight-month -- 18-month follow-up from last patient enrolled. As a reminder, we announced the completion of enrollment of Innovate-3 during our Q3 2021 earnings call. Metis and Panova-3 continue to enroll patients in line with expectations.

We are pleased with the progress made in the second quarter. The updates this period represent deliberate steps to strengthen the fundamentals of our business and to plan for pending data releases and potential expansion into new large indications. We remain excited and inspired by the prospect of treating many more patients in the near term. I will now pass the call over to Ashley to run through our second quarter financial performance.

Ashley Cordova -- Chief Financial Officer

Thank you, Bill. The second quarter was another period of strong financial performance with gross profits from the core GBM business, funding investments in clinical and product development as we advance the Tumor Treating Fields platform. I know you have seen our press release and 10-Q this morning, so let me provide a few brief highlights regarding the financials. Revenue was strong, up 6% with 3,454 global active patients on therapy as of June 30.

Bill spoke to the broader adoption trends earlier on this call, so I will focus now on revenue, and in particular, the dynamics in Germany. As a reminder, in Q4 of last year, we announced that we reached agreement with the largest public German payers on a price for Optune. This year, we formalized the terms with payers that represent approximately 70% of the covered lives in Germany. These contracts will enable price stability and provide a strong pricing foundation as we pursue reimbursement in additional European markets.

The negotiations impacted our net revenue as some payers withheld approval for new patients and began to deny approval for many active patients under the coverage criteria established in the DME listing. We expect revenue to grow over time, as more patients are treated under the updated contract term. In the U.S., the exceptional execution of collections processes provided a material tailwind to revenue in the second quarter. Revenue operations is a core competency at NovoCure, and the U.S.

benefit business is benefiting both from collections on previously denied and appealed claims and from an increase in the average price realized for current active patient volumes. Strength in the U.S. price was more than sufficient to offset the headwinds from Germany and foreign exchange. Gross margin for the second quarter was 80%.

Excluding purchases made by Zai Lab, our cost of revenues per active patient per month was down 5% year over year as any impact from broader economic challenges was more than offset by continued proactive work to optimize our supply chain, alongside other cost reduction initiatives. We did not experience a material impact to our cost of revenues from inflation in the second quarter. SG&A expenses for the second quarter totaled $76 million, an increase of 14% year over year. G&A expenses decreased year over year due to lower spending on corporate-enabling functions, while sales and marketing expenses increased to support geographical expansion and early commercial marketing activities as we approach multiple pivotal data readouts.

We invested $57 million in research and development in the second quarter, an increase of 13% from the same period in 2021. R&D dollars are one of our best uses of capital, and we are investing aggressively in projects across our preclinical research, clinical, and product development verticals. Our net loss for the second quarter was $0.23 per share or $24 million. Adjusted EBITDA was $7 million, and we finished the period with $949 million in cash and short-term investments on the balance sheet.

We believe our cash position ensures we can pursue growth opportunities across the business with maximum flexibility. NovoCure's financial foundation is strong and our commercial execution is secure and stable. We will continue investing aggressively in the Tumor Treating Fields platform so that we are prepared to fully leverage the outcome of multiple pivotal trials and potential subsequent launches in the coming quarters. With that, I will pass the call to Asaf.

Asaf Danziger -- Chief Executive Officer

Thank you, Ashley. This quarter, we continued to advance our mission of extending survival in some of the most aggressive forms of cancer. Our commercial team is focused on driving adoption of TTFields. We see mounting clinical support for our therapy, both from internal and external researchers.

As we approach readouts from several pivotal studies over the next year, we are motivated by the prospect of treating many thousands more patients in the near future. I would like to thank my NovoCure colleagues for their passion and determination in advancing the science and adoption of TTFields. We have made immense strides in recent years but we have only just begun our journey. I know as we move forward, you will all keep our patient-forward mission in your hearts and minds.

To close, I would like to share a patient's story. In 2019, DJ Stewart was an average skateboarder who spent his free time surrounded by family and friends. DJ who set to start a new job, had just become engaged and bought a house in Kansas City. In May of 2019, DJ had a seizure and was rushed to University of Kansas Medical Center, where he was diagnosed with GBM and prescribed Optune.

DJ's GBM journey is the focus of the documentary RARE ENOUGH. I encourage all of you to watch this short film. RARE ENOUGH takes you through DJ's diagnosis and treatment and includes candid reflections on his GBM journey, which are both heartbreaking and inspirational. DJ recently joined Head for the Cure, a charity focused on inspiring hope in the brain cancer community.

It is patients like DJ that drive our company forward every day. With that, I will now turn the call over to the operator for Q&A.

Questions & Answers:

Operator

[Operator instructions] Our first question comes from Cory Kasimov with J.P. Morgan. Your line is open.

Cory Kasimov -- J.P. Morgan -- Analyst

Hey. Good morning, guys. Thanks for taking the questions. I had two for you.

First, on the commercial side, I believe you previously guided to 2% to 5% active patient growth for fiscal year '22. Are you still confident in that number? And if so, what do you expect to be the primary driver of reacceleration in the second half? And then secondly, on the clinical side, just in terms of next steps for gastric cancer, any comments yet on what a pivotal trial might look like and the breadth of it? Would you be looking to target just HER2-positive patients? Or do you have a broader strategy for this indication in mind?

Bill Doyle -- Executive Chairman

This is Bill. I was going to just start by saying our team has gathered virtually today from points all over the world. So I'm going to be a little bit of the MC, and I'm going to turn it over to Ashley to take your first question, and then Uri will talk about the gastric trial.

Ashley Cordova -- Chief Financial Officer

Perfect. Thanks, Cory. So just to keep ex Germany, our active patient growth year over year was 3%. Asian and other European markets remain strong.

And we're focused, as we've talked about, on a variety of commercial drivers in the U.S. But given the abrupt fluctuation in German active patient volumes, we are not providing forward-looking cover. It's just we don't have a clear enough line of sight as to the pace of recovery in Germany to reiterate that 2% and 5%.

Cory Kasimov -- J.P. Morgan -- Analyst

Yes. That's great. And then on the gastric side?

Uri Weinberg -- Chief Science Officer

On the gastric side, so yes, 31 was our first study in gastric cancer, which has a high incidence, especially in Asia, of course. But each incidents are anticipated to rise also in the U.S. And the study was designed for patients with unresectable disease who received their first-line therapy concomitantly with TTFields to the abdominal region. And beyond the very strong signal of efficacy, which the study provided, we're always encouraged by the fact that we have another evidence supporting the broad applicability of TTFields in yet another malignancy.

So we certainly anticipate the Phase 3 study in the coming time. And we are considering the design of the study, given the fact that nivolumab has demonstrated efficacy in this malignancy through the CheckMate-649 study, and we are seriously considering having another study incorporating immune checkpoint inhibitors in another malignancy going to be the sixth or seventh study to involve immune checkpoint inhibitors with Tumor Treating Fields.

Cory Kasimov -- J.P. Morgan -- Analyst

OK. That's helpful. Thank you.

Operator

Our next question comes from Jason Bednar with Piper Sandler. Your line is open.

Jason Bednar -- Piper Sandler -- Analyst

Hey. Good morning. Thanks for taking the questions here. I wanted to start with the Lunar update.

It really sounds like just entirely wanting to make sure that top-line data gets as much attention as possible and isn't it all related to data issues or data collection. But if I can push you a little bit and just to be a little blunt, if this is just top-line data, not the full data set comparing all the different arms of the study? Does the timing of the headline data really matter? And maybe you can talk about what changed in your view to drive the shift in timing that's been in place now for several months?

Bill Doyle -- Executive Chairman

Yes. So thanks for the question. I want to underline what I said in the prepared remarks that this slight shift has nothing to do with any trial issues or operational issues. We heard loud and clear from essentially all of our constituents that any data announcement between Christmas and New Year just was not desirable.

And so this is purely for the convenience of our stakeholders to push this into early Q1.

Jason Bednar -- Piper Sandler -- Analyst

OK. All right. Understood. I guess I'll squeeze two in here and a follow-up.

First is just an easy, quick housekeeping item. Ashley, on the revenue side, can you size the previously denied Medicare claims that you referenced? What impact was that in the second quarter? And then maybe a bigger picture on Germany. Maybe expand on what's changed more specifically with respect to the reimbursement dynamics in that market and the coverage dynamics. Is it just newly diagnosed patients that are being treated and covered and it's the recurrent GBM patients that are no longer covered by some payers? Just what shifted in those coverage dynamics that you alluded to? And then for the active patients that are now being denied therapy in care, can those come back into the fold, these treated patients? It doesn't sound like they can just from the way you answered Cory's question.

But I guess, really just what's the best way to think of the current active patient figure in Germany with respect to the run rate here going forward?

Ashley Cordova -- Chief Financial Officer

Yes. Thanks, Jason. I appreciate the question because it is important for everybody to understand these puts and takes. So I'll start with the U.S.

strength, which is a bit of an easier story, right? So we anchored everybody, I'll remind you, to the Q4 2021 price as a stable and durable price. So if we look at the tailwinds versus that price in the U.S. in the second quarter, I would put about two-thirds of it to aged and previously denied claims and about one-third to the strength in the fundamental business. So that's how I put it out relative to Q4 of last year, which is a good baseline.

So then if we shift over to Germany, let me -- I'll spend a bit more time on this question because I know it's new this quarter and important for everybody to understand. If we take a step back, I'll just remind everybody that we've been working purposefully toward coverage and pricing in Germany, be an established reimbursement pathway for years now. This is important because having coverage and contracts with major payers in Germany will enable price stability and a strong pricing foundation as we pursue reimbursement in other European markets and in Germany and other indications. Similar to Medicare, this is a significant milestone as we are the first life-saving -- life-extending oncologic therapy to seek a DME listing in Germany.

So if we look at the milestones along the way, in March 2020, the GBA issued a directive mandating coverage for Optune in line with the EF-14 protocol. In Q4 of last year, we announced that we had reached agreement on a price for Optune with the largest German payers. And then importantly, earlier this year, we now have official DME listing. And as of the end of the quarter, we have formalized contract terms with payers representing 70% of covered lives in Germany.

So that's the background context. But then when we look at what specifically happened in the quarter, prior to the DME listing, many of our payers were approving Optune on a case-by-case basis, and they were not confirming coverage criteria in line with the EF-14 protocol. With this newly established DME listing, we had many payers withhold approval for new patients and begin to the value approval for existing [Inaudible] patients if they did not cleanly match the EF-14 protocol and that did represent a material portion of our existing active patient business. We did not take any of those patients off therapy, of course, but we adjusted our process in Germany during the second quarter to ensure compliance with the DME criteria prior to a patient start.

But given the recurring revenue stream we have and the duration of therapy, which can extend a year or more, we now have a challenging patient mix as less than 15% of our active patients started under this new coverage review process. And as a result, we have both the updated price but also a lower portion of our active patients covered under the new terms. So that's the background in the quarter. But just looking ahead now, we have clear line of sight to which patients will be approved.

We have established DME policy. We have established payer terms. We've adjusted all of our processes to ensure compliance with these. And I do expect that the patient starts and the patient mix will improve each quarter from here and revenue will return over time.

But this will play out over the course of several quarters just given the duration of therapy that we have. That was a long-winded answer, Jason, but I think important to kind of walk through. So happy to take any questions if additional clarification is necessary.

Jason Bednar -- Piper Sandler -- Analyst

Yeah. Now I'll head back to queue. That was very helpful, Ashley and we can follow up with others. Thank you.

Ashley Cordova -- Chief Financial Officer

Perfect. Thanks.

Operator

Our next question comes from Greg Fraser with Truist. Your line is open.

Greg Fraser -- Truist Securities -- Analyst

Good morning, folks. Thanks for taking the question. Ashley, can you talk about what's driving the higher prices in the U.S.? And how should we think about net revenue per month in the U.S. going forward? I think your comments that you made were on a global basis, but if you could provide some color on the U.S., that would be helpful.

Ashley Cordova -- Chief Financial Officer

Yeah. Again, thanks for the question, Greg. So if we look at the U.S. strength in price, it comes from two primary buckets.

One is success on previously denied in NPL claims. This is about two-thirds of the strength in that U.S. price, if you look versus the Q4 2021 baseline, which is our anchor price. And about the remaining third comes from fundamental improvements in expanding coverage policies at the margin and just price negotiations with additional contract players over time.

So I would say one-third of it is durable and really related to just ongoing market access work and two-thirds is really the performance of our U.S. revenue operations teams as we continue to go after those aged claims that we have in the pipeline. I will remind everybody that the predictability of those aged claims is not high. And so I wouldn't -- when we look ahead, I would think on the enduring improvements and not the aged claims.

Greg Fraser -- Truist Securities -- Analyst

Understood. On Japan, prescriptions declined, although you added patient number group. Can you talk about demand trends that you're seeing there? And are [Inaudible] headwinds to prescribe you in Japan?

Bill Doyle -- Executive Chairman

Go ahead, Pritesh.

Pritesh Shah -- Chief Commercial Officer

Thank you, Bill. Greg, thanks for the question. So the short answer is we're not seeing any new headwinds. I would say that's just the cyclical nature of how we see within a rare disease like GBM prescriptions flow through.

So we would expect just based on the historical performance in Japan, the strength of our data, and our ongoing efforts there, the business will continue to be stable in Japan.

Greg Fraser -- Truist Securities -- Analyst

Got it. Thanks for taking the questions.

Operator

Our next question comes from Emily Bodnar with H.C. Wainwright. Your line is open.

Emily Bodnar -- H.C. Wainwright and Company -- Analyst

Hi. Thanks for taking the questions I just have one on your next-generation arrays that you plan to launch later this year in Europe. I guess, what are you looking to see with the initial launch to kind of determine if you want to take that out more broadly? And what would you want to see in order to potentially implement that into the label for Optune? Thanks.

Bill Doyle -- Executive Chairman

Yes. Again, taking a step back with device delivery therapies, the first incarnation of the device is almost never the final incarnation. Improvements can be made through engineering to optimize the usability and the therapeutic benefit. You can think of almost any medical technology, and we can see the progression.

We believe we're in the earlier innings in terms of the form factor and the ability of our device to help patients. And the next major step forward is with the new arrays that we anticipate to launch in Europe later this year. What we're looking for really is to test all of our systems. This is a major change in form factor.

So we have to update all of our manufacturing capability so that we can serve all of our markets. We are going to look to patient user factors to make sure that we have the right instructions for use and that our people are well trained to bring this new therapy to patients. And we always look for surprises. We don't anticipate any, but that's the nature of the word surprise.

They're not anticipated. And if we do see something that's surprising, we can take whatever steps are needed in instructions for use or in manufacturing to overcome whatever the surprise may be. So I can't overstate how excited I am about this development. And as soon as we get the experience from the initial launch, we'll incorporate that into our regulatory plans throughout the world.

Emily Bodnar -- H.C. Wainwright and Company -- Analyst

OK. Thank you.

Operator

Our next question comes from Jason Wittes with Loop Capital. Your line is open.

Jason Wittes -- Loop Capital Markets -- Analyst

Hi. Thanks for taking the questions. Maybe just first a clarification on the U.S. strength and the denied claims.

Was that all Medicare? Was that a mix of Medicare and private? Or could you give some indication of where those denied claims that were permitted came from?

Ashley Cordova -- Chief Financial Officer

It's a mix, but it's largely Medicare. That's where our largest opportunity is, in the backlog.

Jason Wittes -- Loop Capital Markets -- Analyst

Great. That's fair. And on the Merck trial for GBM with checkpoint inhibitors, as you mentioned, checkpoint inhibitors have not been effective for GBM. I take it there's evidence that they do pass the blood-brain barrier and they are present around the tumor.

Is that the right assumption?

Bill Doyle -- Executive Chairman

Uri, do you want to just give a little background on our work with checkpoint inhibitors in the brain?

Uri Weinberg -- Chief Science Officer

Yes. Of course. So as you remember, there is a growing level of evidence demonstrating that concomitant use of tumor treating cells and immune checkpoint inhibitors actually leads to greater inflammatory antitumor reaction against the tumor. And this has been demonstrated throughout the work of our own in-house lab, but also through the work of other external collaborators, one of which is Dr.

David Tran from the University of Florida and this publication that JCI really showed how you could potentially achieve to make immune response with later adaptive immune response with the generation of memory response against the cancer. So that's on the scientific preclinical side. But at the same time, there is more and more evidence that on the clinical side, we see that effect and one such preliminary evidence is coming from the 2-THE-TOP study where the concomitant use of Keytruda, pembrolizumab with TTFields led to a significant increase in median overall survival. This was a single -- this is a single-arm study, but concomitant matched control comparison already showed that while the 2-THE-TOP study population achieved a median overall survival of 25.2 months, on EF-14 matched controls, it was about 10 months less so than incorporation of new checkpoint inhibitors to Optune in the intended use or a good indication led to a significant improvement.

So it's true that immune checkpoint inhibitors have unfortunately failed to demonstrate the efficacy in newly diagnosed and recurrent GBM, but it seems that there are potential penetration across the blood-brain barrier, be it lower or decreased, still results in a very significant immune response and leads to a clear clinical benefit coming from this study. And that is the basis for the planned Keynote D58, our second clinical collaboration with Merck with MSD. The first was in non-small cell lung cancer. And we are looking forward to conducting this Phase 3 pivotal study.

Jason Wittes -- Loop Capital Markets -- Analyst

OK. Great. That was very helpful. And also, I think I heard correctly that you mentioned for the gastric trial that you did look at genetic differences.

Is that something that may lead to future screening for potential patients for TTF? Or could you expand upon kind of what the indications were when you looked at that criteria?

Asaf Danziger -- Chief Executive Officer

So the EF-31 gastric study was a small single-arm study for about 25 patients. And we did not take the opportunity to look into genetic variations in this patient population because of the preliminary nature of the study design and the number of patients included in the study. And despite the fact that we see this especially in GBM to date, of course, that TTFields is effective in really broad patient population. And as you recall, in EF-14, we broke it down to different subpopulations, whether it's MGMT promoter, methylated or unmethylated, older patient population, younger patient population.

At the same time, we always try to see if there are subpopulations that could benefit more from TTFields, and we are planning to do this on the immune response front, collecting more data and trying to characterize the immune response and see how it could potentially increase it. And also when it comes to genetic variations and alterations at the level of the tumor itself. And one key project came actually from the post-approval setting and was published in Advances in Neuro-oncology recently demonstrating by independent investigators in the U.S. in several different centers that certain genetic alterations correlate very well with improved outcome in newly diagnosed GBM.

So again, this -- the treatment itself is effective in the broader population, but we are always trying to find biomarkers and other findings that will support the identification of patient population that could generate and even improve the outcome from applying TTFields.

Jason Wittes -- Loop Capital Markets -- Analyst

Thank you very much. I'll jump back in queue.

Operator

Our next question comes from Vijay Kumar with Evercore. Your line is open.

Ashley Cordova -- Chief Financial Officer

Vijay, I don't think we can hear you. Operator, perhaps we go back to the queue. All right. Michelle, we can go back to the queue.

Operator

There are no further questions. I'd like to turn the call back over to Bill Doyle for any further remarks.

Bill Doyle -- Executive Chairman

Thanks, Michelle. I'd like to thank everyone on the line for joining us this morning. I'd also like to join Asaf and extend my thanks to the NovoCure employees who have dialed in. I know I speak for myself, Asaf, and for the entire management team when I say we appreciate the hard work and dedication.

We're very pleased with the progress this quarter. We continue to take deliberate action to strengthen the fundamentals of our business and prepare for the future. The science behind Tumor Treating Fields continues to grow. And in the coming quarters, we will have pivotal data from a number of our late-stage trials.

This is an exciting time at NovoCure, and we look forward to updating you on progress in the coming months. Thanks again.

Operator

[Operator signoff]

Duration: 0 minutes

Call participants:

Ingrid Goldberg -- Vice President, Finance and Investor Relations

Bill Doyle -- Executive Chairman

Ashley Cordova -- Chief Financial Officer

Asaf Danziger -- Chief Executive Officer

Cory Kasimov -- J.P. Morgan -- Analyst

Uri Weinberg -- Chief Science Officer

Jason Bednar -- Piper Sandler -- Analyst

Greg Fraser -- Truist Securities -- Analyst

Pritesh Shah -- Chief Commercial Officer

Emily Bodnar -- H.C. Wainwright and Company -- Analyst

Jason Wittes -- Loop Capital Markets -- Analyst

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