Thor Medical ASA (TRMED) Earnings Call Transcript & Summary

Good afternoon, everyone. Welcome to our first Capital Markets Update in Thor Medical. I am Ludvik Sandnes, I'm Chairman of the Board. I am very proud to say that it's less than 1.5 years ago since I presented to the AGM the Nordic Nanovector's acquisition of Thor Medical's technology and that we now, on budget, on time, have achieved so much with this very skilled team. As you know, I think we also have to say that we stand on the shoulders of some of the greatest entrepreneurs of Norway, Alf Bjørseth, Roy Larsen and Øyvind Bruland. And Roy and Øyvind also created the first and only FDA-accepted medicine based on alpha emitters. So we have good traditions to follow up. And they sold the company to Bayer, and we're very pleased that we have now got back from Bayer, Jasper Kurth as our CEO. So I leave it to him to introduce to you the speakers of this conference. Jasper?

Thank you, Ludvik. Good afternoon also from my side. It's a true pleasure standing here in front of you today and actually sharing the great things that this company has been doing over the last couple of months and also to invite you to -- on a journey to understand the medical needs of alpha emitters in targeted cancer therapy and also what sets Thor Medical apart in their mission and their technology. And we have prepared a packed agenda. So first of all, I would give you a brief introduction to the company, and then I'm very pleased that I have with me today Jane Sosabowski, Professor of the Queen Mary University Hospital of London, who speak about targeted alpha therapies. And then we have also Emanuele Ostuni, CEO of ARTBIO with us, as most of you know, a strong partner of Thor Medical that will fill also in what the pharmaceutical industry believes is the future in targeted alpha therapy. And then we take it from there going more internally what our technology is so special about and how we see actually the long-term vision of this company unfolding. And we round this up with a Q&A session where all the questions will be addressed. So if you have a question, please use the online tools or raise your hand here in the room. Now before we go into the slides, there's this usual disclaimer about forward-looking statements and assumptions made by management. So it's important. But let's talk about the company first. So you all would agree that pharmaceuticals and radiopharmaceuticals are a very emerging and upcoming field. And anticipating that this market will grow exponentially, we believe that there is a need for an isotope supplier with alpha isotopes that is scalable and is the partner of choice of many pharmaceutical companies for the future, traversing through development pipelines and then actually hitting the commercial market. And we believe this constitutes an opportunity to gross out about USD 1 billion long term. That's the long-term ambition for this company here because the market will be so big in the end. And we are actually 10 years in the making. So it was a proof of concept on lab scale that is now becoming a brick-and-mortar building. So we have opened up our pilot site on time and on budget, and we are running our production. We have shipped the first sample. So it's actually happening, which is a very rewarding experience for the entire team and me. And while we are having this ambition in mind and our vision to make a difference for millions of cancer patients, we keep our feet on the ground and actually make the next steps in a prudent way. And we are planning to take from a pilot site that is currently up and running to a commercial site we call AlphaOne. So where we're looking into funding the site actually to provide commercial doses to millions of patients in clinical studies, and this is the next step for our company. You can see this picture actually. And for me, it sends 2 messages. This is taking as a screenshot of the leading network in Norway. And we are cutting the ribbon of our pilot site here in September. So the 2 messages are there is a high visibility and a high need that is perceived by the public for players in the field like us and that also policymakers, not only the mayor of the municipality actually showed up, but also here, the lady in red, that's Norway's Minister of Industry, a high-ranking government official that actually spent time with us being still a very small company. I think this is a testament to the visibility we have achieved with this. And just briefly speaking of the team, I can only say that I'm humbled every day to serve alongside these fantastic individuals that are laser-focused on our mission to make a difference for millions of cancer patients worldwide. But let's talk about radiopharmaceuticals, and I hope I'm not stealing the thunder of Jane or Emanuele, but just a very -- in very broad strokes, we are talking about a targeted radiopharmaceutical that has the ability to connect to cancer cells since cancer cells here pictured on the right, have a specific surface you can target and address with proteins or peptides that actually fit like a key to a keyhole on the surface. And with that, you can bring like a cruise missile, a warhead, in this case, a nuclear warhead. This is where we work, the radioactive compound to the cancer and emit the radiation only there to eradicate the cancer on site by leaving most of the healthy tissue around intact. So this is really a milestone in precision type of medicine. But we will hear about this from much more competent voices from Emanuele and Jane later. Back to our company, just to share a few milestones that we have achieved over the last couple of months. So I mentioned the pilot site. We have completed it in time, in budget, and it's up and running, producing radioisotopes as we speak that are being shipped out to customers that then verify our production technology and that this actually works for the intended purpose. I'm very happy that Emanuele is with me today here also to present the ARTBIO story. ARTBIO is a very strong partner for us. We have signed this 5-year supply agreement with ARTBIO, which is a cornerstone of our strategy. So very pleased to have that. But also, of course, we are an independent supplier. We are speaking to different other companies using a lead-212 isotope. And of course, there will be more news coming out of here. We have shipped the first batch of thorium-228, which is a testament to our production process. And while this pilot facility shows that we can scale our technology and that our technology works, we need to make up our mind how we want to scale it up in a commercial way and a commercial capacity, and this is what we call AlphaOne. And AlphaOne would be a decision that the Board and the management will take in Q1 next year to invest in a site which requires around USD 30 million. But now before diving into further details of our organization, I would like to give it over to Jane Sosabowski to talk about targeted alpha therapy. So Jane, thanks.

Thank you very much, Jasper, and thank you for inviting me to talk today about the topic that is of extreme interest to me. I'm a radiochemist, and I've been in radiopharmaceutical development for about 30 years. And I have to say this is one of the most exciting times I have experienced in my career because of the activity that's going on at the moment. So first of all, I would like to talk about what is radiopharmaceutical therapy. So as Jasper said, in general, radiopharmaceutical therapies are formed of 2 components, a targeting molecule that binds specifically to cancer cells, but not to most other normal cells in the body. So this is important because we don't want to see any off-target toxicity. And then we have also a radioactive atom, which is a radionuclide. Sorry, Jasper, do you have the -- and we also have the radioactive atom, the radionuclide that's attached to the targeting molecule. The radionuclide then undergoes a radioactive decay, emits particles, which are beta or alpha particles, there are other therapeutic particles, but we won't talk about those today. And these beta or alpha particles cause DNA damage and ultimately, tumor cell death. So the important thing to take away from this is that radionuclides are an essential starting material for radiopharmaceuticals. And not only that, they are the active ingredient of radiopharmaceuticals because they are the component that actually causes the DNA damage. So when we have a look at radionuclides for radiopharmaceutical therapy, there are various that we can choose. So they, first of all, have to have suitable emissions. So in order to -- for them to have an effect, they need to damage the cancer cells sufficiently. And for that, we need an alpha therapy, we need an alpha particle or beta particle, and we'll talk about the differences between those 2. We also need to have a good radioactive half-life. So this needs to be long enough to be able to be produced in a manufacturing facility or radiopharmacy turned into a drug, administered to a patient and then still be useful, have enough radioactivity left in order to carry out an efficacious effect. So it also needs to be short enough to limit the radiation dose to patients. So we don't want something that's 3 days when it only needs to be 10 hours or we don't want something that can be 60 days. And there's got to be minimal waste issues. We don't want collection of waste at the hospitals. And this is a huge logistical problem for some radionuclides. The radioactive half-life should match the biological half-life of the targeting molecule. So the component that carries the radionuclide to the actual cancer cell has its own biological half-life. And if it's an antibody, it might stick around in the circulation for a really long time, say, of days to a week, whereas a small peptide may only be in the bloodstream for minutes to hours and have to cause its effect during that time. You can see those pictures on the side showing the exponential decay of a radionuclide. And you can see the concentration time curve for something that you might be injected into the bloodstream. And if we think here, this might be -- the time might be 1 hour, then you need a radionuclide that's really -- if this is the concentration in the blood, then you need a radionuclide that's going to decay in that period of time so that you can get the maximum effect. It doesn't help if this period here is perhaps 3 days and your radionuclide is only 45 minutes, then of course, this is a complete mismatch and you can't get any dose to the tumor because by the time your targeting molecule gets to the tumor, then of course, your radionuclide will have decay. So you need to have this match between the biological half-life and the radioactivity half-life of the radionuclide. So let's talk about alphas versus betas. So alpha emissions do more damage than betas. And although this may sound like a bad thing, it's a good thing when we're talking about cancer cells. So we want these beta particles. If we have a look at beta particles first, and these are radionuclides such as lutetium 177, you can see here or I-131, which have half-lives of order of days. They have something called a low linear energy transfer. So this is the energy that they emit along their path. So they give off energy as they travel through the tissue, and it's the amount of energy they give per micron. So you can see that the linear energy transfer, they only give off 0.2 kiloelectron volts per micron. They generally cause single-strand breaks, which can be easy for cancer cells to repair. So cancer cells are very good at repairing themselves. That's why they manage to keep going when we throw all sorts of therapies at them. And this is what we call resistance. And there's the development of radiation resistance when cancer cells repair themselves. Alpha particles on the other hand, are much more massive. They are helium atom. So they've got 2 protons, 2 neutrons, whereas beta particles, as you may know, are electrons, they're much lighter. And they're high LET particles. So they've got high linear energy transfer. They cause double-strand breaks and really complex DNA damage, and this is difficult to repair. So it leads to cell death. And you can see that the linear energy transfer for the alpha particle is 50 to 230 kiloelectron volts per micron. So that's really much more -- you're getting the emission of a very large amount of energy, and it's also importantly, over a very short path length. So if we have a look at the range of alpha particles versus beta particles in tissues, you can see this is a depiction of the cells, and there's about 10 cell diameters here. And you can see that for the alpha particles, they can go between 1 and 10 cell diameters. You might think that's a bad thing, but actually, they are emitting all of their energy in that path length and causing all the ionizations that kill the cancer cells within that path length. Now beta particles, they travel up to 1,000 to 10,000x further in tissues. So the upshot of that is that when you are looking at the alpha versus beta radiation, if you have -- this is a beta particle, it's yttrium-90, and you can see that the range in tissue is 11 millimeters, whereas for the alpha particle, this is bismuth-212, if you compare the range in tissue, it's 80 microns. So what you're doing is you're using -- if you use an alpha radiation, you're using a radionuclide that can kill the cells that are very close to it. And this is important because sometimes with a beta particle, you get the emission of radiation that actually kills the normal tissue. And you can see that some of the radiation is being deposited outside of the tumor volume. And this is where you get toxicity and you get off-target effects. So the other important thing that alpha therapy that we need to think about is that the cancer cells that actually cause tumors to spread are very -- they're very, very small called micrometastases. They're very small clusters of cells. It's not possible to treat those very small clusters of cells with beta therapy because the range is simply too high. So alpha therapy, importantly, can treat micrometastasis. So when cancer is spreading, and this is when it is malignant, if it all stays in one place and all stays within the primary tumor, quite often, it's benign. So it can be easily removed and there will be no spread and the patient will do very well. However, if it spreads to other parts of the body through the bloodstream, forming these micrometastases, then that will not be able to be treated by a beta therapy because the range is too great. So the important things are that alpha therapy is very good at killing cells, and it can kill the cells very close to where the radionuclide decays. Beta therapy is not so good at killing cells because it has a much greater range and some of the energy is deposited outside of the tissue, and it doesn't have this really cytotoxic double-strand breaks. So one of the other things to consider when we're thinking about the field of radiopharmaceuticals is that we can also image the cancer. We can replace this radionuclide here that's in the targeting molecule attached to the targeting molecule. And we can replace it with the radionuclide for imaging. And quite often, this is a positron emitter, something like gallium-68. So this is a really nice system where we can image the patient to see if they express the receptors that we need to target on their cancer, and then we can follow it up with the therapy. Right. So having gone into that background, I just want to talk a bit about the field of radionuclide therapy. And as I said, it's the most exciting time that I've experienced during my career in the field. And as was alluded to earlier, this really started with the development of radium chloride. And in 2013, it was a proof of bone metastasis in prostate cancer. Now this was important because it's the first alpha therapy in the clinic. And it convinced everyone that alpha therapies could be safely used in the clinic. And this was followed by some other approvals in beta therapies, lutetium-dotatate, which was first bought by AAA and then Novartis approved for neuroendocrine tumors in 2017 and then the huge game changer in the field, lutetium-PSMA-617 for prostate cancer was approved in August 2022. The reason I say it's a game changer is although this is a very effective therapy, the octreotate, PSMA treats patients with a much larger indication. So there are many millions of patients with prostate cancer. It's a huge indication. So this really became a game changer. And then Novartis was interested. They had bought the PSMA, and they're interested in doing an alpha therapy, which they have not managed to do yet, but they're still obviously thinking about it because in the field, there had been a lot of work going on in compassionate use. So alpha therapies have been tested in the clinic, outside of clinical trials, but simply giving these therapies to patients on a compassionate use basis. And from this information that was gained from these patients, we really saw that alpha therapies could make a difference. However, actinium stocks worldwide were very low via chemical extraction from thorium-229, there was enough for about 2,600 patients per year. However, if you take Russia out of that equation, then there are far fewer doses. So immediately, the radiopharmaceutical industry went into looking at production of actinium-225 by other routes, including accelerator-based routes. Now actinium-225 is -- it's an alpha therapy. However, it does have some issues with the production by accelerator-based routes. It needs infrastructure, expensive infrastructure. And also, there were -- some of the targets for the accelerator-based routes are radioactive themselves and give off radioactive gas. And in addition, they also have produced a small amount of a very long-lived radionuclide, which is logistically difficult for hospitals. So actinium, although a very, very exciting and game-changing radionuclide may not be the perfect alpha therapy for targeted therapy. So if we have a look at those results that we saw that really set everybody off on this really exciting journey, we can see here that this is the results of the lutetium therapy trial. You can see the gallium-68 scan, which is the positron emission tomography, the PET scan, showing where the tumors are. You can see the tumors all around the body. And then after treatment with the lutetium therapy that targeted the same receptor on those tumors, the gallium-68 scan was clear. And the VISION trial that was run by Novartis showed a 38% reduced risk of death and 60% reduced risk of progression. And on the back of that, they gained FDA approval. And this is what was going on in the background with actinium-225 therapies that we're doing on a compassionate use basis. And you can see that this is a patient here with visceral metastases that received lutetium-PSMA and had no response. In fact, the patient got worse with the beta particle therapy. However, coming in with the alpha particle therapy, it seemed that this patient responded really remarkably. And you can see their PSA levels go right down from 419 to 3.5 nanograms per ml, that is a biomarker for response looking at dropping PSA levels. So this is a really exciting set of images in the field and really induced a lot of investment in trying to get actinium off the ground. And again, these are compassionate use. This is not a controlled -- randomized controlled clinical trial, but looking in South Africa chemo-naive patients, you saw this remarkable PSA response. This is 8 weeks after 1 cycle of actinium PSMA-617. So we can see from this that there is really a -- the alpha therapies are really exciting. But we have to ask ourselves really, is it the perfect radionuclide because there are other alpha therapies out of there at there that also show really exciting results. And this is lead-212 DOTAMTATE Phase I that was being run in the U.S.A. in somatostatin receptor positive expressing neuroendocrine tumors. And looking at these patients here, this is the first 10 patients in the study. And you can look -- if you look at the differences between the scans before and then after the DOTAMTATE, the lead-212 alpha therapy, you can see there's really some remarkable differences in these patients that have been treated. And remember, this is a Phase I trial. It's a dose escalation trial. So you're not really looking for efficacy in a trial like this. But in fact, really exciting data from this. And you can see that looking at the response, that most of these patients, some of them had stable disease, some had partial response and some had complete response. So for a small Phase I, this is a really exciting result. So let's have a look at a summary of what we said, first of all. We've shown alpha particle therapy to be safe in routine clinical use. The therapies have shown great promise in the compassionate use setting and early phase trials. The decay properties of alpha emitters could have an impact on metastatic disease and thus improve patient outcomes. And the clinical potential of alpha emitters has pushed targeted alpha therapies really to the top of the priority list for pharmaceutical companies. And one thing I would add here is development of these new therapies is completely dependent on radionuclide supply. You cannot run clinical trials unless you have a really robust supply of radionuclides. And if we have a look here, what usually happens in this cycle is some research is done, that's exciting. This creates a real demand. And we hope a supply. This supply cycle keeps on going around until we reach this like utopia-holy-grail type of situation where you have a robust affordable supply that can then keep the cycle going, create doing more research, innovation that leads to more demand and leads to this really good supply situation. If we don't have a supply, we can't do research and the demand just drops because it's too difficult. So if we have a look at clinical trials and radionuclide therapy, this is something that I do every now and again. I just have a look at the number of clinical trials recruiting or not yet recruiting. I'm just looking at the radionuclides that are being used in these trials. Now you can see lutetium-177, the beta particle emitter, is always top of the trials being done, 173, just having a look in this month. Radium-223, the first alpha emitter has been gradually going down. Actinium 225, considering the supply difficulties, a remarkable amount of clinical activity going on. Astatine-211, another alpha emitter also with supply and logistical difficulties. And then we see here lead-212, which is also starting to come up and some clinical development being done, which is really exciting. So there's 2 things going on here. First of all, the reason so many trials are being done with lutetium-177 is there's 2 products in the -- on the market that are approved already. So clinical trials can quite easily be done because there is a chain where these can be studied in combination and all sorts of different settings. But also, there was a really robust supply of lutetium-177. I'm not saying it's enough, but there was a good supply. All the other radionuclides here do not have a good supply apart from radium-223, and radium-223 has its own issues around its chemistry that limits its use, I would say, in the field. So what we're seeing here is that it's not possible to expand these clinical trials that are being done with these really exciting alpha emitters and without a robust supply of radionuclides. So let's have a look at lead-212. It's a radionuclide, very suitable for therapy. It has a decay chain with 1 beta and 1 alpha emitter. So you can see here, there's a beta decay that leads to bismuth-212, which either decays with a beta and an alpha or an alpha and a beta. So whichever way it goes down that chain, you will end up with a beta -- 2 betas and 1 alpha. So unlike actinium-225, it does not decay in a chain of alpha emissions. So this is important because it's a reduction in toxicity. I can go into and explain that in greater detail if anybody would like me to, but there are some issues around actinium having 4 alphas. It also -- actinium also has a 10-day half-life. Now to me, 10 days is not a suitable half-life for looking at something that's a small peptide that has a half-life in vivo, biological half-life in vivo of perhaps 3 hours, 1 hour, 15 minutes. We're looking at small molecules that have really fast pharmacokinetics. And actinium-225 is kind of wasted, I think, on molecules that have really short half-life. We should be matching the half-life to the half-life of the radionuclide to the biological half-life. There is a transition from lead-212 to bismuth-212, where 60% of it remains in DOTA, which is not a particularly good chelator or it's a chemical entity that holds the -- attaches the lead-212 to the targeting molecule. For actinium, it's a case with an alpha, as soon as there is 1 alpha decay, then that molecule falls apart. So if it's not in the tumor, you get toxicity. So there's a good variety of feasible sources of thorium-228, which Thor Medical has their own supply, and there are other suppliers also around the world that could feed into this market and feed into the whole supply and demand cycle. Generator systems can be developed, and there have been some promising Phase I clinical trials results. So future prospects for the field as a whole, where do we see this going? And is there space for it, for lead-212? I would say, absolutely. What we see here is the use of drug earlier in the patient pathway. These are all being done with lutetium beta therapies, but I would foresee in the future, these will be done with alpha therapies as well. It's just the radionuclide supply that's holding this work back. There's expansion into other indications, not just prostate, neuroendocrine tumors and thyroid, but also into breast, paraganglioma, pheochromocytoma with the molecules that we already have. Combination therapies with immunotherapies, for instance, PARP inhibitors and chemotherapies, all of these clinical trials are being done only with lutetium at the moment, but I see these also going into alpha therapies. Increased number of targets, very exciting for the alpha therapies as well. These are small molecules that have a really good biological half-life suited to the half-life of the radionuclide. And also the number of disease areas are increasing, breast, lung cancer, colon cancer. These are all large indications. So just as one example of that, this is the NETTER-2 results with the lutetium-dotatate therapy, where it has been given much earlier in the patient pathway than it would normally be given. And this is in first-line treatment in solid cancer. So this is the first-line treatment that has been given with a radiopharmaceutical therapy, and you can see that there's a really good difference between those that received the lutetium beta therapy versus those that received the octreotide alone. So if this is what is achievable with a beta particle therapy, imagine what can be achieved with an alpha therapy if we had the supply. So in conclusion, radiopharmaceutical therapy field has seen an unprecedented level of investment in the last 10 years. and targeted alpha therapies have enormous potential to be more effective than the beta therapies that I've been showing you. Initiation of early phase trials shows really encouraging number of -- an encouraging amount of clinical activity and agents in clinical development despite the supply problems. Development is hindered by a lack of radionuclide supply. Lead-212, I think, is a really exciting radionuclide. It has a potentially robust and scalable supply chain that doesn't have the infrastructure needs, for instance, with actinium-225 that we see. And new suppliers coming into the market will drive innovation, create a positive supply and demand dynamic, that cycle that we saw and accelerate clinical development. And for patients, this means new treatment options and improved outcomes, and that's what we all want to see. Thank you. So I'm just going to hand over now to Dr. Emanuele Ostuni, who is from ARTBIO, and he's going to talk to us about unleashing the power of alpha radioligand therapy.

Thank you, Jane. It's a real pleasure to be here, first and foremost, to follow Jane, who is very distinguished in our field. And thanks for the opportunity to speak here at Thor Medical. Thank you, gentlemen here in the audience. Very quickly, I'll take some time to tell you what we do as a company with the thorium-228 that we're getting from Thor Medical and what we're going to continue to do with it over time. So as a company, we're entirely focused on the pursuit of therapeutics, alpha-based therapeutics, hence, the name ARTBIO, based on lead-212, as you just heard from Jane. So I'll take some time to spend -- to tell you a bit more about why we're so excited about it and then how we're going to do it because the how is usually where all plans go arrive. So with that in mind, we also stand on the shoulder of giants. As Ludvik mentioned before, we share our founder, Roy Larsen, was Co-Founder of ARTBIO as well and helped us put the company together. We believe strongly in something Jane said before. One must match the half-life of the payload that one takes to a tumor with the actual half-life of the molecule that makes it to the tumor. To use maybe a more simplistic analogy, you need to be able to shoot all the bullets that you bring to that tumor as opposed to not shooting all of them, which is what happens in the case of lutetium and actinium in many cases. So we're focused on lead. We're focused on using its short half-life and high power to deliver a lot of energy into tumors. And we've developed technology that uses thorium-228 as a starting material to proprietarily isolate lead-212 at extremely high purities so that we can then supply drug product that requires its own manufacturing arrangement that doesn't fit the normal models of big pharma of centralized manufacturing. And we're doing all of this work to supply a pipeline of agents that starts with one that's entering the clinic shortly and several others behind it, and we'll talk a little bit about that. I won't spend too much time to tell you who we are, but very briefly, we're a U.S.-based company. We are operating in addition to the U.S. in 3 locations in Norway, Switzerland and the U.K. We are venture-backed with about $130 million of funding over the last 2.5 years. And we're backed by U.S. investors. And importantly, we're supported by our Chair, Ted Love, who is a distinguished investor and clinician as well as Susanne Schaffert, who's one of the very few big pharma execs who actually understands radiopharma. She ran the AAA acquisition after it was done at Novartis, and she was responsible for driving the acquisition of Endocyte for Pluvicto. So we feel like we've got a good company in the Board and a lot of support. The team is sourced from leading companies in the space. The folks you see on this page here were instrumental in taking Lutathera through approval as well as scaling up the manufacturing network of Pluvicto. You'll understand in a second why that's important, along with the development of several important drugs. So why lead-212? Maybe to put a double-click on it so that everyone remembers it based on also Jane's really useful talk. The short half-life delivers a lot of energy in a very short period of time into that tumor. That decay -- that fast decay also minimizes how much safety concerns we may have. The dosing flexibility that we have with lead-212 is actually a lot higher than what is available with other longer-lived payloads. And the waste management point at the hospital is a very important point. I never thought that it would be sexy to talk about waste management, but it is a real issue in hospitals, and they're worried about long-lived isotopes. Importantly, the decay chemistry is simple. It's only a single alpha. We don't have to worry about a lot of other daughter isotopes in the body, and the chemistry to make the final product is very straightforward. I can say that as a chemist, I've never seen something as simple as 30 minutes at room temperature. Not only does lead have a single alpha decay, but it also eventually, as Jane showed you, decays into something that is a gamma emitter. That gamma emitter is something that we can very easily see using conventional equipment that's available today for conventional SPECT and CT. And importantly, we have the potential for far better outcomes and far better safety. To pick up on where Jane mentioned, there are several trials that have been run on the same target, effectively almost the same molecule in very similar patient populations. These were not head-to-head trials, but we're putting together next to one another 3 different -- several trials actually that give us an indication of what may happen when trying to keep all things equal, one switch is just the payload and goes from lutetium to actinium to lead. And what you see here is the thesis that Jane mentioned before at play. The alpha emitters are doing better than the beta emitters in the middle panel here. This is the comparison to the Lutathera approval trial, where you see higher ORR rates, overall rates of response and also importantly, with lead, higher CR rate. CR is complete response. In oncology, it's our holy grail. We want to get to that because we want to give patients as full a remission as we can. And importantly, in the later lines of trial of therapy, lead also did better in the post-Lutathera setting with a far higher rate of response. So this is part of the real-world data that we're using to back up our hypothesis and support what we are doing. And what we're doing is building not just one program, but a whole pipeline of programs that will use this payload in order to try to provide much needed relief to many patients. So we have done that by boiling a notion of targets that are overexpressed in tumors and have all the right properties that we think are needed for radiotherapy, radioligand therapy, first and foremost, and secondly, for radioligand therapy with lead-212. And we identified a group of 20 that we then had to figure out how to bring the lead to them. Not to take you all back to a chemistry class from high school or college, but different chemistries are needed to hit different targets. And we figured out which chemistries are needed and have then gone out and sourced those chemistries through a variety of partnerships that include also in-license and co-development partnerships with the likes of 3B Pharma, Parabilis Pharmaceuticals and others. And so that has led us to a pipeline that looks like this today. The undisclosed bit is where there's a lot of activity, and we think we'll be able to bring a lot more therapies forward, starting with the lead program in prostate cancer, which we call AB001. And I want to give you a glimpse of what's possible with these therapies by showing you results from our 3-patient Phase 0 trial that we just published a few weeks ago in 3 patients with metastatic castration-resistant prostate cancer in Norway, where we showed the ability to dose our therapy at very low doses and see the therapy itself. Lead has a unique twist to it, which, as Jane mentioned, sometimes in radiopharma, you have to separate and have one molecule for targeting the tumor and one molecule for imaging. Lead actually can be imaged at the same time. So what you're seeing there in that yellow light in the middle is that very bright lymph node lesion that is lighting up at a very low dose of therapy. And what you're seeing here on the left is the image of where the patient expresses the PSMA target that we're trying to reach with our therapy. What's very exciting is that in -- when we looked and looked very hard at the salivary glands, which is the dose-limiting organ for many therapies in PSMA expressing prostate tumors because of the damage that these therapies can do to salivary glands, we see -- we saw nothing in the salivary glands. So this shows us that we have the likely potential to deliver something that's differentiated, both in terms of efficacy as well as safety against this tumor, which is still affecting many. And I should say that xerostomia, which is the fancy word for burning out your salivary glands is a big problem for both Pluvicto as well as all the actinium-based PSMA programs. So this gives us a lot of confidence to move forward. And importantly, there's another vignette of data I'd like to show you that hints to us why lead can be even better than other isotopes. We think there will be a place for all isotopes overall, but we think there are some things that are quite specific about lead that open it up to important differentiation. We're showing you here experiments where the gray bar shows you the median survival of the subjects with no treatment in a very aggressive prostate cancer model. In the middle bar, you see what happens when we give the mice single dose that we know is equivalent to what would be a human dose. And then the bottom bar shows you what happens when we not give more radiation, but simply divide that radiation up into 4s and give it once a week for 4 weeks. I think the picture is very loud in terms of describing what happens. But what the takeaway we have here is that low and frequent damage to the tumor can be more efficacious than a onetime dose. And this is very important in very aggressive tumors, which is where we're going. This is something that is very hard to do with other isotopes that are very long-lived because, as Jane mentioned before, we need to give the body a chance to release these isotopes. So for that reason, there's a lot to like about lead in our view, and that's why we're putting all of our eggs in that basket and pushing it forward. So now talking about how do we make lead because we talked about short half-lives, and I know there's folks in the back already thinking how do you get this from point A to B. So first and foremost, we start with thorium-228. We've developed a proprietary technology for converting that thorium-228 into lead-212, and doing so at extremely high purities that are unmatched elsewhere. So what we need to function properly in the supply chain, we need a great source of thorium-228. And that's what we're getting from Thor Medical today, and we're very pleased to have that access, potential access long term to that supply. And today, the thorium-228 stockpiles, although there's many out there in the world, they're not pure enough. They don't meet the specs of what we need to safely and effectively make lead-212 from it. So we're very glad to see that there's movement with Thor Medical trying to create a new way of isolating thorium-228 that is potentially more sustainable as well than what everyone else is doing. And I'd like to highlight a little bit how the supply chain changes when we talk about lead-212-based therapies. The thorium-228 we use from Thor Medical has a 2-year half-life. That 2-year half-life ensures that our box, Alpha Direct can sit somewhere and has a very long use-life. So we're using that to generate lead-212 on a daily basis and making drug product that we can ship out to patients and physicians on a daily basis. And so our ability to respond to changes in demand is actually quite quick. It's on a daily basis. What happens for all the other isotopes is that first one has to find a source material, then that source material has to be irradiated for several days. And then that has to be purified, shipped to a central location typically where then it is made into drug product and then shipped over. So what you see is that there's almost a 2-week period for responding to a very big shift in demand, and that shift actually is problematic and requires that those manufacturers have to stockpile a lot of material that often goes unused. And so for lead-212, the supply chain we envision is a supply chain where localized hubs of manufacturing containing thorium-228 are set up. We're setting them up and optimize the ability to deliver therapy within a window of about 10 hours as well as manufacture at the proper COGS and at the proper shelf life that allows us to create that network that's adequate. What's important here is that the network also -- each point in the network is independent from the others. So each point makes the network stronger and does not actually suffer if one of the hubs goes down. It's a much more resilient supply chain. And so that supply chain is now being built. We have 5 hubs across the U.S. -- 4 in the U.S. and 1 in Europe, where we're creating the manufacturing lines in order for us to supply lead-212 using that thorium-228. And in China is a completely different story. We have a partnership with co-development and license to create that. So in the interest of time, I'd just like to wrap up and share with you why we're so glad to be here. We're excited to have a thorium-228 supply chain that we can trust and that allows us to pursue lead-212-based therapeutics using our technology and using our ability to manufacture, which I showed you in a second, so that we can ultimately supply pipeline to patients that will change the course of their therapy, their standard of care and ultimately, we hope to provide long much needed survival. And so with that, I thank you very much. And now I have the honor of giving you a 5-minute break before we come back with Jasper and continue the conversation. Thank you.

[Technical Difficulty] Again to Jane and Emanuele to walk us through this exciting view on cancer therapy using lead-212. I would like to leave the scientific field just a bit to talk about basically the same thing just from a commercial standpoint. So when you look at the market of radiopharmaceuticals, and I would like to take you on a journey going from a bird's eye view and then zooming into the respective field and the market we play in. And then hopefully, we can give a convincing take on why Thor Medical actually is set out to be a strong player in that respective market. But let's start with the general assumptions, which I think many of you share that the radiotherapeutics market is actually about to explode. We have seen that, Xofigo being the first product on the market. Now we have 2 more targeted therapies using beta emissions. So we will basically see this continuing, and we at Thor Medical believe this market will grow to the size of around USD 30 billion in just 10 years. And this is, of course, very ambitious, but the data we have seen and all the indications that are out there point to that direction. And we also believe because it's supported by a lot of noise in the market. So for instance, oncology trials are on an all-time high. It's still an unmet need. So we have 10 million patients die from cancer each year. That's 10 million lives being impacted, 10 million families suffering from that deadly disease. And we see this being reflected in new paradigms of treatments like with targeted alpha therapies. And in that general field of therapeutics, we have observed more than USD 12 billion being invested in M&A transactions, just meaning larger players scooping up promising pipelines on the market, but also with start-ups and up-and-coming companies, including those that produce isotopes, there is a lot of success rates in them raising capital. And only just a few non-exhaustive snippets and newspaper extractions here, so just to confirm this. But speaking about targeted alpha therapies, basically, and this is what we have just learned also from Jane and Emanuele, it's beta versus alpha. And we are, of course, are in the camp that alpha emission makes a big difference to patients in terms of their ability to break 2 DNA strands and many other aspects that we have heard before. And in particular, in alpha, this is a bit of simplified view because we also see actinium and lead-212 on the list as contenders in the race of alphas. We feel, and this is confirmed now by the 2 talks, we have seen that, lead-212 is the ideal isotope to actually treat cancer. And I won't hopefully repeat what has been said. But for me personally, and I think many people can relate to this, that there are cancer cases in every family. And what is sometimes left out when you consider clear facts and data reading on clinical studies, it's the impact of life that has on patients. So we're talking about patients that are late stage because they typically get it not first line, but rather when they -- the other therapies have failed. The traditional way of using lutetium, for instance, or also actinium, there is a big strain on how these patients can lead their lives because they become themselves radioactive. So they cannot hug their grandkids, for instance. They have to isolate themselves, the waste management that Emanuele mentioned. This means that the hospitals are exposed to a logistical challenge managing this waste for 10x the half-life. So this has a real impact on life, and I think this is underrepresented in many cases. So another reason why lead-212 could be a very potential isotope, a very strong contender in this race. Looking at the list of companies, and this is non-exhaustive and of course, very prominently ARTBIO being represented here today in person. It's a very important partner. But rest assured, as an independent company, we have mature discussions with all of these players basically to safeguard the supply chain going forward. And when it comes to market development, we see it happening in 3 phases as indicated here on the picture. So for us, as Thor Medical, it's a very attractive field to play in already in the small market of clinical trials. So we support isotopes to the ARTBIO and other players in the field alike for them to use this in clinical trials on patients, making sure that they develop the drugs they will need to bring it to market maturation and actually have a rubber stamped by the FDA or any authorization body that actually can bring it to the market effectively. And from there, we actually see the market growing quite fast due to the fact that we expect these treatments to move up the lines of treatment, sometimes maybe for some cancers, first-line treatment, meaning patients will receive these treatments earlier than usual. So typically, as I said, radiopharmaceuticals are not necessarily the first-line treatment, but we believe in the future, this will happen, which will cause the market actually to react in that way. And then eventually, when this is standard of care, we believe there will be a multibillion U.S. dollar market for pharmaceutical companies. And that, of course, entails that isotope supplier us actually bringing the active ingredient, if you will, to the drug that there is still a growing market for us as part of this. And of course, we have understood now that this is a very promising field in oncology and that there is a need for lead-212. But of course, this market is very attractive. This attracts other players as well, maybe players that are not as advanced as we are, but we won't be alone in the market. But as CEO, I strongly believe that we have a competitive edge on most of these players due to our proprietary technology and the way we run our operations. And I'm very happy to invite to the stage my dear colleague and friend, Brede Ellingsæter, who is the CFO of Thor Medical and has been very much involved in not only the financial operations of the company, but also in building these plants and making sure that we scale up the capacity as we do. So Brede, please join me here and take it over. Thank you.

Thank you very much, Jasper. It's a pleasure to be here and to give you guys an update on our operational plans and how we see the future unfold over the next decade or so. So we are building a value chain for next-generation cancer therapies, and we're doing that together with our partners, including ARTBIO in a way that we create available and reliable supply of radioisotopes. So one of the drawbacks of lead, as has been mentioned, has been the short half-life, how to actually get those therapies into the patients. And we play a critical role in that process. So we are working with raw material suppliers that is the, what is called, natural thorium-232. It is naturally occurring. It is naturally abundant in the world. And we are working with a handful of suppliers to secure our own feedstock of that. Then we are manufacturing thorium-228 and radium-224, 2 alpha emitters that are used as generator material for the pharmaceutical companies. ARTBIO was mentioned, they are using the thorium-228. And we can supply that with a decent half-life in a way that they can manufacture lead locally and timely to treat the patients. So there are alternative routes to produce these isotopes. We believe that what we have is a competitive advantage in the sense that we produce from naturally occurring resources. It is capital efficient. And it is scalable in a way that we can modularly scale up as demand from customers increase. The alternative routes are typically using a nuclear reactor or accelerator to irradiate a target material, and that is a target material that is radium-226. It's a scarce material, and it has also had impact on the supply of actinium recently also this year, creating bottlenecks that potentially could be the same issue for lead if apply those kind of production routes. So without diving into too much details, we believe that we have a technology that is cost efficient. It is timely in the sense of time to market and can be scaled at a cost competitive position compared to some of the other alternatives that are still, in our view, not fully proven apart from the nuclear reactor base that is what the DOE in the U.S. is producing with. It's a research reactor that has been supplying these isotopes for research purposes, but in the long term, will not be a reliable supplier. So talking about our proprietary process. It is called Alpha Cycle. And it is a process of continuously extracting radioactivity from naturally occurring sources that is thorium-232. It is based on chromatography. And let me take you through the decay of the natural thorium, which is our raw material. It has a half-life of 14 billion years. So it will definitely survive us, and it can be used infinitely in a way that we create an ever-lasting raw material. And we can -- from thorium-232, we can extract radium-228, which is our intermediate product. It has a half-life of 6 years. And as we accumulate our intermediate products, we also increase our capacity to produce thorium-228 and radium-224, which are our salable products that we sell to the customers. We also have a capability in the production line based on the same principles to do lead-212 directly, but that is creating some requirements in terms of logistics, obviously, since the short half-life. And hence, we are also -- then we are basing our distribution on partners such as ARTBIO. So the process itself is self-scaling, and it can be self-sustained based on the reuse of raw materials once this market eventually reaches steady state. And that is very important for us. It's a competitive advantage, and we believe it will be a cost competitive advantage as we continue to scale up. And when we are looking at the production capacity of AlphaOne, which is our first commercial plant, we are targeting a capacity of 15,000 patient doses after 3 years. It will continue to scale, which means that we will reach 25,000 patient doses after 5 years and eventually 40,000 patient doses after 10 years. So it's a continuous ramp of approximately 50% increase year-over-year in this period. And it can continuously be sustained by reusing all the raw materials in the process in a way that we cycle it back and that's, hence, the name AlphaCycle. So AlphaOne, the first commercial-scale plant. It is set to produce isotopes to supply the leading companies working with lead in clinical development. I mentioned the capacities of 15,000 tonnes -- 15,000 patient doses after 3 years, 25,000 after 5 years. And we have made a concept study, engineering study to estimate the capital required for this plant, and that is $30 million. It will be in the same location as the current pilot facility in Herøya, Norway. It will be an expansion of that facility. And we estimate that it will be completed approximately 12 months from investment decision, which we target to be done in first quarter next year, provided that we have financing in place. And in terms of revenues, this plant has a capability to generate revenues of NOK 250 million after 3 years, NOK 400 million after 5 years, which will be sufficient to get the company cash positive operations in a way that we can maintain ourselves up until the next expansion. And if we look a bit broader in terms of strategy and go-to-market, Emanuele just explained how they envision a distribution of generators. And based on our proprietary process and the products that we supply, we envision to do something similar in a way that we can do a centralized production of the radium-228, which is a massive separation process going from thorium-232. We are taking milligrams out of tons which is the most capital-intensive part of our process and also requires the largest footprint. And then we can ship radium-228 with much lower logistic cost, closer to the key markets, that is definitely the U.S., also potentially something in Asia, where we can extract thorium-228 and radium-224, improving logistics going out to the customers. So when we start with AlphaOne, we will be centralized in Norway, but it will be a natural step for us to expand with something of a production hub structure on the downstream purification part, basically producing the products closer to the customers. And we envision a quite ambitious and sharp ramp-up over the next decade to be a relevant supplier in this field when lead eventually becomes the leading isotopes, which we believe. And it's based on 10 years of development, where we did a proof-of-concept from 2015 up until 2022. We are now currently doing piloting. And we are looking for what will be the next step, which is AlphaOne, but that will also just be a next step. So we envision to having to do AlphaTwo coming to some 200,000 patient doses and eventually what we call AlphaGlobal in a way that we can supply more than 1 million patient doses of lead equivalents, which is what will be relevant if these therapies succeed. Of course, there's -- with such a ramp-up plan, there's always risks, but we are doing a lot of risk-mitigating actions to reduce that from an investment point of view. We are doing the pilot facility right now. We have shipped the first samples. We have signed customer agreements to reduce commercial risk. We are working already now in engineering phase of the AlphaOne and on the regulatory side in a way that we manage also the project in a good way. And then going a bit from strategy and ramp-up plans, talking about financials of the next step that is AlphaOne plant. We have an estimated capital requirement of $30 million to get that plant operational. And it is a rather small investment in biotech benchmarks, but it will be enough to take us into a position where we can stay cash positive for the company. An investment decision targeted in Q1, as mentioned. And in terms of financing, we are looking at debt. We're looking at equity from existing and new shareholders. But I can share today that we have an indicative loan offer on the table that could cover approximately 25% of the capital needed for this project. And in addition, we are working with working capital finance that will come on top of that. So in summary, we are looking at sources that potentially could be 30% to 40% debt and the remaining 60% to 70% as equity of this project. And then if we look at the uses of this project, about 60% will be CapEx. Then we have a share of working capital, which is a large extent related to the feedstock raw materials. And we have some overheads and we have some contingency. And with that, I'd like to give the word back to Jasper to wrap things up and look ahead.

Thank you, Brede. Just to recap, I think it was very clear what Brede presented, but our technology, I think this is -- it took me actually a month to really understand what it means, but we actually can recycle the raw material due to the way it decays, and this gives us an edge by making sure that we can increase capacity without adding investments. And for me, this is absolutely fascinating in terms of having an input to a production process that we can actually continuously reuse and stating the fact, living and having this aside in a very scenic and beautiful country like Norway, we have a very limited environmental impact. So if you compare it to the other production routes that Brede has presented, we are not creating a long-lasting radioactive or nuclear waste. We are not using much water or energy for it, and the environmental impact in general is very limited. For me, this is very close to my heart and exciting actually to see this is possible. But let's take a bit the view to the horizon and look ahead what we believe this company is capable of achieving, maybe not this year or next year, but rather long term. And we spoke about AlphaOne, our main production site where we actually have the first commercial volumes being produced in 2026. You have seen the ramp. We want to build more plants to supply the market and the market will be there. AlphaTwo is capable of producing 10x that amount. And luckily, if you look at the investments, it's not 10x the investment. And also these 10x depends on where you look at it and when the self-scaling ability kicks in with the 50% increase every year. And then when we talk about millions of patient doses when we have established AlphaGlobal, which will be along the side of what Brede presented with our geographic footprint, having maybe an upstream facility somewhere else, very close to the raw materials and taking these bulk masses of tons into milligrams and then have maybe the downstream facility closer to customers in North America, Europe, the Asia Pacific. So this is how we see it in terms of long-term scaling our supply to these million patient doses, which are needed to support oncologists treating patients suffering from cancer. As an organization being still somewhat embracing the start-up mode and the mindset of the team being very committed and very agile, we, of course, need to mature as an organization. And just let me highlight a few things here. When we build the site, we need to, of course, engage with real leaders in production, making sure that we have a plan that actually delivers on time. And on quality, we need to keep innovating our production process. We need to actually maybe also expand toward customers to add more value to their value stream. So we need to strengthen these departments for the time being. So once the capital is there and we can make the investment decision, immediately, we will actually help the organization mature together with the market. In terms of medical expertise, maybe this is another highlight to make. We are not seeing as a pharmaceutical company. Hence, we rely when it comes to these expertise on external partners like Jane, for instance, or our customers that we believe that we, as an isotope suppliers can only work hand-in-hand with our customers and partners like ARTBIO here. But of course, all the other supporting functions we need to develop and we evolve from outsourcing maybe to in-sourcing of critical things. So this is a task that my leadership team and myself will be busy evolving and shaping up. But let me end with our vision for 2035, which is somehow 10 years into the future. So we are setting course to transforming cancer care. This company has been 10 years in the making, and we are leaving the world of PowerPoint into brick-and-mortar, having the pilot side, thinking of AlphaOne and we want to make a contribution, unlocking this paradigm of treatment that can actually help so many patients with our technology. And I think Jane said it very nicely that this only works when this supply chain topic is solved. And we believe that we have a key to solving the lead-212 supply chain issues, and that's why we're here. So we're looking at 1 million patient doses long term when building this plan. And this can make a difference to so many individuals and families in this world. And financially speaking, it's very attractive. We talked about this ambition of grossing out USD 1 billion, which is a massive number, of course. And with our technology, I think we can have very attractive profitability margins from this, meaning that our technology not only works toward having an environmental impact that is manageable, but also from a financial standpoint, we can offer affordable isotopes to our partners and enabling this therapy also from a commercial standpoint for payers like governments or health insurances that this is an affordable therapy and it could also help developing countries and patient populations that are not able to afford these cancer treatments. So that's also very important to mention that we need to keep this in mind. It's our license to operate to bring these innovations to all patients worldwide. And with that, I would like to close our presentation and invite back to the stage, Jane, Emanuele and Brede, please, join me here. And our friends of Carnegie will moderate the Q&A session. I'm sure there will be tons of questions on the line, maybe here also in the room. So if I can hand over to you, Avid, that would be nice.

Okay. Thank you all very much for that great introduction to the radiopharmaceutical field and to Thor Medical, of course. I'd sort of like to start off with what took us to where we are today. I mean it's no secret that biopharma's pace of innovation has increased immensely over the past couple of decades and many new modalities have emerged. But despite that way, the pharmaceutical seems to be one of the really hottest trends right now. So perhaps directing that towards you, Jasper, initially, why do you think that is? Why are we seeing this right now? What has sort of spurred this interest?

The interest in radiopharmaceuticals as such? Or can you rephrase the question?

Yes, in radiopharmaceuticals as such.

Again, I'm not a medical doctor, so take it with a grain of salt. But if you ask me what is most promising in the oncology field, also for decades, maybe even a century to actually cure cancer to have a complete response rate, there is only surgery and there is radiation. External beam radiation has been proven as a very effective way of treating cancer with a high efficacy. And I think if you combine it with the precision medicine idea of bringing it only where it matters and leaving the healthy tissue intact, I think having that technology out there is very promising. And I think this explains at least partially why there is a lot of interest in that field. So the actually idea of making a leap in oncology, I think this is driving many patients and many people in that field.

Perhaps for you, Jasper, but also for you, Emanuele, I think it's -- if you want to add on to it, for a while, I guess, it seemed like Novartis and Bayer were really the ones believing in this field. You've spent quite a bit of time at Bayer, Jasper, with Novartis essentially buying everything they could get their hands on. So what was it that they saw that the rest of the industry overlooked?

Maybe that's a question for you, Emanuele.

I think it's -- I don't think that they saw something that others overlooked. I think they saw data. They saw patient benefit and they saw a path to go from wherever those technologies were in the beginning to where they could go in the future. Most of biopharma is driven by data, right? So if we can show something really useful for patients, that will drive acquisitions. I think that in spite of all of the supply chain complexity, I would say Novartis was probably a little bit ahead of the game based on having done a lot of complex supply chains with CAR T and gene therapy. I think looking at it now, the world has learned that we can develop supply chains that are complex and still be able to deliver hard-to-make drugs.

Okay. And over the past year, I guess, we've seen a few more companies join the pack on the back of a couple of quite sizable acquisitions. Was there a sort of decisive event that drove these players into the radiopharma space, do you believe? Or was it just a matter of letting things take its time?

We can only speculate, right? But I would say that the approval of Pluvicto and its early revenue trajectory probably really convinced a lot of people that this had a chance. Your thoughts?

No, I would agree. I think there is no single or singular event that actually caused this decision. It's just a combination of readiness of the medical and clinical community to accept these technologies and these new drugs. And I think what also added to the fact is that the way treatment centers and hospitals have been handled radioactive substances in the past, it's tried and tested. So it's not a new field they are entering. It's just taking it from a more or less exclusive diagnostic use case to a therapeutics use case, which I think is an important step, but it's managing the same regulations. It's managing the same people. The training is very similar. So I think this is also an advantage of bringing this now to a therapeutic application.

I guess for us, on the investor side, we like to believe that we can catch trends early on. But what we can invest in, at least for us, looking at investments in public markets has usually been brewing for a long time. So perhaps for you then, Professor Sosabowski, what -- in the scientific community, how would you describe the evolution of interest in radioligands over the past few years? Has it sort of been in line with what we've seen in the industry with lots of acquisitions suggesting a really rapid surge in interest over the past year? Or has the trend been a bit different on the -- within the medical community?

I think that when Novartis came in and looked at Lutathera, for instance, that molecule had been around in the nuclear medicine community for a long time, and it had really been stress tested. There were a lot of -- especially in Germany, a lot of compassionate use treatments going on, a lot of retrospective trials. So I think it was -- within the academic community, they were pretty convinced about PSMA for -- as a target. So -- and Lutathera had been around for a while as well. So there was all this data already existing. So Novartis was the one who kind of saw that AAA had done this trial and snapped them up and then saw that the PSMA was in the same situation. I think they were just in snapping up Endocyte like that, they really did after only a Phase II. So it was quite a risky acquisition for them. So I think the academic community has done an enormous amount actually to push these therapies forward and they haven't stopped. There are -- we are very excited about new radionuclides. And the issue has been that we haven't had much access to them. With the actinium-225, the Carlsberg JRC did a fantastic job of sending out doses of actinium to academic centers and allowing them to get their first experiences with actinium-225. That has not been the case with lead-212. There really has not been a lot of academic supply, and it's been much more difficult to get our hands on this very promising and exciting radionuclide. So you see Orano Med having created -- they were first in the field and they kind of created this system that they could -- this plant basically that they could produce lead-212, but they're not interested in supplying anybody in academia or in fact, anybody with lead-212, they just want to make radiopharmaceuticals. So it didn't open things up at all. So I think for -- in the academic community, we're very excited to see independent suppliers coming in and saying we will provide radionuclides to academia for doing innovative research. I think that is the thing that drives -- if you look where FAP comes from, you look where the PSMA comes from, they all come from the academic community and you need to feed back into that to get the leads out that pharma can come along and snap up. So I think it's really important what Thor Medical is doing.

Okay. But is it -- Professor, is it all about the supply, this sort of surge in interest that we're seeing? Or is there also a dimension where our understanding has increased significantly in terms of how we should design these molecules. There's, of course, many aspects to it. There's the choice of target receptor and the targeting molecule with its affinity specificity, et cetera. There's the stability and release profile on the linker, which isotope should we use, et cetera. Has our understanding of how to approach this increased significantly and as a consequence, increase the interest for this therapeutic approach?

Yes. I think it's been a mixture of old targets and new targets, everybody looking for new targets, but at the same time, saying, can I use my old target with a different radionuclide and get a different effect. I mean the interest in radiopharmaceuticals is really in a systemic radiotherapy. We have been used to dealing with external beam radiotherapy, but a systemic radiotherapy can treat tumors that you can't see on imaging. So for external beam radiotherapy to work, you have to be able to image that tumor and say, yes, I can see it's right there, and we can irradiate it with our linear accelerator. And it depends on you being able to image it and it being big enough to image. Injecting systemic therapies that are DNA damaging agents that are radiation therapies gives a whole new treatment modality really. So I think this is what has been so exciting and adding alpha to that has really added to the excitement as well.

And as a reminder, of course, if we have questions from the audience, feel free to raise your hands. Before we go on to the next topic being alpha versus beta, I thought we'd take some questions from the online audience. So this would perhaps be for you, Emanuele, and but also Jasper. Emanuele mentioned that the current supply of thorium-228 might not be of high enough quality. Can you give a bit more color on that? Are there any impurities in the current stock of thorium-228?

Yes. So there's -- I think, first of all, there's not many suppliers to begin with. And as I'll quote the number wrong, but I think between Brede and Jasper will tell you how many millions of tons of thorium-228 are there out there in the world. They're just not there at the right level. We do worry quite a bit about thorium-229 as the impurity because that is very long-lived and can potentially create a real safety concern for the folks handling it. And it really just needs to be sufficiently pure that it can be handled safely and that there's no competing radiation from anything else. So today, there is one supplier that we are aware of is the Department of Energy in the U.S. They're not in the business of being a commercial supplier. They're in the business of supplying strategically to the field. But once there are more suppliers out there, they will step away from the business. And that's why we're excited about having a different way of getting it as well, right? The mining approach is different than the radiation approach, less energy intensive. And if there's a lot of thorium-228 out there in the world, we should just find it and purify it as opposed to trying to recreate it every time.

Yes. And just to add to this, also the production pathway and especially long-lived isotopes, that's the topic that is generated in reactors. So if you just purify it, you don't have that issue. And we believe that with our production process, there is a very high purity of the end product that doesn't contain these long-lived isotopes. So it's another advantage and a testament that we are on the right track with this technology.

Okay. And I guess related to that then, Jasper, we have a question here. So who do you view as your largest competitor today?

That's a very loaded question. I think our current competitor -- actually it's not a competitor. It's the Department of Energy. They own this old reactor in Tennessee. They produce all sorts of medical isotopes for medical applications, and we couldn't be more grateful for their existence because without them, there wouldn't be research. Without them, there wouldn't be preclinical or clinical development of these drugs. They have a very clear mandate in their status that is to support the development of medical applications with isotopes worldwide for the benefit of U.S. citizens. That's what they do. That's why they also provide companies outside of the U.S. soil. And they currently provide also isotopes to the companies we speak to about offtake. I wouldn't consider them a competitor because they will eventually go away when there is a market. But there are other companies out there using reactor routes or accelerator routes as Brede presented in the slide deck. And I'm sure there will be players out there that use a similar technology that we have. And I'm very happy that we filed patents before the summer to make sure that we own this technology also from an IP protection standpoint. But we are not naive to think that there will not be any competitors that are strong and that give us a run for our money, but we are prepared for that.

Okay. And then looking a little bit at sort of how you ramp up your operations, perhaps for you, Jasper and Brede. So assume you get the investment in -- an investment in Q1 2025, how long before AlphaOne becomes fully operational? Subsequently, how many doses per annum would you need to supply for the facility to be profitable post maintenance CapEx?

Brede?

Yes. So if we take the investment decision in Q1 as we have targeted, the plant should be completed in roughly 12 months. Following that, we will have to have some commissioning process, ramping up the plant that could take a quarter, maybe a little bit more. And then we start putting out product. And based on the natural ramp that we have, it will take some quarters until we are in a position where we are actually able to cover our own cost. But we aim that towards the end of 2027, we will be in that kind of position that we start covering our own cost.

Can you give us a little bit of a better understanding for the revenue model. So there's a question here. Would you expect upfront payments from customers when reaching AlphaTwo phase?

Well, that is quite far ahead. We have not been thinking about that, to be honest, upfront payments. We have negotiated payment terms with -- such as ARTBIO and others that we are talking to. And upfront payments could be something that we evaluate. But for now, it's on a case-by-case situation.

Okay. And when it comes to the agreements or the deals you signed with your customers, are they all the same in terms of the revenue model? Is it a pure supply agreement? Or would you sometimes target to get a stake within the drug project itself? Could there be royalties on the table? Should it become a profitable product, et cetera?

Yes. So we are not a pharmaceutical company. So we are not trying to get a piece of the cake of the therapy. We are supplying an active ingredient in the therapy. So that is our business model. There can be additional services that we provide outside of the actual isotopes related to, for example, recycling of the product, things like that. Emanuele mentioned that the thorium-228 will be sitting for 6 months in their generator. After 6 months, there will still be a lot of activity left. And if we can provide services in a way that we also create the kind of a subscription with the customers in a way that if they work with Thor Medical, they can recycle the product, get a higher efficiency within their own operations. That is something that we are considering. So it's not only a supply agreement, but we are not targeting to be a pharmaceutical company.

Okay. Thank you very much,. So jumping back a little bit to the science then and to the topic of alpha versus beta. And perhaps I'll start with you, Dr. Emanuele. So in summary, I guess, what are the key advantages that made you choose an alpha emitter over a beta emitter for your programs? So was this always a given for your first program?

Yes. I will quote Jane because I think she explained the alpha versus beta, I think, really well, higher energy, much more tumor cell kill and a more final cell kill as opposed to a single-stranded break, which leaves the room open for cancers, which are unfortunately adaptive and quite astute that way to try to repair the damage made and maybe even build some kind of resistance to the pathway. So we think that alpha is much more final and alpha can be more on the road towards something that we may want to start called curative, but we're very far away from there today.

If I may add to this, and I think we are still at the beginning to understand the immune system's role in radiotherapeutics. So with the short half-life, at least this is our belief that the immune system has a chance to respond and to actually create antibodies to wash out the cancer cells due to the fact that the half-life is not hampering the T cells and macrophages that actually come to the destroyed tumor side, if you will, that could be the case in using longer-lived radioisotopes like actinium or radium. So I think this is another element that could add to the logic here.

So -- and that's the case for lead versus like other alphas, right? That's why we're excited about lead because short makes that immune system compatibility much better.

Yes.

Okay. Yes. And then just out of sort of curiosity on ARTBIO specifically, Emanuele, what is it that makes you really optimistic that the magnitude of improvement we will see with an alpha molecule will be significant? Pluvicto was mentioned earlier, of course, had some great results, but what are sort of the key [Technical Difficulty]?

[Technical Difficulty] for other isotopes as well at different settings. We think that the combination of high efficacy and better safety drives the potential to be earlier line therapies as opposed to last line when there's nothing left to do. So that's where we are focused on. And I think the data is starting to point to that direction, right? The data shown with the neuroendocrine tumors. We have our own unpublished data that's showing us that as well in prostate cancer. there's a lot to like, and there's a lot of stability and safety potential. There's data out there already suggesting the potential toxicity from actinium instability and the daughter isotopes from actinium going all over patient body. So we'd like to stack the deck and the probability in the favor of highest efficacy and highest safety overall.

Thank you, Emanuele. And then perhaps one question on the same theme for Professor Sosabowski. I guess related to this, a common opinion that you hear among biotech and pharma companies is -- and I think especially those developing beta-emitting molecules is that beta will still be relevant for some indications, could be indications where you have a fixed stroma to penetrate, for example. Is that still your -- is that aligned with your view? I think one thing that makes one a little bit skeptic is at least that some of the targets that were pursued with beta-emitting molecules are now pursued with alpha emitters and the industry seems even more positive essentially. So is there a part of the story that doesn't add up? Is alpha simply better? Or could beta still be relevant in some applications?

I think that we don't really know that yet because we haven't got enough evidence from the alpha trials that have already been done. And I think that the betas, maybe there would be -- you say the range, perhaps they would be better for the range. I'm kind of a little bit more on the side that alphas are going to be better than -- I'm not saying there won't be -- there might be some indications where actually patients would -- there would be greater toxicity with alphas. I can't think of an indication right now or -- but I think it needs to be taken on a patient-by-patient basis in those types of -- we have to be very careful about toxicity. So I think for children who are potentially going to live a long time, these may be issues that we need to be much more careful about that secondary malignancies and things like that. But we really haven't progressed much beyond last-line therapy at the moment. And I would love to see the data on -- like they've just done in the NETTER trial, I'd love to see that with an alpha emitter. So we've got such a lot of work to do, and we need your radionuclides to do it with. So it really is a lot of work that needs to be done in the field. We cannot underestimate how many things need to be tested and combinations need to be tested and maybe combinations even with beta and alpha need to be tested. It's really -- it's a wide open field at the moment, and that's what makes it so exciting.

Thank you, Professor. So I think we have a question from the audience here.

So with the different processes to get important is that [indiscernible] for the customer? And separately, what percent of the total cost of your product [indiscernible]?

Right. So the question was you have different production processes for thorium-228, resulting in different purities. How important is that for customers? And the production cost of thorium, how much does that constitute of the total cost for your customers?

Do you want to say something?

You can start.

Yes. Well, talking about alternative routes, the irradiation route, it has -- among other things, it has the thorium-229. We do not have thorium-229 in our decay chain. It means that it is an important quality aspect of our product. The only long-lived isotope that we have in our process is the thorium-232, which is our raw material. But we are purifying that in such a way that whatever thorium-232 that we have, we can recycle back in the process and reuse as raw materials. So from that perspective, the quality aspect of our process is in a very good position. In terms of cost, one thing is to look at the clinical -- the cost per clinical trial. Another one is to also imagine when you come to commercial scale and commercial approval of these therapies, how much of the cost will be radioisotopes. And what we have seen in the past is it could be in the range of 10%. 5% to 10% is not unrealistic. And I think that what is good for Thor Medical is that eventually, we will have a cost position that allows us to compete even if it's lower than that. So I think we are in a good position. Do you want to add something, Emanuele?

Sure. I think the purity point is not just our requirements. It's also regulatory requirements where the agencies are quite worried about isotope escape and unwanted situations in patients. So it comes from multiple angles, not just us as customers.

Let me maybe add to what you gentlemen have said. I think when it comes to costs and production pathways, for the fact that we don't have these long-lived isotopes in our production and we have a high purity, only then we can offer recycling. And the recycling, of course, has a positive impact on the environment, but mainly it is also a cost advantage since we're taking back activity into the pool of our raw material. And with that, we give a cost advantage that we can also give over to the customer and with that, of course, to payers. So I think this is another element why the separation technology bears a lot of advantages when you look at the different production pathways.

Okay. We have quite a few online questions that came in. So we'll try to get to as many as possible. So for Jasper and Brede, so you gave -- let me see, you gave some estimates on the ramp-up in terms of patient doses. What is the current supply from the DOE in terms of patient doses?

We believe that what they are supplying today is in the range of 25,000 patient doses, something like that.

Okay. And what is the estimated OpEx for AlphaOne? What kind of -- and what kind of manpower is foreseen for AlphaOne?

Well, we need somewhere between 15 and 20 people to manage that operations. We will also have some maintenance cost, running operations cost. We will have a raw material cost that initially is quite high as we are not turning out that many doses. And as we come towards the end of that ramp, it will be also very low. So in terms of COGS, we start turning a profit a little bit earlier than what I indicated before, a gross profit and then to cover also the fixed cost, we need to get to somewhere between, yes, let's say, towards 10,000 patient doses. And then we are covering cost of somewhere between NOK 100 million of fixed cost in addition to COGS.

Okay. And thank you. And let's see. So on financing that, does the USD 30 million requirement cover all the costs for the company until 2027?

Yes, that's correct. So that's the capital requirement. And then CapEx is roughly 60% of that, a little bit less than NOK 200 million. And then we also consider the working capital requirement that we will also try to get some additional financing for and the overhead and the burn of the company until we reach a profitable point.

Okay. Yes. And then we have a question on the recycling process. In the recycling process, how long do you have to wait for a suitable amount of radium-228 to go back into facilitate reprocessing?

Well, it's -- from the one hand side, it's really dependent on what is the price of your product also. If the price is higher, then you want to extract earlier. If the price is lower, you want to wait longer to get a better yield. But we envision that it would be in the range of 5, 6 years until it has such a level that it makes sense to reprocess.

Okay. And then moving on then to lead specifically and Jasper, Emanuele, whoever sees fit to answer this. We've seen a rise in popularity for lead. What makes you confident that the short half-life can be overcome in clinical practice?

So again, I need to remind everyone of an important data point so that we put the question in perspective. There are 40 million PET procedures done each year using isotopes that have a 1- or a 2-hour shelf -- excuse me, half-life. So we make 40 million PET procedures with 1- or 2-hour half-life isotopes. So what that tells you is that when things arrive at a hospital that need to be infused that have a relatively short isotopes with short half-lives, hospitals know how to move that quickly, right? And they know that they can't just sit around and wait for something before they infuse. So I don't think that moving quickly inside the hospital is a challenge. What needs to happen is that the shelf life of the product, which is driven by its half-life, has a certain duration. That duration, we can play with by changing what we put inside the vial that gets to a patient. Depending on that duration, that sets the frequency of delivery and therefore, the density of the network. So to deliver 40 million PET procedures a year, it's a very dense network of radiopharmacies. If you look at the U.S., there's nearly 1,000 of them. It is not necessary to have 1,000 manufacturer points for lead in our view because by adjusting quantities and doses and the driving time, right? That drives a circumference around each single hub, will address the question.

Yes. Maybe to add, in this discussion, there's sometimes made the mistake that you confuse half-life with shelf life to your point. So there is a much longer shelf life done right than these 10.6 hours of the isotope's half-life.

Very good. So going back to my battery of questions since we were on this topic anyway, if you summarize it, why do you think lead has been so underinvested compared to actinium? Whoever sees fit to, but feel free, Emanuele.

I think it's a technology evolution. It really is an evolution of the technology where 3, 4 years ago, no one thought that they could isolate lead and build all that was needed in order to supply lead-based therapeutics out there. We and others have technologies now to do that, and we're building the infrastructure that allows us to deliver those therapies. I think what's worth remembering is that oftentimes, we look at if big pharma jumps in and whether that's a metric for us, for interest and success. I would say that because big pharma tends to favor centralized manufacturing over a more distributed model, as we shared, I think that help people back to jump into lead initially. Although I think now the data is starting to really point to the fact that if one wants a certain efficacy, then one needs to also envision a different kind of supply chain and manufacturing. And there's enough of us companies out there working on this now that are making it happen, that it doesn't look quite as daunting as it may have looked 3, 4 years ago.

Yes. And I think we all need to look at the paramount objective of what we are here today, and that is bringing a therapy to the patient that works. So let alone the whole logistics discussion, what matters in the end is that the therapy is efficacious. And if it's what you showed with your mice model that we can apply smaller doses more frequently to treat cancer, and this is possible with lead, then let's find a way that this logistic works. And I think we are on the way.

Okay. I see that we're almost out of time. So thank you all for your great presentations and good discussions. I will hand the word back to you, Jasper, for some concluding remarks.

Okay. Thank you, Avid. Okay. [Technical Difficulty] trying to understand what we do here and why it matters to patients and why it matters to the industry. And for me, it's a very rewarding experience to see that. My special thanks goes out to Jane Sosabowski, who joins us here today and Emanuele Ostuni for enriching this presentation and bringing perspectives on to the stage that I could never share. So thanks for that. And yes, stay tuned for more updates from our company. Thank you very much for joining us today, and have a nice rest of this Monday.