Good afternoon, everyone. Welcome to the B. Riley Securities oncology conference. I'm Yuan Zhi, a healthcare active research analyst at B. Riley Securities. Today, it's my pleasure to have Raphi, CFO of Alpha Tau, which is developing localized diffusing alpha emitter radiation therapy for solid tumors. Raphi, now the floor is yours. Excellent. Thank you very much, Yuan, for having us. Great, thank you, everybody, for joining. My name is Raphi Levy. As Yuan said, I'm the CFO of Alpha Tau, and I'm excited to spend a few minutes giving you an overview of the company and our technology and progress. I'll start with a quick introduction. We are the only ones who have figured out how to inject alpha radiation directly into a tumor. I'll talk about why that's important and what that means, it allows us to get an incredibly precise dose of potent radiation at relatively low levels to looking to destroy the tumor and spare the surrounding healthy tissue. This is fundamentally a local therapy. We've been doing this now for over a decade. We've done this in multiple preclinical models. At this point, nearly 20 different tumor types, and we have yet to find a tumor type that doesn't respond. Every type that we've injected this source into has responded to the treatment because this is fundamentally a physics-based treatment more than it is biology. We believe it is indifferent to histology, to mutations, to antigens. We believe this can be the best local tumor control for nearly any solid tumor. Again, we're operating in the local space, competing with surgery or other forms of radiation, where a clinician will look at an image and say, "I want to treat that tumor over there." We believe that we have an incredibly compelling local form of alpha radiation. What's really exciting for us is that beyond being the best local tumor control, we've seen quite a bit of evidence, some of which we'll have time to see during this presentation, that treating one tumor locally with our treatment may actually be catalyzing a systemic immune response. Where we treat one tumor, it gets irradiated and hopefully destroyed, we find that we're also awakening the immune system to the presence of these tumors, and this may offer the ability to take a local therapy and make it part of a systemic solution for tumors across the body. The potential here for combinations with other therapies like immunotherapies is quite exciting. I'll talk about some of that, some of that data and explain why we think this is so exciting for us. We've had fantastic clinical data so far. Our first clinical study was done in Israel and in Italy in squamous cell carcinoma of the skin or the head and neck. We saw a 100% overall response rate. Every tumor we treated shrank by at least 30%. We also saw a 78% complete response rate where the tumor disappeared completely. Again, an outstanding outcome for any trial and certainly considering how difficult this patient population was, where we had an elderly population, 81 years old on average, and largely refractory after other forms of surgery or radiation. Since then, the data has gotten better and better. We've now treated well over 100 tumors of this sort in multiple trials around the world. Our most recent data release was from our U.S. pilot study, which was led by Memorial Sloan Kettering Cancer Center in New York and a number of other oncology centers around the U.S. In that pilot study, we saw a 100% complete response rate. This was a pilot study in skin cancer. Again, while it was our first foray into the U.S., very similar to the data we've seen elsewhere, again, outstanding outcomes for these patients where every tumor disappeared during the life of this trial. I think just as importantly, the safety profile here is quite attractive. As compared to other forms of radiation, you know, which generally have systemic side effects like nausea and fatigue, we don't see those sort of side effects. We only see local side effects in the area of the treatment, and that's because of the tight nature of the control of the range of the alpha particles. We see local side effects, generally grade 1 or grade 2, mild or moderate, itching, swelling, redness, things that can be managed pretty easily and tend to go away pretty quickly. Again, we're getting these outstanding outcomes for these patients, but also they're paying a very mild clinical cost to get them, which is very exciting. I will go through some of our clinical trial strategy. We have quite a number of trials going on now. Our lead study right now is for our lead indication in the superficial tumors. In the U.S., we now have a pivotal study open, waiting for its first patient in recurrent cutaneous squamous cell carcinoma. We're doing this under the guise of the FDA's Breakthrough Designation. We have two Breakthrough Designations for our product, one of them for recurrent skin cancer and another one for recurrent glioblastoma. Again, very interesting to see that broad range of tumors that both we're looking at as well as the FDA. I'll talk about logistics. This has historically been an Achilles heel for many of the radiotherapy companies, either because of poor access to supply of isotope or because of the logistics involved with a decaying product and a hazardous product that needs to be handled appropriately. In our case, it's quite a bit more manageable. The isotope we use is very easily accessible. We have plenty of sources of it, and we use incredibly low levels because of the tightly controlled and very efficient nature of its distribution. Generally dosing hundreds or thousands of times less activity than what's normally used in radiation oncology. We'll talk about this a bit later, but we have these logistics in hand. Relatively simple to ship this product. We are focused on building out a number of manufacturing facilities across the world, and I'll go through that as well. We have a very strong IP franchise around the product. Over 90 patents that are granted, over 120 applications that are pending around the world. Again, a very strong franchise, we believe, to be able to protect this product from multiple angles. Again, we also have a very strong management team to take this from the clinic and out into the commercial setting. Just quickly to set the stage here with a treatment that we believe is indifferent to the nature and histology of the tumor. We have to find where we want to focus our therapeutic focus areas. We've chosen three core pillars for our therapeutic focus. The first one is what we call the localized and unresectable. These are tumors that have other available therapy options like squamous cell carcinoma, like prostate cancer. The patients who have localized tumors who are non-surgical or recurring after surgery, who are resistant to radiation, those patients run out of local options very quickly. We find that we can offer them a new local option at a later line, and as those earlier trials that I mentioned have shown, can be very helpful there. The second one is those patients with a high unmet need. Again, if we have a treatment which is indifferent to the type of the tumor, we may as well go after those patients who have the poorest outcome, poorest prognosis. Ones that come to mind include GBM, pancreatic cancer, etc., where the opportunity to save lives is just fantastic. Finally, again, you'll hear this theme come up a few times, the idea of treating metastatic patients, again, to the extent that we can continue to demonstrate that our product is not only treating the tumor, but is also catalyzing the systemic immune response and helping the body find these tumors elsewhere in the body. Again, we can potentially take a local therapy and make it part of a systemic solution. Particularly as we think about the multitude of patients who are not responding to immunotherapies like checkpoint inhibitors, perhaps because their body has now unleashed the immune system but has not directed towards the tumor. If we can show that our form of cell death is immunogenic and is increasing the awareness and the priming of the immune system to those tumors, the potential synergy there is just fantastic. If you look at our clinical trial program, there's quite a bit going on here, but I'll summarize very quickly. This is a medical device pathway, of course. This is a local medical device, radiation product injected into the tumor, so that it's regulated like a device. Means we generally look to do a feasibility trial followed by a pivotal study in order to get approved. I will note that in our lead indication, which is our first focus, is those superficial tumors, skin or oral cavity. In Israel, in our home market, we're already approved, so we can market this for skin and oral cavity squamous cell carcinoma. In Japan, we've announced that we finished our pivotal study in head and neck cancers, and we also expect to submit that shortly to the PMDA. Finally, in the U.S., as I mentioned, we finished that early pilot study with fantastic results at Sloan Kettering and four other centers and have now moved into a pivotal study waiting for its first patients. This trial, we'll talk about in a bit, but it's a relatively straightforward study similar to our previous ones, looking at 86 patients in recurrent cutaneous squamous cell carcinoma. Our goal is to recruit that trial over the course of this year and then receive the data and read out and apply for approval next year. The other half of our clinical trials are focused on dipping our toes into a few different tumors, as it were, in order to prove out this thesis that we are actually indifferent to the type of the tumor. As you can see here, we've treated breast cancer. We have a prostate cancer trial open now. We have a pancreatic cancer trial awaiting its first patients. We hope to open a liver cancer trial soon and then further down the line, GBM and lung and others. Again, trying to try out a few different cancers there. We also have a trial being run right now in metastatic head and neck patients in combination with Keytruda. The idea being that we treat one tumor while the patients get systemic Keytruda in the background, and we monitor the untreated tumors to see if we can see a systemic effect there as well. Just to go through a bit of the physics here, we are using alpha radiation, which is known for years to be incredibly more potent than the existing forms of radiation used for local radiation therapy. Everyone today is using the traditional forms of gamma and beta radiation. Those are a radioactive isotope releasing photon like a high-energy X-ray or a beta particle like an electron. These forms of radiation are used because of their ability to penetrate tissue and the walls, and they generally get stopped by metal or by concrete. They're useful because as they encounter oxygen and generate free radicals, those free radicals may encounter tumor DNA and cause single-strand breaks, which are often repairable. This is inherently a less efficient form of radiation and one which requires oxygen. This paradigm requires significant doses of radiation to try and overcome all of these probabilities and repair abilities. This is a really a relatively inefficient form of radiation. The alpha particles are known for many years to be incredibly more efficient. This is when an isotope breaks down and releases a heavy alpha particle, two protons, two neutrons. It's got both size and mass to it. It directly breaks through both strands of the DNA. Those breaks are generally irreparable. It does so without requiring oxygen. Whereas one may need a few dozen hits to a cell to kill it with gamma or beta radiation, just one, two, or three hits can be sufficient with alpha particles. Again, incredibly more efficient in their use of radiation. Now, no one's been able to get alpha particles to move into a tumor. The issue there is that because they're so large and unwieldy, because they transfer energy so quickly, they quickly run out of steam. When we place an alpha emitter inside of a tumor, we find that we get 40 microns - 90 microns of range, which is 40 millions-9 0 millions of a meter, which of course means that we've killed 3 three cells or four cells, which are incredibly dead, but there's really no clinical utility from a treatment which can't get beyond 40 microns in a tumor. This is the reason people have largely given up on the use of local alpha radiation and have moved on to other systemic therapies, which are a different solution for a different problem in the radiopharmaceutical drug world. In terms of the paradigm of saying, "I see a tumor over there and I want to radiate it," no one can get those particles to move into enough depth into the tumor to be of any use. We've figured out how to do that, and the way in which we do that really is by releasing alpha emitters, isotopes, into the tumor in a very controlled fashion. What we're doing is we are coating a stainless steel source, a piece of metal, with radium two two four. The radium is useful for us because it breaks down one, two, three, four, five, six times until it stabilizes. It's no longer radioactive. The majority of these breakdowns will release alpha particles, which won't get very far. They'll smack into something, they'll kill it, and they'll stop very quickly. Whereas the radium is fixed to the source and is unable to leave it, these daughter atoms, as we call them, these steps in the chain, which are themselves alpha-emitting isotopes, they will actually recoil off of the source into the tumor. By Newton's second law, same way a gun will recoil when you fire it and fly backwards. Here, the alpha particle flies in one way, the Radon flies in the other direction. These isotopes recoil into the tumor, and they continue to float around the tumor for an average of 12 hours, that's their half-life, firing off these alpha particles farther and farther away from the source. As you can see here, again, we're inserting these sources into the tumor. As the radium breaks down, again, the radium is trapped on the source. Once it breaks down, its daughter atoms move into the tumor, and they will continue to move deeper and deeper into the tumor, propelled by a mix of diffusion and convection, and also recoil. Again, when they fire off the heavy alpha particle, they fly in the opposite direction. What you end up with is these alpha particles, they don't travel themselves any farther, but they're being released deeper and deeper in the tumor as those alpha emitters fly into the tumor for their short life. Now instead of 40 microns of range, which is really useless, we can get about 5 mm of range, which is quite a bit more useful. You can see here, this is a tumor grown in a mouse with a single dart, as we call it, stuck into the paper. On a cross-section, you can see the radioactivity is incredibly hot in that 5 mm range, completely cold outside of it, right? This is the holy grail of radiation therapy, a very high dose and a very rapid dose drop-off, which gives you potent but very tightly controlled radiation. If this had been a gamma ray emitter, for example, you'd probably see red going slowly to yellow, to green, to blue because of that very long tail. Here you've got this very focused dose, and so you can see from the next slice of the same tumor, the tumor is completely dead in the center of that 5 mm range. So dead, in fact, that it's actually sloughing off these dead tumor cells into the body, again, potentially providing fodder for the immune system. Yet outside of that range, it thrives just fine, right? We've got an incredibly potent but tightly controlled dose of radiation here, which again, is exactly what you want in a radiation therapy. There's an interesting side effect, which I won't get into in this discussion, but we find that because of the nature of the diffusion of these isotopes, in addition to the fact that we're only gonna put these sources into tumors, we also see that the damage is significantly more extensive in tumors as opposed to healthy tissue. What that means for us again, is that we can dose, for example, in the margins around the tumor relatively comfortably without having to worry about too much damage in the healthy tissue because we see that the radiation moves into the tumor and not in the opposite direction into the healthy tissue. For us, what we wanna do is place a couple of these sources inside the tumor, so that we cover the entire range of the tumor. We can cover the margins as well, knowing again that we're not gonna do very much damage there. For us, our pipeline is not one of new molecules. Our pipeline is one of engineering new access solutions to get into tumors. We've developed a whole range of applicators to do this, seven and counting. We've got solutions for the brain, and the pancreas, and the prostate, and the liver, and the skin. I won't go through all of them, of course. Just to give you an example here. This is how we treat superficial tumors. What you can see here. Excuse me. What you can see here is that the shiny pieces of metal are the sources. They're hollow, and they're strung onto a suture, up to six of them on a single suture. They arrive in the hospital ready for use in a loaded needle, which is then deployed into the tumor. The doctor will inject on one side of the tumor, come back out the other side, leave the sources inside of the tumor. As he or she withdraws the needle, they'll just tie off that suture a little button, like a washer on a screw, so it can't move around and send the patient home. This is a single treatment. It's not fractionated for five days a week for eight weeks, like radiation is done today. It doesn't require any CapEx, doesn't require general anesthesia. This whole procedure takes one hour, maybe two hours. It doesn't even require any protection. Again, because the alpha particles are so limited in range, can't even travel through the air. The levels that we're using are orders of magnitude less than other forms of radiation. We don't do this in a radiation oncology suite. We do this in any room in the hospital or in a field or in an outpatient setting or a community clinic. It doesn't really matter. Again, there's no need for the traditional forms of lead vests and other forms of protection. The entire procedure takes about an hour or two. It's been planned in advance. The patient comes in. We insert these sources under local anesthesia and make sure they're in the right place. Send the patient home. Two weeks later, the radiation has been delivered. The patient comes back. We snip that string, pull out the sources, and the patient is good to go. Internal organs obviously require a bit more creativity. What we're doing here, and what is generally our approach is to, you know, our sort of modus operandi is to try and leverage existing workflow as much as we can, try and use existing methods to be able to leverage the equipment and the methods of injection that the doctor is using. What we do is, in the case of the pancreas, we leverage the endoscopic ultrasound procedure, which is done for biopsying the pancreas. One of the ways to biopsy the pancreas is to take an endoscope, guide it down into the stomach under ultrasound. Then perforate with a fine needle aspirator and take samples of the pancreas up the work channel of the endoscope. What we've done is we've developed our loading device, which loads any standard fine needle aspirator with these darts. Again, wherever the doctor can get with a biopsy needle to take a sample, they can reverse the flow in that work channel and instead push in these darts using their existing equipment, existing procedure, no need to learn many new skills. Again, this is just some examples. We've got a whole bunch of other applicators that we've developed, I think, very successfully getting into these tumors. As I mentioned, we've done this in a range of tumors, nearly 20 tumor types and counting. We have yet to see a tumor type which doesn't respond. We fundamentally believe that if we could deliver these sources successfully into the tumor, we would expect those tumors to respond. We've done a whole slew of work on the immunotherapy side. As I mentioned, we see this tremendously exciting side effect where treating one tumor seems to be catalyzing a systemic immune response. I won't have time to go through all of it. I just wanna show you some recent data that was presented at the SITC conference in Boston in November. What you can see here, this is tracking the growth of squamous cell carcinoma tumors in mice. You can see here that the black line is the control group with no treatment. The red is the group that received the PD-1 inhibitor. You know, these mice were not responding. As you can see, the contribution of the PD-1 inhibitor did nothing to slow down the growth of those tumors, right? This is the 70%-80% of patients who are not responding to a checkpoint inhibitor because their body doesn't know where to look once the immune blockade has been removed. The blue is the group that received a single Alpha DaRT in the middle of a large tumor. I'm not covering this tumor because if I cover the tumor, I'm destroying it, I can't look for synergies. That's not helpful. I'm underdosing with one DaRT in the center of a tumor, and you can see here that obviously there's a response that's not surprising. What's really exciting, though, is the green line, which is the combination of the two, right? Where you can see that whereas previously adding in a PD-1 inhibitor did nothing to slow down the growth of the tumor. In the presence of the Alpha DaRT, it actually has quite a meaningful effect. Again, this is part of our theory that we are activating the body's immune system and effecting the ability of the, of the checkpoint inhibitor to add value. You can actually see this in the immunohistochemistry slides. This one here, for example, is looking at CD3 T cells, but we have similar slides for Granzyme B and CD8 T cells. You can see under the staining for the CD3 T cells, there is a population of those T cells in the PD-1 group, but it is meaningfully higher in the group with the Alpha DaRT and the PD-1. Again, this very much speaks to our theory that you can see physical, observable proof of a local radiation therapy driving a systemic immune response. I'll show you where that comes into humans in just a second. I'm gonna speed up here. In our first trial, as I mentioned, skin and oral cavity, head and neck squamous cell carcinoma, in Israel and Italy. Putting in these sources, each one has two microcuries. As you may be aware, in radiation oncology, it's generally dosed in millicuries or tens of millicuries, so we're looking at orders of magnitude less, which is why it's outpatient local procedure, no radiation protections. Insert these sources and take them out two weeks later. The data was published in the Red Journal, which is the official journal of the American Society for Radiation Oncology. It's the top journal in our field. Very well received, including an unsolicited editorial and support by the president of the society. The data speaks for itself, I think. 100% overall response. Every tumor shrank by at least 30%, especially important considering that 42% already had radiotherapy. These are patients who were deemed radioresistant because they didn't respond to radiation, and we see that they all respond. 79%, of course, had a complete response, which is just fantastic as well. For example, this patient, 80 years old, already had radiation and surgery, has multiple recurring tumors of the ear. What they can offer this patient is to cut off his ear, which is not an attractive option. Instead, we insert these sources, and to my knowledge, the patient is still cancer-free almost si years later, again, without having to, you know, avoiding any drastic treatments. Side effects, as I mentioned, only in the area of the treatments, only localized side effects, grade 1 or grade 2, mild or moderate. No systemic toxicity. An outstanding safety outcome. We had one patient that came in in Italy presenting multiple tumors on the legs. The doctors decided here to treat one tumor before the others. You can see here this is a 3 cm lesion. A month later, the suture from a biopsy where they confirmed the cancer had disappeared. This was a complete response. They then said, "Let's schedule the other treatments," and they found that the other untreated tumors had spontaneously disappeared. We never touched these tumors. We also know that their alpha radiation has no range from one leg to the other. It's possible that this patient had a systemic immune response as we'd expected. Again, this happened by accident. It's the only patient in this trial where we treated one tumor before the others, but we've now seen this in subsequent trials in a few patients as well. Hopefully you get a sense for why we're so excited about a local therapy potentially having part of that systemic solution. I mentioned we finished a pilot study in the U.S., 10 patients that were treated in late 2021. Outstanding outcome in these skin cancer patients. Again, only side effects grade one or grade two, localized side effects as we saw previously in other studies. Again, a 100% complete response rate. Every tumor disappeared at the 12-week measurement and stayed disappeared over the six-month life of the trial. We now stand to embark on our multicenter pivotal recurrent squamous cell carcinoma study. This is an 86-patient trial for patients who have recurrent skin cancer without any obvious curative standard of care. We're gonna be measuring overall response rate based on DOR for six months. Again, looking forward to running this one because it's very similar to what we've won elsewhere, and we've been very successful with these trials, so we're hoping to have a successful outcome here as well. We are doing quite a bit in the internal organ space as well. As I mentioned, we have a trial in prostate cancer running, one that's open in pancreas and breast cancer, and looking to move into the brain, liver, lungs, and colorectal. In glioblastoma, we've had spent a lot of time. We've seen some good responses in combination with Avastin. I'm gonna skip ahead in the interest of time. I will note again, as I mentioned, the supply chain, excuse me, is quite a bit easier. Even though it is a decaying product and it leaves our factory and goes straight to the hospital, we can account for the decay in the shipment time. However long it takes to get there, we can overcharge and allow it to decay during the shipment. We've also qualified as an accepted package, meaning because the levels of radioactivity are so low, this goes in a standard cardboard box on DHL or FedEx or whoever, so it doesn't require special handling. That said, for purposes of efficiency, we want to be manufacturing close to our patients, and so we have a facility at our headquarters in Jerusalem, another one just north of Boston. Again, in Japan, as we look to apply for approval, we're planning a facility there as well now. In terms of our upcoming milestones, so again, 2023 should be a very exciting year. We should see patients coming in our pivotal study in the U.S. and then finish recruiting by the end of the year. Hopefully see a patient soon in pancreas and potentially see data there as well later in the year. Apply for approval in Japan and of course, the timeline there depends on the PMDA response, but again, a lot of exciting milestones for the company over the coming months. We've been public now for almost a year. We went public in March of 2022. We had $109 million nearly of cash at our last quarterly readout. I will note that our last annual report in 2021 had a $15 million burn rate, one five. If you look at our last quarterly, it was about $4.3 for the quarter, so that's about $17 million for the year. We've communicated that we have at least two years of cash, if not more. Again, we're feeling quite comfortable just given how leanly we run and how careful we are managing our cash. We're comfortable that regardless of how markets perform, we can take this quite far with the cash that we have. We're very excited to be continuing to execute on the plan with that plan and with the cash in hand. I think I've just hit my time of 25 minutes. I'm gonna stop there and say thank you very much for your patience and Yuan for having me, and I'd love to answer any questions. Thank you, Raphi. That's a very helpful overview of Alpha Tau story. Maybe if you can comment on the regulatory path for DART for skin cancer especially. After the data you are planning to read out later this year, what's the next step? For audience not familiar with this type of therapy, what level of data does FDA require for approval? Yeah, absolutely. Thank you. As I mentioned, we are going down a medical device pathway. We expect to apply under a PMA. Again, the trial we've been asked to run is an open label, single arm, 86 patient trial. We've never been asked by anybody for a comparator arm for any sort of randomized controlled trial. The main reason is because we're treating patients who don't have an obvious standard of care. There isn't really much to randomize them. Certainly, if they've run out of local options, this is what they have left, there isn't an obvious arm to compare them to. What we do is we treat these patients, and we measure primarily local response. That's what we get measured on. We do look at some systemic parameters, but we get measured as a local therapy primarily on the overall local response as well as the durability of that response. We would expect to recruit patients over the course of this year. We'll probably see the initial response data at the beginning of next year, and then that six-month durability data should be six months later. Call that kind of mid-next year. Once we have that, we will, you know, type it up as quickly as we can with the fastest typist we possibly could find, and submit that to the FDA. Again, we have that Breakthrough Device designation, and we're running that trial under that designation. We would expect to also get the fast-track review from the FDA. Got it. That's very helpful. I think that we do not have any further questions. Thank you for the time, and thank you for the interest from the audience. Absolutely. Thank you, thank you for having me, and thank you to everybody who joined. Hope everyone has a great day.