Good afternoon, I'm Jason Bednar. I cover med tech here at Piper. Next fireside chat is with Novocure. Very happy to have with us today, Executive Chairman Bill Doyle, and CFO Ashley Cordova. Thanks a lot for being here, both of you. Really appreciate it. So why don't we get right into Q&A? You know, a lot going on with the business right now. We did just. I first wanted to touch on really the latest news. We had a press release yesterday, 8-K, discussing a fairly large restructure. I think the first that I can recall for the business. Some headcount reductions. I think it looks to me like maybe just some good corporate hygiene. I don't...
Maybe that's insensitive, but, you know, really trying to prepare the business for that, you know, that next stage of growth. So I don't want to put words in your mouth, but how did you come to the kind of conclusion that now is the right time to restructure? And, you know, how did you settle on, you know, the, I guess, the parameters you did that are involved in the restructuring?
Yeah. So, you know, neither Ashley nor I want to be insensitive about this either. But I think this is really an obligation of leadership of companies to, on a regular basis, take a look at what's going on in our markets and in the outside world. And at the same time, take very hard looks at the internal structure of the company, the employee makeup, and really revisit the priorities of the company. And that's exactly what we've done. Our focus was to maintain and really double down on our priorities to drive growth in the near and mid-term. And at the same time, look at opportunities in the longer term, and make decisions about where we invest.
I mean, we're in a very privileged position at Novocure. One, that we have a very stable business in GBM that throws off cash, that we have the opportunity to invest in a very robust platform that has, you know, in some ways, more opportunities to advance than, quite frankly, we can fund responsibly right now. In an era where capital was essentially free, we had more latitude to pursue more programs simultaneously. Those days are over, right? At least for the time being. And so we wanted to focus our activities on this near and medium term. And I think I'm going to turn it over to Ashley to describe exactly the strategic priorities that we're investing in.
Yeah, great. And I mean, we outlined this all in the press release, but-
Yeah.
What we effectively did was take $60 million out of what we call our residual operating income. That's kind of the day, and then we're turning around and investing that right into the business, which is lung launch, right? We're preparing to launch lung in multiple geographies. It's also data readiness for our metastatic pancreatic trials, which we'll read out next year. And then it's continuing to fund increasing investments in the pipeline, and we focus that pipeline on GBM, lung, and again, additional data readouts, which are indications where we have established efficacy, and we have line of sight to the ability to go earlier to larger patient combination IO. So I would expect our burn rate to be consistent year-over-year, next year, and our total OpEx to be roughly in line.
What this enables us to do is to invest in tomorrow without increasing the OpEx burn.
Okay. All right. Perfect. Yeah, and I think that was all pretty clear, but I appreciate all the, the color here. Why don't we go to probably your favorite topic, everyone's favorite topic, we'll go to LUNAR. You know, what's... Refresh us on where you stand in the process, the regulatory approval process for non-small cell lung, you know, over in Europe and all, as well as, you know, prepping for a PMA submission here in the U.S., as well as a possible panel with the FDA.
Sure. So, you know, for those of you who are newer to our story, LUNAR is a shortcut word for our focus in non-small cell lung cancer. So in June, we reported data from a Phase III trial in metastatic non-small cell lung cancer for patients after platinum failure. And those data we presented at ASCO, they were published in Lancet Oncology, so now peer-reviewed, and we are in the regulatory process. The regulatory process in Europe is the CE process, and we announced earlier this year that we have completed that submission, and we are now in the process of working towards labeling and final approval. In the United States, we are under the PMA framework, so this will be a new PMA submitted to the FDA.
This submission is a what they call a modular submission, so it doesn't go in all at once, it goes in pieces. We have submitted the first three pieces to the FDA, and the interactions on those pieces are underway, and we are on track to submit the final piece, the final module by the end of the year. So, very shortly now. We expect, and it's always impossible to determine with precision these regulatory processes, but we would expect the first approval to come in Europe, and we're saying mid-next year, and that would be followed by the approval in the U.S. that we would expect later, you know, sometime in the second half of next year. And while we haven't mentioned it, we're also preparing the submission in Japan.
And that will go in after, sometime after the FDA submission, and then we would expect approval in Japan in due course as well. We are preparing for success here because we know the data, we know the process. We don't know the timing precisely, but we're preparing to launch, and we will launch first in Germany, second, likely, in the U.S., and then followed by Germany. And again, with some regulatory process luck, Germany will come first mid-next year and followed by U.S. later in the year, and it's still a little too early to say exactly when it will happen in Japan.
Okay. Germany, Germany, US, Japan. Yep. Okay. And then on... In Germany, 'cause there's, there's a lot of, just a Germany issue, but there's a big question out there from the investment community of, will clinicians use it? Will patients fit into the label? Will there be any exceptions to that label based on what we saw in the data and how the trial was designed? So, I guess, how do you feel about kind of some of those questions as we sit here today? You know, what do you think that label is actually going to look like? And do you think payers are going... Sorry, payers. Will clinicians actually put those patients and payers pay for those patients, you know, within that are actually fall within that label?
Sure. So that's a big question...
Right. Yeah.
...that you just asked. I have to tell you what I think, right? Because I don't know.
Yeah.
So this is what I think. This was a very well-designed, clean trial where we met the primary endpoint with, you know, absolute certainty, number one, the efficacy endpoint. Number two, as always, with our therapy, there's essentially no toxicity. So if you look at the, you know, the risk-reward between efficacy and tox, we also score very well on, on that perspective. And so I would expect that the labels in the U.S., Europe, and Japan will be consistent with the primary endpoint, which is for patients with metastatic non-small cell lung cancer after platinum failure with either chemotherapy or immunotherapy. So that's, you know, the definitive answer to what I believe for your first question.
Sure.
Now, the second question, which is, will prescribers prescribe it? And, and the root of this question, it comes from the fact that while we hit the primary endpoint, when we looked at the powered secondary endpoint, we saw contribution from both arms, but we saw a trend in the combination with chemotherapy, and we saw overwhelming statistical significance in the arm combining with IO. And so the genesis of this question is, given that IO has moved from second line to front line, are there any patients in the second line, for whom this would be applicable? And the answer that we're hearing from the community, and when I say the community, from prescribing physicians, and we've been doing ad boards since ASCO, actually since before ASCO, under NDA and now since ASCO.
These ad boards start with the question: Do you have patients? And we usually get an answer, "Some." Then we go through a process... Because remember, this is a new therapy. These doctors didn't study it in medical school. It has not been applied in thoracic oncology. Then we really explain the data, both the efficacy data and the safety profile, how it would be used, how it would be prescribed, what their burden is, and by the end of the day, we ask the same question, and we get back an overwhelming, "I absolutely have patients.
I have patients who I'm planning to give chemotherapy, who want the best possible combination, and with this safety profile, I understand that it wasn't statistically significant in that small arm, but I want to give it to those patients.
And then for my patients who I am continuing on IO, it's a no-brainer, and I'm probably gonna consider even more patients, to continue IO with these data." So, you know, will it be Keytruda? Will it be used for every patient? The answer is no. Is there a significant number of patients for whom it will be prescribed? We believe yes. And to put it in context, we believe that it will certainly be larger than our GBM business that's already in hand. So I hope that was as clear as I could possibly make it. And I think people who think there's no market here, you know, we're gonna have to prove it. We're gonna have to show it, but it just doesn't make sense.
This is a patient population where there's been no progress in over seven years. These are patients in the doctor's office, where the only thing they have to offer today are old chemotherapies with you know, terrible side effects. And the patients and their families are asking for more, and now the doctors are gonna have something to give them.
I'm gonna ask you to humor me one more time on some speculation, though. It was really helpful. But the next piece is payment rate. Sure. All right. And again, we can, we're probably just going to be sitting here and speculate, but we have at least a reference rate in GBM. That's a smaller patient population. Payers are not in the game to be paying more. So you have a larger patient population with non-small cell. Where do you expect it shakes out, Germany or U.S.? And Ashley, you're kind of nodding along. I think you're totally prepared for this question, so go ahead.
Sure.
Yeah. I mean, I think at the beginning, we would expect the GBM reference price to be the right reference price. You know, with volume, as volume grows, these are always dialogues that you have with payers. But at the beginning, I think that's the best anchor. And I mean, this is the value of it being launched in GBM and going into the markets and establishing the path to reimbursement. We don't have to start from ground zero. We know how we will get reimbursed. We have fee schedules in markets that anchor the discussions, and we would expect that payers would, you know, on the volumes of the LUNAR patient population, that GBM is a sustainable price point. Now, with incremental volumes and over time, the lung opportunity grows, I think, you know, we'll see where that goes.
But we feel like the GBM price point is an appropriate anchor from where we'll start the discussion.
Okay, and you're willing...
And the other thing I'll add.
Sorry.
I mean, just to...
Yeah, please
... jump on this. I mean, you know, the ultimate leverage that payers have is competition, right?
Yep.
We're in a very privileged position, because we deliver our therapy through a medical device that we're continuing to improve. So in the important markets, you know, the markets that respect intellectual property, we're the only company that has Tumor Treating Fields therapy. So, you know, we start with that perspective. It's not, I'm going to pay for this IO or that IO or, you know, another IO. We're the only party with whom we're negotiating to bring this, bring this therapy.
Okay. All right. Makes sense. And then the last, last question here. I mean, you are willing to go at risk even without payer coverage, as long as those patients are fitting within the defined labeling guidelines that you, you end up receiving?
We would expect to do that in Germany and the U.S., which would be our two first large markets. Again, we won't, we'll go at risk for patients for whom we would expect to ultimately get reimbursed. So this is not going to be an all-comers. They would need to fit the profile of the patients that would align with the protocol of our trial. But yes, we're comfortable going at risk with that, and we have experience in collecting those on a patient basis.
Yeah. And again, to remind everyone, we went at risk in GBM and ultimately collected the vast majority of the revenue from those on-risk patients. We learned a lot during GBM. And, you know, first and foremost is, you know, really stay on label. That's the... And even though doctors want to prescribe it more broadly, from an ultimate collection point of view, that's the limitation, to stay on label.
Sure, and probably important in Germany, where you already have had that experience.
It is. I mean, it does, as everybody looks at the model, it does mean, though, that revenue will lag...
Yep
... when we have demand today. So I would just remind everybody of that.
Yep. Perfect. Well, let's, let's move on. There's a lot more to talk about in the pipeline. Next, Phase III, where we'll have some form of update is METIS. Now, this is a little bit of a unique Phase III for you. It's the only one where you're, you're using TTFields as a monotherapy. Also, the, you know, one where you're treating the mets, not the primary cancer. So how do we handicap success here? You've got a proven indication in GBM, but you're going after, you know, something that's entirely different. The primary endpoint, progression-free survival, not an overall survival metric. So how do we handicap success on our side?
So, you know, as you point out, we have two Phase III readouts on the calendar for next year.
Yep.
METIS and PANOVA-3, the first to come. These are now fully enrolled and just, you know, on the clock for follow-up. You're absolutely right. METIS is a bit of an outlier as a clinical trial for us, but an outlier for anyone who is treating mets. So it's very consistent with trials for metastases. You ask how you handicap, and I'll say, first and foremost, wait till March, and then you'll know. But if you need to handicap in the meantime, we've actually absolutely proven that we can treat cancer in the brain. You know, this is clear with our extensive GBM experience, both in terms of our clinical trials, but also now in terms of five-year real-world evidence. This really works in the brain.
Also we've shown that we can treat non-small cell lung cancer both in our phase IIs and in LUNAR. We're treating the full extent of the cancer when we treat in the brain, and the comparator is watchful waiting. So in a sense, we're treating with monotherapy, although we're treating with whatever systemic therapy is on board for the primary tumor. So it's us, plus the systemic therapy, compared to the systemic therapy alone. And the endpoint is progression within the field. So, you know, I think those are all positive. You know, if you have to handicap the negative, and just to give both sides, is that this is a heterogeneous patient population. So, you know, when we do GBM, you almost don't need a control group, right? Because, you know, the control hasn't changed in 20 years.
Pancreatic cancer, you know, it's almost the same thing. You know, it's very clear. In brain mets, it's younger patients, older patients. We have limited the study to patients with between one and 10 mets. You know, so that does, and of course, it's randomized. But that's the complexity, the inherent heterogeneity of this population.
Okay. And I know you said March, just to level set everyone. So headline data in March, maybe it's April. I know sometimes we have a little bit of movement in the calendar, but, somewhere March, April is when we should see headline data, and then, you'd look to present that when, where?
At the first appropriate conference.
Yes.
Okay. All right, why don't we move over to the other phase III. You mentioned PANOVA-3, advanced pancreatic cancer, phase III trial. You know, this one has a lot of similarities to GBM, right? It afflicts patients of all ages, really aggressive cancer. IO doesn't work, and it's another, but it's another study that's pairing TTFields with chemo, which the data's been a little mixed, to be very candid here, the last couple of years, with not necessarily in pancreatic, but across the studies you've been looking at TTFields plus chemo. So I guess, why should we feel more optimistic or less optimistic about PANOVA-3?
Yeah. So I'll start with the obvious fact that we are a regional therapy, so we're applying our electric field to either the head, the chest, or the abdomen. When you say mixed, I assume the two trials you're referring to are the chemo arm of the LUNAR and then the INNOVATE trial in ovarian, which did not succeed in the top line, even though there are, you know, there are really important signals that we're, you know, we've talked about a little bit and that we're analyzing for subgroups. Both LUNAR and INNOVATE-3 were trials in metastatic populations where the cancer had spread beyond our treatment. Now, as I said, we still showed a trend, and we still showed important signals in INNOVATE.
But I think in the long term, with metastatic disease, the real win is to treat with Tumor Treating Fields and immunotherapy, where you get all the benefit of Tumor Treating Fields, plus the benefit of exposing the immune system. Back to PANOVA-3, this is locally advanced pancreatic cancer, so it's in a population like GBM, where we're treating the full extent of the cancer. We know we can get our electric fields there. We are combining with a weekly paclitaxel and gemcitabine, which are chemos. We know it works together.
Yeah.
But the key difference is that it's locally advanced, which is about, you know, round number 40% of the of the diagnoses for pancreatic cancer, 60% when it is metastatic. And for that, we have our trial where we're combining - that we're doing with Roche, where we're combining with their immunotherapy. And that's what I would expect to be used, ultimately for metastatic disease.
It's first line.
Yeah, first line.
In the locally.
Okay.
Early on, when the patients can comply, locally advanced. Based on everything that we know today, you know, if you asked me the question, "If you could go back, you know, four years and design the trial, what would you change?" In the case of PANOVA-3, it's nothing. In the case of INNOVATE, there are a number of things we would have changed based on what we know today in terms of how we would have designed that trial.
Yeah, to be fair, you know the INNOVATE data, you don't know the PANOVA data, but...
To be absolutely fair.
Okay.
But you asked, you know, about...
No, I know.
...handicapping.
Okay.
Those are, you know, the facts that...
Yeah
... you know, allow us to, you know, to start investing, I would say now.
Yeah
F or success in pancreatic.
That's all helpful. I wanted to take, you know, take a little bit of time in the time we have left. You know, it feels like we're maybe on the cusp of a, you know, a little bit of a maybe philosophical shift in how we think about the pipeline and how we think about the strategic approach to using TTFields in future trials. I've been following your stock, your company for quite a while. You know, originally it was, "Hey, we're going to go after really aggressive forms of cancer," and it made a lot of sense. You know, these aggressive forms of cancer weren't responding to anything else. You had some really old data you were comparing against. Also meant you didn't have to show a ton of survival improvement in order to theoretically get approved.
But the other dynamic, as we started to see with some of these, some of the trials you've been running, is they're late-stage diseases. Patients are really, really sick, and we've started to hear, you know, whether it's on some of the phase II data or even on some of the phase III data, that, you know, "Hey, it worked, but it worked in the less sick patients." So, you know, with that kind of preamble out there, do we need to see a little bit of a shift like, again, a philosophical shift in how we go about treating or starting new trial work and treating patients that are a little bit less sick and just, you know, end up having larger trials, larger ends, in order to prove out that statistical significance?
I don't think there's a philosophical shift at all.
Okay.
We've known for a very long time that you have to use Tumor Treating Fields for it to work, which means compliance and time on therapy. We've seen this in GBM, that for patients who use it at the time of diagnosis, they have a much better prognosis than if they wait to their first recurrence. I would say what is the newer news is that, when you combine with immunotherapy, you get a profound synergy. Our second-line data in lung cancer is as good as Merck's first-line data.
Yeah.
I don't know that that's a philosophical shift. You want to start early, and you want to combine with IO. And I think that's the future of solid tumor therapy. The way oncology works, sometimes you have to start with the sicker patients. It's not always possible to go right to first line, but I think we're at a point now where that's clearly the target: first-line therapy, combinations with IO, and that's where, you know, I expect to see the profound difference. And in GBM, we have a trial combined with IO. IO didn't work as a single agent...
Yeah
...i n GBM. In our phase II data, it's the best data anyone's ever reported. I already mentioned IO, and you mentioned IO has not worked as a single agent in pancreatic...
Yeah
... but we're combining it now in metastatic, and we're working to the front line in metastatic lung cancer. So we're not stopping with LUNAR. We're going to, you know, the next LUNAR trial...
Yeah
to move it to the front line.
Okay. Really, to summarize, catch it earlier, and that's, that ends up being...
Yep, catch it earlier and add IO.
Add IO. Add, add IO where applicable. Okay.
Yeah.
Perfect. You know, great, very informative, great color. You know, thanks so much for being here, Bill and Ashley. And everyone, please thank me, and, or join me in thanking Bill and Ashley for their wonderful presentation.
Thank you, Jason.
Sorry. Long day.