A very welcome back to DNB Carnegie Small and Micro-Cap Seminar. We are moving on in the schedule, and the next company to present is Spago Nanomedical, and with me, I have CEO Mats Hansen. Very welcome. Thank you very much. Please, Mats, go ahead with your presentation. Thank you, Claus. Good morning, everybody. I am here to present Spago Nanomedical, and specifically our optimized platform for tumor delivery of therapeutic radioisotopes, which we certainly believe now is a differentiated, de-risked, and expandable clinical stage opportunity, which we will go a little bit more into detail. I should say, there is a lot of information on these slides, but I will try to keep it brief, and will be happy to take any questions afterwards, or in the break. Spago Nanomedical has developed a first-in-class nanoparticle radiopharmaceutical platform. We are deploying this in a tumor-agnostic approach, which we will come back to later, to fill those treatment gaps in many cancer indications that are out there, specifically cancer tumors that cannot be treated with effective radiopharmaceuticals today. Our main asset, Tumorad, is now in clinical stage, and it's actually completing phase I studies as we speak in cancer patients. We shall come back to that, and I'll show some encouraging data out of that trial. We believe that our technology represents a multi-indication expansion platform, which means that compared with other agents out there, specifically radiopharmaceutical agents using radioisotopes to treat cancer, we are able to use our technology in several different tumor types. This is actually addressing one of the main problems in radioligand therapy or radiopharmaceutical treatment today. Current agents, which are mainly termed RLTs, or radioligand therapies, are dependent on molecular targets on the cancer cells. This sort of represents what we call a lock and key approach, where you need a key to unlock the tumor for the treatment. We are bypassing that, and I shall come back to that, but the key to this is that it actually leaves the vast majority of tumors behind when it comes to treatability. Around 85% of tumor types today are underserved by radiopharmaceutical treatments that we know is effective, because we know that radioisotopes kill tumor cells. The approach we are taking is to use the tumor physiology rather than the tumor molecular profile. I will not go into detail unless somebody asks me to, but in principle, what we're using here or actually taking advantage of is the physiology of the growing tumor, which frequently leads to a leaky vasculature surrounding the tumor tissue. This leakiness allows for extravasation or leakage of macromolecules, or nanoparticles in our case, out into the tumor tissue independently of this lock and key approach that is used by many others. We like to call this a master key approach, because this is a phenomenon that is currently or generally occurring in tumors, in solid tumors. By that, we believe that our Tumorad asset can be used to treat many types of tumors. Very briefly about Tumorad. It's receptor independent. It's based on our nanoparticles. The particles have been designed to be exactly the size that has been explained in the literature to be the optimum for nanomedical targeting of solid tumors. They are carrying lutetium-177, which is a proven isotope. It already occurs in a few of those radio treatments that are on the market, so we know it works, which de-risks the project. We have a very strong IP position for this. There is no one out there that has taken this or actually succeeded in this. Many are trying to find stable complexes between isotopes and carrier molecules. That is a difficult thing. The stability of our particles together with the radioisotope is unprecedented. It's excellent. With this, we really believe that we are offering a first-in-class radiopharmaceutical approach for expanded treatment. This really offers a class-wide type of treatment. Does it work? Well, as I said, we're in clinical trials. We are beginning to see, and this is actually data that we communicated a while ago. We are seeing excellent uptake of our particles with the radioisotope in patients with head and neck cancer, and specifically, this is a patient with a rare tumor type called adenoid cystic carcinoma, which is a lethal condition when it reoccurs after initial treatment. There is really no good treatment opportunities out there today or no gold standards. The benefit we see with Tumorad and using these particles to carry the radioisotope into the tumors allows for a sustained intratumoral radiation. Which means that there is a good chance to have a treatment effect downstream by providing Tumorad to these patients. We also see that there is a combination potential, and this is generally known with radiopharmaceuticals because radioactivity typically opens up the tumor for other treatments. It causes release of molecular factors that can be targeted by other agents. This is something we are really interested in, and we are looking for development partners to exploit that a little bit more. But our main focus is the clinical development of Tumorad. And this, again, I mentioned adenoid cystic carcinoma. We've also seen excellent tumor uptake in another type of head and neck cancer, which is a more common type called squamous cell carcinoma. In this case, it was in the tongue of an unfortunate patient. I should say we are running this trial in Australia. The trial actually met its primary endpoint, which was a maximum tolerated dose earlier in the spring. We are now recruiting the final two patients for the study and specifically targeting patients with head and neck cancer because we believe they represent a good way forward in the development. Safety-wise, we are seeing exactly the pattern we were expecting, both based on preclinical data, but also based on what has been seen with other lutetium-177-based agents. The dose-limiting toxicity, which was the primary endpoint of the study to find out, is mainly blood-based, which is typical for radiopharmaceuticals. It's manageable, it's asymptomatic in our case, which means that the patient doesn't notice it. It's been seen on laboratory findings. But this means we now know what dose to target for the coming patients in the coming development. With the good uptake we've seen in ACC, we are now paving our way forward in the ACC indication as our main or lead indication, and we are going for an Orphan Drug strategy. This is a small indication, which means that we can apply for Orphan Drug Designation with the FDA, which will provide us with a more accelerated development pathway. We are planning to go ahead with the phase IIa, starting or continuing actually in Australia and continuing after that also in the U.S. So we have a lot of activities ongoing in the U.S. right now to prepare for that. The trial we are looking to conduct also contains other arms or cohorts, as you can see, all of them in the head and neck space. Head and neck cancer is a very diverse type of cancer with several different types of tumors. We believe we can go in each one of them, or at least try to go in each one of them. We already know, as I mentioned, squamous cell carcinoma is one where we see good uptake. So there is room for expansion within this trial, which I think is very attractive to a potential partner and also for an investor, of course. As I said, we have activities ongoing in the U.S. We are now preparing for regulatory advice and applying for Orphan Drug Designation. We believe that the trial design we are looking to conduct after the phase I is a very efficient one. Since this is a niche indication, the ACC one, we believe that we need maybe 25 to 30 patients for a pivotal trial. That means for a trial that will take this drug to approval in ACC, or likely followed by a post-approval trial. Of course, Orphan Drug Designation offers market exclusivity. As I mentioned, we already have very good IP protection as well, so we do not believe that will be an issue here. The market, going into that a little as well. ACC is a niche indication. There are not that many cases, but we believe it still represents an attractive way forward. Since we can go fast to approval, we can do it with relatively limited resources. We still believe that there is room to claim quite a high price. I will actually say that the figures here are quite conservative in my mind, given that this is a deadly indication where there are no gold standard treatments today. Of course, as I said before, there is room for expansion from ACC, adenoid cystic carcinoma, into broader head and neck. We are also, and I have been speaking a lot in the past about triple-negative breast cancer, which we still believe is a very interesting indication. There are few approved drugs to treat that condition. We think given the nature of our technology and the fact that we have already had a product before, SpagoPix, which was a contrast agent for MRI that showed really good uptake in breast cancer tumors. We think that is an interesting indication. Then beyond that, of course, several other solid tumors. To conclude, we truly believe we have a first-in-class and now also a clinically proven modality to deliver therapeutic radioisotopes to cancer tumors. Given that it is receptor independent, we can use this to unlock underserved tumors, as I said, the master key approach that we have. We see that it works in phase I, and we also see that phase I probably supports an accelerated regulatory pathway. As I said, a multi-opportunity market in the future. Again, coming back to the good IP protection that we have, which gives a robust protection and market exclusivity. So with that, I will leave the field open for questions. Thank you. Yeah. Thank you so much, Mats, for the presentation. If you have any questions for Mats, please raise your hand and I will hand you the mic. Also, all you following the presentation online, you are also free to send in questions. But let me start with perhaps the phase I study that is still ongoing and the images that you have seen that looks very promising. Is it possible, even though it is difficult to show this in a presentation, but is it possible to describe what you have seen and how much this sort of is evidence of the mechanism of action? Yeah. Well, the good thing with radiopharmaceuticals is that even at the very early stage, you can actually see where the agent is going in the body, and that is what we see here. That means that even if we do not, in this early clinical development stage, are able to generate the traditional efficacy data, which is difficult with any agent in cancer actually. Like survival or progression-free survival, we are actually able to see that this is taken up in the tumors. Yeah. Given that and given the fact that we know that lutetium-177, which is a beta emitter, has a good treatment effect in other cancer types like prostate cancer and like neuroendocrine tumors, there is a very good chance that if the exposure level holds up in these tumors, there will be a good treatment effect. These results, and coming to your question, the fact that we actually see this very encouraging tumor uptake in cancer patients is a big step on the way. To sort of validate our technology. The two patients where you have seen the clearest evidence of uptake in the tumor is head and neck cancer patients. Why do you think this is the case? I think there are probably many explanations. All of them are probably very difficult to understand and to go into. It could be, of course, that these, or at least ACC in some cases, is a very aggressive tumor type. It has been described that the so-called vascular leakiness in aggressive tumors is higher than in more slow-growing tumors. That is one type of explanation. Another explanation could be methodological or technical. These are tumors that are quite relatively, sort of say, superficial to the skin, which means that the detector of the SPECT, in this case, measuring radiation is closer to the tumors, closer to the radiation source, for instance. We have seen uptake also in other tumors. Like prostate tumors and some lymph nodes, which is also encouraging. Is that shown on images? That is shown on images, yes. Okay. That sounds good. Are you not doing any other sort of analysis of the tumors, like biopsies or something like that? Not in this trial, no. It would be, unfortunately- Okay too complicated. The study's still ongoing. You are doing something called fractionated dosing. Could you please just describe what this means? Yes. In the last two patients of the trial, we wanted to use those patient to explore whether we could sort of divide the dosing into smaller fractions. Instead of giving one dose, which in our case would be 15 megabecquerel per kilo, we would divide that dose in, let's say, 110 and 105. This would be a way to potentially increase the dose without causing the effects on the blood cells that we see with higher mono doses, if you wish. This could be a way of treating the patients in the next phase? Yes, absolutely. Okay. Where do you stand when it comes to recruiting the patients? It's ongoing. It's ongoing. Will we have data before year-end? That's the plan. You mentioned then also that the dose-limiting toxicity was quite similar with other lutetium therapies approved. Is it possible to describe a little bit, the level of adverse events and how that fits into perhaps combination therapies? It's a broad question. It's a very broad question. To start with, comparing to other agents on the market from the safety perspective, as I said before, the overall pattern is similar. What we don't see is adverse effects on the kidneys, which is common with at least one of the other lutetium agents. That is very encouraging because we have spent a lot of research time on optimizing our particles so that they would not be stuck in the kidney. That seems to hold up. So that's really encouraging. We knew that bone marrow would be a risk. Bone marrow is probably the dose-limiting organ given what we see on the blood, let's say the overall blood picture. We knew that the liver would take up a lot, and we knew that the spleen would take up a lot, but that doesn't seem to be such a big problem either. Overall, I would say the translatability from what we saw in the animals and from what we knew about lutetium agent before, is holding up very well in the humans. Mm-hmm. But to go back, perhaps rephrase my question then. Combination therapies is very common in cancers. Would you say your safety profile better fits into immunotherapies than perhaps chemotherapies? Probably. I think there are theoretical reasoning why combination with chemotherapies like platinum agents, for instance, cisplatin, would probably work well. If you could manage the toxicity of cisplatin, which is not a question. It would probably work well with immunotherapies like checkpoint inhibitors, like you say, because radiation is known to open up. There is a common saying, you could turn cold tumors hot again. That is what radiation can do. It sort of opens up the tumors for other treatments. There are DNA damage inhibitors like the ones used in breast cancer, for instance, olaparib by AstraZeneca is a common example. Those are very interesting as a combination with an agent like this. Because you're targeting primarily the adenoid cystic carcinoma as a start, at least. How well does this fit into the current treatment? Well, the thing with ACC is that there is no gold standard. There are medical doctors out there trying different agents with limited success. One of them is Avastin, which is an angiogenesis inhibitor. Others are trying the immune checkpoint inhibitors. None of them has shown any real good evidence of effect as far as at least what is seen in the literature. That's why I think that given that we know the tumors are generally radiosensitive, we know that these people die from lack of treatments. There is a good chance. If you could open up that niche with ACC, get to the market, then I think there will be a good chance of doctors out there trying Tumorad in combinations with all sorts of agents in these patients. So, yeah. Perfect. Do we have any questions to Mats? I will go ahead. You are planning for a pivotal study, if I understand you correctly. Yes. Is that something doable to do on your own? We believe so, and that is also one of the reasons we are choosing an Orphan Drug Designation like ACC, because it is a reasonably sized trial, like I said, probably around 25-30 patients. It can be kept in a reasonable small number of specialist sites. We already have one of them in Australia in the current trial, and we have identified a few others in the U.S. Yes, I believe that is doable with the quite limited organization we are running today. You have been in contact with the authorities about the design? It is ongoing. It is ongoing. As well. First of all, we are appointing a U.S. agent to help us, and we are having regulatory discussions around that. Why are you particularly interested in the Australian and the U.S. market for running a trial? The Australian one because we are already there. Because it really gives the opportunity to run the trial in a very cost-effective way. I did not say it before, but we chose to run the phase I in Australia, which may sound a bit weird, but it actually paid off quite a lot. We get 43%-47% cash back on expenses for the trial in Australia, which is significant. We also identified very good sites there. There is easy access to radioisotopes, and the whole supply chain, which can be a huge issue in radiopharmaceuticals, has actually worked out very well in Australia. I can name a lot of advantages of Australia. The reason why we are looking at the U.S. is, of course, that is where the market is, and also that we need to get some sort of regulatory endorsement going forward for this plan. Then there is really the question, should we go in Europe or should we go in the U.S.? The fact is that it takes too long in Europe. It will cost more. Yeah. What will it cost? Sorry, what? What will a study cost, do you think? That will depend. Yeah. I won't go into that here. A returning question from on my side is, of course, partnering and how you are working with partners. Maybe you can give us an update if you are out there and promoting the program on conferences and such. Yeah. So that is something that we are doing very actively now, especially again, targeting the U.S. and both investors and strategic partners in the U.S. We are working with American bankers for that as well. This is sort of the first time in the history of Spago that we actually have some really robust clinical data to go to the U.S. with and to attract the interest over there. So that is really what we are pushing for now. Generally, the radiopharmaceutical field continues to be one of the hottest areas in cancer. There is no doubt about that. The number of deals made in that field has been significant over the past years, and it seems to continue as well. But as you mentioned in your presentation, a lot of those deals have been centered around targeted therapies. What kind of interest do you get for your EPR mechanism? Increasing interest, I would say. Yeah. Because I think one of the limitations with targeted agents is really the limited amount of targets out there. Not only that, because besides from being able to design a molecule that binds to a certain molecular target, it needs to be stable when it carries a radioisotope, which is not a given at all. That's a really tricky one. That's why I'm saying that the stability of our complex, our particle together with the radioisotope, that is important. That is really important. Also that it's stable when it gets into the body so that you don't have a sort of loose radioactive ion circulating around in the body and ending up where it shouldn't. I think it's a difficult technical field. We've been able to sort it in this way. Do you see any competitors moving forward? There are lots of companies- When it comes to EPR effect. Not really EPR, but the thing is also, I think many are sort of missing the fact that the EPR effect, this vascularity, the deficiency in growing tumors, is really a prerequisite for many agents. Because if the molecule you are putting into the patient does not come out to the tumor tissue, then it will not reach the tumor cells, and then there will be no effect. What we have done is really to optimize for it. To optimize the material that stays in the tumor and carries a radioisotope in a very stable way. That is why I was saying before as well, we have this sustained sort of radiation in the tumor. We have taken images of these patients up to day eight after administrations, which would be very difficult with one of the other agents out on the market today. We know that we are irradiating the tumor for a long time, and that should add to the therapeutic exposure in the tumors. Okay. The final question is just, what should we expect when it comes to news flow in the next six months or so on? If it is doable to start a pivotal trial, let us say in late 2027, if you get the right feedback from authorities and you of course, get some more money to your balance sheet. Yeah. As I said, we are looking to file for Orphan Drug Designation. That's a milestone. Obviously, closing the phase I trial. Hopefully, we'll get some more exciting images to show in presentations like this. I think there's a lot coming. Okay. Great. Thank you so much, Mats, for the presentation. Thank you. Thank you.