Hello, everyone, and welcome to the last day of the J.P. Morgan Healthcare Conference. My name's Léo Kensicher. I'm an associate in our healthcare investment banking team, and it's my pleasure to introduce the Alpha Tau Medical team. With us today, we have Uzi Sofer, CEO, and Raphi Levy, CFO, who will be presenting. Uzi?
Thank you. Thank you very much. Thank you, everybody, for joining. I'd say this is the best day of J.P. Morgan, so happy you guys are here for the conference, and happy to share our story with you, so thank you for the time. So we are the only ones using alpha particles for local delivery into tumors. It's different than what others are doing with systemic drugs. This is a local paradigm where I see a tumor in imaging or visually, and I want to cut it out or radiate it. No one's been able to do that using alpha radiation to date. Even though we appreciate the relative efficiency and potency of alpha particles, we just can't harness them to be used in that kind of an application, and I'll show you why that is. We've come up with a way to do this quite simply.
We use it across indications. We've tested this in over 20 tumor types preclinically and have never seen a tumor type that doesn't respond because, fundamentally, it is physics. It is a straightforward treatment, releasing alpha particles to wherever it is injected, and we believe it could be relevant to a very broad range of tumors. We are using it now on its own, together with other therapies. I'll talk about that in a bit, and have a number of important data milestones coming up, including in just a week and a half, and I'll touch on that later in the presentation. As I said, we're testing multiple indications and are looking for our first potential U.S. marketing authorization next year, as well as a number of other opportunities thereafter.
So we are the only ones doing local alpha radiation, and the reason for that is that alpha particles, while they're known to be significantly more efficient and more potent, one can use a fraction of the same dose to destroy a tumor and doesn't require oxygen or other indirect mechanisms to do so. No one's able to do that simply because of the range in tissue. Whereas beta sources will travel through a tissue in its radiation, gamma rays can be shot externally like X-rays. They'll cover the tumor, but they'll also bleed into the surrounding healthy tissue and do damage there because of their long range. Alpha particles have an incredibly short range, about 40-90 microns in tissue, which means that three or four cells around an alpha emitter will be very, very dead, but outside of that range, there'll really be no clinical utility whatsoever.
This inability to get alpha particles to move into a tissue to any useful range is the reason nobody does local alpha radiotherapy. They have largely given up on this idea and moved on to other systemic forms of alpha therapy using some sort of targeting mechanism to try and find tumors throughout the body after injection into the veins. The traditional paradigm of, "There's a tumor, and I want to deliver radiation into it," has been impossible because of the short range in tissue. The way in which we've overcome this has been not by getting the particles to move any farther, but actually by releasing radioisotopes into the tumor in a very controlled fashion. What we'll do is we will take Radium-224 and coat a small piece of metal, a source, with that radium for use in implanting into the tumor.
Now, the radium is useful because it naturally breaks down one, two, three, four, five, six times before it stabilizes. It will release a number of alpha particles along the way, each of which will smack into something and kill it and stop very quickly. But what's unique here is that where the radium is fixated onto the source in a way in which it's unable to leave, it's right next to the surface, and when it decays, it recoils off of the surface by Newton's third law, equal and opposite reaction. It flies off into the tumor, and now the rest of this chain has been released in the tumor and is floating around, releasing these particles again and again. And so we're not actually shooting the particles any harder, as it were. We're effectively throwing the gun on autofire into the tumor until it runs out of bullets.
They are traveling their same short distance, but they are being released deeper and deeper into the tumor, right? Even though the radium is fixated onto the source, once it's decayed and its daughter atoms have broken down and moved into the tumor, they will continue to release these alpha particles until they reach the end of the decay chain and are stabilized, and so in doing so, we have extended the effective range of this alpha particle from about 40 microns to about 4-5 millimeters, which gives us a much more useful tool that we can cover tumors with by inserting a number of these sources every few millimeters apart to get good coverage, so the message I want to share today is more about the broader vision we have for the company, where we are and what we've done with this.
Again, we believe the treatment is relevant to any solid tumor. We have to figure out where we want to spend our time. The first pillar of our strategy, we call the localized and unresectable tumors, relates to where we spend most of our time taking stubborn later-line tumors already refractory to surgery or radiation or both, and showing that we can be a very helpful later-line treatment for patients who run out of local options. So we started doing this in superficial tumors when we first set out, and that was because they were easy to access, to inject directly into the tumor. They were easy to control delivery and place them precisely. They were easy to monitor, so we could see any side effects from this very potent radiation.
Obviously, if you start in internal organs and find out three months later on imaging the guy's had a hole in his stomach for the past three months, that's not an attractive outcome, and so we wanted to monitor very carefully, and also, we had strong preclinical data to support this initial entrance, and so we started in tumors of the skin or the head and neck as our first proof of concept, and so we've now treated hundreds of tumors. We've seen a very strong safety profile. We generally don't see serious adverse events. We don't see systemic effects at all. There's this sort of normal radiation oncology side effects of nausea, fatigue, vomiting that are not something we see very commonly, and that's because the radiation is so tightly controlled that it's not really escaping the tumor in any meaningful amount.
What's historically been the shortcoming of the alpha particles, which is its short range, has now become its strength on the safety side. And on the basis of this data, we've already received approval in Israel, which is where we started, in order to treat patients in skin and oral cavity squamous cell carcinoma. We have that approval. We've submitted for approval in Japan from the PMDA for recurrent head and neck cancer and are hoping to hear back now early this year or in the next quarter or so. Hopefully, we'll get a positive response. We're waiting to hear. And most importantly, our U.S. pathway, which is our focus for our first launch, is. We are in the middle of a pivotal study. We call it our ReSTART study. It's underway now for recurrent cutaneous SCC, and I'll mention that in just a bit.
We've seen great data so far on the efficacy side. In our first-in-human study, we ran in head and neck and skin squamous cell carcinoma, and even the first time we did this, we saw a 100% overall response rate and a 79% complete response rate. Again, the radiation is incredibly potent. With a fraction of the dose that one would use for other forms of radiotherapy, we find it stays in the tumor, it destroys the tumor, and so we're able to overcome these difficult, stubborn tumors that have failed other forms of therapy. From there, we ran a U.S. study, a pilot skin cancer study. Again, like the other ones, we saw fantastic data. You take a stubborn tumor that's going to cost somebody part of their nose.
You treat them with a very simple injection, and three months later, the nose looks great and has not been chopped off, so the guy had a very simple solution for what would have otherwise been a very unfortunate surgical option. In that study, we saw, again, no treatment-related SAEs and a 100% complete response rate. Every tumor we treated disappeared and stayed disappeared over the life of the study, so again, we've seen fantastic efficacy data as well across hundreds of patients in this first proof of concept, which was the superficial tumors, and as I mentioned, we are now in the middle of a pivotal study in the States. This is an 86-patient study running across 20 centers in the U.S. looking for overall response as well as six-month durability.
It's been a very interesting study for us as we've learned over the course of the trial where we can find these patients. Many of these patients with the most difficult recurring localized skin cancers are at the Mohs surgeons, which is a dermatological subspecialty. We've been shifting our focus increasingly in the trial towards those clinicians in preparation for the ultimate commercial target here when we launch the product, which will primarily be the Mohs surgeons, and so now, as we move along that study, we expect to complete the recruitment sometime around the middle of the year, with a six-month durability endpoint, we'll have to wait at least another six months for that, and so we are targeting roughly an early 2026 submission for that marketing authorization in skin SCC, so that's what people have seen so far from us. This is data we published in the past.
I think people very much associate us with that. But we do have two other important pillars of our strategy where we think we can add real value with a very determined and potent local form of radiation. One of them we call the high unmet need for obvious reason, right? And the thought process here, which is that even if on the localized tumors that have other options like skin, there's good logic to going so stratifying and taking the most difficult patients, the ones who have failed other therapies, because there are good therapies available to some of the patients. In the case of some of these tumors in the middle pillar, right, pancreas, GBM, right, these are killers with very poor options.
If we truly are indifferent to the nature of the tumor because it is straightforward physics and is completely irrelevant, the nature of the mutations and histology, etc., as we've always thought, then we may as well go after some of these tougher tumors like the pancreas, like the GBM, and no longer need to think about stratifying and taking the last-line patients. We may as well go after some of the first-line patients in these indications if we can show that we can be helpful there. And so to that end, we have a number of programs underway. We've started treating patients in the pancreas, in the liver, in the lung, in the prostate. We're about to start treating in the brain. Again, there are a number of internal organs here in focus where we believe we can add real value to very, very high unmet needs.
I want to quickly show you, anticipating questions, how it is that we're doing this to be able to deliver a minimally invasive treatment into some of these organs and deliver, hopefully, a very powerful local therapy, and I'll start with the pancreas just as an example.
Revolutionary alpha emitters radiotherapy, the Alpha Loading Device Applicator. Alpha Tau has developed the Alpha Loading Device Applicator, designed for the delivery of highly conformal alpha radiation into the pancreas. This applicator loads an FNA needle, which is commonly used for pancreatic biopsies, with the Alpha DaRT sources. To load the device with the Alpha DaRT sources, the assistant fixes the stopper to the FNA handle and sets the stopper configuration according to the number of Alpha DaRT sources that are needed.
Next, the needle is pushed outside from the sheath and inserted into the needle adapter that is located on the loading device until it reaches the stopper. Then the assistant turns the needle adapter screw to lock the needle in place and releases the piston screw to remove the spacer. Next, the piston screw can be closed to push the Alpha DaRT source out from the loading device and into the needle. The assistant opens the needle adapter screw and removes the loading device from the needle and then retracts the needle back into the sheath and secures it. Now the physician can start the procedure by inserting an endoscope equipped with ultrasound into the digestive system. The physician navigates through the digestive system, identifies the malignant tissue tumor, and evaluates the dimensions of the tumor using the ultrasound.
Next, the physician can insert the loaded FNA needle into the tumor until the tip of the needle is clearly seen on the ultrasound monitor. To deploy the sources inside the tumor, the physician pushes the stylet until the sources are released and can be visualized by ultrasound. Once the sources are deployed, the needle is drawn outside and a new loaded needle is inserted into the endoscope. At the final stage of the DaRT sources deployment, the physician removes the FNA needle and the endoscope while the Alpha DaRT sources are designed to remain in the tumor and release alpha emitters into the tumor. The alpha emitters diffuse into the tumor and emit alpha radiation, which is known to cause double-strand DNA breaks and tumor destruction. Alpha Tau, treating cancer with precision.
So this very much follows the way we like to fit into the treatment workflow, right?
What we've done here is we've taken an existing biopsy procedure. We've taken off-the-shelf diagnostic tools, right? Whichever particular biopsy needle that the clinician is comfortable using can be preloaded with these darts before the clinician comes in, before the patient comes in, pull 20 of these needles off the shelf, load them with the darts, have the clinician and the patient come in, and the procedure follows the same workflow they would have done for biopsy. Put the endoscope in place, perforate with that needle into the pancreas. Just instead of sucking out a sample, inject this dart. We're just reversing the flow. And so in doing so, the training here is quite minimal because the clinician is doing this anyway. This is the same procedure they would have done for biopsy, now turning into a therapeutic delivery instead.
And so in doing so, we have a trial running in Canada. We have a similar study running in Jerusalem as well. These are our first foray into the pancreas. We are taking unresectable patients, stage two, three, or four, which is probably about 85% of patients, and they're eligible to come to us for this treatment where we are treating patients under this ultrasound guidance using the endoscope, delivering directly into the pancreas. We did read out some initial data last year at J.P. Morgan where we looked at the first five patients getting minimal amounts of radiation just as we tested for feasibility, and we saw not only great feasibility and safety, but also some initial hints of efficacy.
We are going to look shortly at the outcomes of some of these patients, and I'm going to get to that in a minute, talking about what's coming up in the next few weeks. I'll quickly touch on one other point here with respect to the internal organs. I think it's instructive how we deliver into the brain as well, and this is something we're going to start very soon, and it's very illuminating as to how we try and find creative ways to deliver into these organs. So I'll play one more video, and then we'll move on.
Revolutionary Alpha-Emitters Radiotherapy, the Alpha Radium Applicator. Current treatments of brain tumors still provide results with a poor prognosis. Alpha Tau has developed the Alpha Radium Applicator, which is designed to distribute the Alpha DaRT sources in a precise spacing while potentially minimizing the damage to the brain.
How it is used: A stereotactic navigation biopsy needle is inserted into the brain until it reaches the desired depth and location. The Alpha Radium Applicator is affixed to the biopsy needle hub. The physician opens the needle's window and pushes the flexible applicator tube into the tumor. Once the tube is in place, the physician pushes the stylet forward and retracts the tube. Once the source is deployed, the needle is rotated to the next position. This way, a layer of Alpha DaRT sources is evenly distributed around the needle without the need to reinsert the needle repeatedly. After the first layer of sources has been inserted, the biopsy needle and the applicator are drawn upwards to deploy the next layer of sources as may be necessary per the relevant treatment plan.
At the end of the procedure, the biopsy needle and the applicator are removed while the Alpha DaRT sources are designed to remain in the tumor and release alpha emitters into the tumor. The alpha emitters diffuse into the tumor and emit alpha radiation, which is known to cause double-strand DNA breaks and tumor destruction. Alpha Tau, treating cancer with precision.
So I like this video because I think it also shows, on the one hand, how we like to integrate into the treatment workflow. We're taking the same stereotactic biopsy systems that are used for taking biopsies, and we're working on top of it to allow the clinician to turn it from a diagnostic procedure into a therapeutic one. I think it's particularly instructive in that we felt that for the brain, it would be difficult to keep inserting needles again and again, repeatedly into the brain.
It's a very sensitive area, of course, and we wanted to get the maximum we could out of a single insertion. This idea of rotating around the axis and dropping off a number of these injections, stopping on the way out, doing it again, stopping on the way out, doing it again, means we can deliver a meaningful amount of radiation with a very limited insertion, just one injection down in and then stopping on the way out. And so again, I think very instructive into how we think about using novel adjustments to existing workflow to make this very intuitive for the clinicians. So we talked about our initial foray into the localized and unresectable world. We talked a bit about what we're doing in the high unmet need of the internal organs.
The last element that we have also laid out as an area of focus for us is the metastatic patients. And the reason for this is that we've seen quite a bit of evidence, and I'll walk through a bit, that when we treat a tumor, we not only help ablate that tumor but also trigger immune recognition of the tumor potentially elsewhere in the body. And I've got plenty of data on this. I'll just show through a little bit here. So this, for example, is tracking the growth of tumors in mice, the black line being the control group, the red line being the group that received a PD-1 inhibitor. You can see that those lines are overlapping. These mice are effectively non-responders. They have seen no incremental benefit in slowing down the growth of the tumor from the addition of a PD-1 inhibitor, right?
This is the 80-some-odd% of patients who just do not respond to a checkpoint inhibitor. The blue line is a single Alpha DaRT placed in the middle of a large tumor, deliberately underdosing because if I don't leave residual tumor, I can't look for synergies. So I'm just going to put one Alpha DaRT in the middle there. And you can see there's obviously an impact. That's not surprising. We know there's a locally ablative effect. What's really cool, though, is the green line, which is the combination of the two. So whereas previously, in the absence of the Alpha DaRT, there is no benefit from adding in a PD-1 inhibitor, once you add in the Alpha DaRT, you see a significant benefit here, right, where suddenly these mice seem to be responding to the checkpoint inhibitor. And you can see, for example, why that is.
We see significant T-cell activation. Here, I've got a slide looking at CD3-positive TILs, but we have similar data for CD4 and CD8 and G ranzyme B, all sorts of biomarkers where we can actually see an immune response in response to the treatment. Right here, you can see there is a population of CD3-positive TILs in the group that received the PD-1 is meaningfully higher in the group that had the PD-1 and the DaRT together, right? So here you have visually observable proof of a local radiation therapy driving immune response. Just another very, very straightforward design that we did and we presented late last year, looking at cold tumor models, trying to see whether supposedly tumor models like pancreas, which are known to be poorly immunogenic, would also have a similar effect.
This is an incredibly simple design: give two separate pancreas tumors to a mouse, treat only one tumor, measure only the growth of the untreated tumor, the one that we didn't touch, and as you can see here, at a p-value of 0.002, we're seeing a very significant impairment of the secondary tumor in the mice for whom we treated the first tumor, right? A distant response, as it were, from treating one tumor being seen elsewhere, again, in these supposedly cold tumor models. Most importantly, in quite a number of patients now, we've seen a handful of patients showing a similar effect here where distant metastases will disappear, so here, for example, this is a British patient who came into one of our early Italian studies, had multiple SCC tumors of the legs. As you can see here, we treated a 3-centimeter lesion.
A month later, the tumor is gone. All you see is a stitch from a biopsy looking for the cancer and not finding it. So she had a complete response on that tumor. We then said, "Let's measure the other tumor and schedule the next treatment," excuse me, "and see how large the other tumors have grown." And we found the other untreated tumors had spontaneously disappeared, right? We never touched the other leg. We know the alpha radiation has no range to go from one leg to the other, so she may have had a miraculous recovery, which is fantastic. Or, as we've always suspected, treating one tumor may be helping the immune system find these tumors elsewhere in the body. And we've seen this now in a number of patients where treating a tumor is causing distant tumors to disappear as well.
And so the question is, how can we harness this and test this more systematically? And so we're doing that using a study running right now. It's a really interesting study for us. It's our first combination study, in this case with Keytruda pembrolizumab. It's also interesting for us because it's our first time looking at systemic response. Normally, we treat a tumor or a set of tumors, and we look at how those tumors respond. But here, we're going to treat a tumor and look at how the rest of the body responds. Are there other metastases that are going to disappear? And so we're modeling this off of KEYNOTE-048, which is the trial for which Merck got approval in metastatic head and neck squamous cell carcinoma. We're taking the same patient population.
They're still getting their regular cycles of pembrolizumab, but we've added on top of it the Alpha DaRT into one or two of the tumors. And so they're going to get pembrolizumab. We're going to insert the Alpha DaRT. They're going to keep getting pembrolizumab. We're going to take out the Alpha DaRT, and they'll keep with their pembrolizumab on schedule. And the question is, can we trigger a systemic response more successfully than has been seen in the past? Now, we're benchmarking this against the KEYNOTE-048, which, again, is the pivotal data that got it approved in this indication. Across the various populations, the data is fairly consistent. We're treating CPS greater than one, so that's probably the right area here to focus on, but they're fairly consistent here. About 19% systemic overall response and about 2% of complete responses was what got Keytruda approved in this indication.
And so for us, we're going to look now, as we use Alpha DaRT in just one small tumor, one part of the set of tumors in the body, do we see a broader response to Keytruda in response to the kickstarting of the immune system by using Alpha DaRT in one of the tumors? And really, the question we're asking ourselves here is, can a local therapy be part of a systemic solution? Excuse me. Can we show that in delivering a local therapy into one or two tumors, we have contributed to the systemic response to the systemic drug? And so queuing up now, getting you all excited for a week and a half from now when you've all recovered from everyone's favorite conference of the year, we will be having an R&D update day coming on Monday, January 27th.
It's a virtual conference at 11:00 A.M. Eastern Time. We hope to see all of you in the front row of the virtual classroom. We're going to be sharing data, I think, some very, very meaningful data points for us, probably some of the most meaningful we've shared to date across a number of areas. First of all, we're going to look at interim data from those pancreatic cancer studies. The feedback that we've gotten in the past is that people want to see, obviously, more patients. They want to see survival data, right? They want to understand how does a local therapy play a role in driving patient survival. We're going to examine that as well, looking at some of these patients.
We're going to look at the tumor responses and safety, of course, but across a broader range of patients, probably 35 to 40 patients of data coming across our various studies being presented by the clinicians involved in these various studies. We are going to give some case studies of patients who've been treated for other organs. So recently, again, as I mentioned, we've made a big push into internal organs, and we have started treating patients in the lung, in liver mets, in the rectum, and we're going to give just a flavor of that with some case studies as to how these patients are doing. Again, all of this to give a broader picture of what the ability is of Alpha DaRT to be used in the unmet need in the internal organs.
And then finally, we're also going to take a look at where we stand so far on these patients who are getting Keytruda together with Alpha DaRT, and can we deliver those systemic responses better than what's seen by Keytruda alone? So we are all waiting with bated breath to see the data, at least as much as the rest of you, but we're very excited for this as soon as the data is available because we think this is going to be a very meaningful, not only set of data for us, but giving a broader vision if the data look good, right? People have historically seen us in the localized and unresectable space. I think those who follow the story are familiar with our data in skin, head, and neck, and that's an incredible indication. We've got plenty of thoughts on pricing power there, pricing attractiveness, market size.
We think we could be a great company in that space, but we think people don't see the full potential necessarily for how this can really treat tumors with an unmet need and how this can potentially be part of the way in which we treat metastatic patients, and we're hoping the data will look good and really help make that case and broaden that vision. Just to quickly touch on what we're doing, there's a lot of stuff here on the slide, and I won't go through all of it. Our lead indication has historically been those superficial tumors, as I mentioned. We're already approved in Israel, and we've submitted for approval in head and neck in Japan. Our focus remains on getting that recurrent cutaneous SCC to approval in the U.S.
And at the same time, as I said, we've been dipping our toes into a few different cancers to show that just with a handful of patients, can we demonstrate proof of concept there just as we've seen great data in the skin and head and neck? And so I talked about our pancreas trials in Canada and in Israel, our liver mets study. We've been treating prostate cancer and vulvar cancer. We're about to start treating brain cancers as well in Israel. And so again, a couple of really interesting studies going on here to generate that proof of concept data. Looking forward, there's going to be some meaningful milestones coming up. So we, as I mentioned, we are looking to finish around the middle of the year that pivotal study in SCC and then get the data to submit early in 2026.
Obviously, we know now the 27th of January will be our readout for pancreas and for the combination with pembrolizumab, looking for that feedback from the PMDA sometime in the first half of this year, and again, targeting our first brain cancer patients over the next quarter or two. We've been a public company now for almost three years. It's gone by in a flash. We raised $104 million, and we went public in March of 2022. We still had $68 million in our bank at Q3. I'd argue we are an incredibly lean company. We have about 130-135 employees. We spend about $5 million or so a quarter in cash on a run rate basis. We do have some one-off CapEx as we build out plants, but on a general basis, we spend about $5 million or so a quarter.
I think you'd be hard-pressed to find companies in San Francisco or Boston doing that with 15 or so different clinical programs, so obviously, the CFO is doing something right, but we're very proud of how carefully we manage our cash balance and the fact that I sleep well at night knowing that we can fund the existing program for the next few years quite comfortably. Obviously, we are accelerating plans, and if the data look good, we will continue to do so, but for now, we're very happy with our financial position in the ability to fund what we're doing right now, so I will stop there. We'll be happy to take questions, and thank you very much for the attention.
Thank you, Uzi. Maybe I'll kick it off with.