Good morning. Thank you to all of you who are joining us today in the webinar from your offices or from home in your pajamas to hear an incredibly exciting update from Alpha Tau on the R&D we've been conducting over the past few months. My name is Raphi Levy. I'm honored to be here today together with some of my esteemed colleagues discussing some of what we've seen in our trials. I will be introducing each one of our speakers as we go through today's presentation. But first, I just want to give a quick introduction as to what it is we want to discuss and what we're setting out today. Just to remind you, Alpha Tau has developed the Alpha DaRT, which is a treatment for locally injected radiotherapy using alpha particles being delivered directly into a tumor. We believe this is an incredibly broadly applicable treatment, having tried it in 20 different tumor types preclinically and yet to see tumor resistance or a type that doesn't respond. We also see this relevant not only for a broad range of tumors, but potentially for use in combination with other therapies, such as immunotherapies, which we'll discuss today. We have trials underway in multiple indications, and we're going to have a number of milestones throughout the course of this year and next year, and we're looking for our earliest potential authorization in the U.S. as early as next year. Just to remind some of you, while local radiation today is being dominated by beta and gamma radiation, these are the forms of radiation that penetrate tissue and can easily cover a tumor, the issue there being the large dose needed, the inefficiency of that radiation, and the tendency to spread to surrounding organs and do damage. Alpha particles are known to be incredibly more efficient. We can use lower doses. They're much more tightly controlled. However, they are so short in range that when we insert an alpha emitter into a tumor, we find we get 40 to 90 microns of range, which is incredibly useless, and this inability to get the alpha particles to move to any real range inside of the tumor is the reason nobody until now has been able to use alpha particles locally inside of a tumor. The way in which we overcome this, as many of you know, is by the Alpha DaRT, which is a small metal source coated with radium-224. Radium is useful for us in that it breaks down six times before it stabilizes. It releases a number of alpha particles along the way. But while the radium is trapped onto the source, its daughter atoms will escape off of the source into the tumor and will float around, diffusing into the tumor, releasing alpha particles as they go. So the idea is that we can inject one or more of these sources into the tumor. We can leave it there with the radium trapped right near the surface. Once the radium breaks down and its daughter atoms escape, over their 12-hour half-life, they will diffuse deeper and deeper into the tissue, and in doing so, they'll decay deeper in the tissue. And the alpha particles, which remain short in range, are being delivered at a deeper distance because of those diffusing alpha emitters. And so we've effectively extended the range of these alpha particles from a couple of tens of microns to a few millimeters. Now, as you know, we've had to think for years as to what do we do with the treatment, which is quite straightforward in its physics. We believe not to be specific to any particular tumor type, and we have to figure out where we want to focus our time. And we've historically focused or talked about three core focus areas where most of the data we've shown to date has been on the first focus area, the localized and unresectable tumors. These are tumors that may have other available local options. When those local therapy options have been exhausted, we have found we may have potential as a later line source of hope. As many of you know, we initially started in that area, particularly in superficial tumors, tumors of the skin or the head and neck. The decision there was based on the fact that there was ease of access to these tumors. It was straightforward to control the delivery into these tumors. We were able to monitor safety because these delivery sites were close to the surface. Once we had strong preclinical data in squamous cell carcinoma, we initiated our trials in these superficial tumors. Since then, we've treated hundreds of tumors. We've seen a very mild safety profile. We've secured approval in Israel to treat SCC of the skin or the oral cavity. We’ve submitted to the PMDA in Japan a request for authorization to treat recurrent head and neck cancer. Of course, our flagship remains the ReSTART study, which is our pivotal study underway in the U.S. to secure that hopefully our first approval from the FDA. We’re treating patients with recurrent cutaneous SCC. That’s a skin cancer. We’ve been running this trial, but increasingly shifting our focus to Mohs surgeons, as we’ve discussed in the past, as we note that these surgeons who are dermatologists specialized in tricky surgical resections of skin cancers are really the ones who have many of our patients. And so, as we've learned that, we've increasingly taken our time in the study to shift towards the Mohs surgeons, to involve them in the trial, bring them on site, and show that we can actually use the Alpha DaRT, which has a very limited need for radiation safety protections, to use this treatment in the Mohs surgeons' office as well. And so now we've talked about how we're going to be treating patients over the course of this year. We expect a complete recruitment in that study in Q3 of this year. We have a six-month durability benchmark. So that would give us data in early 2026 for potential submission to the FDA in the first half of 2026. I think this is what people know about us so far. Where we really want to spend our time today is showing you part of the broader vision about how we see the Alpha DaRT's relevance in our other two pillars of our therapeutic strategy, so one of them is, as we've always discussed, has been the high unmet need. If we have a treatment which is truly indifferent to the nature of the tumor, we may as well go after those tumors with poor first-line options, and examples that come to mind include pancreatic cancer, glioblastoma, et cetera, and so some of our colleagues here today will discuss their experiences using the Alpha DaRT in treating pancreatic cancer, as well as a number of other internal organs. The other third focus area we've always talked about has been the metastatic patients. This really owes to some of the evidence we've seen that the Alpha DaRT appears not only to be destroying the tumor into which it's delivered, but also seems to trigger an immune response across the body. Now, we've seen this manifest in a couple of different ways. We've seen this in the fact that mice, for example, in preclinical work, will become immune to a particular cancer that they're given, that they're treated for, but susceptible to other cancers. We've shown the ability to activate checkpoint inhibitors. Mice that are not responding to checkpoint inhibitors will respond potentially in the presence of the Alpha DaRT. Most notably, we've seen a number of cases in humans where we will treat one tumor, and an unrelated tumor elsewhere in the body will spontaneously respond or disappear. This remains an area we want to continue to explore with the idea being, can we use the Alpha DaRT as a local therapy to be part of a systemic solution to help the body fight tumors elsewhere in the body? We will also spend time today discussing how we've translated the preclinical work that I mentioned earlier, showing the ability of the Alpha DaRT to trigger a systemic response and to trigger effecting the activation of the checkpoint inhibitors into a human clinical study as well. Let's start with the pancreatic cancer data. It's my pleasure to call on my colleague and friend, Dr. Robert Den, who's been the Chief Medical Officer of Alpha Tau since 2019. Dr. Den has a BS from Yale University and an MD from Harvard Med School. He trained in radiation oncology at Thomas Jefferson University, where he remains an associate professor. Please, Dr. Den. Good morning, everyone. Thank you so much. Truly a pleasure to be here. And thank you, Raphi, for the introduction. So what I'm going to do over the next 20-25 minutes is discuss the current up-to-date results from our trials, which are enrolling patients with pancreatic cancer. So we currently have three trials in which patients with pancreatic cancer are eligible to receive Alpha DaRT technology. The first trial is the PANC-101 trial. This is a monotherapy trial of the Alpha DaRT for patients with unresectable pancreatic cancer. It is currently being run in two sites in Montreal, Canada, and can enroll up to 37 patients in total. We have a second trial specifically for pancreatic cancer, again for an unresectable, locally advanced, or metastatic cohort that is currently running in one site in Jerusalem. And this trial can enroll up to 15 patients in total. Finally, as Raphi noted, given that Alpha DaRT technology is effective across multiple different tumor types, in conjunction with the Ministry of Health in Israel, we have opened a trial that we call the TARGETS trial, which is a flexible basket trial which allows for enrollment of any patient without a current standard of care. Within this trial, we have enrolled pancreatic patients on it as well. Most of these patients have been with locally advanced or metastatic unresectable disease. And for various reasons, we're not eligible for the PANC-02 trial. But for the purposes of understanding the Alpha DaRT technology within the context of pancreatic cancer, we are including them here in this analysis. Just some notes in terms of chemotherapy with Alpha DaRT. So in the PANC-101 trial, which is the trial currently running in Canada, we do not allow for concurrent use of chemotherapy. But chemotherapy can be delivered after 30 days of the DaRT insertion. On the PANC-02 trial, we've done a modification to the trial after we've seen initial safety data that we have published based on PANC-101 that we will allow for concurrent use of chemotherapy. So therefore, we are currently showing you the results of all three trials combined to gain a better understanding of the role of Alpha DaRT within the context of pancreatic cancer. So looking firstly at the patient characteristics, it should be noted that we have a total of 41 patients who've been treated thus far with pancreatic cancer across all three trials. Just to note, we've previously published on the first five patients treated out of Canada, and they are included within this 41-patient total. If we look specifically at the patients, you can see 24 patients were enrolled in Canada, 17 were enrolled in Israel. We have parity in terms of the gender of the patients with 50% male, 50% female. The median age was around 71, and as you can see, one-third of all patients enrolled on these trials had locally advanced disease, and two-thirds of these patients had metastatic disease. When we look at previous lines of chemotherapy, what we see is that approximately nine patients had not received any prior chemotherapy, 15 patients had received one prior line of chemotherapy, and 17 patients had received two prior lines of chemotherapy. Now, given that these were pilot trials, the primary endpoints were both feasibility and safety. When we look specifically at feasibility, we see that we had a 100% success in delivering the Alpha DaRT sources to all patients. Every patient that we intended to treat with Alpha DaRT was able to receive treatment with the therapy. When we look across safety, we see very strong safety results. There were a total of 151 adverse events reported. But when we specifically look at those adverse events that were associated with Alpha DaRT or the procedure itself, you can see that there were 38 total events. Approximately 20% of the adverse events were related to Alpha DaRT, of which the vast majority, two-thirds, 29 were grade 1, five were moderate grade 2, and four were grade 3 or severe. Now, of those four, three were classified as serious adverse events. And these included two cases of elevated liver functions. In one case, the patient required hospitalization and was discharged. In the second case, although the patient was recommended to undergo hospitalization, they actually declined to be hospitalized and were able to recover at home without any further intervention. And the third SAE was one case of sepsis, in which case the patient was treated with antibiotics, hospitalized, and discharged home, resolved. Again, it's important to note, as we've published in our prior trials, we have seen no grade 4 or grade 5 related events. And as you can see, the four grade 3 events listed here. And the types of events that we see are expected within the context of treatment of pancreatic cancer. Now, looking specifically at results. So what I'm first going to show you are early results, specifically looking at the objective response rate as well as the disease control rate. Just to remind you all, the objective response rate includes patients that had both a complete as well as a partial response by RECIST criteria. And disease control rate includes complete response, partial response, as well as patients that have stable disease. Now, as you can see, we have broken this down into two distinctions, one where we include the first two patients and one where we exclude the first two patients. The reason for this is because in the Canadian study, as it was the first-in-human study of delivery of Alpha DaRT via endoscopy, there were numerous safety concerns that we had that were also expressed by the Ministry of Health. And because of that, we specifically and judiciously decided to slowly increase the amount of sources that we would put into patients. And we would only treat one patient per month for the first five patients. Thus, we knew that for the first two patients, they were underdosed, again, because we wanted to be cautious with regard to safety, specifically with concerns of infection, bleeding, or acute pancreatitis, and it should be noted that we have yet to see a case of acute pancreatitis. Now, when we include those first two patients, what we can see is we have 33 total patients in which an objective response rate was measured. Five patients are currently awaiting response, and three were discontinued on the trial prior to their evaluation. Including those first two patients, as you can see, we have an objective response rate of 18% and a disease control rate of 91%, and again, this is based on best overall response using RECIST. Now, when we exclude those first two patients, again, who were purposely underdosed, we see that the objective response rate is 19%. But we see an increase in the disease control rate to 97%. And it should be noted that only one patient after the first two had evidence of progressive disease following Alpha DaRT treatment. What I will do now is I will spend the rest of the time discussing survival data on these patients. Now, again, these are small trials. The data is still being collected as patients are still enrolled and accruing on the trial. But what we are trying to show is give you a sense of the potential overall benefit of Alpha DaRT, specifically in pancreatic cancer, which is thought to be a systemic disease. So when we look specifically, what we see here is, again, we are seeing the 33 patients. Out of the 41, we are excluding five of them who were treated more recently and do not have enough time on trial follow-up to be included in the analysis, as well as the three patients who left the trial early before the primary endpoint of response rate. What we can see is in the total 33 patients, when we use Kaplan-Meier analysis, we can see that since receiving Alpha DaRT, the overall survival rate is 10.9 months. Now, this is a heterogeneous population. And so therefore, in order to understand and be able to put this within the context of the published literature, we did a second look at overall survival. But this time, taking the starting point either at the time of initiation of the prior chemotherapy line or for those patients that had not received any prior chemotherapy, we looked at the time starting from their date of diagnosis. What you can see based on this, we have an overall survival of 18.6 months. Of the 33 patients analyzed, 13 have died, and 20, including the five more recently enrolled patients, remain alive. Now, given the heterogeneity of this population, which includes both locally advanced as well as metastatic patients, it includes patients who had been ineligible to receive any chemotherapy, those that had received DaRT after the first line, and those that had received DaRT after the second line, what we decided to do was to specifically analyze different subpopulations where we had a substantial amount of patients within that subpopulation to further give us insight into the overall benefit of DaRT in terms of overall survival for these different patient populations. The first patient group that we are looking at here are patients who are newly diagnosed and were ineligible for chemotherapy. These are either patients who could not or would not receive chemotherapy. They were all enrolled onto one of our three trials. We had eight patients that met this criteria. What you can see, with a median follow-up time of 6.3 months, based on Kaplan-Meier analysis, we have a median overall survival of 7.5 months. To put this in context within the literature, and here I am showing you two different and unique studies, we would anticipate a median overall survival for this population of those that are ineligible for chemotherapy with newly diagnosed locally advanced or metastatic pancreatic cancer to be between 3-3.5 months. Here, again, we're seeing an improvement in that survival now to 7.5 months. Turning to a second patient population, here we are looking only at patients that have metastatic disease and only patients that received first-line FOLFIRINOX, which is the most common regimen here in the United States. We had 10 patients that met that profile. With a median follow-up of 15.1 months, we can see that the median overall survival has not yet been reached in this patient population. Eight of 10 patients still remain alive. We would anticipate, with the use of front-line FOLFIRINOX, that we would see a median overall survival between 10-11 months. Although our median follow-up has surpassed this, we see that we have yet to reach our median overall survival. Finally, turning to the last subgroup that we are analyzing, we're now looking at patients with both locally advanced and metastatic pancreatic adenocarcinoma who progressed after second-line Gem/Abraxane. This includes seven patients with a median follow-up of 18.9 months. We see that the Kaplan-Meier overall median survival is 23 months. Again, to put this in context, we would anticipate a survival for patients on second-line Gem/Abraxane of anywhere between 7.5-10 months. It should also be noted that within this patient group that received Alpha DaRT, using the date of DaRT insertion to last follow-up, we have a median overall survival of nine months by Kaplan-Meier analysis. So given all of this exciting data in these three different trials for locally advanced as well as metastatic patients, we have received approval here in the U.S. from the FDA under an IDE for a pilot trial. And the trial will consist of 12 patients, all with newly diagnosed metastatic pancreatic adenocarcinoma. All of these patients will receive between eight to 12 cycles of modified FOLFIRINOX, again, standard of care for front-line metastatic patients. These patients will then undergo the Alpha DaRT insertion anytime between cycles one to four of modified FOLFIRINOX. So this will be a single DaRT procedure occurring anytime between cycles one through four. The primary endpoint is a safety endpoint of incidents of treatment emergent adverse events, and we will have several secondary endpoints, including overall survival, progression-free survival, as well as pain improvement. Now, as many of you are aware, Alpha Tau is an international company. We are running trials not only here in the U.S., but worldwide, and what I'm showing you is an approved trial that will be opening shortly in France. This is a multicenter trial. This is for patients with locally advanced pancreatic adenocarcinoma. These patients have already received modified FOLFIRINOX before enrolling onto this trial, so we are taking patients who had previously received modified FOLFIRINOX, who, based on RECIST, either had stable disease or a partial response after that front-line chemotherapy regimen. They will then undergo screening to be followed by the Alpha DaRT insertion, again, through endoscopy, at which point the patient will then receive maintenance chemotherapy consisting of capecitabine. The patients will then be on follow-up for up to 12 months and undergo CT scans every eight weeks, by which RECIST criteria will be determined. The primary endpoint on this study, again, is safety, as it is a direct combination of DaRT with maintenance chemotherapy. The secondary endpoints include objective response rate based on best overall response rate. We will also be looking at overall survival, progression-free survival, as well as resectability rate. There will be further exploratory endpoints on this trial where we'll be looking at blood samples from peripheral blood, as well as circulating tumor DNA analysis. The physicians on this trial will have the options of either continuing maintenance chemotherapy for those that are stable or responding. The patients are eligible to undergo surgical resection if they become surgically resectable. They may also undergo a therapeutic pause. If, unfortunately, the patients are found to be progressing, they will then be switched to either second-line chemotherapy or best supportive care. This trial enrolls 40 total patients across 13 different sites within France and will help provide further data demonstrating the potential benefit of Alpha DaRT in the context of locally advanced pancreatic cancer. Thank you very much. Thank you very much, Dr. Den. First of all, thank you for that. That was the summary of the overarching data, looking back and taking a view as to the survival on chemo and Alpha DaRT together afterwards versus a survival on chemo on its own. Very exciting to see coming out ahead of all the various chemotherapies and the groups that we did. Now we're going to dig into a specific case of one of the patients that we treated to be presented by Dr. Philip Blumenfeld. Dr. Blumenfeld is a radiation oncologist and the head of the Thoracic and Pancreatic Cancer Radiation Services at Hadassah Medical Center in Jerusalem. He earned his medical degree from Tel Aviv University and a Master's in Public Health from Hebrew University of Jerusalem and completed his residency in radiation oncology at Rush University Medical Center in Chicago. He's actively involved in a number of research studies and will talk today on two different elements. One of them will be a pancreatic cancer patient that we'll discuss now. The second discussion will be on his research on novel ways to re-irradiate patients who already had radiation before. So let's start with a discussion of one of the patients we've treated so far. Please, Dr. Blumenfeld. Thank you very much. So today, I'd like to share with you the first pancreatic cancer patient treated at Hadassah Center. This is a 70-year-old male who was diagnosed with pancreatic adenocarcinoma, which was metastatic to the liver at diagnosis. He was treated with FOLFIRINOX between the dates of May through November 2023, but unfortunately, he developed progressive disease. Subsequently, he was treated with second-line chemotherapy with gemcitabine and Abraxane from December 2023. And unfortunately, then demonstrated further progression at the primary tumor, but otherwise stable disease, including disease in the liver. He was subsequently enrolled on the Alpha DaRT trial. And in January 2024, we delivered a DaRT treatment together while he was continuing his chemotherapy. So I'd like to share with you some of the observed response rate that we demonstrated in this patient. The first PET of the patient with pancreatic tumor, as you can see in November 2023, we have the PET scan demonstrating a tumor in the head of the pancreas, which was PET avid, as well as his markers were going up at this time. At 30 days post-treatment, we demonstrated minimal uptake in the lesion, which was but distal to the lesion. We noted some post-treatment inflammation. At 30 days, at 90 days, there was no avidity in the pancreatic tumor, and the inflammation distal had since regressed. What was very interesting, at 90 days post-treatment, the lesion no longer remained evident on PET, despite no change in systemic therapy. As you can see, there was also a liver lesion, not only that regressed from 30 days to 90 days, no longer evident on further PET-CT. Cancer markers subsequently dropped significantly, and the patient continued his systemic chemotherapy. Excellent. Thank you, Dr. Blumenfeld. So now we've had the broader picture of the response rates. We've had the specific dive into one particular patient with a fantastic response, a complete response in a tumor that was treated, and a complete resolution on the PET in metastases as well. Now we want to talk a bit about the user experience on the clinician side. Obviously, as we've discussed in the past, we continue to focus at Alpha Tau on novel ways to deliver the Alpha DaRT into tumors of various parts of the body in a way which is both intuitive and easy to use for the clinicians. And so Dr. Miller has been at the forefront of that work with us in the work in the pancreas. He serves as an assistant professor at McGill University's Department of Medicine and practices at Jewish General Hospital in Montreal. He has a BA from the University of Pennsylvania, as well as an MD from McGill University, and has a Master's in Experimental Medicine from McGill with a thesis centered around endoscopic anastomosis. He completed his medical residency and GI fellowship at McGill and a clinical fellowship in advanced endoscopy at Beth Israel Deaconess Medical Center of Harvard Medical School. His clinical research interests include ERCP, EUS, and other advanced endoscopic techniques, particularly on endoscopic interventions to improve outcomes for patients with pancreatic cancer, which is what he'll discuss today. Please, Dr. Miller. Thank you, Raphi, for the introduction. Good morning. It's great to be with you all. I'll imagine as if you're here with me in this beautiful room as we have this discussion so pancreatic cancer from the perspective of an endoscopist, just as a reminder, in 2025 and for a while now, endoscopic ultrasound is really the best way of accessing the pancreas. It is the standard of care now for a while for diagnosing, for biopsying the pancreas. In addition, of course, the background, which is already described well by my colleagues, the treatments for pancreatic cancer in 2025, other than those who are able to be resected surgically, which is the minority, and even those who do end up undergoing surgical resection, it ends up being very challenging local treatment and treatment in general. Having said all of that, there is no standard for pancreatic cancer for local, regional, for people who cannot have a surgery for the pancreatic cancer. There is no standard local treatments today. To compound that, there are local symptoms related to pancreatic cancer other than the spread of the disease and its effect on the body. Locally, it can cause pain. It can block different parts of the GI tract and the biliary tract as well. Here's a bit of an overview of the technique, if you would, in cartoon fashion. Briefly, this is the loading device. A standard needle that we're all familiar with in endoscopy is loaded with this innovative loading device. That standard needle then is ready to go with the echo endoscope passing into the patient. That's me putting in, as we'll go through, one source under ultrasound guidance, and then the second source under ultrasound guidance. And then, as you can see, it has its amazing effect, as described, and the tumor shrinks just like that in real time. I'm just joking, but it could be. So a brief word on our lay of the land. This is Montreal, Quebec, and this is where we started doing this thing. And this is our procedural setup. We're here with an amazing team, which we're able to assemble. I'll talk a bit more about that, how everything comes together in a very interesting way. But we have our anesthesia, which is separate from the loading area with our needles that have the preloaded sources of the DaRT of Alpha DaRT. And just to go now through the insertion technique, the first thing I want to say is, again, on this topic of ease of use and applicability to the advanced endoscopists, this is a standard technique. It's really an extension of everything that anyone who's trained in endoscopic ultrasound and advanced endoscopy is used to. It's a small learning curve for the expert endoscopist. Essentially, this is what's called the adjustable stopper. So the way of deploying through a standard FNA needle, through a standard EUS, where you're visualizing the tumor, and you basically just compress from this adjustable stopper, has a button on the top, and it pushes the source exactly where you'd like to go under your live ultrasound guidance into the tumor. It's the same feel that we're all used to for biopsying pancreas or inserting a pain ablation technique and other things that we do with standard EUS. I do want to mention there was an innovative retraction handle that we developed during the course of the pilot trial when we started treating patients to answer some of the challenges that have come up in this fascinating new way of treating pancreatic cancer. What it does, the retraction handle allows one to load four sources at the given time at the same time. The retraction handle has the advantage, one, that it has multiple sources. One puncture, one placement, and you're able to put multiple seed sources. That's an advantage with time efficiency and position and ease of use. But the other thing that's very innovative and very accurate in that the design is such that the retraction handle pushes the seed out as it moves the needle back. And it's actually first of its kind in the world of endoscopy and therapeutic endoscopy. So it's quite effective in placing the source precisely where you want it to be. Having said all of this, I do want to show you one of our very first cases in Montreal. This is real-time what I'm looking at when I'm treating pancreatic cancer using this technique. So here's a quick video. There's the tumor. You can tell, I'm sure. You don't even need to have an advanced endoscopy training for that. And there's that needle, the seed going out. And then you can see it placed. I'll show that one more time, actually. There's the needle on the top right of the screen, and you can watch carefully as the needle's pulled back, the seed's going forward. You can even see some previously placed seeds on the bottom of the screen, and the sources are in place, ready to do their work in the tumor, so the endoscopist experience, it's a natural extension of the skill set that we have. As I mentioned, if we're doing a celiac plexus neurolysis for pain, we're injecting something into the pancreas or the surrounding areas. The biopsy, the technique is intuitive. With the safety data that we have that Dr. Den went through in detail that we've seen so far, there's confidence not just from the technique, but with the knowledge that it seems to be very much safe. And then in terms of practicality and in terms of potential barriers to adoption, it's not prohibitive the length of the procedure, especially when you get started with your team and you've done a couple of these cases. It's not more than about 45 minutes if you want to take your time. And that's really not more than a standard, well-done, thorough EUS exam. And then finally, in terms of the room setup as well, with a little bit of practice, so a couple of cases for a learning curve to get the hang of it, it's also not a barrier and it's not hard to do. A word on radiation safety. Many would be worried. We hear radiation and now you're combining it within endoscopy, sort of outpatient clinic, et cetera. We did actually look at the data from the first, this is from the first five patients in our study in Montreal. And we measured radiation detection, so the endoscopist's radiation exposure at my skin and then 10 millimeters deep to the skin, as well as the technologist who's working with me, passing me the needles and the sources. And what we find, lo and behold, just a summary statement here is that using all of it together and the standard limits for the general population, we would be able to perform, just me and this one technologist, 25,000 cases in a year before reaching our yearly limit of the, sorry, of the public. And if you're a nuclear worker, a nuclear energy worker, that tolerance is even higher. From a patient perspective, just a word on that. Again, outpatient procedure, every single one of our patients were discharged the same day as the procedure. It's minimally invasive, of course. The safety profile, as Dr. Den went into in some detail, I will just also assert from my perspective, it seems to be very much safe, and that's the objective of our trial. Some minor discomfort that is transient and the vast majority with no symptoms at all, and very interestingly, although this wasn't the focus of such an early pilot study, which was feasibility and safety, we do see this overwhelming stability in terms of the tumor size and the lack of growth in the majority and pain relief, which seems to be happening frequently and quickly. Just a word on moving forward and future prospects and this exciting new modality. As we're looking to overcome, let's say, refine and optimize this technique, which is new, an extension of standard endoscopy practice, but a new concept. We're looking to consider, and we have plans to do so, to make a better visualization of the pancreas tumor, a real-time model that we can actually track the tumor and enhance our coverage. And we have a grant with the Quebec government and other institutions with multiple universities coming together, the R&D team of Alpha Tau and engineers from universities as well to make this happen. So it's very exciting. This is our team, and there are many others now forming across the world. Now the U.S. is starting and France as well. I've met some of these teams. And again, people coming from different backgrounds within the hospital system to make it all work, which is part of the fun. Just to summarize, we see as endoscopists, pancreatic cancer, a very challenging clinical entity. We see it from the beginning, from the diagnostic stage, and we see it at the end when we're alleviating complications. It is a natural extension to me of the endoscopist practice that we'd be able to do something like this. It's straightforward to put Alpha DaRT from a technical standpoint, from potential barriers to adoption in the unit, the endoscopist, the technologist, and the setup and everything in between. It's very much a natural extension to incorporate this into an endoscopy clinic, as far as I can see. And then early benefits through pain relief, and the disease seems to be stable in many. And then we are even looking for potential effects in the future on metastatic disease, local pain control, and tumor burden. With all of that, I will thank you for your attention. Excellent. Thank you very much, Dr. Miller. Okay, so that completes the first part of our discussion, looking at what we've learned so far from treatments to pancreatic cancer. We're going to move now to talk just about a few select case studies where we treated other internal organs and have an initial flavor of what it looks like to use Alpha DaRT, and I'm going to start with Dr. Blumenfeld again to talk about some of his research on the challenges of re-irradiating patients. Please, Dr. Blumenfeld. Thank you so much. So the treatment of recurrent or new primary cancers within or close proximity to previously irradiated tissue is a very clinically challenging problem as radiation oncologists. And that's primarily due to the tissue tolerance concerns. Specifically, re-irradiation with stereotactic body radiation therapy, a very highly conformal type of radiation for ultracentral lung tumors, such as tumors in the mediastinum, can carry a very high risk of severe toxicity. It can include inflammation of the lung, inflammation of the esophagus, and in certain cases, even fatal hemoptysis. In addition, patients can receive radiation to their bronchial tree, which potentially can cause bronchial stenosis and other significant issues. In terms of the pelvis, such as patients with recurrent rectal cancer, re-irradiation can carry a high risk of rectal dysfunction. It can carry risk of nerve damage as well as fibrosis of the tissues. Therefore, balancing the need to optimize tumor control while also minimizing adverse effects is much more difficult when we're dealing with prior radiation therapy. As mentioned, in certain scenarios, we opt as radiation oncologists either for non-curative systemic therapy or when giving re-irradiation with conventional or advanced techniques, such as stereotactic body radiation therapy, as mentioned, or proton beam radiotherapy. Specifically, SBRT or SABR is a technique that's very well and often used in this type of scenario. However, the literature points out that patients that undergo SBRT for recurrent thoracic tumors can have significant toxicities, as mentioned. There are several studies that have demonstrated the feasibility of this technique, however, and with reasonable high local control of the tumor, however, with significant potential collateral damage and even several cases of grade 5 toxicities. One of the other scenarios in which we treat or modalities in which we treat thoracic cancers can be in the recurrent setting can be proton therapy. Proton therapy has distinct advantages in that when the beam is delivered, there's no exit radiation into potential organs nearby. And so this can have significant potential in the case of re-irradiation. However, still, even with proton external beam radiation therapy, we still see in the recurrent setting significant toxicities and not always the best control rates. And therefore, while this is definitely an option, the radiation oncologist, when dealing with re-irradiation, has to think hard whether or not he should deliver this treatment. I'd like to share with you the first lung cancer case study in a patient first time ever delivered Alpha DaRT re-irradiation. So this was a patient with locally recurrent lung cancer. He was 70 years old with a diagnosis of limited stage small cell lung cancer. He received external beam radiation to the primary lung lesion as well as to the mediastinum, as you can see in this figure here. We have the dose that was delivered to the lymph nodes in the mediastinum as well as the primary tumor. He received this in August 2023 with standard concurrent chemotherapy. Unfortunately, as with many of these patients, he had metastatic progression six months post-treatment. And he received chemotherapy and external beam radiation to several locations with a very good response. However, again, in PET CT in August 2024, his tumor in the mediastinum progressed and it was enlarged, and there was uptake in a peritracheal lymph node. Now, this is a very tricky area for radiation oncologists because of the close proximity to the proximal bronchial tree, the esophagus, the great vessels, and therefore further external beam in this scenario can pose significant risk to the patient. So he was referred to the Alpha DaRT trial with the goal of attaining good local control and hopefully, potentially keeping this patient off systemic therapy for a little bit longer in time. So this patient, as mentioned, was referred to the Diffusing Alpha DaRT radiation therapy protocol for recurrent lung cancer, and 10 Alpha DaRT sources were implanted with our bronchoscopists into the peritracheal lymph node. The lymph node initial volume was 3.6 cc, and subsequently, at 30 days, it reduced to 2.1 ccs, and at 60 days post-procedures, 1.7 ccs. You can see in the figure the Alpha DaRT sources are visible within the treated lesion, and you can see in panels B and C. There was, as noted in the chart here, you can see the percent change was quite significant in terms of the volume of the lymph node post-treatment. We also see post-treatment PET-CT at 60 days, an initial reduction of the PET SUV to 7. What was, as mentioned, one of the things very difficult in this type of scenario is the dose that was received to the organs at risk. With Alpha DaRT, we were able to deliver a good dose to the lymph node, a very high dose, an ablative dose to the lymph node, but at the same time, really zero dose to the organs at risk. The proximal bronchial tree max dose was zero, esophageal dose zero, and the mean dose to the lungs was very close to zero. This is unheard of with external beam or even proton beam radiotherapy. In this specific patient, we had no treatment-related adverse events following the radiation treatment. I'd like to give you another rectal cancer case, a case study in which we delivered DaRT treatment. So this is a patient who's 70 years old, and he presented to our institution after undergoing chemoradiotherapy followed by chemotherapy for a low-lying rectal adenocarcinoma. Unfortunately, when subsequent PET exams were done, there was still residual tumor at the rectum involving the sphincter, and therefore, he was recommended to undergo abdominoperineal resection. This would mean that the patient would have a stoma for life, and he would have a non-functioning rectum. The patient subsequently declined. In September 2022, the patient underwent Alpha DaRT insertion. A year later, post-treatment, his exam was totally normal. His rectal function was absolutely intact, and his PET-CT SUV uptake was down to 4. Two years post-treatment, March of 2024, his PET-CT uptake was none. On exam, he was totally normal. When I saw him and spoke to him in follow-up, he had denied any bowel or bladder issues. There was absolutely no treatment-related adverse events in this patient with a complete response to Alpha DaRT radiation therapy in a patient who otherwise would have required an abdominoperineal resection, leaving him without use of his rectum. In conclusion, despite the high risk associated with re-irradiation, our initial cases of re-irradiation of internal organs, specifically lung and rectum re-irradiation using the Alpha DaRT treatment, demonstrated high efficacy and very minimal to no toxicity. Thank you. Thank you very much, Dr. Blumenfeld. To wrap up this section, looking at some case studies of where we've seen Alpha DaRT used in other internal organs, I'm going to reintroduce my colleague, Dr. Den, to talk about our first patient treated for liver metastases. Please, Dr. Den. Thank you again, Raphi, so as a way of introduction, what I would like to do is to discuss the current trial that we have open for patients with liver metastasis. Specifically, this is a trial for patients with colorectal liver metastasis. It is being delivered in the setting of a two-stage hepatectomy, which I will explain in the next slide, but just to give a context of this trial, the primary objectives on this pilot trial are feasibility and safety of Alpha DaRT implementation into liver metastases. We have secondary as well as exploratory endpoints to evaluate both pathological as well as radiological response to determine the immunological impact, and we are stratifying the results based on response of histopathology based on the histopathologic growth patterns, which have been described by the investigators of this trial between a vascular versus an immunologic background histological growth pattern. As you can see, these are patients who are referred for a two-stage hepatectomy. There is no prior use of any systemic investigational agent allowed on this trial. We are enrolling a total of 10 patients. They are all having the Alpha DaRT procedure being performed intraoperatively. And the way that this procedure works is they undergo two unique operations. The first operation is one in which the patient undergoes metastasectomy from one side or one lobe of the liver where all visible metastases are removed. During that procedure, on the contralateral lobe of the liver, Alpha DaRT sources are implanted. The patients then undergo three to four cycles of chemotherapy. And then they have a second operation in which the lobe of the liver that had metastases, including the ones treated with Alpha DaRT, are removed, and they remain with a partial liver that is currently disease-free. Here again, to show specifically the procedure, it is two-stage. In the first stage, there is removal of tumors from one lobe of the liver. After this point, we are inserting the Alpha DaRT sources into a lesion in the contralateral lobe. The patients will undergo a portal vein ligation to the lobe. This will then cause the lobe in which all of the tumors have been removed to grow. Over four to eight weeks in which the patients are receiving chemotherapy, this lobe of the liver has grown to approximately 30% of the total liver. This allows for the removal of the contralateral liver, and in which case, the patients are able to continue to live with the 30% of the first liver. Now, it is important to note in this trial that we have a unique ability to really look at the impact of DaRT. We have the baseline tumors that are removed prior to any intervention at all. We're also able to look specifically at the lesion in which the DaRTs were inserted, but just as intriguing, especially in light of the comments that Raphi made earlier about the potential immune effect of DaRT, we're also able to look at these untreated lesions that remained in place after the insertion of DaRT, so I'm now going to describe to you the first patient that was treated. This was a 48-year-old male who had bilateral colorectal metastases to the liver. The patient was off chemotherapy for eight weeks prior to the first stage of the two-stage hepatectomy. This first stage was performed on May 9, 2024, with resection of primary colorectal tumor as well as sigmoidectomy, and the patient had liver metastases resected from segments two and four. Then they had 25 Alpha DaRT sources implanted into a lesion in the liver segment eight. This represented approximately 6% coverage of the tumor itself. Now, what did we see after seven days at the initial scan? We found that the patient clinically was doing well with no signs of distress or dyspnea, no evidence of jaundice. When we specifically looked at the initial imaging and specifically looked at the lesion that was treated with the Alpha DaRT, we see that the treated lesion in segment eight reduced in size from a longest dimension of 6 cm to 4.9 cm. Fascinatingly, the largest untreated lesion had also regressed, with the largest hepatic metastatic lesion in segment seven reducing in dimension from 4 cm to 2.9 cm. Importantly, there were no newly developed hepatic lesions, and the portal and hepatic veins remained patent. And just to note, on this scan, the patients had yet to receive the interim chemotherapy between the first to the second stage of the hepatectomy. Here you can see on imaging, the image on the top shows to the left, excuse me, shows you the treated lesion. So here you can see in the pre-insertion versus the post-insertion with the reduction in size. But as importantly, you can see in the untreated lesion also a reduction in size of the liver metastasis, as was noted on the previous slide. Now, the patient then underwent the second stage of the two-stage hepatectomy in June, five weeks after the initial operation. The entire right liver was resected, including the Alpha DaRT treated lesion. There were no significant complications or unexpected events during the postoperative period. The patient was discharged as planned, and the recovery post-discharge was uneventful without any complications. So from both a feasibility and safety perspective, this patient was a success on the trial. Specifically turning to the pathology, we can see that the treated tumor was non-desmoplastic, which is quite interesting as this has a prognostic significance in colorectal metastases. Now, the adjacent and non-treated but responding tumor was desmoplastic. But just as importantly, as was mentioned previously by Dr. Blumenfeld, there was minimal to no damage observed in the surrounding liver parenchyma despite delivering a definitive treatment to part of the tumor. When we specifically look at the immune response, we saw both an adaptive immune response, as you can see here, with an increased infiltration of the CD8 positive T cells in the right liver lesions, both treated and untreated. And this supported the hypothesis that enhanced antigen exposure was induced by Alpha DaRT that can activate cytotoxic T cells. In addition, we saw an innate immune response as well, with an increase in dendritic cells and neutrophils, but a lower abundance of macrophages in the DaRT-treated tumor compared to the untreated tumor. So in summary, the Alpha DaRT implantation was performed intraoperatively without any significant technical difficulties. There were no adverse events related to the Alpha DaRT treatment observed throughout the clinical course of the patient. There was no evidence of any source migration, and there was complete removal of all the Alpha DaRT sources from the liver. There were no safety concerns observed regarding the insertion to either the medical staff, nursing staff, or the patient. There was no excessive hemorrhage. The patient's recovery followed the normal trajectory, and we saw a more pronounced adaptive immune response as well as reduction in macrophages, potentially indicating a reduction in the immune suppressive nature. We know that the liver is specifically an immunosuppressive microenvironment. Finally, we saw a decrease in tumor size in the untreated lesion despite a long period without the patient being on any systemic chemotherapy. Thank you, Dr. Den. That wraps up our second portion, which is looking at the selected case studies of internal organs other than the pancreas that have been treated with the Alpha DaRT. We saved the best for last. We're now going to discuss the combination of the Alpha DaRT together with pembrolizumab, and I'm pleased to introduce, last but not least, Professor Aron Popovtzer. Professor Popovtzer is the director of the Sharett Institute of Oncology at Hadassah Medical Center in Jerusalem. He graduated from Hadassah and finished his ENT residency at Beilinson Hospital in Israel. He completed a double residency in oncology and radiotherapy, specialized in head and neck cancer at the University of Michigan in Ann Arbor, did training in brachytherapy at Beth Israel Hospital in New York, and additional training at Memorial Sloan Kettering in New York in the field of radiosurgery. He serves as the chairman of the Israeli Society for Head and Neck Tumors, Israel's representative to the World Society of Head and Neck Cancer, and is active in the European Organisation for Research and Treatment of Cancer, or EORTC. It's my pleasure to introduce Professor Popovtzer. Okay. So good morning, everybody. I thank you, Raphi, for your introduction. We're going to shift gears a little. Until now, basically, we have been discussing many studies that basically focus on the fact that Alpha DaRT can kill tumors. If we go back, we started with skin cancer, then that was our first studies. Then we moved to head and neck cancers, and now we're doing it in pancreas cancers and liver cancers, as we've just mentioned, in lung cancers. We're starting a GBM program. We are all over. However, I would like to introduce a new concept in which the Alpha DaRT is not serving as a killer of tumor, but as a radio enhancer. How does it work? This is our first trial, the first trial ever in which we used the Alpha DaRT as an enhancer of checkpoint inhibitor. This trial is what we called our head and neck cancer checkpoint inhibitors zero, so what were our criteria for this study? We took all recurrent and unresectable, very resectable or metastatic head and neck squamous cell carcinoma, like we have in the KEYNOTE-048, which is a classic metastatic study. In all these patients, there was no previous treatment for metastatic disease. Our primary goal was to see objective response rates. Our secondary objectives were to evaluate safety, progression-free survival, and I think the Holy Grail, obviously, is overall survival and duration of response. When we planned this study, our initial goal was obviously, and it still is, to recruit 43 patients, and we want to achieve at least 12 successes a month, 43 patients. Now, when we planned the regimen, and we are sticking to this regimen, as you can see here, the decision was to start with immunotherapy and after one course of immunotherapy to put in the DaRTs and then continue on a regular protocol of immunotherapy for all the patients. Now, what stands and what's the rationale behind this study? First of all, if we go back and look at our check, the studies we have mentioned, the KEYNOTE-048, the response rate in head and neck, the best response rate is, and those are for the patients for high CPS. And we know that CPS stands for Combined Positive Score standing for the level of PD-L1. We know that even the best patients only respond in 23%. And those who have less numbers respond to 17%, 19%. I think in general, when we talk about immunotherapy, and this is important for at least from my perspective, if we go back 10 years ago, we thought that immunotherapy would change the world in metastatic disease, and I mean overall diseases. What we have seen so far is that in melanoma, it really has changed the world. We think that we are curing patients with melanoma, and we probably see 80% response. In all other diseases, including head and neck, the response rates are more or less 20%, meaning that 20% of our metastatic patients with head and neck cancer will respond to immunotherapy. Our overall survival rate is 15 months, which has not really changed much since our prior overall response rates were and our overall survivors were 11 or 12 months. Only 23% of our patients are responding, meaning that 75% of patients receiving immunotherapy are not responding. If you think of it, it's kind of a type of failure. This has led to numerous vast number of studies in which we are combining immunotherapy with almost any drug, with biological treatments, now with ADCs, with chemotherapies, and even with regular radiation. The results so far are also not kind of frustrating and are failing. What is the specific, what is the specific goal behind under this study? We know there is a meaning in the combination between immunotherapy and radiation. As Bobby mentioned and Dr. Den has mentioned, there are several perspectives. The first thing we do know about radiation, when radiation kills cells, it leads to the higher levels of antigens, which can improve the effect of radiation, I mean, improve the effect of immunotherapy. The second way in which we believe radiation can improve immunotherapy, immunoenhancer, is by the fact that it changes the tumor cell itself. We know that the levels of the PD-L1 go higher after receiving radiotherapy. The third system is probably through the tumor microenvironment. What we know as far as that is that if you give radiotherapy and then you give immunotherapy, the thought is that it will suppress the tumor suppressor genes, the tumor immunotherapy genes like the Tregs. The fourth, which we think is more like a curious, but we still believe in it, is that it might induce abscopal effect. I must mention that in one of my first cases in which we treated skin cancer with immunotherapy, this was seven years ago, we treated with Alpha DaRT. We had a patient who had two large skin cancers. Unfortunately, we did not have enough DaRTs to treat both of the skin cancers. We treated one, and we thought we would go back and treat the second one several weeks later. At the end of the day, the second one died without being treated. This is like there. This does show us that once in a while, we do see an abscopal effect with the combination of DaRTs. Now, what's behind this study specifically? We just explained the rationale between the combination of radiation and immunotherapy. Unfortunately, there have been also numerous studies in the combination of head and neck cancer between radiation and immunotherapy. We've received SBRT, and then we gave immunotherapy. We received regular radiation and then gave immunotherapy. And despite the fact that in mice, it works very well, we have cured, and the whole society has cured many mice. In human beings, so far, the studies are failing. What's the difference in DaRT? Why should DaRT work better? One of our thoughts about DaRT is the fact that its radiobiological effectiveness is much stronger. We have a lot higher radiobiological effectiveness. The second, I think, important fact is the fact that the DaRT does not only break one DNA strand, but it breaks two DNA strands. If we mention, and we go back to the rationale about the combination, we understand that if you break the DNA totally in two areas, you probably will give in more tumor suppressor effect, and you will probably send, and you will allow yourself to have more antigens, which can affect the whole area. So what happened in this specific study we have treated? This is what we have done so far. We have screened 10 patients. We had two screen failures, and we have treated eight patients. These are our first patients. As you can see here, there are different types of patients. Most of them are old, and we can see that they had a large tumor volume. And some of them were 2.6 centimeters, and we had up to 210 tumor volumes in one of these patients. As you can see here, most of these patients were stage IV patients. When we talk about stage IV and head and neck, there are two types of stage IVs. There are unresectable stage IV and metastatic stage IV, and these patients were in both of these subgroups. We had patients who had tumors in the neck, the tongue, the mandible, the jaw, which is a very frustrating area, and we have all these types of patients. As far as the adverse events and I think this is most important to say that primarily non-melanoma, we don't want to cause damage to the patients. As you can see here, we didn't have much of toxicity. However, we did have two patients who died. This was in the beginning, and both of them did not die of the disease itself, of the treatment itself. Actually, they died before they were treated with DaRTs. They were elderly patients with other problems, and they died after the first course of immunotherapy. What is our response? So if we take our first eight patients who were treated, we had three patients who had complete response, and we'll describe them later on. We had three patients who had partial response. And unfortunately, as we mentioned, we had two patients who died before basically being treated. And if we talk about this in general, you see that all our patients are responding. And it's a small study. We're the first eight patients. However, if we compare to this, to what we've seen and known in regular immunotherapy, we can see that results are much better. Usually, what I see, at least in my career, and when I treat head and neck patients with immunotherapy, I see something like 10% of the patients who really respond. The rest will have some sort of basically either stable disease or very small partial response, and here we see all our patients are responding. These are examples. This patient, it might be one of our Beilinson or Benelux. She was a 96-year-old patient who had a very large, as you can see, alveolar ridge cancer, and she has what we call dermal metastasis. What is dermal metastasis? Her whole skin was infiltrated with tumor, and when you have tumor which involves the skin itself, we call this a metastatic disease. The patient had a positive lymph node, and it was a big debate what to do with this patient. Once you have dermal involvement, basically, the patient is doomed and has no chance to get out of it. She was offered, despite this in some hospitals, to undergo a large surgery. Other hospitals, including us, offered to just start pembro alone, which is a standard treatment, and at the end of the day, she agreed to go into the study. As you can see, she's an elderly patient with a little dementia, with cardiac background, with a performance status III, which is not that great, and despite this, we decided to try and treat her in the DaRT study. As you can see here, we see the insertion of DaRTs, and what we've seen interesting in this study so far is, in contrast to what we do when we try to cure patients with DaRTs, in these cases, we don't have to cover the whole tumor. Why don't we have to cover the whole tumor? Because our goal in this treatment is not to kill the treatment by the DaRT, but to create an immune effect by the DaRTs. And therefore, we have to create at least a small area within the tumor that we are focused on. We cover the tumor well, but we're not worried about complete coverage of the tumor. And as you can see here, we didn't put too many DaRTs here. We have put several seeds. This was done under local anesthesia in one of our treatment rooms. Here we can see how she looked after insertion, which was two weeks later. She continued with immunotherapy and looked at her skin. The whole dermal metastasis has gone away. And look at this. This is how her alveolar ridge looked before, and this is how she looked after nine weeks. Now I'm still been following her for years. Basically, we decided to stop our immunotherapy after a year. Basically, we're three years after treatment. The patient has no disease. She's doing very well. She's continuing on with her life. Her dementia got a little worse, but in general, she's in great health. Her family, I must say, is so happy about this whole treatment. Here we can see her PET follow-up. You can see the disease in the lymph node. You can see the dermal metastasis. Here we see a while afterwards, no evidence of any disease. As we mentioned, the patient stopped pembro. The patient is alive without evidence of disease. Just to conclude, I can say, so up to now, we have treated eight patients. The patients are doing very well. I think that the next goal from this is that we learned a new concept, which is that we can combine immunotherapy and radiation not only as a treatment to cure patients, but also to enhance the immunotherapy. And the goal in the future, in the near future, we'll combine this also as for now adjuvant treatment in head and neck cancer and potentially in other types of cancers, like in lung cancer, in pancreas cancer. And this, I think, is a new dream in DaRT as a treatment for radio enhancement. Thank you very much. Excellent. Well, thank you very much, Professor Popovtzer. Thank you to all of our distinguished speakers. So now you've all seen it all, right? This is what we know. This is what we wanted to share, looking at three different sets of data: our pancreatic cancer data and comparison of the treatment with chemo versus chemo alone in terms of survival, some of the initial things we've learned from treating other cancers in internal organs, as well as how we start to see that immune combination together with checkpoint inhibitors. So what we wanted to do here really, of course, was to give you the broader vision. As I said, we've historically shown most of our data in that first pillar, the localized and unresectable tumors, particularly those superficial tumors. Our goal now, of course, being to give you that vision as to why we see the Alpha DaRT being so relevant to tumors of high unmet need, as well as the potential for treating metastatic patients using a local therapy as part of a systemic solution. Again, trying to explain why it is that we are so focused on doubling down on these two pillars, the unmet need and the metastatic patients. And so in light of that, I want to just quickly talk about where we see this going forward. For 2025, our focus on discussions with the FDA will be on bringing new studies to the U.S. One of them, of course, is the pancreatic cancer study that Dr. Den mentioned earlier, which we are pleased to announce today. We have already secured that IDE from the FDA. So we will hopefully get started soon on that trial with that approval in hand. The second one we'll focus on will be recurrent GBM to run an early feasibility study. Remember, we have the breakthrough device designation from the FDA in recurrent GBM. We also were very proud to be inducted into the TAP program, which is a very prestigious program, an FDA accelerator for taking unique breakthrough devices and giving them early access to leaders in the commercial space, payers, etc., to begin those discussions even when planning clinical studies. And so we are hoping to submit a request for a recurrent GBM study as well. And then finally, in light of the fantastic data that Professor Popovtzer just shared in terms of what we've seen from the combination with pembro, we've also indicated to the FDA that we would like to initiate a study of head and neck patients for Alpha DaRT in combination with pembrolizumab. So as we look to a number of important milestones to look for over the coming year, year and a half, again, on the flagship U.S. study, the pivotal study in recurrent cutaneous squamous cell carcinoma, as I mentioned earlier. Look for completion of recruitment of those patients in Q3 of this year, and then data for submission coming out in the first half of next year. As I mentioned, we do have that pancreas trial approval in the States and are looking to start as soon as possible. First patient hopefully coming in next quarter, recruiting, finishing up towards the end of the year and getting data middle of next year. Similar in GBM, we'll be submitting soon and hope to get the IDE before the middle of the year and then get the readout from that data around the middle of next year as well. At the same time, starting to treat brain cancer patients in Israel, as we already do. We already are We already are looking for patients there, getting that pancreatic cancer multi-center study underway in France, and again, looking to hear back from the PMDA on our request for approval in recurrent head and neck cancer, turning the final response in Q2. As you all know, we're incredibly active. We remain active with a number of trials underway. That includes our studies we've just discussed, together with a number of other studies, again, dipping our toes into a few different cancers: lung cancer, pancreatic cancer, prostate cancer, vulvar SCC, etc. Again, looking to bring more of this data on feasibility in these different tumors, but ultimately driving that towards the studies in the U.S., as we've now done with skin cancer, and are about to embark on as well with the pancreas as well. With that, I'm going to pause, and we're going to take questions here for our group here. We're joined, of course, at the panel by all of the esteemed guests who've spoken so far, as well as by our CEO, Uzi Sofer. And so I'm going to start going through the questions we've received. And again, there are quite a number of them. We'll get through as many as we can before we let people go. So one question, I think the first question we received related to the initial discussion on the Mohs surgeons and whether they're permitted to perform the Alpha DaRT procedure in their practice office or need to go to the hospital. It's a great question. The answer is that exactly the goal is to be able to let them do this procedure in their clinic. We can help them getting the radium license that they need and securing an authorized user for the product. But absolutely, the goal and what we've been doing has been enabling these Mohs surgeons and other community dermatologists to deliver the treatment in their office. And from there, of course, if we can demonstrate that in the context of the Mohs surgeons, hopefully we can use that as well in the future as we think about other clinicians who may wish to do this in their office. Next question we got around the pancreas section was a couple of different parts. I'll break them up. One of them related to any challenges regarding doctor recruitment or adoption in terms of the appropriate training for Alpha DaRT use. Maybe I'll turn to Dr. Miller on that one from his experience. My pleasure. So it's a great question. My answer would be no. It does not seem to be an issue at all, and I would just highlight a couple of things. One is last week when we were in Paris in the investigator meeting to kick off the multi-center French trial that was spoken about today, we met with many endoscopists from each of the 13 centers going to be participating in the trial after giving an overview with a little more technical detail than I gave you, but barely, and then we broke out into models for hands-on sessions, and I could just say, that engaged audience, very poignant, straightforward questions. They were all able to gain comfort with both techniques of delivering the seeds, the sources, and there really was only positivity from the endoscopist audience, so really, it was a very, very small learning curve, and then confidence attained. I got that feedback regularly. The other thing I would mention is that while I'm the only interventionist for the trial in my hospital in Montreal, our sister hospital, the Université de Montréal, uses two, with the second one only having started recently with a very, very brief sort of orientation. And again, he's an expert endoscopist and had no barrier whatsoever to beginning. And he had a successful case as well. Excellent. Thank you very much, Dr. Miller. The other parts of that question related to limitations on supply or on patient location. Maybe I'll quickly address patient location in saying that because the radium has a 3.7-day half-life, we're comfortable that we can ship this from our factory to the hospital in time for use. So there doesn't need to be a specific location limitation where the patient might be. Obviously, we don't want to ship it very far unnecessarily, and we are building out a number of manufacturing facilities so that we are relatively close to our patients, but there's no doubt that treating a patient across the country should not be an issue. Maybe in terms of the question received on manufacturing capacity build-out, I'll turn to our CEO, Uzi Sofer. Yes, absolutely, so today we have a few factories. The first one is in Jerusalem. We plan to move to two shifts and by the end of the year for three shifts in Jerusalem in order to produce and to get all the demand that we have from the different clinical trials all over the world that we are running. The second facility is in Lawrence, Massachusetts. This one is only for Thorium-228 generators. We are building now a very big project, very big facility in Hudson, New Hampshire. This big project has a few phases. The first phase, the building will be finished in Q2 this year. We hope to be ready for production by the end of this year. This is for phase one. Immediately, we'll start phase two. Absolutely, we are preparing ourselves to mass production. Thank you, Uzi. All right, I'll take the next question here. I'm just going in order. I think, Professor Popovtzer, I'll direct this to you. Was there anything learned from the complete response in the pancreas patient with the liver mets in terms of the potential for seeing abscopal effects in other patients? As we actually mentioned during my talk, we have seen some abscopal effects. I don't know if we should call this abscopal effect, but we definitely know that radiation has an effect on the tumor environment, and this might cure patients. What we've seen in general, as mentioned here previously, is that the overall survival for these patients in our pancreas study is extremely good, so probably we are seeing some effect, which is beyond the treatment of the tumor itself. We are checking this now in the lab to check if there's any meaning of this, and hopefully, we'll be seeing this more. And as we mentioned, we will combine this with immunotherapy, and then we might even see a stronger abscopal effect. Thank you. All right, thank you very much. Next question I got here was for Dr. Den. Do you see the future treatments in pancreatic cancer, Alpha Tau, using Alpha DaRT in a monotherapy setting or in combination with chemotherapy or something else? That's an excellent question, so I think we see a diversity of opportunities to use the DaRT within the context of pancreatic cancer, so we are actively working to look at new intraoperative delivery. This would be done in the postoperative setting and would be as a monotherapy, but would be followed, of course, by systemic chemotherapy. We're also looking at different delivery devices in terms of percutaneous delivery in addition to the endoscopic delivery that we currently have, and this could be used both in combination with chemotherapy or other novel agents. What we hypothesize, and based on some of the data that you saw here, and our preclinical data, is that we may be able to reintroduce prior immunologic-based therapies that unfortunately did not show the response that we would ideally want in this patient population, but in the context of delivery with DaRT, may actually have a better effect than was previously seen. So the answer is yes to all of the above. Okay, thank you very much, Dr. Den. We've received a number of questions about treatment planning and dosimetry. I would point out, in an attempt to try and get to those questions more generally, we do provide a treatment planning software, which is done in partnership together with MIM Software for planning the treatments in advance. We have a significant amount of work available on our website. If you look at our publications in terms of our diffusion and leakage model, you can see a number of physics papers there as well on the dosimetry. I think that you'll find that helpful as well. I do see a question here, which came in, which I'm going to shift to Dr. Blumenfeld. The question is more generally looking at what you've seen so far. How do you think about the toxicity that you found in reirradiating patients with Alpha DaRT versus your other options available for reirradiation of patients? So I think Alpha DaRT, there's significant potential in terms of the reirradiation cases, as I mentioned. Often, with reirradiation, we have to decide between target coverage and organ at risk. And I think with Alpha DaRT, we can accomplish both delivering high doses of treatment to the tumor definitively while gaining very minimal collateral damage. So I think Alpha DaRT holds significant promise in the reirradiation setting. We have, in the pancreatic setting, three of our patients had previously received external beam or external beam radiation therapy. And all of those patients did quite well following the Alpha DaRT treatment. And as well as the two cases that I mentioned previously in the thoracic and rectal cases, we've seen very minimal to no toxicities. Thank you. I see that Professor Popovtzer also has something to add. So I would like to mention that in our paper that we have published in the Red Journal for our head and neck and skin cancer, we have treated almost 40% of the patients with reirradiation. The toxicity was really minimal. And we have cured many patients who failed prior to the external radiation. This just exemplifies the fact that the Alpha DaRT has a different way of mechanism than radiation, meaning that it can be more effective and less toxicity. Thank you. I'm going to try and wrap up here with two last questions, given we're over on time. One of them is specifically directed to Dr. Miller in terms of the number of DaRTs that's been delivered so far and any limitations on the number of DaRTs that you believe you can deliver. So it's a good question. We certainly have seen sort of an increase as we started out, especially focusing on feasibility and safety, as was also, I believe, mentioned. As we published as well in our first five patients in the interim analysis, we really wanted to make sure that we could have it done, they go in the right place, technically no issues before going further with coverage. I could say that we have had a curve in our study. We went from just a few sources placed to now the routine and norm is to put in dozens. Limitations to placement, we haven't yet seen anything such as localized bleeding issues with duration of procedure, anesthesia, pain, things like that. No, there technically are not that we have seen. Of course, we always follow the pre-modeled analysis per our pretreatment planning software. There is to not go above the maximum amount of sources as calculated by our physicists. But no, we have not seen any ceiling there yet. Excellent. Thank you very much. All right, looking to move along here. And I know we're over on time. I'll quickly address, again, we're overwhelmed with questions. So thank you for everybody who's sending them over. I will quickly address two more of the questions here. One of them relates to whether we saw any specific tumor resistance in pancreatic cancer or tumor types that have not responded at all to the DaRT. The answer is no. We haven't seen that so far. And I did receive a series of questions about the pathway in pancreatic cancer and the trial we've just revealed today that we now have approval for and why we're looking at metastatic patients. The truth is we are also in discussions with the FDA about adding in non-metastatic patients as well. So that is something we may explore in the future. The goal right now is to get our pilot study up and running. And then from there, turn that hopefully into a pivotal study in the future to get us approved. With that, I know we're a couple of minutes over. So I'm going to thank all of our participants here for their time, all of the viewers from home or from the office, and everyone who sent in questions. And again, please follow along. We're incredibly excited about the story. We're incredibly excited about the data that we shared today. And we hope this will be only the first of many fantastic data updates to come in the coming months and years. So thank you very much.