Thank you.
Good afternoon and welcome to the Jefferies 2025 Global Healthcare Conference. It is my pleasure to now introduce Ashley Cordova, CEO of Novocure. Just a reminder that this will be a 25-minute presentation.
Thank you and welcome, everyone. It is my distinct pleasure to be with you this afternoon to give an overview of Novocure. Here are our standard forward-looking statements. I'll start with a brief introduction of Tumor Treating Fields. Novocure is solely focused on the development and commercialization of Tumor Treating Fields, which are electric fields that harness electrical properties of dividing cancer cells in order to have their effect. The original insight behind the company founding was that if I can get an electric field inside the cancer cell, I can disrupt the formation of the tubulin spindle because microtubules are highly polar, and I can also impact the, I have a downstream antimitotic effect. What we have since learned is that the way that electric fields kill cancer cells also induces immunogenic cell death.
In fact, we can be combined with immune activating events to have an immune effect as well. We also believe that we have an effect on the DNA damage repair mechanism. A multifaceted mechanism of action is able to target cancer cells through many entry points. Importantly, we're able to selectively target cancer cells with this therapy because the cell membrane itself acts as a capacitor and has electrical properties that filter out electric fields depending on cell size and actually can be specifically tuned to cancer cells. Also importantly, because this is a differentiated mechanism, we are able to combine with other therapies in use to target the cancer cell division. We're able to combine very well with systemic agents, and we don't have additive toxicity. That's a little bit about the mechanism of action.
Here on the screen is a picture of how Tumor Treating Fields are delivered. We are an oncology therapy delivered via medical device. What you see up here on the screen are the two primary components of our device. We have the electric field generator, which connects to a set of transducer arrays, and those are worn surrounding the region of the tumor on the patient. For CNS tumors on the head, they are wearing them front to back, side to side on their head, as with Optune Gio. As you can see on the right side of the screen with Optune Lua, that is our lung cancer application, they are wearing them under their clothes, front to back, side to side on the torso. This same form factor is used across all of our indications.
We frequency-tune the device to the specific tumor type, and the size of the array differs depending on the location and the region of treatment, but the fundamental device looks the same. We are able to provide this device as a home use therapy. It is home use DME, where we're charging one all-in therapy cost per month of therapy, and we have a recurring revenue stream by providing the device to this patient. Those are the fundamental building blocks of Novocure. I will take us up to where we are, which is a very exciting time in the company building. Novocure has been around for 25 years, the first 15 years of which was principally a research company where we were developing both the core insights and the mechanism, but also developing the engineering to be able to deliver the therapy to the patients.
We then launched in GBM, and over the last 10 years, we built the business, a commercial business in glioblastoma. We have all of the infrastructure of how to provide the therapy to patients, how to get reimbursed, and we also really have expanded our geographical footprint. We spent the first five years launching in the U.S., and over the prior five years has extended into Germany, Japan, France, now Spain, and we have a very well-established footprint across most of the major markets that pay for high-volume oncology therapies. We are entering in a very exciting new phase of company building where we get to take the solid foundation we built in GBM and extend the access to therapy across multiple indications.
We just launched last year in non-small cell lung cancer in the U.S.., and we have data with the FDA now in pancreatic cancer and data that we're preparing to submit in brain mets. We are entering in a new era whereby the end of next year, we believe we will have four products on the market and really a lot of catalysts as we look at the quarters to come. I want to spend a minute and talk about the solid foundation we have established in glioblastoma. Glioblastoma is the most common form of primary brain cancer. We have a business of more than $600 million on an annual run rate in glioblastoma, where we are the standard of care used after radiation concomitant with temozolomide, so a chemotherapy anti-alkaline agent. In the U.S., as I said, Germany, Japan, France, and many other countries across Europe.
This is an extremely solid foundation where we've established the business model. We have patient support services in place. We have reimbursement operations in place. We are able to get paid. We have NCCN category one recommendations, and we have a full suite of IP to protect the durability of this revenue stream. The glioblastoma business in and of itself is generating a consistent mid-single-digit top-line growth, and it provides us with a solid financial platform upon which we can invest in the future. Invest in the future we have. If we look at the prior five years, we've invested $1 billion in R&D to advance the platform, which is Tumor Treating Fields.
What you can see on screen here is the outcome of that research, where we now have in four solid tumors consistent data where we have shown a profound effect from adding Tumor Treating Fields to the standard of care. I think it's actually quite striking when you see this side by side on the screen. If you look at the left there, what you see is our data in glioblastoma. Again, this was the first indication that we had with extensive commercial reach, where you see an increase in five months overall survival on top of the standard of care. If you go next over, you see our data in metastatic non-small cell lung cancer.
Again, this is post-platinum treatment for metastatic non-small cell lung, where you see a significant benefit when you add Tumor Treating Fields on top of physician's choice, either immunotherapy or docetaxel in that setting. This three-month benefit we see in the combined population was even more profound when we look at the IO combination, where we saw an eight-month extension in overall survival in metastatic non-small cell lung cancer. Going farther to the right, this is the data in pancreatic cancer, locally advanced pancreatic cancer that is with the FDA now. We started our 180-day clock in August, and the review is proceeding as expected in an interactive format. This is the first time specifically in locally advanced pancreatic cancer that we've seen a randomized overall survival benefit. We see two months in the overall population.
When we look at pain-free survival, we see an important six-month extension in the time to pain progression. Really impactful data that we're engaging in discussions with regulators and in early outreach to the medical community around medical education of this data as well. Finally, you see our data in brain metastases, where we were also able to show an extension in time to intracranial progression. In aggregate, what you see is a consistent benefit across multiple solid tumors when we add Tumor Treating Fields on top of the standard of care and importantly with different standard of cares in the background. You're able to see the combination potential. Okay, where do we go from here? This is turning that clinical data into a really diversified revenue stream.
This is what is so exciting about the year we are about to enter at Novocure. We have built the infrastructure. We have built the business in glioblastoma. We have taken 25 to get the data to the FDA. As we look ahead, we now see the ability to access many more patients with needs. On the left-hand side, you see glioblastoma and non-small cell lung cancer. Those are our two currently active commercial products, Optune Gio, where we have about a 40% penetration rate in our large markets, and on the bottom, non-small cell lung cancer, which is Optune Lua. On the right-hand side, you see the two launches that we would anticipate next year in 2026, locally advanced pancreatic cancer and brain metastases from non-small cell lung cancer. I am going to spend a minute and talk about the three launches that we have.
GBM is the established business, but I want to talk a minute about the three launches we have as we look ahead to top-line revenue growth. We are entering into a medical oncology space with these launches, and lung was first. For those that know Novocure and know our story, what we said is that lung is probably the hardest of these three because we're having to introduce a device into a drug-based world with a medical oncologist that has a very busy office and a lot of competition. That launch is proving challenging, but I will say worth it when we look to the long-term opportunity. A few key updates here on non-small cell lung cancer. You can see that we had 100 patients on therapy at the end of the third quarter.
We did recently receive news that Optune Lua was not included in the NCCN guidelines updates, that the panel voted that additional data would be needed to include Optune Lua into the guidelines. We are looking ahead to how can we make sure that we build upon the solid foundation of medical education that we have with the thoracic oncologist to help pivot and support the pancreatic cancer indication, which is around the corner. If we look there, the next indication we would expect to have in market would be locally advanced pancreatic cancer. The physician call point for Optune Lua and the pancreatic cancer indication shares many commonalities, and we would expect to use that same sales force across lung and pancreatic. There is a significant amount of leverage when we look at the combination potential of those two indications.
As we think of investments, we're thinking about investments in the medical education of medical oncologists in the torso. Brain metastases is a call point that will be shared with our glioblastoma field force. It is primarily the radiation oncologist that is treating stereotactic radiosurgery in brain metastases. This is a radiation oncologist that treats glioblastoma patients today and is comfortable with Optune Gio in the CNS setting. We would expect, if I could compare and contrast these three indications for pancreas and lung, we need to do the device education to a medical oncologist. The opportunity is very real. It's worth doing, but it will take time. Lung is more competitive than pancreas, so we do anticipate pancreas will be an easier path and a journey to chart that relationship. We're committed to investing in that pancreatic cancer indication.
Mets will be the same customer that we know today with a new setting for the therapy. Those are our four commercial opportunities and the diversified revenue streams we can look at as we look ahead to 2026. We also continue to take the strength from GBM and invest it in our R&D dollars. If you look at this slide, what I will say is in light blue are four indications that we would expect to either have through the regulators or with new data in hand in 2026. It will be a very catalyst-driven year next year as we look ahead. I'll just walk through in order of time, not in order of slide here. If we start at the bottom, the first data readout we will have is in Panova IV.
This is a phase II trial in metastatic pancreatic cancer, which looks at the combination of Tumor Treating Fields, gemcitabine, and atezolizumab. Atezolizumab is a PD-L1. It's an IO agent that has not shown an effect in pancreatic cancer. This is a cold tumor microenvironment. We are hopeful that electric fields will be able to activate the immune system, and we will see a strong signal there in that phase II trial. A very interesting data readout for us, not because of its registrational potential, but because of the signal it can show us with regards to the ability to activate the immune system in pancreatic cancer, which has henceforth not shown to respond to IO. A very exciting data readout that we would expect in Q1 of next year.
If we then go up to the top here and look at Trident, this is a trial in newly diagnosed GBM where we look at starting Tumor Treating Fields two months earlier and the treatment journey concomitant with radiation instead of waiting to the current label, which is post-radiation. There are two things we're able to do with this. We're able to say, if we start even earlier, can we extend survival beyond what we saw in our EF14 data that supports our label today? We're also able to ask the question around the benefit of the DNA damage repair mechanism because we know that the way DNA damage self-repairs relies on electrical properties. If Tumor Treating Fields can impact that, we believe we can have a profound benefit.
It answers a very key scientific question, but also is very applicable directly in the commercial setting today because it provides us a chance to start two months earlier. In a therapy where we bill per month of therapy, that should be quite accretive to the top line. I do think there's a couple of important points when you're contextualizing the Trident data that we want on everybody's radar. This trial starts concomitant with radiation, which means it is an all-comers trial in newly diagnosed GBM. Our EF-14 trial started after radiation, which means the patients that progressed during radiation were not included in the trial. About 25% of glioblastoma patients will progress during radiation.
When we think about what I would expect in terms of an OS, you should expect that the control arm in Trident does worse than what we saw the treatment arm do in EF-14 simply because it's an all-comers and you're going to have the rapid progressors included in that population. An important context point when you look at comparing that data. It is randomized, so we'll have the statistics to show the effect of Tumor Treating Fields regardless of how the control arm performs. All right, that's our two data sets. As I said before, we also have two sets of data that have already read out with the FDA that we would expect to progress to launch next year. That's pancreatic that will likely be first. That is with the FDA now.
We would expect a launch mid-next year with that data. The METIS, which is our data in brain metastases for non-small cell lung cancer, we would expect to be at the FDA before the end of this year. We are also not done with that. If we look ahead beyond 2026, we do have two additional large randomized phase III trials which continue to enroll. The first is in LUNAR II, which looks at taking the metastatic non-small cell lung cancer indication and moving it first line. That is the combination of pembro with Tumor Treating Fields and first line non-small cell lung. We are also looking at the IO combination in glioblastoma with KEYNOTE D58.
This data is supported by a very interesting set of translational research that is published that looks at the ability to activate the immune system and the STING pathways when we combine Tumor Treating Fields with pembro in the brain. Pembro as a monotherapy did not show activity in glioblastoma. This really opens up the potential to add IO to a disease state similar to pancreatic that has been privileged from IO in the past. We are very excited about both of those trials. They are large randomized trials that are just now in the early enrollment phase with overall survival endpoints. They will be several years out, but certainly speak to our platform potential and our commitment to continue to invest. All right, in a nutshell, Novocure is on a roadmap to becoming a profitable multi-indication oncology company. We have more than 4,000 patients on therapy today.
We have very real near-term opportunities that you can measure us against quarter by quarter as we look ahead in GBM and the success of our non-small cell lung cancer launch, as well as rollouts of product enhancements like our HFE array. As we look to 2026, we really have an opportunity to transform this company from a single indication to a multiple indication diversified revenue stream with four products on the market: PANOVA, METIS, non-small cell lung cancer, and Optune Gio. We will also continue to advance our product development and bring some of the improvements we brought into the head this year into the torso array. As we think about kind of medium-term opportunities, which I would think about in 2026, we have a catalyst-rich year ahead of us. We are not planning to be done there.
Twenty-seven and beyond, we have a clear path to profitability, and we will continue to invest in the pipeline and look forward to sharing future updates and future calls about our journey to really transform the way that many of these aggressive cancers are treated. All in with our mission, it is what drives all of our employees and what provided the spark of inspiration to found this company is that there are so many aggressive cancers that need an additional treatment option that can use a profoundly different treatment pathway, such as electric fields, to access solid tumors that really need an additional tool in the armamentarium. We can be used in combination with systemic therapies. We do not add systemic toxicity on top. Our only side effect is skin irritation under the placement of the arrays.
We really are committed, together with our patients, to extend survival in some of the most aggressive forms of cancer. With that, I'm going to open the floor in the room to any questions.
Please. You talked a little bit about the whole GBM indication growing at mid single digits. What do you think you can do there to increase penetration further, ignoring the Trident trial?
Yeah. Yeah. I think when we think about penetrations in GBM, 40% has proven to be a pretty sticky plateau in our large markets with the data set that we have today. We are looking always to field force effectiveness and incentivizing just general growth, but that's the backbone of that mid-single digit growth. I would say the other two opportunities are geographical expansion. That's what gets us ahead of that mid-single digit growth. Spain, we're looking at ahead.
As we look around the corner of Spain, we have Italy, and we will have other big five EU markets such as the U.K. and Canada to come. Beyond just execution in those large markets, we will be looking to incremental data. You said beyond Trident, I would actually have to say Trident is a key factor in that. When we look at what could give us a step function increase, I do think it is additional data. We have two opportunities there with Trident and with the keynote D58 trial.
How does the benefit of efficacy, the benefit of two-month overall survival on TPM compare to quality of life, usability?
Yeah. It is significant. I will say for anybody that has family members or friends who have been impacted by pancreatic cancer, it is a very challenging, dismal prognosis, right?
Every month of survival we can add, particularly in a randomized phase III trial with a significant benefit, is meaningful. We know that. We hear that from the physicians that treat pancreatic cancer, and we hear that from the advocacy group. We do strongly believe that two months is a meaningful benefit. I will also say it's beyond just the OS benefit. You have to look at the pain-free survival as well. This is where we saw a six-month extension in pain-free survival. The challenge with pancreatic cancer is not just how long can you live, but how long can you live with manageable pain. We saw reduction in opioid use. We see all of the hallmarks of pain management benefit from the addition of Tumor Treating Fields.
Can you say anything about the reimbursement for non-small cell lung cancer and what are your expectations for pancreatic cancer?
Yep. As a reminder, we are DME, which means we go through a device-based pathway for reimbursement, not a drug-based, which means we have to negotiate coverage policies after we get the approval. It's not automatic. We expect that across indications to take on average about a year for commercial payers and about two years for Medicare. In lung cancer, I will say we are ahead of that expectation in the commercial payers for lung, meaning the volumes are lower. What we're seeing is that we're able to engage with payers and win on a named patient basis case appeals for these patients. We are hopeful that reimbursement in the commercial setting will not be our challenge in lung.
We need to get the volumes up before we get routine coverage policies because you need volumes before payers will engage in coverage discussions with you. I think our bigger kind of lookout is always on making sure that we can get Medicare reimbursement. This will be something that we've submitted for an LCD reconsideration for lung, but we'll also be talking to them across the platform over the course of the next couple of years. I think I'm down with time. It's blinking red on me, so I'll say last question.
Turning a computer from code to bot kind of initiates my interest. Any data on this?
Definitely. I mean, we see it in Lunar II where we have the combination with IO, right? We see it in the translational research that supports keynote D58 and GBM. We do know that we trigger an immunogenic cell death.
We see calreticulin exposure. We see all the classical signals that you would expect, the hallmarks of ICD. Again, the way that the antimitotic effect occurs actually triggers a downstream immune response. It is actually the antimitotic that is kind of the first domino and it is triggering immunogenic cell death. I will say, although the time is blinking at me, that because we are electric fields, we are able to potentially do that in areas that are privileged to systemic therapy. You can think about the blood-brain barrier preventing chemo agents from entering the brain and triggering that, but we have the potential in the same with the stromal tissue or just the challenging tumor microenvironment of the pancreas. That is the promise.
All right. Thank you.