Hello, welcome to the SynAct Pharma Audio Conference Teleconference. Throughout the call, all participants will be in listen-only mode, and afterwards there'll be a question and answer session. Today I'm pleased to present CEO, Jeppe Øvlesen. Pleased to begin your meeting. Thank you very much. Thank you very much for listening in on this call, and very nice to see that so many of you have joined today. We look very much forward to discuss additional and existing results from our COVID-19 study. I'm delighted to be joined by our Chairman, Dr. Torbjørn Bjerke, our CSO and founder, Dr. Thomas Jonassen, and very especially by Professor Mauro Teixeira joining us from Brazil. Mauro has been instrumental as primary investigator in getting the study up and running in a very short timeframe, and we have been very impressed with our collaboration. Move to slide number two. We will take you through a short slide presentation on our key findings, and followed by a Q&A session. I'll hand over the word to you, Thomas. Please move on from slide number three. Thank you. Slide number three, please. I will go through a short introduction to the principle behind the AP-1189 compound and the way it addresses inflammatory disease, and put that into perspective with regards to viral infection, and more specifically COVID-19 infection. The compound is a small molecule, a biased agonist to melanocortin receptors, and it works in a two-fashioned mode. It reduces inflammatory responses and at the same time, it promotes resolution, meaning that it stimulates antigen pathways, and thereby facilitates clearance on inflammatory responses. The compared effect of this is that hyperinflammation, which is one of the devastating effects of COVID-19 infection, is moderated in a fashionable way. Next slide, please. The target for our compound is melanocortin receptors who are present on white cells, meaning in immune competent cells. We are focusing on, our compounds stimulate the MC1 and MC3 receptors, which is both present on white cells, including macrophages. To the right you can see here a model of how the compound's dual action is mediated. In this case, we have a macrophage here. It is stimulated with a pro-inflammatory stimulus that could be a virus infection. In this case, by stimulating melanocortin type 1 and melanocortin type 3 receptors, we reduce the pro-inflammatory activities of the macrophages, meaning that the release of pro-inflammatory cytokines, including IL-1, IL-6, is reduced but never blocked, meaning that we never induce immunosuppression but modulate the inflammatory response of pro-inflammatory pathways in a beneficial way. At the same time, we have a large fraction of the macrophages who go for a classical pro-inflammatory phenotype to a pro-resolving phenotype, meaning that it, through what is called efferocytosis and phagocytosis, clear up the ongoing inflammation. Again, this is a process that is significantly stimulated by our melanocortin receptor agonist compound. Next slide, please. Macrophages play a pivotal role in development of hyperinflammation and respiratory distress in COVID-19 infections. They are stimulated, as you can see, as highlighted here, and we're not going to details to the left, through viral infections, and macrophages is then generated from circulating white cells that goes into the lungs and then plays a role very, very high up in inflammatory cascade. The concept for our compound is, among other, to block, or not block, but inhibit and modulate macrophage activity. If you have the ability to reduce the macrophage's pro-inflammatory activity, you will reduce the influx of neutrophils and other pro-inflammatory white cells, and also reduce the release of pro-inflammatory cytokines by these T cells. All in all, the macrophage is central for our understanding of how our compound works. Next slide, please. Our compound is a biased agonist. It means that it stimulates the receptor, the cyclic AMP, not through cyclic AMP was a classical way to stimulate melanocortin receptors. As you can see to the cartoon and to the graphs up to the right, it worked through ERK phosphorylation and thereby specific stimulation of this pathway. It does through binding to an allosteric binding site from the receptor and thereby have a unique pharmacological effect on the receptors and thereby also on the inflammatory responses. These responses, as I showed on the other slide, is associated with reduced pro-inflammatory activity and at the same time, promoting resolution. By this, we decided to set up a collaboration, and please go to slide number seven. Next slide. Where we have made a collaboration called RESOVIR Resolution in Viral Infection together with Mauro Teixeira, who is present on this call today. With Mauro Perretti at the William Harvey Research Institute in London, who is also a pioneer in resolution therapy, with the aim to explore the possibilities to, with our pro-resolving compound AP-1189, to see whether it would be possible to modulate viral infection, where the first aim is to go for COVID-19. We therefore set up an investigator-driven study in this RESOVIR collaboration with Mauro Teixeira, a Principal Investigator. The setting is that we started up with an open-label study where we tested safety of the compound given once daily for up to two weeks in COVID-19 patients. Following this initial part, we continued in the second part of study, which was a double-blind, placebo-controlled study in a 2-to-1 randomization, meaning that we give for every two who gets active, we have one on placebo treatment, and the compound is then given to patients as an add-on to standard therapy. The inclusion criteria is that the patients who have positive COVID-19 infection, they had to be adult, meaning that in lifespan or age between 18 and 85, a disease history for less than 15 days, and they would have a need for supportive respiratory assist, meaning that they were having a need for supplementary oxygen on mask on a nasal cannula. Of course, they should have signed an informed consent. The primary efficacy endpoint was time to respiratory recovery, defined as the time from initiation of treatment to the time where a patient's saturation was defined to be 93 or higher on ambient air, meaning that they would have a normal saturation in the absence of supplementary, in the absence of extra oxygen. Secondary readouts including date of hospitalization, oxygen-free days, need for mechanical ventilation, and circulatory, inflammatory markers, which is still a work in progress, and we would look very much forward to quite extensive exploratory work that we have initiated on this part. The study, as I said, was conducted in Belo Horizonte, with Professor Mauro Teixeira as principal investigator. With this, I would like to give the work to Mauro. Thank you very much, Thomas. Great pleasure to be here. I'll just add in the slide that at the time the study was conducted, we virtually only had the P.1 variant of the virus, which is the Gamma strain, the Brazilian strain. In other words, we were actually dealing with a more severe variant of the virus at the time the study was conducted. Next slide, please. Just to show that the baseline characteristic of patients was very similar. They were on average 51, 52 years of age. That was mostly due because at the time, again, vaccine was introduced to older people, so we were left with middle-aged individuals, well balanced in terms of gender and well balanced in terms of comorbidities. Indeed, most patients who were hospitalized and were given medication or placebo had some degree of comorbidity, which actually explains the reason they were actually in hospital. The severity is moderate to not so severe, an NEWS2 score of around five. They all needed oxygen supply around four to five liters and had an oxygenation index of about 200. The baseline characteristic of patients was very similar between them, which allows for the comparisons. Next slide. I think this is really the cream of the result. The mean time to recover, it was around 10 days in placebo, 9.9, and it went down to 5.9 in treated patients. This is a decrease of four days in need of oxygen to reach a saturation of over 93% on ambient air. I think if you look here to the right, a significant amount of patients actually got better significantly faster. There were a significant amount of patients that were actually not needing oxygen supply by day four. That actually needing less oxygen translated well in terms of hospital stay. Indeed, there was a significant drop of three days in hospital stay. Again, if you look here to the right, because fewer patients needed oxygen until day three, four, it means that patients that were released from hospital at day four were mostly patients who were treated with the compound. That is shown better here. If you look here to the right, about a third of treated patients were discharged from hospital on to day four because there was 50% of them already actually reached respiratory recovery. This is actually really exciting because you had four days less of oxygen and three days less of hospital stay. Obviously, that actually reflects the more severe phases of the disease. Fewer patients needed oral intubation or mechanical ventilation. 17% of the placebo-treated patients went on to have an oral tube and mechanical ventilation, and about a third of that in treated patients. If one looks at acute kidney injury as affected by increase in serum creatinine, about a third of control group patients had a degree of kidney injury, and that was decreased almost by half in treated patients. As far as the safety, there were no. I think we have to ask for— Sorry. —going through the slides. Next slide. I forgot. Please forgive me. We are actually on slide 13 now. I apologize for this. On slide 12, we actually showed the research on the more severe patients, which is mechanical ventilation and acute kidney injury. On slide 13, the next slide, we are actually looking at the adverse events. Very much so, we had no major adverse events that were associated with the medication. Usual adverse events were nausea and vomiting. At present, the medication is given as an oral solution, and you can imagine giving an oral solution to someone who has shortness of breath is not simple, because it's difficult to breathe and taking something by the oral route as a solution. Nausea and vomiting were the really most important adverse events, and they were more associated with AP-1189 compared to the control. Otherwise, adverse events were comparable between groups, and there were no severe adverse events that were associated with the compound. With that, I will pass it on to you, Thomas. Well, thank you. The side effect profile that we see here is very comparable to what we have seen in phase I in the healthy volunteers, as well as in our ongoing rheumatoid arthritis study. Nausea and vomiting is the most prominent. We have also seen temporary increases in transaminases in previous studies, but we also have identified that in placebo-treated patients, and especially we have reported from the rheumatoid arthritis study that the increases was present in placebo and not in 100-milligram dose level. All in all, this side effect profile was what we expected, and we believe at least some of it is to be, as Mauro mentioned, is attributed to the formulation that we are currently working with, which is a liquid suspension. Therefore, we look very much forward to continue our development in the autumn with our newly developed tablet. As we did not go through, as there was not shipped through the different slides, I think it might be worthwhile just to jump back to slide number 11 or 10 actually, because when Mauro, he went through the data, and he mentioned and showed very nicely that we had a reduced time to respiratory recovery that reached clinical significance. He also very highlighted very importantly that average time for hospitalization was reduced with 3.3 days. As you can see here on slide number 10, there is discharge from hospital is present in a significant amount of the AP-1189-treated patients already from day one, whereas the first discharge on placebo-treated was on treatment day five. The next slide here, slide 11, showed what Mauro also highlighted, that the oxygen needed for respiratory recovery at treatment day four was markedly lower on the AP-1189-treated patients compared to placebo-treated. Hospital discharge, one-third of the patients had left hospital before the first placebo-treated. With that in mind, I would go to slide 14 for the study conclusions. The conclusion is that we gave the compound as add-on therapy to standard therapy that includes low-dose dexamethasone. The typical dose is 6 milligrams per day in hospitalized patients with a need for supplementary oxygen treatment. Under these circumstances, the compound significantly reduced time to respiratory recovery by four days compared to placebo. It reduced the time to discharge from hospital by 3.3 days compared to placebo as an average in the full data material. It facilitated early discharge from hospital, with 33% of all AP-1189-treated patients discharged following four days of treatment, compared to none of the placebo-treated patients. It was associated with a reduced fraction of patients who developed need for mechanical ventilation. The numbers are small, the take-home message was that we more than halved the need for mechanical ventilation in the active compared to placebo. Also from a purely exploratory point of view, we looked into changes in creatinine, to make a rough estimate on development of acute kidney injury. Again, the picture was clear that a smaller fraction of the patients on active had increased or had affection of the kidneys. Importantly, there were no treatment limiting adverse events attributable to the compound. All in all, that is where we are right now with this compound, with this study, which we find very interesting and look very much forward to proceed with additional activities within our RESOVIR collaboration. Let's go to the next slide, please, which is slide number 15. The disease development in COVID-19 is associated first with a viral response phase and then gradually with an inflammatory phase in the patients who gradually developed with this hyperinflammatory response. Typically, the initial presentation is shortness of breath, and then eventually you could have developed more severe lung affection, what's called acute respiratory distress, but also affecting other organs, including the kidneys, circulatory and brain. The aim is, of course, to get rid of the infection if we have it, then to control this inflammatory phase of the infection. Today, NIH have a recommendation is to use monoclonal antibodies. If possible, give them pre-hospital. They are expensive and limited to use to where you actually have the money and availability of these monoclonal antibodies. Dexamethasone following a very compelling study from last year showed that low dose dexamethasone treatment given at time of hospitalization could have beneficial effects. It has to be low dose, and thereby you reduce the unwanted side effects. It is known that dexamethasone also in COVID-19 patients associated with infections, and more than anything else, the black fungus disease as described from India is to highlight as an example of a very severe dexamethasone induced side effects. Despite that, dexamethasone actually low dose control fashion works. That not at least that we on top of dexamethasone actually can show a four days with a reduction in terms of recovery. We find that very interesting. remdesivir is also recommended by NIH, and again, has to be given in-hospital. Where do we see AP-1189? The potential use could be as going in earlier than we did in the actual study. We'll go in as soon as the first symptoms of shortness of breath was initiated and from there on. In other words, when the patient inflammation phase is initiated. The RESOVIR-1 study was designed in a way where we went in and gave the compounds in patients who already were on dexamethasone. The potential is, of course, to stay in these patient population, but there will also be a potential to go early on and dose prior to in the disease development. Eventually you'll get the potential to reduce hospitalization. With this in mind, and these data, we feel an obligation that we And also a very high demand and within our company to continue the work within viral infection. One of the first thing is to discuss with relevant authorities, including the authorities of Brazil, to have to potentially could come to an emergency use of this compound. Immediately, and also in parallel with that, set up a next study, a confirmative study of this compound's ability to speed up recovery in these patients. Speed up recovery, respiratory recovery, potentially reduce hospitalization, and then the aim is to conduct that with our newly developed tablet, who is going to be available at the time where we could have this study initiated, and the study would from natural reason be in a continued collaboration with Professor Teixeira. With this, I would give the work to our Chairman, Torbjørn Bjerke. Next slide, please. Thank you very much, Thomas. On slide 17 we are now. First of all, I would like to take the opportunity to thank Professor Mauro Teixeira and his team, and also thank very much the patients participating in this study. Remember that the study was done in a very busy period in the hospitals of Brazil, and this busy period continues to be. We are very grateful for that. I would also like to take the opportunity to express our gratitude to SynAct Pharma shareholders. We really like all the constructive feedback we get from you. Thank you very much, and please continue to give us that feedback. The drive for us at SynAct Pharma, but also for all other biotech companies, is really to develop new innovative medicine that can transform the patient's life, that can transform how we treat the patients. It gives value to society, but it also gives value to the company shareholders. We believe that the data coming from this study gives value to the patients. We believe that we can have a potential transformation of how to treat severe inflammatory disorders like COVID-19 inflammation. Please remember that COVID-19 inflammation is one of the worst inflammation you can think of. Based upon these results, it seems that AP-1189 is tailor-made for that inflammation. That's why we both see a big medical need. As you know, with current geographic hotspots like Brazil and India, I think the last week it has been about 50,000 new cases every day in these countries. We also see some vaccine hesitancy, a new emerging virus variants, the Delta variant coming up, and also the possibility of seasonal recurrences. We believe that effective new treatments are still needed, there are not many treatments, as Thomas said, that can really go in and change the pathophysiology, the course of the COVID-19 inflammation. We believe there's a big medical need out there to come up with new and safe and effective oral therapies. We have a clear plan forward. As Thomas said, we'll discuss the next step with regulatory authorities. Of course, they need to give us feedback on what they see in a potential opportunity to get emergency use authorization. We are indeed keen to bring this therapy forward to the patients as soon as possible. In that work, we also need to scale up the so-called active pharmaceutical ingredients, the API, and tablet manufacturing. Thomas Jonassen, our Chief Operating Officer, do have the responsibility for that. As you have heard today, this is definitely going in the right direction. I also want to point out that the results here also gives, let's say, a good feeling or a good path forward to the opportunity to treat other very severe virus inflammation. I'm thinking about influenza. I'm thinking about dengue. That is, again, a big problem worldwide, especially in Brazil. This gives us the opportunity actually to look into this in more details in the RESOVIR collaboration, where we have what we believe are the best investigators in the world within this space. We are looking forward to the next steps. We'll work as compliant and as quick as we always do in order to secure these. There are of course uncertainties in it, but we look forward to have the discussions with the authorities. The new chief medical officer, Anders Hill, will have the responsibility together with Thomas Jonassen to initiate these discussions. Of course, also together with Professor Mauro Teixeira in Brazil. From that, In parallel will set up a study that can give even more light on the opportunity for AP-1189 to fight COVID-19 infections. On the right side here, we have put up the expected milestones. As a shareholder of SynAct Pharma, you have been witness to quite some progress during the last one to two years. Of course, the first one was the interim data in rheumatoid arthritis, and this is still our main focus. It is to bring AP-1189 to a proof of concept and third run, hopefully, in rheumatoid arthritis that do have a big medical need as well. Among the other milestones, I can mention the new potential intellectual property for AP-1189. We are building several layers of protection which is important, of course, in terms of the market exclusivity for AP-1189 in different diseases. We are working on the tablet and will soon come with more news on the tablet formulations. We also are, of course, looking forward to have the full top-line data in the rheumatoid arthritis study in the end of Q3 this year, and then decide on how to proceed with further development of the pipeline. All in all, I think it's a fantastic good opportunity. We have a good start here with AP-1189 showing even effect in the worst-case inflammatory disease. I would like to open up for Q&A, so please, operator. Thank you. If you wish to ask a question, please dial zero one on your telephone keypads now to enter the queue. Once your name has been announced, you can ask your question. If you find it answered before it's your turn to speak, you can dial zero two to cancel. Once again, that's zero one to ask a question or zero two if you need to cancel. And we have a few coming through. The first is from Adam Karlsson of ABG Sundal Collier. Please go ahead. Your line is open. Hi. Thank you for taking my questions. A few from me, if that's okay. First one, just wanted to confirm that the data presented last week was based only on the randomized blinded portion of the trial, i.e., the 36 AP-1189-treated patients versus the control arm, and that this was the primary statistical efficacy analysis outlined in the statistical analysis plan, or whether this additional with the six patients from the safety run-in was part of the statistical analysis plan originally. Thank you very much, Adam. Thomas, can you take that one? The data we presented last week was, yes, from the randomized part II of the study. The data we present here is from the full dataset, which we considered would be logic to do and also a part of the original plan as the comorbidity in the patients and the way it was treated was comparable to what has been done in part II, except for the fact that the first six patients was open label. In any case, you have to have in mind that this is the first exploratory data, and that we are planning, and we will continue development of this compound. Great. Thank you. On further potential efficacy measures, were there other secondary or exploratory endpoints that you recorded? I'm thinking specifically about survival, if there's anything to be said about that. Obviously, a small sample size, but it would still be interesting to hear. On the endpoints not yet reported or so, if there's anything you can say on how they stack up relative to the data we've seen so far in terms of trends towards benefits, if there's anything that looks more neutral or so. First of all— Thomas? Yeah. Within the study period, we did not have any fatal cases, and that means we followed them up to day 28. With regard to additional readouts, there will be. Importantly, and more than anything else, we have all the samples for exploratory and secondary readouts, including for cytokines, other inflammatory pathways, also a lot of exploratory pathways to get more understanding and mode of action and the potential of our compound, as well as resolution therapy in COVID-19 infection. Great. Thank you. On the safety tolerability side of things, just curious on the frequency but also the severity of the nausea, whether that was comparable between the two arms, and beyond that, whether there were any treatment-related discontinuations or dose reductions in the study. We did not have— Thomas. Yeah. Sorry. Yeah. What we can say is that we had all the patients was treated with the compound. In some patients, both on active or placebo stopped treatment when they left hospital. I think that Mauro, Dr. Teixeira, he highlighted that currently we are working with a suspension, which for the more severe cases was an issue, meaning that if you are very, very short on breath, to drink our suspension was challenging, but we managed to get through with it. That's an important part also for the future that we will continue developing with the tablets. With regards to intensity of the side effects, it has been reported, and also highlighted, that the frequency of adverse events were higher in active than in placebo, and most likely has to do, again, with the compound. In most cases, for not to say all, it was a moderate to low intensity. What we typically have seen with nausea is that it's something that comes relatively fast after intake of the compound, in most cases, actually, before we reach Tmax in blood, meaning that we believe that it had been very much to do with the current formulation that has been applied. Okay, great. A question on any other potential treatments or if there's the same investigational use of anti-IL-6 or JAK inhibitors as well for the treatment of COVID-19. Presumably, none of the study participants received any other treatments than standard of care dexamethasone and placebo or the 1189, or were there any investigational or other treatment use? Thomas. No one can answer that? Hello? What I can say is that, let me take it. Dexamethasone, the setting in Brazil is that patients in this study here typically were referred from a polyclinic, you could say a secondary ward, when they came with initial symptoms of shortness of breath. The patients are set on low-dose dexamethasone and in some cases also on antibiotics. If they develop further a need for supplementary oxygen, they were referred to hospital, at which time point we then offered them the opportunity to participate in the study. As I understand, there's not giving remdesivir, there's not giving IL-6 antibodies, antagonist or any of the monoclonal antibodies. Okay, great. Can I just add, so remdesivir is not approved for use in Brazil, and actually the effects of remdesivir at this group, which is already hospitalized, is very low. anti-IL-6 is again not widely available at all. It's reserved for patients who are a little bit more severe. In all of our patients, they had an indication for dexamethasone. They were given prophylactic heparin, and they were given antibiotics until we were sure they did not have any bacterial infection at the time antibiotics were removed. This is standard of care for Brazilian healthcare industry. Okay. Sorry, steroids were given for five days. That's also, again, standard of care. Great. Thank you. I don't know if it was shown in the slide on the baseline characteristics for the two groups, but was there any difference between the two treatment arms in terms of the course of the disease, say, days post first symptoms that they were randomized and initiated in the trial? Was that equivalent between the two arms? It was not realistic equivalent as well. It is around 10-15 days after onset disease, so we are really dealing from 13. Great, thank you. Maybe just one last question from my side. Just curious on the, obviously, discussions ongoing now about next studies and design and funding support and so on. Is there anything that you can say about the degree of funding support you would need to move forward with a confirmatory trial? Just put another way, how much of your current cash reserves would you be willing and able to put towards another COVID-19 study? Yeah. Thank you for that, Adam. We first need to talk towards the authorities and think about the next step in terms of how big should such a trial be done or how big should it be. However, remember, this was a trial with a total of about 60 patients, right? We showed the results we did. With the power calculations involved in that, I think we can do it smart. Thomas is already, together with Mauro, thinking about this next trial. We don't foresee a very big trial. In terms of the funding, we do have cash in the bank through the last financing. We will talk to authorities as well about funding, but we are a public company. What we believe is important here is that we get the next trial out to the patients to see if we can move this forward. As soon as we have the next trial set up, we will report back to the market about how big it should be and the potential progress with the authorities. Okay, great. No, that's helpful. Just one final follow-on on that question, perhaps for Mauro. Just curious to understand the dynamics in Brazil a bit more in terms of EUAs. If you look at the COVID treatments granted EUA in the U.S. by the FDA, trials of a few hundred to a few thousand patients have been needed. Is there anything that you can say in terms of the evidential burden that would be typically required for an EUA in— —in Brazil, would it be comparable to what the FDA are looking at, or is it reasonable to suspect that they would be happy with a far smaller trial? I think, as long as we design the trial for an N number for showing efficacy, Brazilian authorities, which these will totally align with FDA and EMA in terms of the acceptance stringency. We will just have to make sure that we design the trial with appropriate N numbers. I think for most studies with drugs, we are talking about below 100 to show an efficacy, whereas vaccines are typically in the thousands. The rate of disease in these patients is very high, so that tends to lower N number considerably. Did that answer your question, Adam? Adam, did that answer your question? Yes. No, that's helpful. That gave me some clarity. Thank you. Thomas, would you add something? Yeah, it was just to say that one thing is to show efficacy, the other thing is to convince or agree with the authorities that the safety database is sufficient. There we have to have in mind that we, in parallel with this program, have our main program in ongoing RA trials, where we also, on a continuous basis, generate data to the overall safety database, which would eventually be part of the overall evaluation from the authorities. Okay, great. Thank you very much. Okay. Thank you, Adam. Okay, could we have the next question, operator? Of course. That's from the line of Sebastian [inaudible]. Please go ahead, your line is open. Hi, guys. Thank you for taking my questions and congratulations on the results. Thanks. I did not really quite catch the comment that Dr. Mauro made regarding the Gamma strain versus Delta variant, could you please repeat that? Mauro? Delta is only coming into Brazil at this stage. We've had a few dozen cases at the moment. That's why everyone is really worried that the epidemic may revive in the second semester of the year. What I meant is that during our study, we had more than 80% P.1 strain, which is the Gamma strain that is circulating in our region at the moment. Virtually, there are no wild-type strains anymore. At this present moment, most cases are still P.1. They're worried that Gamma has arrived. In every single place that it has arrived, Delta has arrived. It has taken over for Gamma in most places that it arrived. That is the outcome for Brazil, and I suppose one of the advantages of inflammation host-based therapies is that actually you don't focus so much on the virus itself but on the disease caused by the virus, which it seems to be similar, and perhaps more severe in the new virus because the viral load is much higher. Okay, got it. Thank you. Regarding the rationale for designing the open label part of the trial, why was that included, and were there maybe patients selected more specifically for that open label part of the study? What's the rationale? Thomas? Yeah. The rationale was very clear that it was first time this compound should be given to COVID-19 patients. From a safety perspective, and also to be in alignment with the local authorities, we made the decision to start off with an open-label, six patients to get a grip on the safety profile and could report that back, and then ignore it, so you could say, so that safety first before anything else. The next thing is then if you go in and look at the profile of these six patients, with regard to comorbidities, and severity of disease at time of inclusion is comparable to the rest of the population. Sebastian, please remember that the selection criteria for these patients were exactly the same as for the randomized study. Yeah, very clear. Thank you. Then I was thinking regarding the complementary study, do you think that a similar design is possible? I saw what you showed in the slide, but regarding the endpoints, what are you thinking of? Then also, you mentioned that you wanted to conduct the trial with the tablet formulation. Does that also mean that the trial will likely start after the bioequivalence study is completed? Thomas? Let me start from the back with regards to the tablet. From a strictly regulatory point of view, we have all data from all in vitro experiments, all characterizations, including dissolution profile and so on. In addition to that, we have relevant exposure data from animals that support that we can go directly into man. The reasons why we would like to spend time and money to make a PK bioequivalence study in parallel with the activity we are going to set up here in COVID-19 is, of course, to have this confirmed in humans. That also from historical reasons, as we, at an early stage in this company, developed a tablet that turned out to have a very, very unpredictable PK profile. That was simply completely lack of knowledge of where we are now, and now we have a tablet and we will go fast into various patients. We actually believe that in parallel with the set up of study and also we will be fully ready and whatever we are doing with bioequivalent will not be a stopper for the development of the next central study in COVID-19. Okay, regarding timing, would that then be Q3 or Q4? Realistically, it takes at least from now to get the interaction with authority and set up the study, get the study medicine down there, get all the approval, it would take three to four months. Okay, great. Thank you. Sebastian, just a note here from me also on the results, for example, in the acute kidney injury. As we know, about 90% of patients with very severe COVID-19 ARDS infection, they develop acute kidney injury, which prolongs the disease tremendously. The signal we get here is also quite positive. We know this back from the Action Pharma days where we did development of another molecule, another melanocortin receptor agonist in acute kidney injury that we can actually impact the degree of acute kidney injury. That's an interesting observation we see here as well. Just a note. Yeah, no, that's interesting to know. Thank you. My last question. You mentioned that this collaboration was set up to investigate the use of AP-1189 also in other infectious diseases. Are there any specific indications that you are thinking of and that you would look forward to quickly enroll maybe next year? Yeah. Thomas and Dr. Mauro? Would you comment? Yeah. Actually, Mauro Teixeira, I think that it would be fair to say that you have been a pioneer in understanding of resolution therapy in viral infections with regard to not at least with influenza and dengue. Perhaps you could comment. I actually lost a little bit of the comment that she made. In a nutshell, I think we will try. We are already working with local authorities to plan the study and start this semester. In terms of outlook for other viral infections, we have actually tested it experimentally in virus models. Before COVID, we have a line of research actually checking for resolution therapy in the context of influenza. Results are as exciting, at least experimentally, as for COVID-19. To be honest, that's what we were aiming for before the COVID-19 epidemic. Obviously for our setting, there's a huge interest in dengue and diseases caused by other viruses. I think there is also a lot of interest there as well. I'm not sure whether that was your question specifically, but that's my feeling towards the whole area of research. Yeah. Thank you. That was exactly what I was asking. Thank you. And just my— Yeah, come on, Mauro. No, I was just going to add experimentally as well. One of the problems of viral infections is that they are commonly followed by bacterial infections, and that actually is the cause of death in many given circumstances. Again, experimentally, what we've shown is that we've never seen any form of immunosuppression caused by pro-resolution therapies. In other words, because pro-resolution therapy decreases the viral damage, the bacterial infections that follow viral infections tend to be much less severe, and they are safe in the context of bacterial infections. I think there's a lot of mileage in this whole field of research. Okay. That's very insightful. Sebastian, we see a big medical need both in dengue, of course, but also in influenza. As we all know, we are hit by influenza at least every second year, if not every year. Especially the elderly population die from severe inflammation in, for example, in the lung. We see a big medical need here. Okay, got it. Thank you very much. I will jump back into queue. Okay. Operator, do we have any more questions on the Q&A? Yep, we have one further one in the queue. That is from the line of Hans Sweder of Private Investor. Please go ahead, your line is open. Thank you, and thank you very much for the nice presentation and the very interesting results. I have a question regarding the adverse events, and I would like to hear if you could elaborate a little more about the increase in the transaminases. Was it very severe, and do you see any interaction between that inflammation and AP-1189? Could you please elaborate a little more about this? Thank you. Thomas? Yes. We saw one was reported to have a more than three times increase in transaminases. It was patients who at the same time developed sepsis. The question is, and it is expected in such patients that the liver can be affected as well. Besides that, it was typically what we have seen was one to two times up compared to upper normal level. It was also seen in the placebo-treated patients. Honestly, it's expected in this patient population. In order to perhaps answer the question the other way around is that we have, and we reported last year in November, that we had increase in our rheumatoid arthritis patients where we give the same dose of the compound on top of methotrexate. We have seen no treatment-related increases in transaminases. Again, what we have seen has, in all cases, been isolated increases that was coming back to normal within a few days. Okay. Thank you very much. Okay. Operator, do we have any more questions here? Currently, there are no further questions in the queue. Okay. We have received some questions. Maybe we should take one or two of those before we stop. One of them is a statement/question. It says, "ARDS is acquired in hospitalized patients, mainly by bacterial infections. What are the plans to look at this in the RESOVIR collaboration? Is this in the pipeline, or will you first go the viral route, dengue and flu?" Thomas and Mauro? I think that it would be, as Mauro just highlighted, bacterial infection is often coming secondary to the viral infection. You could say that we, and one potential benefit of the resolution therapy with our compound would be to reduce the risk for bacterial infection. I think that the right answer would be that we, in the RESOVIR collaboration, is focusing on the viral infection as a first step, and then explore into the possibility and what is actually going on with bacterial infections and the severity in the patients that we are going to examine in the future. Okay. Thank you. I have another one here, "Thanks to the results in ARDS, would you revise your current plans for other indications in the inflammatory diseases?" The answer is no. We will add to this task in COVID-19, as we have talked about today. However, the indication in rheumatoid arthritis is running as planned, and the indication in nephrotic syndrome, exactly the same. We expect in nephrotic syndrome, we expect results in the end of this year. In rheumatoid arthritis, we expect top-line results in the end of Q3. Let me take a last question here. That goes, "Can we expect the authorities to be pragmatic when it comes to emergency use, considering the great need? Or will they criticize the unusual method of combining open label data and double-blinded data when demonstrating statistical significance?" A good question. I would say that they look at the totality of the data, and as we have talked about today, we do expect, in the base case, that we will do another study in order to confirm these results that we have talked about today. However, we cannot predict how the authorities will react. We will need to have the discussions with them, and then go from there. That is our commitment, is that we will have those discussions in due course. Now the clock is a bit over 2:00 P.M. I would like to, on behalf of the team, SynAct Pharma team, and Mauro, I would like to thank you so much for participating in this call. We appreciate all the feedback that we get, and talk to you soon. Again, thank you very much.