Welcome to the SynAct Pharma Presentation. For the first part of the conference call, the participants will be in listen-only mode. During the questions and answer session, participants are able to ask questions by dialing star five on their telephone keypad. Now, I will hand the conference over to the speaker, CEO Torbjørn Bjerke, CSO Thomas Jonassen, and Chief Business Officer James Knight. Please go ahead.
Thank you very much, and thank you everybody for listening in to this webcast. I am Torbjørn Bjerke, I'm the CEO of SynAct Pharma. The purpose of this call is to explain more the data that came out this morning on the EXPAND phase II-b top-line data. And especially, Thomas Jonassen, our CSO, will walk us through where we see that at the moment. We need to remember, though, that this is an early phase. We only have the top-line data, but we will explain where we are today.
And then, Jim Knight, our Chief Business Officer, will talk more about the RESOLVE study that will come out in October, and speak a little bit also about the differences between EXPAND and RESOLVE, but also talk about the big market opportunity we see in the RESOLVE group of patients. So, of course, we are quite disappointed, because we did not show a clinical significant difference between the active medicine, resomelagon, and also called AP1189, and the placebo on the ACR20 score, which was the primary readout for this EXPAND study.
We have some observations and some important elements in the study that we want to discuss with you. One of those are the subjective assessment. There is quite a big difference from the BEGIN study. However, there are also some very good elements of the study supporting the efficacy of AP1189, and that's the objective parameters that was more in line with the BEGIN study. Another very positive element is the very favorable safety profile after three months of therapy, which is an important part of the profile of the compound. So the top-line data that we show today, we also saw an unusually high placebo effect and different between different sites.
This is an important observation that Thomas will take us more into and what that means for the data. And as I said, further analysis of the data has to be completed. We are thinking about really having a good assessment during the next two weeks, and we'll get back to our stakeholders after that. So in terms of EXPAND and RESOLVE, as I said, Jim will get more into this, but it's a different patient population. The RESOLVE patient has longer disease duration and documented incomplete response to methotrexate.
methotrexate, as many of you know, is the first-line treatment in a newly diagnosed RA patients, and in the RESOLVE, where they have been for that treatment for a very long time and without having a good response. So it's a quite a different population of patients. And the second one is the geographical split, and RESOLVE also includes U.S. sites, which is quite important in this context. So, these are the top line, and now we are getting more into the details here. So, Thomas, could you please take over?
Yes, thank you very much. The EXPAND study was set up as a continuation of our BEGIN study, where we have tested the compound in treatment-naïve patients with high disease activity. So rheumatoid arthritis patients referred to rheumatologists with the aim to initiate anti-rheumatic treatment were eligible to methotrexate, and who were qualifying for the inclusion criteria, meaning high disease activity, defined as clinical disease activity higher than 22, and with a minimum of six tender and swollen joints, and without concomitant glucocorticoid treatments, were eligible for this study. And they were then offered to participate in the study, which were either the active compound, the resomelagon, what's also the AP1189 treatment, once daily, alternatively, placebo.
In both the active and placebo, the compound was given on top of methotrexate, and the very first dose of the study medicine was given at the same day as the very first dose of methotrexate. So methotrexate was then given on discretion of the investigators. Following the successful BEGIN study, where we recruited patients both in Europe, both here in the Nordic countries as well as in Eastern Europe, we made a number of very interesting observations. Both in the BEGIN study, we had very nice treatment effect, both in the Eastern European as well as in the Nordic countries.
We identified a really nice and small placebo effect in the Eastern European sites, patients. So as we were very interested in seeing the potential of the compound for a prolonged treatment in these patients, to see whether we could go further and with dosing beyond the first four weeks, as in the BEGIN study, we decided to take these patients as they go to the Eastern European sites. As they were having high disease activity, they were treatment-naive. There is a tradition to not use glucocorticoids in the initial months of treatment, and they are not as aggressive on methotrexate treatment as they are, for example, in the Nordic countries.
So all in all, the intention was then to give us the opportunity to test the compound as an add-on to standard therapy. We have included these patients during the autumn last year and the first half of this year, and now we are in the reporting phase. The aim was to dose for 12 weeks, and very importantly, we had safe tolerability as well as the ACR score as the primary readout. And in addition to that, a number of secondary endpoints where we do not have the reporting from the statistician yet.
So I will focus on the primary, on the safety and tolerability, as well as the primary readout. Then I also highlight here that we have a sub-study in MR, and that is also something that will be reported in the coming weeks. What we were able to recruit 120 patients. We had 63 patients of resomelagon, and we had 64 patients on placebo. Of these 63 on resomelagon, 53 completed, meaning that we had 10 discontinuations, whereas five were due simply just to withdrawal of consent of different reasons, including traveling abroad. We had three who was discontinued due to adverse event.
I will go through that on the adverse event, when I go through the adverse events, and we do not have any patient in that group that was lost in follow-up. In the placebo group, we completed 61 patients. Three was discontinued, one due to withdrawal of consent, 1 due to an adverse event, and one was simply lost in follow-up. The baseline characteristics of the patient was that, the vast majority of the patients in the study were women, slightly higher than in the background population of rheumatoid arthritis. But in general, it's easier to recruit women to studies, and they also to stay in the studies better than men, especially in the sites where we worked.
A mean age in mid to late 80s, 50s, slightly higher in the resomelagon group than the placebo group. Recently newly diagnosed patients with RA. Study of an average of 42 weeks in the resomelagon group, compared to 19 weeks in the placebo group. This is a somewhat longer duration of the disease in the active group, which was simply just a result of the randomization, but could potentially also be taken into the overall evaluation of the study. You can see here that we had the last-
We had only a fraction of the patients did have increased CRP at baseline, which is normal in these early stages, and the disease activity at baseline was slightly higher in the resomelagon group than in placebo group. And then with the characteristics of these patients, they were classified as most of them were in ACR class two. Importantly, no co-treatment with glucocorticoids during the study.
And let me then go through the safety readouts. We had one serious adverse event in each group. In the placebo group, it was a patient who very early in the treatment, already on day two of treatment, developed a pulmonary embolism, which and was referred to hospital and, and the disease was. And again, left the hospital after the disease was disappeared. In the 1189 group, it was a patient who after two months of treatment, developed an increased creatinine, showed to be urine retention, severe urine retention.
So following hospitalization, 4 L of urine was taken from that patient, and then everything went back to normal, and it was identified there were morphological changes in the bladder that could explain this finding, which- So both versus both the serious adverse event was considered not to be related to study medicine. With regard to the treatment-emergent adverse events, we had a total of 88, that was equally distributed between the two groups. And again, the intensity relating to the intensity of the adverse events, that we had a little more than half in each group that were mild, and then the rest were moderate. We had equal distribution of patients with more than one treatment-emergent adverse events.
We did have, but we did in the active group, in the resomelagon AP1189 group, we had a larger number that discontinued. That was three patients who, following vomiting and nausea, decided not to continue in the study. It was the AKI patient, and it was one patient who had developed hair loss, was explained that most likely had to do-mild hair loss, most likely had to do with methotrexate and decided then not to take methotrexate anymore, and they, of course, had to leave the study. In the placebo group, the patient who was discontinued due to a treatment adverse, an adverse event, was the patient who developed an acute cholecystitis.
With regard to the number of the most common adverse events, we had. The most common adverse event in this study was infections, but what we most of them were observed during the winter. And we have a slide, we had 10 in the placebo group versus seven in the active group. We saw, as we saw in the beginning study, we saw higher numbers of elevated adverse events related to liver enzymes in the placebo group than in the resomelagon group, which is now the second study where we show that, and which is very, very interesting finding.
We did not see any headache in the active group, where it was actually the most dominant one of the most dominant adverse event in the study. We did not have any, whereas we saw six in the placebo group. And with regard to abdominal pain, it was seen both in active and placebo group, with abdominal pain, nausea, and vomiting. But in the active group, we had three discontinuations who presented both vomiting, nausea, and abdominal pain. And that most likely can be explained by mineralocorticoid receptor activity. So overall, we can make the conclusion that the compound given for 12 week is safe and well-tolerated, and that we have a very satisfying safety profile.
When it then comes to the primary readout, and then the primary readout is the only one I can report here today, as it's the only one that we have presented in our press release, and the only one that we really have got in a validated format from the statisticians. We'll get the rest of the data in days to come, and we will then dig into them and further look and present at a later various convenience. The primary outcome, the ability to reach ACR20 was equal in the two groups.
ACR20 scoring in the resomelagon group and in the placebo group each reached approximately 55%. So the study could not show a treatment-related effect of resomelagon relative to placebo. When we then look into these patients, it is patients who had a very high disease activity, and we knew from the beginning study that the subset of patients who had very, very high disease activity, after full dosing, had had, especially the placebo patients in the beginning study, had a very, very low rate of ACR20 scores.
So based on that, and the fact that we have with high disease activity, we have without any co-treatment of any kinds with glucocorticoids, and with the fact that the patients have not been treated aggressively with methotrexate, we consider a score at ACR20 score after these 12 months as unexpected high. But this is what we see, and I will try to, in the next slide, try to set you in where we are at this time points for understanding of the finding. So discussion points.
When we are looking into scoring systems for rheumatoid arthritis, and especially here, the ACR scoring, but it will also come from CDAI, that is used for the baseline characteristic, and was the primary readout in the beginning study. Then it consists of a composite of readouts, where we have subjective readouts, and we have objective readouts. The objective readouts is the tender joints and the swollen joints, and the CRP. That is, the tender joints and the swollen joints is counted, and we look at changes in the numbers. The CRP is measured and changes as it can then be evaluated on the plasma concentration at baseline and then at different time points.
When it comes to the subjective readouts, we have the investigator's assessment of disease activity. That is what is called, it's scored on a VAS score, meaning a visual analog scale, where you give it a number on a line. The total, the max number is 10, and go from zero to 10. Similarly, the patient assessment of disease activity scored in the same way. The patient pain assessment is scored that way, and the Health Assessment Questionnaire, the so-called HAQ of physical functioning is another example of what is scored. In our case, we had a dedicated computer, and each patient had a dedicated login to the computer, and without the presence, without interference with the investigator, had to make this self-assessment on the computer after they have been through the training.
So we have done that in a way that should be state-of-the-art. With regard to the quality improvement in ACR scores, it's very important to have in mind that in order to qualify for ACR20, for example, then you need to have a minimum of 20% reduction in tender and in swollen joints, and then in addition to score on three of the five other outputs, which where four of them are subjective. So in other words, it is so subjective readouts in a study like this do play a major role. And when we then have and this is preliminary evaluation because we only have a very few very short time frame to have looked into the unblinded data.
And as I said, we still need most of the data from the statistician are still pending. So we have been into the database and looked and what we can see, we're trying to highlight here. In the EXPAND study, reduction in tender and swollen joint in the resomelagon group seems to be reduced to a degree we could expect from the BEGIN study. The patient and investigator assessment of disease activity in the EXPAND study did, however, not reflect the reduction seen in tender and swollen joints. And we consider that as very surprising, as the reduction in joint counts is in favor of resomelagon treatment rather than placebo treatment, and that nothing in the adverse event profile indicates that the compound is less well-tolerated.
So this is, of course, something that we dig very much into and try to further understand. And then in addition to that, we have also identified between-site variability in clinical score. It was rather high, which most likely contributed to the ability to discriminate between the active and the placebo treatment. And this variability seems, not least, to be driven by subjective measures. So we do not have a full explanation of what we see, but what we have seen so far is that when it comes to the objective scores, the compound acted as it should.
But for some reason, the very, very beneficial effect of the compound evaluated by the patient in BEGIN study seems not to show up to the same degree in this. Actually, in the placebo group, especially the patient-driven self-assessment scores are very high and come in very early in the patient group, in the placebo group. And with that, so we will continue to dig into this to further understand it. And then we will come with second line and further data when we are able. And with that, I will give the word to Jim.
Thank you, Thomas. So as I to run it online, I want to share a little bit about the differences, a little bit more about RESOLVE and a little bit of difference between the RESOLVE and the EXPAND studies. So here is an overview of the RESOLVE study. It's a phase II-A, II-B trial in DMARD-IR , or in our case, in methotrexate inadequate responders. We are expecting data from the phase II-A portion, a four week dosing of three different doses, and we're expecting that this October. In regard to key differences, you know, there are a few, and I think they bear a little time to go through here. The first is disease duration.
As Thomas shared with you, he showed you the average months, or the average, sorry, weeks, that patients has had since their diagnosis with RA. You know, it's definitely below a year. I think on the average mean high was about 10 months. But in general, treatment-naive patients are these studies are less than a year of disease duration. DMARD-IR can be quite a bit longer. They've had disease for a much longer period of time. Some of the published studies have it, you know, in the six to eight year time frame. So these are patients that are much more experienced with the disease.
They know- you know, probably have a better idea of how the disease affects them and are probably better judges of how the disease affects them over time. Probably the biggest difference is in regard to the use of prior therapy, in this case, especially methotrexate. For our treatment-naive studies, both for BEGIN and for EXPAND, patients were not supposed to be exposed to methotrexate prior to study initiation. Here with the DMARD-IR patients, patients need to have a documented incomplete response to methotrexate after an adequate course of therapy of at least three months, and many in the study will have an exposure to methotrexate of a year or more.
The doses used in the RESOLVE study, and the patients experience are higher than those typically used in the EXPAND study. In regard to this incomplete response, I mean, that can take a form of a few things, but that is a judgment on the part of the patient physician that after, again, at least a three-month course of methotrexate, the patient is either still experiencing moderate to severe disease activity, so they really haven't got a level of efficacy they think is required or that they deserve at that point in time. It could also encompass some tolerability issues. There are some different tolerability issues that can be associated with methotrexate therapy.
Or it could, you know, be in the case of a patient that did really well in methotrexate and just lost that response over time. The other point on regards to previous medication use is concurrent steroid use. Again, steroids were not allowed in either the begin or the EXPAND trial, only as rescue medicine. And so new use of steroids at study entry. And DMARD-IR trials, again, as long as the doses of steroids are steady below 10 mg, they are allowed in. They can stay and allowed in. Again, some of the published trials have steroid use at entry in the ballpark of about 40% or so of patients.
Perhaps the last key difference between the EXPAND RESOLVE study is RESOLVE is being operated under our new U.S. IND. With the U.S. sites, they've recruited well and account for about 25% of the patients thus far in RESOLVE. I want to share a little bit about, you know, sort of the opportunity or what happens, frankly, more the unmet need with methotrexate therapy. As has been discussed, methotrexate is almost the every time, sort of first-line agent that's used. There are some other DMARDs, but they much much much lower use than with methotrexate. You know, and, you know, there's two sort of patterns that happen with methotrexate.
So at initial use of methotrexate, and this is both based upon the literature as well as some market research that we conducted, you know, roughly 50% or so of patients will not have an initial adequate response. Of the patients that do have an adequate response, you know, for the first, say, six months of methotrexate therapy, up to another 20% or so will lose that initial response. So at the end of a year, if you start a patient on methotrexate today, and follow them through for a year, only about 30% of those patients will have a meaningful longer duration response to methotrexate therapy.
Meaning that about 70% of patients that are initially started on methotrexate will not have an adequate response within one year of initiating therapy. The other reason that's on the box side here, too, is that, you know, methotrexate while, you know, again, document efficacy and a good first-line agent does have its issues. And GI side effects are probably a key one. You know, just referencing one paper there at the bottom, where even after five years of utilizing methotrexate therapy, patients still experience these GI side effects caused by methotrexate. Moving on just a little bit about the sort of size, the unmet need size of the opportunity. You know, so currently, you know, DMARD-IR patients are not well served by existing therapy.
Advanced therapies like biologics and JAK inhibitors come with significant safety concerns. Those are mainly driven by the mechanisms of those products are immunosuppressive in nature. So we're really, you know, suppressing the immune system to be able to, you know, quell or to lower the inflammation that's going on within the joints for RA. And these can cause, you know, quite a few issues in terms of opportunistic infections, some which in the product labels are known to be lethal in certain cases. You know, in the case of JAK inhibitors, there are cancer concerns, pulmonary embolism concerns.
You know, they're strong medications, if you will, but they do come with documented, again, side effects and safety concerns, most notably tied to their level of induced immunosuppression. You know, probably, you know, more of a U.S. piece, but I think, to some degree, definitely a global issue as well, that payers and insurers can restrict use of access to these advanced therapies. These advanced therapies come, especially in the U.S., at a very high price tag. And insurers want to reserve those for as long as possible, right? Keep those in reserve for as long as possible before allowing access. And in the U.S., you know, JAK inhibitors used to be able to be used for DMARD- IR patients.
You know, and that's when they were counting their first development target, right? So these are oral, and mostly once daily medicines, that, again, are a nice convenience, for this much larger, earlier stage, RA population. But because of safety concerns with the class of therapies, the FDA mandated that the, a course of a, TNF blocker must be used prior to initiating therapy with a JAK inhibitor. And, and there have been some, some other restrictions of a similar nature, a little bit, different, twist, but that have been put in place by the EMA as well. About 40% of overall global RA population is managed on DMARDs alone, which is about 8 million patients.
You know, again, it's got long-lasting side effects, but you know, you know, these therapies, you know, provide them some level of efficacy. So, you know, the treatment algorithm for RA is one that's a bit more additive. So patients will start on methotrexate, they'll get some type of response, and more than likely, if they had to go to, you know, today, an advanced therapy, with say, an anti-TNF agent, they will likely stay on the methotrexate therapy as they initiate the TNF agent. And the global RA market is big and growing.
It's projected to be in the range of $30 billion by the year 2030. Given that, we're talking about, you know, about 8 million patients of that, or about 40% of total patients, a convenient, safe, and oral medication, much like resomelagon, would command a nice market position with multi-billion-dollar market potential. I think with that, I'm going to turn back over to Torbjørn.
Thank you very much, Jim. So the results we presented today, the top line data on the EXPAND study, we found very unexpected. During this call, we have outlined some of the errors or discrepancies we can see so far in the study. We will continue to investigate the inaccuracies we find, potential inaccuracies we find in the study, and when we have done that in one or two weeks, we will come with a more complete picture of what we believe. However, make no mistake, we believe today that the rather high placebo effect we saw in the especially the subjective measures in the placebo group is a providing factor of the data that we see.
However, our belief in resomelagon and AP1189 is still significant. We have plenty of data, including the BEGIN data. We have plenty of data also from the COVID-19 study, showing a very good efficacy. We have plenty of preclinical data supporting the mode of action. So we will continue to look at this. We are eagerly waiting for the result data, and as Jim alluded to, quite some differences around the patient population and how long time they have been treated, which gives us a very clear hope.
So we will continue to elucidate this. We also find the objective parameters in this study that we believe is quite in line with the BEGIN study. We need to have validated statistics on that before we come back to you and show you these. So, all in all, we are still on the horse. We will continue the development and talk to you again soon. So now I think there's time for questions. Operator, please.
If you wish to ask a question, please dial star five on your telephone keypad to enter the queue. If you wish to withdraw your question, please dial star five again on your telephone keypad. The next question comes from Gonzalo Artiach from ABG Sundal Collier. Please go ahead.
Hello, and thank you for taking my questions. First one, it's on the ACR20 results. You have mentioned that the lack of difference between the two arms seems partly justified by a higher than expected effect in the placebo arm. But in the BEGIN study, your methotrexate on the arm, the placebo arm, the effect in terms of ACR20 was around 34%, and the full effect of methotrexate is usually not seen until two to three months of treatment. So a higher number than 34% could have been expected. So what is the ACR20 percentage that you were expecting to see in this placebo arm? Thank you.
Good question. What we saw in the BEGIN study, the 33%, was in the average of the Nordic countries and the Eastern European. And as I put it, and as I said during the presentation, we saw somewhat lower ACR20 in the placebo group, in the Eastern European count- patients from the Eastern European sites. So with that in mind, we had had the expectation and that we would end in the 40s somewhere, and with regards to the, to the-
And therefore, proportionally also higher in the active group. So yes, we did see. So yes, we conclude that it might have to do with some kind of disproportional higher response in the placebo group. But just as important, what, in the BEGIN study, was very, very clear was that we had the tender and the swollen joint, as well as the subjective scores, all went in the same direction. Oops!
Okay, thank you. And-
Okay. Did you- I briefly lost contact to the computer. Did you hear my answer?
Yes, I did.
Okay. Thank you.
Thank you very much.
Uh, yeah.
No, finish, finish. Sorry.
No, I think I said, well, what we saw was that all the readouts went in the same direction, very favorable with the investigator and patient scores, which seems not to be as dominant, if not, in this study. Whereas it's. So all in all, it makes it clear that we lose signal on the active and get a higher signal on the placebo group.
Mm-hmm. Mm-hmm. Okay, great. Understood. And the second question, it's in for the resomelagon arm, and it's beyond this higher effect in the placebo arm. You are reporting a lower number than in the BEGIN study, which was 61%. Why was that? I mean, did you expect to see an ACR20 in the same range as the BEGIN study, or did you expect to see a better performance in these patients, based on the mechanism of action of the drug?
Yeah, it's like two, two part of, you can answer that with, with, with- Yeah, let me answer, try to say that. As for the placebo group, we also had slightly higher, lower response rate in the Eastern European groups in the active, in the begin studies, but, but still, around 50.
So, yes, we had expected that we could bring it further up, and, but where we end with this setting is, of course, not at least, as I just said, we did not see the same, same, same parallel increases in the, on the, on the objective, on the subjective readouts, which explain the, the lower, the lower scoring rate on resomelagon. And that we have to dig in and understand. Right now, what we know is that the joint counts were as they should and what we expected they would be, but the other readouts, we simply have to understand that better.
Okay, great. One last question from my side. It's with the results now in hand, what are the expectations for the RESOLVE study? If we account by the fact that these patients are allowed to take steroids, even if it's a low dose, but how much does this compromise the efficacy of resomelagon in the trial?
We have planned to give this compound on top of standard therapy in the DMARD-IR patients. And there we know that a fraction of these patients will be treated with glucocorticoids. So, that's a given when you start, and we believe that in this compound as well as for other compounds, we would be able to show a treatment effect. The inclusion and exclusion criteria has been spot on to what have been used in the development of the JAK inhibitors. So we would like to take the same patient population, so it could be comparable to what to do.
Another thing to have in mind is that we ran the resomelagon study in COVID-19 study, all the patients were on glucocorticoids. And despite that, when they came to hospital, they came from a secondary ward to a tertiary ward, and then were for oxygen therapy. And there we were able to get them out of oxygen therapy much faster than we were without on placebo, indicating that the compound in this, in that patient population, at least, work on top of glucocorticoids. So well, we still believe that we will see a treatment effect in the RESOLVE study. We have to highlight that the part one, Part A is not dimensioned to show statistical significance, but we will have three doses of active, one versus placebo, and we look very, very much forward to get the results.
Great. Thank you very much.
The next question comes from Sebastian van der Schoot from Van Lanschot Kempen. Please go ahead.
Hi, everyone, and thank you for taking my questions today. Just two from my side. The first one is regarding the RESOLVE study. There's a time frame of four weeks, and it's in the DMARD-IR setting. Can you maybe comment on what ACR scores you would consider to be clinically meaningful for AP1189 in this particular setting? Thanks.
I think meaningful effect of a compound you test in a clinical trial will always be relative to placebo response. But surely, I mean, we expect, we expect, and I have seen previously, I said that at the end of the EXPAND study, we had planned the study to show statistical significance if we had a 20% improvement or 20% higher ACR score, ACR20 score than in the placebo group. We did not reach that. When we come to the RESOLVE study, it's the...
After four weeks, depending on mode of action and others, you would expect to see a higher dose, but most important in the RESOLVE part, I would like to see whether there is some kind of dose response in the three doses given or whether we have reached the ceiling already of one of the doses. So that's most important for us right now, is to get a signal where it show dose response, and at the same time, hopefully, that it meaningfully gives a better response than placebo. But dose response more than anything else, and from there, we then decide, set up the doses to be tested in Part B.
Got it. Thank you. That's very clear, Thomas. And then, maybe can you go over one more time regarding the effects that caused the high placebo, and why this will be different in the RESOLVE study? Thank you.
Yes. What we have, and it's still. I've been going through all the data during the weekend, all the data based on where we have. Because we are waiting for all the data from the full data set from the statistician. So I have been sitting with the rest of the team, and we have been digging into all the different readouts. So that's why I was a little reluctant to show too many details here, because as soon as you show numbers, then it's kind of final.
But what we saw here very, very, very, and in complete disagreement, completely different from what we saw in the BEGIN study was that we saw a rather high activity on the VAS scores, especially already after 2 weeks, and unfortunately, very, very high in the placebo group. And that is really, really tricky for us to understand. And even more difficult for us, it is to understand that in the BEGIN study, we saw such a nice dose response on the investigators' judgment of disease activity. So we had the 50 and the 100 mg, and it was so nice, dose response compared to placebo, it even reached statistical significance.
This dose-response, of course, we only have one dose, but at the different time points, it seems not to be. Investigators seems not to look at the score in benefit for the active. So we do have the signal on the tender and swollen joints, but the other objective scorings very, very fast go very high in the placebo group, and we do not see a higher response rate, at least on these parameters we have looked at so far that we saw in the BEGIN study. That is, of course, very frustrating. There's two possibilities. One of them is, well, that is just how it is. The other is that there is, for someone, some kind of skewed observation. I did understand that if it was so that we had a very, very unfavorable or an unfavorable safety profile, but that seems not to be the case.
Okay, very clear. Thank you, Thomas.
As a reminder, if you wish to ask a question, please dial star five on your telephone keypad. There are no more questions at this time, so I hand the conference back to the speakers for any closing comments.
Okay, thank you. Thank you for your time today. And as we said, we will continue to investigate the results here. We will continue to monitor the RESOLVE study coming in October. So, there will be more news from us both on the secondary endpoints as well as the mode of action study. So, thank you very much for your time today. Bye-bye.