A very, very warm welcome. You are going to be allowed to talk very much soon. So a very, very warm welcome to this year's Investing in Oncology Forum. It's arranged by Cord Communications, where I work as a partner, and my other fellow partners are here. Just raise your hands. This is us. And a couple of more people. So we did this four or five years ago, then the pandemic came in between, but it was a very appreciated seminar when we did it last time because all the companies who are here, they will only focus on their most valuable asset. So this is not the regular seminar you would hear normally. So it's just the most valuable asset, and we have a fantastic panel of clinicians who are in the real world and getting some use of these drugs, hopefully in a couple of years at least, but they have a need for what is developed, and they will tell you more about that. And we also have a panel of investors to help us, both these panels to help us with the questions to the companies presenting. And before I present our first speaker here today, I'd just like to very briefly get a short presentation from all of you in the panels. Can we please start with the clinicians? Okay. Do you hear me? Yeah. My name is Nils Wilking, oncologist. I've been working in clinical oncology for some 40 years. I've been having had different roles. I've been head of the oncology clinic in, in Lund Malmö for some years. But I've also done quite a lot of work together with the Institute of Health Economics in Lund. We've done several reports on access to oncology and oncology drugs in Europe. We are presently updating a report, on behalf of EFPIA on, on this matter, and, we've also done some research on societal impact of different drugs like trastuzumab, the life cycle impact of that drug, and, I work, with, some different European projects at the moment and do still a little bit of clinic. Thanks. My name is Samuel Rotstein. I'm also an oncologist. I've been working with breast cancer and GI cancer for also about 35 to 40 years. I was previously head of the department of oncology at Danderyds Hospital, and I'm now continuing to work at Karolinska Hospital with breast cancer patients. My name is Cecilia. You have to push it. So my name is Cecilia Lind. I haven't worked 20, 30 years as a medical oncologist, but at least 20. I have also had different roles in the pharma. I've been working for Novartis and Sanofi in the past, and part-time I also support small and midsize companies, especially in early development. Hareth Nahi. I'm a hematologist. Lately I've been monitoring immune therapy in cancer, mostly in hematological cancer, but even in other oncological diseases. Thank you. Thank you very much. Can we have an applause for this fantastic. It's amazing, all these years of experience. Please, Ted, go ahead. Ted Fjällman. I come from Flerie. Flerie Invest is an investment company based in Stockholm, but we have representation in London, in Brussels, and in Zurich as well. We invest primarily in pharmaceutical development, a little bit in med tech, and of course a fairly large part of our portfolio is in oncology, so I think that's why I'm here. Of course, cheering on our portfolio company among the four, which is Mendus, where I also sit on the board. A little bit about Flerie: we have about SEK 3.5 billion of net asset value. Those are split around 28 companies and also three investments into funds. So, out of those 28, seven are listed companies, and the rest are private companies. We actually invest pretty early, but that depends a little bit on who you talk to because different people say what is early and what is late. Actually, we invest mostly in clinical stage companies. Thank you. My name is Bengt Julander, and I represent Linc, which is very similar to Flerie. I would say I could say exactly the same things, almost. We invest in pharma and med tech, and one of our companies is here. You have to guess which. I'm Johan Kördel. I'm from Sound Bioventure s. I'm a drug research and developer from the pharmaceutical industry that over the last 15 years have been doing venture investments into primarily private companies, where oncology, of course, is an important part. Hi. My name is Mårten Steen. I'm with HealthCap. We are an early-stage venture capitalist. We have invested in more than 125 companies, of which a significant portion have been in oncology as well. We also have one of the portfolio companies speaking later today. I can also guess that. But yeah, I'm just happy to be here and excited for the discussion. Thank you very much. In the name of equality, do you, can you give them an applause? Okay. So as you can see, we are not following the schedule, but don't worry, that's my task. I'll try to keep the schedule going forward. Now it's time for our guest, from Citeline, our international flavor. It's Alex Bohr. You're going to talk about oncology in a global perspective. Thank you very much. Thank you. Hi everyone. Good afternoon. Just going to place this here. So for the next 10 minutes or so, I'll try to give you a, a perspective on what the space looks like externally, globally. But before I get into that, I'm Alex Bohr. I'm a principal consultant at Citeline, and I'll go into more detail about what we do in Citeline and what we are, etc. beyond just an introduction into what the company is and, and, how sort of we can bring our resources to bear to help you guys understand the space a bit better. I'll go into a discussion around the top oncology indications by revenue from a commercial perspective. What does the market look like right now and historically as well, and a bit of forecasting. One of our companies, our parent company in Norstella is gold standard in the industry for forecasting, Evaluate, if you're familiar with them. We'll also go into a little bit of the key value drivers in the global oncology market. So with all the value that we're seeing created within the space commercially, what's actually underlying those, and how has it been sustained, and what does that mean for the future for you guys here as well? Beyond that, we'll take a sort of a closer look into precisely at the IO space. We know how much the IO space has grown quite significantly over the last few years, over the last two decades or so. And we want to take a closer look as to why that is, what the key developments are within IO. Then beyond that, we want to look into trends in the funding space. So obviously, most people here are thinking about funding and access challenges that they're facing. We'll look at the trends historically and also looking forward what the funding has looked like so far and what lessons we can learn from them. So just to start with, a few years ago or about a year or so ago now, I guess, Citeline, which is a life science industry data company and consulting firm, was acquired by a company, a large company known as Norstella. Norstella had four companies underneath it. One of them was Evaluate. Evaluate specializes in more sort of commercial data, so forecasting, PTRS data, analytics, and data of that nature, some clinical stage data as well. Citeline is far more sort of stronger within the from the clinical perspective. So, the objective of this acquisition was to try to build a single source of truth, effectively, a place, a one-stop shop for people like yourselves to go to, to gather data to help you do your day-to-day work. As you can imagine, through this sort of data gathering and housing and curation, we're also able to do quite very good custom projects and custom consulting, which is where my team sits, ostensibly. But for today's conversation, I'll be focusing more on pulling data from both the Citeline side, which is more of a clinical data, and a little bit from the commercial side, which is the Evaluate side of the company. With the two, we'll be able to tell a fairly comprehensive story about what the space has looked like in the past, what the trajectory looks like, and again, what the implications of these might be. Let's start with a high-level view of what the oncology space has looked like for the seven major markets. As you can see, from 2017 onwards, we've seen a consistent growth of the oncology market in terms of revenues across these seven major markets. Now, what you'll see later on from 2024 onward to 2031, you see a slowdown of that growth. That's important to highlight here because there are certain key reasons why some of this slowdown might be happening. There are a number of challenges such as we see at the patent cliff for some of the major brands within this particular window is due. So straight away, that creates challenges. Of course, beyond that particular challenge within the 2024 to 2031 window of slowdown, we also expect there to be saturation within the breast cancer and prostate cancer spaces as well. As more and more of these assets mature, we expect to see a bit of a slowdown and stagnation within that area. So overall, we've seen really significant growth for quite a number of years now, and now we're expecting a bit of a slowdown. It's important to bear in mind, of course, that these are simply projections based on current data, based on pipeline information that we have at the moment, but there's still room for a lot of this to be evolved on an annual basis. We do refreshes of our approach projections to ensure that they are as up-to-date as possible. So who knows, in the next 12 months or so, things might change. But it's good to understand where we are right now, where we're going based on the current data so we can best make our decisions about where to focus our attention, where to focus our efforts going forward. As I mentioned earlier about the growth that we've seen, again, bear in mind this is sustained growth over quite a large period of time, and the slowdown in the latter years of the projection notwithstanding. But this is underpinned by five major areas, five major trends that we've seen, which we think support a lot of the growth here. It goes all the way from, you know, increasing investment in basic science, so funding for academic research increasing over the last two decades or so, focus on precision oncology. And precision oncology, of course, this is something that's been happening for quite a few decades now, but the innovation continues to drive more and more, and this is, of course, where value lies the most. Beyond that, obviously, IO, and later on I'll go into depth, how IO has been maturing over the last decade or two or so and how the pipeline still looks as it relates to IO versus the rest of oncology. There's, of course, also advanced therapeutics, you know, cell and gene therapy, ADCs, PROTACs. These are all reasons for some of the value creation that we're seeing. Again, the slowdown notwithstanding. And then, of course, some of the successes we've seen in the markets as brands such as Keytruda and Tagrisso performing well in terms of the patient outcomes that they're able to achieve all means that the focus when it comes to funding support, but also when it comes to, you know, success commercially, tends to trend more and more towards biologics. IO being the larger umbrella that we want to make sure that we highlight here. So again, five key drivers for a lot of the value we're seeing so far, and it creates a bit of an optimism, as far as we're concerned because it means there's still room for growth. There's still room for optimism, as far as we're concerned. Again, the long-term view being what it is right now, it may evolve. We're seeing some upticks in the funding cycle in 2024. Slow start, but it's taken up. So again, optimism. Going a little bit deeper into the landscape and what that looks like right now, the pipeline, the oncology pipeline as it looks like right now. First thing that stands out straight away is, of course, immuno-oncology, right? We're looking at something between 30%-80% of the assets within oncology across the phases being from immuno-oncology. There's good reason for that. Again, it's value creation. It's a space that's been maturing over the last, you know, two decades or so. You know, it's come leaps and bounds. The more research there is, the more launches there are in IO, the more we understand it, the better we understand it, the more we can actually trust the decisions that we can make when it comes to supporting IO projects in the long-term future. If we then look at IO more closely and break it down a bit further, you can see that there's still a bit of a way to go when it comes to the different types of IO, the different flavors of IO that are around. We've gone from, you know, currently we're looking at over 2,500 or so trials going within IO from companies that are currently in clinical stage or indeed commercial stage companies as well. So, well, industry-sponsored trials are still leading when it comes to IO trials. The predominant focus still remains within mAbs. So monoclonal antibodies are still driving the IO space with a few bispecific and tri-specific antibodies on the horizon as well. In terms of targets, as you can see here, the CD3s are currently in the lead as relates to the top 10 targets within the IO space. About a decade or so ago, this would have been PD-1s. So it goes to show perhaps the early signs of perhaps saturation of a PD-1 target as it relates to companies or funding and investment for new agents that can actually make a difference on the market when they launch on the market. PD1s are a little bit on the decline there, versus CD3s. Moving a little bit away from the commercial and clinical side of things and looking a bit more at the funding trends, first thing that stands out, of course, is the huge spike we see looking for a pointer, the spike we see in 2021 for the volume of financing rounds in Series A that happened. The number of reasons for that we can think of, of course, one thing that stands out is the post-pandemic optimism around looking for the next Moderna or the next BioNTech. So investors flooding the market trying to find these nuggets in the pool. But of course, after that, we start to see a decline, again, a decline in volume. We'll go into value later, but in volume, we're seeing a bit of a decline there, going to almost the, you know, pre-pandemic levels of funding that was given to early-phase companies. What this tells us, of course, is that perhaps it might be a case of budget tightening or indeed a lack of value from the investors' perspective. They're not seeing the value that they'd like to see before they make a decision. But when you compare that to or at least when you marry that up to the values chart over there on the right-hand side, you see that the average deal value has been creeping up consistently, even after the peak of 2021 volume of deals. So they're going from about $50.3 million to $63.6 million in 2023. The outlier there for 2022 is the Altos deal, which was $3 billion, which sort of put things a little bit more askew. But the point still remains that actual deal value or sorry, actual value of an asset is far more important than investors looking for sheer volume of deals, which is perhaps what previous years might have looked like. Certainly 2021 looked like it was more of a case of scattergun approach trying to see what works and seeing what sticks. What we're seeing now more and more is that there is a smaller volume of deals, but the value still remains. So I think this is good news for a lot of the companies here who are doing very innovative work, trying to really make a difference on the world stage, trying to really bring some focus on some of the more challenging to treat conditions, and even some areas that are relatively stayed. But again, approaching it with novel technology to try to make a difference, continuing on that path, can be a way to unlock the value that you're looking for when it comes to financing. Again, following the historical data, that's what it seems to tell us anyway. And I'll round off by showing you a view of the landscape as it relates to, first of all, you know, the top 10 disease areas that investors are focusing on for funding. Unsurprisingly, oncology, you know, is almost double the next one, with neurology in terms of value. Of course, what this means is that everybody here, the clinicians, the investors, we're in the right place. We're in the right space. We're in the right disease market area in terms of looking for solutions to real challenging problems that people have in their daily lives, with in terms of the disease itself, but also as people in the investment space looking for good value deals, looking for a way to make your money make a difference. You are in the right place in terms of what we've seen historically. You turn your attention to the right-hand side, of course, in terms of number of deals that we've seen and where the deals lie the most. Unsurprisingly, most lie in the U.S. in terms of Series A funding and where the companies come from. What this tells me is that there's great room to grow. There's a lot of opportunities still remaining that there's a lot of opportunity to do more within Europe and within the Nordics specifically, within Sweden. So I, for one, I'm optimistic about a lot of these companies here in terms of what it is that you can do, bring in your wonderful assets and technologies to bear, and hopefully we'll be able to see a few more of these numbers show up in the Nordic region in the future to come. So yeah, I'll leave it here for now. Any questions? Thank you, Alex. All right. Do we have any questions? Yes. Use the microphone in this chair, please. An explosion of assets coming through into the clinic in the space, presumably massively outstripping the growth of patient populations that they're being targeted at. What's the read-through for the difficulty of actually executing on clinical development given the number of assets which are chasing these patients? That's a very good question. We have a lot a number of companies come to us with that very question in mind. How do we target the right patients? How do we find patients to even use in our trials? Not meant to be a plug, but my company does do consulting work to actually help companies to tailor and link companies with sites to actually get that part of the work done. In terms of the overall picture, as in the challenges, challenges are there, absolutely. It becomes a case of knowing where to go for what disease area. So there's a lot of pre-work needing to happen to put together a clinical development plan that actually is more, you know, tailored and strategic than simply just hoping that you find the right patients all over the world. It requires a lot more thinking than it used to, basically, is what it comes down to in the end. Yeah, but it is definitely a challenge. Absolutely. There's no question about it. Ted, please. Yeah, thanks for that presentation. I was going to ask a question about metabolic, but then I realized we're here for an oncology session. So I'll keep to oncology. If you split that $1.3 billion there into subsectors, because obviously oncology is very broad, right? Which areas are which medical needs actually being met quite well, meaning they're sort of less interesting for future investment, versus which ones are just these oncology areas that you know, it's still such a big unmet medical need? If you were to nuance it a little bit among that big window. I'll have to find the actual data for that and share another time if, if you're interested afterwards. But, I'd say I mentioned earlier about breast cancer and prostate cancer being a little bit, a bit more saturated than, than, than the others. So this is where a lot of the value is a bit, you know, waning. But CLL and, and, non-small cell lung cancer are certainly the two areas that we're seeing a lot of, you know, the growth, the again, slow growth, but some growth in 2024, 2031. A lot of that's coming from NSCLC and CLL. In terms of the, the real unmet need areas, we're, we're seeing a lot of work happening, a lot of deals happening in the rare cancer spaces. So the rarer it is, the more likely it is that the regulatory pathways are more smoother as well. So we've seen a lot of companies, investors moving that direction because they know that the path to market's a little bit smoother than it would otherwise be if they were going for a more saturated market space like breast or prostate. That's sort of what we're seeing right now. So Alex is actually going to be helping me moderate this day. So please, Alex, now come sit with me here, and it's time for our first company. So Jens Lindberg, please. Medivir. So looking at TED then, liver cancer is actually one of the more challenging tumors to treat. It's quite rare, and the need for treatment options are significant. At Medivir, we believe we've found a way to target the tumor locally and selectively kill cancer cells. We believe we have a very realistic opportunity to become the first approved treatment options for the second-line population, a market that will be worth around $2.5 billion by 2030. My name is Jens Lindberg, and I'm the CEO of Medivir. We are a Swedish pharmaceutical company developing innovative medicines for primary sort of areas of unmet medical needs. We do focus on cancer, and we spend most of our time driving the development of the in-house compound, which we call Fostrox. It has a much longer name. We can go into later. That is basically a selective cancer cell, cancer killer for liver cancer. We do have a fast-to-market strategy where we are focusing on the second-line advanced liver cancer population because there are no approved treatment options in that patient population today. Charlotte said, "Don't talk about other stuff." I'll just say the following. We do have a broader pipeline, but we also have a history of developing drugs to market, two drugs that have reached the market at Medivir. Currently, we do have four other partnered compounds that we have outlicensed, and we believe that they are better in the hands of others. We can drive that faster and sort of cheaper from a Medivir perspective. Two of four compounds are in the clinic, and one of the other two is entering the clinic this year. Let's focus on liver cancer and Fostrox. So I'll take a slight step back. Liver cancer is different than other cancers, particularly because most of the patients will have an underlying liver disease. 80% will have liver cirrhosis, and that provides challenges. That means that sort of patients will have bigger difficulty tolerating and benefiting from systemic treatments. So that's making them a bit more challenging to treat. Secondly, also different from other tumors, the primary challenge, though sort of kind of from a mortality point of view, will come from the primary tumor. In many other tumor areas, it is actually the spread of the disease, the metastasis that will provide the challenge. So if we take lung cancer, it's brain metastasis that will cause many times the bigger problems. In liver cancer, you want to treat the primary tumor. And for these reasons, again, an organ-targeted approach we believe is critical. These reasons also contribute to why liver cancer is difficult to treat. Alex spoke a lot about IO. IO has made its way into this space as well as of late, but not until around two years ago when we saw the entry of an IO combination of Tecentriq Avastin. So in first-line, every patient basically gets Tecentriq Avastin today. One-third of patients will respond. And if we then go to second-line treatment, it gets even worse in the sense of outlook for patients. At best, we've seen a 10% response rate in the second line. And today, there are actually no approved treatments after Tecentriq Avastin in second-line HCC. So remember that sort of 5% to 10% response rate. Fostrox then is a smart chemotherapy targeting cancer in the liver. And what it is, it's an oral small molecule, oral drug, oral administration. It's stable and inactive in GI and in blood. It's not until it reaches the liver that it's activated or converted. So it's rapidly activated in two phosphorylation steps in the liver where it then sort of starts killing cancer cells. And it actually selectively kills cancer cells and spares healthy cells, the reason being that normal healthy cells, normal healthy cells, normal liver cells or healthy liver cells, they rarely divide. And Fostrox needs a cell to divide in order to induce DNA damage and cell death. So it's a very nice way of targeting the tumor locally in the liver and selectively killing only cancer cells. We're in a what we believe to be quite an exciting phase. We have an ongoing study taking place in the UK, Spain, and Korea. It's a phase 1b, phase 2a study, combination study, where we are combining with a kinase inhibitor, called Lenvima, which has shown benefit in first-line treatment of HCC. Combination is, not sure how much Alex spoke about that, but sort of a lot of the development today is combinations. You want to attack the tumor from two different sort of angles, and there's clear rationale for synergy here. The study is fully recruited. Still around 40% of patients are on treatment. The interim results we have seen so far, and we'll go into that sort of on the next slide, are actually quite promising. If we start by looking at sort of the patients, from a response perspective, what we're seeing is a higher share of patients responding to treatment than what has been shown in previous second-line studies. Remember the 10% I spoke about before. The response rate here is 24%. But I think that the most important element on this slide, and the bars here represent tumor growth. So if the bar is going down, that's good because it means the tumor is shrinking. What we see is that all of these patients, they came out of basically Tecentriq Avastin. Tumor was growing at the stage, so they were all progressing. And more than 75% of patients have tumor shrinkage. So we've been able sort of to stop the tumor from growing and actually induce shrinkage in the majority of patients. So highly encouraging in and of itself. But more importantly, it's to look at long-term treatment. And these patients, historically, they have progressed quite rapidly. On average or median-wise, three, 3.5 months is what you could have expected in the past. Each bar represents a single patient. The patient who has been longest now on treatment, still responding, is now at 18 months with tumor shrinkage. Median-wise, we are with 40% of patients still on treatment. We are at 6.3 months with it at the data cut in February. And that has been growing quite nicely and continues to grow. So again, from a time to progression, seeing sort of a clear difference from what has been seen previously in second-line studies. Equally important is that the patients actually do tolerate the treatment because it's a combination. And if, 66% of the patients, they are able to stay on Fostrox, full dose, no dose modifications. And we've only had one patient that actually had to discontinue due to side effects. So they're able to stay on treatment. And that's quite important because we have designed the study and the treatment so that they are treated until progression, not for sort of 46 cycles. So they are able to stay on treatment for the duration of the treatment. The second-line population has historically been a small population. Few patients have been treated. Few patients have been fit enough to be treated. What we're seeing is that quite a change here is that so there's more patients. HCC is growing. We'll continue to grow. On the back of the obesity pandemic, it will sort of HCC caused by fatty liver disease will grow drastically. But we're also seeing more and more second-line patients fit enough to be treated. So when we do the calculation, and I was looking at bengt now. Bengt asked me before, today, sort of around 100,000 second-line patients. If you do the math on in terms of what it costs today, we assume a treatment duration of six to seven months, we are at $2.5 billion market worth in 2030. And there are no approved treatments as of today. So the unmet need is clear. It's an orphan disease. We are quite encouraged by the data and the efficacy we're seeing. So we have scaled up our ambition going forward. And this is a bit of a simplified approach. But traditionally, we would now have embarked on a smaller randomized 2b to inform a phase 3 for an approval somewhere around 2030, 2031. We believe there's an opportunity for an accelerated approach. that means a slightly larger phase 2b, looking at maybe 250 patients scaled up for statistics and safety with the opportunity and the possibility of filing for accelerated approval. So that's our plan. It means a larger investment upfront, clearly, but sort of a smaller investment in terms of reaching the market as we would then, in that case, cut time to market by maybe three or more years. We communicated last year in Q4 the ambition to sort of scale this up or accelerate development because of the maturity of the data and what we saw. We embarked on a number of activities to accelerate development. CMC had to be sort of accelerated quite a bit with a new formulation for registrational purposes. We did a capital raise to drive things forward. In 2024, it's an important year. We're looking forward to delivering on a number of activities such as then confirming study design with authorities and experts. We are also looking to establish a commercial development partnership with a focus on Asia with regards to also sort of funding sort of the way forward. With patients staying on drug, we are looking especially forward to presenting more data at upcoming congresses, one in Q2, Q3, and one later in the year. So I hope I've been able to show that we have an inspiring opportunity to change the outlook for patients with advanced liver cancer. We are uniquely targeting the cancer locally in the liver, selectively killing cancer cells. It seems like we are bringing sort of benefit, improving outcomes for patients, sort of doubling response rates and closing in on doubling time to progression, and an opportunity to be the first approved treatment in a population worth $2.5 billion. I would say once-in-a-lifetime opportunity, but maybe that's a strong expression. I hope I've sparked your interest in terms of kind of joining us on the journey of changing lives for liver cancer patients. Thank you. Thank you, Jens. Thank you, Jens. I'm really interested to hear what you guys say about this mode of action. What do you want to ask? Please start. Just a question. I mean, you talked about first-line Avastin and Tecentriq. I mean, there is another first-line approved drug now, which is not only targeting the PD-L1 but also the CTLA-4, I mean, with durvalumab and tremelimumab. I mean, from my perspective, that sounds perhaps like a very strong competitor in the first-line setting. I wonder if you have any thoughts of going in your second-line setting with any IO combination. I didn't show the details here. But in the current study, we actually had a dose escalation arm of Fostrox plus Keytruda for that reason. The interesting part is that it recruited coming back to we had another recruitment question. It recruited very slowly because physicians weren't interested in switching to another IO arm. So they wanted to sort of Tecentriq Avastin or, for that matter, Imfinzi-Durva because that's where it's used in Korea. When patients came out of that, and all of them did, they were looking to target the tumor with different mechanisms. So the interest in moving to a Keytruda arm in second-line was very low. And so it recruited slowly. So in the end, we decided to and again, quite strong steer from our experts in the advisory council to target sort of second-line in combination with Lenvima. They are saying to us that you should, however, also explore Fostrox together with IO, but in first-line. You should sort of try to move it up. But from a second-line, stay with the TKI. Yeah, but what I'm asking is, I mean, the new first-line also targets CTLA-4. And I mean, we can see combination data in several IO treatment arms that actually the combination, the double targeting is more potential has more potential than just targeting PD-1 and PD-L1. Okay. See if I follow that. From our perspective I'll sort of maybe I'm not answering the question. But from our perspective, we are quite agnostic to what they are using in first-line. So as we move forward, if they would use Durva-Tremy in first-line or Tecentriq Avastin, sort of that, from our perspective, is less relevant. From a second-line, we are looking to sort of change the modality or sort of use Fostrox together with the TKI. So we switch mechanism of action completely because what we're seeing is that there's a lot of development in first-line, and there are other combinations in first-line as well. And our anticipation is that sort of there will be a winner. And maybe the PD-L1, CTLA-4 is the best option. But when they've used that option with an immunotherapy in first-line, they will be looking to switch to something else in second-line, which is why we would we would not be looking to combine with IO in second-line. But that's, but maybe someone else. The steer we have from our advisory council has been very clear in the sense that the rationale for if you've progressed on an IO and then you switch to another IO in second-line, the scientific rationale is quite low. The benefit shown in other tumors has been not super impressive. Cecilia, do you want to? Yes. Thank you for a very nice presentation. I have a question regarding biomarkers because we saw in your slide where you show us the time to progression. There was quite a difference between patient one and patient 17. Do you have any insights when it comes to how to select patients that would benefit best from your treatment with respect to biomarkers? With respect to biomarkers, no. But with respect to another element, yes. This is actually a slide I took out for the sake of time. What we have looked at is because there's been an anticipation that second-line patients will respond sort of patients who have responded well on first-line will respond well in second-line and vice versa. We've looked at that, and there's no correlation whatsoever. The quite encouraging part is that we have a number of patients who have progressed very rapidly on Tecentriq Avastin primarily that have then sort of had benefit for a long time. So the patient number one at the top is a patient that progressed very rapidly on Tecentriq Avastin. So the opportunity to benefit from Fostrox Lenvima seems to be with patients who have progressed well or quickly or benefited well on first-line. But biomarker, no. Because I think that is quite important, you know, how to select patient predisposition. How to select patient predisposition from their financials. Yeah. One of the challenges with and I didn't say that upfront sort of being hesitant. I'm sort of the non-scientific person here with the commercial background. So when I get into these areas, I'm a bit sort of hesitant. But liver cancer being quite a heterogeneous sort of tumor, sort of the likelihood of identifying a good biomarker is seen as relatively low. But clearly, it's an area to continue to explore. We have another biomarker company this afternoon. So let's ask. I should have had my CMO with me today. Thank you, Jens. Thank you very much. Done. Yes. Okay. Thank you very much. And welcome, everybody. I will give you a quick overview in the next 10 minutes about BioInvent. We're a company based in Lund, Sweden, and focus primarily on the tumor microenvironment. We try to change the tumor microenvironment in order to induce response against cancer. We're listed in Stockholm. Maybe just very briefly, a quick snapshot of the company. Within our focus, we are pushing ahead with a portfolio. You can see that we have six clinical programs currently that we're running, five different compounds. They have been all generated in-house. We're a quite integrated company, which means we do target discovery, antibody discovery, manufacturing, formulation, and clinical development all under one roof. As you can see, that's the second bullet, the technology that we're using. I will explain to you that very briefly on one slide has been validated nicely through a number of collaborations. We're currently around 110 people listed in Stockholm, as I mentioned. But we have a very international ownership. As you can see, 65% are in the hands of strong institutional investors such as Redmile, Van Herk Investments, Forbion, HBM, Omega, AP4, Invus, Swedbank Robur, and Handelsbanken, which is a nice collection. We have been quite active during the last two years, a little bit more than that, raised quite some money, around $260 million in financing as well as in deals. And we currently still have $125 million, which gives us a very nice runway until the end of Q1, 2026. And that gives us comfort to really execute on our programs. So we heard a lot about immuno-oncology. And one reason why there's still a high unmet need in oncology, of course, there's a lack of targets. Because when you look at most of the companies, they're working on five to 10 targets. We try to add a couple of new targets. For that purpose, we developed our first platform, which is a reverse functional screening platform that allows us to screen directly on patient material. That's what we do. That is followed then by a very vigorous functional screening in vitro and in vivo. Once we see antibodies, that is our modality that we're working on, showing very strong therapeutic effects in a number of animal models, then we identify the target. That's the way it works. It's phenotypic screening, functional screening, and reverse in that sense that we find later the target based on the functional activity in those tests that we are running. That's the platform that we have used in our collaborations that I mentioned on the previous slide, and we have used to build the portfolio. Of course, as already outlined, we will not go through the portfolio but focus on the two lead programs, actually. But on the left-hand side, you see that we are currently working mainly on two targets, TNF receptor two, which is a very interesting target that we identified on ovarian cancer in one of our screens. And it might be potentially a new checkpoint target. Come back to that later. And then FcγRIIB, which is the only inhibitory receptor of dendritic cells in the tumor microenvironment. And for both targets, we have two different compounds that we're running in different trials. And today I will focus on 1808, which is a lead program on TNF receptor two. Then I also will briefly give an update on the FcγRIIB program, TNFR2. So starting with 1808, so we basically identified a couple of hundred specific antibodies to the target. And out of those, we selected two, 1808, which is a ligand-blocking FcγRIIB-engaging monoclonal antibody, and 1910, which is an agonistic antibody, which is also in clinical development. And you can see on the right-hand side the competition. So when we started the journey, we were the only one besides the group in Boston. Now we have a couple of follow-ons. The good thing is that we are quite ahead, at least a year of our competition, and already have the first clinical validation for our lead compound, as I will show you on the next slide. So we presented data from the dose escalation. I will come to the clinical trial design in a minute at SITC last year. This is one of the cases that we have shown there. This is a patient case, as you can see on the right-hand side, a 50-year-old male patient with GIST, with clinically progressive disease for more than six months, with multiple metastatic lesions, has received 12 prior lines of treatment. You see the result on the right-hand side. Each curve is a lesion. You can see that at the beginning, it looked like progressive disease. That's quite common because what this antibody does, it attracts CD8-positive cells to the tumor microenvironment. That means you have at the beginning, you have some swelling. Once those cells do their work, there you have a clear regression of the tumor size. Sometimes down to 40%, sometimes they disappear. That patient is still under treatment and still improving. So that's actually quite nice. And I should mention, this is, of course, single-agent activity. We run this trial. You will see on the next slide two ways. So we have on the top the single-agent activity. And the data that I showed the example for is from the left upper part, which is a dose escalation as a single agent where we went from 25 mic up to 1,000 mic, very well tolerated the antibody, no toxicity at all. And based on that data, we have moved now into the phase 2 part that's on the right-hand upper side where we're basically focusing on lung cancer, ovarian cancer, melanoma, and T-cell lymphomas. And that data should be available during the second half of this year and maybe already some update during ASCO. And on the lower bar, you see the combination that we run with pembrolizumab because preclinically, we saw strong single-agent activity as well as very nice synergies with pembrolizumab. And that is running in the dose escalation. And that data, the dose escalation data, will be available by the first half of this year, so around summer, just before or just after. So that is actually quite interesting. And then on the FcγRIIb side, so there we have two antibodies. And I'm talking about BI-1206. And as you can see on the right-hand side, the FcγRIIb is the only inhibitory receptor on dendritic cells in the tumor microenvironment. So quite an interesting target. And we developed BI-1206 in two ways. We develop it in non-Hodgkin lymphoma. And that's the data that we have here. So that's the dose escalation data where we focus on patients that do not respond anymore to anti-CD20-based therapy. We run that in combination with rituximab. Saw a nice overall response for complete responses, three partial responses during the dose escalation. The remarkable thing here really is that the complete responses are long-lasting. So in many cases, more than 2.5 years now, which is actually quite exciting and quite interesting. We have partnered that program with CASI Pharmaceuticals They run the equivalent in China. They just released data, which is a little bit earlier because they were hampered during the COVID times. They couldn't run any clinical trials. But you see a similar response still early than we have seen, confirming the data that we have generated in Europe, which is actually quite nice. So that's the study. I mentioned we are focusing on relapsed or refractory indolent non-Hodgkin lymphoma. We have finished the dose escalation. We're now moving to the part B, the dose expansion. The phase 2a dose expansion is ongoing. We have also a subcutaneous formulation that we develop in parallel to our IV formulation. That data should be available by mid this year. Then we just had an announcement a couple of weeks ago. So going forward with the IV, we'll combine it with acalabrutinib from AstraZeneca under a supply and collaboration agreement. We should have the first patients of that trial by the end of this year. That will be quite interesting. It's also a very interesting positioning in the non-Hodgkin lymphoma space. As I said, we are developing this also in solid cancer. So basically, we are exploiting the target two ways. In non-Hodgkin lymphoma, the target is expressed on the tumoral B cells. In the solid cancer case, it's expressed by the dendritic cells in the tumor microenvironment, overexpressed actually. And in the solid cancer case, we just have modulation. In the non-Hodgkin lymphoma cell, we have both direct killing as well as blocking resistance mechanism to anti-CD20-based therapy. In the solid cancer case, we're a little bit more not as advanced, so still in dose escalation, but we saw already nice responses. And there we also have an update by mid this year. And that we are running under a clinical supply agreement with Merck. So we have two companies on one compound. On the non-Hodgkin lymphoma side is AstraZeneca. And on the solid cancer side, it's MSD. Just coming to the end because then we might have a little bit more time for discussions. Just to remind you, I mentioned on the initial slide, on the snapshot slide, that we are working with a couple of partners already. So this is an external portfolio that we have with our partners. You see the names, Mitsubishi, Takeda, etc. Those programs are running in phase 1, phase 2, obviously financed and guided by the pharma companies. But we have attached milestones and royalties in case it becomes a product. And then for this year, it actually will be quite eventful, as you already can guess, because now I just talked about two programs of our portfolio. So we have early phase 2 data by the end of this year for 1808 as a single agent. And that looks quite promising. Then for 1206, the triplet study, we will have the first data by the end of the year. By mid this year, we have those dose escalation programs reading out at least initial data, BI-1808 plus pembro, as well as BI-1206 plus pembro. On the right-hand side, we have a program that we run in collaboration with Transgene, BT-001, which is a combination of our proprietary anti-CTLA-4 with the oncolytic virus. And there we will have the data in combination with pembro. We had already data as a single agent where we saw objective tumor response and it was well tolerated. So that should be also quite interesting. And then last but not least, the second anti-TNF receptor two program, BI-1910, will also read out as a single agent by the end of the year. Thank you very much for your attention. Thank you, Martin. You go on, please. Martin, thank you. You have a very impressive list of specialist investors, not only from Europe but also from the US. What's your advice to other Swedish biotech companies that would like to have equally prominent investors? Yeah. So obviously, you first need to have something that is really interesting, at least also appealing to U.S. investors. And then I think it's worthwhile just to crank the wheel and talk to those guys. So what we do now for a number of years, not only to the investors, we have also ongoing discussions to the 10 top banks in the U.S. since two years, to the analyst teams, to really market our programs, our ideas, our strategy. And that's how you get interest because most of the companies in the U.S., investors and also banks, they wouldn't know what you have. So you have to present it. And you have to do that on a regular basis. So really have to spend some time in the U.S. But if you had to answer your own, how much better your projects are than your competitors? I mean, how much better portfolio do you need to have to get the U.S. investors? Well, it has to be compelling and competitive to what is out there. I think you provided a very nice overview. In that context, basically what you have is outstanding. You will get interest for sure. Because you've been very good, as you once said, to attract institutions from abroad. Question on that. I wonder, did you have to do any work pre the outreach that you were doing to the U.S. investors? Did you take a step back to try to understand which banks or which investors were worth approaching with your ideas, or was it just a case of see who's out there and what you can do with them? No, I had already some previous contacts already before from my previous work. So I'm in the industry now for almost 30 years. So I have some contacts. And then, of course, you're right. So you have to tailor. You have to know that maybe this specific program or this portfolio could be interesting for investor X, maybe not so much interesting for investor B. So I think that's important. And otherwise, I think it's very much cranking the wheel. So we have to talk to many parties all the time. The volume and quality at the same time. Absolutely. Absolutely. Erik. Yeah. Martin, to fuel the discussion a little bit in the broader context, there have been thousands of trials with checkpoint inhibitors, right? What we know now today is that they've all failed basically to improve the effectiveness of checkpoint inhibitors, which is a pretty drastic discussion. When you look at the cancer immuno-oncology landscape as a whole, we can speculate on why that has been the case. But the question is more, what makes your approach different? Why do you think that you have mechanistically or in other ways a key to a potential success that maybe has failed in the past? Yeah. I think our approach, as I tried to do very briefly on this platform slide, is purely functional so that we not so much rely on genomics and other things, and then basically by scientific publication or theory, come up with a target. So we really basically use patient materials, screen directly on the patient material, find specific binders, and then before we go after the target, really prove them for function in a number of animal models. And there we would have hot tumors, cold tumors, and something in between, so non-inflamed to inflamed. And there we really only pick the best. And this platform, as you could see from the TNF receptor two program, results in the initial screen, specific antibodies that do something in hundreds of different specifications. So we really have also something to select from. I think that's important to have this functional approach. By this, we'll automatically identify stuff that could be helpful therapeutically. Yeah. Niels, please. Just wonder, you're collaborating with MSD. I believe they put a lot of emphasis now on that collaboration with Moderna, with INT, tailoring, let's say, mRNA vaccines in combination. Do you have comments, or do you feel that there is some, let's say, what do you expect the development will be based on your concept and based on these concepts? So what we also have, and that's part of our research and discovery, we have also ongoing developments of vectorization of antibodies. The first program is what you see there, where we clone it into an oncolytic virus in order to express it directly in the tumor material. We also have other ideas how you could vectorize an antibody such that you have local targeting. Basically, you could use vesicles, you could use RNA, you could use DNA. There are various ways. I think for us, what comes first is really the unique mode of action. That could also do a naked antibody. Once we have shown that and proven that, then we can think what else we can do with that antibody in that context. Okay. Thank you very much, Martin. Thank you. Thank you. To cut the long story short, we're trying to change the course of cancer treatment. We try to do that in two ways, which is one by addressing where there's currently the highest unmet medical need, which is related to tumor recurrence. If we put it very simple, the overall survival rate in cancer has still not improved as we want. The main reason is tumor recurrence. First treatment with chemo and now also much more targeted therapies is generally effective. But in a lot of tumors, the disease comes back very quickly. It relates to residual disease, which is lingering and which is difficult to target, certainly with the drugs that were used initially for first-line treatment. It addresses a very high unmet medical need. Secondly, we believe cancer treatments can be a lot more safe. Right? Chemotherapy is a pretty harsh treatment. Everything else, surgery, radiotherapy, is also a pretty harsh treatment, which is not only useful, it's also necessary to treat initial tumors. But again, with the highest unmet medical need being tumor recurrence, we believe we can develop more safe treatments to prolong the time to disease recurrence. That's called cancer maintenance therapy. So maintenance therapy means after the initial line of therapy, we try to intervene with a method that allows patients to live longer without disease and hopefully in the end, of course, make sure they live much longer lives without the disease coming back at all. We have experimented in different disease indications. Our current lead program called vidadencel is in acute myeloid leukemia, which is a very aggressive blood-borne tumor. We have presented end of last year at ASH, which is a large hematology conference, in an oral presentation, our data. We were invited to present the data because we showed long-term survival in AML in a monotherapy trial, which was very exciting data. That's also the basis for the main program of the company moving forward, which is towards a registration trial. And I will tell you more about it in the upcoming slides. We have additional programs based on our technology basis in solid tumors. One program in ovarian cancer, which is also a tumor that is very aggressive and is actually the deadliest gynecological disease because it comes back so quickly in the majority of women after initial treatment. We have an intratumoral primer called ilixadencel, which we use for tumors that are poorly responding to currently available therapies, including immunotherapies. This is actually touching on the topic that I also asked Martin about. What was the big excitement about immuno-oncology? First of all, there is a role of the immune system in controlling cancers. For a long time, that was not accepted as an idea for treatment. Also, the chemo has a detrimental effect on the immune system. So generally speaking, the immune system had failed to control the cancer. So there was not a lot of hope that the immune system would actually have a big impact in treating cancers. And then the checkpoint inhibitors changed the whole landscape. So what the checkpoint inhibitors do is they reactivate existing immunity. Active immunity, and this goes back to very basic immunology. Active immunity is the immunity that your own body builds up, that your own immune system develops, which comes with immunological memory, which is long-lasting. It's the only form of long-lasting immunity. If you inject antibodies into the bloodstream or subcutaneous, they will also have an effect. If you go on a holiday and you need some hepatitis protection, you can get two weeks in advance a shot of antibodies. They will protect you for a short period of time, and they will wash out. That is called passive immunity. Today, we know that this also holds up for cell-based therapies. So cell-based therapies, for example, like CAR-T or NK cells, they can have a very immediate effect on tumors, but they are not long-lasting. So this is a big difference between active and passive immunity. Checkpoint inhibitors stimulate active immunity, which is pre-existing, often in the form of tumor-infiltrating lymphocytes, which are inhibited by so-called immune checkpoints, which are expressed by cancer cells. When you block that, you unleash the immune system again, and you see long-term survival, long-term survival in cancers that were previously thought to be untreatable, like melanoma, lung cancer. That's the good news. The disappointing news is it works in 10% to 20% of patients in tumors that build up a lot of mutations, like melanoma and lung cancer. So there's a lot of tumors which are not responding, and we were unable to raise the bar. So in the last decade, there have been thousands of trials, and none of those trials have really led to a raising of the bar of that 10% to 20% of patients responding long-term, right? Survival. So that's what we're after. So something is missing in the equation, and that's the next step in the development of immuno-oncology, finding the key to raise the bar and have more patients benefit from long-lasting immunity and long-term survival. Now, what we try to do is to stimulate active immunity. We have a vaccination approach based on a whole cancer cell. That active immunity will only be built up in a low disease setting. When there's active disease, so cancer cells specifically like AML that are growing very fast, you will not stop them with an active immunotherapy. You simply don't have the time to build up immunity. And also, the cancer cells completely disturb the immune system. So they will only work in low disease settings. But again, that's also where there's the highest unmet medical need because that's where we develop cancer maintenance therapy. So our product is a bit of an odd one. It's a cancer cell that we basically force to express dendritic cell phenotype. Dendritic cells have an immunogenic effect, so they stimulate the immune system. Cancer cells are very good in evading the immune system. We have developed a platform, which we call DC1. It's a cell line that belongs to us. We have a manufacturing process, which makes this scalable and also attractive as a commercial product. During the manufacturing of those cells, which we grow to large quantities, we shift those cells with some cytokines, secret mix, to express a dendritic phenotype. That turns them highly immunogenic. We irradiate the cells for safety purposes. They're stored frozen. It's, from a logistics perspective, a very straightforward product, again, administered as a vaccine, so via intradermal injection. What we have shown is that the product is immediately phagocytosed, so it's immediately processed by antigen-presenting cells in the skin. Skin is a natural barrier to entry, so a very good site for vaccination. We have shown not only in preclinical work, but also in our clinical trials, that the immune cells in the skin very quickly recognize the product, phagocytose it, so process the product, and then boost a very broad immune response. Also, that is a very important element of our approach. If you target individual antigens or individual targets, cancer cells have a tendency to evolve very quickly and basically escape the pressure that's put on them, whether it's immunological or a targeted approach. So to have a very broad boosting of immunity is a very important pillar under our concept. It's a robust platform, also with a strong regulatory dossier and also validated by a so-called ATMP certificate for the manufacturing process. About acute myeloid leukemia, as I mentioned, it's a very aggressive tumor. It basically comes back in all patients unless you are fortunate enough to find a bone marrow transplant or a hematopoietic stem cell transplant. That is unfortunately not available for many patients in time. Also, five-year survival of AML is still at 30%, which has been for as long as we can remember since the introduction of bone marrow transplants. So it's unresolved disease. And relapse is the major reason for survival in AML being so poor. Another important part, like I mentioned, is safety. Currently, there's two backbone drugs in AML. One is called azacitidine, which is relatively safe but not very effective. The other one is called venetoclax. It's a newer drug, which is very effective, but also very toxic, so not suitable for maintenance therapy. What we are trying to do with this active immunotherapy approach is to have a very safe treatment. The only side effect we've observed in the clinic is redness where we inject the product, but also with a long-lasting effect because we boost active immunity. This is the current standard of care for AML maintenance. This is a tablet form of azacitidine. The red line is the drug. The blue line is placebo. And what you can immediately see is that there's only a very narrow difference between the drug and the placebo, and also that in the end, the survival levels are very similar, meaning that long-term survival is still a big unmet medical need in AML. Patients that have so-called measurable residual disease, so if you do a test with a PCR or a flow-based assay, so sensitive molecular biological methods, and you pick up some residual cells, that's called MRD or measurable residual disease. They relapse almost immediately. When you look into this trial, which was a registration trial by BMS for oral azacitidine, the median relapse-free survival after very harsh initial chemotherapy was 2.7 months. So patients relapse immediately when they are MRD positive. And with azacitidine, the median relapse-free survival is seven months. So we apply a vaccination approach. We basically do four biweekly vaccinations. After two months, we give two additional boosters. And this is the result we presented at ASH. And the reason we're so excited about it is that you start to see a plateau. So initially, six patients, this is 20 patients monotherapy. six patients relapsed very quickly and also passed away very quickly, basically within the first 12 months. But then all of a sudden, 14 patients were still alive at the end of the active study phase, which was 70 weeks. Today, they are still alive, the longest patient already five years after initial treatment. This is why we think we now have a breakthrough potentially in the AML maintenance with our treatment. What we've also done as part of the trial, we've asked participants in our trial to donate blood samples and skin samples so that we can have a closer look at how the immune system responds to our therapy. What we have observed is a very broad boosting of immune responses, not only T-cell responses against multiple antigens, but also B-cell responses and other compartments of the immune system contributing, and also a decrease of inhibitory T-cells. There seems to be a rebalancing of the immune system, and that also correlates, as you can see in the top right panel, with survival. We are now running together with the Australasian Leukaemia and Lymphoma Group a larger trial, up to 140 patients. The trial is starting as we speak. It's first going to be 40 patients divided over azacitidine only versus azacitidine plus our drug, Vidadencel, and then after the initial safety assessment, an additional 100 patients. And this is for us a step up towards a registration trial. There's a broader opportunity in the AML maintenance space. We're currently focused on patients that have undergone high-dose chemo and are not eligible for transplant, but also post-transplant. MRD is a big problem, and relapse is actually the main reason for transplant failure. So post-HCT is an additional patient population, which we may address in the future. And also now with more patients achieving complete remission with venetoclax, so a combination actually of AZA and venetoclax. That's also an interesting patient population because it's growing, and it's also requiring maintenance treatment. So this is the plan going forward. Very importantly, we have secured a manufacturing alliance with a company called NorthX Biologics as part of a financing round, which we did last year. And that collaboration allows us to scale up the manufacturing of Vidadencel. It's on track. We've just provided the business update. The facility is built. We're tech transferring to NorthX our process. So that will allow for large-scale manufacturing mid-2025. Also, we've had initial positive FDA feedback on the different steps we want to take towards a registration trial and for the large-scale manufacturing. And as I said, that will put us in a position mid-2025 to start a registration trial in AML, and there's the opportunity to expand the potential additional AML indications. So with that, to summarize, the positive data we saw in the ongoing trial, which is called ADVANCE II, encouraged us to continue to develop our main product, Vidadencel, in AML. Everything is in place now with a large-scale trial starting with ALLG. With the large-scale manufacturing alliance we have with NorthX and also the plan forward to develop the registration trial protocol. And we expect to be pivotal stage ready in mid-2025. We have a strong regulatory dossier, good interactions with the regulatory agencies to guide us. And then we have two additional programs, one phase one ongoing in ovarian cancer, which we'll read out in the second half of this year, and a new trial which we're planning for with the intratumoral primer, ilixadencel. So with that, thank you, and I hope we have some minutes left for the Q&A. We have some minutes left. Thank you. It's fantastic to see, and I was so glad when I heard Martin as well. This is why we're all here, to see patients live longer. It's fantastic. Thank you. Do we have any? Yes, we have Tim. Thanks for a good presentation, first of all. Lots of insight and lots of information in that condensed presentation. But could you please elaborate a little bit? Obviously, it's a very innovative idea to sort of vaccinate for recurrence of cancer. But how do you go about sourcing for patients here? Is there any sort of way you do that? And also, could you elaborate a little bit on your IP protection? Sure. Well, I think to start with the letter, everything we do is owned by us, which means the manufacturing process, the cell line is proprietary, it's relatively fresh IP, which we are expanding, but also the physical control over our product is one that basically creates a different barrier to entry. So we have physical control over our GMP cell banks, which are the starting material for the manufacturing process. So basically, that's ours. And it will be difficult to copy this cell line, we know, because it took a long time to develop it. And with respect to your question on how we source our patients, does that relate to clinical trials or, in general, the patients we treat? In general, what might? Sure. Yeah. So the basic decision we took actually was two decisions. One was to not go where the checkpoint inhibitors are effective and to look for maintenance treatment. And people have basically overlooked it. There was not a lot going on in cancer maintenance treatment. Nowadays, the whole vaccine field, also because big companies like Moderna are stepping in and BioNTech, and now everybody's saying, "Oh, of course, they will only work in low disease settings." But when we started, there was no real maintenance-focused companies. And AML was wide open, which is why we could do a monotherapy trial. And for ovarian cancer, it's more or less the same situation. Whether or not that trial will also deliver significant clinical benefit, we don't know yet. We'll have to wait for the second half of this year. So actually, it was a nice opportunity to step into that window. So far, we haven't seen, let's say, a lot of difficulties in the recruitment of patients. We see more opportunities, but it starts with choosing the right indication, seeing clinical data, and then, of course, pushing through. Harald? Thank you. Surely, it's an unmet need area in AML. But in my experience, most of the patients died during induction treatment, and you're not approaching this patient population. You treat patients who are already in response in MRD negative status. Could you comment on that? Yeah. It was actually the other way around. So we only selected MRD positive patients. So the one thing we learned, it was in the phase 1, which I didn't show for time's sake, but it was black and white. And you know, as a hematologist, how AML manifests itself. It's there or it's not. And if it's there, it's deadly disease, right? So in the phase 1, we saw either patients relapsing very quickly and passing away, and they had high disease burden, more than 10% blasts, or they had a 36-month median overall survival in the phase 1 already, which was all poor cytogenetic risk profile patients. So the phase 2, we designed only on patients in a complete remission, so they indeed responded, but they all had an MRD positive status confirmed. Sam, please. Thank you for a very nice presentation. I have a question about selecting patients in solid tumors. How do you select those patients that you think are appropriate for such trials? I mean, do you go with markers? I mean, with AML, it's easier because you take a blood sample and you can see if you have residual disease or not. But in solid tumors, it's a quite different question. People are moving there. Also, the new big trial of Moderna with BMS will be in melanoma in MRD settings. So it's more and more commonplace to do, let's say, biomarkers to see if there's still residual disease and to then focus on that. By the way, sorry, I made a mistake. It's Merck and Moderna who are doing the big melanoma trial in an MRD setting. So what we basically did is we looked for medical need. Ovarian cancer is basically also still untreated disease. So the hospital we work with in Groningen, they basically said, "Let us try the product." So in all modesty, that's also the only decision we took. We did spend two years on preclinical research with patient material, with mouse models, to confirm that the product has a potential immunogenic overlap with ovarian cancer cells and that it also works in a mouse model. But then we just went for it. So there's not much more to it. And if we find this clinical signal, we will pursue it. If we don't find it, then we have to let it go. But it's worth the effort. Thank you. Thank you for a very nice presentation. I have an additional question regarding select new patients. But I think it's very good that you will go for sarcoma patients. That's, from my point of view, a little bit unexpected. Could you please give us a rationale for why you would go for sarcoma patients? Because from my perspective, maybe it should be more easy to go for, as you said, ovarian cancer or small cell lung cancer, for example. Yes. Again, we try to take data-driven decisions. The program was already quite advanced, actually. When I joined as CEO, we had completed an 88-patient trial in renal cell carcinoma. We saw a 78% complete response rate, 42% objective response rate. Very nice, but not competitive versus checkpoint inhibitors. So we had to take a pretty harsh decision, which is we stopped the program. Then we looked at all other data. We had data in HCC. We had data in GIST, so gastrointestinal stromal tumors, that looked rather promising. We talked to a global KOL panel, and in the end, we decided that the GIST data looked very promising. In soft tissue sarcomas, there's high unmet medical need. After first-line treatment failure, basically nothing helps. The checkpoint inhibitors don't work. So that was what guided us towards soft tissue sarcomas. We hope to announce details shortly, but we're quite advanced in preparations for that trial. Thank you very much, Erik. Thanks. Yeah. Good afternoon. Thank you, everybody. Well, we are a publicly listed company in Madrid, so I need to draw your attention to this. We are developing basically epigenetic drugs in the fields of CNS, NDD, and oncology. We do that basically developing drugs against LSD-1 and histone demethylase, which is a fascinating target where we have two programs in phase two. The company, as I said, is publicly listed, and we have right now a market cap of around EUR 120 million. We have an expected cash runway so far till first, second quarter next year. We are expecting to get some initial additional financing in the next time. As I said, LSD-1 is a fascinating target and histone demethylase. But besides being able to demethylate histones and opening or closing regions of the chromatin, it's also a usual partner in crime and normally one of the key ones in different transcriptional programs in these complexes where there are other methylating or demethylating agents, transcription factors, and so on, governing the expression of key genes for specific diseases. In the case of some subset of cancers, we know that LSD-1 is playing a fundamental role. The mechanistic way where LSD-1 is involved in the tumor progression has been very nicely characterized in leukemia, in AML, also in small cell lung cancer. We know the different transcription factors which are involved with LSD-1 in the progression of the disease. In terms of clinical development, Oryzon is one of the companies leading the pack, but there are also other competitors. We have been focusing in AML and in small cell lung cancer as a part of an endocrine tumor effort, but it's being developed also in other areas of interest like myelofibrosis, polycythemia vera, et cetera. Our compound, iadademstat, has right now the Orphan Drug designation from the FDA for AML and small cell lung cancers. Also, we are expecting the same for EMA. In terms of small cell lung cancer, we got the Orphan Drug designation in AML some time ago. So this is how our pipeline in oncology looks like. We completed a study in AML and FLT3 patients, first line, some time ago. And now we are busy, and I'm going to explain to you today a bit about our clinical trial ongoing in refractory relapse AML patients harboring the FLT3 mutation in combination with gilteritinib. But also, we are leveraging on the agreement that we did with the CRADA agreement that we did with the National Institutes of Health, the National Cancer Institute in the US, which is basically helping us to broaden our clinical development. And particularly, we have recently announced the IND approval. So we expect to start recruiting in the next couple of months an NCI-sponsored trial in small cell lung cancer, first-line maintenance, which is we think a very interesting concept. So we started developing iadademstat some years ago. We know we and others, we have demonstrated that LSD1 is required for leukemic stem cell survival. That LSD1 ablation produces leukemic stem cell death. We did a first-in-man study at phase 1 where we saw it was well tolerated. We saw very clear differentiation effects and a modest in monotherapy therapeutic benefit. We started some time ago a combination with azacitidine and fit AML patients. We were invited to do an oral presentation at ASH in 2022. We were selected as one of the 25 most prominent AML abstracts. Very briefly, we recruited 36 patients. Basically, we got a high level of responses between PRs, CRs, and CRis. Most of them, they were high-quality responses, CRs, CRis, and most of them were having a nice duration of response. So we still have four patients which are being in compassionate use for more than four years and still in remission. We see an interesting degree of MRD negativity in the CR, CRi set. All that was really promising, especially in some subsets of patients which are responding poorly to the current approved therapy, which, as you know, is the combination of venetoclax plus azacitidine. So we saw, for instance, a promising improvement in patients with p53 mutations where we were increasing not only the level of responses but the duration of responses and the overall survival of these patients. Also, in four and five patients, we saw a very interesting increase in responses. But of course, being venetoclax in the market for us, it would be absolutely difficult to challenge venetoclax in a phase 2b trial, global trial, 400 patients, five years, EUR 30 million. And to be in submarine, to be in radio silence all this time is something that you, as a small company, cannot afford. So we decided to move to more greener pastures. And for us, the more obvious option was this population, as I said, refractory relapsed AML harboring the FLT3 mutation. Why? Because this is still a prominent population, meaning a prominent market opportunity, but also because in this setting, the approved drug, gilteritinib, Xospata, is providing only a modest benefit. We are seeing here basically maybe an event-free survival of not even three months with a CR, CRI levels of 30% to 34%. So we thought that that was a good opportunity. But I mean, these kind of considerations are not the only ones. We and others, we have published that the combination of gilteritinib with iadademstat, the LSD1 inhibition, produced an extraordinarily synergistic effect in all kinds of preclinical settings. So we thought that that could be the basis for a nice clinical trial, clinical trial which is right now up and running and is being led by the Massachusetts General Hospital. It's being run only in the US. And initially, it was designed as a phase 1/2 trial. But as the FDA changed their mind because of the Optimus policy, now we have to demonstrate which is the minimal effective dose, which is basically useful for patients. So we have right now started this with a trial in which we are dosing progressively lower the patients. I didn't mention, but our compound is the most potent LSD1 inhibitor under clinical development. We are dosing, as you can see right now, in the dose level minus one, 75 micrograms per square flat dose once per day. So this is progressing. We are seeing we have done the first cohort, which was 100 micrograms. It was safe. We saw a very strong antileukemic activity. One patient was moved to bone marrow transplantation. We were going down and to the dose of 75. Again, very strong antileukemic activity. In terms of target engagement, we have an ELISA method to quantify that. We are at the same level. So we are right now at this dose level 3. And we have preliminary data compared to FLT3-ITD, which are very promising. So we think we are going to present some preliminary data at EHA and hopefully more complete data at ASH by the end of the year. We have also, as I said, a neuroendocrine program, which is basically leveraging on the specific effect that LSD1 is playing on a subset of small cell lung cancer, which are the A subtype, the one driven by ASCL1 oncogene representing 40% of the tumors. Small cell lung cancer is a strong unmet medical need. It's still a serial killer. And despite the approval of durvalumab and atezolizumab as ICIs for this space, the benefit of these patients is still very, very modest. What is very interesting is that we know that LSD-1 inhibition is basically boosting in a very nice manner the immune system. And it's not only changing the way that the cells, the tumor cells, are expressing their genes, but also this is interesting because it's boosting the T cell production and inhibiting the T cell excretion. This is a paper published by the Memorial using our compound. And as you can see on the top, I mean, well, there is no it's not working. ORY-1001, which is our compound, was producing a relatively modest effect, much better than the anti-PD-1. But when they combined with both drugs, they saw in these PDX experiments coming from material from relapsed patients, they were seeing a very nice effect. And what is nice is that they were able to characterize how this is working. So basically, our compound is able to change the way that the tumor cells are expressing the receptor, sorry, the receptor. And not only that, I mean, it's also boosting the expression of a number of T cells subtypes. So that was also very strongly supported by studies done by the same team at the Memorial where looking retrospectively to the studies of Nivo and Durva, they saw that the largest proportion or the higher survival rate is strongly linked to lower levels of LSD1. So with all this in mind, the Memorial went to the NIH and they request us to do a clinical trial. So we approved this clinical trial, which is, as I said, a trial in maintenance. So patients are treated with carbo plus the ICI. The patients which are responding are then randomized after the final doses of chemo. Then you have an arm. It's a randomized trial. You have an arm with iadademstat plus the ICI or only ICI. So the estimated enrollment is around 50 patients. The primary objective is the progression-free survival. Secondary objectives, overall survival, and objective responses. And as you can see, we have the best hospitals in the U.S. starting this trial. So we feel very, very honored and very happy. So this is, of course, a very strong opportunity. We think that the information that we will get from this trial might be the basis for setting a small randomized sponsor trial, which can lead to an accelerated approval. So in conclusion, what we have here is a compound in phase 2 in AML and in small cell lung cancer with very clear signs of efficacy, with a clear developmental path towards approval in both settings. It's a compound which is safe, is well tolerated. The only toxicity that we see is on target because it produces temporary immunosuppression, temporary thrombocytopenia, which recovers. There are additional development fields which are contemplated by the company, especially sickle cell disease and myelofibrosis. With that, I would like to thank you for your attention today and take any questions. Thank you, Carlos. Mahir, please. I mean, good luck. You're trying to treat the two most difficult to treat cancer diseases. My spontaneous thoughts was in AML, of course. Have you any result or thoughts about combining your drug with AZA and venetoclax in first line because this is the natural way to go rather than second line? No, indeed, we are doing that. We are actually doing that towards another CRADA agreement with the Oregon University in the U.S. So it's, as I was very rightly pointed out, venetoclax is a very difficult drug. And nobody is using according to the label. Everybody is subdosing the patients because it's too difficult, too toxic. But we are doing that. We are doing this triple treatment with these guys who are very experts on de-escalating Ven. So we will see how it goes. Think about adding it in later cycles, not in the first cycle because if the patient is developing side effects of venetoclax, they will show up already in the first cycle. So if you combine, you might do it in second and third cycle. Thank you. Thank you. You're here to pose the questions. Can I ask? Please, Alex. I think earlier we spoke, you mentioned challenges in getting financing in the market space. What's been the main challenge when you speak to likely investors to come on board? What's been the biggest hurdle that you've come across consistently, would you say? Well, I mean, it is clear that, and we have been listening in some cases, very successful cases. But I mean, it's clear that for European companies in general, it's a challenge to go to the U.S. and to present yourself in the U.S. ecosystem. I have been doing that for the last seven years. I am constantly in circuit and doing presentations of the company. And it always comes to the point of being able to capture the good institutional investors, the U.S. long-term institutional investors. And this is a catch-22 because it is not only about the scientific proposition. The scientific proposition is needed, but it's not sufficient. So I mean, when you are listed only in NASDAQ, you get immediately levels of liquidity, which are the ones that the institutional investors, American institutional investors, like to see. We are a kind of hybrid situation because we are one of the most liquid European companies in Madrid. But still, I mean, this is also one of the problems when you talk to them. I mean, they like to see good science, a good developmental plan to market, and also that you are basically trading in a platform where they feel comfortable to write a big check because if it need be, they can leave. You can talk to Martin later about how to secure institutional investors in the U.S. Do you have any tips from the investor side? No? Okay. We'll have a lot of time to talk together, all of us, in the coffee break. But that's it. I would like to add that we have been able to secure several rounds with American banks and American investors. So we have done that in the past, and we will do again. You will, I'm sure. Thank you very much, Carlos. Thank you. Bye. Before we are off for coffee, we are having some time just with our panels. You have been very busy here today posing some questions to our companies. I'd like to hear the first general view of these four companies. Do you have any wrapping-up thoughts of where are we? You've heard Alex talk about the international arena out there. What is your view on what you've heard today? Any spontaneous thoughts? Niels, please. Yeah, I'm impressed by the way that you worked with the U.S. institutions. That's impressive. And also, I guess, I mean, it's a lot of hype around IO. It's been there for 10 years. And we're sort of struggling against some challenges still with IO. And I still think there is a huge unmet need in this area, and everything cannot be solved with IO. I guess 10 years ago, we thought that we saw the answer in the tail, in the long-term survival. And we thought we could reproduce that in other tumor types, not only in melanoma and perhaps in lung cancer. But I think there is a sobering up now. And I think that is essential and that we have forgotten some other therapeutic interventions that are needed to really get to the unmet medical need in many areas of oncology. Cecilia, you were nodding. I just want to say that it was great to hear our presentation. I think there is some hope for oncology patients in the future. I just want to add to Niels that we need to remember there is only about 30% of all patients that actually respond to immune therapy. That's very important that we try to look in different kinds of ways to approach this unmet need in special patient groups. But I think also, I'm impressed because my own experience is that most of these small companies don't really have a strategy. They don't know the mode of action of the drugs and so on. But I think the percentage today are actually getting what's crucial out there. So really impressive. Thank you. Ted, please. Yeah, I was also impressed by the international nature. I think all four of you have worked really hard to both do clinical trials everywhere and well, not everywhere, but in many countries. I actually have a specific question for Jens at Medivir, which is really around the yeah, there you are. The strategy you took with Korea and advanced liver cancer, of course, is an orphan drug in Europe and the US, but it's by no means orphaned in Asia for various reasons. How have you thought about the different approach to launch it in well, if you launched it yourself, but you have done in the past, so it's a possibility at least. How do you think about that in, say, China or Korea or Japan where it's not orphaned? No, I think there are a couple of different elements to it. One, in order to maximize the value of the compound that we need to develop it in Asia as well, we're not looking to specifically in Asia. We're not looking to commercialize ourselves. We're actually, at the present, aiming to establish both development and commercial partnerships specifically for Asia. But it was important to include Korea and having an Asian country in order to attract partnerships from Asian countries. And that's where and then we looked at sort of pros and cons for different countries where China we tried to stay a little bit away from for a few different reasons. Japan can be challenging and take time and be quite expensive. So we kind of looked at Taiwan and Korea with regards to having Asian patients. And it was also an element coming back. There was a recruitment question before, being able to recruit patients with speed because HCC patients are more frequent in Asia. So there were a number of different reasons why it was important to include Korea in this study. When you're ready, right now, Korea is going through quite a difficult time with their life science. The KOSPI stock has done quite badly. But I think they will recover when you want to. We have co-invested with Korea Investment Partners in four companies. I'll be happy to make an introduction for you if you want. Let's speak. So I'm thinking from the clinical side of this, you are out in the clinic, and you say that you are impressed by the companies. But what is it that you see out there that companies today miss or areas they should go into? Or what do you lack? Please. I can just start. What I'm missing is that one of the big challenges with having the clinic is the older population. Patients get older and older. I think it's a big challenge in the clinic to know how to treat patients that are 80 or over because these patients have not been included in clinical trials. A lot of patients that are 75 or 80 are quite fit. But we also know they don't really tolerate the drugs that we have in the market. So I think the challenge is trying to include these patients in clinical trials so we can get some evidence and some background, so to speak, to stand on how to approach those patients. Niels, please. I like to think that new drugs are not too expensive, but they are not effective enough. So I think that is a problem that we're paying a lot of money for drugs that, in most cases, are not effective. And the problem from a clinical point of view is that we don't really have any clue about it because we look at efficacy from clinical trials. But we totally lack. I know that hematologists are much better at that. We lack clinical follow-up data. We don't have any clue on implementation of a lot of these drugs. We don't know what follow-up. We don't know what the population that we are treating, what the outcome is there. I think that is a key problem. But that's a problem for healthcare. We've been used to spending quite a lot of money. But we really don't look into what we are spending the money on and what kind of effectiveness we are getting. Do you have any solutions? Yeah, please. I will connect to Niels' words here. Also, when we see the results of the clinical trials and we use the drugs in our day-to-day work, we see that it's a difference from the results from even phase 3 trials into reality. There is a need for phase 4 trials just to see because there is a difference from the patient population in the trials and in reality, as Niels and you said. I'm impressed that all the company introduced a new mechanism of action. So thank you very much. Please keep on the good work. We and the cancer patients need you. What could we do about this then, the results being different? I think the registry is my suggestion to my colleague. Registry studies. Yeah. I think this is a work I mean, the companies are generally not so interested as they finish the phase 3 trials, and they have the results, and they start marketing the drugs. But it's up to us as clinicians to also see what's happening in the clinic. But you're talking about how we distribute the funds to the medical community. And often, when you see how much money goes into different sectors of the medical community, oncology gets a lot of money. But still, we haven't gotten the efficacy we would have wanted for that investment. How could we do this better? Well, oncology gets a lot of money. But I mean, I guess in all other parts of society, you have to come back with information on what you're doing with the money. I think that's a clinical problem that we are not providing the healthcare providers, this part of the stakeholders, with information on what kind of efficacy we are getting from the investments. And I think we really have to rethink that. I mean, there are some examples that we've seen in the clinic, some drugs that we spent a huge amount of money on, but we have no idea if they've been providing any clear benefit for patients. So I think it's up to the clinician through the profession. The hematologists are much better at this, and the pediatric oncologists are much better. But we who treat solid tumors have been quite reluctant. We have the resources. I mean, now with the new data science or whatever you try to call it, we should be able to generate data out of the electronic patient charts without having to really get into doctors being involved in that process. That we should be able to retrieve automatically from our patient charts. Some positivism. But it's very interesting, sorry. It's very interesting sort of the miscommunication in incentives almost that these guys are speaking of because, obviously, from an investor perspective, you have sort of set milestones. And it's a fairly clear path to getting market approval or whatnot and then to be acquired by a strategic buyer, which is sort of the investor role in this. So if the mismatch is in the implementation of this, obviously, the incentive structure needs to change on the way there, I assume. But it becomes a bigger question than just a five-minute discussion on a panel because it's yeah. Bengt, what is the solution? I think it's totally up to the healthcare system. You should have a quality follow-up over what you're doing whereas providing the drug. And then you should follow up what you're doing in the quality. And I think there are better systems in orthopedics and in cardiology than they have registers to follow up five year, 10 year, what happened. It's up to you. Yeah, you're right. I mean, if you look, let's say the breast cancer register has been in place for 16 years, but there is basically no information on metastatic disease, which is basically where we're spending the major part of our healthcare budget. I just agree. We need to be much better in-house, so to speak, how to evaluate the patients that we treat because most patients we treat are older. They have a higher performance status. They are not performance status 0 to one. They're usually two, three. So we really need to, I think, every department in Sweden needs to go back and do their homework. I don't want to defend the system in any but this is a very complicated question when evaluating metastatic patients because there are an enormous—I wouldn't say enormous, but there are a lot of drugs to use. And every drug has been approved. But you come to a situation where, even if the drug has been approved, they are no longer effective. And there is a pressure, emotional pressure from the doctor's side to the patient's side to continue treatments. And it's not an easy task to tell a doctor, "Stop here." And this is the problem because we use a lot of drugs which are not effective in various situations because of the complicated situation with the patient. It's a good question. Good point. Is there a role in here for regulators, governments, to set the bar and have it filter down from there? So, for example, the FDA, the EMA requiring data gathering beyond phase 3, beyond approval, and so on. I guess, I mean, now you have a collaboration ongoing, let's say, with the EMA and health technology assessment. I mean, I think that needs to be coordinated. And I do guess we need to have the capacity of throwing out some treatments that don't really fulfill the anticipations that we have. The problem is, if you look at a healthcare provider, you're very reluctant to let new technology in because you know that you can't get it out if it proves not to be of value. And as long as you don't know if it's of value or not, you basically are stuck in a similar situation. Now, I do believe that you need to have some kind of feedback from the healthcare system to both the drug companies but also to drug developments. Is there a need for another IO or whatever? Because, I mean, we see a lot also with the industry. There's a lot of focus that everybody starts running in the same direction. And that's perhaps not the best way to try to go into an area so complex like oncology. That's our character. We are a flock. We tend to run after what's trendy. Do you know what's trendy now? Coffee. Coffee. Coffee. Let's have coffee, and we'll be back soon. So now we've come to our second block. It is time for Helén from Active Biotech. Please. Thank you so much. It's nice to be here and present tasquinimod and present a little bit on Active Biotech as well. I don't know how many of you know what that is, the little fellow, green fellow here. It's a myeloid cell. The myeloid cells are present, for instance, in the tumor microenvironment in the bone marrow. Certain cells are driving disease in the bone marrow, driving, for instance, multiple myeloma, myelofibrosis, MDS, and AML. tasquinimod targets myeloid cells in the tumor microenvironment in the bone marrow, specifically cells like the MDSCs, the myeloid-derived suppressor cells, megakaryocytes, and stromal cells, and affect both the accumulation activity of these cells. I will focus my presentation today on tasquinimod in myelofibrosis. But before we go into that, I will say a few words on Active Biotech. I was advised earlier on to speak out loudly. I don't know if you hear me. Yes, that's good. Active Biotech develops novel immunomodulatory treatments, treatments for diseases with large unmet medical need and value potential. Our wholly-owned projects, tasquinimod and laquinimod, are targeted towards hematological malignancies and inflammatory eye disorders, respectively. In tasquinimod, we have a study ongoing in relapsed refractory multiple myeloma patients. We had results or interim results presented at ASCO last year. We expect the full data set to be available late this year. In parallel, we are planning for started two trials in myelofibrosis during this year. In laquinimod, we have confirmed the safety of a newly developed eye drop formulation. Right now, we have a biodistribution study ongoing in patients. That is done in collaboration with Stanford. We have a partner project, naptumomab, which is partnered to NeoTX Therapeutics. It is in phase 2 in selected solid tumors. tasquinimod and laquinimod are small molecules. naptumomab is an immune therapy. We expect results from the study with naptumomab in lung cancer late this year. Also, we expect start of an expansion cohort with naptumomab in combination with durvalumab this year. We have opportunity to leverage prior-generated documentations for laquinimod and tasquinimod to accelerate development and for cost-efficient development. If we look at this year, we have multiple near-term clinical milestones. We are a publicly listed company with a strong shareholder base, including MGA Holding and AP3 and AP4, Peter Thelin. They have been with us for many years. Going over then to tasquinimod. tasquinimod targets cells in the tumor microenvironment in the bone marrow. This is different from most other cancer treatments. So tasquinimod offers a new method to treat hematological malignancies. There is a strong rationale for tasquinimod in the broader sense of hematological malignancies. Like I said, we have an ongoing study in multiple myeloma. We are doing preclinical work in myelodysplastic syndrome. But our focus right now is on myelofibrosis. And I can already now say that we have preclinical data that indicates that tasquinimod could have a disease-modifying potential in this disease. We are starting two studies during this year, one together with MD Anderson in the U.S. and one together with Erasmus MC and in the HOVON network in Europe. tasquinimod is an oral immunomodulatory new type of treatment. We have shown significant PFS benefit in prostate cancer up to phase 3. Before, it was terminated, the development in prostate cancer, due to that the PFS benefit didn't translate into overall survival in these studies. We have an opportunity, though, to leverage all the established regulatory package with preclinical, clinical safety, long-term exposure in patients, and a full commercial-scale CMC documentation. tasquinimod has orphan drug designation in the U.S. in multiple myeloma and myelofibrosis and is covered by patents and patent applications to at least 2042. Oh, sorry. So myelofibrosis is a rare chronic blood cancer where a blood-forming stem cell is mutated and leading to abnormal production of blood-forming cells, replacing the healthy bone marrow with scar tissues or fibrosis. The hallmarks of the disease include an enlarged spleen, sometimes also the liver, reduced blood cell production, bone marrow fibrosis, and disease-related symptoms like weight loss, fatigue, and bone pain. And, of course, altogether means impaired quality of life. Current treatments include bone marrow transplantation for a small portion of patients and JAK inhibitors to decrease the enlarged spleen and other symptom-directed treatments, for instance, to manage anemia. There is only one drug class approved for treatment of myelofibrosis today. There is an unmet medical need for a disease-modifying treatment, a treatment that can affect more than just the spleen size, for instance, the fibrosis. If you take a quick look at the market, this is a less developed market given that there is only one drug class approved for treatment. There are currently four JAK inhibitors approved in the U.S. and three approved here in Europe. But there is a significant opportunity for a new treatment that can modify the disease, being antifibrotic, and can be used second-line to treatment or after JAK inhibition treatment. The market is expected to grow and reach around $3 billion around 2031. The dysfunctional bone marrow environment is driving the disease. tasquinimod targets some of the cells that are important. You remember the green fellow from before. Specifically, the immune suppression is restored by tasquinimod, restored antitumor immunity. Secondary pro-inflammation and fibrosis is mitigated. We have a restored hematopoiesis. The targets for tasquinimod that have been identified are the alarmins S100A8/A9 specifically and HDAC4. This is also confirmed, the effects on the bone marrow by tasquinimod is confirmed when we look at preclinical experiments. In this case, a transgenic mouse has been used. This has the same mutation as is the most common mutation in patients, the JAK2 mutation. This means that the mouse developed a disease which is similar to the human disease. After tasquinimod treatment, we see significant effect on reduced fibrosis. We have reduced spleen size. tasquinimod treatment's normalization causes normalization of the leukocytosis. These results come from a collaboration we have with Professor Rebekka Schneider at Erasmus in Rotterdam. We see similar results in a PDX model of post-MPN or advanced myelofibrosis. tasquinimod in red, both here and over there, reduced the spleen size when given as a monotherapy and prolonged survival as monotherapy. But when combined with a BET inhibitor or a JAK inhibitor, we see superior effects of the combination. This indicates synergy when tasquinimod is combined with these two treatments. This data comes from our collaboration with MD Anderson. These data were presented at ASH last year. Based on the strong supportive preclinical data, we are starting two proof-of-concept trials in patients with primary or secondary myelofibrosis in 2024. The TASQFORCE trial is a monotherapy trial in patients that are JAK ineligible or intolerant. This trial will be done in the HOVON network. It will be done in Europe, in the Netherlands, and in Germany. The second trial will be performed at MD Anderson. In this trial, we will assess tasquinimod monotherapy in a similar population as in the TASQFORCE trial. In the second part, there will be a combination of tasquinimod and ruxolitinib, the most commonly used JAK inhibitor, in suboptimal responders. The endpoints are similar, but even if the primary endpoints are a little bit different. Spleen volume reduction will be assessed in both studies, reduction in the myelofibrosis symptom score, safe tolerability, and fibrosis grade, the most important endpoints or readouts in the study. These studies were set up or have been set up to guide for an optimal path to registration. Dependent on the outcome of the trials, there are at least two different ways to go. tasquinimod as monotherapy in second line after JAK inhibition treatment or tasquinimod in combination with ruxolitinib or another JAK inhibitor. So and that will be in first-line treatment. So this is, the concept or how we are thinking for tasquinimod. It's early days. It's too early to say, at what time point we will, be able to submit the NDA. But this is a rare disease. It will take some time to recruit all the patients for this program. So just to sum up, myelofibrosis is a high unmet need disease. There is a significant commercial opportunity, specifically for a new type of treatment that could affect the whole disease, being a disease-modifying treatment, being an antifibrotic treatment. We are planning to start two proof-of-concept studies at well-renowned centers in Europe and the US. They will start in 2024. They are backed by strong preclinical data supporting that tasquinimod has potential as being a disease-modifying treatment. There are clear paths to registration with opportunity to leverage prior documentation to accelerate the development. So. Thank you. I'm looking at you. Well, do you have any data on other diseases than rather than myelofibrosis? I'm thinking about essential thrombocytosis and. So we have a lot of preclinical data. JAK-positive patients, of course. Yeah. From the only data we have in the hematological space is in multiple myeloma. I know that. Yeah. So. That's not my question. No, so sorry. When you have essential thrombocythemia. Yeah, yeah, yeah. Well, most of these will develop myelofibrosis, as you know. So do you have any early data before the development of myelofibrosis? No. No, no, we do not have. That's a good point. I understand. Sam, please. How are the studies with solid tumors going? I know that you also have some programs for solid tumors. We have a partnered project in solid tumors, the naptumomab program. And there will be, I think, final data quite soon from the study in combination with docetaxel in lung cancer. And there were interim data reported from the combination with durvalumab together with AstraZeneca last year at the AACR. And the plan is to start an expansion cohort in that study. And according to the timelines from NeoTX, it should be during this year. I have an additional question. Great presentation. Thank you. Regarding side effects, because the focus in early phases is actually safety. So could you comment something about safety compared to JAK inhibitors? Is the safety profile different or how does it look? So the safety for tasquinimod is well known from prostate cancer and some other advanced cancer patients. And we do not see any hematotoxicity with tasquinimod, which is great compared to JAK inhibitors. And it's also great because it's easy to combine with in that case. Otherwise, we have what's seen for tasquinimod is grade one to two gastrointestinal side effects, which are mostly transient during treatment. We also see musculoskeletal pain, sometimes also or mostly transient during treatment. Some like more like flu-like side effects related to the immunomodulating activity, I would say. Thanks for the presentation. Two questions related to each other, I guess. The first one, what's your general fundraising strategy and what are your fundraising needs? And then the second question is around your interaction with MD Anderson. Do you have any, have you had any fundraising associated with that, either Cancer Focus Fund or anything else? Yeah, that's a really good questions, of course. And if we start with MD Anderson, this is, I mean, they contacted us and wanted to do something together. We have, there are grants from, or more general grants related to MD Anderson that will be part of the funding of the trial. Otherwise, we will support a trial with study drug and associated cost with the drug supply and things like that. And so it means a minor study budget for Active Biotech. And most of our trials are more or less investigator-sponsored trials, which means lower budget. Can you say anything about your sort of current shareholder base and what support you have? So our current shareholder base, MGA Holding and Peter Thelin and AP4 and AP3, they have been supportive so far. We have been in a situation lately that we have been able to raise money on a more or less a yearly basis. It's not optimal for us. It should be it had been much better to have some or have money for a longer period, I would say. So that is something that we are investigating and discussing internally, how to do that. So we are open for any initiatives or suggestions, of course. Cecilia. I have just an additional question regarding if you compare IITs comparing with in-house trials, so to speak, what do you think of course is the cost of course much lower with IITs. But could you just comment what you see from your perspective when it comes to the disadvantages with an IIT? That's a very good question. We have done a lot of in-house sponsored trials before. And with all the data we already have for tasquinimod, we decided to primarily try to go for IITs because we know the drug, the safety is well known. We know that the drug can be clinically active. And it has been very easy to attract good centers to work with us. Then we have spent a lot of time on negotiating the contracts with the different centers. A not very easy task, specifically not in the U.S., I would say. But it's important, of course, to keep all the rights to the company, the rights to use all the data that's generated for regulatory and commercial purposes. Then establish good relationship. So I think mostly, I mean, it's not just a cost perspective. For us, it has been, I would say, very important to establish an early contact doing preclinical work together and translate that into the clinical setting. Sounds good. Because usually one of the big issues is the recruitment of patients. It can be quite slow if it's IIT. As a company, sometimes it's very hard to be able to, how to speak, change sides or trying them to speed up, so to speak. So that's usually one of the known hurdles. But it sounds like it works very well for you. Yeah, but that is, of course, a challenge. You need to have some kind of mitigation plan in place. For instance, how to attract new sites, new centers to come into the trial. It all starts with good collaborations. As always. Yeah, as always. Thank you very much, Helén. Yeah, thank you. Thank you. Göran and Cantargia, please. Thank you so much. A pleasure to be here and present Cantargia to you. I guess most of you have heard the story, but maybe there are some newcomers to quickly go through it. We're a company based in Lund. We are focusing on antibody therapy against one molecular target called IL1RAP. It's really from a biological point of view, it's a really intriguing target because you have three different cytokine systems signaling through it, IL-1, IL-33, and IL-36. It's also overexpressed on a large number of tumor forms, both solid tumors as well as liquid tumors. So plenty of opportunities both in cancer as well as in the autoimmune inflammatory space. This is an oncology day today, so I'm will try to, let's say, stay focused, but I may switch over sometimes. Anyway, the lead program, nadunolimab, is being developed in cancers. Today we treated about 300 patients with various solid tumors. We've done monotherapy, we've done combination therapy with chemo, as well as with the immune checkpoint inhibitors. Let's say once we have analyzed all this data, we see that we get really good signals in pancreatic cancer, which is obviously a very high medical need and very interesting for us. We also see interesting signals in non-small cell lung cancer. Also a very interesting indication, but very competitive. And finally we see initial very early results in a relatively small group of patients, but similar type of results when we do chemo combinations. So what we have done to stay focused is to continue the development in pancreatic cancer and triple-negative breast cancer at the moment, while analyzing and getting more data in non-small cell lung cancer where we still have patients on treatment. In triple-negative breast cancer, we have a randomized phase 2 trial ongoing in 100 patients. We are planning to start a phase 2b trial in pancreatic cancer during the summer. So we have FDA approval to start this trial. CAN10 in autoimmune inflammatory diseases. It's a very hot area, but as I said, oncology day, so I'm not going to say more about that, but keep an eye open. It's going to happen lots of things here as well. From a corporate perspective, we have cash for about one year to go, about SEK 200 million in the bank. So if you look at the pipeline then, pancreatic cancer, the focus is first-line patients in combination with Gem/Abraxane. In triple negative breast cancer, the trial we're currently doing is in first and second-line patients with carboplatin gemcitabine. And this trial is done as a together with the Spanish cooperative group in breast cancer, so it's done only in Spain. The pancreatic cancer has been recently done in Europe, and both Baltic states as well as Western Europe. The phase two B will be done in both Europe and the United States. And lung cancer, finally, we've done basically looked at patients that have relapsed on PD-1 therapy and then used platinum doublets in those patients that have received monotherapy with Keytruda. If you just look at the number of diseases that gets into play, IL1 RAP is overexpressed in somewhere between 70% to 90% of all patients when it comes to the tumor cells. But interestingly, there is a really high component in the tumor stroma as well, in both fibroblasts, monocytes, macrophages, neutrophils, and other cells. But the normal tissue reactivity is very low, so we haven't really seen any side effects because of normal tissue reactivity so far. So this is really interesting. And the mechanism of action of nadunolimab is that it's binding to IL1RAP. And IL1RAP is part of the interleukin-1 receptor. And... As some of you know who have listened to me, there are two forms of IL-1, IL-1 alpha and IL-1 beta. And both are present in the tumor microenvironment and both are creating an immune-suppressive tumor microenvironment. So by blocking the receptor, we actually block the activity of both. And this is really important. And then, since it's an IgG1 antibody and it's non-fucosylated, it has a very strong NK cell activating activity. So it will attract NK cells into the tumor area to also kill cancer cells. And then, again, to focus and not go through all the results we have, I'm going to present what we have in pancreatic cancer in first line. So here we treated 73 patients with the combination, Gem/Abraxane plus nadunolimab. And looking into all these data, if you start to the right, you can see that the waterfall, which is basically how... well do the patients respond to the therapy, looks much better to what you expect from Gem/Abraxane alone. You have lots of patients with deep responses and lots of patients with very durable responses. And this then... sums up to a very good progression-free survival, which is about two months longer than you would expect from the combination or chemotherapy combination. And perhaps four months longer survival than you would expect with Gem/Abraxane. So 13 months versus about perhaps nine months. But what has excited us even more is that we managed to get biopsies from most of these patients in the trial. And since I heard a question about this beforehand, I can say that pancreatic cancer is very, it's a horrible disease, but from a biopsy perspective, it's great because these patients are newly diagnosed and have biopsies. So it's very easy to get access to material and measure if they have high levels of the target or if they have lower levels. What we see is that there is actually a statistically significant difference in overall survival here between those that have high levels of IL-1RAP versus low. So our interpretation is that the antibody is actually having a better chance to get into the tumor if you have high levels and doing its job, which results in longer survival. Even more interestingly is that high IL-1RAP correlates with several KRAS mutations and it's actually giving a worse prognosis. So I think this is a really interesting story. If you look to the right, you can also see the waterfalls. So the patients that have high IL-1RAP and now I can't see this one. Yeah, it doesn't matter. To the left, IL-1RAP high, you can see we have much more pronounced tumor shrinkages compared to those that have low levels. So, a result we are super enthusiastic about. And then side effects. This was also a question, so trying to respond to everything. When we give combination chemotherapy, obviously there are lots of side effects. And you don't want to make the situation worse because it's you're really on the borderline of what patients can cope with. And to start on the positive end, there are actually side effects like neuropathy, which is a serious clinical problem that is much less pronounced. And I'm coming back to that. There is also fatigue and diarrhea that may also be lower. And there are some preclinical data supporting that. The negative side is that we see more neutropenia, so obviously something is happening here as well. The good news is that neutropenia can be treated with addition of G-CSF, and during the trial we learned how to use that in the first cycle of therapy. So we believe that this is an historical problem, which we won't see in the future, and we're adding G-CSF routinely in all future trials. But then coming back to the neuropathy, because I think this is really a very beneficial feature, which has attracted lots of interest. So why do you get neuropathy from chemotherapy? And especially if you target tubulin. So one thing is that tubulin gets damaged, but the other thing is that you create a neuroinflammatory response. And obviously IL-1 is in the center of this neuroinflammatory response. So what we've done is that we've seen already from the previous slide that grade three or four neuropathy was lower than expected in these patients. But we now also analyzed much more into, let's say, the minor, the grade 1 and grade 2s. And we can see that there is... a correlation here, which will be presented at a scientific conference... in the not too far away future. And we're still working on it, so... we have to wait. But very very exciting data. We're also working with an academic group who has animal models in chemotherapy-induced neuropathy. And we see really exciting results in those models, so... more to come here as well. And... if we then look into the future... ADCs are definitely coming more and more into play, so antibody-drug conjugates. But there are also lots of these payloads that have side effects that are of inflammatory nature. And we can see that these payloads induce the IL-1 system, so we believe that... We can probably be a very good combination agent with ADCs in the future as well. So, keep an eye open on that. Then in triple-negative breast cancer, we've not done as many patients. But what we've seen is exciting. So we've done 15 patients in combination with gemcitabine and carboplatin. And what we see here is that we have again, very deep responses, much more pronounced than you expect with the chemotherapy alone, including one complete responder. And the progression-free survival and survival also looks better than you expect from the chemo alone. And where we are right now is that we have this phase two trial ongoing in Spain, two times 50 patients. Half of them getting nadunolimab plus chemo, half getting chemo. Recruitment is still ongoing. But we hope to have results before New Year. Or at least response data. We will not have PFS and OS, it's too early. So if we look at the upcoming milestones for the company, we have the pancreatic cancer trial, which is an ambitious undertaking, so somewhere 150 to 200 patients, which we are planning to start in mid this year. And I'm not going into the design, but what we're planning to do is to have an interim analysis after 60 patients. So we will have some data on that during 2025. And if that looks good, obviously we will have a database to take to the FDA to start discussing accelerated approval and/or breakthrough designations. But we need to have that data before we're ready to have a discussion. And then it can take us when we'll be on the market, that's the obvious question. So in the most aggressive scenario, 2027, in the more conservative 2028, and then obviously... It can take longer time as well. But we are fully committed to make it as to be prepared if there is a signal in the new material. Triple-negative breast cancer, I said with full recruitment during second half this year, randomized phase 2 data late this year, which will be based on responses. What I haven't mentioned so much is that we got a grant last year to do a trial in AML and MDS, so now we're into the hematological space as well. And it's interesting because Cantargia was founded on findings in AML and MDS or and CML, and not in solid tumors, but for various reasons drug development is not always a straightforward way. But we got a grant from the Department of Defense in the United States to do a trial in 40 patients, which will be both monotherapy as well as combination therapy. We hope to submit that protocol soon, which means that we'll be ready to start during summer. The CAN10 program is autoimmunity, so we ignore that, but lots of things happening in that program as well. Finally, we have more lung cancer data to present in the trials we've done, which is about 40 patients in combination therapy. We will have efficacy and biomarker data being presented later this year. New clinical data from we started so in 2021 everything was glamorous and the market was flooding with money, which we all know. So we started the program to do some broadening, but we realized that we had to do some more focusing, so those programs were stopped halfway, which doesn't mean that money was thrown away. We learned a lot from those programs. We have documentation in other diseases. But we still haven't presented that to the market and it's coming. But we just haven't had the energy to do it and we would like to have long-term follow-up before we go out. And we also have lots of preclinical translational studies ongoing. So... I have to say I'm very excited about where we're taking Cantargia and I really look forward to the rest of this year and next year. And short-term I look forward to getting more questions. Good, Göran. Yeah, please. Thank you for a very, very good and interesting presentation. Just have a couple of questions around your pancreatic study. Why did you pick Gem/Abraxane? Was it any specific? I mean, a lot of people use FOLFIRINOX. Is there any specific... Microphone. Yeah, so I think... So obviously historical reasons. So when the trial started, we were still in 2019, where... It was still debated if Gem/Abraxane or FOLFIRINOX would be the standard choice. I think it's still... I think, as far as I understand, both are used. But we had... very interesting preclinical data on gemcitabine combinations, which guided us to go in that direction. And also... when you're doing... you don't want to get problems with toxicity and FOLFIRINOX is a tougher... regimen. And one of the trials we've done here is a FOLFIRINOX combination. And it's definitely... it's more difficult to do a FOLFIRINOX combination. It's not impossible and we have data, but... it's definitely been more straightforward to go with Gem/Abraxane. I was just interested in sort of the scientific background. Yeah, no, so gemcitabine... so we had gemcitabine, but... with neuropathy data, we know that oxaliplatin was probably... and we have more data with platinum, so... I'm not sure I would make the same decision today. The second question is, do you stratify for KRAS status? No, but we measure the... So we don't have unlimited amounts of biopsies, but where we have biopsies, we have analyzed for KRAS. But if I understood you, you had also more activity in the mutated cases? No, but so high IL1RAP levels correlate with the especially the KRAS G12D mutation. Okay. And we're investigating this. We don't have enough material to make any firm conclusions, but we have scientific collaborations between us and other hospitals in Europe and the United States. So some more to come. You have so much to talk about, Göran. It was hard for you to focus on. Yeah. Actually, on that... There's quite a few indications there. Is there a strategy for prioritizing which one to sort of move forward with? And yeah, effectively, what's the rationale behind or the strategy behind the choices for prioritization of indications when you go forward? No, but I think pancreatic cancer is very so much speaking for it. We have very exciting data. We obviously competition is much more limited. It's very straightforward how to do things. In triple-negative breast cancer, we're doing a trial now; we're trying to get a signal. But next step in triple-negative breast cancer is so dependent on what's happening on the competitive levels as well. So, I think I will guide you next year on what the next step would be there. And then in lung cancer, we've done trials, but I think everything has been you want to have several shots on goal when you start. And then you pick the ones that are most promising, and I think we are... that's where we are. Please, Cecilia. I just had an additional question regarding the cohort for the triple-negative breast cancer. Was that the one that had a low CPS score and were PD-1 negative? Sorry, low CPS score, meaning that they were not eligible for immunotherapy. So I think... Why I'm asking is that... Yeah, no, no, but we're not... Yeah, but I think... it's a changing landscape. Okay. So I think you would typically get that these patients would be second line then. But then you also have ADCs entering the field, so it's becoming more and more complex. Yeah. You might. But... Microphone. When the immune therapy was not approved, maybe when you initiated the trial? Or no, it has changed, but as far as I understand, the immune therapy is used both, let's say, in the neoadjuvant or adjuvant setting all the way through. And then you can also... or you can start using it in the metastatic setting. And that will affect the downstream therapy. So very quite a few... alternatives here. But it's definitely not all comers any longer. Okay, thank you. Sam, please. Thank you for a very interesting talk. I was very intrigued by the results of the side effects with the neuropathy. Yeah, neuropathy. And this is a very serious side effect, a very long-lasting side effect. And I wonder if you have any data or a clue of if this is a lasting effect or is this... you know an effect that you don't see after a while. I mean, if the effect of neuropathy is long-lasting or not. Yeah, no, but I think it's long-lasting. So these patients have been followed during the trial. So we've been looking at... So typically we onset this after three or four months of the taxane therapy. Hope I'm saying the right thing, but that's how I understand it. And we've been looking... So we see some patients... it's a delayed onset of the neuropathy and it's not as intense. But obviously we have no data of what happened after they stopped the chemo. Okay, Max, please, very fast. Just a short question. Maybe I missed it, but do you have any plans on doing ADC combinations in triple negative, like with sacituzumab govitecan, similar drugs? So let's say it's a different between what's reality and what's... in your mind. In my mind, I would like to do these trials, but we have nothing set in stone yet. Okay, but I think it's a way to go with some of these data we have. Hi, and thank you for a great presentation. Could you please just stay on the pancreatic cancer and talk a little bit about the competitive landscape? Because you said it's, you know, not as competitive as in the breast cancer space, obviously, and that's, you know, what was mentioned in the initial talk as well. So if you can just share your thoughts on it. Yeah, no, but I'm not aware of anything which is more advanced than us that we feel is competitive. And I think it's really sad to say this because I would like it to be more competitive, not for us, but for patients, but it is so little in the pipeline. But there are obviously interesting phase 2 programs. But there is nothing in phase 3 that I'm aware of that has, let's say, a major impact on our development thoughts. Thank you. And just to sort of stay on this initial thinking there about the saturation of the breast cancer industry, this being triple-negative, have you... is there any problem in recruiting patients in this... in that indication? It's not quick. So triple-negative breast cancer, it's only a fraction of... so somewhere 10% to 15% of all breast cancer cases, and obviously all of them are not eligible. So it's a relatively uncommon disease and... we do not see the same recruitment rates as we would do in pancreatic cancer. It's... pancreatic cancer, it's almost like we're recruiting quicker than planned. That's not true for anything else we're working on. One last question, Ted, please. Yeah, I try to keep it brief, but it's a difficult one. So... obviously the public markets have been tricky. You peaked out at the end of December 2020, I think, and it's not been that pretty since. If you had any... I think we're all here trying to improve the Swedish ecosystem of life science. If you could give a tip and actually think about the fact that you've made progress, yet it's not really reflected in the share price, would you have been able to... to do better as a private company? And that's a big question. So if I can start very general, I think there are... and Cantargia is an example of that. I don't think we should have become a public company as quickly as we did. But there are lots of reasons behind that. But now the reality is that... It's much easier to attract funding as a... or at least it was much easier 10 years ago to get funding in the public market than in the private market in Sweden. Lots of companies were forced to go in that direction. I think you should stay private as long as you possibly can until you have at least... well into clinical development. Thank you very much,. Thank you. Good luck. Now it's time for Biovica. It's... a bit of a different story than the others here today. Henrik Winther, please. Thank you. Thank you very much. Yeah. My name is Henrik Winther and I'm a Senior Vice President at Biovica, which is a diagnostic company. We are completely switching gear now. I've been in the diagnostic industry for approximately 25 years, mainly focusing on collaborating with pharmaceutical companies in developing these companion diagnostic tests and getting them into the market. So for Keytruda and for Herceptin test and all these tests. As the only diagnostic company presenting today, I guess we are here because we have developed a diagnostic technology that will allow pharmaceutical companies to develop safe and effective oncology drugs. So I have kind of three bullet points I want to touch upon during this presentation. Just a short intro to the CDX playing field, companion diagnostic playing field. And then I'll actually present our own CDX tool. And then I'll discuss a little bit about our market potentials within the CDX field. So CDX playing field, let's start off by what is a CDX? If you read, you know, the FDA terms, a CDX is a diagnostic test that provides information which is essential for the safe and effective use of a drug. That's a companion diagnostic test. High level, you have two types of companion diagnostic assays. You have these assays that are used to or developed to... select patients for a specific treatment. So it's a subset of the patient group that is selected because they are, for example, expressing a certain biomarker and therefore they will benefit from a specific drug. That's most of the CDXs known out there, those predictive tests. But you also have the CDX monitoring test. So this is a test... which is actually used during treatment. It's used repetitively and it's used to make sure that the patient continue to respond optimally to a treatment. So the difference between the two are really that the first one is one test upfront, select, stratify patients. The other one is used repetitively during treatment. So what are the unmet needs that are actually solved by using a companion diagnostic assay? There are multiple. So patients and doctors, they require safe and effective treatments. Which can be partly solved by actually using a companion diagnostic assay to select and monitor patients for optimal treatment. And you have the healthcare providers, they really focus on costs. And it's super obvious that if you select the right patients to treat... then you won't spend... you won't spend money on those patients that are not responding to the treatment. And you will also avoid... that if you don't treat those patients that are not responding, you will avoid actually side effects from these patients. In the US, I think approximately 100,000 people a year actually die from side effects. When it comes to pharma companies, and I've been listening to pharma presentations today, and none of them are actually mentioning, you know, building in biomarkers when they kind of select their patients for their clinical trials. What we have learned... what I also learned in my past is that more and more pharma companies actually do build in biomarkers in their clinical trials to stratify patients, to identify the right patients for their clinical trials, and by that actually achieve better outcome data. Better data in general and data that will actually help them go through the regulatory approval process, shorter development time, and also at lower costs. So because of all these benefits of the CDXs, the national health authorities like FDA, they have established guidelines and or guidelines that actually describe how to develop and also how to implement a CDX. And that has actually resulted in approximately three to four CDXs are released per year. And within oncology, we have approximately 60+ companion diagnostics now on the market representing different oncology drugs. If you look at the market potential within companion diagnostics, in 2030, it's estimated to $8.2 billion. Next one is looking at the CDX tool that Biovica has developed. I know this is way too simple for the audience here, but this is how a tumor is actually developing. So far to the left, you know, you have the normal cells and far to the right, you have a full-blown tumor being developed and cells going through different mutation steps. The first important small mutation is really this cell here now turning into a cell that starts to proliferate. This is the key hallmark of cancers. Biovica has spent 15 years on developing, validating, registering, and latest actually also commercializing an assay that measures cell proliferation. As you can see, also below the cartoon here, we do it in a way that we measure an enzyme, TKa, which is expressed when you do DNA synthesis or the cells do DNA synthesis. This TKa is leaking into the blood below, you know, the proliferating cells. Hence, you know, we can measure TKa or the activity of TKa in a blood sample. As you also can see, we can really pick up very early changes in cell proliferation. We can also, if we were to treat, you know, this proliferation here and stop the proliferation, this would also be reflected in the TKa measurement. It would go down. So we have a tool that is able to really early on detect a tumor growing or responding to therapy. We have some competitors out there. We have circulating tumor DNA, we have imaging, but they are all later on in the growth of a tumor as compared to our technology. Now, what we've also done is, of course, we have applied our assay in a lot of clinical studies. When looking into all the data generated in those clinical studies, it's obvious that we can use our assay as a monitoring CDX. An example is given here where we have used the assay as a monitoring device. Monitoring in this case, metastatic breast cancer patients receiving a combo treatment of CDK4/6 inhibitors and endocrine treatment. It's what I show here is actually representing, you know, two studies, the BioI and the Pythia study. But it's actually also what we see in our daily testing in our CLIA/CAP lab in the U.S. We see that our assay, excuse me, can actually stratify patients into four different responding groups depending on the TKa dynamics. When we measure TKa, when we measure that at three time points. We measure it initially before patients they received treatment, two weeks into treatment, and four weeks into treatment. And what you see here is that we have four different patient types. We have the red patients up there. Remember, a high TKa level is equal to a lot of cell proliferation, tumor growing, tumor not responding to therapy. So what you see here is that, you know, the red patients, they start off high, tumor is growing, they get the drug, not really making any progress. They just keep high on TKa, they're not responding to the drug. And you have, you know, the yellow one here. Patients start high, they get the drug, the drug combo in this case, and they're suppressed, so they're responding to the therapy. But then they rebound. It's 60% of those patients that actually receive this treatment that will rebound. And you have, you know, the purple line here. These are the patients... these are patients that also, you know, start high, get the treatment, no proliferation, low TKa, and they stay low because they keep responding to the drug. Finally, you have a group down here. This is, you know, a patient group that are low right from the beginning. They stay low. You could ask the question whether you're actually overtreating those patients. Perhaps they would not, you know, not need both of these two drugs. So you might actually get rid of one of them and also get rid of some side effects. So... as I said, you know, seen in two studies, published, you know, in those studies, and we also see it today. What is important here is, of course, this group of patients, the yellow group of patients. This is where we see a big interest from pharmaceutical companies because those patients, you need to do something, switch them to a new new drug, perhaps, you know, the next generation of the CDK4/6 inhibitors or adjust, you know, the drug doses, the schedule. So this is exactly what we are doing right now. We are moving into a study together with a pharmaceutical company where the the key eligibility criteria for that company really is patients with TKa rebound. So to Biovica, even if it's just a pilot study, I should say this is a pilot study. But still for Biovica, this means that they're actually using our assay as a CDX monitoring tool to enroll patients in into the into the trial and then follow the patients with our assay. So that's where we are currently, you know, with with our our our CDX tool here. So if I say a few words on the financial aspects of the CDX market with our biomarker, we have kind of a business model where we initially offer ourselves as a service partner to pharma. So we provide TKa testing in our lab, both in Uppsala, but also in our CLIA lab in the US. We also provide expertise on TKa in interpreting, you know, results, but also how to include it in clinical trials. So this is on the service project side, what we're doing. Right now, we put a lot of efforts into onboarding pharmaceutical companies. We have, you know, currently 18 customers. 14 of these are master service collaborators. They're both, you know, tier one, tier two, and tier three pharmaceutical companies. Most of them, which is two-thirds of them, are focusing on CDK4/6 inhibitors or the next generation of CDK4/6. But we also have six companies that are looking at, you know, other therapeutics. And then we have in pipeline, you know, a long list of pharmaceutical companies that we have identified and we have started, you know, the outreach. So after having, you know, been a service provider, you know, we start discussions on the CDX assay development with these pharmaceutical companies. And that's where I said, you know, we have now a pilot study ongoing with a pharmaceutical partner. This is where I have a lot of experience in collaborating with pharma. So I know that it comes with a very, very attractive business case when you work together with pharma on building a companion diagnostic assay because both the development of the CDX assay and the registration will be fully funded by pharma. I also know that sometimes you can have the commercialization of the companion diagnostic assay also funded by pharma because it will differentiate the pharmaceutical product if you have a companion diagnostic assay tied to your drug. So typically, you know, this part up here is, you know, around these, you know, $10 million that a diagnostic company will receive to develop a companion diagnostic. This is, you know, the $10 million is typically if you develop an assay based on a single biomarker. If it's more about, you know, multiplexing, it can be, you know, around the $20 million just to develop a product. So you actually have, you know, full funding of developing a product and you get to own the product. And this about owning the product leads to the last part of our business model. This is the CDX product sales. According to the guidelines, the industry guidelines right now, they refer to, you know, a CDX revenue typically equal 2% to 4% of the drug revenue. In our case, in the Biovica, what I call the Biovica upside is because we are developing a monitoring CDX, which means repetitive testing. The 2% to 4% number is really built on all the CDXs that are out there out there right now, and they are one-off tests, whereas our assay will be a repetitive testing and hence there's an upside on that number. So with the current customers we have in our pipeline and the focus they have primarily on the CDK inhibitors, the CDX product total addressable market would be around, you know, $1.2 billion. Then we have lately actually had a press release around a positive patent notification within immune therapies for our assay. And if we move into this field of immune checkpoint inhibitor drugs using companion diagnostic assays together with that field, we're talking about a completely different total addressable market of $5.1 billion. So where are we now? And in this forum, these are, you know, really, really small numbers. I know I'm from a diagnostic company, so it's completely, you know, different as compared to pharmaceutical companies. I think the message from this here is more about, okay, so as I said, we are building a robust customer base right now, onboarding pharmaceutical companies, signing master service agreements, moving into discussions on companion diagnostics. And, you know, we ended Q3 with a work order book, you know, SEK 8.5 million. Now two months into the fourth quarter, that has actually, you know, increased by another three, a little bit more than SEK 3 million. So we have a really, really good momentum with our assay because of the strong clinical data that we have created and also the new data that pharma is now seeing when they use our assay. So to summarize, what we have and what we offer is a 510(k) cleared, validated assay. This is what we actually offer to our pharmaceutical customers. And this is not seen that often to actually have a validated assay they can use in their research use only clinical trials. We also offer a CAP accredited and CLIA certified lab in the U.S. where we can perform the testing for pharma. We have solid clinical data demonstrating that it actually works as a CDX tool. We have 14 signed master service agreements with different pharmaceutical companies. Then lastly, you know, I also presented here, I think, an attractive business model collaborating with pharma and also an attractive or significant market potential. Thank you. Please go ahead. Thank you for a very interesting presentation. But I mean, your concept should be very attractive from a payer's perspective because we spend a lot of money treating patients for maybe three months before we evaluate them. Here we can basically throw out an ineffective treatment within two weeks. Yeah, no, absolutely agree. And that is certainly also something we are, you know, discussing with payers. Yes. The second thing, we have a different climate in Europe and the US. We talked about that in the coffee break because in the US, you have a clear link which specific CDX you should have for a drug. That's not the case in Europe. Do you have an explanation for that? I think the regulation in the U.S. is about to change. We know it is about to change. Some are even saying that the regulation in Europe is going to be more tough than in the U.S. Let's see, you know, what happens when the guidelines arrive on our table. Okay, thank you. Thank you so much for an interesting talk. Besides what Nils said here, I also see an opportunity to, from the beginning, select the right treatment for the patients. I mean, today, for instance, treating hormone receptor positive breast cancer patients, we usually treat as a first-line endocrine therapy with CDK4/6 inhibitors. And if you use such a method, then you could maybe choose patients that would respond only by endocrine therapy and save them first a lot of side effects. The CDK4/6 inhibitors are toxic to a certain degree and also save a lot of money for the healthcare. Yeah, no. So this also could be a very important... Yeah, no, I agree. ...from a clinical point of view. Indeed, yeah. Cecilia, please. Thank you for a great talk. This might be my lack of knowledge, but today, you know, we usually use CA 15-3 to monitor patients with breast cancer. Could you just say something around, have you compared with that? I guess it's a less sensitive test, but please, could you just... It depends on which one you say is less sensitive. CA 15-3. Agree. I would agree to that. Yeah, yeah. But could you... because I think it's a... Yeah. That would be the one that you would compete with the market. I would love to, you know, present some data where we have really compared the two biomarkers head to head and in a fair way. We haven't performed that test. We know that CA 15-3 is not the really preferred test out there because of the lack of sensitivity and other issues. I guess that's where we are currently. Thank you. Yeah. Just a short one. Do you have any comment on IU and what we call pseudo-progression with your marker? I mean, we sometimes try to don't pay attention to the first evaluation and we see patient progressing, but they're still in the end responding. Could you repeat that, please? What has been described, especially in melanoma, is what we call pseudo-progression that you initially see. Can you see any pattern in your analysis? Not that I know of. I would need my clinical team to answer that question. Yvonne. So I'm sitting here thinking, knowing very little about diagnostics and even less about oncology. Hence the invitation. But as I understand it, your main competitive edge is early detection. But today, we don't have big screening programs. So I question to the clinical panel. I assume patients are, apart from in the screening programs, they are detected because they got metastasis and get problems from them. So your edge is to work in the other area. So how are you going to get hold of that market where you actually have a competitive edge compared to all the other later stage technologies? Yeah, I think. I mean, so there are actually two things, you know, that we are trying to promote. I mean, one is, yeah, the early detection. That's one thing. I guess the other part is really the monitoring capability of the assay, really to detect early response or lack of response to a therapy. It's not the actual, you know, early diagnosis. It's more. So when I was using the cartoon up there, it was more to illustrate that even small changes in tumor or cell proliferation will actually be registered by our assay. So that is, you know, also during drug treatment. We're not into the minimal residual disease, you know, area with very, very early detection. We don't have the data there yet, at least. I guess we have the clinicians here to answer. Would you use this tool in your clinical practice? I think it would be very useful to use such a marker, especially in endocrine therapy. It might be that if you use chemotherapy, that it will have a different pattern. But in the endocrine therapy, there is a very clear pattern, as was shown here. I think some data in when you use chemotherapy shows that there could be an increase immediately, and then you see the same pattern, but you don't see it as clearly as with the endocrine therapy. That's correct, Sam. And actually, you know, with other drug types, for example, you know, the immune checkpoint inhibitors, it's also a different dynamic pattern we are looking at. And that is actually what we have, you know, patented because suddenly, you know, you're not necessarily only looking at the tumor cells. You might also be looking at the immune system and the proliferation in the immune system. So it's a different pattern we see and opens up, you know, for possibilities on algorithms. Thank you very much, Henrik. Okay, thank you. There we go. So last session of the day is always a challenge, but I would like to thank all of you who are still here showing interest and being curious about Oncopeptides. So my name is Sofia Heigis and I'm the CEO of Oncopeptides, which is a small biotech company. And we are focused on research, development, and the majority of time we currently spend on commercializing our first drug across Europe. We were founded all the way back in 2000 and listed on NASDAQ 2017. We've been on a bit of a journey. Today, we are 75 people and a growing company. The majority of our people are located here in Stockholm, in our headquarters, but also in our research facility in Solna. But where we are growing the most is across Europe. My talk will focus on our European commercialization journey because that's the core of the company and that's what we're building the company from. But we obviously also do have a pipeline. We have two different platforms that we are progressing in preclinical. We also have commercial opportunity outside of Europe that I will just briefly touch upon. But if we look at our European commercialization case for Pepaxti, which is our first product to market, we are addressing multiple myeloma, which is still an incurable disease, and we do see an expanding market opportunity. The current market potential for Europe alone is estimated to SEK 1.5 billion. And that is not the total value of the market. I would argue it's the addressable and very realistic potential that we could grab with Pepaxti. Pepaxti is fully approved in Europe. That means we have no regulatory risk left. We have no post-marketing commitments. That is, we have no large investments we need to do into clinical development. But the evidence generation we are doing is to support the commercialization of Pepaxti. And we are approved in a late stage population where there are very few treatment options left. We have exclusivity in Europe until 2037, meaning that we have quite a good amount of time to generate value for both patients as well as our shareholders. We have just planted the seed of our launch. So we're currently selling at low volumes. We started last year. And I will share more about how we're progressing. But in brief, we're selling in Germany. And we have found a way to sell from Germany to Greece. We are working hard to unlock more markets. I will show you the roadmap of how we're going about. We are looking forward to an opportunity of highly profitable business where we aim to become profitable in 2026. We have actually just announced a rights issue that is fully guaranteed and that will take us to profitability. If we're looking at our European commercialization plan, of course, profitability is a matter of both cost and revenue. So there are two sides of the coin, and we are working actively with both. Our highest priority is, of course, to accelerate revenue, reaching sales of EUR 400 million in 2026 for the full year, which will make us profitable. To get there, we need to unlock the markets in our first two launch phases. I will speak more about that. So to this case, we, of course, have an upside should we unlock more markets that we have planned on launching a bit later than this period. But also, if we manage to commercialize and generate deal value or some revenue outside of Europe, that's also an upside to our case. And our current focus there is in terms of regulatory approval and market access to find a partner and to go full speed ahead in China and Japan. We already have active discussions with regulatory authorities, and we also have a number of partners that we are engaging with for those geographies. For the rest of the world, we have decided to focus and initially prioritize named patient sales. That is, we allow patients to get access to Pepaxti, and we distribute from Europe with a partner facilitating that mechanism in the different geographies. We just recently announced a deal with the World Orphan Drug Alliance and one of their partner companies, Vector, for Middle East and North Africa. That's the first step we're taking outside of Europe. Named patient sales is always a limited potential to start with, but we believe it's a clever strategy when you have limited resources to start in that manner because then you act with little resource. You have a quite clean commission fee split between the partners, and you can also then assess and explore whether it makes sense to go for full entry into the country based on the demand and the perception of the product. We have a strong research organization that is primarily working hard on pushing forward our two pipeline platforms in preclinical. We have a couple of more peptide drug conjugates that are soon ready for the clinic. Then we have an NK cell engagement platform where we are currently selecting our first candidate drug. But otherwise, we are not investing any further in any large trials for Pepaxti because it doesn't make sense based on the position we have. That is a very clear and focused position. So, rather than focusing on generating evidence such as real-world evidence, we are sponsoring investigator-initiated trials to look into further hypotheses that we actually could use for our other pipeline compounds of PDC. When it comes to the cost side then, I said it's important to consider both to accelerate revenue and also have a sound cost base. And we had the opportunity to really build Europe from a blank paper because we had little heritage given that we had to start all over again once we got our approval in Europe. That means that we have been able to really look at what's needed within the countries and what can we actually support with from Sweden, which is a fairly cheap market compared to putting resources, for example, in Germany or Switzerland or Italy and Spain. We are operating with a true local model where we have resource gathered in Sweden to support the countries. In the countries, we have a very competent local team that is needed for the stakeholder management and the access, etc., in the country. We are not, even though we are opening entities out in Europe, we are not building full-blown organizations because we don't believe it's needed at this time point. In that sense, we can have a sustainable cost base over time. Taking a step back, what is key to a successful commercialization in rare disease? I have a background from AstraZeneca. I've launched more than 20 products across many different countries and geographies and across many different disease areas. Rare disease is special in itself. Obviously, when you launch in rare disease, it's important, given that there are very few patients compared to other therapeutic areas, that you really have a product with a specific position that addresses a high unmet need. I will tell you how our product is doing just that. It's, of course, also important to have a good medical understanding of your product, to be able to identify the right patients and get a positive clinical experience. I would argue, based on the experience we had in the U.S. where I was part of the launch, but also based now on the initial launch in Germany, that we know very well how to do that. But we still have a work to do in some of the European markets, in particular, where there has been little awareness about us. To generate that awareness, you, of course, need an organization tailored exactly to those needs. I've already been touching upon our business model. What I can share is that we today have a full team in place in Germany, which is our first launch market. We are building in Spain, Italy, Netherlands. We also have a very lean resource for Nordics. Looking then at the disease and unmet need that we are addressing, so multiple myeloma is a disease that is diagnosed in patients that are on average around 70 years of age. You get a treatment, you can get a transplant or not, dependent on your profile. Then you hopefully stay on treatment for a while without progressing, but at some point you will progress and relapse. Then you enter the second line of therapy that lasts hopefully for some time, and then you progress. This is how it goes about. Commonly, the tumor becomes more and more aggressive. Pepaxti, our product, is indicated in patients who got three prior lines of therapy and who already exhausted the options of the most common drug classes. The reason why I'm mentioning this is because multiple myeloma, luckily, there have been many drugs launched just recently. There are a lot of different combinations being studied, showing good efficacy results. There are also quite a lot of immunotherapies being launched currently. All of the drugs are commonly always launched into the later lines, and then they move up front. So right now, looking at Germany, which is the best example in Europe of a market where you have access to almost all the drugs always, it's a very interesting dynamic because there are so many different combinations to choose from up front. You have CAR-Ts that are moving up front. And in the late lines, you basically have the choice either of bispecific antibodies that can be very efficacious for the patients who can access, tolerate, and get the right efficacy out of those. But otherwise, you have to go either for some conventional calculation or cytotoxics. And if you are refractory to the most common drug classes, you can, of course, try to rechallenge if you wish. But there is certainly a need for a new mode of action. If we look at the need, these are three of the experts that are commonly investigators in the large trials. What they testify to and what we also hear a lot is that once you enter this phase of the disease, you've had a lot of side effects from your treatments. Your tumor has become more difficult to control. And that is, of course, impacting your quality of life. And that is where we can really make a difference. And we have a strategy to stay very focused on this segment because there is less competition here, and you have the ability to keep your price higher across Europe in this space. So rather than trying to go earlier, up front, having a lot of competition, maybe being able to grab a very small market share to a much lower price because the prices are really pushed down in that setting, we have decided to continue to work with the highest unmet need at the higher price for every treatment cycle. And so what is Pepaxti then? Well, let's keep it simple. Pepaxti is an improved cytotoxic drug. That and cytotoxic drugs are known for being very powerful. They are known for also being difficult to tolerate if you raise the dose too high. So you can use low-dose cytotoxics, but to have a high-dose cytotoxic at this time of the disease, you can try it, but you can commonly not get a very long duration of treatment. Pepaxti is addressing that issue because it's a very clever mode of action or actually distribution that activates or cleaves off the cytotoxic part of the drug inside of the cell, and it stays at large inside of the cell. This is happening more in the sick cells than in the healthy cells. So this means we have a very high concentration of cytotoxic inside of the tumor cells for certain tumors such as multiple myeloma, where we are launching currently, but we know there is also potential in other tumor types. And with that, we can control the tumor with the clinically meaningful efficacy that we've seen in our studies while it's manageable and fairly tolerable. This is showing then, if we look at our published data, that we can sustain the quality of life of this patient, which is really important when you come to this stage of the disease. Moving then over to our launch sequence. We have a quite simple, but I think important principle here, and that is to move into the markets as fast as possible, but with a speed that allows us to keep a price that's reflecting our innovation across Europe. Based on that, we have built a launch sequence where, as I said, in the first phase, we already have the ability to sell. So we have the German-speaking region where we are focused on Germany, and we're also now initiating some efforts in Austria. Then we have Greece, actually, in this phase. That is due to that, as we are operating in rare disease, we have found a way to get an authority in Greece to distribute the drug based on requests from Germany. We have a partner in Greece that is facilitating this, and we have a lot of investigators from our clinical trials in Greece. The reason why I'm telling you this is twofold. First of all, it shows you that we are here to find innovative and creative ways of entering the different markets and t stick to this principle that we have set up. Because if we would go for regular market access in Greece, we would have seen parallel export at a much lower price from Greece to the other markets, and we would have diluted the price across. In this manner, we keep the price up. The second reason why I'm telling you this is because it shows the demand for the drug with clinicians that have used the drug. Obviously, people can look at Pepaxti or physicians, patients, whoever can say, but what's the innovation here? Isn't this just a cytotoxic? The confidence that I have, and actually the reason why I joined the company, is because I thought this is clever because it's giving a positive clinical experience. There is no overpromise, but you rather see a positive surprise when you use the drug. That's exactly why we are selling in Greece, because the investigators are demanding the drug based on their experience. That is also what we see in Germany with the clinicians that have started to use the drug. These two phases, or the first phase together with the second phase where we are working on market access, where we have Italy, Spain, Nordics, Netherlands, and Ireland, will take us to profitability. If we would unlock access in France, UK, or Central Eastern Europe, that would be an upside to our case. Just to double-click on Germany, I said that we have just started to sell at low volumes. And why is that? Because we got our approval back in 2022. Well, at that time point, we basically had no people. We had no organization. We had managed to prepare a value dossier to submit in Germany. And that's based on where we came from, and we could not invest until we actually had our approval. But we started to work very hard to build a team, which we did last year. With the build and, of course, the partnership in Greece, we also could see a positive growth of sales, even if at low volumes. We managed to negotiate a price in Germany within our year, which is not to be taken for granted. The price is EUR 7,000 per cycle, and we are considering that to be a good price. We increased the spontaneous awareness, and what is making me most happy is that we see a really positive clinical experience. We also started to prepare a real-world study that will capture this experience, and that study, we have the first sites initiated now. Looking then at the rest of Europe, where do we stand? So if we look at the market access process, you move from value dossier creation and expert input to price negotiations, basically. The countries in our first launch phase are currently in cost-effectiveness benefit discussions with authorities or have moved to price negotiations. The next country in plan is Spain, where we actually, in just five months, managed to conclude and get a positive pricing opinion. If we look at our competitors, it took one year or two years for them to conclude. So I believe that this is a testament to both our competence, but also our strategy in how we fit into this landscape. When it comes to Sweden and France, those countries are part of the later phase. In Sweden, we don't have basically any experience. We are not falling into the national authority reimbursement system. But we are discussing with regions to see whether there will be a potential for negotiations with regions. In France, we have been working with the experts to find the right position for the French landscape, and we are soon to initiate the second phase in France. This journey of commercialization of ours, as I said, is now fully financed, which feels, it's I think it's really positive for the company because it's stabilizing the company, in many ways, that we can now move full speed ahead and just focus on becoming profitable. We've done that through a decision to carry out the fully guaranteed new share issue of SEK 314 million. We just announced the terms the other day. To summarize, we are working with an incurable disease. We have an expanding market opportunity, and it's expanding because, of course, with a lot of innovative treatment and options in the earlier lines, more patients are moving to the later line setting. We are looking at the current market potential of SEK 1.5 billion. We are fully approved in Europe. We have no regulatory risk. We have no development risk left for Pepaxti. We are looking at the segment in the late stage with very few treatment options left. We have just started to launch, so still selling at low volumes, but looking forward to accelerate, where we have initiated the sales in Germany and Greece. We're looking forward to start to sell in Spain the second half of this year. We are looking forward to the opportunity of a highly profitable business in 2026. By that, I would like to say thank you and open up for questions. Thank you very much. Do we have any questions? Bengt, please. In the price discussions with the authorities, do you get any questions to have a direct comparison with melphalan? Initially, yes. I think it's their duty to try to compare to melphalan. But so far, we have managed to make them understand that it's not fair to compare to melphalan. So we have never ended up so far with a direct comparison with melphalan in the actual price negotiations and the list of comparators that we have seen. Just a short question. I didn't follow your German experience, but do you expect to have the price kept at that level? Even after the evaluation, I'm not sure how you avoid the clinical evaluation in Germany. So we have been through the clinical evaluation, actually. And we concluded as most, many drugs do, no additional benefit. But still, you know, it's a special methodology and technology that they are using. I think that we have a very well-equipped team to understand how to work with that. What we ended up with was a physician's choice basket of drugs and a price comparator based on that basket. Then we managed to show the value and have a fruitful discussion and negotiation based on that. We have already been through that. Yes, we do expect to keep this price. Okay, congratulations. Thank you. That it's a tough exercise, and I'm really proud that we managed to get through it. Great, great talk, Sofia. I thank you very much. Presumably, safety comes up a fair bit for your representatives when they speak to stakeholders. How do they typically handle that conversation? Yeah, so, I assume you're also pointing towards the U.S. and the FDA, safety warning alert. The side effect profile of Pepaxti is very clear, and it's actually quite clean if you may say that the side effect profile is clean. Because if you look at the most common side effects, it's cytopenias. Cytopenias are well known to hematologists and how to manage them. We have a comparative trial versus pomalidomide dex, which used to be standard of care, and there we see almost half the number of infections, which is, of course, something that is welcome in this quite frail population. When it comes to the clinical sequelae of the cytopenias, that is bleedings and infections, we do have, you know, we don't see that really in our studies, and we also don't see that in the real world so far. So, yes, it's a question that pops up, and it's an objection we need to manage. When the physicians, you know, read up, and in particular when they use the drug, they are commonly very, I would say, positively surprised. Harald? One final question. Use an alkylating agent, the patient might end up in prolonged, lifelong bone marrow suppression. Have you seen any such side effects? And if not, why not? Because it's seen we see that in every alkylating agent. Yeah, so we have long-term follow-up data on our OCEAN phase III trial. And yes, we do see cytopenias, which is bone marrow suppression, but we don't see the sequelae of those. And we do see, I mean, if you look at our patient population, the average number of cycles that we are counting on, also in our financial projections, is four treatment cycles. So it's, of course, a fairly short duration of treatment, and these are late-stage patients. But if you ask me about the long-term follow-up, we see cytopenias, but we don't see any clinical sequelae of those during the treatment period where the drug is used. Please. So this, thank you for a great talk, by the way. And obviously, this is a bit of a different animal than the rest of the companies, being more of a commercialization effort rather than a clinical program so far. So what's your sort of key risks to this sort of European expansion with the potential to go east, if you will? Yeah, I think that's probably the beauty of the investment in us at this time point, because given that we have the regulatory approval, that we have no post-marketing commitments, the key risk is that we wouldn't succeed with our commercialization and that we wouldn't be able to negotiate prices. Now we have proven that we have been able to negotiate the price in Germany that is sustainable for us. We have released, as I said, that we have agreed upon a price in Spain, which is commonly also very difficult and takes a very long time. By that, I hope I bring confidence to our shareholders that we have both the strategy and the competence to achieve this in more markets. But that's the key risk, that we wouldn't be able to access some of the key markets where we've already unlocked two of them. Thank you very much, Sofia. Thank you. Could we have some closing remarks from our panelists? Are you hopeful after hearing all these companies? Göran? I'm very hopeful. Great. And I say that because it's quite impressive to see these companies stick together and seeing that there are clear patient benefits being demonstrated in not early, but relatively advanced clinical trials. But I'm also concerned because there isn't enough money to make sure that all of these companies grow up to be the next Astra and Pharmacia. There's no pharmaceuticals anymore. And there's only one out of three sites of Astra in Sweden. That's where all of we were trained. So where's the next generation going to be trained? So I think it's very promising to see all these results. And I want to hand over this question to maybe one of the Lund CEOs to respond to. What should we do in order to get you the money you need? Göran. So where to start? So obviously, there has to be more funding. I guess, Johan, you have to be more successful to raise more money. I also think that there is lots of innovation in Sweden. I think lots of these companies have, let's say, been financed through retail. We need also these Swedish institutions to take part of this journey in a stronger way. It's not that we're not doing it, but I think more can be done here if it's going to be sustainable. The other thing is also we need to be visible in the United States and in the areas where it can get good money and make sure that it's attractive for U.S. funds to come here and invest. First of all, thank you for very good presentations. It's been impressive. I have a question also, not from financing, but do you feel that the clinical environment is the right in Sweden? I mean, there are very few institutions that have phase one facilities, et cetera, et cetera. And it's been a struggle to get these institutions up and running. So I believe that sort of the clinical environment locally for development of new drugs is not really top-notch. Can I answer that one as well? It's one of my favorite topics. I would love to say yes, but among the 300 patients we treated, we treated patients at one clinical center in Sweden, which was Karolinska. The others, I think we got approval to start in one site, but at that point in time, the trial had already finished recruitment. And then there were a few others where we had to go through various web-based pages to start to make all the applications to create an interest. And we never got any replies. I think it hopefully has become better, but I think Sweden is lagging behind, unfortunately. What is the reason for that, do you think? I think it's a political reason, but I'm not sure I'm the right person to step into that debate. I feel that there are one country which I think is really good, is Belgium. It's very easy to go ahead and do clinical trials. The Belgian authorities at least have been very responsive. Now we have a European initiative, so everyone is, let's say, from a regulatory point of view, handled in the same way. But it used to be really, really good. There are lots of academic centers that are more or less designed for clinical trials in a way which I don't, unfortunately, see here. It's very interesting because maybe 20 years or 30 years ago, everybody was talking about the good situation in Sweden for clinical trials. Everybody wanted to perform the trials in Sweden. Those trials were considered very reliable, very good performance, and so on, had a good quality. May I interject? It seems that times are changing. Well, first of all, I'm probably the rara avis here because I represent Spain. I would say that the question of how we fund the new generation of the pharma companies, not only in Sweden, all around Europe, is a bit the same. This is an industry which is based in science. It's based on performing good clinical trials. It's based on very strong financial fundamentals. I think that we have a sort of challenge in Europe to stop a silo thinking. I mean, in our case, we are a small company. We have run quite a number of clinical trials. We have been running clinical trials in England, in France, in Germany, in Serbia, in Bulgaria, I mean, in the U.S., of course. We try to do the clinical trials where there is the best access to patients, where there is the best specialists, and so on and so forth. Spain is a very good country to do clinical trials. But we have, for instance, probably the lack of a more refined or sophisticated financial community. So I think that we can leverage across Europe on the strengths of each other and try to benchmark. So I'm sure that the clinical possibilities or options here in Sweden would be great if the problems that you might recognize, you benchmark in Belgium or in Spain or in, I mean, it's not inventing the wheel again. I mean, it's basically to have a political will. But my reflection here is that we are competing against the U.S. We are competing against China. And unless we develop a new way, more dynamic, more interconnected way of pushing the new clinical products, we are going to suffer. That's my reflection. I would like to add one thing because I'm not completely negative about us being have to go to other countries. I think we learn a lot by working together in a global this is a global business. And we cannot stay local because we will never be competitive. So I think it's really important that we are forced to go out. But I hopefully Sweden will attract more inbound or, let's say, trials from the outside. I just think that being working in the healthcare system on and off, I would say, because I've also been in pharma a couple of years, the environment, the working environment had changed huge, I would say, the last 20 years. Today, when I started as an oncologist, there was much more focus, including patients in clinical trials. I never worked in Karolinska and Gothenburg, but we were all aware of where we could send the patients for phase one, phase two studies. Today, what we are doing is survival. We are putting down fires every day. We are trying to treat our patients. There is no focus at all on clinical trials. It's just about putting down fires and trying to survive day by day. That's how Swedish healthcare is actually working today. It's terrible, but that's the truth. Another change. When I started as a physician, the head of department was a professor. The head of the hospital was a professor. Today, there is no academic physician leading the clinic or leading the hospitals. This is a quiet change. Please. I believe there is a light at the end of the tunnel because after 20 years, we now have three comprehensive cancer centers in Sweden: Lund, Gothenburg, and Karolinska. They are obliged to have a clinical development or also early clinical trials, et cetera. Finally, we now have sort of a pressure on these institutions to be in the front line and work in the front line. It spins such a long way there, but we're finally there. So I think there is hope. Could we perhaps end at those positive before someone says anything negative again? No, but I also want to tell you that when we made this seminar, we reached out to a lot of clinicians. And we've had many clinicians who wanted to participate. So next time we do this, we will have even more clinicians. And I think, Lars, that we will add politicians as well so we get some push. Thank you very much for coming.