It is 3:00, and we are live here from SynAct Pharma's Capital Markets Day. Today, we will hear from the company's management, including Jeppe Øvlesen, who is the company's CEO, Thomas Jonassen, who is the company's Chief Scientific Officer, Mads Bjerregaard, who is the Chief Business Officer, as well as Anne-Christine Lade, who is the CFO of the company. We will also hear from external speakers. This includes Professor Philip Conaghan from the NIHR Leeds Biomedical Research Centre, as well as Professor Thomas Benfield, who is from Copenhagen University Hospital. Leading us off here today, I have with me Mads Bjerregaard, who will be leading us off here in the Capital Markets Day. I will simply hand over the word, and I will return during the Q&A. Fantastic. Thank you very much. I will quickly run through the agenda for today. We have done this in buildup in several sections. The first section is gonna be on our autoimmune disease items with focus on rheumatoid arthritis, where you're gonna hear from external speakers and from Thomas and me, and we're gonna have a separate Q&A on that topic. Moving into the second module, which is focused on our host-directed therapies with focus on respiratory infections. We're gonna do the same there, hosting a separate Q&A at the end of that section. A little more than an hour and 45 minutes from now, we're gonna end with more on financial business development and finalize the meeting. With that, I wanna introduce Jeppe Øvlesen, our CEO. Yes. Thank you very much. Great to see you all here in the room. Nice to see that so many of you have taken the time. Also, thank you very much for your joining on the web. Nice to meet you all. Jeppe Øvlesen is my name, and I would like to start out just doing a little bit of a corporate update on where we are with the different programs and where we are with the company as such. The rest of the team will go into details on the specific issues and topics after that. Basically, as many of you know, we have made a lot of progress in the ADVANCE study, our lead project. We have finalized recruitment some time ago in more than 240 patients, a little bit more patients than we expected. That's good. We have now a follow-up period, and that leads us to believe that we'll have data on that study in June. That's a very important milestone for us, and it's also in a very nice timing. We are going to BIO International, which is on the 23rd of June in the U.S., which is the biggest partner event in the world for that kind of deals. We are going with a full focus on business development in that track. As many of you know, we launched a dual strategy last year where we still have the IA program as our lead. We have developed two tracks, basically, where we are focusing on viral infections. We have just initiated a study in Europe. We have also a study within dengue, and that study has been initiated in Brazil. We are just these days waiting for the first patients. Two very important programs. The good thing about them is that they're investigator-driven. That means that we can drive projects into phase two at a very low cost, and it gives us quite a bit of value. At the same time, it's also de-risking the company and the pipeline a bit, but very nice indications with big business potential. Very good for us. TXP compounds, we are moving forward. We have ticked quite a few boxes last year, and we are going to tick a few more boxes this year, making the project phase one ready. We look very much forward to push that one. Big opportunity, again, big potential in terms of business development. Just to sum it up a bit, we are basically getting over the next two quarters a lot of data on the first three indications, which is going to be a major value driver for us. Transforming basically the company from a little bit of a waiting position into action. Those activities are sort of the main drivers for us, being able to do business development. Business development we have talked about also in the past, but really becoming key focus now. We have a lot of potential partners waiting for data, and I think without promising too much, on good data, I'm pretty sure we will be in a position to potentially do a deal. It looks good. Thanks to a lot of you investors, we are also in a nice position financially. We are well-financed into Q3, and it is a very nice feeling. It puts us in a position where we don't get our back against the wall in deal-making, and that is quite critical for us. That's why we have conducted these three, four successful fundraisings during the last 18-24 months. We are very happy with that situation, and it's simply coming out of strengths. It's not in any way a backup strategy, but it is simply because we wanna be well-equipped for doing business development, and as a biotech company to say that we are financed well into Q3 2027, is rather important for us. You can be sure that the partners that we are in discussions with, they will know exactly where we are, and, as said before, we don't wanna have our back against the wall in optimizing on our lead project. That has been the reason. We have strengthened the management substantially here lately. Mads got on board as a CBO, focusing entirely on business development, and we were lucky to recruit Anne-Christine Lade as our new CFO here lately. The good thing about her is that she knows a lot about financing, obviously, but she has also been involved in quite a lot of deal-making in her past career. I would say we are in shipshape. We are definitely ready, and I think we are well-positioned to optimize on things. Thank you. Thank you. With that, we're gonna start on our first module, which is gonna dive into our autoimmune program with rheumatoid arthritis. Forward path here. One is we're gonna hear from an external speaker. I'm gonna introduce Dr. Conaghan in two seconds. Then, Thomas is gonna give you the latest and greatest in what we know in terms of how our drug works, the mechanisms, and how our trials are going. Then I will provide the kind of the market overview and the deal scenarios that we're looking into what's happening in the field of autoimmune disease transactions. That's obviously where we are heading to. Then, top of the hour, we are doing a Q&A. We're gonna be fairly strict on timing, that we're gonna end at four o'clock with that Q&A, because otherwise we'll not make it for the other one. Professor, I'm gonna introduce Dr. Conaghan. I have my cheat sheet here to make sure that I get everything with me. Philip Conaghan is Professor of Musculoskeletal Medicine at University of Leeds and Director of the NIHR Leeds Biomedical Research Centre. He's an internationally recognized expert in arthritis and inflammatory arthritis and has authored hundreds of peer-reviewed publications, contributed to international clinical guidelines, and hold leadership roles in major global rheumatology initiatives. We are delighted to welcome here today. It's a pre-recorded speech that's gonna last around 12 minutes. It's gonna speak about the medical unmet needs in rheumatoid arthritis. With no further ado, here we go. Thanks for joining my presentation today, which is going to overview this rather devastating disease called rheumatoid arthritis and let you know current strategies for our treatment of rheumatoid arthritis. What is this disease? Well, there's a couple of hundred different complaints that rheumatologists see, but probably the best known and the commonest of the immune inflammatory diseases is rheumatoid arthritis, and we still don't know what causes this disease, but we know certain things like smoking predispose people to risk, and we're starting to understand the reasons for that, how smoking can affect the microbiome in our teeth, lead to production of anti-citrullinated peptides like anti-CCP antibodies, and these are key steps in breaking down the immune system so that it starts to attack our joints. It's a whole body disease. It affects all your joints because they're all lined with this smooth layer of tissue we call synovium, and when we examine patients, we're looking for synovitis or inflammation of that joint lining tissue. It affects women more than men. It can have any sort of onset, an acute or an insidious onset, but generally people have prolonged morning stiffness in their joints for more than an hour. They're also associated because the inflamed joint tissue is producing the same chemicals and flu as a flu. Anybody on the call will know that having a cold or COVID, you feel quite rubbish, and that's the rheumatoid arthritis feel that people have. They not only have joint pain and swelling, they feel very unwell, and this disease does not tend to remit spontaneously. It carries on for life. Here's some images of somebody presenting with rheumatoid arthritis in the hands. It tends to affect your big knuckles and your middle knuckles first, and after a while, the inflamed tissue around the joint starts to eat into the bones and ligaments. So we get deformities in the ligaments, as you can see in the right fifth finger here where you've torn some tendons due to rheumatoid arthritis. On the X-ray on the right, you can see little bits of bone nibbled away that we call erosions, and hence why this is called an erosive arthritis. It gnaws away, eats away at joints. Here's some more graphic images. At the top is an arthroscopic view of a knee when we're looking inside. Normally, the lining of the tissue would be smooth, a couple of millimeters thick and look a bit like cling wrap. Here you can see it looks like aggressive shag pile carpet growing across the surface of the joint. On the right here is an ultrasound image of the joint, and here we see some inflamed tissue lighting up with increased blood flow. In the bottom ultrasound image, you can see a hole in the bone in that sonogram image. Indeed, here's the head of a finger joint and finger knuckle, where you can see there's a real hole eaten through the bone. This wasn't a figurative hole, it was a real hole where the inflamed tissue was eaten through joints. This is a terribly destructive arthritis if left untreated. Now, how do we treat rheumatoid arthritis? Well, we've always used a combination of drugs and non-pharmacological therapy, such as physiotherapy and exercise, which are really important. In the last 20 years, we've learned not to escalate slowly our drugs, but to start pretty immediately on diagnosis with drugs we call disease-modifying antirheumatic drugs, or DMARDs, and to then maintain inflammation as much as possible. That means seeing the patient regularly, examining their joints, doing blood tests, and monitoring how active the inflammation in their body is. Now, what drugs do we use? Well, we've had anti-inflammatories or NSAIDs and steroids for many, many years, and we know that they help symptoms short-term, but they're not disease-modifying, and they carry lots of side effects. Then we started to use in the 1980s and 1990s a drug called methotrexate, the commonest drug used around the world for rheumatoid arthritis. It's a drug that patients can tolerate at low dose, and there's other drugs like Sulfasalazine and Leflunomide that we also use for initial drug therapy. If those drugs aren't working very well, we then move on to a range of biological DMARDs, which we've had available now for about 20 years. The TNF inhibitors were the first drugs. These are drugs that target a particular molecule that's driving the inflammation. Tumor necrosis factor, or TNF, is one of those molecules. Along came other drugs like tocilizumab, which is an anti-interleukin 6, rituximab, which targets B cells that are producing antibodies driving this process. Costs of these drugs came down because we developed biosimilars for many of these drugs. In the last 10 years, we've also had some oral molecules. The others are all given by subcut injection or intravenous infusion, and the targeted synthetic disease-modifying drugs called JAK inhibitors are small oral molecules. We've gone back to having some oral therapies we can give. These drugs work intracellularly to have the same effects as the extracellular TNF inhibitors and other drugs. Now, the only point of this slide is to list those drugs, but what I wanted to show to you is it's a constant balance for us when we're prescribing drugs to have a look at benefits and risk. You can see steroids are a drug, and I've got a particular wish that we reduce the amount of steroid use we're doing. Recent surveys we've done in large databases suggest about 10% of people are staying on steroids when they start on them, and these are associated with a lot of long-term problems, including weight gain, diabetes, hypertension, and osteoporosis. Steroids are generally supposed to be used as a bridging short-term therapy, but a lot of people stay on them. Lots of side effects associated, especially over time. We've got methotrexate, our sort of standard first-line therapy. Methotrexate is not well tolerated by about 30% of people. For the others, we do a lot of blood monitoring, looking for liver function abnormalities or bone marrow suppression. At high dose, Methotrexate is a chemotherapy agent used for cancer, but it's well tolerated at lower dose, but some people don't even tolerate it at lower dose. Sulfasalazine and Leflunomide, similar gastrointestinal side effects. Sulfasalazine's got rash problems because it's a sulfur drug like the original antibiotics were, and leflunomide can have quite a lot of gastrointestinal problems, including diarrhea. Drugs that we use a lot but require quite a lot of monitoring. We've got the biologics. The biggest problem across all the biologics, and this is just the TNF inhibitors, where the biggest problem is infection and risk of infection. When we're starting people on any of these drugs, we always do tuberculosis screening. We have to for all patients to make sure there is no reactivation of underlying tuberculosis, and we also have to be careful of some other conditions. Demyelinating syndromes and MS is a contraindication for these drugs and people who've got heart failure because TNF is important in certain functions in the heart. Useful drugs, very good at treating rheumatoid arthritis, but we're always screening patients to make sure they're suitable. Our other biologic DMARDs include Rituximab, the Anti-B cell or Anti-CD20 drug. Again, we're looking for viral infection reactivation, especially Hepatitis B, so we do hepatitis screening for people starting on these drugs. Again, there's some rare immune neurological problems that we look out for. These are given by intravenous infusion, so you need an infusion center for giving those drugs. Abatacept is now subcut or Intravenous. It's probably safer than some of the others, but again, we have to watch out for tuberculosis and do our screening. For Anti-IL-6, there's a small rate of colonic perforation. Again, this is something we will have to watch while we've got people on treatment. There's no screening we can actually do for that, and it's not uncommon to see liver function abnormalities that require dose adjustment. I think you're getting the feel. All these drugs, very good, but come at a price. Lastly, our oral JAK inhibitors or the oral disease-modifying drugs. Here we've got some other worries for these drugs. They're all associated with increased risk of herpes zoster, so we've gotta look at vaccinating patients, and there seems to be increased risks of Venous thromboembolism, especially with Tofacitinib and perhaps Baricitinib, the older of the drugs. There is risk of cardiovascular events and neoplasms, especially in smokers. We've got some concerns about using these drugs in older people, especially with previous DVTs. What I'm coming to here is this is what mostly modern medicine is about, is balancing this, risk-benefit all the time. What's our strategies? When we see somebody with rheumatoid arthritis, immediately at diagnosis, we will start a disease-modifying drug. For most people, that's Methotrexate, but some will get Sulfasalazine or Leflunomide, depending on their contraindications. Then we monitor, and this depends a bit on your health system, and this is two world guidelines. This is the European guideline on the left and the American College of Rheumatology guideline on the right. You can see one says you can use Glucocorticoids as bridging therapy, that's steroids as bridging therapy. The other says, no, you shouldn't be using steroids, but we know they are still used a lot. After three or six months, if you're not responding, then we might escalate and add in other therapies. In more European, U.K. side, we've probably gotta have failed a couple of therapies, but in U.S., you often get to start a biologic a bit earlier. Generally, we watch people monitor their inflammation, and you might need to switch or cycle through drugs over time. The problem is the 3-6 months recommended in this, diagram, which is a summary of the guidelines, may not follow real life, where it can be many months or years before people get dose escalation. Modern reviews suggest we're not getting a lot of people into remission within six months. To summarize, this is, if untreated, a really devastating disease. Modern treatment has made a big impact, and that's by using immediate therapy and watching inflammation and suppressing it completely. We have got good drug therapies. Most of our health systems will limit the use of biologics and targeted DMARDs because of cost. For clinicians, it's all about weighing up risks and benefits for individual patients. It's unfortunate, and I haven't shown this data, but we've seen even in modern American cohorts, and I say that as a country where there's more access to biologics than we might have in some other parts of Europe, even there we're seeing structural progression, which means we are not adequately still controlling inflammation well enough in many people. Our unmet need as a community remains getting more rheumatoid arthritis patients into low disease activity states or remission as quickly as possible 'cause we know that's associated with much better outcomes in terms of joint function, survival, and people's quality of life. Thanks for listening to this summary. Well, I think that that Philip here gave a rather nice introduction of what we have been working with in the last year with the development of Resomelagon or AP1189, that we have called it until recently, in rheumatoid arthritis. I will try to explain a little more of what is going on because what we have learned recently is rather I would start with this slide here, we have shown that before, where we try to. What we are trying to say here is that when an inflammatory, uncontrolled inflammation is ongoing, as in rheumatoid arthritis, all the compounds that was mentioned in the speech do have either unspecific or specific, immune, inhibitory effects. It inhibits the immune system and in many cases induce immune suppression, which most highlighted here with the JAK inhibitors, with increased risk of inflammation. Our compound do have some anti-inflammatory effect, but it's not so that we induce immune suppression, and that's very important from the way it works. We compare to all current treatment approaches. We induce what we call resolution, meaning that we are boosting internal, you could say, pathway in the immune system that helps getting the immune system to another set point. We do not take out the inflammation, but rather bring that to a new set point. We have one of the cell and most likely we are working a lot with is macrophages. Macrophages are present in the synovium, which is the tissue next to the joints. They are pro-inflammatory already in pre-RA stages. We know that we can reduce the activity of those and at the same time get a larger fraction of the cells to be pro-resolving, meaning that instead of secreting cytokines and other mediators, they go into a phenotype where they help clearing up the inflammation with what we call efferocytosis. On this slide, I also have a lot of pictures or graphs from a paper we published many years ago together with Professor Mauro Perretti in London on a compound that we invented in my previous company in Action Pharma. It was a melanocortin receptor agonist, pan agonist stimulating the MC receptors present on the white cells and very nicely showed a combination of anti-inflammatory and for the first publication in that case, showed that we had the ability to stimulate the macrophage ability to efferocytosis and phagocytosis. We also showed that it was associated with stimulation of MC1 and MC3 receptors on these white cells. This slide very much highlights what is going on with our internal preclinical melanocortin receptor agonist, TXP-11. Because it has the same ability, very much the same ability that it stimulates macrophages both on the up to the right in a model of you could say acute inflammation in a peritonitis model where we show that we have more of these macrophages with the ability to efferocytosis. To the down to the right, the same is the case in macrophages from synovial tissue or paw in this case, from a paw from an arthritis animals. The concept of stimulating these three melanocortin receptors is associated with a shift in the phenotype of the macrophages. This slide here then, what are we doing with our current clinical development? Yes, we are working with a biased agonist, and we have highlighted that several times that a biased agonist stimulating the melanocortin receptors, but in a way so we have the beneficial of stimulating the macrophages and some anti-inflammatory effect, but not with unwanted side effects through what would be mediated through a classical agonist as we do not stimulate cyclic AMP and thereby not skin pigmentation, which a great advantage in more, more continuous treatment as we apply in rheumatoid arthritis. This slide to say that, well, with our compound, it works very much like the peptide agonist that we showed a picture with. We have the ability to induce anti-inflammation. We have the ability to stimulate the macrophage's ability to efferocytosis. It works in vitro and in vivo, and again, dependent on stimulating MC1 and MC3 receptors, which are present on the target cells. The compound we are working with is given once daily as a tablet. It's an agonist, so we have to go up into a plasma concentration where it stimulates the receptors, but at the same time also are having a trough value, meaning that the concentration in blood is so low so that we hardly stimulate the receptors. That's very, very important in order to avoid what is a major issue with the whole concept of resolution therapy is desensitization of the systems. Others have tried to, with other targets, to make oral available compound and has shown that continuous stimulation over 24 hours will induce desensitization of the system. We go up with the compounds into a therapeutic level and the dose that we are using into a therapeutic level and stay there for a couple of hours, and then we also have a trough value well below, and then we give the next dose the day after. This slide here highlights the importance of the what recently have been highlighted as important cells in active disease. CD40 positive macrophages, they are present in synovial tissue in pre-RA patient. That means in patients who do not have developed arthritis yet but will develop that within a time frame from months to years. They are also present in more advanced disease if you have uncontrolled disease. Here highlighted in the middle, with the red bars, this one here, that we have much more of these macrophages in patients with uncontrolled disease, meaning that they have a clinical score outside, you could say, so you would say that they have active disease compared to those patients who have been treated and do have disease control. Macrophages plays a significant role for the control of or the development of disease, but also for the control of the disease. This is from ongoing studies with one of our collaborators, where we show that when we take out synovial tissue from rheumatoid arthritis patients, and we stimulate with our compound, resomelagon, then we see a reduction in pro-inflammatory macrophages. In other words, that the and this is again tissue, in this case, tissue for more advanced disease, whereas our current disease or clinical development is in newly diagnosed. When we have macrophages present that is activated, we have the ability to reduce the activities of those. Our compound modulates neutrophils, it modulates macrophages, and thereby has the ability to go in early in disease and control activity of the disease and of course, at later time point, if it's so that we have high macrophage activity. That's what I highlighted here. What are we doing? Yes, we are currently running a clinical development program in newly diagnosed rheumatoid arthritis patients. I think it's one more time important to highlight that the aim of current treatment is to target a maximum response as fast as possible and as safe as possible. That's why you use Glucocorticoids early in disease to try to get control, but it's also a big problem is to get rid of them when you have first started and in some cases or how a little of how you look at up to 50% of all rheumatoid arthritis patient will be treated with Glucocorticoids for prolonged periods. That's important to reduce the need for those. They are probably very well-suited to short-time treatment, but you have to get rid of them as soon as possible. All current treatments are immunosuppressant and associated with safety risk. That's not my wording, that's EULAR wording from the guidelines. Something new is needed, and that's where we see our approach of resolution therapy. This is from, just, again to highlight that we some years ago completed the BEGIN study where we gave the compound to newly diagnosed patients with, if they were eligible to methotrexate they were offered to participate in our study. This is just four weeks treatment where we showed that the blue bar was significantly higher reduction in disease activity when we gave the compound in combination with Methotrexate than when we gave placebo in combination with Methotrexate. To the right you see the same on the ACR scoring that the more than 60% in this study reached ACR20 indicating that the compound worked early and worked very quickly with a quite nice treatment response, clinically relevant treatment response already after four weeks in these patients who were newly diagnosed where the majority of the patients had signs of systemic inflammation as CRP were outside normal range. Of course, they had all high disease activity. This is then from the EXPAND study where we completed two years ago, where we on almost three years ago now to this summer, where we gave the compound to treatment-naïve, not necessarily newly diagnosed. We had, as Philip Conaghan also in his speech highlighted that there is patients who are not treated as effective as they should. We got patient in who had been without proper treatment, appropriate treatment for quite some years, and we also got patient in who did have high disease activity but did not have sign of systemic inflammation. In those patients, the compound is not, at least not at the dose we used, was not the right treatment. When we took half of the patients and looked at those who were newly diagnosed, who had high disease activity and where CRP were outside normal range, we got this picture. Then more than 80% of the patients responded with ACR20 that we had a significantly higher reduction in disease activity, both DAS or DAS28, and we saw that in this study after four weeks, eight weeks and also on the CDAI that was always in the previous and the BEGIN study always was significantly different after four weeks. And this is clinically and the difference you see here is on top. You give the compound on top of methotrexate, you do everything as you normally do, but we did not give glucocorticoids. Still we saw in that setting a clinically meaningful reduction in disease activity. Importantly, it was overall well-tolerated without signs of immunosuppression. We have set up and now we have completed recruitment to the ADVANCE study that is run under U.S. IND. It's patients who are newly diagnosed, they should have the RA diagnosed within six months. Many of them have that within a few weeks from where we start the treatment. They should have high disease activity. That is by definition of the two scoring systems you're looking at, DAS28 is higher than 5.1, and for CDAI it's higher than 22, meaning that you do have quite significant disease. They should have a CRP, which is you could say a non-specific marker of systemic inflammation outside normal range. In this study I can say that is we have the patients average CRP level are slightly higher than the subgroup what we saw. That's from what we have seen on the data so far, slightly higher than what we saw in the patients. You could say the same patient group in the ADVANCE study, those where I just showed the data from. It's not so that they have 3.1, 3.2, there's a lot of patients who present themselves with quite significant inflammation. We then offer them methotrexate. We are uptitrating that according to normal practice. You start the 10 milligram, go up to 20 milligram, and then we give the compound, our compound in one of three doses or placebo in parallel with that start the same day, treat them for 12 weeks. The primary readout is DAS28-CRP, which are recommended by FDA for dose range studies because it makes the statistical, you could say the likelihood to be able to identify differences between doses higher than if you use the ACR20 as a primary readout. In this case, the ACR20 is, or the ACR scoring is, you can say the key secondary readouts. Of course we have the reduction in CDAI score. We have HAQ, which is also a very important readout. This is a health assessment questionnaire where the patients indicate where you get a very clear indication of the overall benefit of the treatment, not just on tender and swollen joint, but really on how the patient they are having their daily life. So far we have, as highlighted, 246 patients randomized. We had the last dosing in May. Based on the ongoing medical monitoring, I think, and we have decided that we can share that with you that we only have four adverse events that resulted in discontinuation from the study. I would say that regard to one of the major problem with methotrexate is liver enzyme increases, and the other one is nausea, and there is one of each. It's not a lot of side effects there. As three out of four is inactive, it could be a good sign. That for the future to say. In any case, that is, it was very encouraging to see. Very few reports of increases in liver enzymes in total. Very few reports of gastrointestinal adverse event. No signs of immunosuppression, and so far we only have one SAE, which has absolutely nothing to do with the study treatment. It's classified as non-related, and it did not induce discontinuation. That's all we have where we are right now. We expect to have the compound, as Jeppe said, to report the data in June and look very, very much forward to that. Then of course, on the back of that, we have an opportunity to go in to present this assuming positive data. Of course then, it would fit extremely well into the treatment guideline highlighted here to the right as a novel treatment in newly diagnosed patients. We of course are working then on getting this. From a clinical perspective, it would be Phase three ready after this data set. That I think was the presentation. Thank you very much. What you just heard from Dr. Conaghan is a walkthrough of the various compounds that is used to treat this disease, when you're treating it, and also this risk-benefit issue that is, you know, always present when as a physician you treat these patients. Safety to go early and to go before the biologics, for example, safety is key. What you've just seen from Thomas here as well is that how the molecule works and how we see this, we can identify activated macrophages. We can do something about that. That is what we see in the preclinical trials. We see from previous studies, we have reached significant clinical levels. What you also heard is from what we know right now is that we think this could come out as a fairly or very safe treatment. Safety is key to this understanding. I'm gonna take you up to the helicopter right now, not, you know, metaphorically, and look at saying, okay, what does this actually look like in, you know, from a market point of view and from when you look at it from a potential partner point of view, what is it you wanna see? The global market for rheumatoid arthritis drugs is clearly dominated by the U.S., mainly from value. It's not that there are more patients in the U.S., it's simply because drug pricing and how that is done. What you see here on the slide here, you see there's approximately two million patients with rheumatoid arthritis in the U.S. and in the major five markets in Europe. Value-wise, you're approaching $21 billion in value from the U.S. and something less in the European side. A key thing here is also to look at what new markets are coming up. Again, with everything here, China is definitely developing. A lot of patients are being diagnosed and have the disease, and knowing from what companies that have research projects in biologics and treatment for RA, there is a lot. There's definitely a market to look for in the future how that develops. That's the kind of the distribution of what you will look into. The major driving part of that is the pricing of biologics and JAK inhibitors. On the right-hand side of the slide here, you see one of the forecasts for the value of the various types of drugs that are used. In here you see like more than 50% of the entire value of the major seven markets comes from TNF blockers. The first biological you will be on, this is including also biosimilars coming to the market. The next one is then the second part of the biologics called the CTLA-4, that's the B-cell modulators, IL-6, CD20s and so forth, and then you have JAK inhibitors, which are the new ones. If you wanna innovate in this, you can add, or if you wanna go into the market like this, you can either develop something that's gonna move the dial or take market share among the biologics or between the JAK inhibitors, that's happening a lot, or you can expand. Obviously we're trying to expand the market and the opportunity here. That's gonna come with innovation. We believe one of those innovations is pro-resolution. There are several pro-resolution mechanisms that are being explored. One of them. They all represent a new area of interest from many companies. One of them is our melanocortin receptor agonists where we are present and what you've just seen we're doing. There are several companies that have products on the market. They have not managed to figure out a way to make this a safe alternative, so they're kind of limited in how they can be used. If you look at companies like Tanabe Pharma, Palatin, and ourselves, well, we have melanocortin receptor agonists, Tanabe has in development, Palatin has development, we have it in development. We're all trying to kind of walk around, can we make something that is effective and safe? Innovation is coming to immune diseases. We believe pro-resolution is one of those levers, and it's not only us saying it. It's actually also, if you look at big pharma, investing into pro-resolution, one just recent example of that is Johnson & Johnson moving into forming a company called Resolve M Therapeutics, to basically forming a platform company to develop new resolution therapies. A lot of excitement, a lot of things are gonna happen in this field over the next couple of years, and we're lucky to be a part of that. How we think that this could change the market, and this is the kind of what we're in it for, is that this is a, an overview of the patient journey in rheumatoid arthritis. You start as unclassified, you get diagnosed early RA, you get a methotrexate. You cycle through, and if it doesn't work, you progress into more progressive RA on the right side, and then you would start your biologics and so forth. Looking at the market, again, this is the vast majority of the value of the market represents only 30%-40% of patients. This is our estimates, the difference obviously in which market is that. That's where, that's the kind of people that companies today are fighting about, 30%-40% of patients where the value is driven. What we think and what we heard so far, we think Resomelagon can be a safe product, meaning that that's the access or the ticket to go in early. Number one access point, you need to be safe, or at least safer than what it currently is. Number one, then it has to be clinically meaningful. What we think is not only meaningful, but imagine that we can actually push the time before you need to get to biologics or even prevent it. That would really be something. Then last but not least, we're focusing on high activity patients or high CRP level patients. That is a poor prognosticator already. Something, it means you need to do something, and we're one of those tickets to do something about it. We think the positioning of the drug can work in an early patient on top of methotrexate to basically either prevent or prolong the time to move on to biologics. We think that could expand the market maybe up to 5%-10% of the patient population you can address with things like this. That needs to be proven in phase III programs, and that's what partners coming into this needs to drive at, and that needs to be the logic for one of the cases. That's obviously going into and say, okay, is this attractive in a market for companies doing transactions in immune diseases? A little bit busy slide is what does the autoimmune disease transaction market look like? I'll walk you through the slide here, because that's important. It's actually a pretty active environment in broadly autoimmune diseases, not RA, but in general autoimmune diseases. Just in the last few years, there are recorded 171 transactions. It's limited in terms of what kind of information that is attached to it, but 79 of them has deal information or deal value information to it. 39 of those deals in the last few years have deal value above $300 million. What you see on the left side here is that among those companies, it's all the big ones. They are all there, they're doing transactions, and they're active in this field. This is just a subset of the companies that are involved. Out of the 39, five M&As, and then 34 license deals. Randomly enough, in RA specific, there are not that many transactions that have happened. I think it boils down to where does the innovation come from? You know, we have all developed these, you know, biologic therapies and the JAK inhibitors. They're in the market. We're fighting for the same patients. Next wave of innovation is also gonna be attractive for making new deals. That's the market that we are in, and that's where, you know, with good phase IIb data, that's the dialogue that we're gonna have with a lot of companies that we have lined up. With that, it's perfect timing here. We're going into a Q&A session. I think Jeppe is the first one. Yes, indeed. Hi, Jeppe. Hi. Before we get deeper into RA, which was the first module we heard here, other than the other one that we will hear in just a moment, I was going to ask a few questions about SynAct as a whole, because you're apart from RA, you're also doing viral respiratory. Doing these dual track development, how does that sort of mitigate risks in the company? Well, you can say that by having these three programs running right now, it of course de-risk in a way where we have more shots on goals. That's a good thing. I think winding back a little bit to how we sort of invented the dual strategy was driven a lot by partner discussions. Every time we had these discussions, they liked the RA, that was fine. They understood the setting pretty quickly. What Mads just described in many slides, they have on their mind the moment you meet them. They are well-educated. They know where they are. But quite quickly in those discussions, they always came to sort of the question, "Why don't you do this and this in other indications?" There we always had to say, "We're a small biotech, we have to focus. We can't. We sort of invented the strategy of a dual track, and we also found out that it was possible to do sort of investigator-driven studies, where a small company for small money could conduct those studies. It has been driven a lot by partner discussions. I think it positions us really well so that when we take the discussions with pharma companies, we can discuss the RA, but we can also show them that we have already been thinking about indication two, three, and four also. Is there a scenario where SynAct would prioritize one program over the other? I would say where we are right now, we have money in the bank. We have a clear focus on RA as our lead. I think that it has been really nice in the discussions so far to be able to show that we are doing other things as well. What would constitute transformational in 2026 from a corporate perspective? I think we are a company that have worked for quite some time, leading up to data now, and over the next two quarters we are getting basically all the data. It's a big transition for us coming from a waiting position into a pretty forward going towards business development. Yes, a lot of transformation. Thank you very much, Jeppe. We will dive deeper now into RA, and we do that with Dr. Connaghan. Are you with us? Dr. Connaghan? Hello. Can you hear me? Yes. Yeah. From a clinician's perspective, how meaningful would a non-suppressive therapy be? Sorry, can you repeat the question? From a clinician's perspective, how meaningful? Sorry, can you repeat. Would a non-suppressive therapy be? I think if it's additive to existing therapies at low toxicity and improves remission rates, especially if it can get rid of corticosteroids, which is one of my personal hobby horses because of their toxicity, then I think it's a step up for the field. At present really, we have very much what boils down to cost-effective in terms of trying csDMARDs first, and a toxicity-driven approach. Both those things govern what choices we have in our therapies. I think that sort of approach is going to be acceptable given price and health system. What clinical endpoints would you consider most compelling from a practice changing standpoint? I think low disease activity or remission is the only thing that's going to be both acceptable to clinicians and regulators now. The field has moved in the last decade, so it is very much about tight control and getting people into at least low disease activity status. The reason I use that more than true remission is that people often have concomitant Osteoarthritis and other problems that makes it very hard to have zero tender and swollen joints when you're examining them. A realistic goal is to get them into a very low disease activity state where we think there's no active inflammation. Thank you, Dr. Connaghan. I am now joined here by Thomas Jonassen. You're the Chief Scientific Officer. We heard from you here for RA, and I thought we could begin with talking about the ADVANCE study. How confident are you that the 12-week treatment window in the study is sufficient to show clinically relevant effect? I think that a 12-week study, a three-month study is the standard prep for phase 2b development, completely according to guideline. The readout based on changes in CDAI, or rather on DAS28 and/or on the HAQ score is what is the clinically relevant readouts and accepted by both the rheumatologist and the regulatory and potential buyers. To show a clinically relevant effect would in our case be to show that it's reduced disease activity to a level, so it's significantly better than placebo. Mm-hmm. We also know from development that in Phase three you have to dose for up to 12 months. Typically what you do is, and you have your primary readout on the remission. Low disease activity remission is after six months treatment simply because it take months to get to that level. That would of course be for the future to show that. What is the key primary endpoint in ADVANCE, and what level of statistical separation would be considered clinically meaningful? Clearly, first of all, DAS28 is a scoring system where you take a number of readouts. I mean, that is the disease activity, most important, described by the patient, it's the number of tender and swollen joints, and it's DAS28 and CRP level. Then you put that into a formula and get a number out of that. High disease activity of 5.1. Disease remission is lower than 2.4, I think it is. What is realistic to see in a treatment period as our 12 weeks from previous study would be around two. In some JAK inhibitors go all the way up to 2.5, but they also have immunosuppressive activity. that would be in that ball game. Of course, to show that is statistically different from placebo, and that would be on the five points level. Recruitment for the ADVANCE study is finished, 246 patients. What specific operational milestones remain before top line read, Q2, and what are the key risk factors? First of all, we have to complete dosing all the patients. That would, as we recruited the last patients in February, it would be in May. You have to clean up, you have to collect all the data and clean up and secure that everyone is reported in the right format and get everything into the database and clean that up, and then eventually you close the database, and then you bring the data into the statistical program, then you run all the analyses, and then we get the results. I mean. Here we are really to speed that up and do that as effective as possible, the whole team who are working on that is doing a tremendous job to secure that everything is online and on time. Thank you very much, Thomas. I will now invite Mads to come up to the stage, and I will ask the final couple of questions before we head into the second module. Partnerships, what sort of a pharmaceutical partner is most aligned with this asset? I showed on the slide a couple of them that already have done deals in this area. I think the perfect one is the one that already has asset in the RA space or adjacent spaces so that they have enough clinical experience, they have boots on the ground, so to speak, to drive a message forward. They have market access expertise, meaning pricing and negotiation power to do that. That would be the perfect partner. What we're looking for is then, and then it's back to some of the geographies. It would obviously be amazing to have a global view on one, but there's also, you know, good reason to say, okay, maybe there are certain regions that we should look for. The U.S. obviously being very important, but Chinese, European, Japanese and so forth could also be very, very interesting from companies who wants to be part of the innovation and wants to take kind of that leap into a market, a very interesting market like RA. What deal structures are realistic in that case supposed to be results in that case? Is it regional licensing, global partnership or full asset sale? Could be all of the above. That's. It's so hard to answer that question. If you look at the statistics, it's mainly license agreements. Many of them global, some regional and so forth. At the statistics level, you know, you get all of the above. I think it would be very kind of straightforward to say, okay, global partners, we invite you for discussion. They would likely look at this as a license development agreement, and then you basically work from there. And then the good thing is that we have enough time that Jeppe spoke about to actually go ahead and say, okay, what is the best deal for us? It could be licensing deal, it could be regional deals, or it could be somebody who actually wants to acquire an entire company. It is time that we head into the second module, respiratory infections. I will simply hand over the word, and I will return later to ask more questions. Thank you very much. We are right on time. It is amazing. Now we're gonna do the second portion of the meeting. We're gonna shift gears from rheumatoid arthritis and into our second leg, so to speak, is the host-directed therapies, focusing on respiratory infections. I need my cheat sheet here. Love it. Because we're gonna have Professor Thomas Benfield to present to us the what's happening in the field today, what's going on, and what are the issues that we are facing. Again, Thomas will walk through some of the data that we have and the reason to believe why Resomelagon is working in this setting. Then, I will take us up in the helicopter again and look at from a market point of view, you know, what does this look like and so forth. I can already say now it looks very different from what we've just seen. There are a ton of new opportunities in this case that we're gonna go to. With no further ado, I wanna introduce Professor Thomas Benfield. Dr. Benfield is a professor of infectious diseases at the University of Copenhagen and a consultant physician at Copenhagen University Hospital, Amager and Hvidovre. He's the director of the Center of Research & Disruption of Infectious Diseases, CREDID. He's an internationally recognized expert in infectious diseases and has led numerous clinical trials, authored hundreds of peer-reviewed publications, and played key roles in advancing evidence-based treatment strategies in infectious diseases. We're delighted to have the opportunity to have him with us today, and just like the Professor Conaghan you saw before, he's gonna join us live online in the Q&A session as well. With that, we're gonna roll the video. Hello. My name is Thomas Benfield. I'm a professor of medicine at the University of Copenhagen and an attending physician at Copenhagen University Hospital. I'll be speaking to you for the next approximately 10 minutes about the impact and burden of severe acute respiratory infections, including influenza, RSV, and COVID-19. What are we talking about? What is SARI, as we also call it. SARI is a lung infection caused by bacteria and viruses, and among the viruses, influenza, RSV, COVID-19, and a number of others predominate and cause epidemics almost every year in most countries worldwide. What you see on your right is a chest X-ray of a woman admitted some years ago with severe influenza. I know most of you don't look at X-rays every day, but this is very abnormal. The lower two-thirds of this woman's lungs are filled with virus inflammation and fluid that naturally impairs her oxygenation, and she was in severe respiratory distress and actually very quickly needed a ventilator and later also progressed and needed ECMO, which also is known as a heart-lung machine. Fortunately, despite the limited availability of therapies specifically for influenza, this woman did improve and was discharged about a month later after having flu. SARI is a major burden of global infectious diseases and is probably one of the leading causes of premature deaths worldwide. On a typical season, you know, one in five persons will experience influenza. Far less are very serious, and I'll touch on that later. We're just at the end of this year's season. It was a long, hard season again for the second consecutive year. It strains our health system and the many patients that are admitted to hospital. What this graph shows you is the situation in Denmark up till about last week. You see, the number of SARI cases is usually pretty stable at about 500 admissions per week. Beginning in October, November, the numbers double to about 1,000, and by February, the numbers had tripled to about 1,500 additional admissions acutely to Danish hospitals. To put this in perspective, this is usually about 70 in the low season that increases to about 200-250 per week in the high season. You have to measure this against the fact that there is usually about 1,500 acute admissions per day, sorry, in Denmark. This is actually a significant increase of about 10%-20% of extra admissions to our hospitals. These patients are usually admitted for longer periods of time than the average patient, so it really strains our health resources and hospitals. SARI is also a leading cause of morbidity and mortality. This is a busy slide, I know, but it's actually pretty simple. In the top panel, what you see is in-hospital mortality from the three major viruses that cause SARI, so it's influenza, RSV, and COVID, and they're compared. What you should note is that on average, the 30-day mortality from SARI is about 5-6%. However, what is unknown to many people is that even post-discharge, so after being discharged from hospital with an episode of SARI, up to 10%-15% of patients will die in the following three months. There's a lot of post-discharge, post-SARI disease going on. What is the typical SARI patient? Like I said, one in five is hit by flu annually. Fortunately, most have a upper respiratory tract infection that's less serious, although lots of people feel really miserable when it's going on. We know that of these, one in twenty approximately will develop some sort of respiratory failure leading to hospitalization. Age and chronic illnesses increases the risk, of course. What we do in hospital is mostly gives respiratory support, which is oxygen supplements or if needed, a ventilator. In general, it's in this country, in Denmark, maybe one in ten will require intensive care treatment. In many other countries where they also oxygen therapy is done in intensive care, maybe in these countries, up to half of all admitted patients with SARI will require some sort of intensive care support. One reason is that current antivirals have limited effects. What are the current antivirals that we have? So for influenza, we have antivirals that are very good at preventing people from progressing to respiratory failure and admission to hospital, but do not seem to work and have not a proven benefit when you're hospitalized. This may actually be because they are suboptimal and because by the time you're admitted to hospital, this is more an inflammatory disease than a viral disease. What you may need is an anti-inflammatory drug more than you need an antiviral. We know quite a lot about this from the COVID-19 pandemic, where a number of large trials prove that combining the two, giving an antiviral together with an anti-inflammatory once you were admitted to hospital and required oxygen, would improve your outcomes and would limit the progression to intensive care and improve survival of these patients. For one of the other viral SARI infections is RSV, and we actually don't have any approved treatments for this disease. For the bacterial SARIs, we have antibiotics, and that's why I haven't touched much on this because these are generally very effective drugs. We pretty much know what to do with bacterial SARI. This brings me to my concluding slide, and as I've tried to convey to you, SARI is a prevalent socioeconomic burden because it leads to a lot of lost working days, reduced productivity, increased healthcare expenditure, and strain on healthcare systems, and it leads to excess mortality. Clearly, there is a huge need for better treatment options to prevent the morbidity and mortality from SARI. Thank you very much for listening to me today. We started some years ago a collaboration with some of our scientific collaborators, and most importantly Mauro Perretti in London and Mauro Teixeira in Belo Horizonte in Brazil, where we examined the potential of our resomelagon compound. From the pharmacology, from the fact that we stimulate macrophages in a beneficial way during the pandemic. We have since then continued the collaboration not least with Mauro in Brazil, Professor Mauro Teixeira in Brazil. Of course also with Mauro Perretti and other collaborators to further understand what is the potential of resomelagon and other pro-resolving compounds in you could say more severe viral infection, severe COVID-19, there we generated a dataset. The patients, they were referred to hospital in a way so they typically have been treated with low-dose Glucocorticoids, which has the ability to have some anti-inflammatory effect. In the dose they give, I would not completely rule out that it might have some indirect effects on a pro-resolving-like effects. They were treated with standard treatment, including Glucocorticoid for a few days, and if they were still in a position where they, this disease could not be controlled, they were sent to hospital and at the hospital to be offered oxygen therapy. What we did was that we then randomized the patients to either get our compound or to get placebo treatment. Then we treated them for up to two weeks. What we saw and highlighted to the right and what we published in 2024 was that we got the patients who were treated with our compounds faster to respiratory recovery, meaning that they no longer had a need for oxygen therapy. We also showed that they had a shorter hospital stay. That was very, very encouraging. Originally, the intention was to continue with additional studies when the COVID-19 phenotype changed. We have since then worked with other viruses. We have worked with the arboviral infection as we have highlighted previously, where we work in dengue fever, which is a major problem, not least in warmer parts of the world. It will eventually be something that you should have focus on in Europe as well as in U.S., as the mosquito who is the bearer of the virus is now endemic. We have initiated this RESOVIR-2 study at sites in Brazil and expect to have the patients recruited here during the next month as the season seems to be started right, as we are talking here. We have also dug further into other viral other arboviral infection, most importantly chikungunya, which is a disease that is also, you could say, spreading as it bears, as again, the same mosquitoes who are bearing the dengue virus also have this chikungunya virus. That is a disease that in the beginning is very similar to dengue, that it develop an unspecific fever condition and then gradually develop into to a disease with severe joint pains and arthritis-like symptoms that can last for years. We have generated data in chikungunya as well as in dengue fever, as well now also in influenza models to support continued development of the compound. Today, a few words about why we believe it makes a lot of sense to run the RESPIRE study that is conducted as a Phase two study here in Europe with the potential then to broaden it out to other parts of the world and hopefully can give us a pharmacological, or you could say a clinical proof that the compound could be applied to patients who are referred to hospital for needs to, as Professor Benfield highlighted, when the patient comes to hospital, it's no longer a viral infection, it's an inflammatory disease. There, the modification of the inflammatory response is, from how we look at it, very, very important. In respiratory infection, we do have this ability to inhibit neutrophil recruitment and activity. We do not suppress them, but we modulate the activity, and we promote the pro-resolution pathway. The slide to the right highlights here in the alveoli, which is the functional unit in the lungs, that macrophages, pro-inflammatory macrophages play a significant role for the initiation of the severe inflammatory state you see in respiratory infections. It can then stay within the lungs, so you develop severe pneumonia, as we saw on the lady's X-ray, or it can even spread to the system for a more systemic inflammatory response, where not least kidney affection and other affection of other organs is important. By stimulating melanocortin receptors on these key cells in the immune system, they strongly indicate that we can modulate this response and thereby have, as we saw in the COVID-19 patients, a benefit for the patients. We show this not only in patients, but in the patient study, but here we have human white cells that is taken out, stimulated with, in this case, a COVID virus, and we can show that by co-treatment with our compounds, and we have the possibility to reduce the pro-inflammatory activity of these cells, indicating that we move that in the right direction to balance the response without suppressing it. Similarly, in murine models of COVID infection, we had the ability to show that we could modulate the disease, reduce. Important here, we give it therapeutically. These models, you can use antiviral compounds. You typically have to give them very early, and that was also what Professor Benfield highlighted, that when the patients come to hospital, an antiviral is probably too late to give that. It's not any longer a question of suppressing the virus, it's a question of modulating the inflammation that has been triggered, this hyper-inflammatory state. We can show here that we could have treatment benefits in this model of COVID-19 infection, reduced these pro-inflammatory cytokines among others. Lung damage as well, again here in SARS virus, in models that we have, treatment benefits that is associated or showing that we protect development of more severe lung damage in the models. All has been peer reviewed and published. Then just one slide here with from our influenza model that we are working with where we show that our compound has the ability, given here, again in the therapeutic fashion, we could, or rather we could avoid mortal cases, fatal cases in the model, and importantly, again here associated with a significant reduction of these pro-inflammatory cytokines that is playing a significant role, and well, many of them are produced by these pro-inflammatory macrophages. Based on that, we decided that, and completely in accordance with our dual strategy that we presented last year, we decided to continue from where we were with the RESPIRE-1 study in COVID-19 patients, to focus, to go and test this compound in a double-blind, placebo-controlled study to evaluate safety and efficacy of the compound in patients with respiratory insufficiency due to viral infection. We have initiated that, and if everything goes well, we can report that in Q3. The setting is the patients we give the compound once daily for up to two weeks or placebo. That would be patients who are hospitalized and would be in the need for oxygen therapy, not patients who need to go directly into an intensive care unit. Our primary readout would, and because then again, it's the, as also Dr. Benfield, Professor Benfield highlighted, it's different with the how you define an intensive care unit in different countries. What we have decided to do is to look at, you could say, a composite of organ readout on organs that indicates that you would be a candidate for intensive care unit. That would be our primary readout in this first proof of concept study. Then of course, we have a number of other clinically relevant readouts, a secondary readout compared to, and together with the. With safety. That is what we are doing right now in the respiratory field. That would, of course, open up positive data, and this study would open up the possibility to very fast going to late clinical development with the potential we see in the disease and with the compound. I think that was it. Thank you. Now we're gonna go in the helicopter again and see why is this very different. The opportunity here, as you heard both from Dr. Benfield and also from Thomas here, this is a case, you come to hospital, you need to do something. It's probably more an infectious disease or an inflammatory disease that you need to treat instead of a viral disease. Looking at the market right now, there's no doubt there is a lot of cases where patients come to hospital each year. Actually, just in the U.S., more than one million patients get to hospital each year because of influenza, RSV, and COVID-19. The exact same numbers are valid in Europe. As you saw from the Danish data, and I would guess it's the same here in the Stockholm area, you know, thousands of patients getting to hospital on a weekly basis. This is significant. Can we do something in this space is very interesting. Right now there are antivirals and there are some anti-inflammatory that has been used. If you look at the top line part here of the slide, there's definitely been a lot of these antivirals being developed for and used for COVID-19. One example is remdesivir from a company called Gilead Sciences, which is also used together with a JAK inhibitor, for example. You have the marriage of the two with the antiviral and the anti-inflammatory. That has very good data. When looking at that, it's all about how can we address patients with higher risk and get them either avoid getting into hospital, that makes sense, but once they get there, how can we get them out of hospital as fast as possible. That is exactly what we are trying to do. If you look at the market, just for the antiviral medicines used in this manner is projected to grow to more than $5 billion. I would say this is a highly developing field. If you look at the pipelines from companies, there is a lot of antiviral medicines in development right now, both for RSV developments out there, but definitely for influenza, which is the big one, that you need to address. Again, something that can even further generate growth and the acceptance of doing something in this market is, for example, strategies from the authorities that sets the direction for how to treat patients. In the U.S., that is the National Institute of Allergy and Infectious Diseases. That's the organization that focused on HIV in the nineties. That was the organization with Dr. Fauci in the lead on during the COVID-19 pandemic. Now, the vision is changed from developing vaccines to developing more things you can do once you hit the hospital, once you have the problem. Host-directed therapies is directly mentioned in their new vision. Something like this gives us a very much hoped that this will gonna spur a lot of innovation in compounds that can be used once you start hitting the hospital, once you have the problem with a lot of these diseases. Just, I love this quote from Dr. Benfield earlier, you know, this is not once you hit the hospital, it's not a viral disease anymore. It is an inflammatory disease. This is what we're doing something about. How we see that we can play a role in that and how pro-resolution therapies can play a role. Obviously, more than one billion people in a year catches influenza. One in five of us globally are gonna contract the disease, and then you add on COVID-19, RSV, and so forth. Dengue, chikungunya, all these others are a completely separate and adds on to this issue. What we think is that focusing on the market where this is where you have enough of an issue that you need hospital therapy. That's become the inflammatory disease issue. You have the pathogens that you work on. You have oxygen therapy. 10%-20% even more goes to the ICU depending on where you are. You have antivirals with some limited effect. There's a lot of innovation coming into this, and other anti-inflammatories are already in there. We think that why don't we apply these safe, effective strategies early on to patients coming into hospital where if you need hospitalization in this field, that means you are at risk. Already there, having something safe, that would be a key for you to use it. What we think is from Resomelagon, and obviously it's early days with a Phase two study in respiratory trials, and as Thomas mentioned, this is obviously for future research also to do. We think that this can be pathogen-independent, so it doesn't really matter how influenza mutates over the course of the year and through time, because it likely will. We have a very simple eligibility criteria. If you need oxygen because of inflammation, you can go. What we're trying to achieve in the study is similar to what we saw in the COVID-19 studies, is the reduction of ICU therapy, and even length of stay in the hospitals. That has a health economic component to it that is very straightforward, and I think that is also why you see innovation development in there. Because if you can save on hospital days, and saving on intensive care unit therapy, then you have a very good argument for saying, you know, what's the value of your compound? And that's coming back to, how does the market actually look at this? And then applying safety on this, that means you can apply this very broadly in your hospital systems. That's what we're thinking that our studies in dengue and in respiratory diseases will give us a hint of, that we can move in that way. Again, looking towards, well, what's happening in the field of transactions? Who's doing what? Compared to what we saw in the immune disease area, there's actually not that many deals happening, and I think that's a part of, if you look at the antiviral and viral infection transaction, again, over the last three years, well, I've only seen 40 of these deals. Again, with, you know, two handfuls with some real deal value in them and a good portion of that with more than $300 million in deal value. Again, it's all the big companies that are associated, that are into this. There's definitely something that is cooking. Looking at the number of development projects in this field, especially for influenza and RSV, for example, but especially influenza, then you would also say, "Okay, there's gonna be a lot of innovation coming through," and that means transactions. I definitely think that a compound that can address some of these major impacts to health systems, like influenza or COVID-19, that definitely attracts some investors into this, and companies into this. One example is the fact that MSD basically acquired a phase III influenza antiviral for $9 billion. That's happening. There's definitely something here that companies are looking towards getting enough proof that this can actually happen and can be applied, and that has value. Obviously, we think this is an area where a compound that are so advanced as ours, with a safe and hopefully also efficacious application, that would also be, you know, attractive to be part of a coming deal in the future. With that, I will go to Q&A. Thank you very much once again. Thank you. I will. Thank you. First and foremost, if Dr. Benfield is here with us now. Dr. Benfield? Yes. Good afternoon. Hello. Good afternoon. We'll begin this Q&A with you. In hospitalized viral respiratory infections, what is it that primarily drives mortality and deterioration? Well, of course, it's mainly the respiratory failure that these patients are experienced that they go through. That's what's really makes the difference when you're hospitalized, that you're in such respiratory distress that you need all the help that you can get really. Would a host-directed resolution therapy meaningfully change hospital treatment paradigms? Well, I guess that's what has to be shown, right? What we know from COVID-19, that it had a huge impact, that we were able to treat the viral infection itself and the inflammatory response. We know very well that as people progress through hospitalization, the inflammatory component becomes more and more important. There's still a lot that we do not know. When talking about solutions, we also talk about the burden. How large is the economic burden of hospitalized respiratory viral infections in Europe and the U.S.? Well, well, I'm mostly a medical doctor. I'm not too much into finances, but this is huge, right? Because just the sheer number of people being admitted every winter to hospitals really drives the cost up, I assume. There are a lot of studies showing that of all infectious diseases, across the board, influenza alone by itself is the single most expensive disease that we know of. Thank you very much, Dr. Benfield. We will now turn our attention to Thomas Jonassen, Chief Scientific Officer at SynAct. What patient selection criteria is most important in the trial? Most importantly, it's patients who are referred to hospital because they have developed disease to a level so they have affecting the respiration. That, I think, is the key, as has now been said quite a lot of times here, that it's not any longer the viral infection that is the main problem. It has triggered a condition where you have a high risk of more development of uncontrolled inflammation. What is the primary endpoint of RESPIRE, and how does it link to regulatory acceptability? As I said, we had set it up, you could say, with a composite of measures for organ dysfunction, including respiratory insufficiency, as a surrogate marker of, you could say, a clinical condition that eventually would end in intensive care unit. The reasons why we have done that is that it's a relatively small proof of concept study, and the number of patients that you should recruit to such a study should be somewhat bigger if you should use going into intensive care unit as the primary readout. You could say that it's a question of getting people back to normal or at least acceptable respiratory function and also protect against other organ dysfunctions, and then eventually get patients to recovery and fast out of hospital. That's the ambition of this program, and that is what we are going to follow. What would a positive readout from the study mean strategically? I think that very much over to Mads' approach, but I would say that it would highlight the potential of host-directed therapy. I think that it has highlighted that even the Americans now, they are really looking into this as a focus area. We know that that was really a game changer during COVID-19, that one thing is infection and another thing is that you get uncontrolled inflammation. If you can show by resolution therapy with our compound that you can modulate that, then I think we have done a big step forward. I'll make sure to ask Mads the same question. Please if it comes up. Before you do that. All right. ... looking beyond RESPIRE, how does the dengue program further validate the host-directed therapy platform? It's the same. I mean, dengue is different in the way that it's the. They have, as I mentioned, previously, like chikungunya, they start with a you could say more or less unspecific fever condition for a couple of days, and then gradually develop into a condition where you have more devastating effects of the circulation, dehydration, and your platelets are reduced in numbers, so you have increased risk of bleeding. Again, driven by uncontrolled inflammation. You could say that if we can do that in would again fit into the overall algorithm of host-directed therapy with pro-resolving compound would make a difference. Thank you very much, Thomas Jonassen. We'll turn our attention now to Mads Bjerregaard. I'll ask you the same question. I expect that. A positive RESPIRE result, what would that mean strategically? I'll try to remember what Thomas just said, but I'll answer it in a slightly different way. I think that's highly interesting. This is an early study in this setting. I think it would open up a lot of fantastic questions for which markets does this. Can this be applied in U.S. hospital systems or across Europe, in China, and so forth? I think that is obviously something that would need to be tried out in later phases. From a strategic point of view, is that already something that could be attractive as a partnering opportunity, or not? Is it something that we would have to develop you know slightly further? That we need to see. Obviously with a positive study in this, it opens up a lot of opportunity. You know, being taking part of all this innovation that goes into it and obviously taking part of discussion with partners and obviously also with how can we move this forward ourself or with somebody or something like that. It opens opportunities. From a commercial perspective, how attractive is the hospital respiratory market? Something back to the slides here, but reflecting what Dr. Benfield was on your question to him, this is a huge problem. With influenza being one of the biggest burdens that we have, you know, as people. Doing something here could have a tremendous impact. If we could play a part in that innovation, I think from a financial point of view and from a financial attractiveness point of view, we're dealing with, you know, very costly hospitalizations with patients dying from this disease. You know, it fits all the buckets of, you know, what is it we wanna see in a attractive opportunity for not just us, but for big pharma, but eventually for healthcare systems and patients around the world. With all of that in mind, could you see a potential for a respiratory partnership to be struck before RA? I don't think before RA. Obviously we're moving forward with RA, and that's coming, data coming very soon. That's gonna spur a lot of discussions, and then we're gonna all in on that. We'll see when we get the data from the RESPIRE study and obviously also RESOVIR-2 with the dengue, where that's gonna lead us. We're definitely gonna have discussions in parallel. I think it's early days to say which one comes first. Right now it's RA that is the main focus, and obviously the one where we're most developed in what we know this compound can do and how to apply it. Also very developed in how we have progressed discussions with a lot of companies out there, knowing about our compound, where it's going to be, and are basically waiting for data to progress that dialogue. What pharmaceutical players are strategically active in the host-directed therapies? We're looking at innovation, pipelines, who's active in antivirals, in the compounds that are being used in hospital. You have the big players in terms of actually some of the MSD with the big vaccine company, Gilead of the world and so forth. But Pfizer is a big one. You can name, you know, the biggest 20 companies in the world that has actions in this. From a development point of view, I think it's very interesting. You also see several smaller companies coming with very innovative antivirals and maybe, you know, pro-resolution therapies along the way. Again, back to some of the earlier comments we have. Pro-resolution is a new field. Mm-hmm. Big Pharma is looking at it and say, "Okay, how can this evolve?" My projection is all the usual suspects plus innovative, new companies coming around, that want to play along. Could respiratory indications provide faster path to market versus autoimmune? That's interesting. That's obviously for discussion with authorities for this. I think the big advantage of the respiratory studies that you can do, and this is what we're talking about when we talk about dengue and the RESPIRE trial, is that you can focus on a season to get your patients. Can you get enough patients in a program during a season? Well, that leaves you a year to do it and maybe another time around. Potentially this can go fast in that sense. With the right muscles behind it, the right companies behind it could potentially actually go pretty fast. In addition, there's a lot of attention from authorities because this is a huge problem. Can you get to markets or some markets earlier? That would be highly interesting to look at. It is something that is evolving. We are not there yet, but it's definitely something that we're looking at, to make good opportunities. Looping back to a little bit commercial perspective. Mm-hmm I suppose. How does pricing logic differ between chronic RA and acute hospital indications? That's also very interesting. If you look at the RA, because it's a chronic disease and you treat for long-term versus treating for 10 days or two weeks in a hospital-based therapy. Obviously there's a difference, and you don't wanna apply a chronic therapy into just using that in hospital if that's your business case. I think that you would generally see a lower per monthly therapy cost in a chronic disease. Then looping to the hospital business, you have to look at what is it you're saving? What are you preventing? The value of that is very high in the respiratory disease or in the acute inflammation because you can save hospital days or mortality and so forth. That you have a potential very high value per two weeks of therapy, that could be very attractive. Which one comes first and how you juggle that, we have some thoughts around that, obviously, and I know any company with a dedicated market access experience and pricing experience would have the same. There's good logic how to bridge that, but we haven't done the golden nuggets on that one. Two good values, one being lower and the hospital being potentially very high. Mm-hmm. Thank you very much, Mads Bjerregaard. Thank you. I know that you have a couple of finishing speakers that will go on, so I will hand over the word again. Thank you very much. Perfect on timing. With that, we have very few points left to speak about. I wanna introduce our new CFO, Anne-Christine Lade, who's gonna take the first point on the next slide, and then I'll take over. Anne-Christine, here we go. Great. Thank you, Mads, and thank you for being here. It's a pleasure to meet all of you. We are off to a good start. Thanks to our shareholders and the team, we just raised additional capital that makes us in a very strong position to continue to our momentum and execution on the clinical trials, but also, secondly, as Jeppe also alluded to, our continuing partnering discussion. That gives us the opportunity, the time, and the leverage that we need to make sure we do take the right decision moving forward here. Lastly, I would say being a smaller company here. Also, not generating any revenue, we continue to be mindful around how we spend our cost and expenditures. I know Mads will speak much more to what is actually going on with these, partnering discussions. Hand it back to you, Mads. Thank you, Christine. That's short and sweet. Sh-short. What are we doing right now? Actually, in less than 15 minutes I have to be out of here, because we have a lot of activities in engaging partners. With the history of the company, we have had a lot of the dialogue with a lot of companies already, and they understand where we're coming from, and they're waiting for data. Then we're basically making sure that everybody's on the same page. Whenever I have the opportunity for it, we'll repeat it, make sure that people understand we have these dual tracks and so forth. Then we're trying to expand the opportunities or expand the number of companies as much as possible, simply to make sure that nobody has not heard about us, that wants to engage in these opportunities. What we're doing in the next couple of months leading up to the phase IIb data, we're gonna be on several of these partnering or BIO conferences. Three of them are happening in China, so there's a lot of things happening in China, and that's why I need to leave. That's to catch a plane to Shanghai. There is a big meeting called the BIO-Europe meeting later in March. Then there's actually also opportunities with the first BIO meeting in the Middle East. Hopefully, we can travel there in Saudi Arabia. That's gonna happen. We're leading up to the big one, which is the BIO International in San Diego in the end of June, and this is obviously where we believe that we're gonna have data to support those discussions. In all our conversations, this is what we're leading into and saying, "You know, where are we? How do you wanna proceed?" 9.9 out of 10, we're gonna say, "Let's do this when we have data." So that's gonna be the conference that we're looking forward to, given that, obviously, we have the data to support that. Until then, it's about broadening our scope, making sure that everybody's tied into the story, knows what we're doing, and are ready to engage once we have that key piece of data. That's the situation right now, and I'm not gonna go into who and how many, and so forth. But also what's very important is the team that's currently in the company. We have done this before, so it's a highly, you know, experienced team that has done execution of transactions before. We're very confident that once we get in the right position, we have the financial parts to do it, and we have the team to actually pull through. We strongly believe that we also have the product to do it. So with that, yeah, just to conclude very briefly. As a CEO, you can see I like simple slides. To summarize a bit and to have a few take-homes from today's presentation. Basically, where we are right now is that over the next 4-6 months, we will have data points on three different studies, and that I think is an important take-home from here. That leads us to move TXP compounds further towards the clinic. I think the important point and the important agenda for us right now is that all focus will go into business development. We need to show that there's partners out there engaged in our projects, and we firmly believe that we'll get there. We have a good feeling of data. We have a good understanding of the compound. We have worked with it for a long time. We are quite confident that we will be in a nice position. And as Mads alluded to, and Christine as well, we are, thanks to your support, in a financial position where we can take the time to do it right, and I would say we are for sure ready. Thank you very much for staying on, and thank you very much to the ones on the web for listening in. Thank you very much.