Good morning, everyone. My name is Jessica Fye. I'm a senior biotech analyst at JP Morgan, and we're continuing the 42nd Annual Healthcare Conference today with Novocure. I'm joined by the company's executive chairman, Bill Doyle. He's going to give a presentation on the business, and then we're gonna move into Q&A. If you're in the room and you wanna ask a question, you can raise your hand, someone will bring you a microphone, or you can always submit questions to me on the portal. So with that, let me turn it over to Bill.
Thanks, Jess. Thanks, JP Morgan, and welcome everyone to day three, first thing in the morning. I'd like to introduce Ashley Cordova. Many of you know Ashley, but she's our CFO, and she'll be joining me for the Q&A today. I hear a little bit of feedback. Are we okay? Okay, great. So, first off, I'll be making forward-looking statements. You can find our full disclosure on the investor portal. But let me start with our mission, which remains unchanged. At Novocure, we're working with our patients, and we'll talk about that. Let's see. The slides are not moving forward.
Okay, I'm one behind here, but that's. Now it looks like we're where we wanna be. Okay, I think we're synchronized now. Thank you very much. So, at Novocure, we work together with our patients and our team to extend survival in some of the most difficult to treat cancers, some of the most difficult diagnoses. We do this by developing and deploying our novel platform, Tumor Treating Fields. Just for those of you who are less familiar with Novocure, Tumor Treating Fields is a completely unique cancer-fighting modality. It was invented by Professor Yoram Palti at the Technion about 20 years ago.
What Professor Palti discovered was that while it had been believed that electric fields go around cells and therefore have no effect on the organelles within the cells, if you tune them specifically, those electric fields can enter the cell and push and pull on the organelles, and in fact, cause cancer cell death. So we tune electric fields to specific cancer types, and I always like putting these little videos up because this sounds so incredible, but, you know, seeing is believing. So on the panel on the left, this is normal cell division.
You can see the chromosomes divide, the daughter cells form, and this is how one cell becomes two, two become four. But in the panel on the right, when that same cell is exposed to, again, an appropriately tuned electric field, so that electric field enters the cell, you now see that the mitosis cannot happen normally, and the cell literally explodes. We deliver our therapy to patients via a wearable medical device. So this is another difference. We do clinical trials like a biotech company, but our therapy does not come in a pill or a bottle or a bag.
It is delivered through this device. There are two components. The first is a reusable box. The current version weighs about two pounds, that the patient carries, and then it is connected to disposable patches, and the patches are placed on the skin in the region of the tumor. These patches are replaced about every 3 days by the patient, and this allows the patient to get continuous at-home therapy. I said that we work together with our patients. Our business model works in this way: We receive the script directly from the prescribing oncologist.
Sometimes that's a medical oncologist, sometimes it's a radiation oncologist, and then our team delivers this system to the patient's home, trains the patient, and then we bill the payer per month of therapy. So it's a unique mechanism of action, it's a unique delivery system, and it's a unique payment model that we've built. Our strategy at Novocure has remained unchanged for 10 years. It's based on three pillars. First and foremost is to drive commercial adoption in the indications where we have approval.
Secondly, because this is a platform, we're focused on clinical trials to expand the number of indications and the number of patients that we can treat. And then finally, as I mentioned, because this is a device-based therapy, we have the opportunity to continue to improve the technology. This allows us to improve the efficacy, improve the comfort, improve the ease of use. A corollary of this is that we continue to file patents as we make the improvement. This whole strategy rests on a very substantial intellectual property platform that effectively creates an IP moat in the important geographies, Europe, Japan, and the US.
Notwithstanding, you know, tremendous macro headwinds in 2023, at Novocure, we made significant accomplishments in working toward our strategic objectives. Again, in terms of driving commercial adoption, we're very pleased at the end of this year to reach the milestone of having now treated over 30,000 patients commercially. That's principally GBM patients, but that's just a tremendous effect that we've been able to have on these patients and their families. We were also very pleased to continue to expand our geographic footprint.
Our big markets going into the year were Japan, Germany, and the U.S. We added France and achieved reimbursement in France. Our launch was extremely successful, quite frankly, the best launch that we've had in any geography to date. We're starting to earn meaningful revenue from France, and we expect that to continue to grow. Our France launch is really going to be a blueprint for us, and it represented sort of the culmination of all the things that we've learned to date.
Importantly, and this goes back to expanding the commercial footprint, we also, I'll talk about this a little more, but we were very pleased to submit our regulatory filings in Europe, U.S., and Japan for the non-small cell lung cancer indication. For any of you who have done this kind of work, you know how difficult it is to take data and actually turn it into a regulatory submission. I'll show you a timeline in a minute, but we expect approvals this year, and we will commence launch as soon as we receive those approvals. In terms of advancing the clinical pipeline, it was also a year full of accomplishment.
We published the phase III data in second-line non-small cell lung cancer. We're pleased to publish that in Lancet Oncology mid-year. We finished the enrollment in our METIS trial. METIS is the trial for brain metastases from non-small cell lung cancer. We also finished enrollment in PANOVA-3. PANOVA-3 is the trial in first-line locally advanced pancreatic cancer. This is new news that we announced yesterday, but we've also completed enrollment in our TRIDENT trial. TRIDENT trial is back to GBM, but this is a trial that is studying using Tumor Treating Fields earlier in the patient journey with radiation rather than waiting until after radiation.
There's significant reasons to believe that this will extend survival by starting the therapy earlier. Then finally, in terms of delivering product innovation, also a big year. I've talked previously about our arrays. The arrays are the component that attach to the patient's body and actually deliver the energy. We've been working for many years on our next generation, I will say cleverly named our new array. The new array is lighter, more flexible, easier to use, more comfortable. We received CE mark early in 2023. We did a pilot launch in Austria and Sweden.
The launch went as well as it could have gone. We're just starting to see year data in Austria, and all the things that we had hoped for are proving to be true in the field. First and foremost, the patients are reporting a markedly improved experience receiving the therapy. With the success of that pilot, we've now launched throughout Europe. Then finally, we have back to FDA filings, we've completed, in this case, a PMA supplement filing in the U.S. With a little FDA luck, we expect to be launching in the U.S. mid-year. Now on to the future here.
We went through a major exercise in the company to sharpen our focus going into 2024, and our focus is really geared to three key activities. We intend, and we expect, and we believe we can continue to grow GBM. I'll talk about this a little bit, but we have been flat in our established markets for the last couple of years. But we think there is significant opportunity to grow that base business, and we'll launch lung. As I said, we expect regulatory approval in Europe first half of the year, in the U.S. early second half of the year. We're preparing for that launch.
Then finally, we continue to work to deliver our pipeline. Let me touch on each of these. I want to remind everybody that one of the real differentiators at Novocure, compared to, you know, many clinical stage biotech companies, is that we have an established, profitable business in GBM. The business today is over $500 million. It's based on an NCCN Category 1 recommendation in the treatment of first-line glioblastoma. It really is built on the only progress that's been made in this field in decades.
We're reimbursed in all of our key markets, and as I said, we ended the year with a record number of patients on therapy, close to 4,000, but only penetrated 30%-40% in those markets, and that's where the opportunity comes. We built this business on this clinical trial, and again, for those of you who have been following us, you'll recognize the EF-14 clinical trial. In this clinical trial, we showed a meaningful increase in the median survival. But from a patient's perspective, what's really important, and when we talk to patients, you know, medians, what does that really mean? They wanna know, "How's my long-term survival?"
And in this case, we now have the data. The 5-year survival is almost triple in this trial from 5%-13%, with nearly half of the patients alive at 2 years. But as impressive as this was, and again, this led to the regulatory approvals and the reimbursement, we now have real-world evidence. The quality of the real-world evidence that's available to all companies, but to us as well, is really markedly different than you know was available, say, a decade ago. So what I'm showing here is data that we've purchased, which is every single patient that was placed on Optune in the U.S. in the second half of 2019.
I picked 2019 because I wanted to get out, you know, show patients with 4-year data. These patients are not showing 13% survival. In the real world, they're showing close to 25% of the patients, and this compares to without Optune, survivals in the low single digits. So these are new data. This is the first time this has been shown. We're working to get this in publication form so that we can, use it, with our prescribers. And I'll note the other number on this page. Many of our patients today start the therapy, and they continue until they progress.
But some patients, and this has been our recommendation, continue the therapy through progression. For those patients, it's not 24% four-year survival, it's over 30%. So we're approaching a third of the patients who are long-term survivors when they use Optune, through their patient journey. And this is before some of the new things that we're doing. Again, I mentioned TRIDENT, bringing the therapy earlier. We've talked previously about, and I'll mention, trials that are ongoing, combining with immunotherapy, all which promise to move that 31% even higher in this terrible disease.
So now on to lung. We presented these data at ASCO, back to another extremely difficult to treat condition. These are in patients that have failed a platinum-based chemo plus standard of care in the first line, so they're now on to the second line. This is really the first progress since the original Keytruda, KEYNOTE-010 trial. And again, you see the data. Significant improvement in the median and a very important improvement in the tail with this data. And these data are now submitted in Europe to the FDA and in Japan.
Now, one of the things and I wanna address this head-on that has been raised about these data has been, "Okay, this is, you know, really important, but does it matter, given that you've shown really important advance, particularly when you're combining with immunotherapy, but that immunotherapy has now moved to the first line? Will it be used? Will our therapy be used?" And our answer is we believe, and we believe, based on the conversations that we've initiated with prescribers, that we have an opportunity that's at least twice as large as our GBM opportunity in non-small cell lung cancer.
There are approximately 114,000 patients in this category, Stage Four metastatic disease. 60% of those will receive platinum-based chemotherapy, and of those, the vast majority will progress, and about half will seek therapy in the second line. This gives us this 30,000 patient target for whom doctors have nothing, essentially. They have old chemotherapies, and that's it. And so when we have the discussion, our therapy with no toxicity is something that, again, we believe many of these patients will seek as a means to extend their survivals. So where are we in the path?
There's a lot of checked boxes here. This again is a slide that we've used many times. I've talked about the clinical data. It's published. We've presented not only at ASCO, but subsets of data at all the big lung conferences during the year. Big accomplishment from the regulatory perspective, everything's in, and we're now in the discussions leading to approval and labeling. Unlike GBM, when we were a small company, and we basically started our launch activities after approval because we had to, here, we have a full team that's focused on launch.
We have education campaigns about Tumor Treating Fields in this new prescriber base that are up and running. DTC campaigns will follow, to get to the patients and the KOL engagement. The ad boards are important and ongoing. Then finally, going to expanding the pipeline. We expect 2024 to be a very big year. I mentioned we've completed the enrollments of METIS and PANOVA-3, so we're now on the clock, counting down till the time from last patient in. We expect the METIS data in brain mets from non-small cell lung cancer at the very end of this quarter, and the pancreatic cancer data toward the very end of the year.
So two new phase III data sets. And then I mentioned TRIDENT. TRIDENT will be a 2026 readout. That's a two-year follow-up, so we continue. And of course, that's not the end. We have taken a very close look at our pipeline, and, you know, one of the, you know, the opportunities and challenges when you have a platform technology that can be deployed against, you know, many, many difficult to treat tumors. We do have to pick and choose and focus, and our focus is on the indications where we have proof.
So in GBM, I mentioned TRIDENT, followed by KEYNOTE-D58, which is the registrational trial combining Tumor Treating Fields and pembro immunotherapy. In thoracic, I mentioned the METIS trial. We have also started recruiting LUNAR-2 in first-line, again, with immunotherapy. And PANOVA-3 is followed in phase II already by PANOVA-4. This is our partnership with Roche, combining immunotherapy with Tumor Treating Fields and pancreatic cancer. So it's robust, but it's focused on these key indications.
And so just to end the prepared remarks here, you may have seen an announcement that we undertook a reorganization at the end of the year. We believe this is what responsible management teams must do. We took a very close look at our organization. We, quite frankly, eliminated some fat that had grown in the middle, that was not directed at the key objectives that I've outlined. And we've reorganized the operations so that, again, to grow GBM, we now have a franchise with full span of control of all activities, generating prescriptions, getting patients on therapy, and then working with them to get the maximum benefit from that therapy.
And this has allowed focused investment. So the GBM business is profitable, but we continue to invest for growth, but we're investing for growth in our non-small cell lung cancer launch and in the clinical trials that I described in GBM, in lung cancer, and in pancreatic cancer. All of this leading to a path to profitability here in the, in the foreseeable future. So I'm gonna end on, on one last slide here. It's going to be a big year. We have METIS data coming, lung approvals that we expect and launch in all of the key markets, and then at the end of the year, the pancreatic cancer data.
All of this built on this foundation that we will continue to report out this profitable business that we're focused on growing in GBM. So with that, I will end the prepared remarks. Jess, and we'll join Ashley, and I'm delighted to answer any questions that you may have.
Great. Thanks for the presentation. You know, heading into this launch in lung cancer, can you just elaborate on kind of how you're gearing up to launch in lung? And maybe elaborate a little more on your commercial expectations for Tumor Treating Fields in that setting.
Sure. So let's... Let me have Ashley answer the question.
Great. Thank you. I appreciate it. So we'll start in Europe. We've already submitted, we noted this CE mark last year in June, so we would expect Europe to launch in the front half of this year. We'll launch first in Germany, and that's because we have a path to a named patient reimbursement in Germany. Our focus will be on the right patient, meaning they're on-label, they have metastatic non-small cell lung cancer, they have progressed post platinum. Those are the patients for whom we think we will eventually get paid, and we're gonna be really focused on a positive first patient experience.
So demand is always important. We will be generating demand across a field force that is ramped up and ready to go, but it's not kind of scattershot demand. We really want to make sure that the medical oncology community understands the right patient, the right time, and is generating a positive first experience, which will turn into a virtuous cycle, as we, you know, move through further adoption. We'll then repeat that process in the U.S. Again, the expectation is, now with the FDA submission in December, that we would have approval in the back half of next year. We will be hiring up a field team.
This year. This year.
Thank you. That's right, we're in 2024. It is in the back half of 2024.
Yeah.
We will be hiring up a field team over the course of the next couple of months. We have the key leaders already in place, and we'll be launching, you know, soon, this year.
When we're looking towards that approval in lung, you know, one of the questions we've gotten from investors is around the trial design and then kind of evolution of the treatment paradigm over the past several years. Do you anticipate any pushback from regulators related to the trial design and that kind of shifting paradigm?
Yes. So we've definitely received that question, and I think it comes from maybe a misunderstanding about how the regulatory process works compared to the physician prescription process. So the FDA is going to look at the data, and we will develop a label with them based on the data. We expect that label to be consistent with the trial design and our achievement of the primary endpoint. And just to remind everyone, the primary endpoint is Tumor Treating Fields plus standard of care, either chemotherapy or immunotherapy, after a platinum failure.
That's the FDA process. The second question, and this is so we don't expect pushback from the FDA with respect to the trial results of the data. The second question is, given that Keytruda has moved from the second line to the first line, will doctors prescribe it? That's not a regulatory question, that's a commercial question. And as I said, our belief is that there. First of all, there's nothing for these patients other than old chemotherapies. We have this successful trial outcome. We have no added toxicity to the standard therapies.
And we're being told by doctors they have patients for whom this is appropriate, and they will prescribe. Back to Ashley, we have to ensure that it's a good first experience and that they learn that this doesn't create a burden for them as prescribers. But those are really two separate questions, not the same question. And from the regulatory perspective, we don't believe it'll be an issue.
Okay. So, so maybe kind of on that point, what has the kind of physician or KOL feedback been on the LUNAR data?
So, I'm trying to decide whether I should start or Ashley should start.
Yeah, yeah.
So let me describe the process. So first of all, the thoracic oncologists really don't know much about Tumor Treating Fields at all, right? So, as a baseline. So we have been active in neuro-oncology for the last, you know, since really 2016 in the front line. And so this is a new prescriber group where we really have to start with educating them about Tumor Treating Fields and the mechanism of action. We do that initially in ad boards, where we gather KOLs, you know, 8, 10, 15 together, and we start with a question: Will you prescribe Tumor Treating Fields to your patients?
And almost at the beginning, it's a small number. Then we educate them, we talk to them about the data, and by the end of the hour, we get a completely different answer. We get the answer: We have these patients in our office who are who have failed first line, but are still relatively healthy. They want to make it to the next milestone. They do not want to give up. That's the 50% of the patients. There is another 50% who are, who are, you know, extremely ill and metastatic, who don't seek therapy in the second line.
But that 50% who do seek, they say, "This is a real therapeutic opportunity for those patients," both, by the way, with chemo and with immunotherapy. And, you know, many are talking about this is one term we hear a lot, which is smoldering progression. So it's progressed, but it has yet to explode throughout the body. These are patients that they keep on.
Either they keep on pembro, or they'll switch the immunotherapy, and this has been a patient group that they've said, number one, is growing, and number two, is the perfect patient group for us to add Tumor Treating Fields. So then the bottom line of all that is that clinicians, once with a little education... You know, again, we're not talking about a, you know, a CME course. We're talking about a, you know, an hour, half-hour introduction, identify the patients in their practice for whom this would be appropriate.
Maybe you flashed it up on the slide, but maybe we could spend a little more time on LUNAR-2 and just take us through how it differs from the original LUNAR trial, and maybe touch on kind of enrollment?
So it's first line. That's the takeaway. So it takes the LUNAR protocol in combination with IO and moves it front line, right? So it's metastatic non-small cell lung cancer, first line treatment in combination with pembro. That's the LUNAR-2 trial design. We are fully through site opening processes right now, so that enrollment is up and rolling, but we're at the beginning of that phase, and we'll give clear line of sight to final data once we have kind of enrollment at a tick that we can predict.
And we believe this is the natural progression, right? We have these great data in second, third line, and that's where, you know, one needs to start in cancer therapy development. But this therapy, with no toxicity that shows this tremendous synergy with IO, belongs in the first line. I mean, one thing, you know, that has been pointed out to me, our data in the second line is as good as the pembro data alone in the first line. You know, so that gives you some perspective on the additive benefit of combining these two therapies.
I guess just sticking with that for a minute, I'm sure you want to kind of get to that data as quickly as possible. Is there anything you can do to kind of speed enrollment for that trial?
I mean, everything we can do, we are doing, is the short answer, right? Lung is a competitive enrollment space, so it will have to play out. But we do have another trial, which is the KEYNOTE-B36 trial, which is a phase II trial, also looking at first-line combination with pembro, you know, just the doublet Tumor Treating Fields and pembro. That's a smaller 100-patient trial that will read out in the interim. So we'll have an early look on the first-line combo as we're waiting for the LUNAR-2 data with the KEYNOTE-B36.
Got it.
And of course, that's precisely designed to provide these data faster than we can do a full, you know, randomized trial.
Great. If that looks good, then the trial can.
Then we can, you know, again, use that in the appropriate channels to help educate the prescribers.
What about price? As you take TTF into lung, should we think about a similar price to GBM in the US, in Europe? What's the right framework there?
Yeah, I mean, I think that should be your base expectation, right? We do expect over time, with significant volume increases, these are always rational discussions that we're having with payers in terms of price, volume discount. But our assumption is that in the second-line metastatic non-small cell lung cancer patient population, where GBM pricing is established, we'll be able to anchor to that GBM price.
We can spend a little time on METIS and the brain mets trial. Can you talk about your commercial indication expectation for that indication, and just should we think about a read-through from GBM to brain mets, and kind of why or why not?
Yeah. So, again, just to remind everyone that the METIS trial is treating lung cancer in the brain, basically. So, the brain mets from lung cancer represent the largest single source of brain mets. Various numbers suggest that it's about half of all the diagnoses. And there's really nothing for these patients. Today, if they have a few mets, they will receive stereotactic radiosurgery, so Gamma Knife. You know, the radiation oncology will ablate these mets, but they come back. And once they come back, the only therapy today is watchful waiting.
You know, formerly, they used to use whole brain radiation, but that has ceased to be used because the toxicity of whole brain radiation is so high. So what we've done with METIS is after stereotactic radiosurgery, we add Tumor Treating Fields. So how do we think about it? We've certainly proven in GBM that we can treat cancers in the brain, and we've proven in LUNAR that we can treat non-small cell lung cancer. So now we are aiming to show an improvement in the brain.
Now, I will say that metastases trials. Virtually all the trials that we do, the primary endpoint is overall survival. Metastasis trials, as a rule, overall survival is not the endpoint because of the primary disease, so the endpoint is progression of the mets. So our endpoint is what we call in-field progression of the mets, so progression of the mets in the region that we're treating. These are the results that we, you know, we expect at the end of the quarter. Now, you asked about commercial potential. So here, this is a very large patient population.
However, it's a very heterogeneous patient population. So if I go back to GBM or, you know, as we approach pancreatic cancer, these are patient populations where in the first line, everybody seeks treatment. And with our ability to extend survival with no effect on quality of life, we are working to very high adoption percentages. The brain mets population consists of a much broader range of, if you will, levels of sickness, right? Some people are very, very, very sick and will not seek therapy. Other people are quite healthy.
They have a brain met, there's nothing they can do about it. So while it's a large patient population, and we would expect significant numbers compared to GBM because it's large, we wouldn't expect as high a percentage penetration. So what does that all mean? I think it's an opportunity that's certainly as big as GBM, but not as big as lung, probably, if I were to put it between the two.
Okay, so larger patient population, lower penetration, maybe ballpark similar to GBM?
That's a guess.
Yeah. But that it will drive.
Yeah. We need to see the data, and we need to... But those are the large patient population and very heterogeneous. Those are the two questions or issues in that indication.
The other big readout this year is the PANOVA trial, right?
Yes.
I think you said it's at the very end of the year?
Yes.
What gives you confidence in a successful readout there?
So, let me describe why. First of all, pancreatic cancer is another cancer that is just a terrible prognosis, right? So, and we know that the chemotherapies that are used are the same chemotherapies that have been used for decades, you know, gemcitabine and FOLFIRINOX. And they've shown a modest life extension with tremendous toxicity, you know, particularly FOLFIRINOX. In this trial, because it's so dire, we were able to start in the first line.
So I mentioned before, in lung, you know, you start in the third line, second line, work your way up to the first line. So the PANOVA trial is in first line pancreatic cancer, and these patients are typically diagnosed in two groups. One group, where it's so-called locally advanced. It's still spread within the abdominal cavity, but it hasn't spread to the bones and, you know, full. And then there is that second group, that's full metastatic disease. PANOVA-3 is treating the locally advanced cohort in the first line.
So if we had to design this trial today, based on everything that we've learned during the recruitment, we would design this exact same trial. So, you know, the reason that, you know, we're optimistic here is because it's first line, the patients are healthier, and we're treating the full extent of the disease with our therapy.
Maybe coming back around to GBM, the kinda commercial side, the existing commercial business. You mentioned the penetration. What can you do to kinda drive that penetration higher?
So I wish there were a magic bullet, right? You know, again, we have the only successful trial in the last 40 phase III trials. We have NCCN Category 1 guidance. You know, we're published in JAMA. There are now not just one publication, but literally thousands of support publications, including the real-world evidence that I showed here. But many centers now have five-year experience, and all of these papers with five-year data are all supporting what we've seen.
So, you know, so the notion that, gee, we don't know what the mechanism of action is, or maybe the trial was a fluke, absolutely not. It's completely supported by... and, and in fact, in almost all cases, exceeded by the data that we're seeing in the field. So for us, we have to get this message to patients, I think, number one, so patients come in asking for Tumor Treating Fields. We have to continue to remind oncologists how easy this is to prescribe. Where we under index is in the academic centers.
These are the centers that are very focused on clinical trials, and, you know, their first response, if they have a patient, is to get them into one of their clinical trials. We have to make sure that Tumor Treating Fields are in the backbones of these clinical trials. I think where we've seen a lot of new excitement is in the combination with immunotherapy. There is really good phase II data that has been developed and published. There's tremendous interest in the clinical trial that we're currently running. I would say, you know, that's... We don't talk about recruitment, but that's a smooth-running trial.
Yeah, it's in the regulatory.
Yeah.
Okay.
But in terms of the centers that are... You know, we just came from the Society for Neuro-Oncology. We had more meetings than we've ever had at any meeting, and you know, there's tremendous interest in being a part of that trial. So this is... As I said, there's not a silver bullet. And then on the organization side, you know, we've learned some things organizationally. You know, we have a new leader of our commercial business, we have a new leader in the U.S., and we've given those leaders full span of control, as I said before, from sales, if you will, to medical education to patient support, is all now under one organization.
And we grow when we get more scripts. We grow when we convert more of those scripts to active patients, and because of our business model, we grow when those patients live longer. And so now we come back to the new arrays, which make it more comfortable, easier to use, longer duration of therapy, better results. All of those things roll up into revenue for us, based on our business model.
Great. We're out of time, so we're gonna stop there. Thank you.
All right. Jess, thank you very much, and thanks, everyone.