All right, good morning, everyone. Welcome to B. Riley Securities Oncology Conference on day two, listening to our fireside chat. I'm Yuan Zhi, healthcare equity research analyst at B. Riley Securities. It's my great pleasure to have Sandesh Seth, CEO of Actinium Pharmaceuticals. Thank you for joining us today, congrats on a very productive 2022, congrats on ringing the closing bell at NYSE today. We had some great news from the SIERRA trial not long ago, it is exciting to see the full data will be presented as a late breaker at the Tandem Meetings on February 18 in Florida. In addition to that, we also had an all-representation at ASH Conference from the Actimab program. Before we talk about this individual progress, Sandesh, maybe you can give the audience a quick overview of your clinical programs and the platform. Yeah, sure. Thanks for having me. Appreciate it. Looking forward to the data on February 18. The company will host a webinar shortly after that at 6:00 PM. on the 18th. Because we run into President's Day weekend, and we want the biggest possible audience, we will have a KOL event a week later, I believe it's on February 28. Looking forward to all of those events. The NYSE closing bell obviously is, you know, very, I think uplifting for the company. People here have been working hard across the board. We're a tiny little company, and, you know, we produce quite a lot, which I'll tell you about in a minute. People are very excited for what we accomplished last year and what we hope to accomplish and will accomplish this year. What is Actinium? Who is Actinium? Actinium is a company that has a radiotherapeutics platform that we deploy to kill cancer. We focus on end-stage cancer. You know, I was, sort of noodling on a logo for, not a logo, but a tagline for what we do. At the end of the day, we nuke cancer to save lives. We focus on end-stage disease. Our aspiration is to take this stellar phase III data, we believe, from Iomab, file a BLA, and then, you know, look for a launch next year and launch into a space that has a high unmet medical need for targeted conditioning prior to stem cell therapy. With Iomab on label, it would be bone marrow transplant. On the backs of that, build a specialty, pharmaceutical or pharma specialty radiotherapeutics company focused on the 100 or so large hospitals in the United States. That's sort of the aspiration for the company. We're well-funded for now. I just want to say that right up front before I go into sort of a bird's eye view of the pipeline. We have enough capital to get us well into 2025. That's a good position to be in this current environment with the kind of value-creating milestones we expect to deliver this year. Let me sort of broadly focus you on the pipeline. While we're not going to use any slides today, for those of you know, you can reference the pipeline chart on in the investor deck. Broadly, we're focused on two broad areas in terms of the pipeline, and then we have a platform. In terms of our lead, our most advanced stage of development, it really is in targeted conditioning. As many of you know, we put out about half a data set. We put out top-line results with a p-value of 0.0001 for the primary endpoint, for our lead product candidate, Iomab-B. We expect to have that full data set, including very important measures, secondary endpoints, which will not be the basis for approval, but nevertheless, very important is event-free survival. We expect to do that on February 18 at this late breaker at the Tandem or TCT Meetings in Orlando. Iomab-B is intended to provide conditioning and replace chemo-based conditioning in the bone marrow transplant setting. Today, the, I would say conventional wisdom for patients, the 20,000 or so patients that get AML in the United States, it's, you know, about 50% bigger in Europe, is try to get them into remission. If these patients are fit. Recall, AML is a disease of the elderly. Median age is 68. If these patients are fit, they tend to get some kind of chemo cocktail. Usually, it's 7+3, you know, and if they're unfit, they tend to get Venclexta or, you know, azacitidine and venetoclax. If they fail, then, you know, they really don't have too many treatment options. They may get a targeted therapy if they have a mutation, or they may get some other variation, or they may go to an experimental trial. However, the goal of that initial remission is to try to put these patients into remission. Because the disease is so heterogeneous, because relapse is so high, the goal is to get them to a bone marrow transplant, which is the only known way of curing patients in AML today. In order to get them into a bone marrow transplant, having gone through that first, I would say, physical challenge, immunologic challenge, from the therapeutic intended to produce that remission, then they have to get a chemical-based conditioning, which is intended to completely wipe out the bone marrow so that they can then get the third challenge, which is the stem cells themselves, the hematopoietic stem cells. As a result of that, you know, the chemo-based conditioning is very limiting. It prevents about half the population that could go to a bone marrow transplant from accessing a bone marrow transplant. That's what Iomab-B does. It does two things in one fell swoop, so to speak. It provides induction, so it kills the disease. We'll get into the mechanism a little bit later. It also provides myeloablation or wiping out of the bone marrow. What we've been able to show in the phase III data, which is replicated across, you know, the 400 or so patients that this radioligand has been used in across various hematologic malignancies, is, 100% access. All of the patients that do get Iomab-B in the phase III and in those 12 other phase I and phase II trials were all able to get the transplant. They were all able to engraft, 100% of them engrafted, and then over time, you know, we tracked them for durable complete remission. Again, I'm sure we'll be talking about the trial later. Iomab-B could change the way patients currently who are unable to access a transplant, and recall, this is all relapsed refractory patients today do not get a bone marrow transplant because relapses are very high. A doctor would never transplant a patient that has active disease. It's a paradigm change. We've been able to show 100% access, and then over time, clearly, as we've shown in the phase III, improved outcomes, as we've shown with that primary endpoint p-value. That's the first and most advanced drug. Within the conditioning space as well, what the company has done over the last several years as cellular therapy has gotten more into the treatment armamentarium with several drug approvals. There's been, you know, an increasingly recognized need for better lymphodepletion, which is conditioning prior to CAR-T or reduced-intensity conditioning, which is conditioning prior to a gene therapy to clear space in the lymph system or to wipe out, you know, parts of the marrow. We have a low-dose version of the same radioligand, and we call that the Iomab-ACT program. That is in a trial with Sloan Kettering and the NIH, and it's expected to have some more results. We did, you know, have a trial's in session poster at ASH of last year. We would expect to have some good data this year. More to come with that program. Very excited. Moving on to the therapeutics, we have a CD33-armed antibody, called Actimab-A. We had an oral session at ASH. what we've shown with this is you can take low doses of our antibody, combine it with chemotherapy and produce results that you know, I think were certainly noted at ASH in that oral presentation. what we were able to show in that data was patients that failed venetoclax and azacitidine, which had 2 or 3 months to live, patients that have TP53 mutations, patients that you know, have failed several lines of prior therapy and on average are expected to live 2 to 6 months. When treated with a low dose of Actimab and CLAG-M, we were able to produce very high response rates across that trial, 67%. In that dose course, you know, which it's a little bit unbelievable. It's 100%. I would just say it's very high response rates, right? we were able to show a median survival of, 52% at one year and then, 32% at two years. These results, you know, certainly were an advanced stage development. We would expect to message our plans on this program later this year. We also have a program with Actimab and venetoclax. The whole notion here is, as AML now starts to evolve in terms of product development into, you know, I think there are 120 trials, maybe 50 or 60 trial sponsors focusing on various genetic mutations, targeted therapies, right, whether it's menin's or what have you, radiation because of its linear energy transfer, because of it has very high killing power. It's very effective on its own. In the heme setting, you can't deliver external body radiation. Obviously, we deliver it in microdoses internally. The other great thing about radiation, especially alpha radiation, is there are really no known resistance mechanisms. It produces double-stranded breaks in the DNA. Over time, because of that, you know, I would say mutation-agnostic, mechanism of Actimab, the vision is to combine this with other targeted therapies over time. I think the CLAG-M was a great proof of concept for us. We're very, very excited with those results, very excited to be able to move ahead into advanced development, and very excited towards the middle of the year to be able to, message what that can be. I will also point out, while it is, you know, that there's a bigger vision building here, Actimab clearly, if you fast forward and assume some success in terms of an approval several years down the road, would be treating relapsed refractory patients as a therapeutic. These patients could either go to transplant, or they could just be, you know, in deep remissions and get maintenance and remain cured, so to speak, or in extended remissions. If they did go to transplant, there's an opportunity to treat them with Iomab-B. The market opportunity and the opportunity for Actinium to really shape outcomes in relapsed refractory AML, which on a prevalence basis is the biggest segment in AML, and it really is a multi, you know, billion-dollar market opportunity here, is slowly coming into view on the backs of what we achieved last year and what we were able to show this year. Very excited to be able to move into 2023, execute on the clinical platform. Equally exciting, I think, for us is, you know, our platform. We have on balance, I would say, arguably, amongst the little radio companies outside of big pharma and maybe even in big pharma, the biggest, you know, 195 patents, right? We have broad patent estate. We've been doing this a very long time. we've made mistakes that some of these startups, you know, still have to make in terms of supply chain, relationships at site, setting up, you know, advanced trials, right? In terms of targets, we're very excited to be, you know, to be working on a bunch of solid tumor targets. we've shown some early data with HER3, which we think is very exciting. we've done some work. you know, CD47 is a little bit checkered now, you know, with people, sort of wondering about the viability of many of these programs. What we've shown is you can combine it with, again, radiation and produce, much better effects. We'll have to see what happens with that program. sometimes, you know, targets go through evolutions. many targets, sort of in that first, HER3, for example, you know, lots of programs failed. Now Daiichi for it, you know, is doing quite well in the phase III with their HER3. There were, you know, some very stellar data with their HER3 ADC at ASCO. Clearly, if you put, you know, an isotope on an antibody versus a toxin, we sort of view it as supercharging a drug, right? For example, Actimab-A is a supercharged Mylotarg. I'm just going to close out on that. Just want to say, you know, we are working on other undisclosed targets as well. We look forward to unveiling more on the pipeline as well later this year and then next year. Well, that's great, the overview. Thanks for the brave, blueprints, for Actinium in the next couple of years. Maybe we can circle back to the most advanced program, Iomab-B. Sorry if there are too many questions around this program because there is a lot of inbound interest. Maybe we can start on the topic. Maybe you have covered some part of it. What's the vision now for developing, a radiotherapy for bone marrow transplant condition? Like you mentioned, the, external, beam, radiation is not probably working in this condition. Then also you if you can put it in context, the antibody used here, CD45, have been without the radioisotope, has been tested in clinical trial before. What's the overall, reason now behind the developing mechanism here or the philosophy here? Yeah. I think, I touched on a little bit about the unmet medical need. It really is, you know, because you can't use external body radiation, in high enough doses, right, they give you a little, total body radiation with many, conditioning regimens. It's too gray. To myeloablate or destroy the bone marrow, you need about 16-18 grays inside the bone marrow. You can't do that with external body radiation because you will kill the patient. Chemo is non-targeted. You know, it has horrible side effects. These are patients that are very sick. They can't really tolerate repeated assaults on their bodies with drugs. That's where Iomab comes in. It's very targeted. It, you know, really, in terms of its distribution, is highly targeted to the bone marrow. We are able to deliver very high doses that within, you know, a few days completely leaves the marrow acellular. It wipes out because we target something called CD45, as you mentioned. It also targets blasts. CD45 is expressed on blasts. You can have circulating blasts that are very, very high. The radiation delivered through the antibody will kill them. CD45 itself, you know, is expressed across the hematopoietic system, the myeloid, and the linear lymphic lineage in stem cells. It's a great target. It's only a great target. It's not a great target for an antibody or an ADC because CD45 internalizes about 10% or 15%. There's just not enough internalization. Antibodies and ADCs really require, you know, they need to get inside the cell in order to work. Radiation, on the other hand, can kill from outside the cell wall, right, because of that linear energy transfer, because of that, you know, radiation dose delivered. It's a great target for a radioligand. That's exactly why I think, you know, the Fred Hutch, three Nobel Prizes to their name, spent about 15 years and did 12 trials across various cancers: AML, MDS, ALL, NHL, multiple myeloma, using different warheads, right, young AML, old AML, and always with the same outcome, you know, they focused on patients that had no hope. There were no drugs that worked on these patients. Transplant was the only known curative regimen. They took these patients that had, you know, a few months to live, two to three, four months. They gave them the CD45 antibody and were always able to show improved access, improved outcomes. We recognize, I think, the value of that. You know, we have been innovative ourselves with the low dose, which is a way to then address the needs, similar needs in radiotherapy. I think, you know, again, I think CD45, not a great target for ADCs, for naked antibodies, but a great target for radioligands. Got it. Got it. You will share the top lines, the SIERRA result, just a little bit. Of course, we will see more data coming out at the medical conference next month. Just to remind the audience, what was the trial design? To the extent you can share, what are the key highlights from this SIERRA trial? What endpoints or clinical benefits should investors focus on when you share? Sure. Conceptually, the trial design was very, you know, it was an experiment that really the FDA set up in conjunction with us versus we setting it up in conjunction with the FDA. In, you know, in our view, it was a pristine experiment designed to determine whether Iomab-B, you know, worked in the setting compared to standard of care, right? The trial design was small, 150 patients because of the power of the proof of concept study. It was 1:1 randomization into control arm. The control arm was designed to exactly replicate anything a doctor would do for these patients in order to keep them alive, right? Typically, recall, these patients do not get a bone marrow transplant because they have active disease. In the control arm, we put in 20 regimens that the doctors could choose, that the transplanters and hematologists could choose in order to get them into a remission. However, recall that many drugs don't work on these patients. If they fail, two things would happen. One is for reasons of equipoise, they would get to crossover so that they could potentially be rescued by Iomab. If they did crossover and two-thirds of the patients did crossover, and I believe 80% of them did not receive a remission, they were counted as failures for the control arm or for the study, for the primary endpoint. If they did get a remission, they were allowed to go to transplant, or the doctor could just keep them in remission using maintenance therapies. It was physician's choice. Be that as it may, post that initial CR, then they would be, at six months, determined if they were in relapse or not. If that remission was durable, then they would qualify as a success for the primary endpoint. That's the control arm. For Iomab, equally, you know, kind of simple. They would get a dosimetric dose to determine the therapeutic dose. Seven days later, they would get the therapeutic dose. Then they got to go to a transplant 7-10 days later. Once the transplant, you know, once they engrafted and then they were determined whether they were in remission or not, then the clock started for that 6-month durable, complete remission primary endpoint. The comparator of those two, was the primary endpoint. I will also say, you know, we did build in some secondary measures. A durable complete remission in the relapsed refractory setting is a regulatory endpoint. You know, that's codified in 21 CFR. It's a very good proxy, ultimately, for how well these patients do, right? Keeping in mind that there was a crossover, you know, event-free survival is also typically in trials that have a crossover. That's also a very great endpoint, because overall survival is pretty much a useless endpoint because it's confounded by the crossover, right? You can't really compare overall survival of the two arms because it's biased by the crossover. You can compare EFS. Those are the metrics we would be looking to put out, you know, in addition to side effects like sepsis. We've already shown, you know, we had materially less sepsis. We had less febrile neutropenia. Overall, you know, this is a much safer drug compared to chemotherapy or targeted therapies. Very excited to show the full data set, you know, in about a month or so. Yeah. Maybe you can also touch on why did you select this conference or this venue to share the full data? You know, the Tandem Meetings or the Transplantation & Cellular Therapy Meetings are really the preeminent meeting. Then there's the European version of that called the EBMT. These are the preeminent meetings for bone marrow transplant and cellular therapy, you know, CAR-T, which is also done by transplanters, right? That is the audience. We are, you know, a specialty company. This is a specialty audience. Many of them don't go to other I mean, you know, there's probably 600, 700 transplanters in the United States. This is their meeting. They don't really go to ASH. You know, this is sort of their specialty. This is the meeting they get excited about. For us, this was a great choice, you know, to be able to show a late breaker here. Super excited. We think we reached the right audience, you know, as we look to launch the drug next year at some point. This is, you know, we need to begin pre-commercial activities. You know, we have, you know, recruited a very talented chief commercial officer who came from Novartis. She was the general manager of their oncology portfolio, the biggest slice of their oncology portfolio. She led the account executive function, account management function for the launch of Kymriah, very high-touch CAR-T product. Obviously, Iomab is way less complex than CAR-T. You know, she understands CML. She built a CML franchise. She understands small, you know, blood cancer. I think as we look to, you know, build a commercial organization over time, we're very well suited to take this data, which could be transformational for these patients, and then work on, you know, other things like an expanded access program and then start to talk about lifecycle management towards the end of the year. Got it. When you share the data, how do you think physicians will react to the data? Maybe you can share how the principal investigators have reacted to the data so far and is the primary endpoint and the secondary endpoints, how important do you think these endpoints are to drive adoptions from these physicians? So what we've heard is it's practice changing. It's a new standard of, excuse me, a new standard of care. You know, I think we will look forward to I don't want to steal the physician's thunder. We will look forward to those results. We will look forward to the KOL webinar. We're also very fortunate to have recruited in the last three or four months, you know, Dr. Dixit, who was a head of bone marrow transplant at UT Southwestern. You'll hear her on the 18th. She'll give you a transplanter's perspective on how the data are viewed. I did sort of, you know, give you a little bit of preview that this is indeed perceived as practice changing, right? These patients die in two or three months. If we are able to keep them alive longer or even and then achieve cures in a percentage of the population, nobody can do that right now. Got it. There's nothing on the horizon. There's nothing on the horizon for five, maybe even 10 years, right, that where there's anything that could provide this type of hope for those patients. Yeah. Since we have a short on time and, I do want to touch upon the Actinium Pharmaceuticals very quickly. before we, circle to that point, maybe you can provide an update on the regulatory path and the commercial plan for Iomab-B. Well, the regulatory path is very simple: file a BLA, right, get it approved, and then launch. We expect all of that to occur, you know, end of this year, second half of this year, the launch next year, right? Typically, you're looking at a nine-month approval process, assuming everything goes smoothly. In terms of launch, you know, again, I don't want to steal our chief commercial officer's thunder. You're looking at a call point that is very finite. You're looking at a call point that is, you know, at peak, about 80 hospitals in the United States. There's no competition. We are in 22 hospitals in the US as a result of the phase III that account for about 30% of volume. Seven of those are PPS-exempt centers where reimbursement doesn't matter. we would expect to be at, you know, maybe 30 or 40 sites at launch, which would capture over half the market and then over time, build from there. The sales force is not going to be large. This is a specialty launch. No competition. We are the class. There's no first-in-class. There's no second-in-class. We are the class. Unmet medical need, lifesaving potential label. This is not a $100 million launch with 50 reps or 75 reps. This is low eight figures, right? The balance sheet is strong. I think we are, you know, fortunate enough to be in a good position right now. Got it. Before we wrap it up, maybe can you quickly touch on the Actimab-A and Iomab-ACT program? What should we expect on any data update from those programs in 2023? Yeah. I think, on the Actimab-A program, you know, clearly, there are other trials outside of CLAG-M that are going on. What we would expect to message is an advanced development plan. Given the nature of the data, you know, what the specifics of that plan are, I think towards the middle of the year, we expect to be in a position to announce that. We're very excited for some of the things we're working on internally. I would watch for that, you know, in the next month or two, I would think. That will sort of speak to the broad-based excitement, you know, we're getting from the physician community in terms of where we can go with this, right? I do want to hit on the fact that AML is evolving towards targeted therapies, right? There's a lot of excitement about targeted therapies. However, none of these are a cure, and they address small slices of the population. What scientists, physician scientists see is that because of the mutation-agnostic mechanism of Actinium and the fact that most cancers in AML as well is a combination situation in terms of therapeutic optionality, Actinium can play a material role in the treatment armamentarium with combinations. That's our strategy. That's what we would expect to announce later this year. There is no company, I think, that would be able to offer the type of, optionality, you know, that this program offers. That's tremendously exciting. We have not been talking about this program a lot because people have been focusing on Iomab. I would ask people to start paying attention to this program because the potential here is immense. Got it. I think. I will also say there's a lot of hype on radiation. We have the most patient exposures with Actinium-225 than any company. We have treated over 140 patients. We have a supply chain where we're going over 45 hospitals. We're very proud of that. I just wanted to put it out there in closing. Yeah. Thanks for the last touching point. Thank you for the interest from the audience. That will be the end of this fireside chat. Thank you. Thanks for having us.