Here at Investor Studios where we are joined by SynAct Pharma, who today has announced the top line results for their phase II-B ADVANCE study. Joining me here today is the company management, including Jeppe Øvlesen, who will open up with a presentation. Afterwards we'll return to ask some questions. Go ahead. We are excited to show the positive top line results of the phase II-B ADVANCE study. This is a result of several years of hard work and support from investors, colleagues, and the rheumatology community. We are very much looking forward to moving the product and the company forward based on these excellent results. I will hand over presentation to Mads Bjerregaard, CBO of SynAct Pharma. Thank you, Jeppe. I am very excited that the top line results from the ADVANCE study supports our key business objectives to reach competitive profile in rheumatoid arthritis. This is what will fuel this development discussions moving forward. We want resomelagon therapy to enable patients to avoid disease escalation. To do this, we want to see a response of ACR20 scores above 75% after 12 weeks of therapy. This is the effect that has been demonstrated with Interleukin inhibitors on top of methotrexate and JAK inhibitors as standalone and combination therapy. The ADVANCE study delivers this level of performance. Response will deepen from ACR20 to reach ACR50 and ACR70 over time. We want to see a trend of response to resomelagon that continues to deepen response for 6- 12 months. This is what physicians and payers will be looking for when assessing whether to adopt the concept. The ADVANCE study provides this trend. We want resomelagon therapy to provide a clear impact on inflammation markers. This will support the translation of how the pro-resolving mechanism of resomelagon actually works in a clinical setting. With a clear impact on inflammation, we believe this will apply across multiple indications. The ADVANCE study provides a clear reduction on inflammation markers. Lastly, we want resomelagon to be very safe to be used as early as possible before the use of immunosuppressant therapies associated with higher risk for patients. The ADVANCE study delivers on this point too, demonstrating resomelagon as a very well-tolerated therapy with no immunosuppressing features. From a business development point of view, the clarity that this data provides in terms of competitive profile relevant for healthcare practitioners and payers in the U.S. should be highly interesting for strategic players looking for potential paradigm shifts in the treatment of RA. With that, I will hand over to our Chief Scientific Officer, Thomas Jonassen, who will walk us through the data and reflections on the data set. Here you go, Thomas. Thank you, Mads. I'm very pleased to present the high-level data, the outcome of the ADVANCE study. The study was set up testing three doses of resomelagon, 40 mg, 70 mg, and 100 mg, given as a tablet once daily versus placebo match tablets, given in combination with methotrexate in newly diagnosed rheumatoid arthritis patients. That means patients who had the RA diagnosis within six months of inclusion into the study, who had high disease activity evaluated by CDAI and DAS28. Importantly, showed sign of systemic inflammation as CRP should be outside normal range. The compound and placebo was given once daily as a tablet, and methotrexate was given a predefined dose escalation approach, starting with 10 mg once weekly, reaching 20 mg once weekly after eight weeks dosing. Glucocorticoids was prohibited and could only be given as rescue medicine according to predetermined rules. Reduction in DAS28 was used as a primary readout, as it according to recommendation from FDA gives better opportunities to discriminate between doses that there are ACR scoring system. However, ACR20 was set as a key secondary endpoint and outcome of this study to be considered just as important. The ACR scoring system will be used for primary readouts moving forward in larger late studies. Other secondary readouts included ACR50/70, CDAI, SDAI, and HAQ. This study was conducted under US IND at sites in U.S. and Europe. Next slide. To the left, you have an overview of the distribution randomization and completion in the four treatment groups. Overall, the study was well conducted with relatively few discontinuations. The most common reason for discontinuation was withdrawal by the subject. The table to the right shows baseline characteristics. There were no major differences in baseline characteristics between the four groups. The majority of participants were women in mean age in the late 50s, and for the 40 mg group, early 60s. For all four group, time from diagnosis was around two months, and the majority of the participant was classified according to ACR/EULAR class II and III. With regard to disease activity based on DAS28 and CDAI, the participants shows slightly higher scores than was seen in the BEGIN and the EXPAND study and confirmed high disease activity. This slide summarize major efficacy finding. Presenting data from the methotrexate placebo control group and the group treated with 40 mg resomelagon in combination with methotrexate. As this turned out to be the most effective dose of the three applied in the study. The 40 mg showed to be superior to the other two groups, who both, as the 40 mg group, showed higher response rates compared to the controls. A finding that strongly support the common recommendation that compounds with pro-resolving capabilities don't show classic dose response linearity. Highlight that the compound, even relatively low dose, induce pharmacological effects. Overall, as shown, the reduction in disease scores and the compound's ability to induce ACR20 is very much in line with what we saw in the subgroup analysis in the EXPAND study. For most readers, the control group had markedly higher response rate. The primary readout based on reduction in DAS28 was not reached. The compound showed a very strong ability to induce ACR20 reaching 76.4%, compared to placebo-treated groups reaching 60.8%, with a p-value reaching 0.06. This clinical meaningful ACR score was supported by significant reduction in simplified disease activity index, that for many reasons could be used interchangeable with the other clinical scores for evaluation of dose response study as presented. Very importantly, resomelagon significantly reduced CRP in all treatment groups compared to what was seen in the control group. Finally, the compound also had the ability to reduce the neutrophil-to-lymphocyte ratio. Again, this was seen at all dose levels compared to what was seen in the control group. A finding that strongly support the compound's ability to modulate the immune system without induction of immunosuppression. The graph to the left shows ACR 50 and 70 scores at the end of the 12-weeks dosing period. As mentioned, ACR20 went as high as 76.4% in the most active dose of resomelagon compared to 60.4% in the control group treated with methotrexate and placebo. ACR50 reads almost 40% and was numerically higher than what was seen in the control group. The graph to the right shows the time course for ACR20 during the 12 weeks dosing period, suggesting that the compound's treatment potential kicks in after eight weeks. It is therefore our interpretation that continued treatment with the compound beyond 12 weeks would have the potential to induce further increases in disease modulation, most likely to be shown by increases in ACR 50 and 70. This to be shown in longer studies, which according to current development guidelines, should be conducted in phase III. This slide shows the ACR scores in the subset of patients who, at inclusion, qualified as class II and III according to ACR/EULAR classification. In the patient who, compared to those in class I, are more affected by the disease. In the class II and III patients, which is the majority of the participants, ACR20 in the 40 mg group had a significantly higher response rate, reaching 76.8%, compared to 56.1% in methotrexate placebo-treated controls, as shown in the graph to the left. Shown to the right, the discrimination relative to control was present throughout. This finding strongly support that resomelagon retained its activity in the more severe patients, whereas methotrexate seems to be specifically active in less severe class I patients. This slide highlights resomelagon's ability to induce CRP, the graph to the left, which strongly support further evaluation of the overall effect of the compound on biomarkers that will be conducted in the coming weeks. Just as importantly, highlight the ability of the compound to reduce disease activity, as shown by the significantly higher reduction in SDAI when compared to control group. Together, these findings further support the potential of the compound and support the further modulation of disease activity could be expected with continuous treatment beyond the 12-week as applied in the current study. The side effect profile is presented on this slide. Overall, the safety profile support that the combination treatment of methotrexate and resomelagon is well-tolerated, with few most transient adverse events with mild intensity. Numerically higher number of adverse events in the 100 mg group was found compared to the lower doses in 40 mg and 70 mg. No serious adverse event was reported in the resomelagon treated patients. The most common adverse event was related to transient increases in liver enzymes and gastrointestinal discomfort. These adverse event were, in most cases, by the investigators, attributed to methotrexate treatment, and consequence of that was that they decided either to stop further increases in methotrexate dosing, reduce in the methotrexate dose, and in a few cases, resulted in discontinuations. No sign of immunosuppression and no increases in infection rates and laboratory finding was identified. This slide shows results from larger clinical trials with, to the left, AbbVie's JAK inhibitor, upadacitinib, Rinvoq. It's from the SELECT-EARLY study, testing the compound with methotrexate treated as control. In previous treatment-naive, with the majority newly diagnosed patients with high disease activity, very comparable to what we saw in our ADVANCE study. In the middle graph, we have data from Eli Lilly's JAK inhibitor, baricitinib, Olumiant, testing the compound as monotherapy or combination with methotrexate, with methotrexate treated as control. Again, in newly diagnosed, previously treatment-naive patients with high disease activity. To the right, we have data from a clinical trial from Karolinska, testing the TNF inhibitor etanercept as monotherapy or combination with methotrexate, with a methotrexate treated group as control. In all three studies, the maximum effect of ACR20 after 12-weeks dosing was in the range of 75%-80%, and the ACR20 reached in the control group reached with methotrexate was between 56%-62%. Interestingly, etanercept had to be combined with methotrexate to reach beyond 70% following 12-weeks dosing. Whereas the studies with the JAK inhibitor showed that the potential of the compounds could reach above 75% as monotherapy, and addition of the compound on top of methotrexate did not have any further treatment efforts. What is also shown is that the ACR20 response at 12 weeks are very much on par with what we showed in the present study. Shown here by the overlay from data from our current study. Strongly supporting that the potential of resomelagon as a potential new treatment option to induce disease modulation without immunosuppressive effect is a very attractive opportunity moving forward. With this, I will give the words to Mads. Thank you, Thomas. I want to try to provide a little bit of business context to what you've just seen. In the U.S. alone, more than 1.3 million people are treated for rheumatoid arthritis. 40% of patients are currently not experiencing adequate response to the first-line therapies and are treated with novel biologic disease-modifying antirheumatic drugs, so DMARDs, such as the TNF blockers and synthetic DMARDs like Janus kinase inhibitors or JAK inhibitors, as you just saw on the slides that Thomas presented. This is a major burden on the cost to the healthcare system, with the majority of the value of the market really stemming from the use of these novel compounds. All of these novel compounds are associated with risk from immunosuppression as well as with cardiovascular risk related to the use of JAK inhibitors. The current U.S. market's value for rheumatoid arthritis drugs is estimated to more than $21 billion. This is the market that we are addressing with resomelagon. The ADVANCE study is really confirming the opportunity to expand the use of novel mechanisms of efficacy, as you've seen with the introduction of JAK inhibitors and the biological cytokine blocker mechanisms, such as TNF blockers, to newly diagnosed patients without the burden of immunosuppressants. On this slide, what you see is you see the patient flow from newly diagnosed patients treated with methotrexate, perhaps getting corticosteroid to establish effect a little early on. If that is not adequate in terms of effect, you need to do something more. Either you add more conventional DMARDs to your regimen, more glucocorticoids, or you change to biologic TNF blockers or IL cytokine blockers and so forth. If that doesn't provide adequate results, you may try the JAK inhibitors. All of these therapies, again, comes with immunosuppressive features and concerns around infections associated with that. JAK inhibitors are associated also with the cardiovascular events. We see that resomelagon being positioned very well into the early treatment because of our safety profile being very benign and highly tolerable, and we can apply a novel mechanism of potential effect really to patients early on and trying to establish effect and avoid escalation in the disease. We have tested this profile with a representative group of thought leaders in the U.S., all physicians who treat a lot of patients with rheumatoid arthritis in the groups that we're talking about. They point out to four key items. Truly novel mechanism of action. That's to resomelagon. It's highly differentiated from the existing therapies. That's one tick mark for why we should use this. The non-immunosuppressant is perceived as a highly attractive feature. That's a differentiator to everything else that is used in the market. Very interestingly, what comes across is the possibility of providing upstream action rather than just blocking downstream inflammation. Treating early with a compound like resomelagon could really point to upstream action instead of downstream blocking. Of course, physicians need to see data to prove these findings and to use it in clinic, and this is exactly what can be produced in a phase III program to show that in a confident manner. We are very confident that the profile that the ADVANCE study supports will be a highly attractive and competitive therapy with the potential to change treatment of newly diagnosed rheumatoid arthritis. With that, I will hand over to our Chief Executive Officer, Jeppe Øvlesen, for a final comment. Thank you, Mads. We are very happy to show promising results in the resomelagon in the treatment of RA. The ADVANCE data support both business development and moving forward towards phase III development. We believe that we are going to have a very constructive business development agenda ahead of us in the coming time. We will start with a busy agenda on BIO International in the U.S. in the coming week, and we are going to speak with many pharma companies of their interest and the possibility for including our project in their portfolio. To conclude, the clarity on the safety profile, the duration of treatment, and especially dosing, enable us to move forward towards a phase III design with great confidence. The clarity on competitive profile, outcome relevant for healthcare professionals and payers enable us to engage with strategic business partners in a constructive and facts-based manner. Our next step are to plan for end-of-phase II meetings with FDA and EMA. As our priority one, two, and three, we will establish partnership around clinical development and commercialization. With that, I will close the presentation and will open the call for questions. Thank you very much. Thank you very much. We are now opening the Q&A, we also do so to you viewers who may ask your questions in the live chat during the Q&A session here. I will start off by asking you, Thomas Jonassen, resomelagon is built around resolution rather than suppression. Now with ADVANCE to be topline readout in hand, what does the data tell us about that mechanism in practice, and what stood out most to you? I think that the data we are generating in this study strongly support the concept of resolution therapy. The concept that you can induce disease modulation without suppressing the immune system. With reaching ACR20 at 75% without inducing immunosuppression is actually very interesting finding, as such large numbers only have been reported, as we said here in the presentation, with JAK inhibitors, TNF blockers, and then of course with glucocorticoids. I really think that it highlights the potential of resolution therapy and look very much forward to further development of the compound. In addition to that, of course, the signal of CRP is a great important as well, as it highlights the potential not only to modulate the inflammatory system by inducing resolution, but also to drive it to another set point with lower inflammatory activity. Based on that, and we have already got the questions about what about then about the primary readouts. Why did we not reach that? The answer is, well, we did reach a reduction on all the clinical parameters of DAS28, CRP, and SDAI that we had expected from previous study. The response rates in the control group that was treated with methotrexate and placebo was somewhat higher than what we had planned for. Therefore we did not reach significance. Nevertheless, we did see significant effect on just as equally important SDAI. Then, of course, we saw the ACR responses, which surely are the most important for the further development of the compound. The chat is very active, and I'll try to get all of the questions that are asked here, but I believe this one is for you, Thomas. Placebo response in ADVANCE was materially higher than in previous studies. What factors may have contributed to this, and how will this influence the design of a phase III program? I think we have addressed some of it already in the presentation as well as in the press release. That when we looked at the patients, you could say based on the ACR classification score, those in class I, which everything else, you can have high disease scores but still be in an early, not really devastating state of the disease. If we took them out of the analysis, which in many ways could be very relevant moving forward, then the response rates in the control group, the methotrexate placebo-treated, was reduced to 55% on ACR20. Which was, you could say, more in line with what we had expected from the previous study and what you could argue would be a relevant response rate in patients where you do not co-administrate glucocorticoids. That's part of it. The other thing is that we did have a higher response. Overall, we had a higher disease activity at baseline, meaning that the statistical phenomenon of regression to the mean probably plays a larger role in this study than in previous one. Even though that, of course, it is disappointing that we did not reach the primary readout based on the DAS. We think that the overall response, especially evaluated through the ACR scores and the effect on SDAI and CRP, are strongly supporting the treatment effect of the compounds. I think that's the answer. Slightly higher disease activity, a number of patients who were very early in the disease and therefore have a higher likelihood to respond to methotrexate. Another question which might be adjacent to that. Do you believe this data set to be strong enough to support phase III initiation, or does it fundamentally require additional clinical validation first? I think we can agree that the compound is well-tolerated, has shown relevant clinical effects during this 12-week study in combination with methotrexate, and therefore it would be logic that the next step would be a longer study to show the full potential of the compounds on not only on ACR20, but also on 50/70 scores after typically six months treatment. The next step would be to go into larger study, which again, logically would be phase III. Thank you very much, Thomas. I will return to you in just a moment. First, I wanted to visit Mads as well. Before the data arrived, you encouraged investors to look beyond the headline number to the full efficacy and safety picture. With the result now in hand, what does that fuller picture tell us about the value of resomelagon? Well, thank you. Now I'm happy and glad that I started initiating that discussion there early on to really look for what's the total picture of what we're going to get here. I think what I was framing or what I alluding to, and I will very much do today, is the fact that what is that you need to show physicians and pairs down the line for why should you use a compound like this, and why should you pay for it? Those two elements are very much linked to performance on ACR scores. The ACR20 scores reaching a good effect on, as we see in this study, as we see in previous study, and to Thomas' point on phase III design, this is really right for a longer duration of treatment where we're going to see the full effects on this. What you reach with ACR20, that deepens the response into ACR50 and 70. Really at the ACR50 scores with this study showing 39% is much, much better than what we saw in the EXPAND trial. That bodes really well for what a long duration style would do. That's going to tell you whether you're going to change to a TNF blocker or whether you're going to stay on resomelagon. The looking broader in terms of what the business logic is, I think that's what the ADVANCE study here really hones in on. ACR scoring, the deepening effects, the fact that we could go into a longer duration of therapy in a phase III trial, that all bodes very well. I think just one more comment to the totality of this, is the fact that we show these highly significant data on inflammation markers, which really tell us something about the mechanisms of action, how that works in the clinic or in clinical setting, which not only benefits how the logic is in rheumatoid arthritis. Really also in other indications that might come down the road. I'm happy that looking at the totality of what is needed from a business logic really is what this study actually is supporting very well. Mads, as the Chief Business Officer of SynAct Pharma, I believe this question is addressed to you. Given the ADVANCE results, do you see SynAct primarily progressing as a standalone phase III developer, or do the data strongly support a partnering or an M&A strategy ahead of the next development stage? I'm not going to speculate on M&A, but definitely on the partnering strategy. Jeppe has been quoted as well, and I've been quoted on our priority number one, two, and three are basically to find the right partners to work with us on clinical development and commercialization of this compound. What we have with the ADVANCE study really hones in on that because back to the logic in the first question you had here, the business logic is sound. This is what the ADVANCE study is going at. We know what we need to do for the phase III. I think that's the logic that we're going to present to partners at, first of all, the BIO International Convention next week, but really continue the dialogue with the many companies we've already had a good dialogue with. That's the business logic that needs to hone in and getting a partner on board to work with clinical development and doing that right, fitting for a commercially good and sound product. That's the best situation and that's our priority, I would say, one, two, and three. We have to talk about the primary goals as well. There is a viewer in the chat who is curious about the prospect of a big pharma deal. You don't have to specify the probability, but just tell us, considering that you had positive results but didn't meet the primary endpoints, how should investors look to that considering a big pharma deal before the results and after results? Have the probabilities increased, decreased, or do they stay the same? Well, basically, from all the discussions we have had during the last 18 months with big pharma and big biotech, we have a pretty precise picture of what they want and what they're looking for. With today's results, we are convinced that we are in an even stronger position to enter into this deal-making. We have several partners that have been in due diligence for quite some time, and they have been reaffirmed by today's data for sure. Primary endpoint is one thing, but big pharma and big biotech, they understand really the need to look at the full package. There we are quite convinced that we tick the boxes that we need, and we are sure that our main asset will tick those boxes. As you all know, this project is our lead compound, it's our main asset, so to speak. Therefore, we need to make sure that we optimize on the deal-making as much as possible. That is what the next many months will address for sure. Jeppe, I think I will continue with you. How did this readout shape the business development agenda over the coming year? Could you elaborate on that? Yeah. Basically, we are having a full focus on, of course, the deal-making. We can, in the meantime, and alongside doing the business development, we can do a lot of other things to shape up the project. As you saw last week, we got an extension on the IP. It is two years extension in the U.S., and that is a really critical one because it do a lot to the valuation of the project. We can also do quite a bit of work on getting more documentation done in order to make the project even more phase III-ready. That is something that we're doing in parallel. That's something we always discuss with big pharma. How ready are we? How fast can we move into a phase III? That is sort of the main topic of that discussion. Another element in that one is that we will have end of phase II meetings with both FDA and EMA, that's another box that we're going to tick. We are very focused on ticking as many of those as possible in order to optimize the deal potential. As many of you know, we have been down that road quite a lot of times before amongst us. I think we have a pretty good picture of what to do. Thank you very much, Jeppe. I will continue to ask Thomas a few questions about dosages. ADVANCE confirmed nonlinear dose response with 40 mg emerging as the lead dose. What does that tell you about the biology as you look to phase III with efficacy endpoints, ACR20 among them? Do you see anchoring the program? I think that the nonlinear dose response as we have shown in this study is in line with what is the overall interpretation of what would be seen with a compound that induced resolution. It's not classical dose response. Actually, very importantly, you have to not have full occurrence of the receptors as that everything else would increase the likelihood for what is called desensitization, and thereby you would lose the effect of the compound. Basically, what we have learned of the compound with this study together with the other studies we have been running and the laboratory finding and so on, is that we probably can start with a higher dose and then for longer continuous treatment, you are going to a lower dose where 40 mg seems to be very attractive and where also during the morning got the question, would it be possible to go even lower? That is for the future to tell us, but 40 mg from a safety profile as well as from efficiency profile seems as well as what we know about exposure and plasma seems to be very attractive for continuous treatment. Then the shorter treatment, the higher doses as we are using in our viral program, is more effective to, you could say, to induce a fast change in a hyper-inflammatory state. This tells us a lot and this study gave a lot of information of dosing and confirmation of the nonlinearity of dose response. Could you also explain to us why exactly it is that 40 mg seems to be the sweet spot, why efficacy doesn't improve along with the dose? It probably has to do with the fact that we are stimulating receptors. We are not blocking receptors. We are stimulating receptors on white cells, and they have to have, you could say, a stimulation but not continuous stimulation. Because if you continuously stimulate a receptor, it would be internalized in the cells and stay in there, and thereby you would have a desensitization of the system, and then other systems you could say take over. In many ways, 40 mg from the plasma concentration we know that we obtain, as well as the duration of stimulation seems to fit very well into once-daily dose regimen. We have previously argued very strongly that we have to be below what would be the expected dose in plasma to stimulate the receptor, and we really think that this further supports that notion. That's not to say that 100 mg was very much different in responses as the 40 mg. We have like a plateau level here with responses where in this case the 40 mg was most effective and probably what should be taken further in longer treatments. A follow-up question on that. Has this now fully de-risked the dose selection for phase III? I think that we have a very good candidate in 40 mg. We can still discuss whether we should start right off with 100 mg or whether you could do something in the first week to reach that state, as we know that 40 mg probably should be given for one week before we reach the plasma concentration we would like to attain. Besides that, I think, yes, we know that 40 mg should be taken on moving forward. Another question regarding dosages, I do believe. CRP levels were noted ranging around the 20 mark. It was clearly lowered in the treatment group. What can be expected from this marker in RESPIRE and RESOLVE? What the data shows clearly was that we, by modulating the immune system, was able to show a significant reduction in CRP, more than a 50% reduction, compared to what we saw in methotrexate placebo-treated, indicating that the compounds do have abilities to modulate the inflammation on top of methotrexate. That, of course, is very important. We are going here during the next week, months to make a quite extensive investigation into biomarkers to get the full picture of the results generated. We know that from the literature and from daily clinic, that some patients are more myeloid driven than other, meaning that other are more fibrotic and other are more T-cell driven when you look at the inflammatory activity in rheumatoid arthritis. Evidently, patients where our compound had the highest likelihood to work, that will be on myeloid cells as well as fibroblasts, which are not the main target for methotrexate. We look very much forward to dig more into that and get the full picture. Thank you very much, Thomas. I'll return to you in just a moment, but I want to ask a question to Mads as well. Considering the size of the global market and resomelagon's mechanism could reach well beyond it into patient group poorly served today. With this data in hand, how do you frame the scale of the commercial opportunity? I don't look at the commercial opportunity different from what I did yesterday. I think the positioning in rheumatoid arthritis of honing in on newly diagnosed patients with high CRP levels, that's approximately half of the patients with moderate to severe disease. Treating them for X number of months and even much, much longer to avoid going into biologics. In the patient population that respond very well to this, they will likely continue on therapy. That's a huge thing. Because we're trying to avoid a trip down in the biologics and so forth, that's a very expensive way to do. That means that from a pricing point of view or the value of resomelagon is also pretty high. When looking at it and say, if you have a market just in the U.S. that is above $20 billion in market value for novel mechanisms that is used, and we can add maybe 5% to the patient population that are treated with novel therapies, albeit maybe at a slightly different price, I think we have a good chance of making a proposition for a drug that clearly reaches beyond the $1 billion revenue frame. I think that is highly likely that with the right data and the push into newly diagnosed patients with these factors showing it works over a 6-12 month basis, that's a drug that is highly likely to reach that. That is not just me saying that. That is also confirmed when we do market research with both healthcare practitioners. I referred to this also in the presentation. Immediately they get the positioning and the mechanism and so forth and what we're trying to do. If the proof is there's pretty high likelihood that that's also going to be used and paid for. I think that we are embarking on something new here, which could have a fantastic effect in how we treat rheumatoid arthritis, that bodes for a significant market value. A viewer is curious about the high sensitivity CRP data, statistically significant. Is that strong enough to trigger a major licensing deal or partnership with Big Pharma in the near future? What do you say? I think the answer is yes. Had we five years ago explained the case, a lot of companies did not understand what resolution therapy was about. We have recently seen that not at least J&J had put money into companies and projects that are focusing on resolution therapy. We also know that BMS had a quite advanced program at one time point in the cardiovascular field where they discontinued, not because of efficacy but strategic reasons, in the cardiovascular field. The concept that we do have modulation of the inflammation in a way that it turns out to not only just modulate macrophages as we were talking about previously, but actually to a degree where we can see that we reach another set point with regard to CRP is very, very attractive because you could say that adds to the overall potential of the compound. That's very attractive and, of course, very, very in favor of the compound. Maybe just to add to that. Of course. If you're a big pharma company, you're obviously looking at multiple indications, and the fact that you have something that can change the course or change the set point for systemic inflammation, that speaks into multiple indications, and that's what J&J has been investing into and several other companies. I think we speak right in that ballpark, and we look really much forward to the discussion that we're going to have starting next week. Thomas, I believe I will continue with you. Sorry, Mads, I'll return to you in a moment. No problem. Considering safety is also, of course, important. Non-suppressive, oral, no immune suppression. How does the profile from ADVANCE support resomelagon's place in first-line treatment? I think it's supportive. First of all, overall, we had very few side effects in the study, in all groups, with slightly increased numbers in 100 mg compared to 70 mg and 40 mg, which is no surprise as compounds, everything equal, will induce some numbers of adverse events. The 40 mg is very, very well-tolerated. It was on par with regard to safety as the control group. We did not find any new unwanted adverse events. What we saw and what we have seen previously is that we, in a few patients, get some upper gastrointestinal discomfort. We do, on all groups, we have seen increases in a few patients in liver enzymes, which, as I also mentioned in the presentation for the investigators, were attributed to methotrexate rather than the compound treatment. All in all, very, very well tolerated. Importantly, the point more important than everything else, we do not have any signs of immunosuppression. We do not increase the number of patients who have infections. We do not see a suppression of white cells in a degree that indicates that the compound in any way should induce immunosuppression. That's the key for moving forward. There is a other question in the chat that wishes to clarify regarding the earlier question on CRP. Is there an expected range of inflammation marker hs-CRP milligram per liter in the patients expected to be included in the RESPIRE and RESOLVE studies? In all the studies we are running, we are looking very much into inflammatory markers. In the RESPIRE, which is a study in a completely different patient group. That's patients who have high disease of acute viral infection, so they are hospitalized. Those patients will have high levels of CRP, among other, and evidently, we are measuring biomarkers, including CRP, in those studies to follow the potential treatment. In this case, it's a question of, you could say, acutely modulate the overactivity in the immune system, as we showed in the RESOLVE I study during the COVID, and have shown in multiple preclinical models that the ability to modulate the inflammation acutely, even in a therapeutic fashion, given after you have applied an antiviral, is a very, very attractive way to modulate the inflammation, and thereby the overall outcome of the patients. Thomas, I believe we have one final question for you before we head to Mads and Jeppe. How unusual was the placebo plus methotrexate response compared to historical RA studies and your own previous studies? Okay, let's start with our own study. In the EXPAND study, we had a response rate of approximately of ACR20 of 52%, and we did see a 1.2 points reduction in DAS28 over the 12 weeks dosing. In this study, the ACR20 was 60%, and the response with DAS28 was 1.75, I think it was, 1.8 points, indicating that it was somewhat bigger. I think I briefly addressed them in a previous study. We did have a number of participants who were qualifying as ACR class I, which everything else responds very well to methotrexate. We had slightly higher disease activity at baseline, meaning that the statistical phenomenon of regression to mean plays a role. Yes, we did see it was higher than in our previous study. When we compared to the literature, which is actually what we did in the presentation, you saw that in these studies with the JAK inhibitors and TNF blocker, ACR20 of 60% with [resomelagon], three months after 12 weeks, three months dosing. That's on par with what we see in this study. However, in these studies, up to 50% of the subjects were treated with glucocorticoids. What we have seen is, you could say, on what previously have been reported, where methotrexate has been given in a comparable dose setting, but where a number of patients, up to 50%, being treated with glucocorticoids of some doses. That's not the same as to say that it's not to see what can be expected, and what we have learned from this is that when we take the patients in early, we have an average disease time of two months. The response rate in the control group reached ACR20 at 60%, and also a substantially higher reduction in the ACR20 as we saw in the EXPAND. That's not the same as to say that But methotrexate is not able to reach ACR20 of 75% or higher within three months. That had never been reported, and that is not what we are seeing in this study. From that perspective, had we had a slightly bigger study, 75% in each group, I think we would have power to show significance of ACR20 in this study, and that is really supportive for moving forward. Mads, with the readout in hand, heading into BIO International, how do you expect the data package to affect potential partnering conversations in San Diego? This is an event, or this data package has been highly anticipated by many of the compound or the companies that we are speaking with, because what they want to see is that they want to have a confirmation can a compound like this, can it be taken into a phase III with a plausible dose, with a plausible timeline, and meeting these requirements around what does ACR20 response and 50 response and so forth, is that plausible to work out and to do a phase III study in doing that? Because that is what makes the compound. That's the discussions, or that's what companies have been looking for and what obviously we have not been able to provide in the past with the EXPAND study. Now we are producing a data set in a bigger population that speaks in that direction and gives that plausibility of moving forward, and I think that's what we're communicating here today. That's exactly what we'll be communicating to all our partners in the discussions that we're going to have. I think that is going to open up a very, we say, plausible and fact-based conversation around what does a collaboration going to look like. Because I think we don't have to reiterate too much at this point. We strongly believe in this compound. We strongly believe that what we see on the ACR20 and moving on 50 scores and so forth, that's going to do the positioning that we're talking about to be competitive. We think the reduction in inflammation markers is highly interesting. Then you have the safety profile that really allows you to be very different compared to everything else out there. Those three components is what is going to be highly attractive to the partner discussions. That's what we're going to take to the table next week in San Diego. Jeppe, to end this broadcast, what are the priorities here between planning phase III, interacting with regulatory, and partnering? What's the next step? Yeah. Basically, the priorities are pretty clear, I would say. We will conduct the end of phase II meeting shortly. We will make sure that we do additional preparation so that the whole project is more advanced towards the phase III, because that's the first question we get. How ready are you guys? Have you done this and that? We can tick many of those boxes, meaning that the big pharma can get into a phase III quicker. We extended the patent base as said before. That means that they have another two years to add to the valuation of the project. There's a lot of things that we can do. Then full traction, full focus on the partnering. We had yesterday 35 meetings booked this morning based on the data. We got another three confirmed. We are full on. We think we have the right package. As said before, we have been down this road a couple of times before amongst us. I think we have really a nice opportunity for getting the job done for sure. Thank you very much, Jeppe. Also, thank you to Mads Bjerregaard and Thomas Jonassen for joining us here today presenting and answering our questions.