Good morning and welcome to the ABG Investor Days. My name is Alexander Krämer. I'm a biopharma analyst here at ABG. Today I have the pleasure to host the CEO of Ascelia Pharma, Magnus Corfitzen. Welcome, Magnus, and the stage is yours. Thank you, Alexander and ABG, for inviting me here to the ABG Investor Days to present Ascelia Pharma, our progress, and our exciting milestones ahead. I will be making a number of forward-looking statements at my presentation here today. In Ascelia Pharma, we're dedicated to identify, develop, and commercialize novel drugs that address unmet medical needs within rare oncology. Our pipeline consists of two products. Our lead program is Orviglance. I'm going to spend most of my time today talking about Orviglance because we have progressed it very far. We have completed phase III development. It's a well-defined patient population with FDA orphan drug designation. We are now preparing for the submission of the application for approval in the U.S., the NDA, in the middle of this year. The other program that we have that I'll touch briefly upon towards the end of my presentation is Oncoral. It's a tablet-based irinotecan product with, you could say, solid data in phase I monotherapy and combination therapy with capecitabine. We're looking into a combination study with LONSURF, which is owned by Taiho Oncology, and I'll come back to that later. Our company is based in Malmö. We've been on the main Nasdaq listing in Stockholm since 2019. First, I'll talk about Orviglance. We're very excited about Orviglance, and here's why. Orviglance is focused on a very well-defined patient population with a very significant unmet medical need. Orviglance is unique in addressing that need. The addressable market opportunity globally is $800 million, and we have demonstrated in nine different clinical studies that Orviglance has a strong efficacy and a good safety profile. We have manufacturing in the U.S. We have manufacturing at commercial scale, and with the completed development, we're now moving into the registration phase. We have also announced that we will not commercialize the product ourselves. We're working to find a partner, a commercial partner, who will commercialize Orviglance, and that process is ongoing. First of all, let me take a step back and talk about what is it that Orviglance is doing. In cancer care, cancer in the liver is a major problem. It occurs frequently. Around 10% in the U.S. and Europe is primary liver cancer, cancer that originates in the liver. 90% of cancer in the liver is metastasis, which means cancer starting in one organ and metastasizes, it spreads to the liver. That is very, very important in clinical care because very often the liver is one of the first organs for metastasis. A first signal, a warning that this is a metastatic cancer, and it needs to be treated differently. Also, very often it's a cause of death in patients. Therefore, early detection, aggressive treatment of liver metastasis is essential for good patient outcomes. The best way to do that in clinical practice is liver imaging. For cancer in the liver, MRI is the gold standard. It's the best imaging modality for identifying cancer in the liver. To get the best possible outcome of the MRI procedure, patients will have an intravenous injection of a gadolinium-based contrast agent. Gadolinium is a toxic heavy metal, and it's bound in a chelate, in a chemical structure to minimize the toxicity. Unfortunately, in patients with severe renal disease, the excretion of the gadolinium is very slow. In some patients, with poor kidney function, this can cause a potentially fatal side effect called nephrogenic systemic fibrosis. That is linked to the gadolinium. Orviglance is based on manganese, which is also efficient for enhancing MRI signal, but does not have this gadolinium-associated risk. The gadolinium products have a black box warning for use in these patients. Orviglance does not have that because it's not gadolinium. That is where we are targeting these patients, where Orviglance is the key, you could say, non-gadolinium product with good quality imaging. Let me give you an example of the impact, and some of you may have seen this image before, but this is from one of the patients we had in a phase II trial. What you see is a cross-section, and here to the left image, you see an unenhanced. I'll show you later from our market research that this is what the most frequent procedure in clinical practice for our target population. To the left, you can see a large structure. That's the liver. It's a large organ. You see some black dots, which are blood vessels and bile ducts. A radiologist will have a lot more images. This is to sort of illustrative purposes, not a full diagnosis. To the right-hand side, you can see what happens when the patient has received Orviglance. It works in the way that the manganese from Orviglance, it's drunk in a glass of water, goes into the small intestine and taken up into the liver. The manganese goes into the healthy hepatocytes, the healthy liver cells, and they become bright. All the healthy cells become bright. Metastasis, they could be colon cells, breast cells, lung cells, do not have this ability, so they will stay black. Also, primary liver cancer, as we have demonstrated, will stay black. You can see the ring marked by the orange ring. That's a metastasis that was not visible on the unenhanced, which is what most patients are getting today. Overlooking cancer spreading to the liver has fatal consequences for patient outcomes. Therefore, this has a very meaningful impact on patient care and survival. This is one example from one patient in one study. Importantly, we announced very solid phase III results last year. I'll talk a little bit about going into not too many details. What you see to the right is the primary endpoint. The primary endpoint is visualization of focal evolutions. This is what is used for other MRI agents, and this is what we have discussed with the FDA and the EMA. What we are measuring here is the difference. It's a four-point scale. We're measuring the difference between Orviglance enhanced and for the same patient, what is the score on unenhanced, which is the comparator. On this four-point scale, you see that we have a difference. There are three different readers, three different radiologists looking at the images, and we see a difference approaching one, which is quite a lot on a four-point scale. Very happy with those results, and you can also see very significant p-value. We've also announced that the key secondary endpoints were positively met. All subgroup analyses were in favor of Orviglance, and we even, you could say, for detection of new lesions in almost half of the patients for all readers, we saw at least one additional lesion. This is a very significant improvement in liver imaging for our target patients. Our safety profile, as mentioned, was consistent with what we've seen in earlier studies, some primarily mild transient GI symptoms, which is to be expected. Very strong results. We took those results and a lot of other information to the FDA. We had a meeting with the FDA in the Q1 to go through the structure and all the analysis for the NDA application that we will send in the middle of this year. The feedback from the FDA was in line with our previous conversations with the FDA. We got some very good concrete feedback in terms of how exactly they wanted the final bits and pieces put together. We are working very hard to get that in place. Hopefully we can put in an application that is exactly how the FDA would want it to be. The NDA is a very significant file, so it is a lot of work. We are consistent in terms of keeping our timeline middle of this year, which as previously announced is July 1st, plus minus six weeks. What goes into the NDA? It goes into a summary and analysis of all the clinical studies, all the non-clinical, the animal studies, the lab studies, and all the manufacturing data. We are well on track. Things are looking good. It's a lot of work, and we are on track for meeting the timeline mid this year. We've met the timelines on the clinical study report from the phase III study and getting the meeting with the FDA and announcing the outcome of the meeting. We are well on track, very excited to be moving into the NDA process with Orviglance. Beyond, once we have the approval, it is about commercialization. The global addressable market is $800 million. It is a focused subset of all the patients that receive liver imaging, but it is a very fragile patient population that has special needs, and Orviglance is well positioned to address those needs. We have also announced that we will be commercializing through partners. That is a long process. Basically, we want a partner that is really dedicated and is willing to invest significantly not only in hopefully payments to Ascelia, but also investing in making a very successful launch. If and when we have a partnership, we will work with our partner to make sure Orviglance is a success. You could say it is a 10-month review timeline. If we submit this year, the launch is going to be next year. It is going to be meaning that any royalties and commercial milestones is pretty close by in time. The commercial opportunity is very attractive. It is not like we are educating the radiology community about risk with gadolinium. They are well aware that gadolinium has its risk. For most patients, it is safe, but it does have its risk. NSF is the most significant and severe side effect. Therefore, clinicians today and for a number of years have used mitigation strategies in terms of how can we avoid exposing patients who may or may not have a disease that come into our radiology clinic or hospital, and we need to diagnose them and they should come out better, not worse. What they are doing, as we have demonstrated here in our market research, is that they do an unenhanced MRI in most of these patients. In some patients, it's not sufficient, or the clinical question they want to solve is not feasible to do with an unenhanced. This distribution of how they image these patients is based on Orviglance not being available. When we present the profile of Orviglance as a non-gadolinium agent, you can see to the right that there is an overwhelming majority who is interested in using Orviglance for these patients. We're focusing on, and that's what our orphan designation is for, patients with severe renal disease. The underlying, you could say, concerns and discussions in radiology is that gadolinium also, whenever it's injected, regardless of how well the kidneys are functioning, some of the gadolinium is deposited in the body. It will stay there for a long time, maybe permanently. There are a lot of ongoing investigations requested by the regulatory authorities into the safety profile of the gadolinium. It deposits in the brain. It deposits very much in bone and skin as well. There are some overall concerns. There's also the concern about patients having worse health after having been exposed to gadolinium and seem to have retained gadolinium to some extent in the body. Another important issue that is increasingly gaining attention is the fact that whenever we inject gadolinium in patients, it will be excreted through the urine. The urine goes into our sewage system. That means the gadolinium goes into our drinking water. Because the concentrations of gadolinium, they are very low, they are extremely difficult and expensive to sort of filter out. That is a concern. There are a number of publications showing that gadolinium in drinking water close to medical institutions is increasing significantly over the last few decades. Certainly something to look out for. Manganese is, you could say, much less of a concern and will already be filtered and adjusted through the filtration systems available today. The industry is, you could say, finally reacting. Gadolinium has been in the market for decades. They are developing lower dose, so reducing the dose of gadolinium to get a comparable image. GE Healthcare has also been vocal in terms of defining that they believe that a future without gadolinium is interesting and have presented last year some good data on a phase I injectable manganese agent. That we think would be complementary to ours, so not a threat. Actually, the contrary, having one of the major players talking about manganese is positive for Orviglance. A very exciting time for us with phase III data and these macro trends in the industry. We're also receiving a very strong interest in Orviglance. We've had a number of presentations here with Orviglance phase III data in various settings. This week is particularly busy. This afternoon, I'll be going to Amsterdam for the European Society of Gastrointestinal and Abdominal Radiology. We have three presentations there by prominent investigators from our phase III study. We will also have a presentation at ISPOR, which is a health economic conference. We have announced that in terms of the real-world evidence on how sick and vulnerable our patient population is, which is important in terms of getting, you could say, pricing. I think very exciting times, a lot of interest about being the lead manganese agent towards the market addressing this unmet medical need. With that, I'll switch gears and go to Oncoral, which is equally exciting, but less far in development. Irinotecan is, you could say, a well-known anti-cancer agent. It's a chemotherapeutic agent, Cellgift in Swedish. It's given usually every second or every third week. Patient will go to the hospital, will have an infusion, a very large dose in one go. When you get a very large dose, you get a very high peak concentration immediately, and patients report very, very significant side effects in the first few days. It's a very potent anti-cancer agent, but the safety profile is a significant issue, and many times patients need to discontinue because the side effects are unbearable. We want to change that. With Oncoral, we can give, because we formulated irinotecan in a tablet instead of an infusion, we can give daily doses. If you give daily doses over a longer period of time, you can give a comparable amount of irinotecan, but you will avoid these very high concentrations that are linked to some of the side effects of irinotecan. Going that route, based on data that others have also demonstrated in the literature, lower, more frequent dosing of irinotecan can lead to better efficacy and better safety. That is what we want to do. We have completed phase I development monotherapy and phase I in combination with capecitabine, which is an all-oral FOLFIRI regimen if you are into that. We are also looking into gastric cancer in combination with LONSURF. LONSURF is a tablet anti-cancer therapy doing north of $500 million for Taiho Oncology. What you can see here to the left is very, you could say, good data showing synergistic effect by combining irinotecan and LONSURF in an animal model. We want to replicate that in a phase II trial where we have a small collaboration with Taiho Oncology, where we want to have one arm, which is LONSURF, which is approved as monotherapy. Then we take LONSURF plus Oncoral and see whether that will lead to better outcome of patient outcomes. Exciting study. The idea has been approved. We have been prioritizing our resources on Orviglance development. We have come very far, and hopefully we will be able to announce a partnership at some point and then put a lot of attention to Oncoral again. Gastric cancer is, you could say, the lead indication as we see it right now. There are a number of other indications that are very interesting. Because irinotecan is out there, it has been studied in a number of different indications. It is approved in colorectal and pancreatic, but also used in some treatment guidelines for other solid tumors. There are lots of opportunities ahead for Oncoral, and we are very excited to hopefully be able to move that program forward in the near future. I will just end my presentation before going over to Q&A in terms of what are the key milestones ahead. We are very focused on capitalizing on all the investments that we have made and all the efforts that have been made in the Orviglance development. We delivered on the completion of the study, getting the study reporting in early Q4. We had the meeting with the FDA in Q1, and we are on track for submitting amid this year. In parallel, we're doing advancing launch readiness, which with our investment focus is primarily educating the medical community. That means part of that is presenting at medical conferences and also making sure that manufacturing and everything is ready for supply for launch. Of course, also working to secure a partnership, finding a commercialization partner for Orviglance is a key milestone for us. With that, I'd like to start the Q&A. Thank you very much, Magnus, for this very interesting presentation. Now we start with the Q&A, and I have a couple of questions. Magnus, of course, it's in all the newspapers these days, Trump's policy, new policy of the so-called most favored nation pricing. I would like to hear your opinion and your thoughts maybe, because I mean, it's of course very early days. It's hard to say anything specific about it, but I would just like to hear your thoughts about how this new Trump policy could potentially impact Orviglance next year once it is commercialized. Yeah, yeah, thanks for the question. I think, to be honest, I probably know as little or as much as anyone else about how that's going to be implemented in any way or form. I think overall we are in a good position for, you could say, these geopolitical changes. We've been thinking a lot about that for a number of years in our supply chain strategy. Our manufacturing is in the U.S.. If we continue to see high tariffs between the U.S. and Europe, we will be in a good place for the U.S. market, which is our key priority. It's the largest market globally. I think in terms of, I think it's been a discussion for decades that the U.S. drug prices are higher than the rest of the world. I understand why Americans want to change that. The cost of commercialization and the structures they have are also more expensive. If you look at profitability, some things have to, you cannot just change one part of the equation. I think that is also interesting to see how those discussions will develop. I think we are in a really good place. U.S. is our key product. If it's reference pricing, there are lots of strategies within Europe where we have reference pricing within the EU, where there's been sort of ways to, you could say, optimize the commercial opportunity. Some of those learnings could probably be applied to the U.S. as well. I see, I see. Great. My second question relates to my idea. You mentioned it just right now, the commercialization in the U.S., the process there, and also a little bit like the target, like the KOLs there in the U.S., the radiologists, like the big, big clinics that really have these kind of patients. Of course, these patients are very frail. They're very complicated due to the kidney problems. I would like to hear some sort of estimates on how many doctors actually you would need to, or your partner would need to address on the U.S. markets, like how many clinics are there and how would you, initially when the drug is approved and launched, how would you target to roll it out, basically the product? Yeah, so a couple of years ago, we were planning to launch Orviglance ourselves in the U.S., which means that we've made a lot of investment into understanding the pricing and market dynamics. What is the, you could say, the heat map? In which institutions are the patients present and so forth? Which means that we have a very solid data package and plans that we will obviously share with the partner and work together to support them in the commercial efforts. The data we have show that 75% of the patients in the U.S. are at 400 medical accounts, which means the large hospitals have the vast majority of these patients because they both have usually cancer and severe renal disease. As you say, they need special attention. You do not want to do that if you are, you could say, a small institution. You want to refer them to a larger place. That also means that we know, you could say, I think we've shared that it's around 2,000 radiologists in the U.S. relative to those 75% of the market. And that's a pretty meaningful focused launch, which where I think the economics of that is going to be attractive for a partner. I think all of those plans, you could say, we have an outline of the plans. Obviously, we need a commercialization partner with the muscle and the infrastructure to roll it out, be very efficient. If they do not have the relationships already with the KOLs that we are speaking to and have been speaking to for years, we're very excited about Orviglance. We'll make the introduction and that will continue kind of seamlessly. Great, great, very interesting. Maybe a last question due to the time running out. Could you comment a little bit on the contrast agent market currently? How does it look like? Which are the major players? You talked a little bit about the current philosophy of these big players, how they think about innovation in the market. I mean, there are some efforts with this kind of half-dose gadolinium, which you mentioned did not solve the problem, but who are the major players and what kind of products are really the big sellers at the moment? Yeah, so gadolinium agents have been on the market since the early 1990s and then there have been some improvements. The key players are GE Healthcare, Bayer, Bracco, a private Italian company, and Guerbet, a French, small listed company. They are sort of leading the gadolinium space. I think originally for many years, there were no really new introductions. Now we have the lower dose agents, which is obviously better to use less, but you still have injection and you still have the gadolinium challenges. GE has been the most vocal about putting in clinical development of manganese, but it is something that if you look at patent applications and other things, it is something that is also on the radar of the other companies. They are looking into this issue. Being in Europe, there is legislation in terms of commercialization and how you could say if you pollute the environment by giving drugs to, and it could not be just contrast agent, could also be other products. If you give it to patients, it goes into the environment, you need to help pay the bill for cleaning up the environment. There are different dynamics that are really interesting, I think. I think we are at a very good time in terms of how these trends are progressing. Perfect. Thank you very much, Magnus, for coming here today. It's been a pleasure. With that, I close the session. Thank you for watching.