Welcome to the Oncopeptides Audio Press Conference 2021. Throughout the call, all participants will be in listen-only mode, and afterwards, there will be a question-and-answer session. Today, I'm pleased to present CEO Marty J. Duvall. Please go ahead, your line is open. Great. Thank you, good morning, everyone. Pleased to provide today updated results on the OCEAN trial, and also a communication of a partial clinical development hold for our lead product melflufen. Joining me on the call, slide two, will be Dr. Klaas Bakker, our Chief Medical Officer, and also Jakob Lindberg, our Chief Scientific Officer. On slide three, we will be making forward-looking statements, so I ask that everyone take a look at our submissions and representations for complete fairness and accuracy that you'll find on our website and in other filings. Looking at slide four, what are the key takeaways here? This is mostly associated, of course, with the OCEAN trial. Recall that this is a bold head-to-head study versus pomalidomide. Two very different mechanisms of action in patients with third and fourth-line relapse refractory multiple myeloma. We are pleased to report today that the independent review committee has reassessed, and the trial now meets its superiority on the primary endpoint of progression-free survival across the intent-to-treat population. We'll provide a little bit more detail on that process and how it came about, but now meeting superiority on the primary endpoint in the intent-to-treat population. We also see in the trial mixed overall survival results. We'll describe to you how that's the case and where those mixed results do reside. Also, we are targeting a particular meeting, the IMWG meeting in September in Vienna. We'll be submitting a late-breaking abstract. We obviously don't control the acceptance of that abstract, but we just wanted to make everyone aware that that was our target for providing the full data set and full data disclosure. We're also working very hard on a publication of the OCEAN trial results. As it relates to clinical development, because of those mixed overall survival results, the trials that we have ongoing, which are in those early lines of multiple myeloma, are now placed on partial hold. We will describe some of those trials and the rationale behind that. Please note that we are committed to work with the FDA expeditiously to get these trials back up and running so that we can further study our drug in this important patient population. Finally, I do want to communicate that our Pepaxto commercialization in the U.S., there is continuation of the marketing based on the HORIZON label. With that, I'll turn it over to Dr. Klaas Bakker. Yes. Thank you, Marty, and good morning, everyone. If we go to slide five, just as a short background, the study design of OCEAN, which is, as Marty stated, a head-to-head study of melflufen plus dexamethasone against pomalidomide plus dexamethasone. Two very different drugs from a mechanism-of-action perspective, and a quite unique study in that it is not often that you see two drugs against each other where you basically can really identify the strength and weaknesses of both drugs. The primary endpoint was PFS, as assessed by the independent review committee, and we'll talk about that more a little bit later. Two key secondary endpoints being overall response rate and overall survival. Go to slide six, please. If we look at what happened, the top-line results were disclosed on May 25, as you may all remember. Today, on the 8th of July, we disclose the final independent review committee PFS results. As Marty stated, in Q3, hopefully at the IMWG, we will present the data to a broader audience at a scientific meeting, and at the same time, we're working on a manuscript. These timelines are all unchanged. With that, because we have a superiority trial, we still expect to file for an expected sNDA around year-end or early next year. Next slide, please. The top-line results were communicated on May 25th. After that, there was a deep dive on the data, and this is normal because you need to prepare data for your clinical study report, the CSR, and also for regulatory interactions, you need to look deeper into the data to prepare your file with the FDA. During that deep dive in the data, we became aware that some of the imaging results were not provided to the IRC at the time of their assessment. This is being done by our statistical vendor who is actually the responsible body to make sure that all the data from the clinical database is actually shown in worksheets to the IRC members. While all the information is there in the clinical database, it's always an extraction of the database that comes in front of the IRC. Note, this is a process completely independent of Oncopeptides. Because of this finding of initially one or two patients where we could see that imaging had been lacking, we asked the CRO to do a full review of all 495 patients to see if there was any discrepancy between what was provided to the IRC and what was in the clinical database. Based on that, we landed on 29 patients where a reassessment had to be performed because of changed data points in the clinical database. Please note that after May 7th, the clinical database has never been opened. This is only about what is extracted from the database and put in front of the IRC members. There were no data points changed, and the database remained locked throughout this program. We made the FDA aware on a very early notice that this was going on, and this was happening in the background, and we had an ongoing dialogue with the agency throughout this process. What did this lead to? If we go to the next slide number eight. The primary endpoint, progression-free survival, as per IRC, now has a hazard ratio of 0.792 with a confidence interval just below one, thereby reaching statistical superiority with a p-value of 0.0311 with a relative median progression-free survival improvement of 39%. You will notice that the relative median progression-free survival improvement is actually a little bit less than what was disclosed during the top-line results, This all has to do with changing medians due to the reassessment. The overall response rate stayed the same. This is logical since responses as such did not change, of course, during this reassessment. It was a reassessment of time to event data for the progression-free survival. Of note, this number didn't change, but because it's a secondary key endpoint, we actually like to show it here again with 32.5% for melflufen and 26.9% for pomalidomide. Very positive results. Next slide, please. The overall survival data. As mentioned, this is a head-to-head comparison of two different treatment modalities. Hence, we saw striking differences between the performance of both drugs across different patient populations. On the ITT level, the overall survival hazard ratio was 1.1 in favor of pomalidomide for the full population. This is not statistically significant, but because it is other direction than the progression-free survival, this, of course, leads to further analysis to see what explains this hazard ratio of 1.1. What we and also the agency have seen is that in pre-specified subgroups, there are large differences. In some patient groups, the Pepaxto or melflufen does really well from an overall survival perspective. In other subgroups, pomalidomide does particularly well. This all adds up to a hazard ratio of 1.1, but we are currently further investigating this in close cooperation and collaboration with the FDA. This is all ongoing. Let's go to the next slide number 10. Because of these striking differences in overall survival, with some patient groups also being in favor of pomalidomide, as is shown by the hazard ratio 1.1, the FDA has requested Oncopeptides to put the program of general development in earlier lines of treatment on a partial clinical hold. A partial clinical hold means that we are no longer recruiting patients into our entire study program until we have a better understanding of the overall survival results, and as such, can determine which patients benefit most from melflufen. Patients on the study can stay under study, and this is subject to reconsent and assessment by the relevant investigator. Patients who derive benefit can stay on the drug. This decision is effective immediately and impacts our LIGHTHOUSE study, which is the randomized study of melflufen and daratumumab dex versus daratumumab, the ANCHOR study, which is the basket combination study with daratumumab and bortezomib. It's the PORT study, which looks at central versus peripheral administration. It's the BRIDGE study in patients with renal and poor impairment, the ASCENT study in MLOE doses. We also put, and this is something that we did ourselves, temporarily suspended the COAST study with OPD5, as this is a very close analog of melflufen. We first want to be absolutely sure, in cooperation with the agency, that we fully understand which patients benefit most from this drug and which patients do not benefit most from this drug. There will be a lot of speculation probably about how long a clinical hold will hold. We currently don't know, but it is reasonable to assume that it won't be couple of weeks, but more in the timeframe of months. Beyond that, it would be speculative to talk about timelines. It's just that we have a very active information flow ongoing with the FDA to resolve this issue as fast as possible. Thank you. Marty, back to you. Great. Slide 11. In summary, we see the OCEAN results. Very pleased to have met superiority on the primary endpoint of progression-free survival in the intent-to-treat population. As we look at the totality of the data, plus reminded on the overall response rate. In addition, we know the clinical benefit rate, duration of response are solid data favoring melflufen, but it's in that overall survival secondary endpoint, important secondary endpoint, where the results are mixed. We look forward to Q3 and the IMWG meeting to present full data. As mentioned, clinical development, we are now on partial hold in those early lines of multiple myeloma treatment, partial clinical hold, and we will work closely with the FDA to resolve those issues as soon as we can. We continue with the commercialization of Pepaxto in the United States based on the HORIZON label. That wraps up the slide part. Now we can move into the Q&A, and for that, I turn it back over to the moderator. Thank you. If you do wish to ask a question, please press zero one on telephone keypad. If you do wish to withdraw your question, you can do so by pressing zero two on a telephone keypad. Our first question comes from the line of Viktor Sundberg from ABG Sundal Collier. Please go ahead, your line is open. Yeah. Hi, thank you for taking my question. First one on overall survival. I'm a bit perplexed why the FDA is looking at the OS data already since it's to be mature at the moment. Could you give any more clarity to this? Also the rationale for the big variations between melflufen and pomalidomide. Yeah, good question. It is immature, and certainly we'll be following it longer over time. With that, I'll turn it over to Jakob for comment. Thank you, Marty. This is Jakob Lindberg, Chief Scientific Officer. I think it just underlines the uniqueness of the results, Viktor. This is the first time you have a head-to-head comparison between two different modalities. As a sponsor here, we have actually failed to find precedent for a successful clinical trial where you have OS hazard ratios in large pre-specified subgroups going from around 0.5 to around 1.5. Given the large differences, it is clear, and it's also clear to us as the sponsors, that hazard ratio 1.5 signals, for example, that those patients shouldn't be in our trials, and they should be excluded from any potential label. There we are in complete alignment with the FDA. Given these very large OS differences, it is also clear that there is a very clear patient population that benefits from melflufen treatment. 0.5, that's around that range, is a very, very good number in the other end. I understand the agency's need to delineate and understand this data before we can continue with our clinical trial program, both that those patients that can benefit will receive the drug, as well as those patients that do not actually receive pom. I think it's important to understand how big the differences are in this material, which is a very unique clinical data set that of course from a scientific point of view is extremely intriguing. Of course, as a sponsor of a study, you would rather have an easier trial result, but it will for sure be discussed in academic settings. Okay. Thank you. Are there any risks that there will be a restriction on the current label that you have in the fourth line tough setting, given this data, or is it only related to this difference with pomalidomide? Yeah, we don't foresee that at this time. Of course, that's a different patient population under accelerated approval, fifth line plus triple class refractory patients. A reminder, about 90% of those patients had pomalidomide. Yeah. How many of the 29 reevaluated patients had their results change when they look at imaging once again? I'll turn that to Klaas for comment. We don't know because we get the data in a blinded way originally. We will look into that to better understand that, but we don't exactly know in what arm the patients were, and we also don't know right now in which directions they have changed overall. Of course, because the numbers have changed towards superiority, it will be in favor of melflufen, but whether that is based on 10 patients that have been like another result or 15 or 20, that would be speculation this time. We don't have full view of that. Okay, sure. was- Thank you. The committee made up of the same clinician as in the first data readout or? Yes. The IRC is the same IRC. Okay. Yeah, I think I jump back in the queue, but thank you for taking my question. Thanks, Viktor. Thank you. Our next question comes from the line of Patrik Ling from DNB Markets. Please go ahead, line is open. Thank you. A couple of questions. When you talk about overall survival varying from zero, with the hazard ratio from 0.5- 1.5, do you have a feeling for, you know, your subgroup, so do you have a feeling for how large proportion of the sort of market that the OCEAN trial addresses that seems to be less suitable for melflufen versus the ones where you can say that it seems to be more suitable? Yeah, good question, Patrik. Obviously, we'd be speculating a little bit there since it's probably not as straightforward as one might think, but let me turn it over to Jakob for comment. I think we should be very careful in speculating exactly where, for example, the FDA's assessment will end here. As you can understand, with these differences and the superior key test results and an ITT OS hazard ratio 1.1, we're talking about significant patient populations on both sides of the fence, so to speak, and then we should have to wait for their assessment. We're not talking about the minority versus the majority. We're talking about two very large groups on different sides of this border. Okay. On the OCEAN trial, you also have a special protocol assessment, and as you communicated about it before, it was primarily based on the primary endpoint of progression-free survival that you needed to reach superiority. You've done that now. Could you see this analysis from the FDA as some sort of early label discussion really for OCEAN? Really find out what subgroups are suitable or not? Yeah. Well, certainly the dialogue is going to be very active, and has been. It's been continuous since the first release of the data. As we've kind of discussed over the past year or so, looking at inferiority or superiority with some regulatory bodies, it's particularly important for a superiority outcome. We're pleased that in the intent-to-treat population, any final IRC results that we have the superiority on progression-free survival. I'll turn it over to Klaas as he thinks about some of the regulatory interactions and how this might proceed. Yes, sure. Please note that SPA is still valid. That means that if you reach superiority, you kind of fulfill the first requirement to sit on the table with the FDA, so to say, to talk about a label expansion. The point is that overall survival is also considered to be a safety endpoint because ultimately the overall survival event is leading. It is the regulatory body's responsibility before taking any actions on approving a drug in a certain patient population to make sure, and to be absolutely sure that there is no harm to patients before you enter that stage. Although the SPA is still leading from a regulatory perspective, the first action that always needs to be taken is around safety. Overall survival is such an important endpoint. It's in the end, the golden endpoint. That leads now to this, I would say, interjection by the FDA to actually first understand that better before we move on. As said before, reaching superiority is very important, will get us a seat at the table. We think we may still have a good shot at the label. It's just that we first need to sort out to see which patients do benefit from melflufen and which do not. Currently, the focus is at least to make sure that we do not provide melflufen who actually do not derive benefit from melflufen. In a way, they are kind of separated from each other, the SPA and the superiority and this investigation that is based on safety. I think Patrik, it's also fair to say, and Klaas that OS is obviously a very critical endpoint as Klaas mentioned. In a trial like this in earlier lines of therapy where patients will live beyond their third and fourth line, there is a confounding factor of subsequent therapy and all of that needs to be worked out in this analysis as well. Okay. When it comes to the difference in overall survival, based on the analysis that you've done up until today, you can be sure that it's not due to any unexpected side effects or anything that has been caused to the patient by your drug? Or if someone- I can comment on that. Thanks for asking that question. The answer is you are correct, and as far as we can see now, there are not unknown adverse events or new safety signals, as we have also already mentioned in the top-line results update. That still stands. We have not identified a new safety signal in toxicological terms. It's only the overall survival that we need to understand, but so far we haven't identified a classical safety issue, so to say, that is associated with this overall survival. What we really look at is various layers of efficacy. One patient group seems to be more benefiting from this drug than other patients, and some do benefit really well from melflufen, some do not really. This has nothing to do, as far as we can say now, with safety as such. When I say a safety measure, that's what I mean, that the FDA just wants to understand who to expose this drug to from an efficacy perspective, but not because they are concerned about more adverse events here. Okay, last question. Do you see any correlation between the variation in overall survival with the overall response rate and PFS? Do you see the same type of variations for the same type of subgroups for the other measures? For some we. Yeah. Go ahead, Jakob. For melflufen, there is a very consistent path between increased response rate, increased PFS, increased OS. The entire surrogate endpoint system, so to speak, from an efficacy point of view, makes perfect sense in the melflufen arm. It is much more tricky in the pomalidomide arm, where the PFS is basically very stable across all subgroups, but the OS varies tremendously across the pre-specified subgroups, which makes this analysis a bit tricky. For melflufen, your statement is absolutely true. The efficacy endpoint and the OS endpoint goes hand in hand. Okay, great. Thank you. I'll jump back into the queue. Thanks, Patrik. Thank you. Our next question comes from that of Christopher Uhde from SEB. Hi there. Thanks for taking my questions. Okay. Maybe I'll just ask this one first, since you sort of alluded to it earlier, but just to be clear. Bearing in mind the OS finding, would you say your confidence in full approval and/or label expansion is increased or decreased compared to when you first announced top line? Do you see any difference in how you view the FDA and EMA processes? Yeah, maybe I'll turn that one. Thanks, Christopher. I'll turn that over to Klaas for a first comment. Right. Thank you, Christopher. We have from the beginning, also on the top-line results, always have said that based on the totality of the data, we feel very confident in our interactions with regulatory authorities. The fact that this now has changed to a superiority result has even further increased the chances of regulatory success. When you speak about full approval, I would say there is a substantial possibility that it will not be a label that covers the full ITT population. If you have a hazard ratio, as Jakob already said, sometimes going to 1.5 on overall survival, and that turns out to be true, it's hard to include these patients in a label. It's not the base case anymore that we will get a full approval on the full ITT population based on these results. Okay, thanks very much. That's helpful. My next question is it initially struck me, I guess your last comment there on related unexpected side effects, whether there are any, suggests that's the case. I was immediately thinking of venetoclax initially. First of all, I guess, is it correct that infections are not part of the problem here in terms of the OS, let's say, deficit in some subgroups for melflufen? Is it anything to do with t(11;14)? Okay. Yeah, I can answer that question. This is a completely different situation when compared to venetoclax. Regarding infections higher in certain subgroups, that is not the case. We don't see a delineation across subgroups according to the t(11;14), what you just mentioned. That is not the case, and we look at a completely different situation than venetoclax here. Jakob, anything to add there? Yeah, I would just echo what you said. Actually, when it comes to infections, it favors melflufen in this study, as will be shown at the future conference. No, we have done a very thorough job at analyzing this. Just like you, Christopher, our first thought was that this was adverse event-driven, and it wasn't. From my interpretation point of view today, this is just a stunning difference in efficacy between two different treatment modalities across different patient populations that we are seeing. We're seeing true efficacy differences between these two drugs. Once again, from a clinical scientific point of view, I think it's a treasure trove of information. Obviously, this may create a complication for us in the regulatory interactions and to determine exactly how to define these two patient groups, those that benefit and those that do not. Okay, thanks. That's very helpful. I guess my last question is just a clarification. Since you've mentioned that the database has been locked throughout since May. Is the OS change, I guess, due to the appraisal then of the existing data coming out of the IRC look again, or is it to actually to maturing data? So- I'll turn to Klaas. Yes, it's a good question. The IRC reassessment has nothing to do with overall survival. That's such a hard endpoint that you don't need to reassess that. From a clinical database perspective, you look at a certain date, and then you extract the data. That hasn't changed, and we have not seen other OS data today than that we had seen on the very first day. What we did understand on the first day was that it was very immature, the overall survival endpoint, and very difficult to read. We needed further analysis to better understand what we're seeing at that time. No, there has been no update in the overall survival results. Okay, thanks. That's all my questions. Thanks, Christopher. Thank you. Our next question comes from the line of Peter Welford from Jefferies. Please go ahead. Your line is open. Hi. Thanks. I've got four questions, and perhaps we'll take them in turn. Firstly, just with regards to the overall survival, again, so I appreciate you say there are no new safety signals, but can you confirm that this is not related to the existing, for example, hematologic toxicity, and it's not the hematologic toxicity that is causing this difference? Equally, that it's not related to duration of therapy, because I guess, duration of therapy, obviously, I guess I'm saying it's not the cumulative effects of those hematologic toxicity events over time that's leading to this OS difference. Yeah. Thanks, Peter. I'll let Klaas touch on that one. Yes. Thanks, Peter, two very relevant questions and two relatively short answers. No, we don't see this being related to hem tox. It's not due to any differences in duration of treatment. If I could just add one thing. Jakob here. Peter. You actually, if you look at the OS while on therapy and within 30 days of the last dose, you have a positively trending OS, and you have a larger amount of patients receiving subsequent therapy in the melflufen compared to the pomalidomide arm. Okay. The second question is just with regards to disclosing this subgroup. I guess, you obviously are approved for the HORIZON indication, and you also have open access programs in Europe. I'm now thinking, what is your thinking regarding the timeline of disclosing these subgroups? I'm thinking ahead of September even, given presumably there are potentially patients who may be later line who perhaps should not get the drug anymore based on these subgroups. Am I misinterpreting? Yeah, no, I don't think you're misinterpreting. I think our initial look and certainly the course, the communication with the agency has been that the current label is not impacted. Based on our look, we don't see later lines of therapy being impacted. Of course, analysis will continue, but that's not where we stand today. Maybe I'll turn it to Klaas also for comment here. Yes, I think for now, I can only echo what you say, Marty. The patient population of HORIZON is so materially different from OCEAN, much later line patients with limited clinical treatment options, and that the subgroup results that we see based on the analysis that we have been doing quite extensive analysis, we don't see a repetition of that in HORIZON, so to say. At this moment in time, we feel comfortable with the patients who are currently getting melflufen within the HORIZON label. We have no concerns about that. We're comfortable with a target of a September disclosure on these subgroups and the full data. Got it. Then the third question is just with regard to the comment that was made on the confidence in approvals, but not for the entire population. I guess I understand the thinking, but if you were to exclude, I guess, the patients that have unfavorable OS, I guess how is your confidence then that the PFS benefit is still going to be meaningful and ideally statistically meaningful if you just take that subgroup of the population? I guess, to get approval for just a subgroup would then rely on essentially and lowering the end of the study. Yeah, I think, I'll turn this to Klaas for comment as well. I mean, Jakob made one point about the overall directionality of the secondaries of overall response, depth of response, duration of response as it relates to PFS. Klaas made mention of the fact that, in the Intent-to-treat population, the PFS meeting superiority makes this a positive trial. With the trial being positive, the analysis of subgroups and the meaningfulness of subgroups becomes more important. We kind of see that sequence of events. I would speculate you'll find directionally the numbers to line up. Maybe I'll turn it over to Klaas and Jakob for their comments as well. I just want to echo what Jakob mentioned earlier. For melflufen, it's quite stable, as we say here. What I mean by that is that when there is a clear PFS benefit, that also translates into an OS benefit, and the reverse. When the PFS benefit is not really there, the overall survival is not going into another direction. It's really pomalidomide which behaves differently here. Going back to your question, we have the firm belief that where we see a benefit on the primary endpoint for melflufen, that also translates into a good overall survival result. We have full confidence that some major subgroups, actually, everything goes in the right direction, so to say. We don't see melflufen specific patient populations where the PFS number doesn't hold in the OS analysis anymore. That makes us pretty confident on that level. It's Jakob here. I can just add one layer more. Under the assumption that your endpoints move in the same direction, which I think, Peter, you have heard that they really do in this trial for melflufen, then it means that you have proven benefit by reaching your primary endpoint, and in this case, of superiority on PFS. What the regulator would do, presumably, and now speculation is, and there's a lot of precedent for this, is that you exclude subgroups based on risk. The bar you need to reach to exclude a subgroup based on risk is, of course, much lower than to prove benefit. You have proven benefit on the ITT level already, which means that the exclusion is based on risk assessment rather than benefit assessment. There is precedent for this in multiple trials, actually, this exact way of thinking. If I have a quick question then, it is just with regards to the call, I guess, just going back to the start of this, really. Just trying to understand what the cause of this was. I mean, it seems as though, the IRC had, I guess, in the sixth amendment, they had time to do this, and since when the study was fully enrolled and then the events occurred and happened. I guess, just curious what the cause is of this error and who's, I guess cut to be short, who's to blame for this? Clearly something, somewhere, I mean, I've done this a long time, and someone somewhere clearly makes a mistake in the analysis of this. I'll turn that to Klaas for comment. Yeah, sure. As always, it's an addition of individual small things that add up to a result like this. What we can say here is that the process that has been followed here, is a sequential read by the IRC of overall survival results in batches. When every three months there is a review of the event, and the IRC reviews that, so that they don't review all 495 patients at the same time, which would be an awful lot of work. This is common practice. Between the last IRC meeting and the database locks, where data, of course, is cleaned, added, subtracted to make sure that everything is correct, there was not a new IRC meeting after that to look at these changes. The IRC is managed by one of our vendors, but guided by us. It's a combination of parties who are involved here. This is as transparent as I can be and just that because of the not looking at everything at one time at the end, but instead looking at it at various time points and then not later on look at patients where things have changed. That's, I would say, the main driver here of the fact that the first IRC read was not complete. Yeah, just for slight clarification, that was on PFS, Peter. Yeah, that's it. Thanks. Thank you. We have a follow-up question from Patrik Ling from DNB Markets. Please go ahead. Line is open. Thank you. Just a short question. Do you think that FDA analysis and partial clinical hold will be over by the time you present the data in September? I think that might be a little tight. I'd be speculating a little bit there, but I'll ask Klaas to comment. Yeah, I think it's really speculative. I wouldn't feel comfortable to specifically comment on that. As I said earlier, I think it won't be weeks. Then how many months is really speculative. The only thing I can say is that we work as fast as we can with the agency, and the agency is working very hard here as well to get this result ASAP, because that is in the interest of patients and all parties involved. No one benefits from a delay here. We're just doing everything we can to get this clinical hold lifted as soon as possible. Okay, great. Thank you. Thank you. Once again, if you do wish to ask a question, please press zero one on your telephone keypad. We have a follow-up question from Christopher Uhde from SEB. Please go ahead, line open. Hi, thanks again for taking my follow-up. Just following on, I guess, from a couple of your comments. The first one in terms of the bar to exclude being much lower than the bar for benefit, it sounds like you're saying, given that you said these are two roughly equal, very large populations. Are you saying that 50% of what we would have considered the addressable market previously would be potentially excluded? Or is it more or less? Also, how do you see this affecting reimbursement in Europe? Thank you. Yeah. Maybe I'll turn it over to Jakob to talk about the first part of that question. I don't want to speculate in exactly because we need to finalize the assessment in collaboration with the agency regarding the exact delineation here. As we have stated, we're talking about two very material groups, right? Looking at the data, it's up to the agency also to make their assessment and exactly where they will come out on that, we don't know. I just want to highlight that your question about reimbursement will then be linked, of course, to what the final data set is in those patients that are selected in a potential label. Okay. To add on that, Jakob, I think it's not unreasonable to state that the European payers in general do like medicines that are effective in almost all patients that are part of a group. When you get approval, and this is highly speculative, if you get approval for a certain patient group where you derive a lot of benefit or who derive a lot of benefit, the bar for reimbursement will be lower than going for a full ITT population with not a benefit for all patients. From a European payer perspective, it's always more interesting to look at a smaller group with higher efficacy. Thank you. Yeah, I think that, and maybe stepping back, Christopher and others, as we think about this, I mean, think about an intent-to-treat population here of 495 patients. On the primary endpoint, as we've described, meeting superiority on PFS and directionally across the ITT population, favorable secondaries on overall response rate, clinical benefit rate, things like that. It's the overall survival that's confounding. What that means is that, and as Jakob mentioned, we've got efficacy results on the melflufen side across the primaries and secondaries that follow one another. Clearly, there are pockets of very large benefit. Again, getting back to the stunning efficacy differences, I think is the way it was described, and this really is a treasure trove of information. Tying that back into the point that Klaas is making relative to reimbursement on the European side, and really where we're at today in oncology and other fields, if we can define the population that benefits, that's the best place we can be, right? The highest priced drug is the one that doesn't work. The better we can define the population that the drug works in, the better off we are. Of course, our commercialization will be more crisp in having more solid results from a benefit risk perspective in those populations. Thanks very much. Thank you. We have a follow-up question from Viktor Sundberg from ABG Sundal Collier. Please go ahead, line open. Yeah. Hi, and thank you for taking my follow-up question. Going back to the MOTIVA study that you often refer to where you showed us overall survival depended a lot on the lenalidomide-free period. Is there anything there that's driving any difference in overall survival trends? Of course, as for median overall survival, just curious about that point. Yeah. I'll turn that to Jakob and Klaas for their comments. We don't want to disclose data today, but the answer is yes, Victor. You can find a lot of patterns in how extensive the lenalidomide use has been and how that impacts. Patients that have used a lot of lenalidomide, those groups, that favor melflufen strongly. Yes. We will most likely disclose this at some point. I'm not sure at IMWG, if we get that presentation, but that's a very interesting set of data as well. Does that go both ways, I guess? If you had a longer lenalidomide-free period, you had better outcome or worse outcome for melflufen or? Yes, it goes bi-directional. That's correct. Yeah. If you have a longer period and you list the lenalidomide before that, it benefits, it favors pomalidomide. If you have a lot of lenalidomide use and short period, it favors melflufen. That's correct. Yeah. Just a final question. On the subgroup that we're talking about, do you expect to show any statistical significant benefits of the subgroup, or will this be showing trends to the FDA, or how should we think about that? I'll turn that over to [audio distortion], Jakob. I can add short comment. One should be careful by talking about statistical significance when you didn't have a null hypothesis around that. What you can claim is that there's still 95% confidence interval either larger than one or smaller than one, right? Yeah. Those differences already exist in the materials. Oh, no. Okay. Yep. Thank you very much. Thank you. We have no more questions from the line. I'll hand it back to our speakers. Okay. Great, well, thankyou everyone for participating. I think the key points here are, as stated, this meeting superiority on the primary endpoint of progression-free survival across the intent-to-treat population is very important. We see overall directionality positively in melflufen's favor across the intent-to-treat population as it relates to response rate, clinical benefit rate, and others. It's the overall survival results that are mixed. We are actively cooperating with the FDA to understand those results better. In the meantime, our trials in earlier lines of therapy are on partial clinical hold while we continue to market Pepaxto in the United States based on the current HORIZON label. We certainly look forward to the IMWG meeting, where we're submitting a late-breaking abstract and targeting a full disclosure of the OCEAN datasets. With that, I'll wrap up. Thank you very much. We'll talk soon. Bye now.